TY  - JOUR
A1  - Abdel-Latif, Rania
A1  - Fathy, Moustafa
A1  - Anwar, Hend Ali
A1  - Naseem, Muhammad
A1  - Dandekar, Thomas
A1  - Othman, Eman M.
T1  - Cisplatin-induced reproductive toxicity and oxidative stress: ameliorative effect of kinetin
JF  - Antioxidants
N2  - Cisplatin is a commonly used chemotherapeutic agent; however, its potential side effects, including gonadotoxicity and infertility, are a critical problem. Oxidative stress has been implicated in the pathogenesis of cisplatin-induced testicular dysfunction. We investigated whether kinetin use at different concentrations could alleviate gonadal injury associated with cisplatin treatment, with an exploration of the involvement of its antioxidant capacity. Kinetin was administered in different doses of 0.25, 0.5, and 1 mg/kg, alone or along with cisplatin for 10 days. Cisplatin toxicity was induced via a single IP dose of 7 mg/kg on day four. In a dose-dependent manner, concomitant administration of kinetin with cisplatin significantly restored testicular oxidative stress parameters, corrected the distorted sperm quality parameters and histopathological changes, enhanced levels of serum testosterone and testicular StAR protein expression, as well as reduced the up-regulation of testicular TNF-α, IL-1β, Il-6, and caspase-3, caused by cisplatin. It is worth noting that the testicular protective effect of the highest kinetin dose was comparable/more potent and significantly higher than the effects of vitamin C and the lowest kinetin dose, respectively. Overall, these data indicate that kinetin may offer a promising approach for alleviating cisplatin-induced reproductive toxicity and organ damage, via ameliorating oxidative stress and reducing inflammation and apoptosis.
KW  - cytokinins
KW  - kinetin
KW  - cisplatin
KW  - reproductive toxicity
Y1  - 2022
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-271223
SN  - 2076-3921
VL  - 11
IS  - 5
ER  - 
TY  - JOUR
A1  - Adam, Alexander
A1  - Deimel, Stephan
A1  - Pardo-Medina, Javier
A1  - García-Martínez, Jorge
A1  - Konte, Tilen
A1  - Limón, M. Carmen
A1  - Avalos, Javier
A1  - Terpitz, Ulrich
T1  - Protein activity of the \(Fusarium\) \(fujikuroi\) rhodopsins CarO and OpsA and their relation to fungus−plant interaction
JF  - International Journal of Molecular Sciences
N2  - Fungi possess diverse photosensory proteins that allow them to perceive different light wavelengths and to adapt to changing light conditions in their environment. The biological and physiological roles of the green light-sensing rhodopsins in fungi are not yet resolved. The rice plant pathogen Fusarium fujikuroi exhibits two different rhodopsins, CarO and OpsA. CarO was previously characterized as a light-driven proton pump. We further analyzed the pumping behavior of CarO by patch-clamp experiments. Our data show that CarO pumping activity is strongly augmented in the presence of the plant hormone indole-3-acetic acid and in sodium acetate, in a dose-dependent manner under slightly acidic conditions. By contrast, under these and other tested conditions, the Neurospora rhodopsin (NR)-like rhodopsin OpsA did not exhibit any pump activity. Basic local alignment search tool (BLAST) searches in the genomes of ascomycetes revealed the occurrence of rhodopsin-encoding genes mainly in phyto-associated or phytopathogenic fungi, suggesting a possible correlation of the presence of rhodopsins with fungal ecology. In accordance, rice plants infected with a CarO-deficient F. fujikuroi strain showed more severe bakanae symptoms than the reference strain, indicating a potential role of the CarO rhodopsin in the regulation of plant infection by this fungus.
KW  - fungal rhodopsins
KW  - CarO
KW  - OpsA
KW  - Fusarium fujikuroi
KW  - Oryza sativa
KW  - rice–plant infection
KW  - green light perception
KW  - indole-3-acetic acid (IAA)
KW  - bakanae
KW  - patch-clamp
Y1  - 2018
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-285125
SN  - 1422-0067
VL  - 19
IS  - 1
ER  - 
TY  - JOUR
A1  - Adam, D.
A1  - Wittbrodt, J.
A1  - Telling, A.
A1  - Schartl, Manfred
T1  - RFLP for an EGF-receptor related gene associated with the melanoma oncogene locus of Xiphophorus maculatus
N2  - No abstract available
KW  - Physiologische Chemie
Y1  - 1988
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-61822
ER  - 
TY  - JOUR
A1  - Adam, Dieter
A1  - Dimitrijevic, Nicola
A1  - Schartl, Manfred
T1  - Tumor suppression in Xiphophorus by an accidentally acquired promoter
N2  - Melanoma formation in the teleost Xiphophorus is caused by a dominant genetic locus, Tu. This locus includes the Xmrk oncogene, which encodes a receptor tyrosine kinase. Tumor induction is. suppressed in wild-type fish by a tumor suppressor locus, R. Molecular genetic analyses revealed that the Tu locus emerged by nonhomologaus recombination of the Xmrk proto-oncogene with a previously uncharacterized sequence, D. This event generated an additional copy of Xmrk with a new promoter. Suppression of the new Xmrk promoter by R in parental fish and its deregulation in hybrids explain the genetics of melanoma formation in Xiphophorus.
KW  - Physiologische Chemie
Y1  - 1993
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-61630
ER  - 
TY  - JOUR
A1  - Adam, Dieter
A1  - Maueler, Winfried
A1  - Schartl, Manfred
T1  - Transcriptional activation of the melanoma inducing Xmrk oncogene in Xiphophorus
N2  - The melanoma inducing locus of Xiphophorus encodes a tumorigenic version of a novel putative receptor tyrosine kinase (Xmrk). To elucidate the mechanism of oncogenic activation of Xmrk, we compared the structure and expression of two oncogenic loci with the corresponding proto-oncogene. Only minor structural alterations were found to be specific for the oncogenic Xmrk genes. Marked overexpression of the oncogene transcripts in melanoma, which are approximately 1 kb shorter than the proto-oncogene transcript, correlates with the malignancy of the tumors. The tumor transcripts are derived from an alternative transcription start site that is used only in the oncogenic loci. Thus, oncogenic activation of the melanoma inducing Xmrk gene appears primarily to be due to novel transcriptional control and overexpression.
KW  - Schwertkärpfling
KW  - Onkogen
KW  - Melanom
Y1  - 1991
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-87584
ER  - 
TY  - JOUR
A1  - Adelfinger, Marion
A1  - Gentschev, Ivaylo
A1  - de Guibert, Julio Grimm
A1  - Weibel, Stephanie
A1  - Langbein-Laugwitz, Johanna
A1  - Härtl, Barbara
A1  - Escobar, Hugo Murua
A1  - Nolte, Ingo
A1  - Chen, Nanhai G.
A1  - Aguilar, Richard J.
A1  - Yu, Yong A.
A1  - Zhang, Qian
A1  - Frentzen, Alexa
A1  - Szalay, Aladar A.
T1  - Evaluation of a New Recombinant Oncolytic Vaccinia Virus Strain GLV-5b451 for Feline Mammary Carcinoma Therapy
JF  - PLoS ONE
N2  - Virotherapy on the basis of oncolytic vaccinia virus (VACV) infection is a promising approach for cancer therapy. In this study we describe the establishment of a new preclinical model of feline mammary carcinoma (FMC) using a recently established cancer cell line, DT09/06. In addition, we evaluated a recombinant vaccinia virus strain, GLV-5b451, expressing the anti-vascular endothelial growth factor (VEGF) single-chain antibody (scAb) GLAF-2 as an oncolytic agent against FMC. Cell culture data demonstrate that GLV-5b451 virus efficiently infected, replicated in and destroyed DT09/06 cancer cells. In the selected xenografts of FMC, a single systemic administration of GLV-5b451 led to significant inhibition of tumor growth in comparison to untreated tumor-bearing mice. Furthermore, tumor-specific virus infection led to overproduction of functional scAb GLAF-2, which caused drastic reduction of intratumoral VEGF levels and inhibition of angiogenesis.
In summary, here we have shown, for the first time, that the vaccinia virus strains and especially GLV-5b451 have great potential for effective treatment of FMC in animal model.
KW  - antibodies
KW  - cancer treatment
KW  - carcinomas
KW  - vaccinia virus
KW  - oncolytic viruses
KW  - viral replication
KW  - cell cultures
KW  - enzyme-linked immunoassays
Y1  - 2014
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-119387
VL  - 9
IS  - 8
ER  - 
TY  - JOUR
A1  - Adolfi, Mateus C.
A1  - Carreira, Ana C. O.
A1  - Jesus, Lázaro W. O.
A1  - Bogerd, Jan
A1  - Funes, Rejane M.
A1  - Schartl, Manfred
A1  - Sogayar, Mari C.
A1  - Borella, Maria I.
T1  - Molecular cloning and expression analysis of dmrt1 and sox9 during gonad development and male reproductive cycle in the lambari fish, Astyanax altiparanae
JF  - Reproductive Biology and Endocrinology
N2  - Background
The dmrt1 and sox9 genes have a well conserved function related to testis formation in vertebrates, and the group of fish presents a great diversity of species and reproductive mechanisms. The lambari fish (Astyanax altiparanae) is an important Neotropical species, where studies on molecular level of sex determination and gonad maturation are scarce.

Methods
Here, we employed molecular cloning techniques to analyze the cDNA sequences of the dmrt1 and sox9 genes, and describe the expression pattern of those genes during development and the male reproductive cycle by qRT-PCR, and related to histology of the gonad.

Results
Phylogenetic analyses of predicted amino acid sequences of dmrt1 and sox9 clustered A. altiparanae in the Ostariophysi group, which is consistent with the morphological phylogeny of this species. Studies of the gonad development revealed that ovary formation occurred at 58 days after hatching (dah), 2 weeks earlier than testis formation. Expression studies of sox9 and dmrt1 in different tissues of adult males and females and during development revealed specific expression in the testis, indicating that both genes also have a male-specific role in the adult. During the period of gonad sex differentiation, dmrt1 seems to have a more significant role than sox9. During the male reproductive cycle dmrt1 and sox9 are down-regulated after spermiation, indicating a role of these genes in spermatogenesis.

