TY - JOUR
A1 - Habenstein, Jens
A1 - Thamm, Markus
A1 - Rössler, Wolfgang
T1 - Neuropeptides as potential modulators of behavioral transitions in the ant Cataglyphis nodus
JF - Journal of Comparative Neurology
N2 - Age‐related behavioral plasticity is a major prerequisite for the ecological success of insect societies. Although ecological aspects of behavioral flexibility have been targeted in many studies, the underlying intrinsic mechanisms controlling the diverse changes in behavior along the individual life history of social insects are not completely understood. Recently, the neuropeptides allatostatin‐A, corazonin, and tachykinin have been associated with the regulation of behavioral transitions in social insects. Here, we investigated changes in brain localization and expression of these neuropeptides following major behavioral transitions in Cataglyphis nodus ants. Our immunohistochemical analyses in the brain revealed that the overall branching pattern of neurons immunoreactive (ir) for the three neuropeptides is largely independent of the behavioral stages. Numerous allatostatin‐A‐ and tachykinin‐ir neurons innervate primary sensory neuropils and high‐order integration centers of the brain. In contrast, the number of corazonergic neurons is restricted to only four neurons per brain hemisphere with cell bodies located in the pars lateralis and axons extending to the medial protocerebrum and the retrocerebral complex. Most interestingly, the cell‐body volumes of these neurons are significantly increased in foragers compared to freshly eclosed ants and interior workers. Quantification of mRNA expression levels revealed a stage‐related change in the expression of allatostatin‐A and corazonin mRNA in the brain. Given the presence of the neuropeptides in major control centers of the brain and the neurohemal organs, these mRNA‐changes strongly suggest an important modulatory role of both neuropeptides in the behavioral maturation of Cataglyphis ants.
KW - allatostatin‐A
KW - corazonin
KW - division of labor
KW - neuropeptides
KW - social insects
KW - tachykinin
KW - Cataglyphis
Y1 - 2021
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-244751
VL - 529
IS - 12
SP - 3155
EP - 3170
ER -
TY - JOUR
A1 - Buchhorn, Reiner
A1 - Baumann, Christoph
A1 - Willaschek, Christian
T1 - Pathophysiological mechanisms of bradycardia in patients with anorexia nervosa
JF - Health Science Reports
N2 - Background
The purpose of this investigation was to examine heart rate variability (HRV), interbeat interval (IBI), and their interrelationship in healthy controls, bradycardic hyperpolarization‐activated cyclic nucleotide‐gated channel 4 (HCN4) mutation carriers, and patients with anorexia nervosa (AN). We tested the hypothesis that neural mechanisms cause bradycardia in patients with AN. Therefore, we assumed that saturation of the HRV/IBI relationship as a consequence of sustained parasympathetic control of the sinus node is exclusively detectable in patients with AN.
Methods
Patients with AN between the ages of 12 and 16 years admitted to our hospital due to malnutrition were grouped and included in the present investigation (N = 20). A matched‐pair group with healthy children and adolescents was created. Groups were matched for age and sex. A 24‐hour Holter electrocardiography (ECG) was performed in controls and patients. More specifically, all patients underwent two 24‐hour Holter ECG examinations (admission; refeeding treatment). Additionally, the IBI was recorded during the night in HCN4 mutation carriers (N = 4). HRV parameters were analyzed in 5‐minute sequences during the night and plotted against mean corresponding IBI length. HRV, IBI, and their interrelationship were examined using Spearman's rank correlation analyses, Mann‐Whitney U tests, and Wilcoxon signed‐rank tests.
Results
The relationship between IBI and HRV showed signs of saturation in patients with AN. Furthermore, signs of HRV saturation were present in two HCN4 mutation carriers. In contrast, signs of HRV saturation were not present in controls.
Conclusions
The existence of HRV saturation does not support the existence of parasympathetically mediated bradycardia. Nonneural mechanisms, such as HCN4 downregulation, may be responsible for bradycardia and HRV saturation in patients with AN.
KW - adolescent
KW - anorexia nervosa
KW - autonomic nervous system
KW - electrocardiography
KW - heart rate
Y1 - 2021
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-244724
VL - 4
IS - 3
ER -
TY - JOUR
A1 - Hagge, Jonas
A1 - Müller, Jörg
A1 - Birkemoe, Tone
A1 - Buse, Jörn
A1 - Christensen, Rune Haubo Bojesen
A1 - Gossner, Martin M.
A1 - Gruppe, Axel
A1 - Heibl, Christoph
A1 - Jarzabek‐Müller, Andrea
A1 - Seibold, Sebastian
A1 - Siitonen, Juha
A1 - Soutinho, João Gonçalo
A1 - Sverdrup‐Thygeson, Anne
A1 - Thorn, Simon
A1 - Drag, Lukas
T1 - What does a threatened saproxylic beetle look like? Modelling extinction risk using a new morphological trait database
JF - Journal of Animal Ecology
N2 - The extinction of species is a non‐random process, and understanding why some species are more likely to go extinct than others is critical for conservation efforts. Functional trait‐based approaches offer a promising tool to achieve this goal. In forests, deadwood‐dependent (saproxylic) beetles comprise a major part of threatened species, but analyses of their extinction risk have been hindered by the availability of suitable morphological traits.
To better understand the mechanisms underlying extinction in insects, we investigated the relationships between morphological features and the extinction risk of saproxylic beetles. Specifically, we hypothesised that species darker in colour, with a larger and rounder body, a lower mobility, lower sensory perception and more robust mandibles are at higher risk.
We first developed a protocol for morphological trait measurements and present a database of 37 traits for 1,157 European saproxylic beetle species. Based on 13 selected, independent traits characterising aspects of colour, body shape, locomotion, sensory perception and foraging, we used a proportional‐odds multiple linear mixed‐effects model to model the German Red List categories of 744 species as an ordinal index of extinction risk.
Six out of 13 traits correlated significantly with extinction risk. Larger species as well as species with a broad and round body had a higher extinction risk than small, slim and flattened species. Species with short wings had a higher extinction risk than those with long wings. On the contrary, extinction risk increased with decreasing wing load and with higher mandibular aspect ratio (shorter and more robust mandibles).
Our study provides new insights into how morphological traits, beyond the widely used body size, determine the extinction risk of saproxylic beetles. Moreover, our approach shows that the morphological characteristics of beetles can be comprehensively represented by a selection of 13 traits. We recommend them as a starting point for functional analyses in the rapidly growing field of ecological and conservation studies of deadwood.
KW - deadwood
KW - extinction risk
KW - forest biodiversity
KW - forestry
KW - functional traits
KW - morphometry
KW - red lists
KW - saproxylic beetles
Y1 - 2021
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-244717
VL - 90
IS - 8
SP - 1934
EP - 1947
ER -
TY - JOUR
A1 - Voigt, Gesche M.
A1 - Thiele, Dominik
A1 - Wetzke, Martin
A1 - Weidemann, Jürgen
A1 - Parpatt, Patricia‐Maria
A1 - Welte, Tobias
A1 - Seidenberg, Jürgen
A1 - Vogelberg, Christian
A1 - Koster, Holger
A1 - Rohde, Gernot G. U.
A1 - Härtel, Christoph
A1 - Hansen, Gesine
A1 - Kopp, Matthias V.
T1 - Interobserver agreement in interpretation of chest radiographs for pediatric community acquired pneumonia: Findings of the pedCAPNETZ‐cohort
JF - Pediatric Pulmonology
N2 - Although chest radiograph (CXR) is commonly used in diagnosing pediatric community acquired pneumonia (pCAP), limited data on interobserver agreement among radiologists exist. PedCAPNETZ is a prospective, observational, and multicenter study on pCAP. N = 233 CXR from patients with clinical diagnosis of pCAP were retrieved and n = 12 CXR without pathological findings were added. All CXR were interpreted by a radiologist at the site of recruitment and by two external, blinded pediatric radiologists. To evaluate interobserver agreement, the reporting of presence or absence of pCAP in CXR was analyzed, and prevalence and bias‐adjusted kappa (PABAK) statistical testing was applied. Overall, n = 190 (82%) of CXR were confirmed as pCAP by two external pediatric radiologists. Compared with patients with pCAP negative CXR, patients with CXR‐confirmed pCAP displayed higher C‐reactive protein levels and a longer duration of symptoms before enrollment (p < .007). Further parameters, that is, age, respiratory rate, and oxygen saturation showed no significant difference. The interobserver agreement between the onsite radiologists and each of the two independent pediatric radiologists for the presence of pCAP was poor to fair (69%; PABAK = 0.39% and 76%; PABAK = 0.53, respectively). The concordance between the external radiologists was fair (81%; PABAK = 0.62). With regard to typical CXR findings for pCAP, chance corrected interrater agreement was highest for pleural effusions, infiltrates, and consolidations and lowest for interstitial patterns and peribronchial thickening. Our data show a poor interobserver agreement in the CXR‐based diagnosis of pCAP and emphasized the need for harmonized interpretation standards.
KW - antibiotic therapy
KW - imaging
KW - infections: pneumonia
KW - TB
KW - viral
Y1 - 2021
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-244705
VL - 56
IS - 8
SP - 2676
EP - 2685
ER -
TY - JOUR
A1 - Bässler, Claus
A1 - Brandl, Roland
A1 - Müller, Jörg
A1 - Krah, Franz S.
A1 - Reinelt, Arthur
A1 - Halbwachs, Hans
T1 - Global analysis reveals an environmentally driven latitudinal pattern in mushroom size across fungal species
JF - Ecology Letters
N2 - Although macroecology is a well‐established field, much remains to be learned about the large‐scale variation of fungal traits. We conducted a global analysis of mean fruit body size of 59 geographical regions worldwide, comprising 5340 fungal species exploring the response of fruit body size to latitude, resource availability and temperature. The results showed a hump‐shaped relationship between mean fruit body size and distance to the equator. Areas with large fruit bodies were characterised by a high seasonality and an intermediate mean temperature. The responses of mutualistic species and saprotrophs were similar. These findings support the resource availability hypothesis, predicting large fruit bodies due to a seasonal resource surplus, and the thermoregulation hypothesis, according to which small fruit bodies offer a strategy to avoid heat and cold stress and therefore occur at temperature extremes. Fruit body size may thus be an adaptive trait driving the large‐scale distribution of fungal species.
KW - Fungal traits
KW - global biomes
KW - latitudinal gradient
KW - mean fruit body size
KW - saprobic and ectomycorrhizal basidiomycetes
Y1 - 2021
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-239808
VL - 24
IS - 4
SP - 658
EP - 667
ER -
TY - JOUR
A1 - Beierlein, J.
A1 - Egorov, O. A.
A1 - Harder, T. H.
A1 - Gagel, P.
A1 - Emmerling, M.
A1 - Schneider, C.
A1 - Höfling, S.
A1 - Peschel, U.
A1 - Klembt, S.
T1 - Bloch Oscillations of Hybrid Light‐Matter Particles in a Waveguide Array
JF - Advanced Optical Materials
N2 - Bloch oscillations are a phenomenon well known from quantum mechanics where electrons in a lattice experience an oscillatory motion in the presence of an electric field gradient. Here, the authors report on Bloch oscillations of hybrid light−matter particles, called exciton‐polaritons (polaritons), being confined in an array of coupled microcavity waveguides. To this end, the waveguide widths and their mutual couplings are carefully designed such that a constant energy gradient is induced perpendicular to the direction of motion of the propagating polaritons. This technique allows us to directly observe and study Bloch oscillations in real‐ and momentum‐space. Furthermore, the experimental findings are supported by numerical simulations based on a modified Gross–Pitaevskii approach. This work provides an important transfer of basic concepts of quantum mechanics to integrated solid state devices, using quantum fluids of light.
KW - Bloch oscillations
KW - exciton‐polaritons
KW - polariton condensation
KW - waveguides
Y1 - 2021
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-239814
VL - 9
IS - 13
ER -
TY - JOUR
A1 - Stangl, Stephanie
A1 - Rauch, Sebastian
A1 - Rauh, Jürgen
A1 - Meyer, Martin
A1 - Müller‐Nordhorn, Jacqueline
A1 - Wildner, Manfred
A1 - Wöckel, Achim
A1 - Heuschmann, Peter U.
T1 - Disparities in Accessibility to Evidence-Based
Breast Cancer Care Facilities by Rural and Urban Areas in Bavaria, Germany
JF - Cancer
N2 - Background
Breast cancer (BC), which is most common in elderly women, requires a multidisciplinary and continuous approach to care. With demographic changes, the number of patients with chronic diseases such as BC will increase. This trend will especially hit rural areas, where the majority of the elderly live, in terms of comprehensive health care.
Methods
Accessibility to several cancer facilities in Bavaria, Germany, was analyzed with a geographic information system. Facilities were identified from the national BC guideline and from 31 participants in a proof‐of‐concept study from the Breast Cancer Care for Patients With Metastatic Disease registry. The timeframe for accessibility was defined as 30 or 60 minutes for all population points. The collection of address information was performed with different sources (eg, a physician registry). Routine data from the German Census 2011 and the population‐based Cancer Registry of Bavaria were linked at the district level.
Results
Females from urban areas (n = 2,938,991 [ie, total of females living in urban areas]) had a higher chance for predefined accessibility to the majority of analyzed facilities in comparison with females from rural areas (n = 3,385,813 [ie, total number of females living in rural areas]) with an odds ratio (OR) of 9.0 for cancer information counselling, an OR of 17.2 for a university hospital, and an OR of 7.2 for a psycho‐oncologist. For (inpatient) rehabilitation centers (OR, 0.2) and genetic counselling (OR, 0.3), women from urban areas had lower odds of accessibility within 30 or 60 minutes.
Conclusions
Disparities in accessibility between rural and urban areas exist in Bavaria. The identification of underserved areas can help to inform policymakers about disparities in comprehensive health care. Future strategies are needed to deliver high‐quality health care to all inhabitants, regardless of residence.
KW - accessibility
KW - breast cancer
KW - evidence‐based medicine
KW - geographic information science
KW - health care service research
Y1 - 2021
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-239854
VL - 127
IS - 13
SP - 2319
EP - 2332
ER -
TY - JOUR
A1 - Höhne, Christin
A1 - Prokopov, Dmitry
A1 - Kuhl, Heiner
A1 - Du, Kang
A1 - Klopp, Christophe
A1 - Wuertz, Sven
A1 - Trifonov, Vladimir
A1 - Stöck, Matthias
T1 - The immune system of sturgeons and paddlefish (Acipenseriformes): a review with new data from a chromosome‐scale sturgeon genome
JF - Reviews in Aquaculture
N2 - Sturgeon immunity is relevant for basic evolutionary and applied research, including caviar‐ and meat‐producing aquaculture, protection of wild sturgeons and their re‐introduction through conservation aquaculture. Starting from a comprehensive overview of immune organs, we discuss pathways of innate and adaptive immune systems in a vertebrate phylogenetic and genomic context. The thymus as a key organ of adaptive immunity in sturgeons requires future molecular studies. Likewise, data on immune functions of sturgeon‐specific pericardial and meningeal tissues are largely missing. Integrating immunological and endocrine functions, the sturgeon head kidney resembles that of teleosts. Recently identified pattern recognition receptors in sturgeon require research on downstream regulation. We review first acipenseriform data on Toll‐like receptors (TLRs), type I transmembrane glycoproteins expressed in membranes and endosomes, initiating inflammation and host defence by molecular pattern‐induced activation. Retinoic acid‐inducible gene‐I‐like (RIG‐like) receptors of sturgeons present RNA and key sensors of virus infections in most cell types. Sturgeons and teleosts share major components of the adaptive immune system, including B cells, immunoglobulins, major histocompatibility complex and the adaptive cellular response by T cells. The ontogeny of the sturgeon innate and onset of adaptive immune genes in different organs remain understudied. In a genomics perspective, our new data on 100 key immune genes exemplify a multitude of evolutionary trajectories after the sturgeon‐specific genome duplication, where some single‐copy genes contrast with many duplications, allowing tissue specialization, sub‐functionalization or both. Our preliminary conclusion should be tested by future evolutionary bioinformatics, involving all >1000 immunity genes. This knowledge update about the acipenseriform immune system identifies several important research gaps and presents a basis for future applications.
KW - evolution
KW - genomics
KW - immune genes
KW - immune organs
KW - immune system
KW - sturgeon
Y1 - 2021
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-239865
VL - 13
IS - 3
SP - 1709
EP - 1729
ER -
TY - JOUR
A1 - Ziegler, Georg C.
A1 - Ehlis, Ann-Christine
A1 - Weber, Heike
A1 - Vitale, Maria Rosaria
A1 - Zöller, Johanna E. M.
A1 - Ku, Hsing-Ping
A1 - Schiele, Miriam A.
A1 - Kürbitz, Laura I.
A1 - Romanos, Marcel
A1 - Pauli, Paul
A1 - Kalisch, Raffael
A1 - Zwanzger, Peter
A1 - Domschke, Katharina
A1 - Fallgatter, Andreas J.
A1 - Reif, Andreas
A1 - Lesch, Klaus-Peter
T1 - A Common CDH13 Variant is Associated with Low Agreeableness and Neural Responses to Working Memory Tasks in ADHD
JF - Genes
N2 - The cell—cell signaling gene CDH13 is associated with a wide spectrum of neuropsychiatric disorders, including attention-deficit/hyperactivity disorder (ADHD), autism, and major depression. CDH13 regulates axonal outgrowth and synapse formation, substantiating its relevance for neurodevelopmental processes. Several studies support the influence of CDH13 on personality traits, behavior, and executive functions. However, evidence for functional effects of common gene variation in the CDH13 gene in humans is sparse. Therefore, we tested for association of a functional intronic CDH13 SNP rs2199430 with ADHD in a sample of 998 adult patients and 884 healthy controls. The Big Five personality traits were assessed by the NEO-PI-R questionnaire. Assuming that altered neural correlates of working memory and cognitive response inhibition show genotype-dependent alterations, task performance and electroencephalographic event-related potentials were measured by n-back and continuous performance (Go/NoGo) tasks. The rs2199430 genotype was not associated with adult ADHD on the categorical diagnosis level. However, rs2199430 was significantly associated with agreeableness, with minor G allele homozygotes scoring lower than A allele carriers. Whereas task performance was not affected by genotype, a significant heterosis effect limited to the ADHD group was identified for the n-back task. Heterozygotes (AG) exhibited significantly higher N200 amplitudes during both the 1-back and 2-back condition in the central electrode position Cz. Consequently, the common genetic variation of CDH13 is associated with personality traits and impacts neural processing during working memory tasks. Thus, CDH13 might contribute to symptomatic core dysfunctions of social and cognitive impairment in ADHD.
KW - ADHD
KW - CDH13
KW - neurodevelopment
KW - executive functions
KW - working memory
KW - Big Five
KW - agreeableness
Y1 - 2021
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-245220
SN - 2073-4425
VL - 12
IS - 9
ER -
TY - JOUR
A1 - Job, Hubert
A1 - Bittlingmaier, Sarah
A1 - Mayer, Marius
A1 - von Ruschkowski, Eick
A1 - Woltering, Manuel
T1 - Park−People Relationships: The Socioeconomic Monitoring of National Parks in Bavaria, Germany
JF - Sustainability
N2 - Questions about park–people relationships and the understanding and handling of the conflicts that may result from the creation and management of national parks in the surrounding area are prerequisites for both successful park management and sustainable rural tourism development. This paper analyzes the roles that research may play in relation to park–people relationships in the context of the two oldest German national parks located in Bavaria. The different fields of action of national parks are used to identify the potential for conflict, using detailed case studies from the Bavarian Forest and Berchtesgaden National Parks using quantitative population surveys carried out in 2018. The overall attitude towards both national parks is overwhelmingly positive, with trust towards park administrations and the perceived economic benefits from rural tourism being the attitudes most strongly correlated to the overall level of park–people relationships. Nevertheless, some points of contention still exist, like the ecological integrity approach towards strict nature conservation and related landscape changes (e.g., deadwood cover). A comparison over time shows in both cases that the spatial proximity to the protected area negatively influences people’s attitudes towards the parks, but less so than in the past. Recommendations for national park management include communicating proactively and with greater transparency with locals and decision-makers, to identify conflicts earlier and, where possible, to eliminate them. Furthermore, developing a standardized method to monitor park–people relationships in Germany is a must and would benefit integrated approaches in research and management based on conservation social science.
KW - park–people relationships
KW - rural tourism
KW - Germany
KW - Bavaria
KW - conflicts
KW - national parks
KW - Berchtesgaden
KW - Bavarian Forest
Y1 - 2021
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-245061
SN - 2071-1050
VL - 13
IS - 16
ER -
TY - JOUR
A1 - Kastner, Carolin
A1 - Hendricks, Anne
A1 - Deinlein, Hanna
A1 - Hankir, Mohammed
A1 - Germer, Christoph-Thomas
A1 - Schmidt, Stefanie
A1 - Wiegering, Armin
T1 - Organoid Models for Cancer Research — From Bed to Bench Side and Back
JF - Cancers
N2 - Simple Summary
Despite significant strides in multimodal therapy, cancers still rank within the first three causes of death especially in industrial nations. A lack of individualized approaches and accurate preclinical models are amongst the major barriers that limit the development of novel therapeutic options and drugs. Recently, the 3D culture system of organoids was developed which stably retains the genetic and phenotypic characteristics of the original tissue, healthy as well as diseased. In this review, we summarize current data and evidence on the relevance and reliability of such organoid culture systems in cancer research, focusing on their role in drug investigations (in a personalized manner).
Abstract
Organoids are a new 3D ex vivo culture system that have been applied in various fields of biomedical research. First isolated from the murine small intestine, they have since been established from a wide range of organs and tissues, both in healthy and diseased states. Organoids genetically, functionally and phenotypically retain the characteristics of their tissue of origin even after multiple passages, making them a valuable tool in studying various physiologic and pathophysiologic processes. The finding that organoids can also be established from tumor tissue or can be engineered to recapitulate tumor tissue has dramatically increased their use in cancer research. In this review, we discuss the potential of organoids to close the gap between preclinical in vitro and in vivo models as well as clinical trials in cancer research focusing on drug investigation and development.
KW - cancer
KW - tumor disease
KW - organoid
KW - patient-derived organoid (PDOs)
KW - patient-derived tumor organoid (PDTO)
Y1 - 2021
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-246307
SN - 2072-6694
VL - 13
IS - 19
ER -
TY - JOUR
A1 - Wroński, Piotr Andrzej
A1 - Wyborski, Paweł
A1 - Musiał, Anna
A1 - Podemski, Paweł
A1 - Sęk, Grzegorz
A1 - Höfling, Sven
A1 - Jabeen, Fauzia
T1 - Metamorphic Buffer Layer Platform for 1550 nm Single-Photon Sources Grown by MBE on (100) GaAs Substrate
JF - Materials
N2 - We demonstrate single-photon emission with a low probability of multiphoton events of 5% in the C-band of telecommunication spectral range of standard silica fibers from molecular beam epitaxy grown (100)-GaAs-based structure with InAs quantum dots (QDs) on a metamorphic buffer layer. For this purpose, we propose and implement graded In content digitally alloyed InGaAs metamorphic buffer layer with maximal In content of 42% and GaAs/AlAs distributed Bragg reflector underneath to enhance the extraction efficiency of QD emission. The fundamental limit of the emission rate for the investigated structures is 0.5 GHz based on an emission lifetime of 1.95 ns determined from time-resolved photoluminescence. We prove the relevance of a proposed technology platform for the realization of non-classical light sources in the context of fiber-based quantum communication applications.
