by Kashyap Chhatbar, Justyna Cholewa-Waclaw, Ruth Shah, Adrian Bird, Guido Sanguinetti MeCP2 is an abundant protein in mature nerve cells, where it binds to DNA sequences containing methylated cytosine. Mutations in the MECP2 gene cause the severe neurological disorder Rett syndrome (RTT), provoking intensive study of the underlying molecular mechanisms. Multiple functions have been proposed, one of which involves a regulatory role in splicing. Here we leverage the recent availability of high-quality...
8h
by Sarah N. Ruckman, Michelle M. Jonika, Claudio Casola, Heath Blackmon Despite the fundamental role of centromeres two different types are observed across plants and animals. Monocentric chromosomes possess a single region that function as the centromere while in holocentric chromosomes centromere activity is spread across the entire chromosome. Proper segregation may fail in species with monocentric chromosomes after a fusion or fission, which may lead to chromosomes with no centromere or...
8h
by Fredrika Åsenius, Tyler J. Gorrie-Stone, Ama Brew, Yasmin Panchbhaya, Elizabeth Williamson, Leonard C. Schalkwyk, Vardhman K. Rakyan, Michelle L. Holland, Sarah J. Marzi, David J. Williams Epidemiological research suggests that paternal obesity may increase the risk of fathering small for gestational age offspring. Studies in non-human mammals indicate that such associations could be mediated by DNA methylation changes in spermatozoa that influence offspring development in utero. Human obesity...
8h
by Suzanne Vogelezang, Jonathan P. Bradfield, Tarunveer S. Ahluwalia, John A. Curtin, Timo A. Lakka, Niels Grarup, Markus Scholz, Peter J. van der Most, Claire Monnereau, Evie Stergiakouli, Anni Heiskala, Momoko Horikoshi, Iryna O. Fedko, Natalia Vilor-Tejedor, Diana L. Cousminer, Marie Standl, Carol A. Wang, Jorma Viikari, Frank Geller, Carmen Íñiguez, Niina Pitkänen, Alessandra Chesi, Jonas Bacelis, Loic Yengo, Maties Torrent, Ioanna Ntalla, Øyvind Helgeland, Saskia Selzam, Judith M. Vonk, Mohammed...
1d
by James A. Watson, Aimee R. Taylor, Elizabeth A. Ashley, Arjen Dondorp, Caroline O. Buckee, Nicholas J. White, Chris C. Holmes Genetic surveillance of malaria parasites supports malaria control programmes, treatment guidelines and elimination strategies. Surveillance studies often pose questions about malaria parasite ancestry (e.g. how antimalarial resistance has spread) and employ statistical methods that characterise parasite population structure. Many of the methods used to characterise...
4d
by Katalin Goda, Yaprak Dönmez-Cakil, Szabolcs Tarapcsák, Gábor Szalóki, Dániel Szöllősi, Zahida Parveen, Dóra Türk, Gergely Szakács, Peter Chiba, Thomas Stockner Several ABC exporters carry a degenerate nucleotide binding site (NBS) that is unable to hydrolyze ATP at a rate sufficient for sustaining transport activity. A hallmark of a degenerate NBS is the lack of the catalytic glutamate in the Walker B motif in the nucleotide binding domain (NBD). The multidrug resistance transporter ABCB1...
5d
by Alexander C. West, Marianne Iversen, Even H. Jørgensen, Simen R. Sandve, David G. Hazlerigg, Shona H. Wood Across taxa, circadian control of physiology and behavior arises from cell-autonomous oscillations in gene expression, governed by a networks of so-called ‘clock genes’, collectively forming transcription-translation feedback loops. In modern vertebrates, these networks contain multiple copies of clock gene family members, which arose through whole genome duplication (WGD) events during...
5d
by Robert L. Baker, Wen Fung Leong, Marcus T. Brock, Matthew J. Rubin, R. J. Cody Markelz, Stephen Welch, Julin N. Maloof, Cynthia Weinig
5d
by Robert M. Erdmann, Colette L. Picard RNA-directed DNA methylation (RdDM) is a biological process in which non-coding RNA molecules direct the addition of DNA methylation to specific DNA sequences. The RdDM pathway is unique to plants, although other mechanisms of RNA-directed chromatin modification have also been described in fungi and animals. To date, the RdDM pathway is best characterized within angiosperms (flowering plants), and particularly within the model plant Arabidopsis thaliana....