Conclusions
For the first time the dmrt1 and sox9 were cloned in a Characiformes species. We show that both genes have a conserved structure and expression, evidencing their role in sex determination, sex differentiation and the male reproductive cycle in A. altiparanae. These findings contribute to a better understanding of the molecular mechanisms of sex determination and differentiation in fish.
KW  - spermatogenesis
KW  - SOX9
KW  - DMRT1
KW  - sex differentiation
KW  - teleostei
Y1  - 2015
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-126486
VL  - 13
IS  - 2
ER  - 
TY  - JOUR
A1  - Adolfi, Mateus C.
A1  - Du, Kang
A1  - Kneitz, Susanne
A1  - Cabau, Cédric
A1  - Zahm, Margot
A1  - Klopp, Christophe
A1  - Feron, Romain
A1  - Paixão, Rômulo V.
A1  - Varela, Eduardo S.
A1  - de Almeida, Fernanda L.
A1  - de Oliveira, Marcos A.
A1  - Nóbrega, Rafael H.
A1  - Lopez-Roques, Céline
A1  - Iampietro, Carole
A1  - Lluch, Jérôme
A1  - Kloas, Werner
A1  - Wuertz, Sven
A1  - Schaefer, Fabian
A1  - Stöck, Matthias
A1  - Guiguen, Yann
A1  - Schartl, Manfred
T1  - A duplicated copy of id2b is an unusual sex-determining candidate gene on the Y chromosome of arapaima (Arapaima gigas)
JF  - Scientific Reports
N2  - Arapaima gigas is one of the largest freshwater fish species of high ecological and economic importance. Overfishing and habitat destruction are severe threats to the remaining wild populations. By incorporating a chromosomal Hi-C contact map, we improved the arapaima genome assembly to chromosome-level, revealing an unexpected high degree of chromosome rearrangements during evolution of the bonytongues (Osteoglossiformes). Combining this new assembly with pool-sequencing of male and female genomes, we identified id2bbY, a duplicated copy of the inhibitor of DNA binding 2b (id2b) gene on the Y chromosome as candidate male sex-determining gene. A PCR-test for id2bbY was developed, demonstrating that this gene is a reliable male-specific marker for genotyping. Expression analyses showed that this gene is expressed in juvenile male gonads. Its paralog, id2ba, exhibits a male-biased expression in immature gonads. Transcriptome analyses and protein structure predictions confirm id2bbY as a prime candidate for the master sex-determiner. Acting through the TGF beta signaling pathway, id2bbY from arapaima would provide the first evidence for a link of this family of transcriptional regulators to sex determination. Our study broadens our current understanding about the evolution of sex determination genetic networks and provide a tool for improving arapaima aquaculture for commercial and conservation purposes.
KW  - evolutionary genetics
KW  - genetic markers
KW  - genome
Y1  - 2021
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-265672
VL  - 11
IS  - 1
ER  - 
TY  - JOUR
A1  - Adolfi, Mateus C.
A1  - Herpin, Amaury
A1  - Martinez-Bengochea, Anabel
A1  - Kneitz, Susanne
A1  - Regensburger, Martina
A1  - Grunwald, David J.
A1  - Schartl, Manfred
T1  - Crosstalk Between Retinoic Acid and Sex-Related Genes Controls Germ Cell Fate and Gametogenesis in Medaka
JF  - Frontiers in Cell and Developmental Biology
N2  - Sex determination (SD) is a highly diverse and complex mechanism. In vertebrates, one of the first morphological differences between the sexes is the timing of initiation of the first meiosis, where its initiation occurs first in female and later in male. Thus, SD is intimately related to the responsiveness of the germ cells to undergo meiosis in a sex-specific manner. In some vertebrates, it has been reported that the timing for meiosis entry would be under control of retinoic acid (RA), through activation of Stra8. In this study, we used a fish model species for sex determination and lacking the stra8 gene, the Japanese medaka (Oryzias latipes), to investigate the connection between RA and the sex determination pathway. Exogenous RA treatments act as a stress factor inhibiting germ cell differentiation probably by activation of dmrt1a and amh. Disruption of the RA degrading enzyme gene cyp26a1 induced precocious meiosis and oogenesis in embryos/hatchlings of female and even some males. Transcriptome analyzes of cyp26a1–/–adult gonads revealed upregulation of genes related to germ cell differentiation and meiosis, in both ovaries and testes. Our findings show that germ cells respond to RA in a stra8 independent model species. The responsiveness to RA is conferred by sex-related genes, restricting its action to the sex differentiation period in both sexes.
KW  - sex determination
KW  - retinoic acid
KW  - meiosis
KW  - gametogenesis
KW  - medaka
Y1  - 2021
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-222669
SN  - 2296-634X
VL  - 8
ER  - 
TY  - JOUR
A1  - Adolfi, Mateus C.
A1  - Herpin, Amaury
A1  - Regensburger, Martina
A1  - Sacquegno, Jacopo
A1  - Waxman, Joshua S.
A1  - Schartl, Manfred
T1  - Retinoic acid and meiosis induction in adult versus embryonic gonads of medaka
JF  - Scientific Reports
N2  - In vertebrates, one of the first recognizable sex differences in embryos is the onset of meiosis, known to be regulated by retinoic acid (RA) in mammals. We investigated in medaka a possible meiotic function of RA during the embryonic sex determination (SD) period and in mature gonads. We found RA mediated transcriptional activation in germ cells of both sexes much earlier than the SD stage, however, no such activity during the critical stages of SD. In adults, expression of the RA metabolizing enzymes indicates sexually dimorphic RA levels. In testis, RA acts directly in Sertoli, Leydig and pre-meiotic germ cells. In ovaries, RA transcriptional activity is highest in meiotic oocytes. Our results show that RA plays an important role in meiosis induction and gametogenesis in adult medaka but contrary to common expectations, not for initiating the first meiosis in female germ cells at the SD stage.
KW  - developmental biology
KW  - molecular biology
Y1  - 2016
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-147843
VL  - 6
ER  - 
TY  - JOUR
A1  - Agoston, Zsuzsa
A1  - Li, Naixin
A1  - Haslinger, Anja
A1  - Wizenmann, Andrea
A1  - Schulte, Dorothea
T1  - Genetic and physical interaction of Meis2, Pax3 and Pax7 during dorsal midbrain development
JF  - BMC Developmental Biology
N2  - Background: During early stages of brain development, secreted molecules, components of intracellular signaling pathways and transcriptional regulators act in positive and negative feed-back or feed-forward loops at the mid-hindbrain boundary. These genetic interactions are of central importance for the specification and subsequent development of the adjacent mid-and hindbrain. Much less, however, is known about the regulatory relationship and functional interaction of molecules that are expressed in the tectal anlage after tectal fate specification has taken place and tectal development has commenced. 
Results: Here, we provide experimental evidence for reciprocal regulation and subsequent cooperation of the paired-type transcription factors Pax3, Pax7 and the TALE-homeodomain protein Meis2 in the tectal anlage. Using in ovo electroporation of the mesencephalic vesicle of chick embryos we show that (i) Pax3 and Pax7 mutually regulate each other's expression in the mesencephalic vesicle, (ii) Meis2 acts downstream of Pax3/7 and requires balanced expression levels of both proteins, and (iii) Meis2 physically interacts with Pax3 and Pax7. These results extend our previous observation that Meis2 cooperates with Otx2 in tectal development to include Pax3 and Pax7 as Meis2 interacting proteins in the tectal anlage. 
Conclusion: The results described here suggest a model in which interdependent regulatory loops involving Pax3 and Pax7 in the dorsal mesencephalic vesicle modulate Meis2 expression. Physical interaction with Meis2 may then confer tectal specificity to a wide range of otherwise broadly expressed transcriptional regulators, including Otx2, Pax3 and Pax7.
KW  - dosage
KW  - quali-chick chimeras
KW  - drosophila embryo
KW  - neural crest
KW  - transcription activation
KW  - hindbrain boundary
KW  - isthmic oragnizer
KW  - sonic hedghog
KW  - expression
KW  - induction
Y1  - 2012
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-132626
VL  - 12
IS  - 10
ER  - 
TY  - JOUR
A1  - Ahmed, Zeeshan
A1  - Zeeshan, Saman
A1  - Dandekar, Thomas
T1  - Mining biomedical images towards valuable information retrieval in biomedical and life sciences
JF  - Database - The Journal of Biological Databases and Curation
N2  - Biomedical images are helpful sources for the scientists and practitioners in drawing significant hypotheses, exemplifying approaches and describing experimental results in published biomedical literature. In last decades, there has been an enormous increase in the amount of heterogeneous biomedical image production and publication, which results in a need for bioimaging platforms for feature extraction and analysis of text and content in biomedical images to take advantage in implementing effective information retrieval systems. In this review, we summarize technologies related to data mining of figures. We describe and compare the potential of different approaches in terms of their developmental aspects, used methodologies, produced results, achieved accuracies and limitations. Our comparative conclusions include current challenges for bioimaging software with selective image mining, embedded text extraction and processing of complex natural language queries.
KW  - humans
KW  - software
KW  - image processing
KW  - animals
KW  - computer-assisted
KW  - data mining/methods
KW  - natural language processing
Y1  - 2016
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-162697
VL  - 2016
ER  - 
TY  - JOUR
A1  - Ahmed, Zeeshan
A1  - Zeeshan, Saman
A1  - Huber, Claudia
A1  - Hensel, Michael
A1  - Schomburg, Dietmar
A1  - Münch, Richard
A1  - Eylert, Eva
A1  - Eisenreich, Wolfgang
A1  - Dandekar, Thomas
T1  - ‘Isotopo’ a database application for facile analysis and management of mass isotopomer data
JF  - Database
N2  - The composition of stable-isotope labelled isotopologues/isotopomers in metabolic products can be measured by mass spectrometry and supports the analysis of pathways and fluxes. As a prerequisite, the original mass spectra have to be processed, managed and stored to rapidly calculate, analyse and compare isotopomer enrichments to study, for instance, bacterial metabolism in infection. For such applications, we provide here the database application ‘Isotopo’. This software package includes (i) a database to store and process isotopomer data, (ii) a parser to upload and translate different data formats for such data and (iii) an improved application to process and convert signal intensities from mass spectra of \(^{13}C\)-labelled metabolites such as tertbutyldimethylsilyl-derivatives of amino acids. Relative mass intensities and isotopomer distributions are calculated applying a partial least square method with iterative refinement for high precision data. The data output includes formats such as graphs for overall enrichments in amino acids. The package is user-friendly for easy and robust data management of multiple experiments.
KW  - stable-isotope
Y1  - 2014
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-120102
VL  - 2014
IS  - bau077
ER  - 
TY  - JOUR
A1  - Akhoon, Bashir A.
A1  - Gupta, Shishir K.
A1  - Tiwari, Sudeep
A1  - Rathor, Laxmi
A1  - Pant, Aakanksha
A1  - Singh, Nivedita
A1  - Gupta, Shailendra K.
A1  - Dandekar, Thomas
A1  - Pandey, Rakesh
T1  - C. elegans protein interaction network analysis probes RNAi validated pro-longevity effect of nhr-6, a human homolog of tumor suppressor Nr4a1
JF  - Scientific Reports
N2  - Protein-protein interaction (PPI) studies are gaining momentum these days due to the plethora of various high-throughput experimental methods available for detecting PPIs. Proteins create complexes and networks by functioning in harmony with other proteins and here in silico network biology hold the promise to reveal new functionality of genes as it is very difficult and laborious to carry out experimental high-throughput genetic screens in living organisms. We demonstrate this approach by computationally screening C. elegans conserved homologs of already reported human tumor suppressor and aging associated genes. We select by this nhr-6, vab-3 and gst-23 as predicted longevity genes for RNAi screen. The RNAi results demonstrated the pro-longevity effect of these genes. Nuclear hormone receptor nhr-6 RNAi inhibition resulted in a C. elegans phenotype of 23.46% lifespan reduction. Moreover, we show that nhr-6 regulates oxidative stress resistance in worms and does not affect the feeding behavior of worms. These findings imply the potential of nhr-6 as a common therapeutic target for aging and cancer ailments, stressing the power of in silico PPI network analysis coupled with RNAi screens to describe gene function.
KW  - Computer modelling
KW  - Embryonic induction
KW  - RNAi
Y1  - 2019
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-202666
VL  - 9
ER  - 
TY  - JOUR
A1  - Akhoon, Bashir A.
A1  - Singh, Krishna P.
A1  - Varshney, Megha
A1  - Gupta, Shishir K.
A1  - Shukla, Yogeshwar
A1  - Gupta, Shailendra K.
T1  - Understanding the Mechanism of Atovaquone Drug Resistance in Plasmodium falciparum Cytochrome b Mutation Y268S Using Computational Methods
JF  - PLOS ONE
N2  - The rapid appearance of resistant malarial parasites after introduction of atovaquone (ATQ) drug has prompted the search for new drugs as even single point mutations in the active site of Cytochrome b protein can rapidly render ATQ ineffective. The presence of Y268 mutations in the Cytochrome b (Cyt b) protein is previously suggested to be responsible for the ATQ resistance in Plasmodium falciparum (P. falciparum). In this study, we examined the resistance mechanism against ATQ in P. falciparum through computational methods. Here, we reported a reliable protein model of Cyt bc1 complex containing Cyt b and the Iron-Sulphur Protein (ISP) of P. falciparum using composite modeling method by combining threading, ab initio modeling and atomic-level structure refinement approaches. The molecular dynamics simulations suggest that Y268S mutation causes ATQ resistance by reducing hydrophobic interactions between Cyt bc1 protein complex and ATQ. Moreover, the important histidine contact of ATQ with the ISP chain is also lost due to Y268S mutation. We noticed the induced mutation alters the arrangement of active site residues in a fashion that enforces ATQ to find its new stable binding site far away from the wild-type binding pocket. The MM-PBSA calculations also shows that the binding affinity of ATQ with Cyt bc1 complex is enough to hold it at this new site that ultimately leads to the ATQ resistance.
KW  - molecular-dynamics simulations
KW  - HIV-1 protease
KW  - structure prediction
KW  - saccharomyces cerevisiae
KW  - I-tasser
KW  - inhibitors
KW  - binding
KW  - malaria
KW  - complex
KW  - protein-protein interactions
Y1  - 2014
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-114882
VL  - 9
IS  - 10
ER  - 
TY  - JOUR
A1  - Al-Warhi, Tarfah
A1  - Elmaidomy, Abeer H.
A1  - Maher, Sherif A.
A1  - Abu-Baih, Dalia H.
A1  - Selim, Samy
A1  - Albqmi, Mha
A1  - Al-Sanea, Mohammad M.
A1  - Alnusaire, Taghreed S.
A1  - Ghoneim, Mohammed M.
A1  - Mostafa, Ehab M.
A1  - Hussein, Shaimaa
A1  - El-Damasy, Ashraf K.
A1  - Saber, Entesar Ali
A1  - Elrehany, Mahmoud A.
A1  - Sayed, Ahmed M.
A1  - Othman, Eman M.
A1  - El-Sherbiny, Mohamed
A1  - Abdelmohsen, Usama Ramadan
T1  - The wound-healing potential of Olea europaea L. Cv. Arbequina leaves extract: an integrated in vitro, in silico, and in vivo investigation
JF  - Metabolites
N2  - Olea europaea L. Cv. Arbequina (OEA) (Oleaceae) is an olive variety species that has received little attention. Besides our previous work for the chemical profiling of OEA leaves using LC–HRESIMS, an additional 23 compounds are identified. An excision wound model is used to measure wound healing action. Wounds are provided with OEA (2% w/v) or MEBO\(^®\) cream (marketed treatment). The wound closure rate related to vehicle-treated wounds is significantly increased by OEA. Comparing to vehicle wound tissues, significant levels of TGF-β in OEA and MEBO\(^®\) (p < 0.05) are displayed by gene expression patterns, with the most significant levels in OEA-treated wounds. Proinflammatory TNF-α and IL-1β levels are substantially reduced in OEA-treated wounds. The capability of several lignan-related compounds to interact with MMP-1 is revealed by extensive in silico investigation of the major OEA compounds (i.e., inverse docking, molecular dynamics simulation, and ΔG calculation), and their role in the wound-healing process is also characterized. The potential of OEA as a potent MMP-1 inhibitor is shown in subsequent in vitro testing (IC\(_{50}\) = 88.0 ± 0.1 nM). In conclusion, OEA is introduced as an interesting therapeutic candidate that can effectively manage wound healing because of its anti-inflammatory and antioxidant properties.
KW  - olive
KW  - LC–HRESIMS
KW  - wound
KW  - Olea
KW  - TNF-α
KW  - virtual docking
KW  - TGF-β
KW  - MMP-1
Y1  - 2022
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-286150
SN  - 2218-1989
VL  - 12
IS  - 9
ER  - 
TY  - JOUR
A1  - Albert, Štefan
A1  - Spaethe, Johannes
A1  - Grübel, Kornelia
A1  - Rössler, Wolfgang
T1  - Royal jelly-like protein localization reveals differences in hypopharyngeal glands buildup and conserved expression pattern in brains of bumblebees and honeybees
N2  - Royal jelly proteins (MRJPs) of the honeybee bear several open questions. One of them is their expression in tissues other than the hypopharyngeal glands (HGs), the site of royal jelly production. The sole MRJP-like gene of the bumblebee, Bombus terrestris (BtRJPL), represents a pre-diversification stage of the MRJP gene evolution in bees. Here we investigate the expression of BtRJPL in the HGs and the brain of bumblebees. Comparison of the HGs of bumblebees and honeybees revealed striking differences in their morphology with respect to sex- and caste-specific appearance, number of cells per acinus, and filamentous actin (F-actin) rings. At the cellular level, we found a temporary F-actin-covered meshwork in the secretory cells, which suggests a role for actin in the biogenesis of the end apparatus in HGs. Using immunohistochemical localization, we show that BtRJPL is expressed in the bumblebee brain, predominantly in the Kenyon cells of the mushroom bodies, the site of sensory integration in insects, and in the optic lobes. Our data suggest that a dual glandbrain function preceded the multiplication of MRJPs in the honeybee lineage. In the course of the honeybee evolution, HGs dramatically changed their morphology in order to serve a food-producing function.
KW  - Hypopharyngeal glands
KW  - Bumblebee
KW  - Bombus
KW  - Brain
KW  - Labial glands
KW  - Immunohistochemistry
KW  - Kenyon cells
KW  - Mushroom bodies
KW  - Honeybee
Y1  - 2014
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-112733
ER  - 
TY  - JOUR
A1  - Albrecht, Marco
A1  - Sharma, Cynthia M.
A1  - Dittrich, Marcus T.
A1  - Müller, Tobias
A1  - Reinhardt, Richard
A1  - Vogel, Jörg
A1  - Rudel, Thomas
T1  - The Transcriptional Landscape of Chlamydia pneumoniae
N2  - Background: Gene function analysis of the obligate intracellular bacterium Chlamydia pneumoniae is hampered by the facts that this organism is inaccessible to genetic manipulations and not cultivable outside the host. The genomes of several strains have been sequenced; however, very little information is available on the gene structure and transcriptome of C. pneumoniae. Results: Using a differential RNA-sequencing approach with specific enrichment of primary transcripts, we defined the transcriptome of purified elementary bodies and reticulate bodies of C. pneumoniae strain CWL-029; 565 transcriptional start sites of annotated genes and novel transcripts were mapped. Analysis of adjacent genes for cotranscription revealed 246 polycistronic transcripts. In total, a distinct transcription start site or an affiliation to an operon could be assigned to 862 out of 1,074 annotated protein coding genes. Semi-quantitative analysis of mapped cDNA reads revealed significant differences for 288 genes in the RNA levels of genes isolated from elementary bodies and reticulate bodies. We have identified and in part confirmed 75 novel putative non-coding RNAs. The detailed map of transcription start sites at single nucleotide resolution allowed for the first time a comprehensive and saturating analysis of promoter consensus sequences in Chlamydia. Conclusions: The precise transcriptional landscape as a complement to the genome sequence will provide new insights into the organization, control and function of genes. Novel non-coding RNAs and identified common promoter motifs will help to understand gene regulation of this important human pathogen.
KW  - Chlamydia pneumoniae
Y1  - 2011
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-69116
ER  - 
TY  - JOUR
A1  - Albrecht, Marco
A1  - Sharma, Cynthia M.
A1  - Reinhardt, Richard
A1  - Vogel, Joerg
A1  - Rudel, Thomas
T1  - Deep sequencing-based discovery of the Chlamydia trachomatis transcriptome
N2  - Chlamydia trachomatis is an obligate intracellular pathogenic bacterium that has been refractory to genetic manipulations. Although the genomes of several strains have been sequenced, very little information is available on the gene structure of these bacteria. We used deep sequencing to define the transcriptome of purified elementary bodies (EB) and reticulate bodies (RB) of C. trachomatis L2b, respectively. Using an RNAseq approach, we have mapped 363 transcriptional start sites (TSS) of annotated genes. Semiquantitative analysis of mapped cDNA reads revealed differences in the RNA levels of 84 genes isolated from EB and RB, respectively. We have identified and in part confirmed 42 genome- and 1 plasmid-derived novel non-coding RNAs. The genome encoded non-coding RNA, ctrR0332 was one of the most abundantly and differentially expressed RNA in EB and RB, implying an important role in the developmental cycle of C. trachomatis. The detailed map of TSS in a thus far unprecedented resolution as a complement to the genome sequence will help to understand the organization, control and function of genes of this important pathogen.
KW  - Biologie
Y1  - 2010
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-68389
ER  - 
TY  - JOUR
A1  - Alizadehrad, Davod
A1  - Krüger, Timothy
A1  - Engstler, Markus
A1  - Stark, Holger
T1  - Simulating the complex cell design of Trypanosoma brucei and its motility
JF  - PLOS Computational Biology
N2  - The flagellate Trypanosoma brucei, which causes the sleeping sickness when infecting a mammalian host, goes through an intricate life cycle. It has a rather complex propulsion mechanism and swims in diverse microenvironments. These continuously exert selective pressure, to which the trypanosome adjusts with its architecture and behavior. As a result, the trypanosome assumes a diversity of complex morphotypes during its life cycle. However, although cell biology has detailed form and function of most of them, experimental data on the dynamic behavior and development of most morphotypes is lacking. Here we show that simulation science can predict intermediate cell designs by conducting specific and controlled modifications of an accurate, nature-inspired cell model, which we developed using information from live cell analyses. The cell models account for several important characteristics of the real trypanosomal morphotypes, such as the geometry and elastic properties of the cell body, and their swimming mechanism using an eukaryotic flagellum. We introduce an elastic network model for the cell body, including bending rigidity and simulate swimming in a fluid environment, using the mesoscale simulation technique called multi-particle collision dynamics. The in silico trypanosome of the bloodstream form displays the characteristic in vivo rotational and translational motility pattern that is crucial for survival and virulence in the vertebrate host. Moreover, our model accurately simulates the trypanosome's tumbling and backward motion. We show that the distinctive course of the attached flagellum around the cell body is one important aspect to produce the observed swimming behavior in a viscous fluid, and also required to reach the maximal swimming velocity. Changing details of the flagellar attachment generates less efficient swimmers. We also simulate different morphotypes that occur during the parasite's development in the tsetse fly, and predict a flagellar course we have not been able to measure in experiments so far.
KW  - multiparticle collision dynamics
KW  - human african trypanosomiasis
KW  - biology
KW  - cytoskeleton
KW  - flow
KW  - flagellar motility
KW  - tsetse fly
KW  - propulsion
KW  - cytokinesis
KW  - parasites
Y1  - 2015
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-144610
VL  - 11
IS  - 1
ER  - 
TY  - JOUR
A1  - Alnusaire, Taghreed S.
A1  - Sayed, Ahmed M.
A1  - Elmaidomy, Abeer H.
A1  - Al-Sanea, Mohammad M.
A1  - Albogami, Sarah
A1  - Albqmi, Mha
A1  - Alowaiesh, Bassam F.
A1  - Mostafa, Ehab M.
A1  - Musa, Arafa
A1  - Youssif, Khayrya A.
A1  - Refaat, Hesham
A1  - Othman, Eman M.
A1  - Dandekar, Thomas
A1  - Alaaeldin, Eman
A1  - Ghoneim, Mohammed M.
A1  - Abdelmohsen, Usama Ramadan
T1  - An in vitro and in silico study of the enhanced antiproliferative and pro-oxidant potential of Olea europaea L. cv. Arbosana leaf extract via elastic nanovesicles (spanlastics)
JF  - Antioxidants
N2  - The olive tree is a venerable Mediterranean plant and often used in traditional medicine. The main aim of the present study was to evaluate the effect of Olea europaea L. cv. Arbosana leaf extract (OLE) and its encapsulation within a spanlastic dosage form on the improvement of its pro-oxidant and antiproliferative activity against HepG-2, MCF-7, and Caco-2 human cancer cell lines. The LC-HRESIMS-assisted metabolomic profile of OLE putatively annotated 20 major metabolites and showed considerable in vitro antiproliferative activity against HepG-2, MCF-7, and Caco-2 cell lines with IC\(_{50}\) values of 9.2 ± 0.8, 7.1 ± 0.9, and 6.5 ± 0.7 µg/mL, respectively. The encapsulation of OLE within a (spanlastic) nanocarrier system, using a spraying method and Span 40 and Tween 80 (4:1 molar ratio), was successfully carried out (size 41 ± 2.4 nm, zeta potential 13.6 ± 2.5, and EE 61.43 ± 2.03%). OLE showed enhanced thermal stability, and an improved in vitro antiproliferative effect against HepG-2, MCF-7, and Caco-2 (IC\(_{50}\) 3.6 ± 0.2, 2.3 ± 0.1, and 1.8 ± 0.1 µg/mL, respectively) in comparison to the unprocessed extract. Both preparations were found to exhibit pro-oxidant potential inside the cancer cells, through the potential inhibitory activity of OLE against glutathione reductase and superoxide dismutase (IC\(_{50}\) 1.18 ± 0.12 and 2.33 ± 0.19 µg/mL, respectively). These inhibitory activities were proposed via a comprehensive in silico study to be linked to the presence of certain compounds in OLE. Consequently, we assume that formulating such a herbal extract within a suitable nanocarrier would be a promising improvement of its therapeutic potential.
KW  - olive
KW  - metabolomic profiling
KW  - antiproliferative
KW  - pro-oxidant
KW  - encapsulation
KW  - spanlastic
KW  - nanocarrier
KW  - docking
KW  - molecular dynamics simulation
KW  - Olea
Y1  - 2021
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-250064
SN  - 2076-3921
VL  - 10
IS  - 12
ER  - 
TY  - JOUR
A1  - Alsheimer, Manfred
A1  - Link, Jana
A1  - Jahn, Daniel
A1  - Schmitt, Johannes
A1  - Göb, Eva
A1  - Baar, Johannes
A1  - Ortega, Sagrario
A1  - Benavente, Ricardo
T1  - The Meiotic Nuclear Lamina Regulates Chromosome Dynamics and Promotes Efficient Homologous Recombination in the Mouse
JF  - PLoS Genetics
N2  - The nuclear lamina is the structural scaffold of the nuclear envelope and is well known for its central role in nuclear organization and maintaining nuclear stability and shape. In the past, a number of severe human disorders have been identified to be associated with mutations in lamins. Extensive research on this topic has provided novel important clues about nuclear lamina function. These studies have contributed to the knowledge that the lamina constitutes a complex multifunctional platform combining both structural and regulatory functions. Here, we report that, in addition to the previously demonstrated significance for somatic cell differentiation and maintenance, the nuclear lamina is also an essential determinant for germ cell development. Both male and female mice lacking the short meiosis-specific A-type lamin C2 have a severely defective meiosis, which at least in the male results in infertility. Detailed analysis revealed that lamin C2 is required for telomere-driven dynamic repositioning of meiotic chromosomes. Loss of lamin C2 affects precise synapsis of the homologs and interferes with meiotic double-strand break repair. Taken together, our data explain how the nuclear lamina contributes to meiotic chromosome behaviour and accurate genome haploidization on a mechanistic level.
KW  - homologous chromosomes
KW  - homologous recombination
KW  - lamins
KW  - Oocytes
KW  - spermatocytes
KW  - synapsis
KW  - telomeres
KW  - testes
Y1  - 2013
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-96285
ER  - 
TY  - JOUR
A1  - Alsheimer, Manfred
A1  - Link, Jana
A1  - Leubner, Monika
A1  - Schmitt, Johannes
A1  - Göb, Eva
A1  - Benavente, Ricardo
A1  - Jeang, Kuan-Teh
A1  - Xu, Rener
T1  - Analysis of Meiosis in  SUN1 Deficient Mice Reveals a Distinct Role of SUN2 in Mammalian Meiotic LINC Complex Formation and Function
N2  - LINC complexes are evolutionarily conserved nuclear envelope bridges, composed of SUN (Sad-1/UNC-84) and KASH (Klarsicht/ANC-1/Syne/homology) domain proteins. They are crucial for nuclear positioning and nuclear shape determination, and also mediate nuclear envelope (NE) attachment of meiotic telomeres, essential for driving homolog synapsis and recombination. In mice, SUN1 and SUN2 are the only SUN domain proteins expressed during meiosis, sharing their localization with meiosis-specific KASH5. Recent studies have shown that loss of SUN1 severely interferes with meiotic processes. Absence of SUN1 provokes defective telomere attachment and causes infertility. Here, we report that meiotic telomere attachment is not entirely lost in mice deficient for SUN1, but numerous telomeres are still attached to the NE through SUN2/KASH5-LINC complexes. In Sun12/2 meiocytes attached telomeres retained the capacity to form bouquetlike clusters. Furthermore, we could detect significant numbers of late meiotic recombination events in Sun12/2 mice. Together, this indicates that even in the absence of SUN1 telomere attachment and their movement within the nuclear envelope per se can be functional.