KW - single-photon source
KW - quantum dots
KW - telecommunication spectral range
KW - metamorphic buffer layer
Y1 - 2021
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-246145
SN - 1996-1944
VL - 14
IS - 18
ER -
TY - JOUR
A1 - Lüdemann, Martin
A1 - Jakuscheit, Axel
A1 - Ewald, Andrea
A1 - Frühmann, Leena
A1 - Hölscher-Doht, Stefanie
A1 - Rudert, Maximilian
A1 - von Hertzberg-Boelch, Sebastian Philipp
T1 - Influence of Tranexamic Acid on Elution Characteristics and Compressive Strength of Antibiotic-Loaded PMMA-Bone Cement with Gentamicin
JF - Materials
N2 - Purpose: The topical application of tranexamic acid (TXA) into the joint space during total joint arthroplasty (TJA) with no increase of complications, has been widely reported. We investigated the influence of TXA on antibiotic release, activity of the released antibiotic against a clinical isolate of S. aureus, and compressive strength of a widely used commercially prepared gentamicin-loaded cement brand (PALACOS R + G). Method: 12 bone cement cylinders (diameter and height = 6 and 12 mm, respectively) were molded. After curing in air for at least 1 h, six of the cylinders were completely immersed in 5 mL of fetal calf serum (FCS) and the other six were completely immersed in a solution consisting of 4.9 mL of FCS and 0.1 mL (10 mg) of TXA. Gentamicin elution tests were performed over 7 d. Four hundred µL of the gentamicin eluate were taken every 24 h for the first 7 d without renewing the immersion fluid. The gentamicin concentration was determined in a clinical analyzer using a homogeny enzyme immuno-assay. The antimicrobial activity of the eluate, obtained after day 7, was tested. An agar diffusion test regime was used with Staphylococcus aureus. Bacteria were grown in a LB medium and plated on LB agar plates to get a bacterial lawn. Fifty µL of each eluate were pipetted on 12-mm diameter filter discs, which were placed in the middle of the agar gel. After 24 h of cultivation at 37 °C, the zone of inhibition (ZOI) for each specimen was measured. The compressive strength of the cements was determined per ISO 5833. Results: At each time point in the gentamicin release test, the difference in gentamicin concentration, obtained from specimens immersed in the FCS solution only and those immersed in the FCS + TXA solution was not significant (p = 0.055–0.522). The same trend was seen in each of the following parameters, after 7 d of immersion: (1) Cumulative gentamicin concentration (p < 0.297); (2) gentamicin activity against S. aureus (strongly visible); (3) ZOI size (mostly > 20 mm) (p = 0.631); and (4) compressive strength (p = 0.262). Conclusions: For the PALACOS R + G specimens, the addition of TXA to FCS does not produce significant decreases in gentamicin concentration, in the activity of the gentamicin eluate against a clinical isolate of S. aureus, the zone of inhibition of S. aureus, and in the compressive strength of the cement, after 7 d of immersion in the test solution.
KW - gentamicin-loaded poly (methyl methacrylate) bone cement
KW - total joint arthroplasty
KW - total knee arthroplasty
KW - tranexamic acid
Y1 - 2021
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-246236
SN - 1996-1944
VL - 14
IS - 19
ER -
TY - JOUR
A1 - Ockermann, Philipp
A1 - Headley, Laura
A1 - Lizio, Rosario
A1 - Hansmann, Jan
T1 - A Review of the Properties of Anthocyanins and Their Influence on Factors Affecting Cardiometabolic and Cognitive Health
JF - Nutrients
N2 - The incidence of cardiovascular and metabolic diseases has increased over the last decades and is an important cause of death worldwide. An upcoming ingredient on the nutraceutical market are anthocyanins, a flavonoid subgroup, abundant mostly in berries and fruits. Epidemiological studies have suggested an association between anthocyanin intake and improved cardiovascular risk, type 2 diabetes and myocardial infarct. Clinical studies using anthocyanins have shown a significant decrease in inflammation markers and oxidative stress, a beneficial effect on vascular function and hyperlipidemia by decreasing low-density lipoprotein and increasing high-density lipoprotein. They have also shown a potential effect on glucose homeostasis and cognitive decline. This review summarizes the effects of anthocyanins in in-vitro, animal and human studies to give an overview of their application in medical prevention or as a dietary supplement.
KW - anthocyanins
KW - antioxidative
KW - blood pressure
KW - hyperlipidemia
KW - diabetes
KW - inflammation
Y1 - 2021
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-245116
SN - 2072-6643
VL - 13
IS - 8
ER -
TY - JOUR
A1 - Marquardt, André
A1 - Landwehr, Laura-Sophie
A1 - Ronchi, Cristina L.
A1 - di Dalmazi, Guido
A1 - Riester, Anna
A1 - Kollmannsberger, Philip
A1 - Altieri, Barbara
A1 - Fassnacht, Martin
A1 - Sbiera, Silviu
T1 - Identifying New Potential Biomarkers in Adrenocortical Tumors Based on mRNA Expression Data Using Machine Learning
JF - Cancers
N2 - Simple Summary
Using a visual-based clustering method on the TCGA RNA sequencing data of a large adrenocortical carcinoma (ACC) cohort, we were able to classify these tumors in two distinct clusters largely overlapping with previously identified ones. As previously shown, the identified clusters also correlated with patient survival. Applying the visual clustering method to a second dataset also including benign adrenocortical samples additionally revealed that one of the ACC clusters is more closely located to the benign samples, providing a possible explanation for the better survival of this ACC cluster. Furthermore, the subsequent use of machine learning identified new possible biomarker genes with prognostic potential for this rare disease, that are significantly differentially expressed in the different survival clusters and should be further evaluated.
Abstract
Adrenocortical carcinoma (ACC) is a rare disease, associated with poor survival. Several “multiple-omics” studies characterizing ACC on a molecular level identified two different clusters correlating with patient survival (C1A and C1B). We here used the publicly available transcriptome data from the TCGA-ACC dataset (n = 79), applying machine learning (ML) methods to classify the ACC based on expression pattern in an unbiased manner. UMAP (uniform manifold approximation and projection)-based clustering resulted in two distinct groups, ACC-UMAP1 and ACC-UMAP2, that largely overlap with clusters C1B and C1A, respectively. However, subsequent use of random-forest-based learning revealed a set of new possible marker genes showing significant differential expression in the described clusters (e.g., SOAT1, EIF2A1). For validation purposes, we used a secondary dataset based on a previous study from our group, consisting of 4 normal adrenal glands and 52 benign and 7 malignant tumor samples. The results largely confirmed those obtained for the TCGA-ACC cohort. In addition, the ENSAT dataset showed a correlation between benign adrenocortical tumors and the good prognosis ACC cluster ACC-UMAP1/C1B. In conclusion, the use of ML approaches re-identified and redefined known prognostic ACC subgroups. On the other hand, the subsequent use of random-forest-based learning identified new possible prognostic marker genes for ACC.
KW - adrenocortical carcinoma
KW - in silico analysis
KW - machine learning
KW - bioinformatic clustering
KW - biomarker prediction
Y1 - 2021
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-246245
SN - 2072-6694
VL - 13
IS - 18
ER -
TY - JOUR
A1 - Seibel, Sebastian
A1 - Volmer, Judith
T1 - A Diary Study on Anticipated Leisure Time, Morning Recovery, and Employees’ Work Engagement
JF - International Journal of Environmental Research and Public Health
N2 - Recovery during yesterday’s leisure time is beneficial for morning recovery, and morning recovery fosters employees’ work engagement, a positive, motivational state associated with job performance. We extended existing research by assuming that both, morning recovery (considered a resource) and anticipated leisure time (considered an anticipated resource gain), relate to work engagement. Anticipated leisure time comprises two constructs: general anticipation of leisure time, which refers to employees’ cognitive evaluation of their entire upcoming leisure time, and pleasant anticipation of a planned leisure activity, which describes a positive affective reaction because of one specific, upcoming leisure activity. We suggested that employees with high pleasant anticipation generate more thoughts of a planned leisure activity (ToPLA), which may distract them from their work, reducing their work engagement. A diary study over five days showed that morning recovery and general anticipation of leisure time were positively related to work engagement. Furthermore, employees with higher pleasant anticipation of a planned leisure activity reported more ToPLA. In contrast to our expectations, neither pleasant anticipation nor ToPLA was related to work engagement. In sum, this study introduced anticipated leisure time as a novel antecedent of work engagement and demonstrated that anticipated resource gains are important for high work engagement.
KW - morning recovery
KW - leisure time
KW - pleasant anticipation
KW - work engagement
KW - thoughts of a planned leisure activity
KW - diary study
Y1 - 2021
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-246090
SN - 1660-4601
VL - 18
IS - 18
ER -
TY - JOUR
A1 - Pereira, Ana Rita
A1 - Lipphaus, Andreas
A1 - Ergin, Mert
A1 - Salehi, Sahar
A1 - Gehweiler, Dominic
A1 - Rudert, Maximilian
A1 - Hansmann, Jan
A1 - Herrmann, Marietta
T1 - Modeling of the Human Bone Environment: Mechanical Stimuli Guide Mesenchymal Stem Cell−Extracellular Matrix Interactions
JF - Materials
N2 - In bone tissue engineering, the design of in vitro models able to recreate both the chemical composition, the structural architecture, and the overall mechanical environment of the native tissue is still often neglected. In this study, we apply a bioreactor system where human bone-marrow hMSCs are seeded in human femoral head-derived decellularized bone scaffolds and subjected to dynamic culture, i.e., shear stress induced by continuous cell culture medium perfusion at 1.7 mL/min flow rate and compressive stress by 10% uniaxial load at 1 Hz for 1 h per day. In silico modeling revealed that continuous medium flow generates a mean shear stress of 8.5 mPa sensed by hMSCs seeded on 3D bone scaffolds. Experimentally, both dynamic conditions improved cell repopulation within the scaffold and boosted ECM production compared with static controls. Early response of hMSCs to mechanical stimuli comprises evident cell shape changes and stronger integrin-mediated adhesion to the matrix. Stress-induced Col6 and SPP1 gene expression suggests an early hMSC commitment towards osteogenic lineage independent of Runx2 signaling. This study provides a foundation for exploring the early effects of external mechanical stimuli on hMSC behavior in a biologically meaningful in vitro environment, opening new opportunities to study bone development, remodeling, and pathologies.
KW - bone tissue engineering
KW - human trabecular bone decellularization
KW - in vitro modeling
KW - shear stress
KW - compressive load
KW - fluid simulation
KW - cell-matrix interaction
KW - mechanotransduction
Y1 - 2021
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-245012
SN - 1996-1944
VL - 14
IS - 16
ER -
TY - JOUR
A1 - Rieser, Jakob
A1 - Veste, Maik
A1 - Thiel, Michael
A1 - Schönbrodt-Stitt, Sarah
T1 - Coverage and Rainfall Response of Biological Soil Crusts Using Multi-Temporal Sentinel-2 Data in a Central European Temperate Dry Acid Grassland
JF - Remote Sensing
N2 - Biological soil crusts (BSCs) are thin microbiological vegetation layers that naturally develop in unfavorable higher plant conditions (i.e., low precipitation rates and high temperatures) in global drylands. They consist of poikilohydric organisms capable of adjusting their metabolic activities depending on the water availability. However, they, and with them, their ecosystem functions, are endangered by climate change and land-use intensification. Remote sensing (RS)-based studies estimated the BSC cover in global drylands through various multispectral indices, and few of them correlated the BSCs’ activity response to rainfall. However, the allocation of BSCs is not limited to drylands only as there are areas beyond where smaller patches have developed under intense human impact and frequent disturbance. Yet, those areas were not addressed in RS-based studies, raising the question of whether the methods developed in extensive drylands can be transferred easily. Our temperate climate study area, the ‘Lieberoser Heide’ in northeastern Germany, is home to the country’s largest BSC-covered area. We applied a Random Forest (RF) classification model incorporating multispectral Sentinel-2 (S2) data, indices derived from them, and topographic information to spatiotemporally map the BSC cover for the first time in Central Europe. We further monitored the BSC response to rainfall events over a period of around five years (June 2015 to end of December 2020). Therefore, we combined datasets of gridded NDVI as a measure of photosynthetic activity with daily precipitation data and conducted a change detection analysis. With an overall accuracy of 98.9%, our classification proved satisfactory. Detected changes in BSC activity between dry and wet conditions were found to be significant. Our study emphasizes a high transferability of established methods from extensive drylands to BSC-covered areas in the temperate climate. Therefore, we consider our study to provide essential impulses so that RS-based biocrust mapping in the future will be applied beyond the global drylands.
KW - biocrusts activity
KW - random forest classification
KW - rainfall response
KW - Sentinel-2 multispectral indices
KW - change detection
KW - Lieberoser Heide
Y1 - 2021
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-245006
SN - 2072-4292
VL - 13
IS - 16
ER -
TY - JOUR
A1 - Beierle, Felix
A1 - Schobel, Johannes
A1 - Vogel, Carsten
A1 - Allgaier, Johannes
A1 - Mulansky, Lena
A1 - Haug, Fabian
A1 - Haug, Julian
A1 - Schlee, Winfried
A1 - Holfelder, Marc
A1 - Stach, Michael
A1 - Schickler, Marc
A1 - Baumeister, Harald
A1 - Cohrdes, Caroline
A1 - Deckert, Jürgen
A1 - Deserno, Lorenz
A1 - Edler, Johanna-Sophie
A1 - Eichner, Felizitas A.
A1 - Greger, Helmut
A1 - Hein, Grit
A1 - Heuschmann, Peter
A1 - John, Dennis
A1 - Kestler, Hans A.
A1 - Krefting, Dagmar
A1 - Langguth, Berthold
A1 - Meybohm, Patrick
A1 - Probst, Thomas
A1 - Reichert, Manfred
A1 - Romanos, Marcel
A1 - Störk, Stefan
A1 - Terhorst, Yannik
A1 - Weiß, Martin
A1 - Pryss, Rüdiger
T1 - Corona Health — A Study- and Sensor-Based Mobile App Platform Exploring Aspects of the COVID-19 Pandemic
JF - International Journal of Environmental Research and Public Health
N2 - Physical and mental well-being during the COVID-19 pandemic is typically assessed via surveys, which might make it difficult to conduct longitudinal studies and might lead to data suffering from recall bias. Ecological momentary assessment (EMA) driven smartphone apps can help alleviate such issues, allowing for in situ recordings. Implementing such an app is not trivial, necessitates strict regulatory and legal requirements, and requires short development cycles to appropriately react to abrupt changes in the pandemic. Based on an existing app framework, we developed Corona Health, an app that serves as a platform for deploying questionnaire-based studies in combination with recordings of mobile sensors. In this paper, we present the technical details of Corona Health and provide first insights into the collected data. Through collaborative efforts from experts from public health, medicine, psychology, and computer science, we released Corona Health publicly on Google Play and the Apple App Store (in July 2020) in eight languages and attracted 7290 installations so far. Currently, five studies related to physical and mental well-being are deployed and 17,241 questionnaires have been filled out. Corona Health proves to be a viable tool for conducting research related to the COVID-19 pandemic and can serve as a blueprint for future EMA-based studies. The data we collected will substantially improve our knowledge on mental and physical health states, traits and trajectories as well as its risk and protective factors over the course of the COVID-19 pandemic and its diverse prevention measures.
KW - mobile health
KW - ecological momentary assessment
KW - digital phenotyping
KW - longitudinal studies
KW - mobile crowdsensing
Y1 - 2021
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-242658
SN - 1660-4601
VL - 18
IS - 14
ER -
TY - JOUR
A1 - Ibebuchi, Chibuike Chiedozie
T1 - On the Relationship between Circulation Patterns, the Southern Annular Mode, and Rainfall Variability in Western Cape
JF - Atmosphere
N2 - This study investigates circulation types (CTs) in Africa, south of the equator, that are related to wet and dry conditions in the Western Cape, the statistical relationship between the selected CTs and the Southern Annular Mode (SAM), and changes in the frequency of occurrence of the CTs related to the SAM under the ssp585 scenario. Obliquely rotated principal component analysis applied to sea level pressure (SLP) was used to classify CTs in Africa, south of the equator. Three CTs were found to have a high probability of being associated with wet days in the Western Cape, and four CTs were equally found to have a high probability of being associated with dry days in the Western Cape. Generally, the dry/wet CTs feature the southward/northward track of the mid-latitude cyclone, adjacent to South Africa; anti-cyclonic/cyclonic relative vorticity, and poleward/equatorward track of westerlies, south of South Africa. One of the selected wet CTs was significantly related to variations of the SAM. Years with an above-average SAM index correlated with the below-average frequency of occurrences of the wet CT. The results suggest that through the dynamics of the CT, the SAM might control the rainfall variability of the Western Cape. Under the ssp585 scenario, the analyzed climate models indicated a possible decrease in the frequency of occurrence of the aforementioned wet CT associated with cyclonic activity in the mid-latitudes, and an increase in the frequency of the occurrence of CT associated with enhanced SLP at mid-latitudes.
KW - Western Cape
KW - Southern Annular Mode
KW - circulation type
KW - Africa south of the equator
KW - mid-latitude cyclone
Y1 - 2021
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-241018
SN - 2073-4433
VL - 12
IS - 6
ER -
TY - JOUR
A1 - Popp, Sandy
A1 - Schmitt-Böhrer, Angelika
A1 - Langer, Simon
A1 - Hofmann, Ulrich
A1 - Hommers, Leif
A1 - Schuh, Kai
A1 - Frantz, Stefan
A1 - Lesch, Klaus-Peter
A1 - Frey, Anna
T1 - 5-HTT Deficiency in Male Mice Affects Healing and Behavior after Myocardial Infarction
JF - Journal of Clinical Medicine
N2 - Anxiety disorders and depression are common comorbidities in cardiac patients. Mice lacking the serotonin transporter (5-HTT) exhibit increased anxiety-like behavior. However, the role of 5-HTT deficiency on cardiac aging, and on healing and remodeling processes after myocardial infarction (MI), remains unclear. Cardiological evaluation of experimentally naïve male mice revealed a mild cardiac dysfunction in ≥4-month-old 5-HTT knockout (−/−) animals. Following induction of chronic cardiac dysfunction (CCD) by MI vs. sham operation 5-HTT−/− mice with infarct sizes >30% experienced 100% mortality, while 50% of 5-HTT+/− and 37% of 5-HTT+/+ animals with large MI survived the 8-week observation period. Surviving (sham and MI < 30%) 5-HTT−/− mutants displayed reduced exploratory activity and increased anxiety-like behavior in different approach-avoidance tasks. However, CCD failed to provoke a depressive-like behavioral response in either 5-Htt genotype. Mechanistic analyses were performed on mice 3 days post-MI. Electrocardiography, histology and FACS of inflammatory cells revealed no abnormalities. However, gene expression of inflammation-related cytokines (TGF-β, TNF-α, IL-6) and MMP-2, a protein involved in the breakdown of extracellular matrix, was significantly increased in 5-HTT−/− mice after MI. This study shows that 5-HTT deficiency leads to age-dependent cardiac dysfunction and disrupted early healing after MI probably due to alterations of inflammatory processes in mice.
KW - chronic heart failure
KW - myocardial infarction
KW - serotonin transporter deficient mice
KW - anxiety
KW - depression
KW - behavior
KW - inflammation
Y1 - 2021
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-242739
SN - 2077-0383
VL - 10
IS - 14
ER -
TY - JOUR
A1 - Müller, Dominik
A1 - Graetz, Jonas
A1 - Balles, Andreas
A1 - Stier, Simon
A1 - Hanke, Randolf
A1 - Fella, Christian
T1 - Laboratory-Based Nano-Computed Tomography and Examples of Its Application in the Field of Materials Research
JF - Crystals
N2 - In a comprehensive study, we demonstrate the performance and typical application scenarios for laboratory-based nano-computed tomography in materials research on various samples. Specifically, we focus on a projection magnification system with a nano focus source. The imaging resolution is quantified with common 2D test structures and validated in 3D applications by means of the Fourier Shell Correlation. As representative application examples from nowadays material research, we show metallization processes in multilayer integrated circuits, aging in lithium battery electrodes, and volumetric of metallic sub-micrometer fillers of composites. Thus, the laboratory system provides the unique possibility to image non-destructively structures in the range of 170–190 nanometers, even for high-density materials.
KW - nano CT
KW - laboratory
KW - X-ray
KW - 3D reconstruction
KW - instrumentation
KW - integrated circuits
KW - nondestructive testing
KW - 3D X-ray microscopy
Y1 - 2021
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-241048
SN - 2073-4352
VL - 11
IS - 6
ER -
TY - JOUR
A1 - Othman, Eman M.
A1 - Bekhit, Amany A.
A1 - Anany, Mohamed A.
A1 - Dandekar, Thomas
A1 - Ragab, Hanan M.
A1 - Wahid, Ahmed
T1 - Design, Synthesis, and Anticancer Screening for Repurposed Pyrazolo[3,4-d]pyrimidine Derivatives on Four Mammalian Cancer Cell Lines
JF - Molecules
N2 - The present study reports the synthesis of new purine bioisosteres comprising a pyrazolo[3,4-d]pyrimidine scaffold linked to mono-, di-, and trimethoxy benzylidene moieties through hydrazine linkages. First, in silico docking experiments of the synthesized compounds against Bax, Bcl-2, Caspase-3, Ki67, p21, and p53 were performed in a trial to rationalize the observed cytotoxic activity for the tested compounds. The anticancer activity of these compounds was evaluated in vitro against Caco-2, A549, HT1080, and Hela cell lines. Results revealed that two (5 and 7) of the three synthesized compounds (5, 6, and 7) showed high cytotoxic activity against all tested cell lines with IC50 values in the micro molar concentration. Our in vitro results show that there is no significant apoptotic effect for the treatment with the experimental compounds on the viability of cells against A549 cells. Ki67 expression was found to decrease significantly following the treatment of cells with the most promising candidate: drug 7. The overall results indicate that these pyrazolopyrimidine derivatives possess anticancer activity at varying doses. The suggested mechanism of action involves the inhibition of the proliferation of cancer cells.
KW - pyrazolo[3,4-d]pyrimidine
KW - anticancer activity
KW - apoptosis
KW - Ki67
Y1 - 2021
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-239734
SN - 1420-3049
VL - 26
IS - 10
ER -
TY - JOUR
A1 - Notz, Quirin
A1 - Herrmann, Johannes
A1 - Schlesinger, Tobias
A1 - Helmer, Philipp
A1 - Sudowe, Stephan
A1 - Sun, Qian
A1 - Hackler, Julian
A1 - Roeder, Daniel
A1 - Lotz, Christopher
A1 - Meybohm, Patrick
A1 - Kranke, Peter
A1 - Schomburg, Lutz
A1 - Stoppe, Christian
T1 - Clinical Significance of Micronutrient Supplementation in Critically Ill COVID-19 Patients with Severe ARDS
JF - Nutrients
N2 - The interplay between inflammation and oxidative stress is a vicious circle, potentially resulting in organ damage. Essential micronutrients such as selenium (Se) and zinc (Zn) support anti-oxidative defense systems and are commonly depleted in severe disease. This single-center retrospective study investigated micronutrient levels under Se and Zn supplementation in critically ill patients with COVID-19 induced acute respiratory distress syndrome (ARDS) and explored potential relationships with immunological and clinical parameters. According to intensive care unit (ICU) standard operating procedures, patients received 1.0 mg of intravenous Se daily on top of artificial nutrition, which contained various amounts of Se and Zn. Micronutrients, inflammatory cytokines, lymphocyte subsets and clinical data were extracted from the patient data management system on admission and after 10 to 14 days of treatment. Forty-six patients were screened for eligibility and 22 patients were included in the study. Twenty-one patients (95%) suffered from severe ARDS and 14 patients (64%) survived to ICU discharge. On admission, the majority of patients had low Se status biomarkers and Zn levels, along with elevated inflammatory parameters. Se supplementation significantly elevated Se (p = 0.027) and selenoprotein P levels (SELENOP; p = 0.016) to normal range. Accordingly, glutathione peroxidase 3 (GPx3) activity increased over time (p = 0.021). Se biomarkers, most notably SELENOP, were inversely correlated with CRP (r\(_s\) = −0.495), PCT (r\(_s\) = −0.413), IL-6 (r\(_s\) = −0.429), IL-1β (r\(_s\) = −0.440) and IL-10 (r\(_s\) = −0.461). Positive associations were found for CD8\(^+\) T cells (r(_s\) = 0.636), NK cells (r\(_s\) = 0.772), total IgG (r\(_s\) = 0.493) and PaO\(_2\)/FiO\(_2\) ratios (r\(_s\) = 0.504). In addition, survivors tended to have higher Se levels after 10 to 14 days compared to non-survivors (p = 0.075). Sufficient Se and Zn levels may potentially be of clinical significance for an adequate immune response in critically ill patients with severe COVID-19 ARDS.