5d
by Aleesa J. Schlientz, Bruce Bowerman The requirements for oocyte meiotic cytokinesis during polar body extrusion are not well understood. In particular, the relationship between the oocyte meiotic spindle and polar body contractile ring dynamics remains largely unknown. We have used live cell imaging and spindle assembly defective mutants lacking the function of CLASP/CLS-2, kinesin-12/KLP-18, or katanin/MEI-1 to investigate the relationship between meiotic spindle structure and polar body...
6d
by Aletheia Atzinger, Jeffrey G. Lawrence A ~10–11 bp periodicity in dinucleotides imparting DNA bending, with shorter periods found in organisms with positively-supercoiled DNA and longer periods found in organisms with negatively-supercoiled DNA, was previously suggested to assist in DNA compaction. However, when measured with more robust methods, variation in the observed periods between organisms with different growth temperatures is not consistent with that hypothesis. We demonstrate that...
1w
by Yann Bourgeois, Robert Ruggiero, Imtiyaz Hariyani, Stéphane Boissinot The interactions between transposable elements (TEs) and their hosts constitute one of the most profound co-evolutionary processes found in nature. The population dynamics of TEs depends on factors specific to each TE families, such as the rate of transposition and insertional preference, the demographic history of the host and the genomic landscape. How these factors interact has yet to be investigated holistically. Here...
2w
by Sarel J. Urso, Marcella Comly, John A. Hanover, Todd Lamitina The conserved O-GlcNAc transferase OGT O-GlcNAcylates serine and threonine residues of intracellular proteins to regulate their function. OGT is required for viability in mammalian cells, but its specific roles in cellular physiology are poorly understood. Here we describe a conserved requirement for OGT in an essential aspect of cell physiology: the hypertonic stress response. Through a forward genetic screen in Caenorhabditis...
2w
by Joe Weber, Zeynep Kabakci, Soumya Chaurasia, Erich Brunner, Christian F. Lehner Regular chromosome segregation during the first meiotic division requires prior pairing of homologous chromosomes into bivalents. During canonical meiosis, linkage between homologous chromosomes is maintained until late metaphase I by chiasmata resulting from meiotic recombination in combination with distal sister chromatid cohesion. Separase-mediated elimination of cohesin from chromosome arms at the end of metaphase...
2w
by Rebecca L. Adams, Susan R. Wente In Saccharomyces cerevisiae, the mRNA export receptor Mex67 is recruited to mature nuclear transcripts to mediate mRNA export through the nuclear pore complex (NPC) to the cytoplasm. Mex67 binds transcripts through adaptor proteins such as the poly(A) binding protein Nab2. When a transcript reaches the cytoplasmic face of the NPC, the DEAD-box protein Dbp5 acts to induce a local structural change to release Nab2 and Mex67 in an essential process termed mRNP...
2w
by Elena Díaz-Santiago, Fernando M. Jabato, Elena Rojano, Pedro Seoane, Florencio Pazos, James R. Perkins, Juan A. G. Ranea Genetic and molecular analysis of rare disease is made difficult by the small numbers of affected patients. Phenotypic comorbidity analysis can help rectify this by combining information from individuals with similar phenotypes and looking for overlap in terms of shared genes and underlying functional systems. However, few studies have combined comorbidity analysis with...
2w
by Elsie E. Adams, Qiutao He, Bruce D. McKee
2w
by Jukka-Pekka Verta, Paul Vincent Debes, Nikolai Piavchenko, Annukka Ruokolainen, Outi Ovaskainen, Jacqueline Emmanuel Moustakas-Verho, Seija Tillanen, Noora Parre, Tutku Aykanat, Jaakko Erkinaro, Craig Robert Primmer A major goal in biology is to understand how evolution shapes variation in individual life histories. Genome-wide association studies have been successful in uncovering genome regions linked with traits underlying life history variation in a range of species. However, lack of...
2w
by Rebecca J. Androwski, Nadeem Asad, Janet G. Wood, Allison Hofer, Steven Locke, Cassandra M. Smith, Becky Rose, Nathan E. Schroeder Stress-induced changes to the dendritic architecture of neurons have been demonstrated in numerous mammalian and invertebrate systems. Remodeling of dendrites varies tremendously among neuron types. During the stress-induced dauer stage of Caenorhabditis elegans, the IL2 neurons arborize to cover the anterior body wall. In contrast, the FLP neurons arborize to...