Author summary: 
Correct genome haploidization during meiosis requires tightly regulated chromosome movements that follow a highly conserved choreography during prophase I. Errors in these movements cause subsequent meiotic defects, which typically lead to infertility. At the beginning of meiotic prophase, chromosome ends are tethered to the nuclear envelope (NE). This attachment of telomeres appears to be mediated by well-conserved membrane spanning protein complexes within the NE (LINC complexes). In mouse meiosis, the two main LINC components SUN1 and SUN2 were independently described to localize at the sites of telomere attachment. While SUN1 has been demonstrated to be critical for meiotic telomere attachment, the precise role of SUN2 in this context, however, has been discussed controversially in the field. Our current study was targeted to determine the factual capacity of SUN2 in telomere attachment and chromosome movements in SUN1 deficient mice. Remarkably, although telomere attachment is impaired in the absence of SUN1, we could find a yet undescribed SUN1-independent telomere attachment, which presumably is mediated by SUN2 and KASH5. This SUN2 mediated telomere attachment is stable throughout prophase I and functional in moving telomeres within the NE. Thus, our results clearly indicate that SUN1 and SUN2, at least partially, fulfill redundant meiotic functions.
KW  - telomeres
KW  - spermatocytes
KW  - Oocytes
KW  - meiosis
KW  - protein domains
KW  - cytoskeleton
KW  - synapsis
KW  - homologous chromosomes
Y1  - 2014
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-111355
ER  - 
TY  - JOUR
A1  - Amatobi, Kelechi M.
A1  - Ozbek-Unal, Ayten Gizem
A1  - Schäbler, Stefan
A1  - Deppisch, Peter
A1  - Helfrich-Förster, Charlotte
A1  - Mueller, Martin J.
A1  - Wegener, Christian
A1  - Fekete, Agnes
T1  - The circadian clock is required for rhythmic lipid transport in Drosophila in interaction with diet and photic condition
JF  - Journal of Lipid Research
N2  - Modern lifestyle is often at odds with endogenously driven rhythmicity, which can lead to circadian disruption and metabolic syndrome. One signature for circadian disruption is a reduced or altered metabolite cycling in the circulating tissue reflecting the current metabolic status. Drosophila is a well-established model in chronobiology, but day-time dependent variations of transport metabolites in the fly circulation are poorly characterized. Here, we sampled fly hemolymph throughout the day and analyzed diacylglycerols (DGs), phosphoethanolamines (PEs) and phosphocholines (PCs) using LC-MS. In wild-type flies kept on sugar-only medium under a light-dark cycle, all transport lipid species showed a synchronized bimodal oscillation pattern with maxima at the beginning and end of the light phase which were impaired in period01 clock mutants. In wild-type flies under constant dark conditions, the oscillation became monophasic with a maximum in the middle of the subjective day. In strong support of clock-driven oscillations, levels of the targeted lipids peaked once in the middle of the light phase under time-restricted feeding independent of the time of food intake. When wild-type flies were reared on full standard medium, the rhythmic alterations of hemolymph lipid levels were greatly attenuated. Our data suggest that the circadian clock aligns daily oscillations of DGs, PEs, and PCs in the hemolymph to the anabolic siesta phase, with a strong influence of light on phase and modality.
KW  - hemolymph lipids
KW  - lipidomics
KW  - circadian rhythm
KW  - feeding
KW  - locomotor activity
KW  - light-driven metabolism
Y1  - 2023
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-349961
VL  - 64
IS  - 10
ER  - 
TY  - JOUR
A1  - Ambrožová, Lucie
A1  - Finnberg, Sven
A1  - Feldmann, Benedikt
A1  - Buse, Jörn
A1  - Preuss, Henry
A1  - Ewald, Jörg
A1  - Thorn, Simon
T1  - Coppicing and topsoil removal promote diversity of dung‐inhabiting beetles (Coleoptera: Scarabaeidae, Geotrupidae, Staphylinidae) in forests
JF  - Agricultural and Forest Entomology
N2  - Central European forests experience a substantial loss of open-forest organisms due to forest management and increasing nitrogen deposition. However, management strategies, removing different levels of nitrogen, have been rarely evaluated simultaneously.
We tested the additive effects of coppicing and topsoil removal on communities of dung-inhabiting beetles compared to closed forests. We sampled 57 021 beetles, using baited pitfall traps exposed on 27 plots.
Experimental treatments resulted in significantly different communities by promoting open-habitat species. While alpha diversity did not differ among treatments, gamma diversity of Geotrupidae and Scarabaeidae and beta diversity of Staphylinidae were higher in coppice than in forest. Functional diversity of rove beetles was higher in both, coppice and topsoil-removed plots, compared to control plots. This was likely driven by higher habitat heterogeneity in established forest openings. Five dung beetle species and four rove beetle species benefitted from coppicing, one red-listed dung beetle and two rove beetle species benefitted from topsoil removal.
Our results demonstrate that dung-inhabiting beetles related to open forest patches can be promoted by both, coppicing and additional topsoil removal. A mosaic of coppice and bare-soil-rich patches can hence promote landscape-level gamma diversity of dung and rove beetles within forests.
KW  - nitrogen uptake
KW  - dung beetle
KW  - forest management
KW  - functional diversity
KW  - insect decline
KW  - rove beetle
Y1  - 2022
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-258296
VL  - 24
IS  - 1
ER  - 
TY  - JOUR
A1  - Ampattu, Biju Joseph
A1  - Hagmann, Laura
A1  - Liang, Chunguang
A1  - Dittrich, Marcus
A1  - Schlüter, Andreas
A1  - Blom, Jochen
A1  - Krol, Elizaveta
A1  - Goesmann, Alexander
A1  - Becker, Anke
A1  - Dandekar, Thomas
A1  - Müller, Tobias
A1  - Schoen, Christoph
T1  - Transcriptomic buffering of cryptic genetic variation contributes to meningococcal virulence
JF  - BMC Genomics
N2  - Background:
Commensal bacteria like Neisseria meningitidis sometimes cause serious disease. However, genomic comparison of hyperinvasive and apathogenic lineages did not reveal unambiguous hints towards indispensable virulence factors. Here, in a systems biological approach we compared gene expression of the invasive strain MC58 and the carriage strain α522 under different ex vivo conditions mimicking commensal and virulence compartments to assess the strain-specific impact of gene regulation on meningococcal virulence.
Results:
Despite indistinguishable ex vivo phenotypes, both strains differed in the expression of over 500 genes under infection mimicking conditions. These differences comprised in particular metabolic and information processing genes as well as genes known to be involved in host-damage such as the nitrite reductase and numerous LOS biosynthesis genes. A model based analysis of the transcriptomic differences in human blood suggested ensuing metabolic flux differences in energy, glutamine and cysteine metabolic pathways along with differences in the activation of the stringent response in both strains. In support of the computational findings, experimental analyses revealed differences in cysteine and glutamine auxotrophy in both strains as well as a strain and condition dependent essentiality of the (p)ppGpp synthetase gene relA and of a short non-coding AT-rich repeat element in its promoter region.
Conclusions:
Our data suggest that meningococcal virulence is linked to transcriptional buffering of cryptic genetic variation in metabolic genes including global stress responses. They further highlight the role of regulatory elements for bacterial virulence and the limitations of model strain approaches when studying such genetically diverse species as N. meningitidis.
KW  - neisseria meningitidis
KW  - MITE
KW  - virulenceregulatory evolution
KW  - systems biology
KW  - metabolism
KW  - cryptic
KW  - genetic variation
KW  - stringent response
KW  - relA
Y1  - 2017
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-157534
VL  - 18
IS  - 282
ER  - 
TY  - JOUR
A1  - Anders, F.
A1  - Schartl, Manfred
A1  - Barnekow, A.
A1  - Schmidt, C. R.
A1  - Luke, W.
A1  - Jaenel-Dess, G.
A1  - Anders, A.
T1  - The genes that carcinogens act upon
N2  - No abstract available.
KW  - Onkogen
Y1  - 1985
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-72704
ER  - 
TY  - JOUR
A1  - Anders, F.
A1  - Schartl., Manfred
A1  - Barnekow, A.
A1  - Anders, A.
T1  - Xiphophorus as an in vivo model for studies on normal and defective control of oncogenes
N2  - The Xiphophorus tumor system has provided the opportunity to reduce the enormous complexity of cancer etiology to a few biological elements basically involved in neoplasia. The development of a tumor requires an oncogene which, after impairment, deletion, or elimination of its regulatory genes is permitted to mediate neoplastic transformation. Emphasis is being placed today in cancer research on the actual oncogenes themselves, but, in our opinion, the most important genes involved in neoplasia are these regulatory genes. However, although detected by c1assical genetics in the Xiphophorus system, th ese genes are not at present open to a more fin ely detailed molecular biological analysis. Their actual mode of action is therefore still far from being understood.
KW  - Xiphophorus
Y1  - 1984
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-80721
ER  - 
TY  - JOUR
A1  - Andreska, Thomas
A1  - Aufmkolk, Sarah
A1  - Sauer, Markus
A1  - Blum, Robert
T1  - High abundance of BDNF within glutamatergic presynapses of cultured hippocampal neurons
JF  - Frontiers in Cellular Neuroscience
N2  - In the mammalian brain, the neurotrophin brain-derived neurotrophic factor (BDNF) has emerged as a key factor for synaptic refinement, plasticity and learning. Although BDNF-induced signaling cascades are well known, the spatial aspects of the synaptic BDNF localization remained unclear. Recent data provide strong evidence for an exclusive presynaptic location and anterograde secretion of endogenous BDNF at synapses of the hippocampal circuit. In contrast, various studies using BDNF overexpression in cultured hippocampal neurons support the idea that postsynaptic elements and other dendritic structures are the preferential sites of BDNF localization and release. In this study we used rigorously tested anti-BDNF antibodies and achieved a dense labeling of endogenous BDNF close to synapses. Confocal microscopy showed natural BDNF close to many, but not all glutamatergic synapses, while neither GABAergic synapses nor postsynaptic structures carried a typical synaptic BDNF label. To visualize the BDNF distribution within the fine structure of synapses, we implemented super resolution fluorescence imaging by direct stochastic optical reconstruction microscopy (dSTORM). Two-color dSTORM images of neurites were acquired with a spatial resolution of ~20 nm. At this resolution, the synaptic scaffold proteins Bassoon and Homer exhibit hallmarks of mature synapses and form juxtaposed bars, separated by a synaptic cleft. BDNF imaging signals form granule-like clusters with a mean size of ~60 nm and are preferentially found within the fine structure of the glutamatergic presynapse. Individual glutamatergic presynapses carried up to 90% of the synaptic BDNF immunoreactivity, and only a minor fraction of BDNF molecules was found close to the postsynaptic bars. Our data proof that hippocampal neurons are able to enrich and store high amounts of BDNF in small granules within the mature glutamatergic presynapse, at a principle site of synaptic plasticity.
KW  - hippocampal neurons
KW  - synapse structure
KW  - presynapse
KW  - synaptic localization
KW  - BDNF
Y1  - 2014
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-119793
SN  - 1662-5102
VL  - 8
IS  - 107
ER  - 
TY  - JOUR
A1  - Andronic, Joseph
A1  - Shirakashi, Ryo
A1  - Pickel, Simone U.
A1  - Westerling, Katherine M.
A1  - Klein, Teresa
A1  - Holm, Thorge
A1  - Sauer, Markus
A1  - Sukhorukov, Vladimir L.
T1  - Hypotonic Activation of the Myo-Inositol Transporter SLC5A3 in HEK293 Cells Probed by Cell Volumetry, Confocal and Super-Resolution Microscopy
JF  - PLoS One
N2  - Swelling-activated pathways for myo-inositol, one of the most abundant organic osmolytes in mammalian cells, have not yet been identified. The present study explores the SLC5A3 protein as a possible transporter of myo-inositol in hyponically swollen HEK293 cells. To address this issue, we examined the relationship between the hypotonicity-induced changes in plasma membrane permeability to myo-inositol Pino [m/s] and expression/localization of SLC5A3. Pino values were determined by cell volumetry over a wide tonicity range (100–275 mOsm) in myo-inositol-substituted solutions. While being negligible under mild hypotonicity (200–275 mOsm), Pino grew rapidly at osmolalities below 200 mOsm to reach a maximum of ∼3 nm/s at 100–125 mOsm, as indicated by fast cell swelling due to myo-inositol influx. The increase in Pino resulted most likely from the hypotonicity-mediated incorporation of cytosolic SLC5A3 into the plasma membrane, as revealed by confocal fluorescence microscopy of cells expressing EGFP-tagged SLC5A3 and super-resolution imaging of immunostained SLC5A3 by direct stochastic optical reconstruction microscopy (dSTORM). dSTORM in hypotonic cells revealed a surface density of membrane-associated SLC5A3 proteins of 200–2000 localizations/μm2. Assuming SLC5A3 to be the major path for myo-inositol, a turnover rate of 80–800 myo-inositol molecules per second for a single transporter protein was estimated from combined volumetric and dSTORM data. Hypotonic stress also caused a significant upregulation of SLC5A3 gene expression as detected by semiquantitative RT-PCR and Western blot analysis. In summary, our data provide first evidence for swelling-mediated activation of SLC5A3 thus suggesting a functional role of this transporter in hypotonic volume regulation of mammalian cells.
KW  - electrolytes
KW  - isotonic
KW  - membrane proteins
KW  - cell membranes
KW  - hypotonic
KW  - hypotonic solutions
KW  - tonicity
KW  - permeability
Y1  - 2015
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-126408
VL  - 10
IS  - 3
ER  - 
TY  - JOUR
A1  - Anelli, Viviana
A1  - Ordas, Anita
A1  - Kneitz, Susanne
A1  - Sagredo, Leonel Munoz
A1  - Gourain, Victor
A1  - Schartl, Manfred
A1  - Meijer, Annemarie H.
A1  - Mione, Marina
T1  - Ras-Induced miR-146a and 193a Target Jmjd6 to Regulate Melanoma Progression
JF  - Frontiers in Genetics
N2  - Ras genes are among the most commonly mutated genes in human cancer; yet our understanding of their oncogenic activity at the molecular mechanistic level is incomplete. To identify downstream events that mediate ras-induced cellular transformation in vivo, we analyzed global microRNA expression in three different models of Ras-induction and tumor formation in zebrafish. Six microRNAs were found increased in Ras-induced melanoma, glioma and in an inducible model of ubiquitous Ras expression. The upregulation of the microRNAs depended on the activation of the ERK and AKT pathways and to a lesser extent, on mTOR signaling. Two Ras-induced microRNAs (miR-146a and 193a) target Jmjd6, inducing downregulation of its mRNA and protein levels at the onset of Ras expression during melanoma development. However, at later stages of melanoma progression, jmjd6 levels were found elevated. The dynamic of Jmjd6 levels during progression of melanoma in the zebrafish model suggests that upregulation of the microRNAs targeting Jmjd6 may be part of an anti-cancer response. Indeed, triple transgenic fish engineered to express a microRNA-resistant Jmjd6 from the onset of melanoma have increased tumor burden, higher infiltration of leukocytes and shorter melanoma-free survival. Increased JMJD6 expression is found in several human cancers, including melanoma, suggesting that the up-regulation of Jmjd6 is a critical event in tumor progression.
The following link has been created to allow review of record GSE37015: http://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?token=jjcrbiuicyyqgpc&acc=GSE37015.
KW  - zebrafish
KW  - cancer models
KW  - microRNA
KW  - Jmjd6
KW  - ras
KW  - melanoma
KW  - miR-146a
KW  - miR-193a
Y1  - 2018
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-196963
SN  - 1664-8021
VL  - 9
IS  - 675
ER  - 
TY  - JOUR
A1  - Ankenbrand, Markus J.
A1  - Weber, Lorenz
A1  - Becker, Dirk
A1  - Förster, Frank
A1  - Bemm, Felix
T1  - TBro: visualization and management of de novo transcriptomes
JF  - Database
N2  - RNA sequencing (RNA-seq) has become a powerful tool to understand molecular mechanisms and/or developmental programs. It provides a fast, reliable and cost-effective method to access sets of expressed elements in a qualitative and quantitative manner. Especially for non-model organisms and in absence of a reference genome, RNA-seq data is used to reconstruct and quantify transcriptomes at the same time. Even SNPs, InDels, and alternative splicing events are predicted directly from the data without having a reference genome at hand. A key challenge, especially for non-computational personnal, is the management of the resulting datasets, consisting of different data types and formats. Here, we present TBro, a flexible de novo transcriptome browser, tackling this challenge. TBro aggregates sequences, their annotation, expression levels as well as differential testing results. It provides an easy-to-use interface to mine the aggregated data and generate publication-ready visualizations. Additionally, it supports users with an intuitive cart system, that helps collecting and analysing biological meaningful sets of transcripts. TBro’s modular architecture allows easy extension of its functionalities in the future. Especially, the integration of new data types such as proteomic quantifications or array-based gene expression data is straightforward. Thus, TBro is a fully featured yet flexible transcriptome browser that supports approaching complex biological questions and enhances collaboration of numerous researchers.
KW  - database
Y1  - 2016
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-147954
VL  - 2016
ER  - 
TY  - JOUR
A1  - Anton, Sylvia
A1  - Rössler, Wolfgang
T1  - Plasticity and modulation of olfactory circuits in insects
JF  - Cell and Tissue Research
N2  - Olfactory circuits change structurally and physiologically during development and adult life. This allows insects to respond to olfactory cues in an appropriate and adaptive way according to their physiological and behavioral state, and to adapt to their specific abiotic and biotic natural environment. We highlight here findings on olfactory plasticity and modulation in various model and non-model insects with an emphasis on moths and social Hymenoptera. Different categories of plasticity occur in the olfactory systems of insects. One type relates to the reproductive or feeding state, as well as to adult age. Another type of plasticity is context-dependent and includes influences of the immediate sensory and abiotic environment, but also environmental conditions during postembryonic development, periods of adult behavioral maturation, and short- and long-term sensory experience. Finally, plasticity in olfactory circuits is linked to associative learning and memory formation. The vast majority of the available literature summarized here deals with plasticity in primary and secondary olfactory brain centers, but also peripheral modulation is treated. The described molecular, physiological, and structural neuronal changes occur under the influence of neuromodulators such as biogenic amines, neuropeptides, and hormones, but the mechanisms through which they act are only beginning to be analyzed.
KW  - antenna
KW  - antennal lobe
KW  - mushroom body
KW  - neuromodulation
KW  - structural synaptic plasticity
Y1  - 2021
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-235820
SN  - 0302-766X
VL  - 383
ER  - 
TY  - JOUR
A1  - Appel, Mirjam
A1  - Scholz, Claus-Jürgen
A1  - Müller, Tobias
A1  - Dittrich, Marcus
A1  - König, Christian
A1  - Bockstaller, Marie
A1  - Oguz, Tuba
A1  - Khalili, Afshin
A1  - Antwi-Adjei, Emmanuel
A1  - Schauer, Tamas
A1  - Margulies, Carla
A1  - Tanimoto, Hiromu
A1  - Yarali, Ayse
T1  - Genome-Wide Association Analyses Point to Candidate Genes for Electric Shock Avoidance in Drosophila melanogaster
JF  - PLoS ONE
N2  - Electric shock is a common stimulus for nociception-research and the most widely used reinforcement in aversive associative learning experiments. Yet, nothing is known about the mechanisms it recruits at the periphery. To help fill this gap, we undertook a genome-wide association analysis using 38 inbred Drosophila melanogaster strains, which avoided shock to varying extents. We identified 514 genes whose expression levels and/or sequences covaried with shock avoidance scores. We independently scrutinized 14 of these genes using mutants, validating the effect of 7 of them on shock avoidance. This emphasizes the value of our candidate gene list as a guide for follow-up research. In addition, by integrating our association results with external protein-protein interaction data we obtained a shock avoidance- associated network of 38 genes. Both this network and the original candidate list contained a substantial number of genes that affect mechanosensory bristles, which are hairlike organs distributed across the fly's body. These results may point to a potential role for mechanosensory bristles in shock sensation. Thus, we not only provide a first list of candidate genes for shock avoidance, but also point to an interesting new hypothesis on nociceptive mechanisms.
KW  - functional analysis
KW  - disruption project
KW  - natural variation
KW  - complex traits
KW  - networks
KW  - behavior
KW  - flies
KW  - temperature
KW  - genetics
KW  - painful
Y1  - 2015
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-152006
VL  - 10
IS  - 5
ER  - 
TY  - JOUR
A1  - Arenas, Andrés
A1  - Roces, Flavio
T1  - Avoidance of plants unsuitable for the symbiotic fungus in leaf-cutting ants: Learning can take place entirely at the colony dump
JF  - PLoS ONE
N2  - Plants initially accepted by foraging leaf-cutting ants are later avoided if they prove unsuitable for their symbiotic fungus. Plant avoidance is mediated by the waste produced in the fungus garden soon after the incorporation of the unsuitable leaves, as foragers can learn plant odors and cues from the damaged fungus that are both present in the recently produced waste particles. We asked whether avoidance learning of plants unsuitable for the symbiotic fungus can take place entirely at the colony dump. In order to investigate whether cues available in the waste chamber induce plant avoidance in naïve subcolonies, we exchanged the waste produced by subcolonies fed either fungicide-treated privet leaves or untreated leaves and measured the acceptance of untreated privet leaves before and after the exchange of waste. Second, we evaluated whether foragers could perceive the avoidance cues directly at the dump by quantifying the visits of labeled foragers to the waste chamber. Finally, we asked whether foragers learn to specifically avoid untreated leaves of a plant after a confinement over 3 hours in the dump of subcolonies that were previously fed fungicide-treated leaves of that species. After the exchange of the waste chambers, workers from subcolonies that had access to waste from fungicide-treated privet leaves learned to avoid that plant. One-third of the labeled foragers visited the dump. Furthermore, naïve foragers learned to avoid a specific, previously unsuitable plant if exposed solely to cues of the dump during confinement. We suggest that cues at the dump enable foragers to predict the unsuitable effects of plants even if they had never been experienced in the fungus garden.
KW  - leaves
KW  - ants
KW  - fungi
KW  - foraging
KW  - animal sociality
KW  - social systems
KW  - learning
KW  - symbiosis
Y1  - 2017
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-157559
VL  - 12
IS  - 3
ER  - 
TY  - JOUR
A1  - Arends, H.
A1  - Sebald, Walter
T1  - Nucleotide sequence of the cloned mRNA and gene of the ADP/ATP carrier from Neurospora crassa
N2  - A cDNA complementary to the mRNA of the ADPIATP carrier from Neurospora crassa was identified among ordered cDNA clones by hybridizing total polyadenylated RNA to pools of 96 cDNA recombinant plasmids and subsequent cellfree translation of hybridization-selected mRNA. Further carrier cDNAs were found by colony fdter hybridization at a frequency of 0.2-0.3%. The gene of the carrier was cloned and isolated on a 4.6-kbp EcoRl fragment of total Neurospora DNA, and the start of the mRNA was determined by Sl nuclease mapping. From the nucleotide sequence of the cDNA and the genomic DNA, the primary structure of the gene, of the mRNA and of the ADP I ATP carrier protein could be deduced. The gene occurs in a single copy in the genome and related genes are absent. It contains two short introns, and a pyrimidine-rieb promoter region. The mRNA has a 46-bp 5 1 end and a 219-bp 3 1 end. There is an open reading frame coding for the 313 amino acid residues of the Neurospora carrier protein. The amino acid sequence is homologous in 148 positions with the established primary structure of the beef heart carrier.
KW  - Biochemie
KW  - mitochondrial ADP
KW  - ATP carrier
KW  - Neurospora crassa
KW  - mRNA and gene
KW  - nucleotide sequence
KW  - hybrid-selected translation
Y1  - 1984
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-62684
ER  - 
TY  - JOUR
A1  - Argos, P.
A1  - Dandekar, Thomas
T1  - Delineating the main chain topology of four-helix bundle proteins using the genetic algorithm and knowledge based on the amino acid sequence alone
N2  - No abstract available
KW  - Proteine
KW  - Strukturanalyse
KW  - Abstandsmessung
Y1  - 1994
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-33807
ER  - 
TY  - JOUR
A1  - Aso, Yoshinori
A1  - Herb, Andrea
A1  - Ogueta, Maite
A1  - Siwanowicz, Igor
A1  - Templier, Thomas
A1  - Friedrich, Anja B.
A1  - Ito, Kei
A1  - Scholz, Henrike
A1  - Tanimoto, Hiromu
T1  - Three Dopamine Pathways Induce Aversive Odor Memories with Different Stability
JF  - PLoS Genetics
N2  - Animals acquire predictive values of sensory stimuli through reinforcement. In the brain of Drosophila melanogaster, activation of two types of dopamine neurons in the PAM and PPL1 clusters has been shown to induce aversive odor memory. Here, we identified the third cell type and characterized aversive memories induced by these dopamine neurons. These three dopamine pathways all project to the mushroom body but terminate in the spatially segregated subdomains. To understand the functional difference of these dopamine pathways in electric shock reinforcement, we blocked each one of them during memory acquisition. We found that all three pathways partially contribute to electric shock memory. Notably, the memories mediated by these neurons differed in temporal stability. Furthermore, combinatorial activation of two of these pathways revealed significant interaction of individual memory components rather than their simple summation. These results cast light on a cellular mechanism by which a noxious event induces different dopamine signals to a single brain structure to synthesize an aversive memory.
KW  - dynamics
KW  - serotonin
KW  - expression
KW  - melanogaster
KW  - neurons form
KW  - olfactory memory
KW  - long-term-memory
KW  - drosophila mushroom body
KW  - sensitization
KW  - localization
Y1  - 2012
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-130631
VL  - 8
IS  - 7
ER  - 
TY  - JOUR
A1  - Audretsch, Christof
A1  - Gratani, Fabio
A1  - Wolz, Christiane
A1  - Dandekar, Thomas
T1  - Modeling of stringent-response reflects nutrient stress induced growth impairment and essential amino acids in different Staphylococcus aureus mutants
JF  - Scientific Reports
N2  - Stapylococcus aureus colonises the nose of healthy individuals but can also cause a wide range of infections. Amino acid (AA) synthesis and their availability is crucial to adapt to conditions encountered in vivo. Most S. aureus genomes comprise all genes required for AA biosynthesis. Nevertheless, different strains require specific sets of AAs for growth. In this study we show that regulation inactivates pathways under certain conditions which result in these observed auxotrophies. We analyzed in vitro and modeled in silico in a Boolean semiquantitative model (195 nodes, 320 edges) the regulatory impact of stringent response (SR) on AA requirement in S. aureus HG001 (wild-type) and in mutant strains lacking the metabolic regulators RSH, CodY and CcpA, respectively. Growth in medium lacking single AAs was analyzed. Results correlated qualitatively to the in silico predictions of the final model in 92% and quantitatively in 81%. Remaining gaps in our knowledge are evaluated and discussed. This in silico model is made fully available and explains how integration of different inputs is achieved in SR and AA metabolism of S. aureus. The in vitro data and in silico modeling stress the role of SR and central regulators such as CodY for AA metabolisms in S. aureus.
KW  - bacteriology
KW  - cellular signalling networks
Y1  - 2021
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-260313
VL  - 11
IS  - 1
ER  - 
TY  - JOUR
A1  - Auer, Daniela
A1  - Hügelschäffer, Sophie D.
A1  - Fischer, Annette B.
A1  - Rudel, Thomas
T1  - The chlamydial deubiquitinase Cdu1 supports recruitment of Golgi vesicles to the inclusion
JF  - Cellular Microbiology
N2  - Chlamydia trachomatis is the main cause of sexually transmitted diseases worldwide. As obligate intracellular bacteria Chlamydia replicate in a membrane bound vacuole called inclusion and acquire nutrients for growth and replication from their host cells. However, like all intracellular bacteria, Chlamydia have to prevent eradication by the host's cell autonomous system. The chlamydial deubiquitinase Cdu1 is secreted into the inclusion membrane, facing the host cell cytosol where it deubiquitinates cellular proteins. Here we show that inactivation of Cdu1 causes a growth defect of C. trachomatis in primary cells. Moreover, ubiquitin and several autophagy receptors are recruited to the inclusion membrane of Cdu1‐deficient Chlamydia . Interestingly, the growth defect of cdu1 mutants is not rescued when autophagy is prevented. We find reduced recruitment of Golgi vesicles to the inclusion of Cdu1 mutants indicating that vesicular trafficking is altered in bacteria without active deubiquitinase (DUB). Our work elucidates an important role of Cdu1 in the functional preservation of the chlamydial inclusion surface.
KW  - autophagy
KW  - Cdu1
KW  - ChlaDUB1
KW  - Chlamydia trachomatis
KW  - DUB
KW  - Golgi
KW  - xenophagy
Y1  - 2020
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-208675
VL  - 22
IS  - 5
ER  - 
TY  - JOUR
A1  - Aupperle-Lellbach, Heike
A1  - Heidrich, Daniela
A1  - Kehl, Alexandra
A1  - Conrad, David
A1  - Brockmann, Maria
A1  - Törner, Katrin
A1  - Beitzinger, Christoph
A1  - Müller, Tobias
T1  - KITLG copy number germline variations in schnauzer breeds and their relevance in digital squamous cell carcinoma in black giant schnauzers
JF  - Veterinary Sciences
N2  - Copy number variations (CNVs) of the KITLG gene seem to be involved in the oncogenesis of digital squamous cell carcinoma (dSCC). The aims of this study were (1) to investigate KITLG CNV in giant (GS), standard (SS), and miniature (MS) schnauzers and (2) to compare KITLG CNV between black GS with and without dSCC. Blood samples from black GS (22 with and 17 without dSCC), black SS (18 with and 4 without dSSC; 5 unknown), and 50 MS (unknown dSSC status and coat colour) were analysed by digital droplet PCR. The results are that (1) most dogs had a copy number (CN) value > 4 (range 2.5–7.6) with no significant differences between GS, SS, and MS, and (2) the CN value in black GS with dSCC was significantly higher than in those without dSCC (p = 0.02). CN values > 5.8 indicate a significantly increased risk for dSCC, while CN values < 4.7 suggest a reduced risk for dSCC (grey area: 4.7–5.8). Diagnostic testing for KITLG CNV may sensitise owners to the individual risk of their black GS for dSCC. Further studies should investigate the relevance of KITLG CNV in SS and the protective effects in MS, who rarely suffer from dSCC.
KW  - tumour
KW  - toe
KW  - miniature schnauzer
KW  - standard schnauzer
KW  - CNV
KW  - ddPCR
KW  - breed predisposition
Y1  - 2023
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-303913
SN  - 2306-7381
VL  - 10
IS  - 2
ER  - 
TY  - JOUR
A1  - Aurast, Anna
A1  - Gradl, Tobias
A1  - Pernes, Stefan
A1  - Pielström, Steffen
T1  - Big Data und Smart Data in den Geisteswissenschaften
JF  - Bibliothek Forschung und Praxis
N2  - Kein Abstract verfügbar.
KW  - Textanalyse
KW  - unstrukturierte Daten
KW  - Natural Language Processing
KW  - Text analysis
KW  - unstructured data
KW  - natural language processing
Y1  - 2016
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-195237
SN  - 1865-7648
SN  - 0341-4183
N1  - Dieser Beitrag ist mit Zustimmung des Rechteinhabers aufgrund einer (DFG-geförderten) Allianz- bzw. Nationallizenz frei zugänglich.
VL  - 40
IS  - 2
ER  - 
TY  - JOUR
A1  - Aydinli, Muharrem
A1  - Liang, Chunguang
A1  - Dandekar, Thomas
T1  - Motif and conserved module analysis in DNA (promoters, enhancers) and RNA (lncRNA, mRNA) using AlModules
JF  - Scientific Reports
N2  - Nucleic acid motifs consist of conserved and variable nucleotide regions. For functional action, several motifs are combined to modules. The tool AIModules allows identification of such motifs including combinations of them and conservation in several nucleic acid stretches. AIModules recognizes conserved motifs and combinations of motifs (modules) allowing a number of interesting biological applications such as analysis of promoter and transcription factor binding sites (TFBS), identification of conserved modules shared between several gene families, e.g. promoter regions, but also analysis of shared and conserved other DNA motifs such as enhancers and silencers, in mRNA (motifs or regulatory elements e.g. for polyadenylation) and lncRNAs. The tool AIModules presented here is an integrated solution for motif analysis, offered as a Web service as well as downloadable software. Several nucleotide sequences are queried for TFBSs using predefined matrices from the JASPAR DB or by using one’s own matrices for diverse types of DNA or RNA motif discovery. Furthermore, AIModules can find TFBSs common to two or more sequences. Demanding high or low conservation, AIModules outperforms other solutions in speed and finds more modules (specific combinations of TFBS) than alternative available software. The application also searches RNA motifs such as polyadenylation site or RNA–protein binding motifs as well as DNA motifs such as enhancers as well as user-specified motif combinations (https://bioinfo-wuerz.de/aimodules/; alternative entry pages: https://aimodules.heinzelab.de or https://www.biozentrum.uni-wuerzburg.de/bioinfo/computing/aimodules). The application is free and open source whether used online, on-site, or locally.
KW  - AIModules
KW  - nucleic acid motifs
KW  - DNA
Y1  - 2022
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-301268
VL  - 12
IS  - 1
ER  - 
TY  - JOUR
A1  - Azzami, Klara
A1  - Ritter, Wolfgang
A1  - Tautz, Jürgen
A1  - Beier, Hildburg
T1  - Infection of honey bees with acute bee paralysis virus does not trigger humoral or cellular immune responses
JF  - Archives of Virology
N2  - We have studied the responses of honey bees at different life stages (Apis mellifera) to controlled infection with acute bee paralysis virus and have identified the haemolymph of infected larvae and adult worker bees as the compartment where massive propagation of ABPV occurs. Insects respond with a broad spectrum of induced innate immune reactions to bacterial infections, whereas defence mechanisms based on RNA interference play a major role in antiviral immunity. In this study, we have determined that honey bee larvae and adult workers do not produce a humoral immune reaction upon artificial infection with ABPV, in contrast to control individuals challenged with Escherichia coli. ABPV-infected bees produced neither elevated levels of specific antimicrobial peptides (AMPs), such as hymenoptaecin and defensin, nor any general antimicrobial activity, as revealed by inhibition-zone assays. Additionally, adult bees did not generate melanised nodules upon ABPV infection, an important cellular immune function activated by bacteria and viruses in some insects. Challenge of bees with both ABPV and E. coli showed that innate humoral and cellular immune reactions are induced in mixed infections, albeit at a reduced level.
KW  - chemosensory protein
KW  - bee larva
KW  - adult bee
KW  - honey bee
KW  - larva
KW  - work bee
KW  - infected bee
KW  - immune response
KW  - young work bee
KW  - capsid protein
KW  - abdominal
KW  - tergite
KW  - haemolymph
KW  - sample
KW  - Imd pathway
KW  - worker bee larva
KW  - antimicrobial
KW  - peptide
Y1  - 2012
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-126863
VL  - 157
IS  - 4
ER  - 
TY  - JOUR
A1  - Baalbergen, Els
A1  - Helwerda, Renate
A1  - Schelfhorst, Rense
A1  - Castillo Cajas, Ruth F.
A1  - van Moorsel, Coline H. M.
A1  - Kundrata, Robin
A1  - Welter-Schultes, Francisco W.
A1  - Giokas, Sinos
A1  - Schilthuizen, Menno
T1  - Predator-Prey Interactions between Shell-Boring Beetle Larvae and Rock-Dwelling Land Snails
JF  - PLOS ONE
N2  - Drilus beetle larvae (Coleoptera: Elateridae) are specialized predators of land snails. Here, we describe various aspects of the predator-prey interactions between multiple Drilus species attacking multiple Albinaria (Gastropoda: Clausiliidae) species in Greece. We observe that Drilus species may be facultative or obligate Albinaria-specialists. We map geographically varying predation rates in Crete, where on average 24% of empty shells carry fatal Drilus bore holes. We also provide first-hand observations and video-footage of prey entry and exit strategies of the Drilus larvae, and evaluate the potential mutual evolutionary impacts. We find limited evidence for an effect of shell features and snail behavioral traits on inter-and intraspecifically differing predation rates. We also find that Drilus predators adjust their predation behavior based on specific shell traits of the prey. In conclusion, we suggest that, with these baseline data, this interesting predator-prey system will be available for further, detailed more evolutionary ecology studies.
KW  - clausiliidae
KW  - evolution
KW  - pulmonata
KW  - albinaria
KW  - behavior
KW  - species gastropoda
Y1  - 2014
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-115963
SN  - 1932-6203
VL  - 9
IS  - 6
ER  - 
TY  - JOUR
A1  - Bachert, Antonia
A1  - Scheiner, Ricarda
T1  - The ant’s weapon improves honey bee learning performance
JF  - Scientific Reports
N2  - Formic acid is the main component of the ant’s major weapon against enemies. Being mainly used as a chemical defense, the acid is also exploited for recruitment and trail marking. The repelling effect of the organic acid is used by some mammals and birds which rub themselves in the acid to eliminate ectoparasites. Beekeepers across the world rely on this effect to control the parasitic mite Varroa destructor. Varroa mites are considered the most destructive pest of honey bees worldwide and can lead to the loss of entire colonies. Formic acid is highly effective against Varroa mites but can also kill the honeybee queen and worker brood. Whether formic acid can also affect the behavior of honey bees is unknown. We here study the effect of formic acid on sucrose responsiveness and cognition of honey bees treated at different live stages in field-relevant doses. Both behaviors are essential for survival of the honey bee colony. Rather unexpectedly, formic acid clearly improved the learning performance of the bees in appetitive olfactory conditioning, while not affecting sucrose responsiveness. This exciting side effect of formic acid certainly deserves further detailed investigations.
KW  - animal behaviour
KW  - animal physiology
Y1  - 2023
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-358064
VL  - 13
ER  - 
TY  - JOUR
A1  - Bae, Soyeon
A1  - Heidrich, Lea
A1  - Levick, Shaun R.
A1  - Gossner, Martin M.
A1  - Seibold, Sebastian
A1  - Weisser, Wolfgang W.
A1  - Magdon, Paul
A1  - Serebryanyk, Alla
A1  - Bässler, Claus
A1  - Schäfer, Deborah
A1  - Schulze, Ernst-Detlef
A1  - Doerfler, Inken
A1  - Müller, Jörg
A1  - Jung, Kirsten
A1  - Heurich, Marco
A1  - Fischer, Markus
A1  - Roth, Nicolas
A1  - Schall, Peter
A1  - Boch, Steffen
A1  - Wöllauer, Stephan
A1  - Renner, Swen C.
A1  - Müller, Jörg
T1  - Dispersal ability, trophic position and body size mediate species turnover processes: Insights from a multi-taxa and multi-scale approach
JF  - Diversity and Distribution
N2  - Aim: Despite increasing interest in β-diversity, that is the spatial and temporal turnover of species, the mechanisms underlying species turnover at different spatial scales are not fully understood, although they likely differ among different functional groups. We investigated the relative importance of dispersal limitations and the environmental filtering caused by vegetation for local, multi-taxa forest communities differing in their dispersal ability, trophic position and body size.
Location: Temperate forests in five regions across Germany.
Methods: In the inter-region analysis, the independent and shared effects of the regional spatial structure (regional species pool), landscape spatial structure (dispersal limitation) and environmental factors on species turnover were quantified with a 1-ha grain across 11 functional groups in up to 495 plots by variation partitioning. In the intra-region analysis, the relative importance of three environmental factors related to vegetation (herb and tree layer composition and forest physiognomy) and spatial structure for species turnover was determined.
Results: In the inter-region analysis, over half of the explained variation in community composition (23% of the total explained 35%) was explained by the shared effects of several factors, indicative of spatially structured environmental filtering. Among the independent effects, environmental factors were the strongest on average over 11 groups, but the importance of landscape spatial structure increased for less dispersive functional groups. In the intra-region analysis, the independent effect of plant species composition had a stronger influence on species turnover than forest physiognomy, but the relative importance of the latter increased with increasing trophic position and body size.
Main conclusions: Our study revealed that the mechanisms structuring assemblage composition are associated with the traits of functional groups. Hence, conservation frameworks targeting biodiversity of multiple groups should cover both environmental and biogeographical gradients. Within regions, forest management can enhance β-diversity particularly by diversifying tree species composition and forest physiognomy.
KW  - body size
KW  - dispersal ability
KW  - environmental filtering
KW  - forest physiognomy
KW  - neutral processes
KW  - plant composition
KW  - regional species pool
KW  - species turnover
KW  - trophic position
KW  - β-diversity
Y1  - 2020
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-236117
VL  - 27
IS  - 3
ER  - 
TY  - JOUR
A1  - Bae, Soyeon
A1  - Müller, Jörg
A1  - Förster, Bernhard
A1  - Hilmers, Torben
A1  - Hochrein, Sophia
A1  - Jacobs, Martin
A1  - Leroy, Benjamin M. L.
A1  - Pretzsch, Hans
A1  - Weisser, Wolfgang W.
A1  - Mitesser, Oliver
T1  - Tracking the temporal dynamics of insect defoliation by high‐resolution radar satellite data
JF  - Methods in Ecology and Evolution
N2  - Quantifying tree defoliation by insects over large areas is a major challenge in forest management, but it is essential in ecosystem assessments of disturbance and resistance against herbivory. However, the trajectory from leaf-flush to insect defoliation to refoliation in broadleaf trees is highly variable. Its tracking requires high temporal- and spatial-resolution data, particularly in fragmented forests.
In a unique replicated field experiment manipulating gypsy moth Lymantria dispar densities in mixed-oak forests, we examined the utility of publicly accessible satellite-borne radar (Sentinel-1) to track the fine-scale temporal trajectory of defoliation. The ratio of backscatter intensity between two polarizations from radar data of the growing season constituted a canopy development index (CDI) and a normalized CDI (NCDI), which were validated by optical (Sentinel-2) and terrestrial laser scanning (TLS) data as well by intensive caterpillar sampling from canopy fogging.
The CDI and NCDI strongly correlated with optical and TLS data (Spearman's ρ = 0.79 and 0.84, respectively). The ΔNCDII\(_{Defoliation(A−C)}\) significantly explained caterpillar abundance (R\(^{2}\) = 0.52). The NCDI at critical timesteps and ΔNCDI related to defoliation and refoliation well discriminated between heavily and lightly defoliated forests.
We demonstrate that the high spatial and temporal resolution and the cloud independence of Sentinel-1 radar potentially enable spatially unrestricted measurements of the highly dynamic canopy herbivory. This can help monitor insect pests, improve the prediction of outbreaks and facilitate the monitoring of forest disturbance, one of the high priority Essential Biodiversity Variables, in the near future.
KW  - Sentinel-1
KW  - canopy herbivory
KW  - defoliation severity
KW  - gypsy moth
KW  - insect disturbance
KW  - intra-annual time-series
KW  - Lymantria dispar
KW  - remote sensing
Y1  - 2022
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-258222
VL  - 13
IS  - 1
ER  - 
TY  - JOUR
A1  - Bahena, Paulina
A1  - Daftarian, Narsis
A1  - Maroofian, Reza
A1  - Linares, Paola
A1  - Villalobos, Daniel
A1  - Mirrahimi, Mehraban
A1  - Rad, Aboulfazl
A1  - Doll, Julia
A1  - Hofrichter, Michaela A. H.
A1  - Koparir, Asuman
A1  - Röder, Tabea
A1  - Han, Seungbin
A1  - Sabbaghi, Hamideh
A1  - Ahmadieh, Hamid
A1  - Behboudi, Hassan
A1  - Villanueva-Mendoza, Cristina
A1  - Cortés-Gonzalez, Vianney
A1  - Zamora-Ortiz, Rocio
A1  - Kohl, Susanne
A1  - Kuehlewein, Laura
A1  - Darvish, Hossein
A1  - Alehabib, Elham
A1  - La Arenas-Sordo, Maria de Luz
A1  - Suri, Fatemeh
A1  - Vona, Barbara
A1  - Haaf, Thomas
T1  - Unraveling the genetic complexities of combined retinal dystrophy and hearing impairment
JF  - Human Genetics
N2  - Usher syndrome, the most prevalent cause of combined hereditary vision and hearing impairment, is clinically and genetically heterogeneous. Moreover, several conditions with phenotypes overlapping Usher syndrome have been described. This makes the molecular diagnosis of hereditary deaf-blindness challenging. Here, we performed exome sequencing and analysis on 7 Mexican and 52 Iranian probands with combined retinal degeneration and hearing impairment (without intellectual disability). Clinical assessment involved ophthalmological examination and hearing loss questionnaire. Usher syndrome, most frequently due to biallelic variants in MYO7A (USH1B in 16 probands), USH2A (17 probands), and ADGRV1 (USH2C in 7 probands), was diagnosed in 44 of 59 (75%) unrelated probands. Almost half of the identified variants were novel. Nine of 59 (15%) probands displayed other genetic entities with dual sensory impairment, including Alström syndrome (3 patients), cone-rod dystrophy and hearing loss 1 (2 probands), and Heimler syndrome (1 patient). Unexpected findings included one proband each with Scheie syndrome, coenzyme Q10 deficiency, and pseudoxanthoma elasticum. In four probands, including three Usher cases, dual sensory impairment was either modified/aggravated or caused by variants in distinct genes associated with retinal degeneration and/or hearing loss. The overall diagnostic yield of whole exome analysis in our deaf-blind cohort was 92%. Two (3%) probands were partially solved and only 3 (5%) remained without any molecular diagnosis. In many cases, the molecular diagnosis is important to guide genetic counseling, to support prognostic outcomes and decisions with currently available and evolving treatment modalities.
KW  - Usher syndrome
KW  - hearing impairment
KW  - combined retinal dystrophy
Y1  - 2022
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-267750
SN  - 1432-1203
VL  - 141
IS  - 3-4
ER  - 
TY  - JOUR
A1  - Bakari-Soale, Majeed
A1  - Ikenga, Nonso Josephat
A1  - Scheibe, Marion
A1  - Butter, Falk
A1  - Jones, Nicola G.
A1  - Kramer, Susanne
A1  - Engstler, Markus
T1  - The nucleolar DExD/H protein Hel66 is involved in ribosome biogenesis in Trypanosoma brucei
JF  - Scientific Reports
N2  - The biosynthesis of ribosomes is a complex cellular process involving ribosomal RNA, ribosomal proteins and several further trans-acting factors. DExD/H box proteins constitute the largest family of trans-acting protein factors involved in this process. Several members of this protein family have been directly implicated in ribosome biogenesis in yeast. In trypanosomes, ribosome biogenesis differs in several features from the process described in yeast. Here, we have identified the DExD/H box helicase Hel66 as being involved in ribosome biogenesis. The protein is unique to Kinetoplastida, localises to the nucleolus and its depletion via RNAi caused a severe growth defect. Loss of the protein resulted in a decrease of global translation and accumulation of rRNA processing intermediates for both the small and large ribosomal subunits. Only a few factors involved in trypanosome rRNA biogenesis have been described so far and our findings contribute to gaining a more comprehensive picture of this essential process.
KW  - infection
KW  - parasite evolution
KW  - parasite genetics
KW  - RNA
Y1  - 2021
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-263872
VL  - 11
IS  - 1
ER  - 
TY  - JOUR
A1  - Balakrishnan, Ashwin
A1  - Hemmen, Katherina
A1  - Choudhury, Susobhan
A1  - Krohn, Jan-Hagen
A1  - Jansen, Kerstin
A1  - Friedrich, Mike
A1  - Beliu, Gerti
A1  - Sauer, Markus
A1  - Lohse, Martin J.
A1  - Heinze, Katrin G.
T1  - Unraveling the hidden temporal range of fast β2-adrenergic receptor mobility by time-resolved fluorescence
JF  - Communications Biology
N2  - G-protein-coupled receptors (GPCRs) are hypothesized to possess molecular mobility over a wide temporal range. Until now the temporal range has not been fully accessible due to the crucially limited temporal range of available methods. This in turn, may lead relevant dynamic constants to remain masked. Here, we expand this dynamic range by combining fluorescent techniques using a spot confocal setup. We decipher mobility constants of β\(_{2}\)-adrenergic receptor over a wide time range (nanosecond to second). Particularly, a translational mobility (10 µm\(^{2}\)/s), one order of magnitude faster than membrane associated lateral mobility that explains membrane protein turnover and suggests a wider picture of the GPCR availability on the plasma membrane. And a so far elusive rotational mobility (1-200 µs) which depicts a previously overlooked dynamic component that, despite all complexity, behaves largely as predicted by the Saffman-Delbrück model.
KW  - G-protein-coupled receptors
KW  - molecular mobility
KW  - temporal range
Y1  - 2022
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-301140
VL  - 5
IS  - 1
ER  - 
TY  - JOUR
A1  - Balkenhol, Johannes
A1  - Kaltdorf, Kristin V.
A1  - Mammadova-Bach, Elmina
A1  - Braun, Attila
A1  - Nieswandt, Bernhard
A1  - Dittrich, Marcus
A1  - Dandekar, Thomas
T1  - Comparison of the central human and mouse platelet signaling cascade by systems biological analysis
JF  - BMC Genomics
N2  - Background 
Understanding the molecular mechanisms of platelet activation and aggregation is of high interest for basic and clinical hemostasis and thrombosis research. The central platelet protein interaction network is involved in major responses to exogenous factors. This is defined by systemsbiological pathway analysis as the central regulating signaling cascade of platelets (CC). 