KW - acute respiratory distress syndrome
KW - selen
KW - zinc
KW - critical care
KW - oxidative stress
KW - nutrient supplementation
Y1 - 2021
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-241112
SN - 2072-6643
VL - 13
IS - 6
ER -
TY - JOUR
A1 - Loh, Frank
A1 - Poignée, Fabian
A1 - Wamser, Florian
A1 - Leidinger, Ferdinand
A1 - Hoßfeld, Tobias
T1 - Uplink vs. Downlink: Machine Learning-Based Quality Prediction for HTTP Adaptive Video Streaming
JF - Sensors
N2 - Streaming video is responsible for the bulk of Internet traffic these days. For this reason, Internet providers and network operators try to make predictions and assessments about the streaming quality for an end user. Current monitoring solutions are based on a variety of different machine learning approaches. The challenge for providers and operators nowadays is that existing approaches require large amounts of data. In this work, the most relevant quality of experience metrics, i.e., the initial playback delay, the video streaming quality, video quality changes, and video rebuffering events, are examined using a voluminous data set of more than 13,000 YouTube video streaming runs that were collected with the native YouTube mobile app. Three Machine Learning models are developed and compared to estimate playback behavior based on uplink request information. The main focus has been on developing a lightweight approach using as few features and as little data as possible, while maintaining state-of-the-art performance.
KW - HTTP adaptive video streaming
KW - quality of experience prediction
KW - machine learning
Y1 - 2021
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-241121
SN - 1424-8220
VL - 21
IS - 12
ER -
TY - JOUR
A1 - Genest, Franca
A1 - Rak, Dominik
A1 - Bätz, Elisa
A1 - Ott, Kerstin
A1 - Seefried, Lothar
T1 - Sarcopenia and Malnutrition Screening in Female Osteoporosis Patients — A Cross-Sectional Study
JF - Journal of Clinical Medicine
N2 - Sarcopenia and malnutrition are important determinants of increased fracture risk in osteoporosis. SARC-F and MNA-SF are well-established questionnaires for identifying patients at risk for these conditions. We sought to evaluate the feasibility and potential added benefit of such assessments as well as the actual prevalence of these conditions in osteoporosis patients. We conducted a cross-sectional, single-center study in female osteoporosis patients ≥ 65 years (SaNSiBaR-study). Results of the sarcopenia (SARC-F) and malnutrition (MNA-SF) screening questionnaires were matched with a functional assessment for sarcopenia and data from patients’ medical records. Out of 107 patients included in the analysis, a risk for sarcopenia (SARC-F ≥ 4 points) and a risk for malnutrition (MNA-SF ≤ 11 points) was found in 33 (30.8%) and 38 (35.5%) patients, respectively. Diagnostic overlap with coincident indicative findings in both questionnaires was observed in 17 patients (16%). As compared to the respective not-at-risk groups, the mean short physical performance battery (SPPB) score was significantly reduced in both patients at risk for sarcopenia (7.0 vs. 10.9 points, p < 0.001) and patients at risk for malnutrition (8.7 vs. 10.5 points, p = 0.005). Still, confirmed sarcopenia according to EWGSOP2 criteria was present in only 6 (6%) of all 107 patients, with only 3 of them having an indicative SARC-F score. Bone mineral density was not significantly different in any of the at-risk groups at any site. In summary, applying SARC-F and MNA-SF in osteoporosis patients appears to be a complementary approach to identify individuals with functional deficits.
KW - osteoporosis
KW - malnourishment
KW - sarcopenia
KW - nutritional status
KW - physical performance
Y1 - 2021
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-239658
SN - 2077-0383
VL - 10
IS - 11
ER -
TY - JOUR
A1 - Ickrath, Pascal
A1 - Sprügel, Lisa
A1 - Beyersdorf, Niklas
A1 - Scherzad, Agmal
A1 - Hagen, Rudolf
A1 - Hackenberg, Stephan
T1 - Detection of Candida albicans-Specific CD4+ and CD8+ T Cells in the Blood and Nasal Mucosa of Patients with Chronic Rhinosinusitis
JF - Journal of Fungi
N2 - Candida albicans is ubiquitously present, and colonization in the nose and oral cavity is common. In healthy patients, it usually does not act as a pathogen, but in some cases can cause diseases. The influence of C. albicans as a trigger of T cell activation on the pathogenesis of chronic rhinosinusitis (CRS) is controversial, and its exact role is not clear to date. The aim of the present study was to detect and characterize C. albicans-specific CD4+ and CD8+ T cells in patients with CRS, with and without nasal polyps. Tissue and blood samples were collected from patients suffering from chronic rhinosinusitis with (CRSwNP) and without nasal polyps (CRSsNP), and from healthy controls. A peptide pool derived from C. albicans antigen was added to tissue and blood samples. After 6 days, lymphocytes were analyzed by multicolor flow cytometry. Activation was assessed by the intracellular marker Ki-67, and the cytokine secretion was measured. Tissue CD8+ T cells of CRSsNP patients showed a significantly higher proportion of Ki-67+ cells after activation with C. albicans antigen compared to peripheral blood CD8+ T cells. Cytokine secretion in response to C. albicans antigen was similar for all study groups. In this study, C. albicans-specific CD4+ and CD8+ T cells were detected in peripheral blood and mucosal tissue in all study groups. In patients suffering from CRSsNP, C. albicans-specific CD8+ T cells were relatively enriched in the nasal mucosa, suggesting that they might play a role in the pathogenesis of CRSsNP.
KW - Candida albicans
KW - chronic rhinosinusitis
KW - T cell activation
KW - nasal polyps
Y1 - 2021
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-239671
SN - 2309-608X
VL - 7
IS - 6
ER -
TY - JOUR
A1 - Makbul, Cihan
A1 - Khayenko, Vladimir
A1 - Maric, Hans Michael
A1 - Böttcher, Bettina
T1 - Conformational Plasticity of Hepatitis B Core Protein Spikes Promotes Peptide Binding Independent of the Secretion Phenotype
JF - Microorganisms
N2 - Hepatitis B virus is a major human pathogen, which forms enveloped virus particles. During viral maturation, membrane-bound hepatitis B surface proteins package hepatitis B core protein capsids. This process is intercepted by certain peptides with an “LLGRMKG” motif that binds to the capsids at the tips of dimeric spikes. With microcalorimetry, electron cryo microscopy and peptide microarray-based screens, we have characterized the structural and thermodynamic properties of peptide binding to hepatitis B core protein capsids with different secretion phenotypes. The peptide “GSLLGRMKGA” binds weakly to hepatitis B core protein capsids and mutant capsids with a premature (F97L) or low-secretion phenotype (L60V and P5T). With electron cryo microscopy, we provide novel structures for L60V and P5T and demonstrate that binding occurs at the tips of the spikes at the dimer interface, splaying the helices apart independent of the secretion phenotype. Peptide array screening identifies “SLLGRM” as the core binding motif. This shortened motif binds only to one of the two spikes in the asymmetric unit of the capsid and induces a much smaller conformational change. Altogether, these comprehensive studies suggest that the tips of the spikes act as an autonomous binding platform that is unaffected by mutations that affect secretion phenotypes.
KW - hepatitis B core protein
KW - hepatitis B virus
KW - peptide inhibitor of envelopment
KW - isothermal titration calorimetry
KW - electron cryo microscopy
KW - low-secretion phenotype mutants
KW - peptide microarray
Y1 - 2021
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-236720
SN - 2076-2607
VL - 9
IS - 5
ER -
TY - JOUR
A1 - Dölken, Lars
A1 - Stich, August
A1 - Spinner, Christoph D.
T1 - Remdesivir for Early COVID-19 Treatment of High-Risk Individuals Prior to or at Early Disease Onset — Lessons Learned
JF - Viruses
N2 - After more than one year of the COVID-19 pandemic, antiviral treatment options against SARS-CoV-2 are still severely limited. High hopes that had initially been placed on antiviral drugs like remdesivir have so far not been fulfilled. While individual case reports provide striking evidence for the clinical efficacy of remdesivir in the right clinical settings, major trials failed to demonstrate this. Here, we highlight and discuss the key findings of these studies and underlying reasons for their failure. We elaborate on how such shortcomings should be prevented in future clinical trials and pandemics. We suggest in conclusion that any novel antiviral agent that enters human trials should first be tested in a post-exposure setting to provide rapid and solid evidence for its clinical efficacy before initiating further time-consuming and costly clinical trials for more advanced disease. In the COVID-19 pandemic this might have established remdesivir early on as an efficient antiviral agent at a more suitable disease stage which would have saved many lives, in particular in large outbreaks within residential care homes.
KW - COVID-19
KW - SARS-CoV-2
KW - antiviral treatment
KW - remdesivir
Y1 - 2021
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-239648
SN - 1999-4915
VL - 13
IS - 6
ER -
TY - JOUR
A1 - Sbiera, Iuliu
A1 - Kircher, Stefan
A1 - Altieri, Barbara
A1 - Fassnacht, Martin
A1 - Kroiss, Matthias
A1 - Sbiera, Silviu
T1 - Epithelial and Mesenchymal Markers in Adrenocortical Tissues: How Mesenchymal Are Adrenocortical Tissues?
JF - Cancers
N2 - A clinically relevant proportion of adrenocortical carcinoma (ACC) cases shows a tendency to metastatic spread. The objective was to determine whether the epithelial to mesenchymal transition (EMT), a mechanism associated with metastasizing in several epithelial cancers, might play a crucial role in ACC. 138 ACC, 29 adrenocortical adenomas (ACA), three normal adrenal glands (NAG), and control tissue samples were assessed for the expression of epithelial (E-cadherin and EpCAM) and mesenchymal (N-cadherin, SLUG and SNAIL) markers by immunohistochemistry. Using real-time RT-PCR we quantified the alternative isoform splicing of FGFR 2 and 3, another known indicator of EMT. We also assessed the impact of these markers on clinical outcome. Results show that both normal and neoplastic adrenocortical tissues lacked expression of epithelial markers but strongly expressed mesenchymal markers N-cadherin and SLUG. FGFR isoform splicing confirmed higher similarity of adrenocortical tissues to mesenchymal compared to epithelial tissues. In ACC, higher SLUG expression was associated with clinical markers indicating aggressiveness, while N-cadherin expression inversely associated with these markers. In conclusion, we could not find any indication of EMT as all adrenocortical tissues lacked expression of epithelial markers and exhibited closer similarity to mesenchymal tissues. However, while N-cadherin might play a positive role in tissue structure upkeep, SLUG seems to be associated with a more aggressive phenotype.
KW - adrenocortical tissues
KW - EMT
KW - epithelial markers
KW - mesenchymal markers
KW - recurrence-free survival
Y1 - 2021
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-236486
SN - 2072-6694
VL - 13
IS - 7
ER -
TY - JOUR
A1 - Zhou, Yang
A1 - Ding, Meiqi
A1 - Duan, Xiaodong
A1 - Konrad, Kai R.
A1 - Nagel, Georg
A1 - Gao, Shiqiang
T1 - Extending the Anion Channelrhodopsin-Based Toolbox for Plant Optogenetics
JF - Membranes
N2 - Optogenetics was developed in the field of neuroscience and is most commonly using light-sensitive rhodopsins to control the neural activities. Lately, we have expanded this technique into plant science by co-expression of a chloroplast-targeted β-carotene dioxygenase and an improved anion channelrhodopsin GtACR1 from the green alga Guillardia theta. The growth of Nicotiana tabacum pollen tube can then be manipulated by localized green light illumination. To extend the application of analogous optogenetic tools in the pollen tube system, we engineered another two ACRs, GtACR2, and ZipACR, which have different action spectra, light sensitivity and kinetic features, and characterized them in Xenopus laevis oocytes, Nicotiana benthamiana leaves and N. tabacum pollen tubes. We found that the similar molecular engineering method used to improve GtACR1 also enhanced GtACR2 and ZipACR performance in Xenopus laevis oocytes. The ZipACR1 performed in N. benthamiana mesophyll cells and N. tabacum pollen tubes with faster kinetics and reduced light sensitivity, allowing for optogenetic control of anion fluxes with better temporal resolution. The reduced light sensitivity would potentially facilitate future application in plants, grown under low ambient white light, combined with an optogenetic manipulation triggered by stronger green light.
KW - optogenetics
KW - rhodopsin
KW - light-sensitive anion channel
KW - surface potential recording
KW - pollen tube
Y1 - 2021
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-236617
SN - 2077-0375
VL - 11
IS - 4
ER -
TY - JOUR
A1 - Franke, Maximilian
A1 - Bieber, Michael
A1 - Stoll, Guido
A1 - Schuhmann, Michael Klaus
T1 - Validity and Efficacy of Methods to Define Blood Brain Barrier Integrity in Experimental Ischemic Strokes: A Comparison of Albumin Western Blot, IgG Western Blot and Albumin Immunofluorescence
JF - Methods and Protocols
N2 - The clinical and preclinical research of ischemic strokes (IS) is becoming increasingly comprehensive, especially with the emerging evidence of complex thrombotic and inflammatory interactions. Within these, the blood brain barrier (BBB) plays an important role in regulating the cellular interactions at the vascular interface and is therefore the object of many IS-related questions. Consequently, valid, economic and responsible methods to define BBB integrity are necessary. Therefore, we compared the three ex-vivo setups albumin Western blot (WB), IgG WB and albumin intensity measurement (AIM) with regard to validity as well as temporal and economic efficacy. While the informative value of the three methods correlated significantly, the efficacy of the IgG WB dominated.
KW - IgG
KW - albumin
KW - immunohistochemistry
KW - Western blot
KW - stroke
KW - tMCAO
KW - blood brain barrier
KW - neuroinflammation
Y1 - 2021
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-234214
SN - 2409-9279
VL - 4
IS - 1
ER -
TY - JOUR
A1 - von Hertzberg-Boelch, Sebastian Philipp
A1 - Wagenbrenner, Mike
A1 - Arnholdt, Jörg
A1 - Frenzel, Stephan
A1 - Holzapfel, Boris Michael
A1 - Rudert, Maximilian
T1 - Custom Made Monoflange Acetabular Components for the Treatment of Paprosky Type III Defects
JF - Journal of Personalized Medicine
N2 - Purpose: Patient-specific, flanged acetabular components are used for the treatment of Paprosky type III defects during revision total hip arthroplasty (THA). This monocentric retrospective cohort study analyzes the outcome of patients treated with custom made monoflanged acetabular components (CMACs) with intra- and extramedullary iliac fixation. Methods: 14 patients were included who underwent revision THA with CMACs for the treatment of Paprosky type III defects. Mechanism of THA failure was infection in 4 and aseptic loosening in 10 patients. Seven patients underwent no previous revision, the other seven patients underwent three or more previous revisions. Results: At a mean follow-up of 35.4 months (14–94), the revision rate of the implant was 28.3%. Additionally, one perioperative dislocation and one superficial wound infection occurred. At one year postoperatively, we found a significant improvement of the Western Ontario and McMaster Universities Arthritis Index (WOMAC) score (p = 0.015). Postoperative radiographic analysis revealed good hip joint reconstruction with a mean leg length discrepancy of 3 mm (−8–20), a mean lateralization of the horizontal hip center of rotation of 8 mm (−8–35), and a mean proximalization of the vertical hip center of rotation of 6 mm (13–26). Radiolucency lines were present in 30%. Conclusion: CMACs can be considered an option for the treatment of acetabular bone loss in revision THA. Iliac intra- and extramedullary fixation allows soft tissue-adjusted hip joint reconstruction and improves hip function. However, failure rates are high, with periprosthetic infection being the main threat to successful outcome.
KW - patient specific implant
KW - custom made implant
KW - revision hip
KW - Paprosky
KW - pelvic discontinuity
Y1 - 2021
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-236513
SN - 2075-4426
VL - 11
IS - 4
ER -
TY - JOUR
A1 - Appel, Alexandra
A1 - Hardaker, Sina
T1 - Strategies in Times of Pandemic Crisis — Retailers and Regional Resilience in Würzburg, Germany
JF - Sustainability
N2 - Research on the COVID-19 crisis and its implications on regional resilience is still in its infancy. To understand resilience on its aggregate level it is important to identify (non)resilient actions of individual actors who comprise regions. As the retail sector among others represents an important factor in an urban regions recovery, we focus on the resilience of (textile) retailers within the city of Würzburg in Germany to the COVID-19 pandemic. To address the identified research gap, this paper applies the concept of resilience. Firstly, conducting expert interviews, the individual (textile) retailers’ level and their strategies in coping with the crisis is considered. Secondly, conducting a contextual analysis of the German city of Würzburg, we wish to contribute to the discussion of how the resilience of a region is influenced inter alia by actors. Our study finds three main strategies on the individual level, with retailers: (1) intending to “bounce back” to a pre-crisis state, (2) reorganising existing practices, as well as (3) closing stores and winding up business. As at the time of research, no conclusions regarding long-term impacts and resilience are possible, the results are limited. Nevertheless, detailed analysis of retailers’ strategies contributes to a better understanding of regional resilience.
KW - resilience
KW - COVID-19
KW - pandemic crisis
KW - regional resilience
KW - retail
KW - owner-operated retailers
KW - textile sector
KW - Germany
Y1 - 2021
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-233991
SN - 2071-1050
VL - 13
IS - 5
ER -
TY - JOUR
A1 - Yu, Yidong
A1 - Wolf, Ann-Katrin
A1 - Thusek, Sina
A1 - Heinekamp, Thorsten
A1 - Bromley, Michael
A1 - Krappmann, Sven
A1 - Terpitz, Ulrich
A1 - Voigt, Kerstin
A1 - Brakhage, Axel A.
A1 - Beilhack, Andreas
T1 - Direct Visualization of Fungal Burden in Filamentous Fungus-Infected Silkworms
JF - Journal of Fungi
N2 - Invasive fungal infections (IFIs) are difficult to diagnose and to treat and, despite several available antifungal drugs, cause high mortality rates. In the past decades, the incidence of IFIs has continuously increased. More recently, SARS-CoV-2-associated lethal IFIs have been reported worldwide in critically ill patients. Combating IFIs requires a more profound understanding of fungal pathogenicity to facilitate the development of novel antifungal strategies. Animal models are indispensable for studying fungal infections and to develop new antifungals. However, using mammalian animal models faces various hurdles including ethical issues and high costs, which makes large-scale infection experiments extremely challenging. To overcome these limitations, we optimized an invertebrate model and introduced a simple calcofluor white (CW) staining protocol to macroscopically and microscopically monitor disease progression in silkworms (Bombyx mori) infected with the human pathogenic filamentous fungi Aspergillus fumigatus and Lichtheimia corymbifera. This advanced silkworm A. fumigatus infection model could validate knockout mutants with either attenuated, strongly attenuated or unchanged virulence. Finally, CW staining allowed us to efficiently visualize antifungal treatment outcomes in infected silkworms. Conclusively, we here present a powerful animal model combined with a straightforward staining protocol to expedite large-scale in vivo research of fungal pathogenicity and to investigate novel antifungal candidates.
KW - fungal infection model
KW - calcofluor white staining
KW - Aspergillus
KW - Lichtheimia
KW - silkworm
Y1 - 2021
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-228855
SN - 2309-608X
VL - 7
IS - 2
ER -
TY - JOUR
A1 - Kelm, Matthias
A1 - Anger, Friedrich
A1 - Eichlinger, Robin
A1 - Brand, Markus
A1 - Kim, Mia
A1 - Reibetanz, Joachim
A1 - Krajinovic, Katica
A1 - Germer, Christoph-Thomas
A1 - Schlegel, Nicolas
A1 - Flemming, Sven
T1 - Early Ileocecal Resection Is an Effective Therapy in Isolated Crohn’s Disease
JF - Journal of Clinical Medicine
N2 - Despite the increasing incidence and prevalence of Crohn’s Disease (CD), no curative options exist and treatment remains complex. While therapy has mainly focused on medical approaches in the past, growing evidence reveals that in cases of limited inflammation, surgery can suffice as an alternative primary treatment. We retrospectively assessed the disease course and outcomes of 103 patients with terminal Ileitis who underwent primary surgery (n = 29) or received primary medical treatment followed by surgery (n = 74). Primary endpoint was the need for immunosuppressive medication after surgical treatment (ileocecal resection, ICR) during a two-years follow-up. Rates for laparoscopic ICR were enhanced in case of early surgery, but no differences were seen for postoperative complications. In case of immunosuppressive medication, patients with ICR at an early state of disease needed significantly less anti-inflammatory medication during the two-year postoperative follow-up compared to patients who were primarily treated medically. Furthermore, in a subgroup analysis for patients with localized ileocecal disease manifestation, early surgery consistently resulted in a decreased amount of medical therapy postoperatively. In conclusion primary ICR is safe and effective in patients with limited CD, and the need for immunosuppressive medication during the postoperative follow-up is low compared to patients receiving surgery at a later stage of disease.
KW - Crohn’s Disease
KW - surgical therapy
KW - ileocecal resection
Y1 - 2021
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-228822
SN - 2077-0383
VL - 10
IS - 4
ER -
TY - JOUR
A1 - Detomas, Mario
A1 - Altieri, Barbara
A1 - Schlötelburg, Wiebke
A1 - Appenzeller, Silke
A1 - Schlaffer, Sven
A1 - Coras, Roland
A1 - Schirbel, Andreas
A1 - Wild, Vanessa
A1 - Kroiss, Matthias
A1 - Sbiera, Silviu
A1 - Fassnacht, Martin
A1 - Deutschbein, Timo
T1 - Case Report: Consecutive Adrenal Cushing’s Syndrome and Cushing’s Disease in a Patient With Somatic CTNNB1, USP8, and NR3C1 Mutations
JF - Frontiers in Endocrinology
N2 - The occurrence of different subtypes of endogenous Cushing’s syndrome (CS) in single individuals is extremely rare. We here present the case of a female patient who was successfully cured from adrenal CS 4 years before being diagnosed with Cushing’s disease (CD). The patient was diagnosed at the age of 50 with ACTH-independent CS and a left-sided adrenal adenoma, in January 2015. After adrenalectomy and histopathological confirmation of a cortisol-producing adrenocortical adenoma, biochemical hypercortisolism and clinical symptoms significantly improved. However, starting from 2018, the patient again developed signs and symptoms of recurrent CS. Subsequent biochemical and radiological workup suggested the presence of ACTH-dependent CS along with a pituitary microadenoma. The patient underwent successful transsphenoidal adenomectomy, and both postoperative adrenal insufficiency and histopathological workup confirmed the diagnosis of CD. Exome sequencing excluded a causative germline mutation but showed somatic mutations of the β-catenin protein gene (CTNNB1) in the adrenal adenoma, and of both the ubiquitin specific peptidase 8 (USP8) and the glucocorticoid receptor (NR3C1) genes in the pituitary adenoma. In conclusion, our case illustrates that both ACTH-independent and ACTH-dependent CS may develop in a single individual even without evidence for a common genetic background.
KW - Cushing’s syndrome
KW - Cushing’s disease
KW - hypercortisolism
KW - glucocorticoid excess
KW - USP8
KW - CTNNB1
KW - NR3C1
Y1 - 2021
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-244596
SN - 1664-2392
VL - 12
ER -
TY - JOUR
A1 - Link, Fabian
A1 - Borges, Alyssa R.
A1 - Jones, Nicola G.
