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Institute
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ResearcherID
- D-1221-2009 (1)
SMART (Simple Modular Architecture Research Tool) is a web resource (https://smart.embl.de) for the identification and annotation of protein domains and the analysis of protein domain architectures. SMART version 9 contains manually curatedmodels formore than 1300 protein domains, with a topical set of 68 new models added since our last update article (1). All the new models are for diverse recombinase families and subfamilies and as a set they provide a comprehensive overview of mobile element recombinases namely transposase, integrase, relaxase, resolvase, cas1 casposase and Xer like cellular recombinase. Further updates include the synchronization of the underlying protein databases with UniProt (2), Ensembl (3) and STRING (4), greatly increasing the total number of annotated domains and other protein features available in architecture analysis mode. Furthermore, SMART's vector-based protein display engine has been extended and updated to use the latest web technologies and the domain architecture analysis components have been optimized to handle the increased number of protein features available.
Loos, Jacqueline ; Krauss, Jochen ; Lyons, Ashley ; Föst, Stephanie ; Ohlendorf, Constanze ; Racky, Severin ; Röder, Marina ; Hudel, Lennart ; Herfert, Volker ; Tscharntke, Teja
Across Europe, calcareous grasslands become increasingly fragmented and their quality deteriorates through abandonment and land use intensification, both affecting biodiversity. Here, we investigated local and landscape effects on diversity patterns of several taxonomic groups in a landscape of highly fragmented calcareous grassland remnants. We surveyed 31 grassland fragments near Göttingen, Germany, in spring and summer 2017 for vascular plants, butterflies and birds, with sampling effort adapted to fragment area. Through regression modelling, we tested relationships between species richness and fragment size (from 314 to 51,395 m\(^2\)), successional stage, habitat connectivity and the per cent cover of arable land in the landscape at several radii. We detected 283 plant species, 53 butterfly species and 70 bird species. Of these, 59 plant species, 19 butterfly species and 9 bird species were grassland specialists. Larger fragments supported twice the species richness of plants than small ones, and hosted more species of butterflies, but not of birds. Larger grassland fragments contained more grassland specialist plants, but not butterfly or bird specialists. Increasing amounts of arable land in the landscape from 20 to 90% was related to the loss of a third of species of plants, and less so, of butterflies, but not of birds. Per cent cover of arable land negatively correlated to richness of grassland specialist plants and butterflies, but positively to grassland specialist birds. We found no effect by successional stages and habitat connectivity. Our multi-taxa approach highlights the need for conservation management at the local scale, complemented by measures at the landscape scale.
Quantitative information is omnipresent in the world and a wide range of species has been shown to use quantities to optimize their decisions. While most studies have focused on vertebrates, a growing body of research demonstrates that also insects such as honeybees possess basic quantitative abilities that might aid them in finding profitable flower patches. However, it remains unclear if for insects, quantity is a salient feature relative to other stimulus dimensions, or if it is only used as a “last resort” strategy in case other stimulus dimensions are inconclusive. Here, we tested the stingless bee Trigona fuscipennis, a species representative of a vastly understudied group of tropical pollinators, in a quantity discrimination task. In four experiments, we trained wild, free-flying bees on stimuli that depicted either one or four elements. Subsequently, bees were confronted with a choice between stimuli that matched the training stimulus either in terms of quantity or another stimulus dimension. We found that bees were able to discriminate between the two quantities, but performance differed depending on which quantity was rewarded. Furthermore, quantity was more salient than was shape. However, quantity did not measurably influence the bees' decisions when contrasted with color or surface area. Our results demonstrate that just as honeybees, small-brained stingless bees also possess basic quantitative abilities. Moreover, invertebrate pollinators seem to utilize quantity not only as "last resort" but as a salient stimulus dimension. Our study contributes to the growing body of knowledge on quantitative cognition in invertebrate species and adds to our understanding of the evolution of numerical cognition.