Results 
The CC is systematically compared here between mouse and human and major differences were found. Genetic differences were analysed comparing orthologous human and mouse genes. We next analyzed different expression levels of mRNAs. Considering 4 mouse and 7 human high-quality proteome data sets, we identified then those major mRNA expression differences (81%) which were supported by proteome data. CC is conserved regarding genetic completeness, but we observed major differences in mRNA and protein levels between both species. Looking at central interactors, human PLCB2, MMP9, BDNF, ITPR3 and SLC25A6 (always Entrez notation) show absence in all murine datasets. CC interactors GNG12, PRKCE and ADCY9 occur only in mice. Looking at the common proteins, TLN1, CALM3, PRKCB, APP, SOD2 and TIMP1 are higher abundant in human, whereas RASGRP2, ITGB2, MYL9, EIF4EBP1, ADAM17, ARRB2, CD9 and ZYX are higher abundant in mouse. Pivotal kinase SRC shows different regulation on mRNA and protein level as well as ADP receptor P2RY12. 

Conclusions 
Our results highlight species-specific differences in platelet signaling and points of specific fine-tuning in human platelets as well as murine-specific signaling differences.
KW  - interspecies comparison
KW  - transcriptome
KW  - proteome
KW  - platelet
KW  - network
KW  - signaling
KW  - mouse
KW  - human
KW  - interactome
KW  - cascade
Y1  - 2020
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-230377
VL  - 21
ER  - 
TY  - JOUR
A1  - Bargul, Joel L.
A1  - Jung, Jamin
A1  - McOdimba, Francis A.
A1  - Omogo, Collins O.
A1  - Adung'a, Vincent O.
A1  - Krüger, Timothy
A1  - Masiga, Daniel K.
A1  - Engstler, Markus
T1  - Species-Specific Adaptations of Trypanosome Morphology and Motility to the Mammalian Host
JF  - PLoS Pathogens
N2  - African trypanosomes thrive in the bloodstream and tissue spaces of a wide range of mammalian hosts. Infections of cattle cause an enormous socio-economic burden in sub-Saharan Africa. A hallmark of the trypanosome lifestyle is the flagellate’s incessant motion. This work details the cell motility behavior of the four livestock-parasites Trypanosoma vivax, T. brucei, T. evansi and T. congolense. The trypanosomes feature distinct swimming patterns, speeds and flagellar wave frequencies, although the basic mechanism of flagellar propulsion is conserved, as is shown by extended single flagellar beat analyses. Three-dimensional analyses of the trypanosomes expose a high degree of dynamic pleomorphism, typified by the ‘cellular waveform’. This is a product of the flagellar oscillation, the chirality of the flagellum attachment and the stiffness of the trypanosome cell body. The waveforms are characteristic for each trypanosome species and are influenced by changes of the microenvironment, such as differences in viscosity and the presence of confining obstacles. The distinct cellular waveforms may be reflective of the actual anatomical niches the parasites populate within their mammalian host. T. vivax displays waveforms optimally aligned to the topology of the bloodstream, while the two subspecies T. brucei and T. evansi feature distinct cellular waveforms, both additionally adapted to motion in more confined environments such as tissue spaces. T. congolense reveals a small and stiff waveform, which makes these parasites weak swimmers and destined for cell adherence in low flow areas of the circulation. Thus, our experiments show that the differential dissemination and annidation of trypanosomes in their mammalian hosts may depend on the distinct swimming capabilities of the parasites.
KW  - swimming
KW  - viscosity
KW  - flagella
KW  - host-pathogen interactions
KW  - cell motility
KW  - blood
KW  - parasitic diseases
KW  - trypanosoma brucei gambiense
Y1  - 2016
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-146513
VL  - 12
IS  - 2
ER  - 
TY  - JOUR
A1  - Barnekow, A.
A1  - Paul, E.
A1  - Schartl, Manfred
T1  - Expression of the c-src protooncogene in human skin tumors
N2  - No abstract available
KW  - Physiologische Chemie
Y1  - 1987
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-61870
ER  - 
TY  - JOUR
A1  - Barnekow, A.
A1  - Schartl, Manfred
T1  - Comparative studies on the src proto-oncogene and its gene product pp60\(^{c-src}\) in normal and neoplastic tissues of lower vertebrates
N2  - No abstract available
KW  - Physiologische Chemie
Y1  - 1987
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-61869
ER  - 
TY  - JOUR
A1  - Barnekow, A.
A1  - Schartl, Manfred
A1  - Anders, F.
A1  - Bauer, H.
T1  - Identification of a fish protein associated with a kinase activity and related to the Rous sarcoma virus transforming protein
N2  - No abstract available
KW  - Physiologische Chemie
Y1  - 1982
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-61946
ER  - 
TY  - JOUR
A1  - Barnekow, Angelika
A1  - Gessler, Manfred
T1  - Activation of the pp60\(^{c-src}\) kinase during differentiation of monomyelocytic cells in vitro
N2  - Tbe proto-oncogene c-src, the cellular homolog of the Rous sarcoma virus (RSV) transforming gene v-src, is expressed in a tissue-specific and age-dependent manner. Its physiological function, although still unknown, appears to be more closely related to differentiation processes than to proliferation processes. To obtain more information about the physiological role of the c-src gene in cells, we have studied differentiation-dependent alterations using the human HL-60 leukaemia cell line as a model system. Induction of monocytic and granulocytic differentiation of HL-60 cells by 12-0-tetradecanoylphorbol-13-acetate (TPA) and dimethylsulfoxide (DMSO) is associated with an activation of the pp60<sup>c-src</sup> tyrosine kinase, but not with increased c-src gene expression. Control experiments exclude an interaction of TPA and DMSO themselves with the pp60<sup>c-src</sup> kinase.
KW  - Biochemie
KW  - c-src
KW  - differentiation
KW  - protein tyrosine kinase
KW  - protooncogene
Y1  - 1986
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-59278
ER  - 
TY  - JOUR
A1  - Barnekow, Angelika
A1  - Jahn, Reinhard
A1  - Schartl, Manfred
T1  - Synaptophysin: a substrate for the protein tyrosine kinase pp60c-src in intact synaptic vesicles
N2  - Expression of pp60 c-src, the first well defined proto-oncogene product, is developmentally regulated and tissue-specific, with neuronal tissues displaying high amounts of the c-src encoded pp60 c-src kinase activity. In the central nervous system pp60 s-src is preferentially expressed in regions characterized by a high content of grey matter and elevated density of nerve terminals. In this study we show for the first time a direct interaction between pp60 c-src and synaptophysin as a physiological target protein in neurons by demonstrating that endogenous pp60 c-src is able to phosphorylate synaptophysin (p38). p38 is a major constituent of the synaptic vesicle membrane protein and is thought to play a key role in the exocytosis of small synaptic vesicles and possibly small clear vesicles in neuroendocrine cells.
KW  - Synaptophysin
KW  - Synaptische Vesikel
KW  - Protein-Tyrosin-Kinasen
Y1  - 1990
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-86168
ER  - 
TY  - JOUR
A1  - Bartel, Karin
A1  - Pein, Helmut
A1  - Popper, Bastian
A1  - Schmitt, Sabine
A1  - Janaki-Raman, Sudha
A1  - Schulze, Almut
A1  - Lengauer, Florian
A1  - Koeberle, Andreas
A1  - Werz, Oliver
A1  - Zischka, Hans
A1  - Müller, Rolf
A1  - Vollmar, Angelika M.
A1  - Schwarzenberg, Karin von
T1  - Connecting lysosomes and mitochondria – a novel role for lipid metabolism in cancer cell death
JF  - Cell Communication and Signaling
N2  - Background
The understanding of lysosomes has been expanded in recent research way beyond their view as cellular trash can. Lysosomes are pivotal in regulating metabolism, endocytosis and autophagy and are implicated in cancer. Recently it was discovered that the lysosomal V-ATPase, which is known to induce apoptosis, interferes with lipid metabolism in cancer, yet the interplay between these organelles is poorly understood.

Methods
LC-MS/MS analysis was performed to investigate lipid distribution in cells. Cell survival and signaling pathways were analyzed by means of cell biological methods (qPCR, Western Blot, flow cytometry, CellTiter-Blue). Mitochondrial structure was analyzed by confocal imaging and electron microscopy, their function was determined by flow cytometry and seahorse measurements.

Results
Our data reveal that interfering with lysosomal function changes composition and subcellular localization of triacylglycerids accompanied by an upregulation of PGC1α and PPARα expression, master regulators of energy and lipid metabolism. Furthermore, cardiolipin content is reduced driving mitochondria into fission, accompanied by a loss of membrane potential and reduction in oxidative capacity, which leads to a deregulation in cellular ROS and induction of mitochondria-driven apoptosis. Additionally, cells undergo a metabolic shift to glutamine dependency, correlated with the fission phenotype and sensitivity to lysosomal inhibition, most prominent in Ras mutated cells.

Conclusion
This study sheds mechanistic light on a largely uninvestigated triangle between lysosomes, lipid metabolism and mitochondrial function. Insight into this organelle crosstalk increases our understanding of mitochondria-driven cell death. Our findings furthermore provide a first hint on a connection of Ras pathway mutations and sensitivity towards lysosomal inhibitors.
KW  - lysosome
KW  - V-ATPase
KW  - mitochondria
KW  - fission
KW  - apoptosis
KW  - lipid metabolism
KW  - cardiolipin
Y1  - 2019
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-221524
VL  - 17
ER  - 
TY  - JOUR
A1  - Bartmann, Catharina
A1  - Janaki Raman, Sudha R.
A1  - Flöter, Jessica
A1  - Schulze, Almut
A1  - Bahlke, Katrin
A1  - Willingstorfer, Jana
A1  - Strunz, Maria
A1  - Wöckel, Achim
A1  - Klement, Rainer J.
A1  - Kapp, Michaela
A1  - Djuzenova, Cholpon S.
A1  - Otto, Christoph
A1  - Kämmerer, Ulrike
T1  - Beta-hydroxybutyrate (3-OHB) can influence the energetic phenotype of breast cancer cells, but does not impact their proliferation and the response to chemotherapy or radiation
JF  - Cancer & Metabolism
N2  - Background:
Ketogenic diets (KDs) or short-term fasting are popular trends amongst supportive approaches for cancer patients. Beta-hydroxybutyrate (3-OHB) is the main physiological ketone body, whose concentration can reach plasma levels of 2–6 mM during KDs or fasting. The impact of 3-OHB on the biology of tumor cells described so far is contradictory. Therefore, we investigated the effect of a physiological concentration of 3 mM 3-OHB on metabolism, proliferation, and viability of breast cancer (BC) cells in vitro.

Methods:
Seven different human BC cell lines (BT20, BT474, HBL100, MCF-7, MDA-MB 231, MDA-MB 468, and T47D) were cultured in medium with 5 mM glucose in the presence of 3 mM 3-OHB at mild hypoxia (5% oxygen) or normoxia (21% oxygen). Metabolic profiling was performed by quantification of the turnover of glucose, lactate, and 3-OHB and by Seahorse metabolic flux analysis. Expression of key enzymes of ketolysis as well as the main monocarboxylic acid transporter MCT2 and the glucose-transporter GLUT1 was analyzed by RT-qPCR and Western blotting. The effect of 3-OHB on short- and long-term cell proliferation as well as chemo- and radiosensitivity were also analyzed.

Results:
3-OHB significantly changed the oxygen consumption rate (OCR) and extracellular acidification rate (ECAR) in BT20 cells resulting in a more oxidative energetic phenotype. MCF-7 and MDA-MB 468 cells had increased ECAR only in response to 3-OHB, while the other three cell types remained uninfluenced. All cells expressed MCT2 and GLUT1, thus being able to uptake the metabolites. The consumption of 3-OHB was not strongly linked to mRNA overexpression of key enzymes of ketolysis and did not correlate with lactate production and glucose consumption. Neither 3-OHB nor acetoacetate did interfere with proliferation. Further, 3-OHB incubation did not modify the response of the tested BC cell lines to chemotherapy or radiation.