A1 - Engstler, Markus
T1 - To the Surface and Back: Exo- and Endocytic Pathways in Trypanosoma brucei
JF - Frontiers in Cell and Developmental Biology
N2 - Trypanosoma brucei is one of only a few unicellular pathogens that thrives extracellularly in the vertebrate host. Consequently, the cell surface plays a critical role in both immune recognition and immune evasion. The variant surface glycoprotein (VSG) coats the entire surface of the parasite and acts as a flexible shield to protect invariant proteins against immune recognition. Antigenic variation of the VSG coat is the major virulence mechanism of trypanosomes. In addition, incessant motility of the parasite contributes to its immune evasion, as the resulting fluid flow on the cell surface drags immunocomplexes toward the flagellar pocket, where they are internalized. The flagellar pocket is the sole site of endo- and exocytosis in this organism. After internalization, VSG is rapidly recycled back to the surface, whereas host antibodies are thought to be transported to the lysosome for degradation. For this essential step to work, effective machineries for both sorting and recycling of VSGs must have evolved in trypanosomes. Our understanding of the mechanisms behind VSG recycling and VSG secretion, is by far not complete. This review provides an overview of the trypanosome secretory and endosomal pathways. Longstanding questions are pinpointed that, with the advent of novel technologies, might be answered in the near future.
KW - cell surface
KW - African trypanosomes
KW - endocytosis
KW - exocytosis
KW - membrane recycling
KW - Rab
KW - clathrin
Y1 - 2021
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-244682
SN - 2296-634X
VL - 9
ER -
TY - JOUR
A1 - Krajka, Victor
A1 - Naujock, Maximilian
A1 - Pauly, Martje G.
A1 - Stengel, Felix
A1 - Meier, Britta
A1 - Stanslowsky, Nancy
A1 - Klein, Christine
A1 - Seibler, Philip
A1 - Wegner, Florian
A1 - Capetian, Philipp
T1 - Ventral Telencephalic Patterning Protocols for Induced Pluripotent Stem Cells
JF - Frontiers in Cell and Developmental Biology
N2 - The differentiation of human induced pluripotent stem cells (hiPSCs) into specific cell types for disease modeling and restorative therapies is a key research agenda and offers the possibility to obtain patient-specific cells of interest for a wide range of diseases. Basal forebrain cholinergic neurons (BFCNs) play a particular role in the pathophysiology of Alzheimer’s dementia and isolated dystonias. In this work, various directed differentiation protocols based on monolayer neural induction were tested for their effectiveness in promoting a ventral telencephalic phenotype and generating BFCN. Ventralizing factors [i.e., purmorphamine and Sonic hedgehog (SHH)] were applied at different time points, time intervals, and concentrations. In addition, caudal identity was prevented by the use of a small molecule XAV-939 that inhibits the Wnt-pathway. After patterning, gene expression profiles were analyzed by quantitative PCR (qPCR). Rostro-ventral patterning is most effective when initiated simultaneously with neural induction. The most promising combination of patterning factors was 0.5 μM of purmorphamine and 1 μM of XAV-939, which induces the highest expression of transcription factors specific for the medial ganglionic eminence, the source of GABAergic inter- and cholinergic neurons in the telencephalon. Upon maturation of cells, the immune phenotype, as well as electrophysiological properties were investigated showing the presence of marker proteins specific for BFCN (choline acetyltransferase, ISL1, p75, and NKX2.1) and GABAergic neurons. Moreover, a considerable fraction of measured cells displayed mature electrophysiological properties. Synaptic boutons containing the vesicular acetylcholine transporter (VACHT) could be observed in the vicinity of the cells. This work will help to generate basal forebrain interneurons from hiPSCs, providing a promising platform for modeling neurological diseases, such as Alzheimer’s disease or Dystonia.
KW - induced pluripotent stem cells
KW - medial ganglionic eminence
KW - Sonic hedgehog
KW - XAV-939
KW - purmorphamine
KW - basal forebrain cholinergic neurons
KW - GABAergic neurons
KW - electrophysiology
Y1 - 2021
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-244607
SN - 2296-634X
VL - 9
ER -
TY - JOUR
A1 - Adam, Pia
A1 - Kircher, Stefan
A1 - Sbiera, Iuliu
A1 - Koehler, Viktoria Florentine
A1 - Berg, Elke
A1 - Knösel, Thomas
A1 - Sandner, Benjamin
A1 - Fenske, Wiebke Kristin
A1 - Bläker, Hendrik
A1 - Smaxwil, Constantin
A1 - Zielke, Andreas
A1 - Sipos, Bence
A1 - Allelein, Stephanie
A1 - Schott, Matthias
A1 - Dierks, Christine
A1 - Spitzweg, Christine
A1 - Fassnacht, Martin
A1 - Kroiss, Matthias
T1 - FGF-Receptors and PD-L1 in Anaplastic and Poorly Differentiated Thyroid Cancer: Evaluation of the Preclinical Rationale
JF - Frontiers in Endocrinology
N2 - Background
Treatment options for poorly differentiated (PDTC) and anaplastic (ATC) thyroid carcinoma are unsatisfactory and prognosis is generally poor. Lenvatinib (LEN), a multi-tyrosine kinase inhibitor targeting fibroblast growth factor receptors (FGFR) 1-4 is approved for advanced radioiodine refractory thyroid carcinoma, but response to single agent is poor in ATC. Recent reports of combining LEN with PD-1 inhibitor pembrolizumab (PEM) are promising.
Materials and Methods
Primary ATC (n=93) and PDTC (n=47) tissue samples diagnosed 1997-2019 at five German tertiary care centers were assessed for PD-L1 expression by immunohistochemistry using Tumor Proportion Score (TPS). FGFR 1-4 mRNA was quantified in 31 ATC and 14 PDTC with RNAscope in-situ hybridization. Normal thyroid tissue (NT) and papillary thyroid carcinoma (PTC) served as controls. Disease specific survival (DSS) was the primary outcome variable.
Results
PD-L1 TPS≥50% was observed in 42% of ATC and 26% of PDTC specimens. Mean PD-L1 expression was significantly higher in ATC (TPS 30%) than in PDTC (5%; p<0.01) and NT (0%, p<0.001). 53% of PDTC samples had PD-L1 expression ≤5%. FGFR mRNA expression was generally low in all samples but combined FGFR1-4 expression was significantly higher in PDTC and ATC compared to NT (each p<0.001). No impact of PD-L1 and FGFR 1-4 expression was observed on DSS.
Conclusion
High tumoral expression of PD-L1 in a large proportion of ATCs and a subgroup of PDTCs provides a rationale for immune checkpoint inhibition. FGFR expression is low thyroid tumor cells. The clinically observed synergism of PEM with LEN may be caused by immune modulation.
KW - tyrosine kinase inhibitor (TKI)
KW - immune checkpoint inhibitor (ICI)
KW - immunohistochemistry
KW - immunotherapy
KW - PD-L1
KW - FGFR
Y1 - 2021
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-244653
SN - 1664-2392
VL - 12
ER -
TY - JOUR
A1 - Gentzsch, Christian
A1 - Hoffmann, Matthias
A1 - Ohshima, Yasuhiro
A1 - Nose, Naoko
A1 - Chen, Xinyu
A1 - Higuchi, Takahiro
A1 - Decker, Michael
T1 - Synthesis and Initial Characterization of a Selective, Pseudo‐irreversible Inhibitor of Human Butyrylcholinesterase as PET Tracer
JF - ChemMedChem
N2 - The enzyme butyrylcholinesterase (BChE) represents a promising target for imaging probes to potentially enable early diagnosis of neurodegenerative diseases like Alzheimer's disease (AD) and to monitor disease progression in some forms of cancer. In this study, we present the design, facile synthesis, in vitro and preliminary ex vivo and in vivo evaluation of a morpholine‐based, selective inhibitor of human BChE as a positron emission tomography (PET) tracer with a pseudo‐irreversible binding mode. We demonstrate a novel protecting group strategy for 18F radiolabeling of carbamate precursors and show that the inhibitory potency as well as kinetic properties of our unlabeled reference compound were retained in comparison to the parent compound. In particular, the prolonged duration of enzyme inhibition of such a morpholinocarbamate motivated us to design a PET tracer, possibly enabling a precise mapping of BChE distribution.
KW - carbamate
KW - enzyme kinetics
KW - fluorine-18
KW - positron emission tomography
KW - radiotracers
Y1 - 2021
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-239904
VL - 16
IS - 9
SP - 1427
EP - 1437
ER -
TY - JOUR
A1 - Li, Kunkun
A1 - Prada, Juan
A1 - Damineli, Daniel S. C.
A1 - Liese, Anja
A1 - Romeis, Tina
A1 - Dandekar, Thomas
A1 - Feijó, José A.
A1 - Hedrich, Rainer
A1 - Konrad, Kai Robert
T1 - An optimized genetically encoded dual reporter for simultaneous ratio imaging of Ca\(^{2+}\) and H\(^{+}\) reveals new insights into ion signaling in plants
JF - New Phytologist
N2 - Whereas the role of calcium ions (Ca\(^{2+}\)) in plant signaling is well studied, the physiological significance of pH‐changes remains largely undefined.
Here we developed CapHensor, an optimized dual‐reporter for simultaneous Ca\(^{2+}\) and pH ratio‐imaging and studied signaling events in pollen tubes (PTs), guard cells (GCs), and mesophyll cells (MCs). Monitoring spatio‐temporal relationships between membrane voltage, Ca\(^{2+}\)‐ and pH‐dynamics revealed interconnections previously not described.
In tobacco PTs, we demonstrated Ca\(^{2+}\)‐dynamics lag behind pH‐dynamics during oscillatory growth, and pH correlates more with growth than Ca\(^{2+}\). In GCs, we demonstrated abscisic acid (ABA) to initiate stomatal closure via rapid cytosolic alkalization followed by Ca2+ elevation. Preventing the alkalization blocked GC ABA‐responses and even opened stomata in the presence of ABA, disclosing an important pH‐dependent GC signaling node. In MCs, a flg22‐induced membrane depolarization preceded Ca2+‐increases and cytosolic acidification by c. 2 min, suggesting a Ca\(^{2+}\)/pH‐independent early pathogen signaling step. Imaging Ca2+ and pH resolved similar cytosol and nuclear signals and demonstrated flg22, but not ABA and hydrogen peroxide to initiate rapid membrane voltage‐, Ca\(^{2+}\)‐ and pH‐responses.
We propose close interrelation in Ca\(^{2+}\)‐ and pH‐signaling that is cell type‐ and stimulus‐specific and the pH having crucial roles in regulating PT growth and stomata movement.
KW - abscisic acid (ABA)
KW - calcium
KW - flg22
KW - guard cells
KW - imaging
KW - ion signaling
KW - pH
KW - pollen tube
Y1 - 2021
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-239847
VL - 230
IS - 6
SP - 2292
EP - 2310
ER -
TY - JOUR
A1 - Kriegel, Peter
A1 - Fritze, Michael‐Andreas
A1 - Thorn, Simon
T1 - Surface temperature and shrub cover drive ground beetle (Coleoptera: Carabidae) assemblages in short‐rotation coppices
JF - Agricultural and Forest Entomology
N2 - Increasing demand for biomass has led to an on‐going intensification of fuel wood plantations with possible negative effects on open land biodiversity. Hence, ecologists increasingly call for measures that reduce those negative effects on associated biodiversity. However, our knowledge about the efficiency of such measures remains scarce.
We investigated the effects of gap implementation in short rotation coppices (SRCs) on carabid diversity and assemblage composition over 3 years, with pitfall traps in gaps, edges and interiors. In parallel, we quantified soil surface temperature, shrub‐ and herb cover.
Edges had the highest number of species and abundances per trap, whereas rarefied species richness was significantly lower in short rotation coppice interiors than in other habitat types. Carabid community composition differed significantly between habitat types. The main environmental drivers were temperature for number of species and abundance and shrub cover for rarefied species richness.
We found significantly higher rarefied species richness in gaps compared with interiors. Hence, we argue that gap implementation benefits overall diversity in short rotation coppices. Furthermore, the differences in species community composition between habitat types through increased species turnover support carabid diversity in short rotation coppices. These positive effects were largely attributed to microclimate conditions. However, to maintain positive effects, continuous management of herb layer might be necessary.
KW - Carabidae
KW - fuel wood
KW - short‐rotation coppice
KW - shrub‐cover
KW - temperature
Y1 - 2021
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-239873
VL - 23
IS - 4
SP - 400
EP - 410
ER -
TY - JOUR
A1 - Schroer, Guido
A1 - Toussaint, Valérie
A1 - Bachmann, Stephanie
A1 - Pöppler, Ann‐Christin
A1 - Gierlich, Christian Henning
A1 - Delidovich, Irina
T1 - Functional Phenylboronate Polymers for the Recovery of Diols, Sugar Alcohols, and Saccharides from Aqueous Solution
JF - ChemSusChem
N2 - The ongoing transition from fossil to renewable feedstocks demands new efficient processes for an economically viable production of biomass‐derived commodities and fine chemicals. Novel energy‐ and material‐efficient product purification and separation will play a crucial role due to altered product and feed composition. The present study comprises the synthesis and tests of cross‐linked p‐vinylphenylboronate polymers for the separation of 18 diols, sugar alcohols, and saccharides, which can be obtained during biomass processing. The separation was based on molecular recognition, that is, esterification of the phenylboronate with vicinal diols. A correlation of the molecular complexation constant, the polymer swelling, and the maximum adsorption capacity was found. The adsorption curves over time were recorded. Preliminary results on competitive adsorption of binary mixtures showed a high potential for the separation of substrates with significantly different complexation constants. Desorption tests implied easier desorption of substrates that only adsorb on the outer polymer shell.
KW - adsorption
KW - biomass
KW - phenylboronate
KW - polymers
KW - separation techniques
Y1 - 2021
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-239889
VL - 14
IS - 23
SP - 5207
EP - 5215
ER -
TY - JOUR
A1 - Emmerich, Petra
A1 - Murawski, Carolin
A1 - Ehmen, Christa
A1 - von Possel, Ronald
A1 - Pekarek, Neele
A1 - Oestereich, Lisa
A1 - Duraffour, Sophie
A1 - Pahlmann, Meike
A1 - Struck, Nicole
A1 - Eibach, Daniel
A1 - Krumkamp, Ralf
A1 - Amuasi, John
A1 - Maiga‐Ascofaré, Oumou
A1 - Rakotozandrindrainy, Raphael
A1 - Asogun, Danny
A1 - Ighodalo, Yemisi
A1 - Kann, Simone
A1 - May, Jürgen
A1 - Tannich, Egbert
A1 - Deschermeier, Christina
T1 - Limited specificity of commercially available SARS‐CoV‐2 IgG ELISAs in serum samples of African origin
JF - Tropical Medicine & International Health
N2 - Objectives
Specific serological tests are mandatory for reliable SARS‐CoV‐2 diagnostics and seroprevalence studies. Here, we assess the specificities of four commercially available SARS‐CoV‐2 IgG ELISAs in serum/plasma panels originating from Africa, South America, and Europe.
Methods
882 serum/plasma samples collected from symptom‐free donors before the COVID‐19 pandemic in three African countries (Ghana, Madagascar, Nigeria), Colombia, and Germany were analysed with three nucleocapsid‐based ELISAs (Euroimmun Anti‐SARS‐CoV‐2‐NCP IgG, EDI™ Novel Coronavirus COVID‐19 IgG, Mikrogen recomWell SARS‐CoV‐2 IgG), one spike/S1‐based ELISA (Euroimmun Anti‐SARS‐CoV‐2 IgG), and in‐house common cold CoV ELISAs.
Results
High specificity was confirmed for all SARS‐CoV‐2 IgG ELISAs for Madagascan (93.4–99.4%), Colombian (97.8–100.0%), and German (95.9–100.0%) samples. In contrast, specificity was much lower for the Ghanaian and Nigerian serum panels (Ghana: NCP‐based assays 77.7–89.7%, spike/S1‐based assay 94.3%; Nigeria: NCP‐based assays 39.3–82.7%, spike/S1‐based assay 90.7%). 15 of 600 African sera were concordantly classified as positive in both the NCP‐based and the spike/S1‐based Euroimmun ELISA, but did not inhibit spike/ACE2 binding in a surrogate virus neutralisation test. IgG antibodies elicited by previous infections with common cold CoVs were found in all sample panels, including those from Madagascar, Colombia, and Germany and thus do not inevitably hamper assay specificity. Nevertheless, high levels of IgG antibodies interacting with OC43 NCP were found in all 15 SARS‐CoV‐2 NCP/spike/S1 ELISA positive sera.
Conclusions
Depending on the chosen antigen and assay protocol, SARS‐CoV‐2 IgG ELISA specificity may be significantly reduced in certain populations probably due to interference of immune responses to endemic pathogens like other viruses or parasites.
KW - SARS‐CoV‐2
KW - seroepidemiologic studies
KW - immunoglobulin G
KW - Enzyme‐Linked Immunosorbent Assay
KW - specificity
KW - Africa
Y1 - 2021
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-239899
VL - 26
IS - 6
SP - 621
EP - 631
ER -
TY - JOUR
A1 - Habenstein, Jens
A1 - Schmitt, Franziska
A1 - Liessem, Sander
A1 - Ly, Alice
A1 - Trede, Dennis
A1 - Wegener, Christian
A1 - Predel, Reinhard
A1 - Rössler, Wolfgang
A1 - Neupert, Susanne
T1 - Transcriptomic, peptidomic, and mass spectrometry imaging analysis of the brain in the ant Cataglyphis nodus
JF - Journal of Neurochemistry
N2 - Behavioral flexibility is an important cornerstone for the ecological success of animals. Social Cataglyphis nodus ants with their age‐related polyethism characterized by age‐related behavioral phenotypes represent a prime example for behavioral flexibility. We propose neuropeptides as powerful candidates for the flexible modulation of age‐related behavioral transitions in individual ants. As the neuropeptidome of C. nodus was unknown, we collected a comprehensive peptidomic data set obtained by transcriptome analysis of the ants’ central nervous system combined with brain extract analysis by Q‐Exactive Orbitrap mass spectrometry (MS) and direct tissue profiling of different regions of the brain by matrix‐assisted laser desorption/ionization time‐of‐flight (MALDI‐TOF) MS. In total, we identified 71 peptides with likely bioactive function, encoded on 49 neuropeptide‐, neuropeptide‐like, and protein hormone prepropeptide genes, including a novel neuropeptide‐like gene (fliktin). We next characterized the spatial distribution of a subset of peptides encoded on 16 precursor proteins with high resolution by MALDI MS imaging (MALDI MSI) on 14 µm brain sections. The accuracy of our MSI data were confirmed by matching the immunostaining patterns for tachykinins with MSI ion images from consecutive brain sections. Our data provide a solid framework for future research into spatially resolved qualitative and quantitative peptidomic changes associated with stage‐specific behavioral transitions and the functional role of neuropeptides in Cataglyphis ants.
KW - brain
KW - MALDI imaging
KW - neuropeptides
KW - neuropeptidomics
KW - social insect
KW - transcriptomics
Y1 - 2021
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-239917
VL - 158
IS - 2
SP - 391
EP - 412
ER -
TY - JOUR
A1 - Postema, Merel C.
A1 - Hoogman, Martine
A1 - Ambrosino, Sara
A1 - Asherson, Philip
A1 - Banaschewski, Tobias
A1 - Bandeira, Cibele E.
A1 - Baranov, Alexandr
A1 - Bau, Claiton H.D.
A1 - Baumeister, Sarah
A1 - Baur‐Streubel, Ramona
A1 - Bellgrove, Mark A.
A1 - Biederman, Joseph
A1 - Bralten, Janita
A1 - Brandeis, Daniel
A1 - Brem, Silvia
A1 - Buitelaar, Jan K.
A1 - Busatto, Geraldo F.
A1 - Castellanos, Francisco X.
A1 - Cercignani, Mara
A1 - Chaim‐Avancini, Tiffany M.
A1 - Chantiluke, Kaylita C.
A1 - Christakou, Anastasia
A1 - Coghill, David
A1 - Conzelmann, Annette
A1 - Cubillo, Ana I.
A1 - Cupertino, Renata B.
A1 - de Zeeuw, Patrick
A1 - Doyle, Alysa E.
A1 - Durston, Sarah
A1 - Earl, Eric A.
A1 - Epstein, Jeffery N.
A1 - Ethofer, Thomas
A1 - Fair, Damien A.
A1 - Fallgatter, Andreas J.
A1 - Faraone, Stephen V.
A1 - Frodl, Thomas
A1 - Gabel, Matt C.
A1 - Gogberashvili, Tinatin
A1 - Grevet, Eugenio H.
A1 - Haavik, Jan
A1 - Harrison, Neil A.
A1 - Hartman, Catharina A.
A1 - Heslenfeld, Dirk J.
A1 - Hoekstra, Pieter J.
A1 - Hohmann, Sarah
A1 - Høvik, Marie F.
A1 - Jernigan, Terry L.
A1 - Kardatzki, Bernd
A1 - Karkashadze, Georgii
A1 - Kelly, Clare
A1 - Kohls, Gregor
A1 - Konrad, Kerstin
A1 - Kuntsi, Jonna
A1 - Lazaro, Luisa
A1 - Lera‐Miguel, Sara
A1 - Lesch, Klaus‐Peter
A1 - Louza, Mario R.
A1 - Lundervold, Astri J.
A1 - Malpas, Charles B
A1 - Mattos, Paulo
A1 - McCarthy, Hazel
A1 - Namazova‐Baranova, Leyla
A1 - Nicolau, Rosa
A1 - Nigg, Joel T.
A1 - Novotny, Stephanie E.
A1 - Oberwelland Weiss, Eileen
A1 - O'Gorman Tuura, Ruth L.
A1 - Oosterlaan, Jaap
A1 - Oranje, Bob
A1 - Paloyelis, Yannis
A1 - Pauli, Paul
A1 - Picon, Felipe A.
A1 - Plessen, Kerstin J.
A1 - Ramos‐Quiroga, J. Antoni
A1 - Reif, Andreas
A1 - Reneman, Liesbeth
A1 - Rosa, Pedro G.P.
A1 - Rubia, Katya
A1 - Schrantee, Anouk
A1 - Schweren, Lizanne J.S.
A1 - Seitz, Jochen
A1 - Shaw, Philip
A1 - Silk, Tim J.
A1 - Skokauskas, Norbert
A1 - Soliva Vila, Juan C.
A1 - Stevens, Michael C.
A1 - Sudre, Gustavo
A1 - Tamm, Leanne
A1 - Tovar‐Moll, Fernanda
A1 - van Erp, Theo G.M.
A1 - Vance, Alasdair
A1 - Vilarroya, Oscar
A1 - Vives‐Gilabert, Yolanda
A1 - von Polier, Georg G.
A1 - Walitza, Susanne
A1 - Yoncheva, Yuliya N.
A1 - Zanetti, Marcus V.
A1 - Ziegler, Georg C.
A1 - Glahn, David C.
A1 - Jahanshad, Neda
A1 - Medland, Sarah E.
A1 - Thompson, Paul M.
A1 - Fisher, Simon E.
A1 - Franke, Barbara
A1 - Francks, Clyde
T1 - Analysis of structural brain asymmetries in attention‐deficit/hyperactivity disorder in 39 datasets
JF - Journal of Child Psychology and Psychiatry
N2 - Objective
Some studies have suggested alterations of structural brain asymmetry in attention‐deficit/hyperactivity disorder (ADHD), but findings have been contradictory and based on small samples. Here, we performed the largest ever analysis of brain left‐right asymmetry in ADHD, using 39 datasets of the ENIGMA consortium.
Methods
We analyzed asymmetry of subcortical and cerebral cortical structures in up to 1,933 people with ADHD and 1,829 unaffected controls. Asymmetry Indexes (AIs) were calculated per participant for each bilaterally paired measure, and linear mixed effects modeling was applied separately in children, adolescents, adults, and the total sample, to test exhaustively for potential associations of ADHD with structural brain asymmetries.