Dunce, James M. ; Milburn, Amy E. ; Gurusaran, Manickam ; da Cruz, Irene ; Sen, Lee T. ; Benavente, Ricardo ; Davies, Owen R.
Meiotic chromosomes undergo rapid prophase movements, which are thought to facilitate the formation of inter-homologue recombination intermediates that underlie synapsis, crossing over and segregation. The meiotic telomere complex (MAJIN, TERB1, TERB2) tethers telomere ends to the nuclear envelope and transmits cytoskeletal forces via the LINC complex to drive these rapid movements. Here, we report the molecular architecture of the meiotic telomere complex through the crystal structure of MAJIN-TERB2, together with light and X-ray scattering studies of wider complexes. The MAJIN-TERB2 2:2 hetero-tetramer binds strongly to DNA and is tethered through long flexible linkers to the inner nuclear membrane and two TRF1-binding 1:1 TERB2-TERB1 complexes. Our complementary structured illumination microscopy studies and biochemical findings reveal a telomere attachment mechanism in which MAJIN-TERB2-TERB1 recruits telomere-bound TRF1, which is then displaced during pachytene, allowing MAJIN-TERB2-TERB1 to bind telomeric DNA and form a mature attachment plate.
Dörk, Thilo ; Peterlongo, Peter ; Mannermaa, Arto ; Bolla, Manjeet K. ; Wang, Qin ; Dennis, Joe ; Ahearn, Thomas ; Andrulis, Irene L. ; Anton-Culver, Hoda ; Arndt, Volker ; Aronson, Kristan J. ; Augustinsson, Annelie ; Beane Freeman, Laura E. ; Beckmann, Matthias W. ; Beeghly-Fadiel, Alicia ; Behrens, Sabine ; Bermisheva, Marina ; Blomqvist, Carl ; Bogdanova, Natalia V. ; Bojesen, Stig E. ; Brauch, Hiltrud ; Brenner, Hermann ; Burwinkel, Barbara ; Canzian, Federico ; Chan, Tsun L. ; Chang-Claude, Jenny ; Chanock, Stephen J. ; Choi, Ji-Yeob ; Christiansen, Hans ; Clarke, Christine L. ; Couch, Fergus J. ; Czene, Kamila ; Daly, Mary B. ; dos-Santos-Silva, Isabel ; Dwek, Miriam ; Eccles, Diana M. ; Ekici, Arif B. ; Eriksson, Mikael ; Evans, D. Gareth ; Fasching, Peter A. ; Figueroa, Jonine ; Flyger, Henrik ; Fritschi, Lin ; Gabrielson, Marike ; Gago-Dominguez, Manuela ; Gao, Chi ; Gapstur, Susan M. ; García-Closas, Montserrat ; García-Sáenz, José A. ; Gaudet, Mia M. ; Giles, Graham G. ; Goldberg, Mark S. ; Goldgar, David E. ; Guenél, Pascal ; Haeberle, Lothar ; Haimann, Christopher A. ; Håkansson, Niclas ; Hall, Per ; Hamann, Ute ; Hartman, Mikael ; Hauke, Jan ; Hein, Alexander ; Hillemanns, Peter ; Hogervorst, Frans B. L. ; Hooning, Maartje J. ; Hopper, John L. ; Howell, Tony ; Huo, Dezheng ; Ito, Hidemi ; Iwasaki, Motoki ; Jakubowska, Anna ; Janni, Wolfgang ; John, Esther M. ; Jung, Audrey ; Kaaks, Rudolf ; Kang, Daehee ; Kapoor, Pooja Middha ; Khusnutdinova, Elza ; Kim, Sung-Won ; Kitahara, Cari M. ; Koutros, Stella ; Kraft, Peter ; Kristensen, Vessela N. ; Kwong, Ava ; Lambrechts, Diether ; Le Marchand, Loic ; Li, Jingmei ; Lindström, Sara ; Linet, Martha ; Lo, Wing-Yee ; Long, Jirong ; Lophatananon, Artitaya ; Lubiński, Jan ; Manoochehri, Mehdi ; Manoukian, Siranoush ; Margolin, Sara ; Martinez, Elena ; Matsuo, Keitaro ; Mavroudis, Dimitris ; Meindl, Alfons ; Menon, Usha ; Milne, Roger L. ; Mohd Taib, Nur Aishah ; Muir, Kenneth ; Mulligan, Anna Marie ; Neuhausen, Susan L. ; Nevanlinna, Heli ; Neven, Patrick ; Newman, William G. ; Offit, Kenneth ; Olopade, Olufunmilayo I. ; Olshan, Andrew F. ; Olson, Janet E. ; Olsson, Håkan ; Park, Sue K. ; Park-Simon, Tjoung-Won ; Peto, Julian ; Plaseska-Karanfilska, Dijana ; Pohl-Rescigno, Esther ; Presneau, Nadege ; Rack, Brigitte ; Radice, Paolo ; Rashid, Muhammad U. ; Rennert, Gad ; Rennert, Hedy S. ; Romero, Atocha ; Ruebner, Matthias ; Saloustros, Emmanouil ; Schmidt, Marjanka K. ; Schmutzler, Rita K. ; Schneider, Michael O. ; Schoemaker, Minouk J. ; Scott, Christopher ; Shen, Chen-Yang ; Shu, Xiao-Ou ; Simard, Jaques ; Slager, Susan ; Smichkoska, Snezhana ; Southey, Melissa C. ; Spinelli, John J. ; Stone, Jennifer ; Surowy, Harald ; Swerdlow, Anthony J. ; Tamimi, Rulla M. ; Tapper, William J. ; Teo, Soo H. ; Terry, Mary Beth ; Toland, Amanda E. ; Tollenaar, Rob A. E. M. ; Torres, Diana ; Torres-Mejía, Gabriela ; Troester, Melissa A. ; Truong, Thérèse ; Tsugane, Shoichiro ; Untch, Michael ; Vachon, Celine M. ; van den Ouweland, Ans M. W. ; van Veen, Elke M. ; Vijai, Joseph ; Wendt, Camilla ; Wolk, Alicja ; Yu, Jyh-Cherng ; Zheng, Wei ; Ziogas, Argyrios ; Ziv, Elad ; Dunnig, Alison ; Pharaoh, Paul D. P. ; Schindler, Detlev ; Devilee, Peter ; Easton, Douglas F.
Fanconi anemia (FA) is a genetically heterogeneous disorder with 22 disease-causing genes reported to date. In some FA genes, monoallelic mutations have been found to be associated with breast cancer risk, while the risk associations of others remain unknown. The gene for FA type C, FANCC, has been proposed as a breast cancer susceptibility gene based on epidemiological and sequencing studies. We used the Oncoarray project to genotype two truncating FANCC variants (p.R185X and p.R548X) in 64,760 breast cancer cases and 49,793 controls of European descent. FANCC mutations were observed in 25 cases (14 with p.R185X, 11 with p.R548X) and 26 controls (18 with p.R185X, 8 with p.R548X). There was no evidence of an association with the risk of breast cancer, neither overall (odds ratio 0.77, 95%CI 0.44–1.33, p = 0.4) nor by histology, hormone receptor status, age or family history. We conclude that the breast cancer risk association of these two FANCC variants, if any, is much smaller than for BRCA1, BRCA2 or PALB2 mutations. If this applies to all truncating variants in FANCC it would suggest there are differences between FA genes in their roles on breast cancer risk and demonstrates the merit of large consortia for clarifying risk associations of rare variants.