2w
by Valentina Stein, Bernhard Blank-Landeshammer, Kira Müntjes, Ramona Märker, Ines Teichert, Michael Feldbrügge, Albert Sickmann, Ulrich Kück The striatin-interacting phosphatase and kinase (STRIPAK) multi-subunit signaling complex is highly conserved within eukaryotes. In fungi, STRIPAK controls multicellular development, morphogenesis, pathogenicity, and cell-cell recognition, while in humans, certain diseases are related to this signaling complex. To date, phosphorylation and dephosphorylation...
2w
by Yuta Hiraike, Hironori Waki, Kana Miyake, Takahito Wada, Misato Oguchi, Kaede Saito, Shuichi Tsutsumi, Hiroyuki Aburatani, Toshimasa Yamauchi, Takashi Kadowaki The transcription factor nuclear factor I-A (NFIA) is a regulator of brown adipocyte differentiation. Here we show that the C-terminal 17 amino acid residues of NFIA (which we call pro#3 domain) are required for the transcriptional activity of NFIA. Full-length NFIA—but not deletion mutant lacking pro#3 domain—rescued impaired expression...
2w
by Tomoaki Mizuno, Kei Muroi, Kenji Irie Autophagy is a fundamental process responsible for degradation and recycling of intracellular contents. In the budding yeast, non-selective macroautophagy and microautophagy of the endoplasmic reticulum (ER) are caused by ER stress, the circumstance where aberrant proteins accumulate in the ER. The more recent study showed that protein aggregation in the ER initiates ER-selective macroautophagy, referred to as ER-phagy; however, the mechanisms by which...
3w
by Tingting Gai, Xiaoling Tong, Minjin Han, Chunlin Li, Chunyan Fang, Yunlong Zou, Hai Hu, Hui Xiang, Zhonghuai Xiang, Cheng Lu, Fangyin Dai Many insects spin cocoons to protect the pupae from unfavorable environments and predators. After emerging from the pupa, the moths must escape from the sealed cocoons. Previous works identified cocoonase as the active enzyme loosening the cocoon to form an escape-hatch. Here, using bioinformatics tools, we show that cocoonase is specific to Lepidoptera...
3w
by Victor N. Rivas, K. Gary Magdesian, Sophia Fagan, Nathan M. Slovis, Daniela Luethy, Laura H. Javsicas, Brian G. Caserto, Andrew D. Miller, Anna R. Dahlgren, Janel Peterson, Erin N. Hales, Sichong Peng, Katherine D. Watson, Mustafa K. Khokha, Carrie J. Finno Idiopathic hypocalcemia in Thoroughbred (TB) foals causes tetany and seizures and is invariably fatal. Based upon the similarity of this disease with human familial hypoparathyroidism and occurrence only in the TB breed, we conducted a...
3w
by Ivana Gaziova, Michael Gazi, Jordan Mar, Krishna Moorthi Bhat Neuronal precursor cells undergo self-renewing and non-self-renewing asymmetric divisions to generate a large number of neurons of distinct identities. In Drosophila, primary precursor neuroblasts undergo a varying number of self-renewing asymmetric divisions, with one known exception, the MP2 lineage, which undergoes just one terminal asymmetric division similar to the secondary precursor cells. The mechanism and the genes that...
3w
by Gurmannat Kalra, Beatrice Milon, Alex M. Casella, Brian R. Herb, Elizabeth Humphries, Yang Song, Kevin P. Rose, Ronna Hertzano, Seth A. Ament Age-related hearing impairment (ARHI), one of the most common medical conditions, is strongly heritable, yet its genetic causes remain largely unknown. We conducted a meta-analysis of GWAS summary statistics from multiple hearing-related traits in the UK Biobank (n = up to 330,759) and identified 31 genome-wide significant risk loci for self-reported...
3w
by Yun Gao, Yun-Cai Liu, Shun-Ze Jia, Yan-Ting Liang, Yu Tang, Yu-Song Xu, Hideki Kawasaki, Hua-Bing Wang The complex stripes and patterns of insects play key roles in behavior and ecology. However, the fine-scale regulation mechanisms underlying pigment formation and morphological divergence remain largely unelucidated. Here we demonstrated that imaginal disc growth factor (IDGF) maintains cuticle structure and controls melanization in spot pattern formation of Bombyx mori. Moreover, our knockout...