Conclusions:
We found that a physiological level of 3-OHB can change the energetic profile of some BC cell lines. However, 3-OHB failed to influence different biologic processes in these cells, e.g., cell proliferation and the response to common breast cancer chemotherapy and radiotherapy. Thus, we have no evidence that 3-OHB generally influences the biology of breast cancer cells in vitro.
KW  - ketogenic diet
KW  - β-Hydroxybutyrate
KW  - ketone bodies
KW  - breast cancer
KW  - seahorse
KW  - metabolic profile
KW  - chemotherapy
KW  - ionizing radiation
Y1  - 2018
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-175607
VL  - 6
IS  - 8
ER  - 
TY  - JOUR
A1  - Bartomeus, Ignasi
A1  - Potts, Simon G.
A1  - Steffan-Dewenter, Ingolf
A1  - Vaissiere, Bernard E.
A1  - Woyciechowski, Michal
A1  - Krewenka, Kristin M.
A1  - Tscheulin, Thomas
A1  - Roberts, Stuart P. M.
A1  - Szentgyoergyi, Hajnalka
A1  - Westphal, Catrin
A1  - Bommarco, Riccardo
T1  - Contribution of insect pollinators to crop yield and quality varies with agricultural intensification
JF  - PEERJ
N2  - Background. Up to 75% of crop species benefit at least to some degree from animal pollination for fruit or seed set and yield. However, basic information on the level of pollinator dependence and pollinator contribution to yield is lacking for many crops. Even less is known about how insect pollination affects crop quality. Given that habitat loss and agricultural intensification are known to decrease pollinator richness and abundance, there is a need to assess the consequences for different components of crop production. Methods. We used pollination exclusion on flowers or inflorescences on a whole plant basis to assess the contribution of insect pollination to crop yield and quality in four flowering crops (spring oilseed rape, field bean, strawberry, and buckwheat) located in four regions of Europe. For each crop, we recorded abundance and species richness of flower visiting insects in ten fields located along a gradient from simple to heterogeneous landscapes. Results. Insect pollination enhanced average crop yield between 18 and 71% depending on the crop. Yield quality was also enhanced in most crops. For instance, oilseed rape had higher oil and lower chlorophyll contents when adequately pollinated, the proportion of empty seeds decreased in buckwheat, and strawberries' commercial grade improved; however, we did not find higher nitrogen content in open pollinated field beans. Complex landscapes had a higher overall species richness of wild pollinators across crops, but visitation rates were only higher in complex landscapes for some crops. On the contrary, the overall yield was consistently enhanced by higher visitation rates, but not by higher pollinator richness. Discussion. For the four crops in this study, there is clear benefit delivered by pollinators on yield quantity and/or quality, but it is not maximized under current agricultural intensification. Honeybees, the most abundant pollinator, might partially compensate the loss of wild pollinators in some areas, but our results suggest the need of landscape-scale actions to enhance wild pollinator populations.
KW  - biodiversity
KW  - pollination
KW  - honeybee
KW  - wild bees
KW  - agroecosystems
KW  - native pollinators
KW  - species richness
KW  - bee pollinators
KW  - wild
KW  - ecosystemservices
KW  - fruit-quality
KW  - oilseed rape
KW  - land-use
KW  - honey
KW  - patterns
Y1  - 2014
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-116928
SN  - 2167-9843
VL  - 2
IS  - e328
ER  - 
TY  - JOUR
A1  - Basset, Yves
A1  - Cizek, Lukas
A1  - Cuénoud, Philippe
A1  - Didham, Raphael K.
A1  - Novotny, Vojtech
A1  - Ødegaard, Frode
A1  - Roslin, Tomas
A1  - Tishechkin, Alexey K.
A1  - Schmidl, Jürgen
A1  - Winchester, Neville N.
A1  - Roubik, David W.
A1  - Aberlenc, Henri-Pierre
A1  - Bail, Johannes
A1  - Barrios, Hector
A1  - Bridle, Jonathan R.
A1  - Castaño-Meneses, Gabriela
A1  - Corbara, Bruno
A1  - Curletti, Gianfranco
A1  - da Rocha, Wesley Duarte
A1  - De Bakker, Domir
A1  - Delabie, Jacques H. C.
A1  - Dejean, Alain
A1  - Fagan, Laura L.
A1  - Floren, Andreas
A1  - Kitching, Roger L.
A1  - Medianero, Enrique
A1  - de Oliveira, Evandro Gama
A1  - Orivel, Jerome
A1  - Pollet, Marc
A1  - Rapp, Mathieu
A1  - Ribeiro, Servio P.
A1  - Roisin, Yves
A1  - Schmidt, Jesper B.
A1  - Sørensen, Line
A1  - Lewinsohn, Thomas M.
A1  - Leponce, Maurice
T1  - Arthropod Distribution in a Tropical Rainforest: Tackling a Four Dimensional Puzzle
JF  - PLoS ONE
N2  - Quantifying the spatio-temporal distribution of arthropods in tropical rainforests represents a first step towards scrutinizing the global distribution of biodiversity on Earth. To date most studies have focused on narrow taxonomic groups or lack a design that allows partitioning of the components of diversity. Here, we consider an exceptionally large dataset (113,952 individuals representing 5,858 species), obtained from the San Lorenzo forest in Panama, where the phylogenetic breadth of arthropod taxa was surveyed using 14 protocols targeting the soil, litter, understory, lower and upper canopy habitats, replicated across seasons in 2003 and 2004. This dataset is used to explore the relative influence of horizontal, vertical and seasonal drivers of arthropod distribution in this forest. We considered arthropod abundance, observed and estimated species richness, additive decomposition of species richness, multiplicative partitioning of species diversity, variation in species composition, species turnover and guild structure as components of diversity. At the scale of our study (2km of distance, 40m in height and 400 days), the effects related to the vertical and seasonal dimensions were most important. Most adult arthropods were collected from the soil/litter or the upper canopy and species richness was highest in the canopy. We compared the distribution of arthropods and trees within our study system. Effects related to the seasonal dimension were stronger for arthropods than for trees. We conclude that: (1) models of beta diversity developed for tropical trees are unlikely to be applicable to tropical arthropods; (2) it is imperative that estimates of global biodiversity derived from mass collecting of arthropods in tropical rainforests embrace the strong vertical and seasonal partitioning observed here; and (3) given the high species turnover observed between seasons, global climate change may have severe consequences for rainforest arthropods.
KW  - trees
KW  - species richness
KW  - beta-diveristy
KW  - strategy
KW  - turnover
KW  - similarity
KW  - biodiversity
KW  - specialization
KW  - herbivorous insects
KW  - assemblages
Y1  - 2015
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-136393
VL  - 10
IS  - 12
ER  - 
TY  - JOUR
A1  - Batram, Christopher
A1  - Jones, Nivola G.
A1  - Janzen, Christian J.
A1  - Markert, Sebastian M.
A1  - Engstler, Markus
T1  - Expression site attenuation mechanistically links antigenic variation and development in Trypanosoma brucei
JF  - eLife
N2  - We have discovered a new mechanism of monoallelic gene expression that links antigenic variation, cell cycle, and development in the model parasite Trypanosoma brucei. African trypanosomes possess hundreds of variant surface glycoprotein (VSG) genes, but only one is expressed from a telomeric expression site (ES) at any given time. We found that the expression of a second VSG alone is sufficient to silence the active VSG gene and directionally attenuate the ES by disruptor of telomeric silencing-1B (DOT1B)-mediated histone methylation. Three conserved expression-site-associated genes (ESAGs) appear to serve as signal for ES attenuation. Their depletion causes G1-phase dormancy and reversible initiation of the slender-to-stumpy differentiation pathway. ES-attenuated slender bloodstream trypanosomes gain full developmental competence for transformation to the tsetse fly stage. This surprising connection between antigenic variation and developmental progression provides an unexpected point of attack against the deadly sleeping sickness.
KW  - antigenic variation
KW  - expression site attenuation
KW  - developmental reprogramming
KW  - cell biology
KW  - genes and chromosomes
KW  - Trypanosoma brucei
KW  - variant surface glycoprotein (VSG)
KW  - monoallelic expression
Y1  - 2014
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-119727
SN  - 2050-084X
VL  - 3
IS  - e02324
ER  - 
TY  - JOUR
A1  - Batzke, Katharina
A1  - Büchel, Gabriele
A1  - Hansen, Wiebke
A1  - Schramm, Alexander
T1  - TrkB-target Galectin-1 impairs immune activation and radiation responses in neuroblastoma: implications for tumour therapy
JF  - International Journal of Molecular Sciences
N2  - Galectin-1 (Gal-1) has been described to promote tumour growth by inducing angiogenesis and to contribute to the tumour immune escape. We had previously identified up-regulation of Gal-1 in preclinical models of aggressive neuroblastoma (NB), the most common extracranial tumour of childhood. While Gal-1 did not confer a survival advantage in the absence of exogenous stressors, Gal-1 contributed to enhanced cell migratory and invasive properties. Here, we review these findings and extend them by analyzing Gal-1 mediated effects on immune cell regulation and radiation resistance. In line with previous results, cell autonomous effects as well as paracrine functions contribute to Gal-1 mediated pro-tumourigenic functions. Interfering with Gal-1 functions in vivo will add to a better understanding of the role of the Gal-1 axis in the complex tumour-host interaction during immune-, chemo- and radiotherapy of neuroblastoma.
KW  - Galectin-1
KW  - radiation response
KW  - neuroblastoma
Y1  - 2018
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-285097
SN  - 1422-0067
VL  - 19
IS  - 3
ER  - 
TY  - JOUR
A1  - Baur, Florentin
A1  - Nietzer, Sarah L.
A1  - Kunz, Meik
A1  - Saal, Fabian
A1  - Jeromin, Julian
A1  - Matschos, Stephanie
A1  - Linnebacher, Michael
A1  - Walles, Heike
A1  - Dandekar, Thomas
A1  - Dandekar, Gudrun
T1  - Connecting cancer pathways to tumor engines: a stratification tool for colorectal cancer combining human in vitro tissue models with boolean in silico models
JF  - Cancers
N2  - To improve and focus preclinical testing, we combine tumor models based on a decellularized tissue matrix with bioinformatics to stratify tumors according to stage-specific mutations that are linked to central cancer pathways. We generated tissue models with BRAF-mutant colorectal cancer (CRC) cells (HROC24 and HROC87) and compared treatment responses to two-dimensional (2D) cultures and xenografts. As the BRAF inhibitor vemurafenib is—in contrast to melanoma—not effective in CRC, we combined it with the EGFR inhibitor gefitinib. In general, our 3D models showed higher chemoresistance and in contrast to 2D a more active HGFR after gefitinib and combination-therapy. In xenograft models murine HGF could not activate the human HGFR, stressing the importance of the human microenvironment. In order to stratify patient groups for targeted treatment options in CRC, an in silico topology with different stages including mutations and changes in common signaling pathways was developed. We applied the established topology for in silico simulations to predict new therapeutic options for BRAF-mutated CRC patients in advanced stages. Our in silico tool connects genome information with a deeper understanding of tumor engines in clinically relevant signaling networks which goes beyond the consideration of single drivers to improve CRC patient stratification.
KW  - in silico simulation
KW  - 3D tissue models
KW  - colorectal cancer
KW  - BRAF mutation
KW  - targeted therapy
KW  - stratification
Y1  - 2019
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-193798
SN  - 2072-6694
VL  - 12
IS  - 1
ER  - 
TY  - JOUR
A1  - Baur, Stefanie
A1  - Rautenberg, Maren
A1  - Faulstich, Manuela
A1  - Grau, Timo
A1  - Severin, Yannik
A1  - Unger, Clemens
A1  - Hoffmann, Wolfgang H.
A1  - Rudel, Thomas
A1  - Autenrieth, Ingo B.
A1  - Weidenmaier, Christopher
T1  - A Nasal Epithelial Receptor for Staphylococcus aureus WTA Governs Adhesion to Epithelial Cells and Modulates Nasal Colonization
JF  - PLOS PATHOGENS
N2  - Nasal colonization is a major risk factor for S. aureus infections. The mechanisms responsible for colonization are still not well understood and involve several factors on the host and the bacterial side. One key factor is the cell wall teichoic acid (WTA) of S. aureus, which governs direct interactions with nasal epithelial surfaces. We report here the first receptor for the cell wall glycopolymer WTA on nasal epithelial cells. In several assay systems this type F-scavenger receptor, termed SREC-I, bound WTA in a charge dependent manner and mediated adhesion to nasal epithelial cells in vitro. The impact of WTA and SREC-I interaction on epithelial adhesion was especially pronounced under shear stress, which resembles the conditions found in the nasal cavity. Most importantly, we demonstrate here a key role of the WTA-receptor interaction in a cotton rat model of nasal colonization. When we inhibited WTA mediated adhesion with a SREC-I antibody, nasal colonization in the animal model was strongly reduced at the early onset of colonization. More importantly, colonization stayed low over an extended period of 6 days. Therefore we propose targeting of this glycopolymer-receptor interaction as a novel strategy to prevent or control S. aureus nasal colonization.
KW  - SREC-I
KW  - clumping factor-B
KW  - scavender receptor
KW  - teichoic acids
KW  - surface proteins
KW  - cotton rats
KW  - carriage
KW  - determinant
KW  - infections
KW  - expression
Y1  - 2014
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-116280
SN  - 1553-7374
VL  - 10
IS  - 5
ER  - 
TY  - JOUR
A1  - Bazihizina, Nadia
A1  - Böhm, Jennifer
A1  - Messerer, Maxim
A1  - Stigloher, Christian
A1  - Müller, Heike M.
A1  - Cuin, Tracey Ann
A1  - Maierhofer, Tobias
A1  - Cabot, Joan
A1  - Mayer, Klaus F. X.
A1  - Fella, Christian
A1  - Huang, Shouguang
A1  - Al‐Rasheid, Khaled A. S.
A1  - Alquraishi, Saleh
A1  - Breadmore, Michael
A1  - Mancuso, Stefano
A1  - Shabala, Sergey
A1  - Ache, Peter
A1  - Zhang, Heng
A1  - Zhu, Jian‐Kang
A1  - Hedrich, Rainer
A1  - Scherzer, Sönke
T1  - Stalk cell polar ion transport provide for bladder‐based salinity tolerance in Chenopodium quinoa
JF  - New Phytologist
N2  - Chenopodium quinoa uses epidermal bladder cells (EBCs) to sequester excess salt. Each EBC complex consists of a leaf epidermal cell, a stalk cell, and the bladder.

Under salt stress, sodium (Na\(^{+}\)), chloride (Cl\(^{−}\)), potassium (K\(^{+}\)) and various metabolites are shuttled from the leaf lamina to the bladders. Stalk cells operate as both a selectivity filter and a flux controller.

In line with the nature of a transfer cell, advanced transmission electron tomography, electrophysiology, and fluorescent tracer flux studies revealed the stalk cell’s polar organization and bladder‐directed solute flow.

