OpenAIRE
Refine
Has Fulltext
- yes (58)
Is part of the Bibliography
- yes (58)
Year of publication
- 2020 (58) (remove)
Document Type
- Journal article (48)
- Preprint (8)
- Doctoral Thesis (2)
Keywords
- boron (6)
- ADHD (4)
- attention (3)
- diborenes (3)
- in vitro selection (3)
- polygenic risk score (3)
- Borylene (2)
- Nonadiabatic quantum dynamics (2)
- RNA Enzymes (2)
- cartilage (2)
Institute
- Institut für Anorganische Chemie (11)
- Institut für Physikalische und Theoretische Chemie (8)
- Institut für Organische Chemie (7)
- Klinik und Poliklinik für Psychiatrie, Psychosomatik und Psychotherapie (6)
- Medizinische Klinik und Poliklinik II (6)
- Institut für Psychologie (4)
- Institut für Klinische Epidemiologie und Biometrie (3)
- Theodor-Boveri-Institut für Biowissenschaften (3)
- Abteilung für Funktionswerkstoffe der Medizin und der Zahnheilkunde (2)
- Klinik und Poliklinik für Unfall-, Hand-, Plastische und Wiederherstellungschirurgie (Chirurgische Klinik II) (2)
Sonstige beteiligte Institutionen
- Agricultural Center, BASF SE, 67117 Limburgerhof, Germany (1)
- Center of Excellence for Science and Technology - Integration of Mediterranean region (STIM), Faculty of Science, University of Split, Poljička cesta 35, 2100 Split, Croatia (1)
- Departamento de Química, Facultad de Ciencias, Universidad Autónoma de Madrid, 28049 Madrid, Spain (1)
- Department of Chemistry, Humboldt Universität zu Berlin, Brook-Taylor-Strasse 2, 12489 Berlin, Germany (1)
- Institute of Organic Chemistry and Center for Molecular Biosciences Innsbruck, CMBI, Leopold-Franzens University Innsbruck, Austria (1)
- Istituto di Chimica dei Composti Organometallici (ICCOM–CNR), Area della Ricerca del CNR, Via Moruzzi 1, I-56124 Pisa, Italy. (1)
Risk Stratification for Bipolar Disorder Using Polygenic Risk Scores Among Young High-Risk Adults
(2020)
Objective:
Identifying high-risk groups with an increased genetic liability for bipolar disorder (BD) will provide insights into the etiology of BD and contribute to early detection of BD. We used the BD polygenic risk score (PRS) derived from BD genome-wide association studies (GWAS) to explore how such genetic risk manifests in young, high-risk adults. We postulated that BD-PRS would be associated with risk factors for BD.
Methods:
A final sample of 185 young, high-risk German adults (aged 18–35 years) were grouped into three risk groups and compared to a healthy control group (n = 1,100). The risk groups comprised 117 cases with attention deficit hyperactivity disorder (ADHD), 45 with major depressive disorder (MDD), and 23 help-seeking adults with early recognition symptoms [ER: positive family history for BD, (sub)threshold affective symptomatology and/or mood swings, sleeping disorder]. BD-PRS was computed for each participant. Logistic regression models (controlling for sex, age, and the first five ancestry principal components) were used to assess associations of BD-PRS and the high-risk phenotypes.
Results:
We observed an association between BD-PRS and combined risk group status (OR = 1.48, p < 0.001), ADHD diagnosis (OR = 1.32, p = 0.009), MDD diagnosis (OR = 1.96, p < 0.001), and ER group status (OR = 1.7, p = 0.025; not significant after correction for multiple testing) compared to healthy controls.
Conclusions:
In the present study, increased genetic risk for BD was a significant predictor for MDD and ADHD status, but not for ER. These findings support an underlying shared risk for both MDD and BD as well as ADHD and BD. Improving our understanding of the underlying genetic architecture of these phenotypes may aid in early identification and risk stratification.
The reductive coupling of an N-heterocyclic carbene (NHC) stabilized (dibromo)vinylborane yields a 1,2-divinyl- diborene, which, although isoelectronic to a 1,3,5-triene, displays no extended p conjugation because of twisting of the C\(_2\)B\(_2\)C\(_2\) chain. While this divinyldiborene coordinates to copper(I) and platinum(0) in an η\(^2\)-B\(_2\) and η\(^4\)-C\(_2\)B\(_2\) fashion, respectively, it undergoes a complex rearrangement to an η\(^4\)-1,3-diborete upon complexation with nickel(0).