Results
There was no evidence for altered caudate nucleus asymmetry in ADHD, in contrast to prior literature. In children, there was less rightward asymmetry of the total hemispheric surface area compared to controls (t = 2.1, p = .04). Lower rightward asymmetry of medial orbitofrontal cortex surface area in ADHD (t = 2.7, p = .01) was similar to a recent finding for autism spectrum disorder. There were also some differences in cortical thickness asymmetry across age groups. In adults with ADHD, globus pallidus asymmetry was altered compared to those without ADHD. However, all effects were small (Cohen’s d from −0.18 to 0.18) and would not survive study‐wide correction for multiple testing.
Conclusion
Prior studies of altered structural brain asymmetry in ADHD were likely underpowered to detect the small effects reported here. Altered structural asymmetry is unlikely to provide a useful biomarker for ADHD, but may provide neurobiological insights into the trait.
KW - attention‐deficit
KW - hyperactivity disorder
KW - brain asymmetry
KW - brain laterality
KW - structural MRI
KW - large‐scale data
Y1 - 2021
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-239968
VL - 62
IS - 10
SP - 1202
EP - 1219
ER -
TY - JOUR
A1 - Wohlwend, Michael R.
A1 - Craven, Dylan
A1 - Weigelt, Patrick
A1 - Seebens, Hanno
A1 - Winter, Marten
A1 - Kreft, Holger
A1 - Zurell, Damaris
A1 - Sarmento Cabral, Juliano
A1 - Essl, Franz
A1 - van Kleunen, Mark
A1 - Pergl, Jan
A1 - Pyšek, Petr
A1 - Knight, Tiffany M.
T1 - Anthropogenic and environmental drivers shape diversity of naturalized plants across the Pacific
JF - Diversity and Distributions
N2 - Aim
The Pacific exhibits an exceptional number of naturalized plant species, but the drivers of this high diversity and the associated compositional patterns remain largely unknown. Here, we aim to (a) improve our understanding of introduction and establishment processes and (b) evaluate whether this information is sufficient to create scientific conservation tools, such as watchlists.
Location
Islands in the Pacific Ocean, excluding larger islands such as New Zealand, Japan, the Philippines and Indonesia.
Methods
We combined information from the most up‐to‐date data sources to quantify naturalized plant species richness and turnover across island groups and investigate the effects of anthropogenic, biogeographic and climate drivers on these patterns. In total, we found 2,672 naturalized plant species across 481 islands and 50 island groups, with a total of 11,074 records.
Results
Most naturalized species were restricted to few island groups, and most island groups have a low number of naturalized species. Island groups with few naturalized species were characterized by a set of widespread naturalized species. Several plant families that contributed many naturalized species globally also did so in the Pacific, particularly Fabaceae and Poaceae. However, many families were significantly over‐ or under‐represented in the Pacific naturalized flora compared to other regions of the world. Naturalized species richness increased primarily with increased human activity and island altitude/area, whereas similarity between island groups in temperature along with richness differences was most important for beta diversity.
Main conclusions
The distribution and richness of naturalized species can be explained by a small set of drivers. The Pacific region contains many naturalized plant species also naturalized in other regions in the world, but our results highlight key differences such as a stronger role of anthropogenic drivers in shaping diversity patterns. Our results establish a basis for predicting and preventing future naturalizations in a threatened biodiversity hotspot.
KW - anthropogenic drivers
KW - beta diversity
KW - island biogeography
KW - naturalized species
KW - Pacific Ocean
KW - plant invasion
Y1 - 2021
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-239925
VL - 27
IS - 6
SP - 1120
EP - 1133
ER -
TY - JOUR
A1 - Wabbels, Bettina
A1 - Fricke, Julia
A1 - Schittkowski, Michael
A1 - Gräf, Michael
A1 - Lorenz, Birgit
A1 - Bau, Viktoria
A1 - Nentwich, Martin M.
A1 - Atili, Abed
A1 - Eckstein, Anja
A1 - Sturm, Veit
A1 - Beisse, Christina
A1 - Sterker, Ina
A1 - Neppert, Birte
A1 - Mauschitz, Matthias M.
T1 - Yokoyama procedure for esotropia associated with high myopia: real‐world data from a large‐scale multicentre analysis
JF - Acta Ophthalmologica
N2 - Purpose
High myopic patients may develop strabismus due to globe dislocation out of the normal extraocular muscle cone. Surgical correction of this strabismus type is possible by joining the superior and lateral rectus muscles without the need for a scleral suture called the Yokoyama procedure. Data from large patient samples and the evaluation of a potential effect of an additional medial rectus recession (MRR) have been lacking so far.
Methods
We pooled retrospective patient data of 14 departments of ophthalmology in Germany and Switzerland and analysed determinants of postoperative results using multivariable regression models.
Results
We included 133 patients (mean age: 59.7 ± 13.4 years, surgery between 2008 and 2017) with a mean preoperative esotropia (both Yokoyama with and without MRR) of 23.8°±4.6°. The angle of preoperative esotropia increased with age. The postoperative esotropia was 8.7° ± 9.9°, and six patients were overcorrected. While preoperative esotropia was highly associated with postoperative results, we found no association of additional MRR with any of our postoperative outcome measures. The Yokoyama procedure had a higher absolute effect in patients with higher preoperative esotropia.
Conclusion
Our study confirms the positive effect of the Yokoyama procedure on strabismus due to high myopia in large‐scale real‐world data. In some cases, MRR may be needed because of muscle contracture, although additional MRR statistically did not affect the postoperative outcome. In patients with bilateral high myopic strabismus, correction of both eyes seems beneficial. The effect size of the Yokoyama procedure appears to be mainly driven by preoperative esotropia.
KW - esohypotropia
KW - heavy eye
KW - high myopia
KW - muscle dislocation
KW - strabismus fixus
Y1 - 2021
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-239939
VL - 99
IS - 8
SP - e1340
EP - e1347
ER -
TY - JOUR
A1 - Sponsler, Douglas B.
A1 - Bratman, Eve Z.
T1 - Beekeeping in, of or for the city? A socioecological perspective on urban apiculture
JF - People and Nature
N2 - The term ‘urban beekeeping’ connotes a host of meanings—sociopolitical, commercial, ecological and personal—beyond the mere description of where bees and beekeepers happen to coincide. Yet, these meanings are seldom articulated explicitly or brought into critical engagement with the relevant fields of urban ecology and political ecology.
Beginning with a brief account of the history of urban beekeeping in the United States, we draw upon urban ecological theory to construct a conceptual model of urban beekeeping that distinguishes beekeeping in, of and for the city. In our model, beekeeping in the city describes the mere importation of the traditionally rural practice of beekeeping into urban spaces for the private reasons of the individual beekeeper, whereas beekeeping of the city describes beekeeping that is consciously tailored to the urban context, often accompanied by (semi)professionalization of beekeepers and the formation of local expert communities (i.e. beekeeping associations). Beekeeping for the city describes a shift in mindset in which beekeeping is directed to civic ends beyond the boundaries of the beekeeping community per se.
Using this framework, we identify and discuss specific socioecological assets and liabilities of urban beekeeping, and how these relate to beekeeping in, of and for the city. We then formulate actionable guidelines for maturing the practice of urban beekeeping into a beneficent and self‐critical form of urban ecological citizenship; these include fostering self‐regulation within the beekeeping community, harnessing beekeeping as a ‘gateway’ experience for a broader rapprochement between urban residents and nature, and recognizing the political‐ecological context of beekeeping with respect to matters of socioecological justice.
KW - environmental justice
KW - honey bee
KW - multispecies studies
KW - policy
KW - pollinator
KW - urban greening
Y1 - 2021
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-239949
VL - 3
IS - 3
SP - 550
EP - 559
ER -
TY - JOUR
A1 - Schuch, Luise A.
A1 - Forstner, Maria
A1 - Rapp, Christina K.
A1 - Li, Yang
A1 - Smith, Desiree E. C.
A1 - Mendes, Marisa I.
A1 - Delhommel, Florent
A1 - Sattler, Michael
A1 - Emiralioğlu, Nagehan
A1 - Taskiran, Ekim Z.
A1 - Orhan, Diclehan
A1 - Kiper, Nural
A1 - Rohlfs, Meino
A1 - Jeske, Tim
A1 - Hastreiter, Maximilian
A1 - Gerstlauer, Michael
A1 - Torrent‐Vernetta, Alba
A1 - Moreno‐Galdó, Antonio
A1 - Kammer, Birgit
A1 - Brasch, Frank
A1 - Reu‐Hofer, Simone
A1 - Griese, Matthias
T1 - FARS1‐related disorders caused by bi‐allelic mutations in cytosolic phenylalanyl‐tRNA synthetase genes: Look beyond the lungs!
JF - Clinical Genetics
N2 - Aminoacyl‐tRNA synthetases (ARSs) catalyze the first step of protein biosynthesis (canonical function) and have additional (non‐canonical) functions outside of translation. Bi‐allelic pathogenic variants in genes encoding ARSs are associated with various recessive mitochondrial and multisystem disorders. We describe here a multisystem clinical phenotype based on bi‐allelic mutations in the two genes (FARSA, FARSB) encoding distinct subunits for tetrameric cytosolic phenylalanyl‐tRNA synthetase (FARS1). Interstitial lung disease with cholesterol pneumonitis on histology emerged as an early characteristic feature and significantly determined disease burden. Additional clinical characteristics of the patients included neurological findings, liver dysfunction, and connective tissue, muscular and vascular abnormalities. Structural modeling of newly identified missense mutations in the alpha subunit of FARS1, FARSA, showed exclusive mapping to the enzyme's conserved catalytic domain. Patient‐derived mutant cells displayed compromised aminoacylation activity in two cases, while remaining unaffected in another. Collectively, these findings expand current knowledge about the human ARS disease spectrum and support a loss of canonical and non‐canonical function in FARS1‐associated recessive disease.
KW - aminoacyl‐tRNA synthetases
KW - cholesterol pneumonitis
KW - FARS1
KW - children´s interstitial lung disease (chILD) lipoid pneumonia
Y1 - 2021
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-238827
VL - 99
IS - 6
SP - 789
EP - 801
ER -
TY - JOUR
A1 - Opitz, Timm
A1 - Schuwerk, Tobias
A1 - Paulus, Markus
A1 - Kloo, Daniela
A1 - Osterhaus, Christopher
A1 - Lesch, Klaus‐Peter
A1 - Sodian, Beate
T1 - No links between genetic variation and developing theory of mind: A preregistered replication attempt of candidate gene studies
JF - Developmental Science
N2 - Genetic variability is being discussed as a source of inter‐individual differences in Theory of Mind development. Previous studies documented an association between variations in DRD4 VNTR 48 bp, OXTR rs53576, COMT rs4680, and Theory of Mind task performance. As empirical evidence on these associations is sparse, we conducted a preregistered replication attempt of a study reporting a link between DRD4 VNTR 48 bp and false belief understanding in 50‐month‐old children [Lackner, C., Sabbagh, M. A., Hallinan, E., Liu, X., & Holden, J. J. (2012). Developmental Science, 15(2), 272–280.]. Additionally, we attempted a replication of studies on the role of OXTR rs53576 and COMT rs4680 in Theory of Mind. In both replication attempts, we did not find any evidence for associations between the sampled genetic markers and Theory of Mind ability in a series of analyses. Extending the replication attempt of Lackner et al., we employed longitudinal data from several tasks and measurement points, which allowed us to run follow‐up robustness checks with more reliable scores. These extensive analyses corroborated our null finding. This comprehensive non‐replication is important to balance current research on genetic markers of Theory of Mind. In a combined evaluation of our own and previous studies, we point to substantial methodological issues that research on the genetic basis of Theory of Mind development faces. We conclude that these limitations currently prevent firm conclusions on genetic influences on Theory of Mind development.
KW - COMT
KW - DRD4
KW - false belief
KW - OXTR
KW - theory of mind
Y1 - 2021
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-238812
VL - 24
IS - 5
ER -
TY - JOUR
A1 - Mayr, Antonia V.
A1 - Keller, Alexander
A1 - Peters, Marcell K.
A1 - Grimmer, Gudrun
A1 - Krischke, Beate
A1 - Geyer, Mareen
A1 - Schmitt, Thomas
A1 - Steffan‐Dewenter, Ingolf
T1 - Cryptic species and hidden ecological interactions of halictine bees along an elevational gradient
JF - Ecology and Evolution
N2 - Changes of abiotic and biotic conditions along elevational gradients represent serious challenges to organisms which may promote the turnover of species, traits and biotic interaction partners. Here, we used molecular methods to study cuticular hydrocarbon (CHC) profiles, biotic interactions and phylogenetic relationships of halictid bees of the genus Lasioglossum along a 2,900 m elevational gradient at Mt. Kilimanjaro, Tanzania. We detected a strong species turnover of morphologically indistinguishable taxa with phylogenetically clustered cryptic species at high elevations, changes in CHC profiles, pollen resource diversity, and a turnover in the gut and body surface microbiome of bees. At high elevations, increased proportions of saturated compounds in CHC profiles indicate physiological adaptations to prevent desiccation. More specialized diets with higher proportions of low‐quality Asteraceae pollen imply constraints in the availability of food resources. Interactive effects of climatic conditions on gut and surface microbiomes, CHC profiles, and pollen diet suggest complex feedbacks among abiotic conditions, ecological interactions, physiological adaptations, and phylogenetic constraints as drivers of halictid bee communities at Mt. Kilimanjaro.
KW - COI
KW - cuticular chemistry
KW - elevational gradient
KW - Halictidae
KW - microbiome metabarcoding
KW - pollen metabarcoding
Y1 - 2021
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-238853
VL - 11
IS - 12
SP - 7700
EP - 7712
ER -
TY - JOUR
A1 - Piselli, Claudio
A1 - Benz, Roland
T1 - Fosmidomycin transport through the phosphate‐specific porins OprO and OprP of Pseudomonas aeruginosa
JF - Molecular Microbiology
N2 - The Gram‐negative bacterium Pseudomonas aeruginosa is an opportunistic pathogen, responsible for many hospital‐acquired infections. The bacterium is quite resistant toward many antibiotics, in particular because of the fine‐tuned permeability of its outer membrane (OM). General diffusion outer membrane pores are quite rare in this organism. Instead, its OM contains many substrate‐specific porins. Their expression is varying according to growth conditions and virulence. Phosphate limitations, as well as pathogenicity factors, result in the induction of the two mono‐ and polyphosphate‐specific porins, OprP and OprO, respectively, together with an inner membrane uptake mechanism and a periplasmic binding protein. These outer membrane channels could serve as outer membrane pathways for the uptake of phosphonates. Among them are not only herbicides, but also potent antibiotics, such as fosfomycin and fosmidomycin. In this study, we investigated the interaction between OprP and OprO and fosmidomycin in detail. We could demonstrate that fosmidomycin is able to bind to the phosphate‐specific binding site inside the two porins. The inhibition of chloride conductance of OprP and OprO by fosmidomycin is considerably less than that of phosphate or diphosphate, but it can be measured in titration experiments of chloride conductance and also in single‐channel experiments. The results suggest that fosmidomycin transport across the OM of P. aeruginosa occurs through OprP and OprO. Our data with the ones already known in the literature show that phosphonic acid‐containing antibiotics are in general good candidates to treat the infections of P. aeruginosa at the very beginning through a favorable OM transport system.
KW - fosmidomycin
KW - lipid bilayer membrane
KW - OprO
KW - OprP
KW - porin
Y1 - 2021
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-238905
VL - 116
IS - 1
SP - 97
EP - 108
ER -
TY - JOUR
A1 - Vogel, Sebastian
A1 - Prinzing, Andreas
A1 - Bußler, Heinz
A1 - Müller, Jörg
A1 - Schmidt, Stefan
A1 - Thorn, Simon
T1 - Abundance, not diversity, of host beetle communities determines abundance and diversity of parasitoids in deadwood
JF - Ecology and Evolution
N2 - Most parasites and parasitoids are adapted to overcome defense mechanisms of their specific hosts and hence colonize a narrow range of host species. Accordingly, an increase in host functional or phylogenetic dissimilarity is expected to increase the species diversity of parasitoids. However, the local diversity of parasitoids may be driven by the accessibility and detectability of hosts, both increasing with increasing host abundance. Yet, the relative importance of these two mechanisms remains unclear. We parallelly reared communities of saproxylic beetle as potential hosts and associated parasitoid Hymenoptera from experimentally felled trees. The dissimilarity of beetle communities was inferred from distances in seven functional traits and from their evolutionary ancestry. We tested the effect of host abundance, species richness, functional, and phylogenetic dissimilarities on the abundance, species richness, and Shannon diversity of parasitoids. Our results showed an increase of abundance, species richness, and Shannon diversity of parasitoids with increasing beetle abundance. Additionally, abundance of parasitoids increased with increasing species richness of beetles. However, functional and phylogenetic dissimilarity showed no effect on the diversity of parasitoids. Our results suggest that the local diversity of parasitoids, of ephemeral and hidden resources like saproxylic beetles, is highest when resources are abundant and thereby detectable and accessible. Hence, in some cases, resources do not need to be diverse to promote parasitoid diversity.
KW - barcoding
KW - deadwood
KW - experiment
KW - host–parasitoid interaction
KW - natural enemy
KW - specialization
Y1 - 2021
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-238892
VL - 11
IS - 11
SP - 6881
EP - 6888
ER -
TY - JOUR
A1 - Leidinger, Ludwig
A1 - Vedder, Daniel
A1 - Cabral, Juliano Sarmento
T1 - Temporal environmental variation may impose differential selection on both genomic and ecological traits
JF - Oikos
N2 - The response of populations and species to changing conditions determines how community composition will change functionally, including via trait shifts. Selection from standing variation has been suggested to be more efficient than acquiring new mutations. Yet, studies on community trait composition and trait selection largely focus on phenotypic variation in ecological traits, whereas the underlying genomic traits remain understudied. Using a genome‐explicit, niche‐ and individual‐based model, we address the potential interactions between genomic and ecological traits shaping communities under an environmental selective forcing, namely temporal positively autocorrelated environmental fluctuation. In this model, all ecological traits are explicitly coded by the genome. For our experiments, we initialized 90 replicate communities, each with ca 350 initial species, characterized by random genomic and ecological trait combinations, on a 2D spatially explicit landscape with two orthogonal gradients (temperature and resource use). We exposed each community to two contrasting scenarios: without (i.e. static environments) and with temporal variation. We then analyzed emerging compositions of both genomic and ecological traits at the community, population and genomic levels. Communities in variable environments were species poorer than in static environments, and populations more abundant, whereas genomes had lower genetic linkage, mean genetic variation and a non‐significant tendency towards higher numbers of genes. The surviving genomes (i.e. those selected by variable environments) coded for enhanced environmental tolerance and smaller biomass, which resulted in faster life cycles and thus also in increased potential for evolutionary rescue. Under temporal environmental variation, larger, less linked genomes retained more variation in mean dispersal ability at the population level than at genomic level, whereas the opposite trend emerged for biomass. Our results provide clues to how sexually‐reproducing diploid plant communities might react to variable environments and highlights the importance of genomic traits and their interaction with ecological traits for eco‐evolutionary responses to changing climates.
KW - environmental variability
KW - genomic traits
KW - mechanistic model
KW - rapid evolution
KW - standing variation
Y1 - 2021
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-238945
VL - 130
IS - 7
SP - 1100
EP - 1115
ER -
TY - JOUR
A1 - Hoesl, Christine
A1 - Fröhlich, Thomas
A1 - Posch, Christian
A1 - Kneitz, Hermann
A1 - Goebeler, Matthias
A1 - Schneider, Marlon R.
A1 - Dahlhoff, Maik
T1 - The transmembrane protein LRIG1 triggers melanocytic tumor development following chemically induced skin carcinogenesis
JF - Molecular Oncology
N2 - The incidence of melanoma and nonmelanoma skin cancer has increased tremendously in recent years. Although novel treatment options have significantly improved patient outcomes, the prognosis for most patients with an advanced disease remains dismal. It is, thus, imperative to understand the molecular mechanisms involved in skin carcinogenesis in order to develop new targeted treatment strategies. Receptor tyrosine kinases (RTK) like the ERBB receptor family, including EGFR/ERBB1, ERBB2/NEU, ERBB3, and ERBB4, are important regulators of skin homeostasis and their dysregulation often results in cancer, which makes them attractive therapeutic targets. Members of the leucine‐rich repeats and immunoglobulin‐like domains protein family (LRIG1‐3) are ERBB regulators and thus potential therapeutic targets to manipulate ERBB receptors. Here, we analyzed the function of LRIG1 during chemically induced skin carcinogenesis in transgenic mice expressing LRIG1 in the skin under the control of the keratin 5 promoter (LRIG1‐TG mice). We observed a significant induction of melanocytic tumor formation in LRIG1‐TG mice and no difference in papilloma incidence between LRIG1‐TG and control mice. Our findings also revealed that LRIG1 affects ERBB signaling via decreased phosphorylation of EGFR and increased activation of the oncoprotein ERBB2 during skin carcinogenesis. The epidermal proliferation rate was significantly decreased during epidermal tumorigenesis under LRIG1 overexpression, and the apoptosis marker cleaved caspase 3 was significantly activated in the epidermis of transgenic LRIG1 mice. Additionally, we detected LRIG1 expression in human cutaneous squamous cell carcinoma and melanoma samples. Therefore, we depleted LRIG1 in human melanoma cells (A375) by CRISPR/Cas9 technology and found that this caused EGFR and ERBB3 downregulation in A375 LRIG1 knockout cells 6 h following stimulation with EGF. In conclusion, our study demonstrated that LRIG1‐TG mice develop melanocytic skin tumors during chemical skin carcinogenesis and a deletion of LRIG1 in human melanoma cells reduces EGFR and ERBB3 expression after EGF stimulation.
KW - ERBB receptors
KW - LRIG1
KW - melanoma
KW - mouse model
KW - skin carcinogenesis
Y1 - 2021
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-238925
VL - 15
IS - 8
SP - 2140
EP - 2155
ER -
TY - JOUR
A1 - Emmert, Adrian
A1 - Kneisel, Christof
T1 - Internal structure and palsa development at Orravatnsrústir Palsa Site (Central Iceland), investigated by means of integrated resistivity and ground‐penetrating radar methods
JF - Permafrost and Periglacial Processes
N2 - The natural cyclical development of palsas makes it difficult to use visible signs of decay as reference points for environmental change. Thus, to determine the actual development stage of a palsa, investigations of the internal structure are crucial. Our study presents 2‐D and 3‐D electrical resistivity imaging (ERI) and 2‐D ground‐penetrating radar (GPR) results, measurements of surface and subsurface temperatures, and of the soil matric potential from Orravatnsrústir Palsa Site in Central Iceland. By a joint interpretation of the results, we deduce the internal structure (i.e., thickness of thaw zone and permafrost, ice/water content) of five palsas of different size and shape. The results differentiate between initial and mature development stages and show that palsas of different development stages can exist in close proximity. While internal characteristics indicate undisturbed development of four palsas, one palsa shows indications of environmental change. Our study shows the value of the multimethod geophysical approach and introduces measurements of the soil matric potential as a promising method to assess the current state of the subsurface.
KW - 3‐D electrical resistivity imaging
KW - ground‐penetrating radar
KW - palsa development
KW - soil matric potential
Y1 - 2021
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-238933
VL - 32
IS - 3
SP - 503
EP - 519
ER -
TY - JOUR
A1 - Müller, Diana
A1 - Bessi, Irene
A1 - Richter, Christian
A1 - Schwalbe, Harald
T1 - The Folding Landscapes of Human Telomeric RNA and DNA G‐Quadruplexes are Markedly Different
JF - Angewandte Chemie International Edition
N2 - We investigated the folding kinetics of G‐quadruplex (G4) structures by comparing the K\(^{+}\)‐induced folding of an RNA G4 derived from the human telomeric repeat‐containing RNA (TERRA25) with a sequence homologous DNA G4 (wtTel25) using CD spectroscopy and real‐time NMR spectroscopy. While DNA G4 folding is biphasic, reveals kinetic partitioning and involves kinetically favoured off‐pathway intermediates, RNA G4 folding is faster and monophasic. The differences in kinetics are correlated to the differences in the folded conformations of RNA vs. DNA G4s, in particular with regard to the conformation around the glycosidic torsion angle χ that uniformly adopts anti conformations for RNA G4s and both, syn and anti conformation for DNA G4s. Modified DNA G4s with \(^{19}\)F bound to C2′ in arabino configuration adopt exclusively anti conformations for χ. These fluoro‐modified DNA (antiTel25) reveal faster folding kinetics and monomorphic conformations similar to RNA G4s, suggesting the correlation between folding kinetics and pathways with differences in χ angle preferences in DNA and RNA, respectively.