Dammert, Marcel A. ; Brägelmann, Johannes ; Olsen, Rachelle R. ; Böhm, Stefanie ; Monhasery, Niloufar ; Whitney, Christopher P. ; Chalishazar, Milind D. ; Tumbrink, Hannah L. ; Guthrie, Matthew R. ; Klein, Sebastian ; Ireland, Abbie S. ; Ryan, Jeremy ; Schmitt, Anna ; Marx, Annika ; Ozretić, Luka ; Castiglione, Roberta ; Lorenz, Carina ; Jachimowicz, Ron D. ; Wolf, Elmar ; Thomas, Roman K. ; Poirier, John T. ; Büttner, Reinhard ; Sen, Triparna ; Byers, Lauren A. ; Reinhardt, H. Christian ; Letai, Anthony ; Oliver, Trudy G. ; Sos, Martin L.
MYC paralogs are frequently activated in small cell lung cancer (SCLC) but represent poor drug targets. Thus, a detailed mapping of MYC-paralog-specific vulnerabilities may help to develop effective therapies for SCLC patients. Using a unique cellular CRISPR activation model, we uncover that, in contrast to MYCN and MYCL, MYC represses BCL2 transcription via interaction with MIZ1 and DNMT3a. The resulting lack of BCL2 expression promotes sensitivity to cell cycle control inhibition and dependency on MCL1. Furthermore, MYC activation leads to heightened apoptotic priming, intrinsic genotoxic stress and susceptibility to DNA damage checkpoint inhibitors. Finally, combined AURK and CHK1 inhibition substantially prolongs the survival of mice bearing MYC-driven SCLC beyond that of combination chemotherapy. These analyses uncover MYC-paralog-specific regulation of the apoptotic machinery with implications for genotype-based selection of targeted therapeutics in SCLC patients.
Steuer Costa, Wagner ; Van der Auwera, Petrus ; Glock, Caspar ; Liewald, Jana F. ; Bach, Maximilian ; Schüler, Christina ; Wabnig, Sebastian ; Oranth, Alexandra ; Masurat, Florentin ; Bringmann, Henrik ; Schoofs, Liliane ; Stelzer, Ernst H. K. ; Fischer, Sabine C. ; Gottschalk, Alexander
Animals must slow or halt locomotion to integrate sensory inputs or to change direction. In Caenorhabditis elegans, the GABAergic and peptidergic neuron RIS mediates developmentally timed quiescence. Here, we show RIS functions additionally as a locomotion stop neuron. RIS optogenetic stimulation caused acute and persistent inhibition of locomotion and pharyngeal pumping, phenotypes requiring FLP-11 neuropeptides and GABA. RIS photoactivation allows the animal to maintain its body posture by sustaining muscle tone, yet inactivating motor neuron oscillatory activity. During locomotion, RIS axonal Ca2+ signals revealed functional compartmentalization: Activity in the nerve ring process correlated with locomotion stop, while activity in a branch correlated with induced reversals. GABA was required to induce, and FLP-11 neuropeptides were required to sustain locomotion stop. RIS attenuates neuronal activity and inhibits movement, possibly enabling sensory integration and decision making, and exemplifies dual use of one cell across development in a compact nervous system.
Osmanoglu, Özge ; Gupta, Shishir K. ; Almasi, Anna ; Yagci, Seray ; Srivastava, Mugdha ; Araujo, Gabriel H. M. ; Nagy, Zoltan ; Balkenhol, Johannes ; Dandekar, Thomas
Introduction
Pro-thrombotic events are one of the prevalent causes of intensive care unit (ICU) admissions among COVID-19 patients, although the signaling events in the stimulated platelets are still unclear.
Methods
We conducted a comparative analysis of platelet transcriptome data from healthy donors, ICU, and non-ICU COVID-19 patients to elucidate these mechanisms. To surpass previous analyses, we constructed models of involved networks and control cascades by integrating a global human signaling network with transcriptome data. We investigated the control of platelet hyperactivation and the specific proteins involved.
Results
Our study revealed that control of the platelet network in ICU patients is significantly higher than in non-ICU patients. Non-ICU patients require control over fewer proteins for managing platelet hyperactivity compared to ICU patients. Identification of indispensable proteins highlighted key subnetworks, that are targetable for system control in COVID-19-related platelet hyperactivity. We scrutinized FDA-approved drugs targeting indispensable proteins and identified fostamatinib as a potent candidate for preventing thrombosis in COVID-19 patients.