RNA sequencing and cluster analysis revealed the gene expression profiles of the stalk cells. Among the stalk cell enriched genes, ion channels and carriers as well as sugar transporters were most pronounced. Based on their electrophysiological fingerprint and thermodynamic considerations, a model for stalk cell transcellular transport was derived.
KW  - halophyte
KW  - polar ion transport
KW  - quinoa
KW  - salt tolerance
KW  - stalk cell
Y1  - 2022
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-287222
VL  - 235
IS  - 5
SP  - 1822
EP  - 1835
ER  - 
TY  - JOUR
A1  - Becam, Jérôme
A1  - Walter, Tim
A1  - Burgert, Anne
A1  - Schlegel, Jan
A1  - Sauer, Markus
A1  - Seibel, Jürgen
A1  - Schubert-Unkmeir, Alexandra
T1  - Antibacterial activity of ceramide and ceramide analogs against pathogenic Neisseria
JF  - Scientific Reports
N2  - Certain fatty acids and sphingoid bases found at mucosal surfaces are known to have antibacterial activity and are thought to play a more direct role in innate immunity against bacterial infections. Herein, we analysed the antibacterial activity of sphingolipids, including the sphingoid base sphingosine as well as short-chain C\(_{6}\) and long-chain C\(_{16}\)-ceramides and azido-functionalized ceramide analogs against pathogenic Neisseriae. Determination of the minimal inhibitory concentration (MIC) and minimal bactericidal concentration (MBC) demonstrated that short-chain ceramides and a ω-azido-functionalized C\(_{6}\)-ceramide were active against Neisseria meningitidis and N. gonorrhoeae, whereas they were inactive against Escherichia coli and Staphylococcus aureus. Kinetic assays showed that killing of N. meningitidis occurred within 2 h with ω–azido-C\(_{6}\)-ceramide at 1 X the MIC. Of note, at a bactericidal concentration, ω–azido-C\(_{6}\)-ceramide had no significant toxic effect on host cells. Moreover, lipid uptake and localization was studied by flow cytometry and confocal laser scanning microscopy (CLSM) and revealed a rapid uptake by bacteria within 5 min. CLSM and super-resolution fluorescence imaging by direct stochastic optical reconstruction microscopy demonstrated homogeneous distribution of ceramide analogs in the bacterial membrane. Taken together, these data demonstrate the potent bactericidal activity of sphingosine and synthetic short-chain ceramide analogs against pathogenic Neisseriae.
KW  - ceramide analogs
KW  - Neisseria
KW  - ceramide
Y1  - 2017
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-159367
VL  - 7
ER  - 
TY  - JOUR
A1  - Beck, Katherina
A1  - Hovhanyan, Anna
A1  - Menegazzi, Pamela
A1  - Helfrich-Förster, Charlotte
A1  - Raabe, Thomas
T1  - Drosophila RSK Influences the Pace of the Circadian Clock by Negative Regulation of Protein Kinase Shaggy Activity
JF  - Frontiers in Molecular Neuroscience
N2  - Endogenous molecular circadian clocks drive daily rhythmic changes at the cellular, physiological, and behavioral level for adaptation to and anticipation of environmental signals. The core molecular system consists of autoregulatory feedback loops, where clock proteins inhibit their own transcription. A complex and not fully understood interplay of regulatory proteins influences activity, localization and stability of clock proteins to set the pace of the clock. This study focuses on the molecular function of Ribosomal S6 Kinase (RSK) in the Drosophila melanogaster circadian clock. Mutations in the human rsk2 gene cause Coffin–Lowry syndrome, which is associated with severe mental disabilities. Knock-out studies with Drosophila ortholog rsk uncovered functions in synaptic processes, axonal transport and adult behavior including associative learning and circadian activity. However, the molecular targets of RSK remain elusive. Our experiments provide evidence that RSK acts in the key pace maker neurons as a negative regulator of Shaggy (SGG) kinase activity, which in turn determines timely nuclear entry of the clock proteins Period and Timeless to close the negative feedback loop. Phosphorylation of serine 9 in SGG is mediated by the C-terminal kinase domain of RSK, which is in agreement with previous genetic studies of RSK in the circadian clock but argues against the prevailing view that only the N-terminal kinase domain of RSK proteins carries the effector function. Our data provide a mechanistic explanation how RSK influences the molecular clock and imply SGG S9 phosphorylation by RSK and other kinases as a convergence point for diverse cellular and external stimuli.
KW  - circadian clock
KW  - Period
KW  - Timeless
KW  - Shaggy kinase
KW  - RSK
KW  - Coffin–Lowry syndrome
Y1  - 2018
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-196034
SN  - 1662-5099
VL  - 11
IS  - 122
ER  - 
TY  - JOUR
A1  - Beck, Sebastian
A1  - Yu-Strzelczyk, Jing
A1  - Pauls, Dennis
A1  - Constantin, Oana M.
A1  - Gee, Christine E.
A1  - Ehmann, Nadine
A1  - Kittel, Robert J.
A1  - Nagel, Georg
A1  - Gao, Shiqiang
T1  - Synthetic light-activated ion channels for optogenetic activation and inhibition
JF  - Frontiers in Neuroscience
N2  - Optogenetic manipulation of cells or living organisms became widely used in neuroscience following the introduction of the light-gated ion channel channelrhodopsin-2 (ChR2). ChR2 is a non-selective cation channel, ideally suited to depolarize and evoke action potentials in neurons. However, its calcium (Ca2\(^{2+}\)) permeability and single channel conductance are low and for some applications longer-lasting increases in intracellular Ca\(^{2+}\) might be desirable. Moreover, there is need for an efficient light-gated potassium (K\(^{+}\)) channel that can rapidly inhibit spiking in targeted neurons. Considering the importance of Ca\(^{2+}\) and K\(^{+}\) in cell physiology, light-activated Ca\(^{2+}\)-permeant and K\(^{+}\)-specific channels would be welcome additions to the optogenetic toolbox. Here we describe the engineering of novel light-gated Ca\(^{2+}\)-permeant and K\(^{+}\)-specific channels by fusing a bacterial photoactivated adenylyl cyclase to cyclic nucleotide-gated channels with high permeability for Ca\(^{2+}\) or for K\(^{+}\), respectively. Optimized fusion constructs showed strong light-gated conductance in Xenopus laevis oocytes and in rat hippocampal neurons. These constructs could also be used to control the motility of Drosophila melanogaster larvae, when expressed in motoneurons. Illumination led to body contraction when motoneurons expressed the light-sensitive Ca\(^{2+}\)-permeant channel, and to body extension when expressing the light-sensitive K\(^{+}\) channel, both effectively and reversibly paralyzing the larvae. Further optimization of these constructs will be required for application in adult flies since both constructs led to eclosion failure when expressed in motoneurons.
KW  - optogenetics
KW  - calcium
KW  - potassium
KW  - bPAC
KW  - CNG channel
KW  - cAMP
KW  - Drosophila melanogaster motoneuron
KW  - rat hippocampal neurons
Y1  - 2018
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-177520
VL  - 12
IS  - 643
ER  - 
TY  - JOUR
A1  - Becker, Nils
A1  - Kucharski, Robert
A1  - Rössler, Wolfgang
A1  - Maleszka, Ryszard
T1  - Age‐dependent transcriptional and epigenomic responses to light exposure in the honey bee brain
JF  - FEBS Open Bio
N2  - Light is a powerful environmental stimulus of special importance in social honey bees that undergo a behavioral transition from in-hive to outdoor foraging duties. Our previous work has shown that light exposure induces structural neuronal plasticity in the mushroom bodies (MBs), a brain center implicated in processing inputs from sensory modalities. Here, we extended these analyses to the molecular level to unravel light-induced transcriptomic and epigenomic changes in the honey bee brain. We have compared gene expression in brain compartments of 1- and 7-day-old light-exposed honey bees with age-matched dark-kept individuals. We have found a number of differentially expressed genes (DEGs), both novel and conserved, including several genes with reported roles in neuronal plasticity. Most of the DEGs show age-related changes in the amplitude of light-induced expression and are likely to be both developmentally and environmentally regulated. Some of the DEGs are either known to be methylated or are implicated in epigenetic processes suggesting that responses to light exposure are at least partly regulated at the epigenome level. Consistent with this idea light alters the DNA methylation pattern of bgm, one of the DEGs affected by light exposure, and the expression of microRNA miR-932. This confirms the usefulness of our approach to identify candidate genes for neuronal plasticity and provides evidence for the role of epigenetic processes in driving the molecular responses to visual stimulation.
KW  - DNA methylation
KW  - insect brain
KW  - light-induced gene expression
KW  - microRNA
KW  - neuronal plasticity
Y1  - 2016
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-147080
VL  - 6
IS  - 7
ER  - 
TY  - JOUR
A1  - Beer, Katharina
A1  - Helfrich-Förster, Charlotte
T1  - Model and Non-model Insects in Chronobiology
JF  - Frontiers in Behavioral Neuroscience
N2  - 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.
KW  - circadian clock
KW  - complex behavior
KW  - diapause
KW  - sociality
KW  - Drosophila melanogaster
KW  - Apis mellifera
Y1  - 2020
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-218721
SN  - 1662-5153
VL  - 14
ER  - 
TY  - JOUR
A1  - Beer, Katharina
A1  - Helfrich-Förster, Charlotte
T1  - Post-embryonic Development of the Circadian Clock Seems to Correlate With Social Life Style in Bees
JF  - Frontiers in Cell and Developmental Biology
N2  - Social life style can influence many aspects of an animal’s daily life, but it has not yet been clarified, whether development of the circadian clock in social and solitary living bees differs. In a comparative study, with the social honey bee, Apis mellifera, and the solitary mason bee, Osmia bicornis, we now found indications for a differentially timed clock development in social and solitary bees. Newly emerged solitary bees showed rhythmic locomotion right away and the number of neurons in the brain that produce the clock component pigment-dispersing factor (PDF) did not change during aging of the adult solitary bee. Honey bees on the other hand, showed no circadian locomotion directly after emergence and the neuronal clock network continued to grow after emergence. Social bees appear to emerge at an early developmental stage at which the circadian clock is still immature, but bees are already able to fulfill in-hive tasks.
KW  - social
KW  - honey bee
KW  - solitary bee
KW  - circadian clock
KW  - activity rhythm
KW  - neuronal network
KW  - development
Y1  - 2020
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-216450
SN  - 2296-634X
VL  - 8
ER  - 
TY  - JOUR
A1  - Beer, Katharina
A1  - Härtel, Stephan
A1  - Helfrich-Förster, Charlotte
T1  - The pigment-dispersing factor neuronal network systematically grows in developing honey bees
JF  - The Journal of Comparative Neurology
N2  - The neuropeptide pigment-dispersing factor (PDF) plays a prominent role in the circadian clock of many insects including honey bees. In the honey bee brain, PDF is expressed in about 15 clock neurons per hemisphere that lie between the central brain and the optic lobes. As in other insects, the bee PDF neurons form wide arborizations in the brain, but certain differences are evident. For example, they arborize only sparsely in the accessory medulla (AME), which serves as important communication center of the circadian clock in cockroaches and flies. Furthermore, all bee PDF neurons cluster together, which makes it impossible to distinguish individual projections. Here, we investigated the developing bee PDF network and found that the first three PDF neurons arise in the third larval instar and form a dense network of varicose fibers at the base of the developing medulla that strongly resembles the AME of hemimetabolous insects. In addition, they send faint fibers toward the lateral superior protocerebrum. In last larval instar, PDF cells with larger somata appear and send fibers toward the distal medulla and the medial protocerebrum. In the dorsal part of the medulla serpentine layer, a small PDF knot evolves from which PDF fibers extend ventrally. This knot disappears during metamorphosis and the varicose arborizations in the putative AME become fainter. Instead, a new strongly stained PDF fiber hub appears in front of the lobula. Simultaneously, the number of PDF neurons increases and the PDF neuronal network in the brain gets continuously more complex.
KW  - apis mellifera
KW  - circadian clock
KW  - immunohistochemistry
KW  - larval and pupal development
KW  - neuroanatomy
Y1  - 2022
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-257300
VL  - 530
IS  - 9
ER  - 
TY  - JOUR
A1  - Beer, Katharina
A1  - Joschinski, Jens
A1  - Sastre, Alazne Arrazola
A1  - Krauss, Jochen
A1  - Helfrich-Förster, Charlotte
T1  - A damping circadian clock drives weak oscillations in metabolism and locomotor activity of aphids (Acyrthosiphon pisum)
JF  - Scientific Reports
N2  - Timing seasonal events, like reproduction or diapause, is crucial for the survival of many species. Global change causes phenologies worldwide to shift, which requires a mechanistic explanation of seasonal time measurement. Day length (photoperiod) is a reliable indicator of winter arrival, but it remains unclear how exactly species measure day length. A reference for time of day could be provided by a circadian clock, by an hourglass clock, or, as some newer models suggest, by a damped circadian clock. However, damping of clock outputs has so far been rarely observed. To study putative clock outputs of Acyrthosiphon pisum aphids, we raised individual nymphs on coloured artificial diet, and measured rhythms in metabolic activity in light-dark illumination cycles of 16:08 hours (LD) and constant conditions (DD). In addition, we kept individuals in a novel monitoring setup and measured locomotor activity. We found that A. pisum is day-active in LD, potentially with a bimodal distribution. In constant darkness rhythmicity of locomotor behaviour persisted in some individuals, but patterns were mostly complex with several predominant periods. Metabolic activity, on the other hand, damped quickly. A damped circadian clock, potentially driven by multiple oscillator populations, is the most likely explanation of our results.
KW  - circadian mechanisms
KW  - behavioural ecology
KW  - damped circadian clock
KW  - Acyrthosiphon pisum
Y1  - 2017
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-170020
VL  - 7
IS  - 14906
ER  - 
TY  - JOUR
A1  - Beer, Katharina
A1  - Schenk, Mariela
A1  - Helfrich-Förster, Charlotte
A1  - Holzschuh, Andrea
T1  - The circadian clock uses different environmental time cues to synchronize emergence and locomotion of the solitary bee Osmia bicornis
JF  - Scientific Reports
N2  - Life on earth adapted to the daily reoccurring changes in environment by evolving an endogenous circadian clock. Although the circadian clock has a crucial impact on survival and behavior of solitary bees, many aspects of solitary bee clock mechanisms remain unknown. Our study is the first to show that the circadian clock governs emergence in Osmia bicornis, a bee species which overwinters as adult inside its cocoon. Therefore, its eclosion from the pupal case is separated by an interjacent diapause from its emergence in spring. We show that this bee species synchronizes its emergence to the morning. The daily rhythms of emergence are triggered by temperature cycles but not by light cycles. In contrast to this, the bee’s daily rhythms in locomotion are synchronized by light cycles. Thus, we show that the circadian clock of O. bicornis is set by either temperature or light, depending on what activity is timed. Light is a valuable cue for setting the circadian clock when bees have left the nest. However, for pre-emerged bees, temperature is the most important cue, which may represent an evolutionary adaptation of the circadian system to the cavity-nesting life style of O. bicornis.
KW  - Behavioural ecology
KW  - Evolutionary developmental biology
Y1  - 2019
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-202721
VL  - 9
ER  - 
TY  - JOUR
A1  - Beer, Katharina
A1  - Steffan-Dewenter, Ingolf
A1  - Härtel, Stephan
A1  - Helfrich-Förster, Charlotte
T1  - A new device for monitoring individual activity rhythms of honey bees reveals critical effects of the social environment on behavior
JF  - Journal of Comparative Physiology A
N2  - Chronobiological studies of individual activity rhythms in social insects can be constrained by the artificial isolation of individuals from their social context. We present a new experimental set-up that simultaneously measures the temperature rhythm in a queen-less but brood raising mini colony and the walking activity rhythms of singly kept honey bees that have indirect social contact with it. Our approach enables monitoring of individual bees in the social context of a mini colony under controlled laboratory conditions. In a pilot experiment, we show that social contact with the mini colony improves the survival of monitored young individuals and affects locomotor activity patterns of young and old bees. When exposed to conflicting Zeitgebers consisting of a light-dark (LD) cycle that is phase-delayed with respect to the mini colony rhythm, rhythms of young and old bees are socially synchronized with the mini colony rhythm, whereas isolated bees synchronize to the LD cycle. We conclude that the social environment is a stronger Zeitgeber than the LD cycle and that our new experimental set-up is well suited for studying the mechanisms of social entrainment in honey bees.
KW  - Social entrainment
KW  - Foragers
KW  - Nurses
KW  - Locomotor activity
KW  - Temperature rhythms
Y1  - 2016
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-188030
VL  - 202
IS  - 8
ER  - 
TY  - JOUR
A1  - Beetz, M. Jerome
A1  - Hechavarría, Julio C.
T1  - Neural processing of naturalistic echolocation signals in bats
JF  - Frontiers in Neural Circuits
N2  - Echolocation behavior, a navigation strategy based on acoustic signals, allows scientists to explore neural processing of behaviorally relevant stimuli. For the purpose of orientation, bats broadcast echolocation calls and extract spatial information from the echoes. Because bats control call emission and thus the availability of spatial information, the behavioral relevance of these signals is undiscussable. While most neurophysiological studies, conducted in the past, used synthesized acoustic stimuli that mimic portions of the echolocation signals, recent progress has been made to understand how naturalistic echolocation signals are encoded in the bat brain. Here, we review how does stimulus history affect neural processing, how spatial information from multiple objects and how echolocation signals embedded in a naturalistic, noisy environment are processed in the bat brain. We end our review by discussing the huge potential that state-of-the-art recording techniques provide to gain a more complete picture on the neuroethology of echolocation behavior.
KW  - biosonar
KW  - neural coding
KW  - naturalistic stimuli
KW  - bats
KW  - acoustic stream
KW  - neuroethology
Y1  - 2022
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-274605
SN  - 1662-5110
VL  - 16
ER  - 
TY  - JOUR
A1  - Beetz, M. Jerome
A1  - Kraus, Christian
A1  - el Jundi, Basil
T1  - Neural representation of goal direction in the monarch butterfly brain
JF  - Nature Communications
N2  - Neural processing of a desired moving direction requires the continuous comparison between the current heading and the goal direction. While the neural basis underlying the current heading is well-studied, the coding of the goal direction remains unclear in insects. Here, we used tetrode recordings in tethered flying monarch butterflies to unravel how a goal direction is represented in the insect brain. While recording, the butterflies maintained robust goal directions relative to a virtual sun. By resetting their goal directions, we found neurons whose spatial tuning was tightly linked to the goal directions. Importantly, their tuning was unaffected when the butterflies changed their heading after compass perturbations, showing that these neurons specifically encode the goal direction. Overall, we here discovered invertebrate goal-direction neurons that share functional similarities to goal-direction cells reported in mammals. Our results give insights into the evolutionarily conserved principles of goal-directed spatial orientation in animals.
KW  - animal behaviour
KW  - navigation
KW  - neuroscience
Y1  - 2023
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-358073
VL  - 14
ER  - 
TY  - JOUR
A1  - Beier, Hildburg
A1  - Gätschenberger, Heike
A1  - Azzami, Klara
A1  - Tautz, Jürgen
T1  - Antibacterial Immune Competence of Honey Bees (Apis mellifera) Is Adapted to Different Life Stages and Environmental Risks
JF  - PLoS ONE
N2  - The development of all honey bee castes proceeds through three different life stages all of which encounter microbial infections to a various extent. We have examined the immune strength of honey bees across all developmental stages with emphasis on the temporal expression of cellular and humoral immune responses upon artificial challenge with viable Escherichia coli bacteria. We employed a broad array of methods to investigate defence strategies of infected individuals: (a) fate of bacteria in the haemocoel; (b) nodule formation and (c) induction of antimicrobial peptides (AMPs). Newly emerged adult worker bees and drones were able to activate efficiently all examined immune reactions. The number of viable bacteria circulating in the haemocoel of infected bees declined rapidly by more than two orders of magnitude within the first 4–6 h post-injection (p.i.), coinciding with the occurrence of melanised nodules. Antimicrobial activity, on the other hand, became detectable only after the initial bacterial clearance. These two temporal patterns of defence reactions very likely represent the constitutive cellular and the induced humoral immune response. A unique feature of honey bees is that a fraction of worker bees survives the winter season in a cluster mostly engaged in thermoregulation. We show here that the overall immune strength of winter bees matches that of young summer bees although nodulation reactions are not initiated at all. As expected, high doses of injected viable E.coli bacteria caused no mortality in larvae or adults of each age. However, drone and worker pupae succumbed to challenge with E.coli even at low doses, accompanied by a premature darkening of the pupal body. In contrast to larvae and adults, we observed no fast clearance of viable bacteria and no induction of AMPs but a rapid proliferation of E.coli bacteria in the haemocoel of bee pupae ultimately leading to their death.
KW  - escherichia coli infections
KW  - honey bees
KW  - bees
KW  - antimicrobials
KW  - bacterial pathogens
KW  - larvae
KW  - pupae
KW  - winter
Y1  - 2013
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-96895
ER  - 
TY  - JOUR
A1  - Beisser, Daniela
A1  - Grohme, Markus A.
A1  - Kopka, Joachim
A1  - Frohme, Marcus
A1  - Schill, Ralph O.
A1  - Hengherr, Steffen
A1  - Dandekar, Thomas
A1  - Klau, Gunnar W.
A1  - Dittrich, Marcus
A1  - Müller, Tobias
T1  - Integrated pathway modules using time-course metabolic profiles and EST data from Milnesium tardigradum
N2  - Background: Tardigrades are multicellular organisms, resistant to extreme environmental changes such as heat, drought, radiation and freezing. They outlast these conditions in an inactive form (tun) to escape damage to cellular structures and cell death. Tardigrades are apparently able to prevent or repair such damage and are therefore a crucial model organism for stress tolerance. Cultures of the tardigrade Milnesium tardigradum were dehydrated by removing the surrounding water to induce tun formation. During this process and the subsequent rehydration, metabolites were measured in a time series by GC-MS. Additionally expressed sequence tags are available, especially libraries generated from the active and inactive state. The aim of this integrated analysis is to trace changes in tardigrade metabolism and identify pathways responsible for their extreme resistance against physical stress. Results: In this study we propose a novel integrative approach for the analysis of metabolic networks to identify modules of joint shifts on the transcriptomic and metabolic levels. We derive a tardigrade-specific metabolic network represented as an undirected graph with 3,658 nodes (metabolites) and 4,378 edges (reactions). Time course metabolite profiles are used to score the network nodes showing a significant change over time. The edges are scored according to information on enzymes from the EST data. Using this combined information, we identify a key subnetwork (functional module) of concerted changes in metabolic pathways, specific for de- and rehydration. The module is enriched in reactions showing significant changes in metabolite levels and enzyme abundance during the transition. It resembles the cessation of a measurablemetabolism (e.g. glycolysis and amino acid anabolism) during the tun formation, the production of storage metabolites and bioprotectants, such as DNA stabilizers, and the generation of amino acids and cellular components from monosaccharides as carbon and energy source during rehydration. Conclusions: The functional module identifies relationships among changed metabolites (e.g. spermidine) and reactions and provides first insights into important altered metabolic pathways. With sparse and diverse data available, the presented integrated metabolite network approach is suitable to integrate all existing data and analyse it in a combined manner.
KW  - Milnesium tardigradum
KW  - Integrated network analysis
KW  - Functional modules
KW  - Metabolic profiles
KW  - Metabolic pathways
KW  - Trend test
Y1  - 2012
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-75241
ER  - 
TY  - JOUR
A1  - Bell, Peter
A1  - Dabauvalle, Marie-Christine
A1  - Scheer, Ulrich
T1  - In vitro assembly of prenucleolar bodies in Xenopus egg extract
N2  - Nuclei assembled in Xenopus egg extract from purified DNA or chromatin resemble their natural counterparts in a number of structural and functional features. However, the most obvious structural element of normal interphase nuclei, the nucleolus, is absent from the in vitro reconstituted nuclei. By EM, cytological silver staining, and immunofluorescence microscopy employing antibodies directed against various nucleolar components we show that nuclei assembled in vitro contain numerous distinct aggregates that resemble prenucleolar bodies (PNBs) by several criteria. Formation of these PNB-like structures requires pore complex-mediated nuclear transport of proteins but is independent of the genetic content of the in vitro nuclei as well as transcriptional and translational events. Our data indicate that nuclei assembled in vitro are capable of initiating early steps of nucleologenesis but that the resulting PNBs are unable to fuse with each other, probably due to the absence of a functional nucleolus organizer. With appropriate modifications, this experimental system should be useful to define and analyze conditions promoting the site-specific assembly of PNBs into a coherent nucleolar body.
Y1  - 1992
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-34233
ER  - 
TY  - JOUR
A1  - Bemm, Felix
A1  - Becker, Dirk
A1  - Larisch, Christina
A1  - Kreuzer, Ines
A1  - Escalante-Perez, Maria
A1  - Schulze, Waltraud X.
A1  - Ankenbrand, Markus
A1  - Van de Weyer, Anna-Lena
A1  - Krol, Elzbieta
A1  - Al-Rasheid, Khaled A.
A1  - Mithöfer, Axel
A1  - Weber, Andreas P.
A1  - Schultz, Jörg
A1  - Hedrich, Rainer
T1  - Venus flytrap carnivorous lifestyle builds on herbivore defense strategies
JF  - Genome Research
N2  - Although the concept of botanical carnivory has been known since Darwin's time, the molecular mechanisms that allow animal feeding remain unknown, primarily due to a complete lack of genomic information. Here, we show that the transcriptomic landscape of the Dionaea trap is dramatically shifted toward signal transduction and nutrient transport upon insect feeding, with touch hormone signaling and protein secretion prevailing. At the same time, a massive induction of general defense responses is accompanied by the repression of cell death-related genes/processes. We hypothesize that the carnivory syndrome of Dionaea evolved by exaptation of ancient defense pathways, replacing cell death with nutrient acquisition.
KW  - Dionaea-muscipula ellis
KW  - Plant utricularia-gibba
KW  - Programmed cell-death
KW  - Genomics data sets
KW  - RNA-SEQ data