KW - folding landscapes
KW - G-quadruplexes
KW - kinetics
KW - real-time NMR spectroscopy
KW - TERRA RNA
Y1 - 2021
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-238917
VL - 60
IS - 19
SP - 10895
EP - 10901
ER -
TY - JOUR
A1 - Hoche, Joscha
A1 - Flock, Marco
A1 - Miao, Xincheng
A1 - Philipp, Luca Nils
A1 - Wenzel, Michael
A1 - Fischer, Ingo
A1 - Mitric, Roland
T1 - Excimer formation dynamics in the isolated tetracene dimer
JF - Chemical Science
N2 - The understanding of excimer formation and its interplay with the singlet-correlated triplet pair state \(^{1}\)(TT) is of high significance for the development of efficient organic electronics. Here, we study the photoinduced dynamics of the tetracene dimer in the gas phase by time-resolved photoionisation and photoion imaging experiments as well as nonadiabatic dynamics simulations in order to obtain mechanistic insight into the excimer formation dynamics. The experiments are performed using a picosecond laser system for excitation into the S\(_{2}\) state and reveal a biexponential time dependence. The time constants, obtained as a function of excess energy, lie in the range between ≈10 ps and 100 ps and are assigned to the relaxation of the excimer on the S\(_{1}\) surface and to its deactivation to the ground state. Simulations of the quantum-classical photodynamics are carried out in the frame of the semi-empirical CISD and TD-lc-DFTB methods. Both theoretical approaches reveal a dominating relaxation pathway that is characterised by the formation of a perfectly stacked excimer. TD-lc-DFTB simulations have also uncovered a second relaxation channel into a less stable dimer conformation in the S\(_{1}\) state. Both methods have consistently shown that the electronic and geometric relaxation to the excimer state is completed in less than 10 ps. The inclusion of doubly excited states in the CISD dynamics and their diabatisation further allowed to observe a transient population of the \(^{1}\)(TT) state, which, however, gets depopulated on a timescale of 8 ps, leading finally to the trapping in the excimer minimum.
KW - excimer formation
KW - tetracene dimer
KW - organic electronics
Y1 - 2021
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-251559
VL - 12
IS - 36
SP - 11965
EP - 11975
ER -
TY - JOUR
A1 - Maier, Jan
A1 - Marder, Todd B.
T1 - Mechanistic and Kinetic Factors of ortho‐Benzyne Formation in Hexadehydro‐Diels‐Alder (HDDA) Reactions
JF - Chemistry – A European Journal
N2 - With the rapid development of the hexadehydro‐Diels‐Alder reaction (HDDA) from its first discovery in 1997, the question of whether a concerted or stepwise mechanism better describes the thermally activated formation of ortho‐benzyne from a diyne and a diynophile has been debated. Mechanistic and kinetic investigations were able to show that this is not a black or white situation, as minor changes can tip the balance. For that reason, especially, linked yne‐diynes were studied to examine steric, electronic, and radical‐stabilizing effects of their terminal substituents on the reaction mechanism and kinetics. Furthermore, the influence of the nature of the linker on the HDDA reaction was explored. The more recently discovered photochemical HDDA reaction also gives ortho‐arynes, which display the same reactivity as the thermally generated ones, but their formation might not proceed by the same mechanism. This minireview summarizes the current state of mechanistic understanding of the HDDA reaction.
KW - Alkyne
KW - Benzyne
KW - Cyclization
KW - Hexadehydro-Diels-Alder
KW - reaction mechanism
Y1 - 2021
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-239006
VL - 27
IS - 30
SP - 7978
EP - 7991
ER -
TY - JOUR
A1 - Berger, Sarina M.
A1 - Ferger, Matthias
A1 - Marder, Todd B.
T1 - Synthetic Approaches to Triarylboranes from 1885 to 2020
JF - Chemistry – A European Journal
N2 - In recent years, research in the fields of optoelectronics, anion sensors and bioimaging agents have been greatly influenced by novel compounds containing triarylborane motifs. Such compounds possess an empty p‐orbital at boron which results in useful optical and electronic properties. Such a diversity of applications was not expected when the first triarylborane was reported in 1885. Synthetic approaches to triarylboranes underwent various changes over the following century, some of which are still used in the present day, such as the generally applicable routes developed by Krause et al. in 1922, or by Grisdale et al. in 1972 at Eastman Kodak. Some other developments were not pursued further after their initial reports, such as the synthesis of two triarylboranes bearing three different aromatic groups by Mikhailov et al. in 1958. This review summarizes the development of synthetic approaches to triarylboranes from their first report nearly 135 years ago to the present.
KW - arylmetalate
KW - boranes
KW - chromophore
KW - Lewis acid
KW - synthetic methods
Y1 - 2021
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-238952
VL - 27
IS - 24
SP - 7043
EP - 7058
ER -
TY - JOUR
A1 - Krüger, Sören
A1 - Leskien, Miriam
A1 - Schuller, Patricia
A1 - Prifert, Christiane
A1 - Weißbrich, Benedikt
A1 - Vogel, Ulrich
A1 - Krone, Manuel
T1 - Performance and feasibility of universal PCR admission screening for SARS‐CoV‐2 in a German tertiary care hospital
JF - Journal of Medical Virology
N2 - Anamnestic screening of symptoms and contact history is applied to identify coronavirus disease 2019 (COVID‐19) patients on admission. However, asymptomatic and presymptomatic patients remain undetected although the viral load may be high. In this retrospective cohort study, all hospitalized patients who received polymerase chain reaction (PCR) admission testing from March 26th until May 24th, 2020 were included. Data on COVID‐19‐specific symptoms and contact history to COVID‐19 cases were retrospectively extracted from patient files and from contact tracing notes. The compliance to the universal testing protocol was high with 90%. Out of 6940 tested patients, 27 new severe acute respiratory syndrome coronavirus‐2 infections (0.4%) were detected. Seven of those COVID‐19 cases (26% of all new cases) were asymptomatic and had no positive contact history, but were identified through a positive PCR test. The number needed to identify an asymptomatic patient was 425 in the first wave of the epidemic, 1218 in the low incidence phase. The specificity of the method was above 99.9%. Universal PCR testing was highly accepted by staff as demonstrated by high compliance. The costs to detect one asymptomatic case in future studies need to be traded off against the costs and damage caused by potential outbreaks of COVID‐19.
KW - admission screening
KW - COVID‐19
KW - infection control
KW - SARS‐CoV‐2
KW - testing strategy
Y1 - 2021
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-238971
VL - 93
IS - 5
SP - 2890
EP - 2898
ER -
TY - JOUR
A1 - Crumbach, Merian
A1 - Bachmann, Jonas
A1 - Fritze, Lars
A1 - Helbig, Andreas
A1 - Krummenacher, Ivo
A1 - Braunschweig, Holger
A1 - Helten, Holger
T1 - Dithiophene‐Fused Oxadiborepins and Azadiborepins: A New Class of Highly Fluorescent Heteroaromatics
JF - Angewandte Chemie International Edition
N2 - Access to dithiophene‐fused oxadiborepins and the first azadiborepins attained via a modular synthesis route are presented. The new compounds emit intense blue light, some of which demonstrate fluorescence quantum yields close to unity. Cyclic voltammetry (CV) revealed electrochemically reversible one‐electron reduction processes. The weak aromatic character of the novel 1,2,7‐azadiborepin ring is demonstrated with in‐depth theoretical investigations using nucleus‐independent chemical shift (NICS) scans and anisotropy of the induced current density (ACID) calculations.
KW - aromaticity
KW - BN compounds
KW - boron
KW - isoelectronic analogues
KW - polycycles
Y1 - 2021
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-238996
VL - 60
IS - 17
SP - 9290
EP - 9295
ER -
TY - JOUR
A1 - Hofmann, Julian
A1 - Ginex, Tiziana
A1 - Espargaró, Alba
A1 - Scheiner, Matthias
A1 - Gunesch, Sandra
A1 - Aragó, Marc
A1 - Stigloher, Christian
A1 - Sabaté, Raimon
A1 - Luque, F. Javier
A1 - Decker, Michael
T1 - Azobioisosteres of Curcumin with Pronounced Activity against Amyloid Aggregation, Intracellular Oxidative Stress, and Neuroinflammation
JF - Chemistry – A European Journal
N2 - Many (poly‐)phenolic natural products, for example, curcumin and taxifolin, have been studied for their activity against specific hallmarks of neurodegeneration, such as amyloid‐β 42 (Aβ42) aggregation and neuroinflammation. Due to their drawbacks, arising from poor pharmacokinetics, rapid metabolism, and even instability in aqueous medium, the biological activity of azobenzene compounds carrying a pharmacophoric catechol group, which have been designed as bioisoteres of curcumin has been examined. Molecular simulations reveal the ability of these compounds to form a hydrophobic cluster with Aβ42, which adopts different folds, affecting the propensity to populate fibril‐like conformations. Furthermore, the curcumin bioisosteres exceeded the parent compound in activity against Aβ42 aggregation inhibition, glutamate‐induced intracellular oxidative stress in HT22 cells, and neuroinflammation in microglial BV‐2 cells. The most active compound prevented apoptosis of HT22 cells at a concentration of 2.5 μm (83 % cell survival), whereas curcumin only showed very low protection at 10 μm (21 % cell survival).
KW - amyloid beta
KW - bioisosterism
KW - natural products
KW - neuroprotectivity
KW - replica-exchange molecular dynamics
Y1 - 2021
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-238988
VL - 27
IS - 19
SP - 6015
EP - 6027
ER -
TY - JOUR
A1 - Haack, Stephanie
A1 - Baiker, Sarah
A1 - Schlegel, Jan
A1 - Sauer, Markus
A1 - Sparwasser, Tim
A1 - Langenhorst, Daniela
A1 - Beyersdorf, Niklas
T1 - Superagonistic CD28 stimulation induces IFN‐γ release from mouse T helper 1 cells in vitro and in vivo
JF - European Journal of Immunology
N2 - Like human Th1 cells, mouse Th1 cells also secrete IFN‐γ upon stimulation with a superagonistic anti‐CD28 monoclonal antibody (CD28‐SA). Crosslinking of the CD28‐SA via FcR and CD40‐CD40L interactions greatly increased IFN‐γ release. Our data stress the utility of the mouse as a model organism for immune responses in humans.
KW - CD28
KW - Th1 cells
KW - cytokine release
KW - interferon γ
KW - Superagonistic antibody
Y1 - 2021
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-239028
VL - 51
IS - 3
SP - 738
EP - 741
ER -
TY - JOUR
A1 - Kamali, Salar
A1 - Rajendran, Ranjithkumar
A1 - Stadelmann, Christine
A1 - Karnati, Srikanth
A1 - Rajendran, Vinothkumar
A1 - Giraldo‐Velasquez, Mario
A1 - Berghoff, Martin
T1 - Oligodendrocyte‐specific deletion of FGFR2 ameliorates MOG\(_{35-55}\)‐induced EAE through ERK and Akt signalling
JF - Brain Pathology
N2 - Fibroblast growth factors (FGFs) and their receptors (FGFRs) are involved in demyelinating pathologies including multiple sclerosis (MS). In our recent study, oligodendrocyte‐specific deletion of FGFR1 resulted in a milder disease course, less inflammation, reduced myelin and axon damage in EAE. The objective of this study was to elucidate the role of oligodendroglial FGFR2 in MOG\(_{35-55}\)‐induced EAE. Oligodendrocyte‐specific knockout of FGFR2 (Fgfr2\(^{ind-/-}\)) was achieved by application of tamoxifen; EAE was induced using the MOG\(_{35-55}\) peptide. EAE symptoms were monitored over 62 days. Spinal cord tissue was analysed by histology, immunohistochemistry and western blot. Fgfr2\(^{ind-/-}\) mice revealed a milder disease course, less myelin damage and enhanced axonal density. The number of oligodendrocytes was not affected in demyelinated areas. However, protein expression of FGFR2, FGF2 and FGF9 was downregulated in Fgfr2\(^{ind-/-}\) mice. FGF/FGFR dependent signalling proteins were differentially regulated; pAkt was upregulated and pERK was downregulated in Fgfr2\(^{ind-/-}\) mice. The number of CD3(+) T cells, Mac3(+) cells and B220(+) B cells was less in demyelinated lesions of Fgfr2\(^{ind-/-}\) mice. Furthermore, expression of IL‐1β, TNF‐α and CD200 was less in Fgfr2\(^{ind-/-}\) mice than controls. Fgfr2ind−/− mice showed an upregulation of PLP and downregulation of the remyelination inhibitors SEMA3A and TGF‐β expression. These data suggest that cell‐specific deletion of FGFR2 in oligodendrocytes has anti‐inflammatory and neuroprotective effects accompanied by changes in FGF/FGFR dependent signalling, inflammatory cytokines and expression of remyelination inhibitors. Thus, FGFRs in oligodendrocytes may represent potential targets for the treatment of inflammatory and demyelinating diseases including MS.
KW - experimental autoimmune encephalomyelitis
KW - FGF/FGFR signalling
KW - multiple sclerosis
KW - oligodendrocytes
Y1 - 2021
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-224354
VL - 31
SP - 297
EP - 311
ER -
TY - JOUR
A1 - Brych, Mareike
A1 - Händel, Barbara F.
A1 - Riechelmann, Eva
A1 - Pieczykolan, Aleksandra
A1 - Huestegge, Lynn
T1 - Effects of vocal demands on pupil dilation
JF - Psychophysiology
N2 - Pupil dilation is known to be affected by a variety of factors, including physical (e.g., light) and cognitive sources of influence (e.g., mental load due to working memory demands, stimulus/response competition etc.). In the present experiment, we tested the extent to which vocal demands (speaking) can affect pupil dilation. Based on corresponding preliminary evidence found in a reanalysis of an existing data set from our lab, we setup a new experiment that systematically investigated vocal response‐related effects compared to mere jaw/lip movement and button press responses. Conditions changed on a trial‐by‐trial basis while participants were instructed to keep fixating a central cross on a screen throughout. In line with our prediction (and previous observation), speaking caused the pupils to dilate strongest, followed by nonvocal movements and finally a baseline condition without any vocal or muscular demands. An additional analysis of blink rates showed no difference in blink frequency between vocal and baseline conditions, but different blink dynamics. Finally, simultaneously recorded electromyographic activity showed that muscle activity may contribute to some (but not all) aspects of the observed effects on pupil size. The results are discussed in the context of other recent research indicating effects of perceived (instead of executed) vocal action on pupil dynamics.
KW - blink rate
KW - eye movements
KW - movement interaction
KW - pupil dilation
KW - vocal responses
Y1 - 2021
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-224425
VL - 58
IS - 2
ER -
TY - JOUR
A1 - Granath, Tim
A1 - Löbmann, Peer
A1 - Mandel, Karl
T1 - Oxidative Precipitation as a Versatile Method to Obtain Ferromagnetic Fe\(_{3}\)O\(_{4}\) Nano‐ and Mesocrystals Adjustable in Morphology and Magnetic Properties
JF - Particle & Particle Systems Characterization
N2 - Oxidative precipitation is a facile synthesis method to obtain ferromagnetic iron oxide nanoparticles from ferrous salts—with unexplored potential. The concentration of base and oxidant alone strongly affects the particle's structure and thus their magnetic properties despite the same material, magnetite (Fe\(_{3}\)O\(_{4}\)), is obtained when precipitated with potassium hydroxide (KOH) from ferrous sulfate (FeSO\(_{4}\)) and treated with potassium nitrate (KNO\(_{3}\)) at appropriate temperature. Depending on the potassium hydroxide and potassium nitrate concentrations, it is possible to obtain a series of different types of either single crystals or mesocrystals. The time‐dependent mesocrystal evolution can be revealed via electron microscopy and provides insights into the process of oriented attachment, yielding faceted particles, showing a facet‐dependent reactivity. It is found that it is the nitrate and hydroxide concentration that influences the ligand exchange process and thus the crystallization pathways. The presence of sulfate ions contributes to the mesocrystal evolution as well, as sulfate apparently hinders further crystal fusion, as revealed via infrared spectroscopy. Finally, it is found that nitrite, as one possible and ecologically highly relevant reduction product occurring in nature in context with iron, only evolves if the reaction is quantitative.
KW - colloidal nanostructures
KW - nanoparticle aggregation
KW - non‐classical crystallization
KW - oriented attachment
Y1 - 2021
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-224419
VL - 38
IS - 3
ER -
TY - JOUR
A1 - Schindler, Julia
A1 - Richter, Tobias
A1 - Mar, Raymond
T1 - Does generation benefit learning for narrative and expository texts? A direct replication attempt
JF - Applied Cognitive Psychology
N2 - Generated information is better recognized and recalled than information that is read. This so‐called generation effect has been replicated several times for different types of material, including texts. Perhaps the most influential demonstration was by McDaniel et al. (1986, Journal of Memory and Language, 25, 645–656; henceforth MEDC). This group tested whether the generation effect occurs only if the generation task stimulates cognitive processes not already stimulated by the text. Numerous studies, however, report difficulties replicating this text by generation‐task interaction, which suggests that the effect might only be found under conditions closer to the original method of MEDC. To test this assumption, we will closely replicate MEDC's Experiment 2 in German and English‐speaking samples. Replicating the effect would suggest that it can be reproduced, at least under limited conditions, which will provide the necessary foundation for future investigations into the boundary conditions of this effect, with an eye towards its utility in applied contexts.
KW - expository texts
KW - generation effect
KW - learning
KW - narrative texts
KW - replication
Y1 - 2021
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-224496
VL - 35
IS - 2
SP - 559
EP - 564
ER -
TY - JOUR
A1 - Miller, Franziska
A1 - Wintzheimer, Susanne
A1 - Prieschl, Johannes
A1 - Strauss, Volker
A1 - Mandel, Karl
T1 - A Supraparticle‐Based Five‐Level‐Identification Tag That Switches Information Upon Readout
JF - Advanced Optical Materials
N2 - Product identification tags are of great importance in a globalized world with increasingly complex trading routes and networks. Beyond currently used coding strategies, such as QR codes, higher data density, flexible application as well as miniaturization and readout indication are longed for in the next generation of security tags. In this work, micron‐sized supraparticles (SPs) with encoded information (ID) are produced that not only exhibit multiple initially covert identification levels but are also irreversibly marked as “read” upon readout. To achieve this, lanthanide doped CaF\(_{2}\) nanoparticles are assembled in various quantity‐weighted ratios via spray‐drying in presence of a broad‐spectrum stealth fluorophore (StFl), yielding covert spectrally encoded ID‐SPs. Using these as pigments, QR codes, initially dominated by the green fluorescence of the StFl, could be generated. Upon thermal energy input, these particle‐based tags irreversibly switch to an activated state revealing not only multiple luminescent colors but also spectral IDs. This strategy provides the next generation of material‐based security tags with a high data density and security level that switch information upon readout and can be, therefore, used as seal of quality.
KW - multilevel luminescence identification
KW - rare earth doped nanoparticles
KW - security tags
KW - stealth fluorophores
KW - supraparticles
Y1 - 2021
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-224469
VL - 9
IS - 4
ER -
TY - JOUR
A1 - Koeniger, Tobias
A1 - Bell, Luisa
A1 - Mifka, Anika
A1 - Enders, Michael
A1 - Hautmann, Valentin
A1 - Mekala, Subba Rao
A1 - Kirchner, Philipp
A1 - Ekici, Arif B.
A1 - Schulz, Christian
A1 - Wörsdörfer, Philipp
A1 - Mencl, Stine
A1 - Kleinschnitz, Christoph
A1 - Ergün, Süleyman
A1 - Kuerten, Stefanie
T1 - Bone marrow‐derived myeloid progenitors in the leptomeninges of adult mice
JF - Stem Cells
N2 - Although the bone marrow contains most hematopoietic activity during adulthood, hematopoietic stem and progenitor cells can be recovered from various extramedullary sites. Cells with hematopoietic progenitor properties have even been reported in the adult brain under steady‐state conditions, but their nature and localization remain insufficiently defined. Here, we describe a heterogeneous population of myeloid progenitors in the leptomeninges of adult C57BL/6 mice. This cell pool included common myeloid, granulocyte/macrophage, and megakaryocyte/erythrocyte progenitors. Accordingly, it gave rise to all major myelo‐erythroid lineages in clonogenic culture assays. Brain‐associated progenitors persisted after tissue perfusion and were partially inaccessible to intravenous antibodies, suggesting their localization behind continuous blood vessel endothelium such as the blood‐arachnoid barrier. Flt3\(^{Cre}\) lineage tracing and bone marrow transplantation showed that the precursors were derived from adult hematopoietic stem cells and were most likely continuously replaced via cell trafficking. Importantly, their occurrence was tied to the immunologic state of the central nervous system (CNS) and was diminished in the context of neuroinflammation and ischemic stroke. Our findings confirm the presence of myeloid progenitors at the meningeal border of the brain and lay the foundation to unravel their possible functions in CNS surveillance and local immune cell production.
KW - hematopoietic
KW - meninges
KW - mouse
KW - myeloid
KW - progenitor
Y1 - 2021
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-224452
VL - 39
IS - 2
SP - 227
EP - 239
ER -
TY - JOUR
A1 - Roy, Dipak Kumar
A1 - Tröster, Tobias
A1 - Fantuzzi, Felipe
A1 - Dewhurst, Rian D.
A1 - Lenczyk, Carsten
A1 - Radacki, Krzysztof
A1 - Pranckevicius, Conor
A1 - Engels, Bernd
A1 - Braunschweig, Holger
T1 - Isolation and Reactivity of an Antiaromatic s‐Block Metal Compound
JF - Angewandte Chemie International Edition
N2 - The concepts of aromaticity and antiaromaticity have a long history, and countless demonstrations of these phenomena have been made with molecules based on elements from the p, d, and f blocks of the periodic table. In contrast, the limited oxidation‐state flexibility of the s‐block metals has long stood in the way of their participation in sophisticated π‐bonding arrangements, and truly antiaromatic systems containing s‐block metals are altogether absent or remain poorly defined. Using spectroscopic, structural, and computational techniques, we present herein the synthesis and authentication of a heterocyclic compound containing the alkaline earth metal beryllium that exhibits significant antiaromaticity, and detail its chemical reduction and Lewis‐base‐coordination chemistry.
KW - antiaromaticity
KW - aromaticity
KW - beryllium
KW - heterocycles
KW - s-block metals
Y1 - 2021
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-224447
VL - 60
IS - 7
SP - 3812
EP - 3819
ER -
TY - JOUR
A1 - Dohrn, Maike F.
A1 - Ihne, Sandra
A1 - Hegenbart, Ute
A1 - Medina, Jessica
A1 - Züchner, Stephan L.