Five compounds containing boron–boron multiple bonds are shown to undergo hydrophosphination reactions with diphenylphosphine in the absence of a catalyst. With diborenes, the products obtained are highly dependent on the substitution pattern at the boron atoms, with both 1,1- and 1,2- hydrophosphinations observed. With a symmetrical diboryne, 1,2-hydrophosphination yields a hydro(phosphino)diborene. The different mechanistic pathways for the hydrophosphination of diborenes are rationalised with the aid of density functional theory calculations.
Identification of articular cartilage progenitor cells (ACPCs) has opened up new opportunities for cartilage repair. These cells may be used as alternatives for or in combination with mesenchymal stromal cells (MSCs) in cartilage engineering. However, their potential needs to be further investigated, since only a few studies have compared ACPCs and MSCs when cultured in hydrogels. Therefore, in this study, we compared chondrogenic differentiation of equine ACPCs and MSCs in agarose constructs as monocultures and as zonally layered co-cultures under both normoxic and hypoxic conditions. ACPCs and MSCs exhibited distinctly differential production of the cartilaginous extracellular matrix (ECM). For ACPC constructs, markedly higher glycosaminoglycan (GAG) contents were determined by histological and quantitative biochemical evaluation, both in normoxia and hypoxia. Differential GAG production was also reflected in layered co-culture constructs. For both cell types, similar staining for type II collagen was detected. However, distinctly weaker staining for undesired type I collagen was observed in the ACPC constructs. For ACPCs, only very low alkaline phosphatase (ALP) activity, a marker of terminal differentiation, was determined, in stark contrast to what was found for MSCs. This study underscores the potential of ACPCs as a promising cell source for cartilage engineering.
The electric propulsion system NanoFEEP was integrated and tested in orbit on the UWE-4 satellite, which marks the first successful demonstration of an electric propulsion system on board a 1U CubeSat. In-orbit characterization measurements of the heating process of the propellant and the power consumption of the propulsion system at different thrust levels are presented. Furthermore, an analysis of the thrust vector direction based on its effect on the attitude of the spacecraft is described. The employed heater liquefies the propellant for a duration of 30 min per orbit and consumes 103 ± 4 mW. During this time, the respective thruster can be activated. The propulsion system including one thruster head, its corresponding heater, the neutralizer and the digital components of the power processing unit consume 8.5 ± 0.1 mW ⋅μ A\(^{−1}\) + 184 ± 8.5 mW and scales with the emitter current. The estimated thrust directions of two thruster heads are at angles of 15.7 ± 7.6∘ and 13.2 ± 5.5∘ relative to their mounting direction in the CubeSat structure. In light of the very limited power on a 1U CubeSat, the NanoFEEP propulsion system renders a very viable option. The heater of subsequent NanoFEEP thrusters was already improved, such that the system can be activated during the whole orbit period.
We present herein an in‐depth study of complexes in which a molecule containing a boron‐boron triple bond is bound to tellurate cations. The analysis allows the description of these salts as true π complexes between the B−B triple bond and the tellurium center. These complexes thus extend the well‐known Dewar‐Chatt‐Duncanson model of bonding to compounds made up solely of p block elements. Structural, spectroscopic and computational evidence is offered to argue that a set of recently reported heterocycles consisting of phenyltellurium cations complexed to diborynes bear all the hallmarks of \(\pi\)‐complexes in the \(\pi\)‐complex/metallacycle continuum envisioned by Joseph Chatt. Described as such, these compounds are unique in representing the extreme of a metal‐free continuum with conventional unsaturated three‐membered rings (cyclopropenes, azirenes, borirenes) occupying the opposite end.
It's costly punishment, not altruistic: Low midfrontal theta and state anger predict punishment
(2020)
Punishment in economic games has been interpreted as “altruistic.” However, it was shown that punishment is related to trait anger instead of trait altruism in a third‐party dictator game if compensation is also available. Here, we investigated the influence of state anger on punishment and compensation in the third‐party dictator game. Therefore, we used movie sequences for emotional priming, including the target states anger, happy, and neutral. We measured the Feedback‐Related Negativity (FRN) and midfrontal theta band activation, to investigate an electro‐cortical correlate of the processing of fair and unfair offers. Also, we assessed single‐trial FRN and midfrontal theta band activation as a predictor for punishment and compensation. We found that punishment was linked to state anger. Midfrontal theta band activation, which has previously been linked to altruistic acts and cognitive control, predicted less punishment. Additionally, trait anger led to enhanced FRN for unfair offers. This led to the interpretation that the FRN depicts the evaluation of fairness, while midfrontal theta band activation captures an aspect of cognitive control and altruistic motivation. We conclude that we need to redefine “altruistic punishment” into “costly punishment,” as no direct link of altruism and punishment is given. Additionally, midfrontal theta band activation complements the FRN and offers additional insights into complex responses and decision processes, especially as a single trial predictor.