KW  - Arabidopsis-thaliana
KW  - Jasmonate perception
KW  - Action potentials
KW  - Stress responses
KW  - Wonderful plants
Y1  - 2016
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-188799
VL  - 26
IS  - 6
ER  - 
TY  - JOUR
A1  - Benavente, Ricardo
A1  - Dabauvalle, Marie-Christine
A1  - Scheer, Ulrich
A1  - Chaly, Nathalie
T1  - Functional role of newly formed pore complexes in postmitotic nuclear reorganization
N2  - Many nuclear proteins are released into the cytoplasm at prometaphase and are transported back into the daughter nuclei at the end of mitosis. To determine the role of this reentry in nuclear remodelling during early interphase, we experimentally manipulated nuclear protein uptake in dividing cells. Recently we and others have shown that signal-dependent, pore complex-mediated uptake of nuclear protein is blocked in living cells on microinjection of the lectin wheat germ agglutinin (WGA), or of antibodies such as PI1 that are directed against WGA-binding pore complex glycoproteins. In the present study, we microinjected mitotic PtKz cells with WGA or antibody PIt and followed nuclear reorganization of the daughter cells by immunofluorescence and electron microscopy. The inhibitory effect on nuclear protein uptake was monitored by co-injection of the karyophilic protein nucleoplasmin. When injected by itself early in mitosis, nucleoplasmin became sequestered into the daughter nuclei as they entered telophase. In contrast, nucleoplasmin was excluded from the daughter nuclei in the presence of WGA or antibody PI1 . Although PtKz cells with blocked nuclear protein uptake completed cytokinesis, their nuclei showed a telophaselike organization characterized by highly condensed chromatin surrounded by a nuclear envelope containing a few pore complexes. These findings suggest that pore complexes become functional as early as telophase, in close coincidence with nuclear envelope reformation. They further indicate that the extensive structural rearrangement of the nucleus during the telophase-G1 transition is dependent on the influx of karyophilic proteins from the cytoplasm through the pore complexes, and is not due solely to chromosome- associated components.
Y1  - 1989
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-40754
ER  - 
TY  - JOUR
A1  - Benavente, Ricardo
A1  - Reimer, Georg
A1  - Rose, Kathleen M.
A1  - Hügle-Dörr, Barbara
A1  - Scheer, Ulrich
T1  - Nucleolar changes after microinjection of antibodies to RNA polymerase I into the nucleus of mammalian cells
N2  - After microinjection of antibodies against RNA polymerase I into the nuclei of cultured rat kangaroo (PtKz) and rat (RVF-SMC) cells alterations in nucleolar structure and composition were observed. These were detected by electron microscopy and double-label immunofluorescence microscopy using antibodies to proteins representative of the three major components of the nucleolus. The microinjected antibodies produced a progressive loss of the material of the dense fibrillar component (DFC) from the nucleoli which, at 4 h after injection, were transformed into bodies with purely granular component (GC) structure with attached fibrillar centers (FCs). Concomitantly, numerous extranucleolar aggregates appeared in the nucleoplasm which morphologically resembled fragments of the DFC and contained a protein (fibrillarin) diagnostic for this nucleolar structure. These observations indicate that the topological distribution of the material constituting the DFC can be experimentally influenced in interphase cells, apparently by modulating the transcriptional activity of the rRNA genes. These effects are different from nucleolar lesions induced by inhibitory drugs such as actinomycin D-dependent "nucleolar segregation". The structural alterations induced by antibodies to RNA polymerase I resemble, however, the initial events of nucleolar disintegration during mitotic prophase.
Y1  - 1988
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-40666
ER  - 
TY  - JOUR
A1  - Benavente, Ricardo
A1  - Rose, Kathleen M.
A1  - Reimer, Georg
A1  - Hügle-Dörr, Barbara
A1  - Scheer, Ulrich
T1  - Inhibition of nucleolar reformation after microinjection of antibodies to RNA polymerase I into mitotic cells
N2  - The formation of daughter nuclei and the reformation of nucleolar structures was studied after microinjection of antibodies to RNA polymerase I into dividing cultured cells (PtK2). The fate of several nucleolar proteins representing the three main structural subcomponents of the nucleolus was examined by immunofluorescence and electron microscopy. The results show that the RNA polymerase I antibodies do not interfere with normal mitotic progression or the early steps of nucleologenesis, i.e. , the aggregation of nucleolar material into prenucleolar bodies. However,they inhibit the telophasic coalescence of the prenucleolar bodies into the chromosomal nucleolar organizer regions, thus preventing the formation of new nucleoli. These prenucleolar bodies show a fibrillar organization that also compositionally resembles the dense fibrillar component of interphase nucleoli . We conclude that during normal nucleologenesis the dense fibrillar component forms from preformed entities around nucleolar organizer regions, and that this association seems to be dependent on the presence of an active form of RNA polymerase I.
Y1  - 1987
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-33247
ER  - 
TY  - JOUR
A1  - Benavente, Ricardo
A1  - Scheer, Ulrich
A1  - Chaly, Nathalie
T1  - Nucleocytoplasmic sorting of macromolecules following mitosis: fate of nuclear constituents after inhibition of pore complex function
N2  - PtK2 cells in which pore complex-mediated transport is blocked by microinjection early in mitosis of a monoclonal antibody (specific for an Mr 68000 pore complex glycoprotein) or of wheat germ agglutinin (WGA) complete cytokinesis. However, their nuclei remain stably arrested in a telophase-like organization characterized by highly condensed chromatin and the absence of nucleoli, indicating a requirement for pore-mediated transport for the reassembly of interphase nuclei. We have now examined this requirement more closely by monitoring the behavior of individual nuclear macromolecules in microinjected cells using immunofluorescence microscopy and have investigated the effect of microinjecting the antibody or WGA on cellular ultrastructure. The absence of nuclear transport did not affect the sequestration into daughter nuclei of components such as DNA, DNA topoisomerase I and the nucleolar protein fibrillarin that are carried through mitosis on chromosomes. On the other hand, lamins, snRNAs and the p68 pore complex glycoprotein, all cytoplasmic during mitosis, remained largely cytoplasmic in the telophase-arrested cells. Electron microscopy showed the nuclei to be surrounded by a doublelayered membrane with some inserted pore complexes. In addition, however, a variety of membranous structures with associated pore complexes was regularly noted in the cytoplasm, suggesting that chromatin may not be essential for the postmitotic formation of pore complexes. We propose that cellular compartmentalization at telophase is a two-step process. First, a nuclear envelope tightly encloses the condensed chromosomes, excluding non-selectively all macromolecules not associated with the chromosomes. Interphase nuclear organization is then progressively restored by selective pore complex-mediated uptake of nuclear proteins from the cytoplasm.
KW  - Cytologie
KW  - Nucleocytoplasmic transport
KW  - nuclear organization
KW  - nuclear envelope
KW  - nucleologenesis
KW  - mitosis
Y1  - 1989
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-40777
ER  - 
TY  - JOUR
A1  - Benavente, Ricardo
A1  - Schmidt-Zachmann, Marion S.
A1  - Hügle-Dörr, B.
A1  - Reimer, G.
A1  - Rose, K. M.
A1  - Scheer, Ulrich
T1  - Identification and definition of nucleolus-related fibrillar bodies in micronucleated cells
N2  - Small nucleolus-related bodies which occur in the nUcleoplasm of " micronuclei" lacking nucleolar organizers have been studied by immunofluorescence microscopy. These bodies stained specifically with three different antibodies directed against proteins that are normally associated with the dense fibrillar component of functional nucleoli, but not with antibodies specific for certain proteins of the granular component or the fibrillar centers. Our data show that, in the absence of rRNA genes, the various constituent proteins characteristic of the dense fibrillar component spontaneously assemble into spherical entities but that the subsequent fusion of these bodies into larger structures is prevented in these micronuclei. The similarity between these nucleolus-related bodies of micronuclei and the prenucleolar bodies characteristic of early stages of nucleologenesis during mitotic telophase is discussed.
Y1  - 1988
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-39423
ER  - 
TY  - JOUR
A1  - Bencurova, Elena
A1  - Akash, Aman
A1  - Dobson, Renwick C.J.
A1  - Dandekar, Thomas
T1  - DNA storage-from natural biology to synthetic biology
JF  - Computational and Structural Biotechnology Journal
N2  - Natural DNA storage allows cellular differentiation, evolution, the growth of our children and controls all our ecosystems. Here, we discuss the fundamental aspects of DNA storage and recent advances in this field, with special emphasis on natural processes and solutions that can be exploited. We point out new ways of efficient DNA and nucleotide storage that are inspired by nature. Within a few years DNA-based information storage may become an attractive and natural complementation to current electronic data storage systems. We discuss rapid and directed access (e.g. DNA elements such as promotors, enhancers), regulatory signals and modulation (e.g. lncRNA) as well as integrated high-density storage and processing modules (e.g. chromosomal territories). There is pragmatic DNA storage for use in biotechnology and human genetics. We examine DNA storage as an approach for synthetic biology (e.g. light-controlled nucleotide processing enzymes). The natural polymers of DNA and RNA offer much for direct storage operations (read-in, read-out, access control). The inbuilt parallelism (many molecules at many places working at the same time) is important for fast processing of information. Using biology concepts from chromosomal storage, nucleic acid processing as well as polymer material sciences such as electronical effects in enzymes, graphene, nanocellulose up to DNA macramé , DNA wires and DNA-based aptamer field effect transistors will open up new applications gradually replacing classical information storage methods in ever more areas over time (decades).
KW  - DNA
KW  - RNA
KW  - data storage
KW  - natural processing
KW  - synthetic biology
Y1  - 2023
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-349971
SN  - 2001-0370
VL  - 21
ER  - 
TY  - JOUR
A1  - Bencurova, Elena
A1  - Gupta, Shishir K.
A1  - Sarukhanyan, Edita
A1  - Dandekar, Thomas
T1  - Identification of antifungal targets based on computer modeling
JF  - Journal of Fungi
N2  - Aspergillus fumigatus is a saprophytic, cosmopolitan fungus that attacks patients with a weak immune system. A rational solution against fungal infection aims to manipulate fungal metabolism or to block enzymes essential for Aspergillus survival. Here we discuss and compare different bioinformatics approaches to analyze possible targeting strategies on fungal-unique pathways. For instance, phylogenetic analysis reveals fungal targets, while domain analysis allows us to spot minor differences in protein composition between the host and fungi. Moreover, protein networks between host and fungi can be systematically compared by looking at orthologs and exploiting information from host–pathogen interaction databases. Further data—such as knowledge of a three-dimensional structure, gene expression data, or information from calculated metabolic fluxes—refine the search and rapidly put a focus on the best targets for antimycotics. We analyzed several of the best targets for application to structure-based drug design. Finally, we discuss general advantages and limitations in identification of unique fungal pathways and protein targets when applying bioinformatics tools.
KW  - Aspergillus
KW  - metabolic pathways
KW  - computational modelling
KW  - drug design
Y1  - 2018
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-197670
SN  - 2309-608X
VL  - 4
IS  - 3
ER  - 
TY  - JOUR
A1  - Bencurova, Elena
A1  - Shityakov, Sergey
A1  - Schaack, Dominik
A1  - Kaltdorf, Martin
A1  - Sarukhanyan, Edita
A1  - Hilgarth, Alexander
A1  - Rath, Christin
A1  - Montenegro, Sergio
A1  - Roth, Günter
A1  - Lopez, Daniel
A1  - Dandekar, Thomas
T1  - Nanocellulose composites as smart devices with chassis, light-directed DNA Storage, engineered electronic properties, and chip integration
JF  - Frontiers in Bioengineering and Biotechnology
N2  - The rapid development of green and sustainable materials opens up new possibilities in the field of applied research. Such materials include nanocellulose composites that can integrate many components into composites and provide a good chassis for smart devices. In our study, we evaluate four approaches for turning a nanocellulose composite into an information storage or processing device: 1) nanocellulose can be a suitable carrier material and protect information stored in DNA. 2) Nucleotide-processing enzymes (polymerase and exonuclease) can be controlled by light after fusing them with light-gating domains; nucleotide substrate specificity can be changed by mutation or pH change (read-in and read-out of the information). 3) Semiconductors and electronic capabilities can be achieved: we show that nanocellulose is rendered electronic by iodine treatment replacing silicon including microstructures. Nanocellulose semiconductor properties are measured, and the resulting potential including single-electron transistors (SET) and their properties are modeled. Electric current can also be transported by DNA through G-quadruplex DNA molecules; these as well as classical silicon semiconductors can easily be integrated into the nanocellulose composite. 4) To elaborate upon miniaturization and integration for a smart nanocellulose chip device, we demonstrate pH-sensitive dyes in nanocellulose, nanopore creation, and kinase micropatterning on bacterial membranes as well as digital PCR micro-wells. Future application potential includes nano-3D printing and fast molecular processors (e.g., SETs) integrated with DNA storage and conventional electronics. This would also lead to environment-friendly nanocellulose chips for information processing as well as smart nanocellulose composites for biomedical applications and nano-factories.
KW  - nanocellulose
KW  - DNA storage
KW  - light-gated proteins
KW  - single-electron transistors
KW  - protein chip
Y1  - 2022
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-283033
SN  - 2296-4185
VL  - 10
ER  - 
TY  - JOUR
A1  - Benoit, Joshua B.
A1  - Adelman, Zach N.
A1  - Reinhardt, Klaus
A1  - Dolan, Amanda
A1  - Poelchau, Monica
A1  - Jennings, Emily C.
A1  - Szuter, Elise M.
A1  - Hagan, Richard W.
A1  - Gujar, Hemant
A1  - Shukla, Jayendra Nath
A1  - Zhu, Fang
A1  - Mohan, M.
A1  - Nelson, David R.
A1  - Rosendale, Andrew J.
A1  - Derst, Christian
A1  - Resnik, Valentina
A1  - Wernig, Sebastian
A1  - Menegazzi, Pamela
A1  - Wegener, Christian
A1  - Peschel, Nicolai
A1  - Hendershot, Jacob M.
A1  - Blenau, Wolfgang
A1  - Predel, Reinhard
A1  - Johnston, Paul R.
A1  - Ioannidis, Panagiotis
A1  - Waterhouse, Robert M.
A1  - Nauen, Ralf
A1  - Schorn, Corinna
A1  - Ott, Mark-Christoph
A1  - Maiwald, Frank
A1  - Johnston, J. Spencer
A1  - Gondhalekar, Ameya D.
A1  - Scharf, Michael E.
A1  - Raje, Kapil R.
A1  - Hottel, Benjamin A.
A1  - Armisén, David
A1  - Crumière, Antonin Jean Johan
A1  - Refki, Peter Nagui
A1  - Santos, Maria Emilia
A1  - Sghaier, Essia
A1  - Viala, Sèverine
A1  - Khila, Abderrahman
A1  - Ahn, Seung-Joon
A1  - Childers, Christopher
A1  - Lee, Chien-Yueh
A1  - Lin, Han
A1  - Hughes, Daniel S.T.
A1  - Duncan, Elizabeth J.
A1  - Murali, Shwetha C.
A1  - Qu, Jiaxin
A1  - Dugan, Shannon
A1  - Lee, Sandra L.
A1  - Chao, Hsu
A1  - Dinh, Huyen
A1  - Han, Yi
A1  - Doddapaneni, Harshavardhan
A1  - Worley, Kim C.
A1  - Muzny, Donna M.
A1  - Wheeler, David
A1  - Panfilio, Kristen A.
A1  - Jentzsch, Iris M. Vargas
A1  - Jentzsch, IMV
A1  - Vargo, Edward L.
A1  - Booth, Warren
A1  - Friedrich, Markus
A1  - Weirauch, Matthew T.
A1  - Anderson, Michelle A.E.
A1  - Jones, Jeffery W.
A1  - Mittapalli, Omprakash
A1  - Zhao, Chaoyang
A1  - Zhou, Jing-Jiang
A1  - Evans, Jay D.
A1  - Attardo, Geoffrey M.
A1  - Robertson, Hugh M.
A1  - Zdobnov, Evgeny M.
A1  - Ribeiro, Jose M.C.
A1  - Gibbs, Richard A.
A1  - Werren, John H.
A1  - Palli, Subba R.
A1  - Schal, Coby
A1  - Richards, Stephen
T1  - Unique features of a global human ectoparasite identified through sequencing of the bed bug genome
JF  - Nature Communications
N2  - The bed bug, Cimex lectularius, has re-established itself as a ubiquitous human ectoparasite throughout much of the world during the past two decades. This global resurgence is likely linked to increased international travel and commerce in addition to widespread insecticide resistance. Analyses of the C. lectularius sequenced genome (650 Mb) and 14,220 predicted protein-coding genes provide a comprehensive representation of genes that are linked to traumatic insemination, a reduced chemosensory repertoire of genes related to obligate hematophagy, host–symbiont interactions, and several mechanisms of insecticide resistance. In addition, we document the presence of multiple putative lateral gene transfer events. Genome sequencing and annotation establish a solid foundation for future research on mechanisms of insecticide resistance, human–bed bug and symbiont–bed bug associations, and unique features of bed bug biology that contribute to the unprecedented success of C. lectularius as a human ectoparasite.
KW  - human ectoparasite
KW  - bed bug
KW  - Cimex lectularius
KW  - genome
Y1  - 2016
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-166221
VL  - 7
IS  - 10165
ER  - 
TY  - JOUR
A1  - Bensaad, Karim
A1  - Favaro, Elena
A1  - Lewis, Caroline A.
A1  - Peck, Barrie
A1  - Lord, Simon
A1  - Collins, Jennifer M.
A1  - Pinnick, Katherine E.
A1  - Wigfield, Simon
A1  - Buffa, Francesca M.
A1  - Li, Ji-Liang
A1  - Zhang, Qifeng
A1  - Wakelam, Michael J. O.
A1  - Karpe, Fredrik
A1  - Schulze, Almut
A1  - Harris, Adrian L.
T1  - Fatty Acid Uptake and Lipid Storage Induced by HIF-1 alpha Contribute to Cell Growth and Survival after Hypoxia-Reoxygenation
JF  - Cell Reports
N2  - An in vivo model of antiangiogenic therapy allowed us to identify genes upregulated by bevacizumab treatment, including Fatty Acid Binding Protein 3 (FABP3) and FABP7, both of which are involved in fatty acid uptake. In vitro, both were induced by hypoxia in a hypoxia-inducible factor-1 alpha (HIF-1 alpha)-dependent manner. There was a significant lipid droplet (LD) accumulation in hypoxia that was time and O-2 concentration dependent. Knockdown of endogenous expression of FABP3, FABP7, or Adipophilin (an essential LD structural component) significantly impaired LD formation under hypoxia. We showed that LD accumulation is due to FABP3/7-dependent fatty acid uptake while de novo fatty acid synthesis is repressed in hypoxia. We also showed that ATP production occurs via beta-oxidation or glycogen degradation in a cell-type-dependent manner in hypoxia-reoxygenation. Finally, inhibition of lipid storage reduced protection against reactive oxygen species toxicity, decreased the survival of cells subjected to hypoxia-reoxygenation in vitro, and strongly impaired tumorigenesis in vivo.
KW  - inducible factor-I
KW  - binding protein
KW  - triglyceride accumulation
KW  - cancer cell
KW  - complex-III
KW  - beta-oxidation
KW  - metabolism
KW  - lipogenesis
KW  - proliferation
KW  - resistance
Y1  - 2014
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-115162
SN  - 2211-1247
VL  - 9
IS  - 1
ER  - 
TY  - JOUR
A1  - Benz, Roland
A1  - Maier, Elke
A1  - Bauer, Susanne
A1  - Ludwig, Albrecht
T1  - The Deletion of Several Amino Acid Stretches of Escherichia coli Alpha-Hemolysin (HlyA) Suggests That the Channel-Forming Domain Contains Beta-Strands
JF  - PLOS ONE
N2  - Escherichia coli α-hemolysin (HlyA) is a pore-forming protein of 110 kDa belonging to the family of RTX toxins. A hydrophobic region between the amino acid residues 238 and 410 in the N-terminal half of HlyA has previously been suggested to form hydrophobic and/or amphipathic α-helices and has been shown to be important for hemolytic activity and pore formation in biological and artificial membranes. The structure of the HlyA transmembrane channel is, however, largely unknown. For further investigation of the channel structure, we deleted in HlyA different stretches of amino acids that could form amphipathic β-strands according to secondary structure predictions (residues 71–110, 158–167, 180–203, and 264–286). These deletions resulted in HlyA mutants with strongly reduced hemolytic activity. Lipid bilayer measurements demonstrated that HlyAΔ71–110 and HlyAΔ264–286 formed channels with much smaller single-channel conductance than wildtype HlyA, whereas their channel-forming activity was virtually as high as that of the wildtype toxin. HlyAΔ158–167 and HlyAΔ180–203 were unable to form defined channels in lipid bilayers. Calculations based on the single-channel data indicated that the channels generated by HlyAΔ71–110 and HlyAΔ264–286 had a smaller size (diameter about 1.4 to 1.8 nm) than wildtype HlyA channels (diameter about 2.0 to 2.6 nm), suggesting that in these mutants part of the channel-forming domain was removed. Osmotic protection experiments with erythrocytes confirmed that HlyA, HlyAΔ71–110, and HlyAΔ264–286 form defined transmembrane pores and suggested channel diameters that largely agreed with those estimated from the single-channel data. Taken together, these results suggest that the channel-forming domain of HlyA might contain β-strands, possibly in addition to α-helical structures.
KW  - membrane potential
KW  - molecular mass
KW  - cations
KW  - membrane structures
KW  - membrane proteins
KW  - lipid bilayer
KW  - red blood cells
KW  - toxins
Y1  - 2014
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-118115
SN  - 1932-6203
VL  - 9
IS  - 12
ER  - 
TY  - JOUR
A1  - Berberich, Andreas
A1  - Kurz, Andreas
A1  - Reinhard, Sebastian
A1  - Paul, Torsten Johann
A1  - Burd, Paul Ray
A1  - Sauer, Markus
A1  - Kollmannsberger, Philip
T1  - Fourier Ring Correlation and anisotropic kernel density estimation improve deep learning based SMLM reconstruction of microtubules
JF  - Frontiers in Bioinformatics
N2  - Single-molecule super-resolution microscopy (SMLM) techniques like dSTORM can reveal biological structures down to the nanometer scale. The achievable resolution is not only defined by the localization precision of individual fluorescent molecules, but also by their density, which becomes a limiting factor e.g., in expansion microscopy. Artificial deep neural networks can learn to reconstruct dense super-resolved structures such as microtubules from a sparse, noisy set of data points. This approach requires a robust method to assess the quality of a predicted density image and to quantitatively compare it to a ground truth image. Such a quality measure needs to be differentiable to be applied as loss function in deep learning. We developed a new trainable quality measure based on Fourier Ring Correlation (FRC) and used it to train deep neural networks to map a small number of sampling points to an underlying density. Smooth ground truth images of microtubules were generated from localization coordinates using an anisotropic Gaussian kernel density estimator. We show that the FRC criterion ideally complements the existing state-of-the-art multiscale structural similarity index, since both are interpretable and there is no trade-off between them during optimization. The TensorFlow implementation of our FRC metric can easily be integrated into existing deep learning workflows.
KW  - dSTORM
KW  - deep learning–artificial neural network (DL-ANN)
KW  - single molecule localization microscopy
KW  - microtubule cytoskeleton
KW  - super-resolution
Y1  - 2021
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-261686
VL  - 1
ER  - 
TY  - JOUR
A1  - Bernards, R.
A1  - Schackleford, G. M.
A1  - Gerber, M. R.
A1  - Horowitz, J. M.
A1  - Friend, S. H.
A1  - Schartl, Manfred
A1  - Bogenmann, E.
A1  - Rapaport, J. M.
A1  - Mcgee, T.
A1  - Dryja, T. P.
T1  - Structure and expression of the murine retinoblastoma gene and characterization of its encoded protein
N2  - No abstract available
KW  - Physiologische Chemie
Y1  - 1989
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-61819
ER  - 
TY  - JOUR
A1  - Bert, Bettina
A1  - Chmielewska, Justyna
A1  - Bergmann, Sven
A1  - Busch, Maximilian
A1  - Driever, Wolfgang
A1  - Finger-Baier, Karin
A1  - Hößler, Johanna
A1  - Köhler, Almut
A1  - Leich, Nora
A1  - Misgeld, Thomas
A1  - Nöldner, Torsten
A1  - Reiher, Annegret
A1  - Schartl, Manfred
A1  - Seebach-Sproedt, Anja
A1  - Thumberger, Thomas
A1  - Schönfelder, Gilbert
A1  - Grune, Barbara
T1  - Considerations for a European animal welfare standard to evaluate adverse phenotypes in teleost fish
JF  - The EMBO Journal
N2  - No abstract available.
KW  - Danio-rerio
KW  - Zebrafish
KW  - Pain
Y1  - 2016
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-188783
VL  - 35
IS  - 11
ER  - 
TY  - JOUR
A1  - Biedermann, Peter H. W.
T1  - Cooperative Breeding in the Ambrosia Beetle Xyleborus affinis and Management of Its Fungal Symbionts
JF  - Frontiers in Ecology and Evolution
N2  - Fungus-farming is known from attine ants, macrotermites, and ambrosia beetles (Scolytinae, Platypodinae). Farming ant and termite societies are superorganismal and grow fungal cultivars in monocultures. Social organization of ambrosia beetle groups and their farming systems are poorly studied, because of their enigmatic life within tunnel systems inside of wood. Ambrosia beetle-fungus symbioses evolved many times independently in both the beetles and their fungal cultivars. Observations suggest that there is evolutionary convergence between these lineages, but also a high variation in the degree of sociality and the modes of fungiculture. Using a laboratory observation technique, I here tried to give insights into the social system and fungus symbiosis of the sugar-cane borer, Xyleborus affinis Eichhoff (Scolytinae: Curculionidae), a currently poorly studied ambrosia beetle. The study revealed a cooperatively breeding system characterized by delayed dispersal of adult daughters, alloparental brood care by larvae and adults, and about half of the totipotent adult daughters laying eggs within the natal nest. Most interesting, there was a tendency of egg-laying females to engage more commonly in mutually beneficial behaviors than non-egg-layers. Fungus gardens covering gallery walls composed of five different filamentous fungi. A Raffaelea isolate was predominant and together with an unidentified fungus likely served as the main food for adults and larvae. Three isolates, a Mucor, a Fusarium and a Phaeoacremonium isolate were most abundant in the oldest gallery part close to the entrance; Mucor, Fusarium and the Raffaelea isolate in diseased individuals. Additionally, there was correlative evidence for some fungal isoaltes influencing beetle feeding and hygienic behaviors. Overall, X. affinis is now the second ambrosia beetle that can be classified as a cooperative breeder with division of labor among and between adults and larvae.
KW  - cooperative breeding
KW  - bark beetle
KW  - insect agriculture
KW  - symbiosis
KW  - fungus community
KW  - social behavior
KW  - fungus-farming
KW  - mutualism
Y1  - 2020
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-215662
SN  - 2296-701X
VL  - 8
ER  - 
TY  - JOUR
A1  - Biju, Joseph
A1  - Schwarz, Roland
A1  - Linke, Burkhard
A1  - Blom, Jochen
A1  - Becker, Anke
A1  - Claus, Heike
A1  - Goesmann, Alexander
A1  - Frosch, Matthias
A1  - Müller, Tobias
A1  - Vogel, Ulrich
A1  - Schoen, Christoph
T1  - Virulence Evolution of the Human Pathogen Neisseria meningitidis by Recombination in the Core and Accessory Genome
JF  - PLoS One
N2  - Background
Neisseria meningitidis is a naturally transformable, facultative pathogen colonizing the human nasopharynx. Here, we analyze on a genome-wide level the impact of recombination on gene-complement diversity and virulence evolution in N. meningitidis. We combined comparative genome hybridization using microarrays (mCGH) and multilocus sequence typing (MLST) of 29 meningococcal isolates with computational comparison of a subset of seven meningococcal genome sequences.