A1 - Coelho, Teresa
A1 - Hahn, Katrin
T1 - Targeting transthyretin ‐ Mechanism‐based treatment approaches and future perspectives in hereditary amyloidosis
JF - Journal of Neurochemistry
N2 - The liver‐derived, circulating transport protein transthyretin (TTR) is the cause of systemic hereditary (ATTRv) and wild‐type (ATTRwt) amyloidosis. TTR stabilization and knockdown are approved therapies to mitigate the otherwise lethal disease course. To date, the variety in phenotypic penetrance is not fully understood. This systematic review summarizes the current literature on TTR pathophysiology with its therapeutic implications. Tetramer dissociation is the rate‐limiting step of amyloidogenesis. Besides destabilizing TTR mutations, other genetic (RBP4, APCS, AR, ATX2, C1q, C3) and external (extracellular matrix, Schwann cell interaction) factors influence the type of onset and organ tropism. The approved small molecule tafamidis stabilizes the tetramer and significantly decelerates the clinical course. By sequence‐specific mRNA knockdown, the approved small interfering RNA (siRNA) patisiran and antisense oligonucleotide (ASO) inotersen both significantly reduce plasma TTR levels and improve neuropathy and quality of life compared to placebo. With enhanced hepatic targeting capabilities, GalNac‐conjugated siRNA and ASOs have recently entered phase III clinical trials. Bivalent TTR stabilizers occupy both binding groves in vitro, but have not been tested in trials so far. Tolcapone is another stabilizer with the potential to cross the blood–brain barrier, but its half‐life is short and liver failure a potential side effect. Amyloid‐directed antibodies and substances like doxycycline aim at reducing the amyloid load, however, none of the yet developed antibodies has successfully passed clinical trials. ATTR‐amyloidosis has become a model disease for pathophysiology‐based treatment. Further understanding of disease mechanisms will help to overcome the remaining limitations, including application burden, side effects, and blood–brain barrier permeability.
KW - amyloid‐directed antibodies
KW - ATTRv amyloidosis
KW - familial amyloid polyneuropathy (FAP)
KW - transthyretin
KW - TTR knockdown
KW - TTR stabilization
Y1 - 2021
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-224481
VL - 156
IS - 6
SP - 802
EP - 818
ER -
TY - JOUR
A1 - Heimberg, Linda
A1 - Knop, Stefan
T1 - Updated Perspectives on the Management of Relapsed and Refractory Multiple Myeloma
JF - Oncology Research and Treatment
N2 - Background: With the availability of T-cell-directed therapy and next-generation compounds of established classes of drugs, the treatment of relapsed/refractory (r/r) myeloma is getting more complex. However, treatment options in practice are limited by availability, approval, and patient comorbidity. The aim of this article is to provide a practical approach toward the choice of treatment for r/r myeloma patients. Summary: Regarding market authorization and current guidelines, at least in Germany, most patients nowadays will have received a doublet or triplet combination as first-line therapy containing a proteasome inhibitor and an immunomodulatory drug, mostly lenalidomide. We focus on the treatment options for patients that are ineligible for (another) stem cell transplantation. We will review treatment options for relapse after first- or second-line therapy and beyond third-line. Key Messages: There is promising data supporting the efficacy and safety of triplet combinations containing anti-CD38-monoclonal antibodies (anti-CD38 mAbs) at first or second relapse in combination with next-generation compounds. For the treatment beyond third-line, comparative studies are scarce but some promising compounds are available via conditional authorization, and there is more to come in the future. We will present some early phase trials featuring promising results.
KW - lenalidomide-refractory patients
KW - myeloma
Y1 - 2021
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-249773
SN - 2296-5270
SN - 2296-5262
VL - 44
IS - 12
ER -
TY - JOUR
A1 - Plassmeier, Lars
A1 - Hankir, Mohammed K.
A1 - Seyfried, Florian
T1 - Impact of Excess Body Weight on Postsurgical Complications
JF - Visceral Medicine
N2 - Background: Obesity is considered a risk factor for postoperative complications as it can limit exposure to the operation field, thereby significantly prolonging surgery time. Obesity-associated comorbidities, such as low-grade systemic inflammation, impaired functional status, and type 2 diabetes, are independent risk factors for impaired anastomotic wound healing and nonsurgical site infections. If obesity itself is an independent risk factor for surgical complications remains controversial, but the reason for this is largely unexplored. Summary: A MEDLINE literature search was performed using the terms: “obesity,” “excess body weight,” and “surgical complications.” Out of 65,493 articles 432 meta-analyses were screened, of which 25 meta-analyses were on the subject. The vast majority of complex oncologic procedures in the field of visceral surgery have shown higher complication rates in obese patients. Meta-analyses from the last 10 to 15 years with high numbers of patients enrolled consistently have shown longer operation times, higher blood loss, longer hospital stay for colorectal procedures, oncologic upper gastrointestinal (GI) procedures, and pancreatic surgery. Interestingly, these negative effects seem not to affect the overall survival in oncologic patients, especially in esophageal resections. A selection bias in oncologic upper GI patients may have influenced the results with higher BMI in upper GI cancer to be a predictor for better nutritional and performance status. Key Messages: Contrary to bariatric surgery, only limited evidence indicated that site and type of surgery, the approach to the abdominal cavity (laparoscopic vs. open), institutional factors, and the type of perioperative care such as ERAS protocols may play a role in determining postsurgical complications in obese patients. The initial question remains therefore partially unanswered. Large nationwide register-based studies are necessary to better understand which aspects of obesity and its related comorbidities define it as a risk factor for surgical complications.
KW - obesity
KW - surgical complications
KW - laparoscopy
Y1 - 2021
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-244890
SN - 2297-4725
SN - 2297-475X
VL - 37
IS - 4
ER -
TY - JOUR
A1 - Böckler, Anne
A1 - Rennert, Annika
A1 - Raettig, Tim
T1 - Stranger, Lover, Friend?
BT - The Pain of Rejection Does Not Depend
JF - Social Psychology
N2 - Social exclusion, even from minimal game-based interactions, induces negative consequences. We investigated whether the nature of the relationship with the excluder modulates the effects of ostracism. Participants played a virtual ball-tossing game with a stranger and a friend (friend condition) or a stranger and their romantic partner (partner condition) while being fully included, fully excluded, excluded only by the stranger, or excluded only by their close other. Replicating previous findings, full exclusion impaired participants’ basic-need satisfaction and relationship evaluation most severely. While the degree of exclusion mattered, the relationship to the excluder did not: Classic null hypothesis testing and Bayesian statistics showed no modulation of ostracism effects depending on whether participants were excluded by a stranger, a friend, or their partner.
KW - interpersonal relationships
KW - ostracism
KW - rejection
KW - social exclusion
KW - social interaction
Y1 - 2021
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-238721
SN - 1864-9335
SN - 2151-2590
VL - 52
IS - 3
ER -
TY - JOUR
A1 - Wittkowski, Joachim
A1 - Scheuchenpflug, Rainer
T1 - Evidence on the Conceptual Distinctness of Normal Grief From Depression
BT - A Multi-Faceted Analysis of Differential Validity
JF - European Journal of Health Psychology
N2 - Background: The distinctness of grief from depression has been the subject of a long scholarly debate, even influencing definitions of diagnostic criteria. Aims: This study aims at clarifying the issue by a multifaceted analysis of data from a large German sample. Method: A community sample of 406 bereaved persons answered the Wuerzburg Grief Inventory (WGI), a multidimensional grief questionnaire designed to measure normal grief in the German language, and the General Depression Scale – Short Version (GDS-S), a self-report depression scale. Data were analyzed by factor analysis to identify structural (dis-)similarities of the constructs, and analysis of variance (ANOVA) to identify the influence of the factors relationship to the deceased, type of death, and time since loss on grief measures and depression scores. Results: Factor analysis clustered items referring to grief-related impairments and depression into one factor, items referring to other dimensions of grief on separate factors, however. Relationship to the deceased influenced the grief measures impairments and nearness to the deceased, but not depression scores if controlled for impairments. Type of death showed specific effects on grief scores, but not on depression scores. Time since loss influenced grief scores, but not depression scores. Limitations: The analysis is based on a self-selected community sample of grieving persons, self-report measures, and in part, on cross-sectional data. Conclusion: Factor analysis and objective data show a clear distinction of dimensions of grief and depression. The human experience of grief contains a sense of nearness to the lost person, feelings of guilt, and positive aspects of the loss experience in addition to components resembling depression.
KW - depression
KW - grief
KW - time since loss
KW - type of death
KW - Wuerzburg Grief Inventory (WGI)
Y1 - 2021
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-236531
SN - 2512-8442
SN - 2512-8450
VL - 28
IS - 3
SP - 101-110
ER -
TY - JOUR
A1 - Bunzmann, Nikolai
A1 - Krugmann, Benjamin
A1 - Weissenseel, Sebastian
A1 - Kudriashova, Liudmila
A1 - Ivaniuk, Khrystyna
A1 - Stakhira, Pavlo
A1 - Cherpak, Vladyslav
A1 - Chapran, Marian
A1 - Grybauskaite‐Kaminskiene, Gintare
A1 - Grazulevicius, Juozas Vidas
A1 - Dyakonov, Vladimir
A1 - Sperlich, Andreas
T1 - Spin‐ and Voltage‐Dependent Emission from Intra‐ and Intermolecular TADF OLEDs
JF - Advanced Electronic Materials
N2 - Organic light emitting diodes (OLEDs) based on thermally activated delayed fluorescence (TADF) utilize molecular systems with a small energy splitting between singlet and triplet states. This can either be realized in intramolecular charge transfer states of molecules with near‐orthogonal donor and acceptor moieties or in intermolecular exciplex states formed between a suitable combination of individual donor and acceptor materials. Here, 4,4′‐(9H,9′H‐[3,3′‐bicarbazole]‐9,9′‐diyl)bis(3‐(trifluoromethyl) benzonitrile) (pCNBCzoCF\(_{3}\)) is investigated, which shows intramolecular TADF but can also form exciplex states in combination with 4,4′,4′′‐tris[phenyl(m‐tolyl)amino]triphenylamine (m‐MTDATA). Orange emitting exciplex‐based OLEDs additionally generate a sky‐blue emission from the intramolecular emitter with an intensity that can be voltage‐controlled. Electroluminescence detected magnetic resonance (ELDMR) is applied to study the thermally activated spin‐dependent triplet to singlet up‐conversion in operating devices. Thereby, intermediate excited states involved in OLED operation can be investigated and the corresponding activation energy for both, intra‐ and intermolecular based TADF can be derived. Furthermore, a lower estimate is given for the extent of the triplet wavefunction to be ≥ 1.2 nm. Photoluminescence detected magnetic resonance (PLDMR) reveals the population of molecular triplets in optically excited thin films. Overall, the findings allow to draw a comprehensive picture of the spin‐dependent emission from intra‐ and intermolecular TADF OLEDs.
KW - color tuning
KW - exciplexes
KW - organic light emitting diodes
KW - spin
KW - triplets
Y1 - 2021
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-224434
VL - 7
IS - 3
ER -
TY - JOUR
A1 - Mechau, Jannik
A1 - Frank, Andreas
A1 - Bakirci, Ezgi
A1 - Gumbel, Simon
A1 - Jungst, Tomasz
A1 - Giesa, Reiner
A1 - Groll, Jürgen
A1 - Dalton, Paul D.
A1 - Schmidt, Hans‐Werner
T1 - Hydrophilic (AB)\(_{n}\) Segmented Copolymers for Melt Extrusion‐Based Additive Manufacturing
JF - Macromolecular Chemistry and Physics
N2 - Several manufacturing technologies beneficially involve processing from the melt, including extrusion‐based printing, electrospinning, and electrohydrodynamic jetting. In this study, (AB)\(_{n}\) segmented copolymers are tailored for melt‐processing to form physically crosslinked hydrogels after swelling. The copolymers are composed of hydrophilic poly(ethylene glycol)‐based segments and hydrophobic bisurea segments, which form physical crosslinks via hydrogen bonds. The degree of polymerization was adjusted to match the melt viscosity to the different melt‐processing techniques. Using extrusion‐based printing, a width of approximately 260 µm is printed into 3D constructs, with excellent interlayer bonding at fiber junctions, due to hydrogen bonding between the layers. For melt electrospinning, much thinner fibers in the range of about 1–15 µm are obtained and produced in a typical nonwoven morphology. With melt electrowriting, fibers are deposited in a controlled way to well‐defined 3D constructs. In this case, multiple fiber layers fuse together enabling constructs with line width in the range of 70 to 160 µm. If exposed to water the printed constructs swell and form physically crosslinked hydrogels that slowly disintegrate, which is a feature for soluble inks within biofabrication strategies. In this context, cytotoxicity tests confirm the viability of cells and thus demonstrating biocompatibility of this class of copolymers.
KW - 3D printing
KW - (AB)\(_{n}\) segmented copolymers
KW - biocompatibility
KW - melt electrowriting
Y1 - 2021
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-224513
VL - 222
IS - 1
ER -
TY - JOUR
A1 - Krahfuss, Mirjam J.
A1 - Radius, Udo
T1 - N‐Heterocyclic Silylene Main Group Element Chemistry: Adduct Formation, Insertion into E−X Bonds and Cyclization of Organoazides
JF - European Journal of Inorganic Chemistry
N2 - Investigations concerning the reactivity of the N‐heterocyclic silylene Dipp\(_{2}\)NHSi (1, 1,3‐bis(2,6‐diisopropylphenyl)‐1,3‐diaza‐2‐silacyclopent‐4‐en‐2‐ylidene) towards selected alanes and boranes, elemental halides X\(_{2}\) (X=Br, I), selected halide containing substrates such as tin chlorides and halocarbons, as well as organoazides are presented. The NHSi adducts Dipp\(_{2}\)NHSi⋅AlI\(_{3}\) (2), Dipp\(_{2}\)NHSi⋅Al(C\(_{6}\)F\(_{5}\))\(_{3}\) (3), and Dipp\(_{2}\)NHSi⋅B(C\(_{6}\)F\(_{5}\))\(_{3}\) (4) were formed by the reaction of Dipp\(_{2}\)NHSi with the corresponding Lewis acids AlI\(_{3}\), Al(C\(_{6}\)F\(_{6}\))\(_{3}\) and B(C\(_{6}\)F\(_{5}\))\(_{3}\). Adducts 3 and 4 were tested with respect to their ability to activate small organic molecules, but no frustrated Lewis pair reactivity was observed. Reactions of Dipp\(_{2}\)NHSi with Br\(_{2}\), I\(_{2}\), Ph\(_{2}\)SnCl\(_{2}\) and Me\(_{3}\)SnCl led to formation of Dipp\(_{2}\)NHSiBr\(_{2}\) (5), Dipp\(_{2}\)NHSiI\(_{2}\) (6), Dipp\(_{2}\)NHSiCl\(_{2}\) (7) and {(Me\(_{3}\)Sn)N(Dipp)CH}\(_{2}\) (8), respectively. The reaction with the halocarbons methyl iodide, benzyl chloride, and benzyl bromide afforded the insertion products Dipp\(_{2}\)NHSi(I)(CH\(_{3}\)) (9), Dipp\(_{2}\)NHSi(Cl)(CH\(_{2}\)Ph) (10) and Dipp\(_{2}\)NHSi(Br)(CH\(_{2}\)Ph) (11). Reaction of Dipp\(_{2}\)NHSi with the organoazides Ad‐N\(_{3}\) (Ad=adamantyl) and TMS‐N\(_{3}\) (TMS=trimethylsilyl) led to the formation of 1‐Dipp\(_{2}\)NHSi‐2,5‐bis(adamantyl)‐tetrazoline (12) and bis(trimethylsilyl)amido azido silane (13), respectively. For 2,6‐(diphenyl)phenyl‐N\(_{3}\) C−H activation occurs and a cyclosilamine 14 was isolated.
KW - arbenes
KW - E−X bond activation
KW - acid/base adducts
KW - Organoazides
KW - Silylenes
Y1 - 2021
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-224507
VL - 2021
IS - 6
SP - 548
EP - 561
ER -
TY - JOUR
A1 - Renner, Rebecca
A1 - Mahlmeister, Bernhard
A1 - Anhalt, Olga
A1 - Stolte, Matthias
A1 - Würthner, Frank
T1 - Chiral Perylene Bisimide Dyes by Interlocked Arene Substituents in the Bay Area
JF - Chemistry - A European Journal
N2 - A series of perylene bisimide (PBI) dyes bearing various aryl substituents in 1,6,7,12 bay positions has been synthesized by Suzuki cross-coupling reaction. These molecules exhibit an exceptionally large and conformationally fixed twist angle of the PBI π-core due to the high steric congestion imparted by the aryl substituents in bay positions. Single crystal X-ray analyses of phenyl-, naphthyl- and pyrenyl-functionalized PBIs reveal interlocked π-π-stacking motifs, leading to conformational chirality and the possibility for the isolation of enantiopure atropoisomers by semipreparative HPLC. The interlocked arrangement endows these molecules with substantial racemization barriers of about 120 kJ mol\(^{−1}\) for the tetraphenyl- and tetra-2-naphthyl-substituted derivatives, which is among the highest racemization barriers for axially chiral PBIs. Variable temperature NMR studies reveal the presence of a multitude of up to fourteen conformational isomers in solution that are interconverted via smaller activation barriers of about 65 kJ mol\(^{−1}\). The redox and optical properties of these core-twisted PBIs have been characterized by cyclic voltammetry, UV/Vis/NIR and fluorescence spectroscopy and their respective atropo-enantiomers were further characterized by circular dichroism (CD) and circular polarized luminescence (CPL) spectroscopy.
KW - Suzuki coupling
KW - perylenebisimide dyes
KW - circular polarized luminescence
KW - chirality
Y1 - 2021
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-249070
VL - 27
IS - 46
SP - 11997
EP - 12006
ER -
TY - JOUR
A1 - Rupp, Mira T.
A1 - Auvray, Thomas
A1 - Hanan, Garry S.
A1 - Kurth, Dirk G.
T1 - Electrochemical and photophysical study of homoleptic and heteroleptic methylated Ru(II) Bis-terpyridine complexes
JF - European Journal of Inorganic Chemistry
N2 - In this study, we investigate the impact of N-methylation on the electronic and photophysical properties of both homoleptic and heteroleptic Ru(II) bis-terpyridine complexes based on the recently reported ligand 4’-(4-bromophenyl)-4,4’’’: 4’’,4’’’’-dipyr-idinyl-2,2’ : 6’,2’’-terpyridine (Bipytpy), with pyridine substituents in the 4- and 4’’-position. The first reduction of the methylated complexes takes place at the pyridinium site and is observed as multi-electron process. Following N-methylation, the complexes exhibit higher luminescence quantum yields and longer excited-state lifetimes. Interestingly, the photophysical properties of the heteroleptic and homoleptic complexes are rather similar. TD-DFT calculations support the experimental results. Furthermore, the complexes are tested as photosensitizers for photocatalytic hydrogen production, as the parent complex 1[Ru(Bipytpy)(Tolyltpy)](PF \(_6\))\(_2\) (Tolyltpy: 4’-tolyl-2,2’: 6’,2’’-terpyri-dine) was recently shown to be active and highly stable underphotocatalytic conditions. However, the methylated complexes reported herein are inactive as photosensitizers under the chosen conditions, presumably due to loss of the methyl groups, converting them to the non-methylated parent complexes.
KW - Ruthenium
KW - Luminescence
KW - Electrochemistry
KW - Ligand effects
KW - Photocatalysis
Y1 - 2021
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-248769
VL - 2021
IS - 28
SP - 2822
EP - 2829
ER -
TY - JOUR
A1 - Chen, Chunguang
A1 - Rawat, Divya
A1 - Samikannu, Balaji
A1 - Bender, Markus
A1 - Preissner, Klaus T.
A1 - Linn, Thomas
T1 - Platelet glycoprotein VI‐dependent thrombus stabilization is essential for the intraportal engraftment of pancreatic islets
JF - American Journal of Transplantation
N2 - Platelet activation and thrombus formation have been implicated to be detrimental for intraportal pancreatic islet transplants. The platelet‐specific collagen receptor glycoprotein VI (GPVI) plays a key role in thrombosis through cellular activation and the subsequent release of secondary mediators. In aggregometry and in a microfluidic dynamic assay system modeling flow in the portal vein, pancreatic islets promoted platelet aggregation and triggered thrombus formation, respectively. While platelet GPVI deficiency did not affect the initiation of these events, it was found to destabilize platelet aggregates and thrombi in this process. Interestingly, while no major difference was detected in early thrombus formation after intraportal islet transplantation, genetic GPVI deficiency or acute anti‐GPVI treatment led to an inferior graft survival and function in both syngeneic mouse islet transplantation and xenogeneic human islet transplantation models. These results demonstrate that platelet GPVI signaling is indispensable in stable thrombus formation induced by pancreatic islets. GPVI deficiency resulted in thrombus destabilization and inferior islet engraftment indicating that thrombus formation is necessary for a successful intraportal islet transplantation in which platelets are active modulators.
KW - basic (laboratory) research / science
KW - coagulation and hemostasis
KW - graft survival
KW - islet transplantation
KW - molecular biology
Y1 - 2021
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-224471
VL - 21
SP - 2079
EP - 2089
ER -
TY - JOUR
A1 - Cullmann, Katharina
A1 - Jahn, Magdalena
A1 - Spindler, Markus
A1 - Schenk, Franziska
A1 - Manukjan, Georgi
A1 - Mucci, Adele
A1 - Steinemann, Doris
A1 - Boller, Klaus
A1 - Schulze, Harald
A1 - Bender, Markus
A1 - Moritz, Thomas
A1 - Modlich, Ute
T1 - Forming megakaryocytes from murine‐induced pluripotent stem cells by the inducible overexpression of supporting factors
JF - Research and Practice in Thrombosis and Haemostasis
N2 - Background
Platelets are small anucleate cells that circulate in the blood in a resting state but can be activated by external cues. In case of need, platelets from blood donors can be transfused. As an alternative source, platelets can be produced from induced pluripotent stem cells (iPSCs); however, recovered numbers are low.
Objectives
To optimize megakaryocyte (MK) and platelet output from murine iPSCs, we investigated overexpression of the transcription factors GATA‐binding factor 1 (GATA1); nuclear factor, erythroid 2; and pre–B‐cell leukemia transcription factor 1 (Pbx1) and a hyperactive variant of the small guanosine triphosphatase RhoA (RhoAhc).
Methods
To avoid off‐target effects, we generated iPSCs carrying the reverse tetracycline‐responsive transactivator M2 (rtTA‐M2) in the Rosa26 locus and expressed the factors from Tet‐inducible gammaretroviral vectors. Differentiation of iPSCs was initiated by embryoid body (EB) formation. After EB dissociation, early hematopoietic progenitors were enriched and cocultivated on OP9 feeder cells with thrombopoietin and stem cell factor to induce megakaryocyte (MK) differentiation.
Results
Overexpression of GATA1 and Pbx1 increased MK output 2‐ to 2.5‐fold and allowed prolonged collection of MK. Cytologic and ultrastructural analyses identified typical MK with enlarged cells, multilobulated nuclei, granule structures, and an internal membrane system. However, GATA1 and Pbx1 expression did not improve MK maturation or platelet release, although in vitro–generated platelets were functional in spreading on fibrinogen or collagen‐related peptide.
Conclusion
We demonstrate that the use of rtTA‐M2 transgenic iPSCs transduced with Tet‐inducible retroviral vectors allowed for gene expression at later time points during differentiation. With this strategy we could identify factors that increased in vitro MK production.
KW - genetic modification
KW - iPS cells
KW - megakaryocytes
KW - retroviral vectors
KW - Tet‐inducible system
Y1 - 2021
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-224565
VL - 5
IS - 1
SP - 111
EP - 124
ER -
TY - JOUR
A1 - Boff, Samuel
A1 - Friedel, Anna
T1 - Dynamics of nest occupation and homing of solitary bees in painted trap nests
JF - Ecological Entomology
N2 - 1. The oil‐collecting bee Centris analis (Fabricius, 1804) is an important pollinator for the Neotropical region. The species can be attracted to nest in human‐made cavities. Such trap nests or insect hotels offer the opportunity to study the behaviour of populations in semifield conditions.
2. We studied a newly established trap nest aggregation of C. analis in Mato Grosso do Sul, Brazil and tested the effect that differentially painted nesting options have on the rate of nest foundation, and on the ability of relocating the nest when returning from a foraging trip (homing behaviour). Moreover, we tested if the duration of foraging trips decreased with time.
3. We found that females preferred to nest in painted nests compared to unpainted nests, with blue nests being the most occupied ones, followed by purple, yellow, white, and green. Furthermore, bees improved their homing behaviour with time, however, nest colour did not seem to have an effect on this process. Moreover, we found that bees reduce the duration of their foraging trips with time. This could be an indicator of improved foraging efficiency through learning.