Background
The prevalence of food allergy (FA) among European school children is poorly defined. Estimates have commonly been based on parent‐reported symptoms. We aimed to estimate the frequency of FA and sensitization against food allergens in primary school children in eight European countries.
Methods
A follow‐up assessment at age 6‐10 years of a multicentre European birth cohort based was undertaken using an online parental questionnaire, clinical visits including structured interviews and skin prick tests (SPT). Children with suspected FA were scheduled for double‐blind, placebo‐controlled oral food challenges (DBPCFC).
Results
A total of 6105 children participated in this school‐age follow‐up (57.8% of 10 563 recruited at birth). For 982 of 6069 children (16.2%), parents reported adverse reactions after food consumption in the online questionnaire. Of 2288 children with parental face‐to‐face interviews and/or skin prick testing, 238 (10.4%) were eligible for a DBPCFC. Sixty‐three foods were challenge‐tested in 46 children. Twenty food challenges were positive in 17 children, including seven to hazelnut and three to peanut. Another seventy‐one children were estimated to suffer FA among those who were eligible but refused DBPCFC. This yielded prevalence estimates for FA in school age between 1.4% (88 related to all 6105 participants of this follow‐up) and 3.8% (88 related to 2289 with completed eligibility assessment).
Interpretation
In primary school children in eight European countries, the prevalence of FA was lower than expected even though parents of this cohort have become especially aware of allergic reactions to food. There was moderate variation between centres hampering valid regional comparisons.
The investigation of the biodistribution profile of a cell-based medicinal product is a pivotal prerequisite to allow a factual benefit-risk assessment within the non-clinical to clinical translation in product development. Here, a qPCR-based method to determine the amount of human DNA in mouse DNA was validated according to the guidelines of the European Medicines Agency and the International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use. Furthermore, a preclinical worst-case scenario study was performed in which this method was applied to investigate the biodistribution of 2 x 10\(^6\) intravenously administered, genetically modified, blood outgrowth endothelial cells from hemophilia A patients after 24 h and 7 days. The validation of the qPCR method demonstrated high accuracy, precision, and linearity for the concentration interval of 1:1 x 10\(^3\) to 1:1 x 10\(^6\) human to mouse DNA. The application of this method in the biodistribution study resulted in the detection of human genomes in four out of the eight investigated organs after 24 h. After 7 days, no human DNA was detected in the eight organs analyzed. This biodistribution study provides mandatory data on the toxicokinetic safety profile of an actual candidate cell-based medicinal product. The extensive evaluation of the required validation parameters confirms the applicability of the qPCR method for non-clinical biodistribution studies.
Objective
To determine whether IgG subclasses of antiparanodal autoantibodies are related to disease course and treatment response in acute- to subacute-onset neuropathies, we retrospectively screened 161 baseline serum/CSF samples and 66 follow-up serum/CSF samples.
Methods
We used ELISA and immunofluorescence assays to detect antiparanodal IgG and their subclasses and titers in serum/CSF of patients with Guillain-Barre syndrome (GBS), recurrent GBS (R-GBS), Miller-Fisher syndrome, and acute- to subacute-onset chronic inflammatory demyelinating polyradiculoneuropathy (A-CIDP). We evaluated clinical data retrospectively.
Results
We detected antiparanodal autoantibodies with a prevalence of 4.3% (7/161), more often in A-CIDP (4/23, 17.4%) compared with GBS (3/114, 2.6%). Longitudinal subclass analysis in the patients with GBS revealed IgG2/3 autoantibodies against Caspr-1 and against anti-contactin-1/Caspr-1, which disappeared at remission. At disease onset, patients with A-CIDP had IgG2/3 anti-Caspr-1 and anti-contactin-1/Caspr-1 or IgG4 anti-contactin-1 antibodies, IgG3 being associated with good response to IV immunoglobulins (IVIg). In the chronic phase of disease, IgG subclass of one patient with A-CIDP switched from IgG3 to IgG4.
Conclusion
Our data (1) confirm and extend previous observations that antiparanodal IgG2/3 but not IgG4 antibodies can occur in acute-onset neuropathies manifesting as monophasic GBS, (2) suggest association of IgG3 to a favorable response to IVIg, and (3) lend support to the hypothesis that in some patients, an IgG subclass switch from IgG3 to IgG4 may be the correlate of a secondary progressive or relapsing course following a GBS-like onset.