Principal Findings
We found that lateral gene transfer of minimal mobile elements as well as prophages are major forces shaping meningococcal population structure. Extensive gene content comparison revealed novel associations of virulence with genetic elements besides the recently discovered meningococcal disease associated (MDA) island. In particular, we identified an association of virulence with a recently described canonical genomic island termed IHT-E and a differential distribution of genes encoding RTX toxin- and two-partner secretion systems among hyperinvasive and non-hyperinvasive lineages. By computationally screening also the core genome for signs of recombination, we provided evidence that about 40% of the meningococcal core genes are affected by recombination primarily within metabolic genes as well as genes involved in DNA replication and repair. By comparison with the results of previous mCGH studies, our data indicated that genetic structuring as revealed by mCGH is stable over time and highly similar for isolates from different geographic origins.

Conclusions
Recombination comprising lateral transfer of entire genes as well as homologous intragenic recombination has a profound impact on meningococcal population structure and genome composition. Our data support the hypothesis that meningococcal virulence is polygenic in nature and that differences in metabolism might contribute to virulence.
KW  - population genetics
KW  - DNA recombination
KW  - meningococcal disease
KW  - recombinant proteins
KW  - genomic databases
KW  - comparative genomics
KW  - neisseria meningitidis
KW  - homologous recombination
Y1  - 2011
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-137960
VL  - 6
IS  - 4
ER  - 
TY  - JOUR
A1  - Biltueva, Larisa S.
A1  - Prokopov, Dmitry Yu.
A1  - Romanenko, Svetlana A.
A1  - Interesova, Elena A.
A1  - Schartl, Manfred
A1  - Trifonov, Vladimir A.
T1  - Chromosome distribution of highly conserved tandemly arranged repetitive DNAs in the Siberian sturgeon (Acipenser baerii)
JF  - Genes
N2  - Polyploid genomes present a challenge for cytogenetic and genomic studies, due to the high number of similar size chromosomes and the simultaneous presence of hardly distinguishable paralogous elements. The karyotype of the Siberian sturgeon (Acipenser baerii) contains around 250 chromosomes and is remarkable for the presence of paralogs from two rounds of whole-genome duplications (WGD). In this study, we applied the sterlet-derived acipenserid satDNA-based whole chromosome-specific probes to analyze the Siberian sturgeon karyotype. We demonstrate that the last genome duplication event in the Siberian sturgeon was accompanied by the simultaneous expansion of several repetitive DNA families. Some of the repetitive probes serve as good cytogenetic markers distinguishing paralogous chromosomes and detecting ancestral syntenic regions, which underwent fusions and fissions. The tendency of minisatellite specificity for chromosome size groups previously observed in the sterlet genome is also visible in the Siberian sturgeon. We provide an initial physical chromosome map of the Siberian sturgeon genome supported by molecular markers. The application of these data will facilitate genomic studies in other recent polyploid sturgeon species.
KW  - Acipenser baerii
KW  - sturgeon karyotype
KW  - whole-genome duplication
KW  - paralogs
KW  - polyploidy
KW  - acipenserid minisatellite
KW  - satellite DNA
KW  - tandem repeats
Y1  - 2020
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-219371
SN  - 2073-4425
VL  - 11
IS  - 11
ER  -