4. These findings could inform a new and fruitful line of research on the behaviour and ecology of trap nesting solitary bees.
KW - foraging activities
KW - nesting ecology
KW - oil bees
KW - painted nest preference
Y1 - 2021
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-224605
VL - 46
IS - 2
SP - 496
EP - 499
ER -
TY - JOUR
A1 - Welker, Armin
A1 - Kersten, Christian
A1 - Müller, Christin
A1 - Madhugiri, Ramakanth
A1 - Zimmer, Collin
A1 - Müller, Patrick
A1 - Zimmermann, Robert
A1 - Hammerschmidt, Stefan
A1 - Maus, Hannah
A1 - Ziebuhr, John
A1 - Sotriffer, Christoph
A1 - Schirmeister, Tanja
T1 - Structure‐Activity Relationships of Benzamides and Isoindolines Designed as SARS‐CoV Protease Inhibitors Effective against SARS‐CoV‐2
JF - ChemMedChem
N2 - Inhibition of coronavirus (CoV)‐encoded papain‐like cysteine proteases (PL\(^{pro}\)) represents an attractive strategy to treat infections by these important human pathogens. Herein we report on structure‐activity relationships (SAR) of the noncovalent active‐site directed inhibitor (R)‐5‐amino‐2‐methyl‐N‐(1‐(naphthalen‐1‐yl)ethyl) benzamide (2 b), which is known to bind into the S3 and S4 pockets of the SARS‐CoV PL\(^{pro}\). Moreover, we report the discovery of isoindolines as a new class of potent PL\(^{pro}\) inhibitors. The studies also provide a deeper understanding of the binding modes of this inhibitor class. Importantly, the inhibitors were also confirmed to inhibit SARS‐CoV‐2 replication in cell culture suggesting that, due to the high structural similarities of the target proteases, inhibitors identified against SARS‐CoV PL\(^{pro}\) are valuable starting points for the development of new pan‐coronaviral inhibitors.
KW - antiviral agents
KW - computational chemistry
KW - drug design
KW - protease inhibitors
KW - structure-activity relationships
Y1 - 2021
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-225700
VL - 16
IS - 2
SP - 340
EP - 354
ER -
TY - JOUR
A1 - Romero‐Olmedo, Addi J.
A1 - Schulz, Axel R.
A1 - Huber, Magdalena
A1 - Brehm, Corinna U.
A1 - Chang, Hyun‐Dong
A1 - Chiarolla, Cristina M.
A1 - Bopp, Tobias
A1 - Skevaki, Chrysanthi
A1 - Berberich‐Siebelt, Friederike
A1 - Radbruch, Andreas
A1 - Mei, Henrik E.
A1 - Lohoff, Michael
T1 - Deep phenotypical characterization of human CD3\(^{+}\)CD56\(^{+}\) T cells by mass cytometry
JF - European Journal of Immunology
N2 - CD56\(^{+}\) T cells are a group of pro‐inflammatory CD3\(^{+}\) lymphocytes with characteristics of natural killer cells, being involved in antimicrobial immune defense. Here, we performed deep phenotypic profiling of CD3\(^{+}\)CD56\(^{+}\) cells in peripheral blood of normal human donors and individuals sensitized to birch‐pollen or/and house dust mite by high‐dimensional mass cytometry combined with manual and computational data analysis. A co‐regulation between major conventional T‐cell subsets and their respective CD3\(^{+}\)CD56\(^{+}\) cell counterparts appeared restricted to CD8\(^{+}\), MAIT, and TCRγδ\(^{+}\) T‐cell compartments. Interestingly, we find a co‐regulation of several CD3\(^{+}\)CD56\(^{+}\) cell subsets in allergic but not in healthy individuals. Moreover, using FlowSOM, we distinguished a variety of CD56\(^{+}\) T‐cell phenotypes demonstrating a hitherto underestimated heterogeneity among these cells. The novel CD3\(^{+}\)CD56\(^{+}\) subset description comprises phenotypes superimposed with naive, memory, type 1, 2, and 17 differentiation stages, in part represented by a phenotypical continuum. Frequencies of two out of 19 CD3\(^{+}\)CD56\(^{+}\) FlowSOM clusters were significantly diminished in allergic individuals, demonstrating less frequent presence of cells with cytolytic, presumably protective, capacity in these donors consistent with defective expansion or their recruitment to the affected tissue. Our results contribute to defining specific cell populations to be targeted during therapy for allergic conditions.
KW - allergy
KW - CD56
KW - human
KW - mass cytometry
KW - T cells
Y1 - 2021
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-225699
VL - 51
IS - 3
SP - 672
EP - 681
ER -
TY - JOUR
A1 - Doryab, Ali
A1 - Taskin, Mehmet Berat
A1 - Stahlhut, Philipp
A1 - Schröppel, Andreas
A1 - Wagner, Darcy E.
A1 - Groll, Jürgen
A1 - Schmid, Otmar
T1 - A Biomimetic, Copolymeric Membrane for Cell‐Stretch Experiments with Pulmonary Epithelial Cells at the Air‐Liquid Interface
JF - Advanced Functional Materials
N2 - Chronic respiratory diseases are among the leading causes of death worldwide, but only symptomatic therapies are available for terminal illness. This in part reflects a lack of biomimetic in vitro models that can imitate the complex environment and physiology of the lung. Here, a copolymeric membrane consisting of poly(ε‐)caprolactone and gelatin with tunable properties, resembling the main characteristics of the alveolar basement membrane is introduced. The thin bioinspired membrane (≤5 μm) is stretchable (up to 25% linear strain) with appropriate surface wettability and porosity for culturing lung epithelial cells under air–liquid interface conditions. The unique biphasic concept of this membrane provides optimum characteristics for initial cell growth (phase I) and then switch to biomimetic properties for cyclic cell‐stretch experiments (phase II). It is showed that physiologic cyclic mechanical stretch improves formation of F‐actin cytoskeleton filaments and tight junctions while non‐physiologic over‐stretch induces cell apoptosis, activates inflammatory response (IL‐8), and impairs epithelial barrier integrity. It is also demonstrated that cyclic physiologic stretch can enhance the cellular uptake of nanoparticles. Since this membrane offers considerable advantages over currently used membranes, it may lead the way to more biomimetic in vitro models of the lung for translation of in vitro response studies into clinical outcome.
KW - alveolar‐capillary barrier
KW - cyclic mechanical stretch
KW - hybrid polymers
KW - in vitro cell‐stretch model
KW - tunable ultra‐thin biphasic membrane
Y1 - 2021
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-225645
VL - 31
IS - 10
ER -
TY - JOUR
A1 - Hanft, Anna
A1 - Radacki, Krzysztof
A1 - Lichtenberg, Crispin
T1 - Cationic Bismuth Aminotroponiminates: Charge Controls Redox Properties
JF - Chemistry – A European Journal
N2 - The behavior of the redox‐active aminotroponiminate (ATI) ligand in the coordination sphere of bismuth has been investigated in neutral and cationic compounds, [Bi(ATI)\(_{3}\)] and [Bi(ATI)\(_{2}\)L\(_{n}\)][A] (L=neutral ligand; n=0, 1; A=counteranion). Their coordination chemistry in solution and in the solid state has been analyzed through (variable‐temperature) NMR spectroscopy, line‐shape analysis, and single‐crystal X‐ray diffraction analyses, and their Lewis acidity has been evaluated by using the Gutmann–Beckett method (and modifications thereof). Cyclic voltammetry, in combination with DFT calculations, indicates that switching between ligand‐ and metal‐centered redox events is possible by altering the charge of the compounds from 0 in neutral species to +1 in cationic compounds. This adds important facets to the rich redox chemistry of ATIs and to the redox chemistry of bismuth compounds, which is, so far, largely unexplored.
KW - aminotroponiminates
KW - bismuth
KW - cationic species
KW - redox chemistry
KW - redox-active ligands
Y1 - 2021
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-225669
VL - 27
IS - 20
SP - 6230
EP - 6239
ER -
TY - JOUR
A1 - Budiman, Yudha P.
A1 - Lorenzen, Sabine
A1 - Liu, Zhiqiang
A1 - Radius, Udo
A1 - Marder, Todd B.
T1 - Base‐Free Pd‐Catalyzed C−Cl Borylation of Fluorinated Aryl Chlorides
JF - Chemistry – A European Journal
N2 - Catalytic C−X borylation of aryl halides containing two ortho‐fluorines has been found to be challenging, as most previous methods require stoichiometric amounts of base and the polyfluorinated aryl boronates suffer from protodeboronation, which is accelerated by ortho‐fluorine substituents. Herein, we report that a combination of Pd(dba)2 (dba=dibenzylideneacetone) with SPhos (2‐dicyclohexylphosphino‐2’,6’‐dimethoxybiphenyl) as a ligand is efficient to catalyze the C‐Cl borylation of aryl chlorides containing two ortho‐fluorine substituents. This method, conducted under base‐free conditions, is compatible with the resulting di‐ortho‐fluorinated aryl boronate products which are sensitive to base.
KW - boronate ester
KW - borylation
KW - cross-coupling
KW - fluoroarene
KW - palladium-catalyzed
Y1 - 2021
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-225687
VL - 27
IS - 11
SP - 3869
EP - 3874
ER -
TY - JOUR
A1 - Weich, Alexander
A1 - Werner, Rudolf A.
A1 - Buck, Andreas K.
A1 - Hartrampf, Philipp E.
A1 - Serfling, Sebastian E.
A1 - Scheurlen, Michael
A1 - Wester, Hans-Jürgen
A1 - Meining, Alexander
A1 - Kircher, Stefan
A1 - Higuchi, Takahiro
A1 - Pomper, Martin G.
A1 - Rowe, Steven P.
A1 - Lapa, Constantin
A1 - Kircher, Malte
T1 - CXCR4-Directed PET/CT in Patients with Newly Diagnosed Neuroendocrine Carcinomas
JF - Diagnostics
N2 - We aimed to elucidate the diagnostic potential of the C-X-C motif chemokine receptor 4 (CXCR4)-directed positron emission tomography (PET) tracer \(^{68}\)Ga-Pentixafor in patients with poorly differentiated neuroendocrine carcinomas (NEC), relative to the established reference standard \(^{18}\)F-FDG PET/computed tomography (CT). In our database, we retrospectively identified 11 treatment-naïve patients with histologically proven NEC, who underwent \(^{18}\)F-FDG and CXCR4-directed PET/CT for staging and therapy planning. The images were analyzed on a per-patient and per-lesion basis and compared to immunohistochemical staining (IHC) of CXCR4 from PET-guided biopsies. \(^{68}\)Ga-Pentixafor visualized tumor lesions in 10/11 subjects, while \(^{18}\)F-FDG revealed sites of disease in all 11 patients. Although weak to moderate CXCR4 expression could be corroborated by IHC in 10/11 cases, \(^{18}\)F-FDG PET/CT detected significantly more tumor lesions (102 vs. 42; total lesions, n = 107; p < 0.001). Semi-quantitative analysis revealed markedly higher 18F-FDG uptake as compared to \(^{68}\)Ga-Pentixafor (maximum and mean standardized uptake values (SUV) and tumor-to-background ratios (TBR) of cancerous lesions, SUVmax: 12.8 ± 9.8 vs. 5.2 ± 3.7; SUVmean: 7.4 ± 5.4 vs. 3.1 ± 3.2, p < 0.001; and, TBR 7.2 ± 7.9 vs. 3.4 ± 3.0, p < 0.001). Non-invasive imaging of CXCR4 expression in NEC is inferior to the reference standard \(^{18}\)F-FDG PET/CT.
KW - CXCR4
KW - NET
KW - NEC
KW - 68Ga-Pentixafor
KW - 18F-FDG
Y1 - 2021
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-234231
SN - 2075-4418
VL - 11
IS - 4
ER -
TY - JOUR
A1 - Mönius, Katja
T1 - Eigenvalues of zero-divisor graphs of finite commutative rings
JF - Journal of Algebraic Combinatorics
N2 - We investigate eigenvalues of the zero-divisor graph Γ(R) of finite commutative rings R and study the interplay between these eigenvalues, the ring-theoretic properties of R and the graph-theoretic properties of Γ(R). The graph Γ(R) is defined as the graph with vertex set consisting of all nonzero zero-divisors of R and adjacent vertices x, y whenever xy=0. We provide formulas for the nullity of Γ(R), i.e., the multiplicity of the eigenvalue 0 of Γ(R). Moreover, we precisely determine the spectra of \(\Gamma ({\mathbb {Z}}_p \times {\mathbb {Z}}_p \times {\mathbb {Z}}_p)\) and \(\Gamma ({\mathbb {Z}}_p \times {\mathbb {Z}}_p \times {\mathbb {Z}}_p \times {\mathbb {Z}}_p)\) for a prime number p. We introduce a graph product ×Γ with the property that Γ(R)≅Γ(R\(_1\))×Γ⋯×ΓΓ(R\(_r\)) whenever R≅R\(_1\)×⋯×R\(_r\). With this product, we find relations between the number of vertices of the zero-divisor graph Γ(R), the compressed zero-divisor graph, the structure of the ring R and the eigenvalues of Γ(R).
KW - EJMA-D-19-00287
KW - Zero-divisor graphs
KW - Graph eigenvalues
KW - Graphnullity
KW - Graph products
KW - Local rings
Y1 - 2021
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-232792
SN - 0925-9899
VL - 54
ER -
TY - JOUR
A1 - Grob, Robin
A1 - Tritscher, Clara
A1 - Grübel, Kornelia
A1 - Stigloher, Christian
A1 - Groh, Claudia
A1 - Fleischmann, Pauline N.
A1 - Rössler, Wolfgang
T1 - Johnston's organ and its central projections in Cataglyphis desert ants
JF - Journal of Comparative Neurology
N2 - The Johnston's organ (JO) in the insect antenna is a multisensory organ involved in several navigational tasks including wind‐compass orientation, flight control, graviception, and, possibly, magnetoreception. Here we investigate the three dimensional anatomy of the JO and its neuronal projections into the brain of the desert ant Cataglyphis, a marvelous long‐distance navigator. The JO of C. nodus workers consists of 40 scolopidia comprising three sensory neurons each. The numbers of scolopidia slightly vary between different sexes (female/male) and castes (worker/queen). Individual scolopidia attach to the intersegmental membrane between pedicel and flagellum of the antenna and line up in a ring‐like organization. Three JO nerves project along the two antennal nerve branches into the brain. Anterograde double staining of the antennal afferents revealed that JO receptor neurons project to several distinct neuropils in the central brain. The T5 tract projects into the antennal mechanosensory and motor center (AMMC), while the T6 tract bypasses the AMMC via the saddle and forms collaterals terminating in the posterior slope (PS) (T6I), the ventral complex (T6II), and the ventrolateral protocerebrum (T6III). Double labeling of JO and ocellar afferents revealed that input from the JO and visual information from the ocelli converge in tight apposition in the PS. The general JO anatomy and its central projection patterns resemble situations in honeybees and Drosophila. The multisensory nature of the JO together with its projections to multisensory neuropils in the ant brain likely serves synchronization and calibration of different sensory modalities during the ontogeny of navigation in Cataglyphis.
KW - ant brain
KW - chordotonal organ
KW - graviception
KW - magnetic compass
KW - multisensory integration
KW - navigation
KW - wind compass
Y1 - 2021
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-225679
VL - 529
IS - 8
SP - 2138
EP - 2155
ER -
TY - JOUR
A1 - Full, Julian
A1 - Panchal, Santosh P.
A1 - Götz, Julian
A1 - Krause, Ana‐Maria
A1 - Nowak‐Król, Agnieszka
T1 - Modular Synthesis of Organoboron Helically Chiral Compounds: Cutouts from Extended Helices
JF - Angewandte Chemie International Edition
N2 - Two types of helically chiral compounds bearing one and two boron atoms were synthesized by a modular approach. Formation of the helical scaffolds was executed by the introduction of boron to flexible biaryl and triaryl derived from small achiral building blocks. All‐ortho‐fused azabora[7]helicenes feature exceptional configurational stability, blue or green fluorescence with quantum yields (Φ\(_{fl}\)) of 18–24 % in solution, green or yellow solid‐state emission (Φ\(_{fl}\) up to 23 %), and strong chiroptical response with large dissymmetry factors of up to 1.12×10\(^{-2}\). Azabora[9]helicenes consisting of angularly and linearly fused rings are blue emitters exhibiting Φ\(_{fl}\) of up to 47 % in CH\(_{2}\)Cl\(_{2}\) and 25 % in the solid state. As revealed by the DFT calculations, their P–M interconversion pathway is more complex than that of H1. Single‐crystal X‐ray analysis shows clear differences in the packing arrangement of methyl and phenyl derivatives. These molecules are proposed as primary structures of extended helices.
KW - chirality
KW - circular dichroism
KW - fluorescence
KW - helicene
KW - organoboron
Y1 - 2021
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-225775
VL - 60
IS - 8
SP - 4350
EP - 4357
ER -
TY - JOUR
A1 - Urlaub, Jonas
A1 - Kaiser, Reinhard P.
A1 - Scherf‐Clavel, Oliver
A1 - Bolm, Carsten
A1 - Holzgrabe, Ulrike
T1 - Investigation of isomerization of dexibuprofen in a ball mill using chiral capillary electrophoresis
JF - Electrophoresis
N2 - Besides the racemate, the S‐enantiomer of ibuprofen (Ibu) is used for the treatment of inflammation and pain. Since the configurational stability of S‐Ibu in solid state is of interest, it was studied by means of ball milling experiments. For the evaluation of the enantiomeric composition, a chiral CE method was developed and validated according to the ICH guideline Q2(R1). The addition of Mg\(^{2+}\), Ca\(^{2+}\), or Zn\(^{2+}\) ions to the background electrolyte (BGE) was found to improve Ibu enantioresolution. Chiral separation of Ibu enantiomers was achieved on a 60.2 cm (50.0 cm effective length) x 75 μm fused‐silica capillary using a background electrolyte (BGE) composed of 50 mM sodium acetate, 10 mM magnesium acetate tetrahydrate, and 35 mM heptakis‐(2,3,6‐tri‐O‐methyl)‐β‐cyclodextrin (TM‐β‐CD) as chiral selector. The quantification of R‐Ibu in the mixture was performed using the normalization procedure. Linearity was evaluated in the range of 0.68–5.49% R‐Ibu (R\(^{2}\) = 0.999), recovery was found to range between 97 and 103%, the RSD of intra‐ and interday precision below 2.5%, and the limit of quantification for R‐ in S‐Ibu was calculated to be 0.21% (extrapolated) and 0.15% (dilution of racemic ibuprofen), respectively. Isomerization of S‐Ibu was observed under basic conditions by applying long milling times and high milling frequencies.
KW - capillary electrophoresis
KW - chiral separation
KW - Ibuprofen
KW - isomerization
KW - validation
Y1 - 2021
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-225852
VL - 42
IS - 17-18
SP - 1790
EP - 1799
ER -
TY - JOUR
A1 - Zahoranová, Anna
A1 - Luxenhofer, Robert
T1 - Poly(2‐oxazoline)‐ and Poly(2‐oxazine)‐Based Self‐Assemblies, Polyplexes, and Drug Nanoformulations—An Update
JF - Advanced Healthcare Materials
N2 - For many decades, poly(2‐oxazoline)s and poly(2‐oxazine)s, two closely related families of polymers, have led the life of a rather obscure research topic with only a few research groups world‐wide working with them. This has changed in the last five to ten years, presumably triggered significantly by very promising clinical trials of the first poly(2‐oxazoline)‐based drug conjugate. The huge chemical and structural toolbox poly(2‐oxazoline)s and poly(2‐oxazine)s has been extended very significantly in the last few years, but their potential still remains largely untapped. Here, specifically, the developments in macromolecular self‐assemblies and non‐covalent drug delivery systems such as polyplexes and drug nanoformulations based on poly(2‐oxazoline)s and poly(2‐oxazine)s are reviewed. This highly dynamic field benefits particularly from the extensive synthetic toolbox poly(2‐oxazoline)s and poly(2‐oxazine)s offer and also may have the largest potential for a further development. It is expected that the research dynamics will remain high in the next few years, particularly as more about the safety and therapeutic potential of poly(2‐oxazoline)s and poly(2‐oxazine)s is learned.
KW - block copolymers
KW - colloids
KW - cytotoxicity
KW - drug delivery
KW - micelles
KW - microphase separation
KW - thermogelling
Y1 - 2021
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-225833
VL - 10
IS - 6
ER -
TY - JOUR
A1 - Hojsgaard, Diego
A1 - Schartl, Manfred
T1 - Skipping sex: A nonrecombinant genomic assemblage of complementary reproductive modules
JF - BioEssays
N2 - The unusual occurrence and developmental diversity of asexual eukaryotes remain a puzzle. De novo formation of a functioning asexual genome requires a unique assembly of sets of genes or gene states to disrupt cellular mechanisms of meiosis and gametogenesis, and to affect discrete components of sexuality and produce clonal or hemiclonal offspring. We highlight two usually overlooked but essential conditions to understand the molecular nature of clonal organisms, that is, a nonrecombinant genomic assemblage retaining modifiers of the sexual program, and a complementation between altered reproductive components. These subtle conditions are the basis for physiologically viable and genetically balanced transitions between generations. Genomic and developmental evidence from asexual animals and plants indicates the lack of complementation of molecular changes in the sexual reproductive program is likely the main cause of asexuals' rarity, and can provide an explanatory frame for the developmental diversity and lability of developmental patterns in some asexuals as well as for the discordant time to extinction estimations.
KW - amphimixis
KW - apomixis
KW - automixis
KW - gynogenesis
KW - hybridogenesis
KW - parthenogenesis
Y1 - 2021
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-225818
VL - 43
IS - 1
ER -
TY - JOUR
A1 - Budiman, Yudha P.
A1 - Westcott, Stephen A.
A1 - Radius, Udo
A1 - Marder, Todd B.
T1 - Fluorinated Aryl Boronates as Building Blocks in Organic Synthesis
JF - Advanced Synthesis & Catalysis
N2 - Organoboron compounds are well known building blocks for many organic reactions. However, under basic conditions, polyfluorinated aryl boronic acid derivatives suffer from instability issues that are accelerated in compounds containing an ortho‐fluorine group, which result in the formation of the corresponding protodeboronation products. Therefore, a considerable amount of research has focused on novel methodologies to synthesize these valuable compounds while avoiding the protodeboronation issue. This review summarizes the latest developments in the synthesis of fluorinated aryl boronic acid derivatives and their applications in cross‐coupling reactions and other transformations.
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KW - homogeneous catalysis
KW - boron reagents
KW - boronates
KW - fluorine
KW - fluoroarene
Y1 - 2021
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-225908
VL - 363
IS - 9
SP - 2224
EP - 2255
ER -
TY - JOUR
A1 - Ravat, Prince
T1 - Carbo[n]helicenes Restricted to Enantiomerize: An Insight into the Design Process of Configurationally Stable Functional Chiral PAHs
JF - Chemistry – A European Journal
N2 - The most important stereodynamic feature of carbo[n]helicenes is the interconversion of their enantiomers. The Gibbs activation energy (ΔG≠(T)) of this process, which determines the rate of enantiomerization, dictates the configurational stability of [n]helicenes. High values of ΔG≠(T) are required for applications of functional chiral molecules incorporating [n]helicenes or helicene substructures. This minireview provides an overview of the mechanism, recent developments, and factors affecting the enantiomerization of [n]helicenes, which will accelerate the design process of configurationally stable functional chiral molecules based on helicene substructures. Additionally, this minireview addresses the misconception and irregularities in the recent literature on how the terms “racemization” and “enantiomerization” are used as well as how the activation parameters are calculated for [n]helicenes and related compounds.
KW - [n]helicenes
KW - configurational stability
KW - enantiomerization
KW - Gibbs activation energy
KW - racemization
Y1 - 2021
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-225871
VL - 27
IS - 12
SP - 3957
EP - 3967
ER -