The predicted 80 open reading frames (ORFs) of herpes simplex virus 1 (HSV-1) have been intensively studied for decades. Here, we unravel the complete viral transcriptome and translatome during lytic infection with base-pair resolution by computational integration of multi-omics data. We identify a total of 201 transcripts and 284 ORFs including all known and 46 novel large ORFs. This includes a so far unknown ORF in the locus deleted in the FDA-approved oncolytic virus Imlygic. Multiple transcript isoforms expressed from individual gene loci explain translation of the vast majority of ORFs as well as N-terminal extensions (NTEs) and truncations. We show that NTEs with non-canonical start codons govern the subcellular protein localization and packaging of key viral regulators and structural proteins. We extend the current nomenclature to include all viral gene products and provide a genome browser that visualizes all the obtained data from whole genome to single-nucleotide resolution. Here, using computational integration of multi-omics data, the authors provide a detailed transcriptome and translatome of herpes simplex virus 1 (HSV-1), including previously unidentified ORFs and N-terminal extensions. The study also provides a HSV-1 genome browser and should be a valuable resource for further research.
Experiments in animal models have shown that running increases neuronal activity in early visual areas in light as well as in darkness. This suggests that visual processing is influenced by locomotion independent of visual input. Combining mobile electroencephalography, motion- and eye-tracking, we investigated the influence of overground free walking on cortical alpha activity (~10 Hz) and eye movements in healthy humans. Alpha activity has been considered a valuable marker of inhibition of sensory processing and shown to negatively correlate with neuronal firing rates. We found that walking led to a decrease in alpha activity over occipital cortex compared to standing. This decrease was present during walking in darkness as well as during light. Importantly, eye movements could not explain the change in alpha activity. Nevertheless, we found that walking and eye related movements were linked. While the blink rate increased with increasing walking speed independent of light or darkness, saccade rate was only significantly linked to walking speed in the light. Pupil size, on the other hand, was larger during darkness than during light, but only showed a modulation by walking in darkness. Analyzing the effect of walking with respect to the stride cycle, we further found that blinks and saccades preferentially occurred during the double support phase of walking. Alpha power, as shown previously, was lower during the swing phase than during the double support phase. We however could exclude the possibility that the alpha modulation was introduced by a walking movement induced change in electrode impedance. Overall, our work indicates that the human visual system is influenced by the current locomotion state of the body. This influence affects eye movement pattern as well as neuronal activity in sensory areas and might form part of an implicit strategy to optimally extract sensory information during locomotion.
In the last few years, monoclonal antibodies (mAbs) such as elotuzumab and daratutumab have brought the treatment of multiple myeloma (MM) into the new era of immunotherapy. More recently, chimeric antigen receptor (CAR) modified T cell, a novel cellular immunotherapy, has been developed for treatment of relapsed/refractory (RR) MM, and early phase clinical trials have shown promising efficacy of CAR T cell therapy. Many patients with end stage RRMM regard CAR T cell therapy as their “last chance” and a “hope of cure”. However, severe adverse events (AEs) and even toxic death related to CAR T cell therapy have been observed. The management of AEs related to CAR T cell therapy represents a new challenge, as the pathophysiology is not fully understood and there is still no well-established standard of management. With regard to CAR T cell associated toxicities in MM, in this review, we will provide an overview of experience from clinical trials, pathophysiology, and management strategies.
The fruit fly Drosophila melanogaster is an established model organism in chronobiology, because genetic manipulation and breeding in the laboratory are easy. The circadian clock neuroanatomy in D. melanogaster is one of the best-known clock networks in insects and basic circadian behavior has been characterized in detail in this insect. Another model in chronobiology is the honey bee Apis mellifera, of which diurnal foraging behavior has been described already in the early twentieth century. A. mellifera hallmarks the research on the interplay between the clock and sociality and complex behaviors like sun compass navigation and time-place-learning. Nevertheless, there are aspects of clock structure and function, like for example the role of the clock in photoperiodism and diapause, which can be only insufficiently investigated in these two models. Unlike high-latitude flies such as Chymomyza costata or D. ezoana, cosmopolitan D. melanogaster flies do not display a photoperiodic diapause. Similarly, A. mellifera bees do not go into “real” diapause, but most solitary bee species exhibit an obligatory diapause. Furthermore, sociality evolved in different Hymenoptera independently, wherefore it might be misleading to study the social clock only in one social insect. Consequently, additional research on non-model insects is required to understand the circadian clock in Diptera and Hymenoptera. In this review, we introduce the two chronobiology model insects D. melanogaster and A. mellifera, compare them with other insects and show their advantages and limitations as general models for insect circadian clocks.