Discussion
Our findings shed light on how SARS-CoV-2 efficiently affects host platelets by targeting indispensable and critical proteins involved in the control of platelet activity. We evaluated several drugs for specific control of platelet hyperactivity in ICU patients suffering from platelet hyperactivation. The focus of our approach is repurposing existing drugs for optimal control over the signaling network responsible for platelet hyperactivity in COVID-19 patients. Our study offers specific pharmacological recommendations, with drug prioritization tailored to the distinct network states observed in each patient condition. Interactive networks and detailed results can be accessed at https://fostamatinib.bioinfo-wuerz.eu/.
Carradec, Quentin ; Pelletier, Eric ; Da Silva, Corinne ; Alberti, Adriana ; Seeleuthner, Yoann ; Blanc-Mathieu, Romain ; Lima-Mendez, Gipsi ; Rocha, Fabio ; Tirichine, Leila ; Labadie, Karine ; Kirilovsky, Amos ; Bertrand, Alexis ; Engelen, Stefan ; Madoui, Mohammed-Amin ; Méheust, Raphaël ; Poulain, Julie ; Romac, Sarah ; Richter, Daniel J. ; Yoshikawa, Genki ; Dimier, Céline ; Kandels-Lewis, Stefanie ; Picheral, Marc ; Searson, Sarah ; Jaillon, Olivier ; Aury, Jean-Marc ; Karsenti, Eric ; Sullivan, Matthew B. ; Sunagawa, Shinichi ; Bork, Peer ; Not, Fabrice ; Hingamp, Pascal ; Raes, Jeroen ; Guidi, Lionel ; Ogata, Hiroyuki ; de Vargas, Colomban ; Iudicone, Daniele ; Bowler, Chris ; Wincker, Patrick
While our knowledge about the roles of microbes and viruses in the ocean has increased tremendously due to recent advances in genomics and metagenomics, research on marine microbial eukaryotes and zooplankton has benefited much less from these new technologies because of their larger genomes, their enormous diversity, and largely unexplored physiologies. Here, we use a metatranscriptomics approach to capture expressed genes in open ocean Tara Oceans stations across four organismal size fractions. The individual sequence reads cluster into 116 million unigenes representing the largest reference collection of eukaryotic transcripts from any single biome. The catalog is used to unveil functions expressed by eukaryotic marine plankton, and to assess their functional biogeography. Almost half of the sequences have no similarity with known proteins, and a great number belong to new gene families with a restricted distribution in the ocean. Overall, the resource provides the foundations for exploring the roles of marine eukaryotes in ocean ecology and biogeochemistry.
HyphaTracker: An ImageJ toolbox for time-resolved analysis of spore germination in filamentous fungi
(2018)
The dynamics of early fungal development and its interference with physiological signals and environmental factors is yet poorly understood. Especially computational analysis tools for the evaluation of the process of early spore germination and germ tube formation are still lacking. For the time-resolved analysis of conidia germination of the filamentous ascomycete Fusarium fujikuroi we developed a straightforward toolbox implemented in ImageJ. It allows for processing of microscopic acquisitions (movies) of conidial germination starting with drift correction and data reduction prior to germling analysis. From the image time series germling related region of interests (ROIs) are extracted, which are analysed for their area, circularity, and timing. ROIs originating from germlings crossing other hyphae or the image boundaries are omitted during analysis. Each conidium/hypha is identified and related to its origin, thus allowing subsequent categorization. The efficiency of HyphaTracker was proofed and the accuracy was tested on simulated germlings at different signal-to-noise ratios. Bright-field microscopic images of conidial germination of rhodopsin-deficient F. fujikuroi mutants and their respective control strains were analysed with HyphaTracker. Consistent with our observation in earlier studies the CarO deficient mutant germinated earlier and grew faster than other, CarO expressing strains.