We investigated the influence of social status on behavior in a modified dictator game (DG). Since the DG contains an inherent dominance gradient, we examined the relationship between dictator decisions and recipient status, which was operationalized by three social identities and an artificial intelligence (AI). Additionally, we examined the predictive value of social dominance orientation (SDO) on the behavior of dictators toward the different social and non-social hierarchical recipients. A multilevel model analysis showed that recipients with the same status as the dictator benefited the most and the artificial intelligence the least. Furthermore, SDO, regardless of social status, predicted behavior toward recipients in such a way that higher dominance was associated with lower dictator offers. In summary, participants treated other persons of higher and lower status equally, those of equal status better and, above all, an algorithm worst. The large proportion of female participants and the limited variance of SDO should be taken into account with regard to the results of individual differences in SDO.
Schizophrenia (SCZ) is a severe mental disorder with immense personal and societal costs; identifying individuals at risk is therefore of utmost importance. Genomic risk profile scores (GRPS) have been shown to significantly predict cases-control status. Making use of a large-population based sample from Sweden, we replicate a previous finding demonstrating that the GRPS is strongly associated with admission frequency and chronicity of SCZ. Furthermore, we were able to show a substantial gap in prediction accuracy between males and females. In sum, our results indicate that prediction accuracy by GRPS depends on clinical and demographic characteristics.
Whereas the reduction of N-heterocyclic carbene (NHC)-stabilised cymantrenyldibromoboranes, (NHC)BBr\(_2\)Cym, in benzene results in formation of the corresponding diborenes (NHC)\(_2\)B\(_2\)Cym\(_2\), a change of solvent to THF yields a borylene of the form (NHC)\(_2\)BCym, stabilised through its boratafulvene resonance form.
Die Reaktion zwischen Aryl‐ und Amino(dihydro)boranen und Dibora[2]ferrocenophan 1 führt zur Bildung von 1,3‐trans‐Dihydrotriboranen durch formale Hydrierung und Insertion eines Borylens in die B=B Doppelbindung. Die Aryltriboran‐Derivate unterliegen einer reversiblen Photoisomerisierung zugunsten eines cis‐1,2‐μ‐H‐3‐Hydrotriborans, während eine Hydridabstraktion zu kationischen Triboranen führt, welche die ersten doppelt basenstabilisierten B\(_3\)H\(_4\)\(^+\)‐Analoga darstellen.
Anhand der ersten Festkörperstrukturen von Dibortetraiodid (B\(_2\)I\(_4\)) wird gezeigt, dass dieses nicht, wie lange angenommen, analog zu den leichteren Dibortetrahalogeniden B\(_2\)F\(_4\), B\(_2\)Cl\(_4\) und B\(_2\)Br\(_4\) in allen Aggregatzuständen in Form diskreter Moleküle mit planaren, dreifach koordinierten Boratomen vorliegt. Röntgenstrukturanalysen, Festkörper‐NMR‐ und IR‐Messungen zeigen, dass B\(_2\)I\(_4\) im Festkörper in zwei polymeren Konformeren vorkommt, die tetraedrisch koordinierte Boratome enthalten. Anhand von DFT‐Rechnungen werden die IR‐Spektren in Lösung und im Festkörper simuliert und mit den experimentellen Daten verglichen.
Nearly all classes of coding and non-coding RNA undergo post-transcriptional modification including RNA methylation. Methylated nucleotides belong to the evolutionarily most conserved features of tRNA and rRNA.1,2 Many contemporary methyltransferases use the universal cofactor S-adenosylmethionine (SAM) as methyl group donor. This and other nucleotide-derived cofactors are considered as evolutionary leftovers from an RNA World, in which ribozymes may have catalysed essential metabolic reactions beyond self-replication.3 Chemically diverse ribozymes seem to have been lost in Nature, but may be reconstructed in the laboratory by in vitro selection. Here, we report a methyltransferase ribozyme that catalyses the site-specific installation of 1-methyladenosine (m1A) in a substrate RNA, utilizing O6-methylguanine (m6G) as a small-molecule cofactor. The ribozyme shows a broad RNA sequence scope, as exemplified by site-specific adenosine methylation in tRNAs. This finding provides fundamental insights into RNA’s catalytic abilities, serves a synthetic tool to install m1A in RNA, and may pave the way to in vitro evolution of other methyltransferase and demethylase ribozymes.