3w
by Liying Guan, Zhigao Zhan, Yongzhi Yang, Yue Miao, Xun Huang, Mei Ding ER stress occurs in many physiological and pathological conditions. However, how chronic ER stress is alleviated in specific cells in an intact organism is an outstanding question. Here, overexpressing the gap junction protein UNC-9 (Uncoordinated) in C. elegans neurons triggers the Ire1-Xbp1-mediated stress response in an age-dependent and cell-autonomous manner. The p38 MAPK PMK-3 regulates the chronic stress through...
3w
by Ya-Yun Wang, Chih-Chun Ke, Yen-Lin Chen, Yu-Hua Lin, I-Shing Yu, Wei-Chi Ku, Moira K. O’Bryan, Ying-Hung Lin Approximately 2–15% of couples experience infertility, and around half of these cases are attributed to male infertility. We previously identified TBC1D21 as a sterility-related RabGAP gene derived from infertile men. However, the in vivo function of TBC1D21 in male fertility remains unclear. Here, we show that loss of Tbc1d21 in mice resulted in male infertility, characterized by...
3w
by Guang-Jie Zhu, Sihao Gong, Deng-Bin Ma, Tao Tao, Wei-Qi He, Linqing Zhang, Fang Wang, Xiao-Yun Qian, Han Zhou, Chi Fan, Pei Wang, Xin Chen, Wei Zhao, Jie Sun, Huaqun Chen, Ye Wang, Xiang Gao, Jian Zuo, Min-Sheng Zhu, Xia Gao, Guoqiang Wan Genetic hearing loss is a common health problem with no effective therapy currently available. DFNA15, caused by mutations of the transcription factor POU4F3, is one of the most common forms of autosomal dominant non-syndromic deafness. In this study, we...
3w
by Christian Groß, Chiara Bortoluzzi, Dick de Ridder, Hendrik-Jan Megens, Martien A. M. Groenen, Marcel Reinders, Mirte Bosse The availability of genomes for many species has advanced our understanding of the non-protein-coding fraction of the genome. Comparative genomics has proven itself to be an invaluable approach for the systematic, genome-wide identification of conserved non-protein-coding elements (CNEs). However, for many non-mammalian model species, including chicken, our capability...
3w
by Olena Poretska, Saiqi Yang, Delphine Pitorre, Brigitte Poppenberger, Tobias Sieberer Higher plants can continuously form new organs by the sustained activity of pluripotent stem cells. These stem cells are embedded in meristems, where they produce descendants, which undergo cell proliferation and differentiation programs in a spatiotemporally-controlled manner. Under certain conditions, pluripotency can be reestablished in descending cells and this reversion in cell fate appears to be actively...
3w
by Jie Yuan, Henry Xing, Alexandre Louis Lamy, The Schizophrenia Working Group of the Psychiatric Genomics Consortium , Todd Lencz, Itsik Pe’er Evidence from both GWAS and clinical observation has suggested that certain psychiatric, metabolic, and autoimmune diseases are heterogeneous, comprising multiple subtypes with distinct genomic etiologies and Polygenic Risk Scores (PRS). However, the presence of subtypes within many phenotypes is frequently unknown. We present CLiP (Correlated Liability...
4w
by M. Reza Sailani, Fereshteh Jahanbani, Charles W. Abbott, Hayan Lee, Amin Zia, Shannon Rego, Juliane Winkelmann, Franziska Hopfner, Tahir N. Khan, Nicholas Katsanis, Stefanie H. Müller, Daniela Berg, Katherine M. Lyman, Christian Mychajliw, Günther Deuschl, Jonathan A. Bernstein, Gregor Kuhlenbäumer, Michael P. Snyder Essential tremor (ET) is the most common adult-onset movement disorder. In the present study, we performed whole exome sequencing of a large ET-affected family (10 affected and...
4w
by Diana K. Summers, Daniela S. Perry, Beiduo Rao, Hiten D. Madhani Qsp1 is a secreted quorum sensing peptide required for virulence of the fungal meningitis pathogen Cryptococcus neoformans. Qsp1 functions to control cell wall integrity in vegetatively growing cells and also functions in mating. Rather than acting on a cell surface receptor, Qsp1 is imported to act intracellularly via the predicted oligopeptide transporter Opt1. Here, we identify a transcription factor network as a target of...
4w
by Hai Wei, Eric J. Lambie, Daniel S. Osório, Ana X. Carvalho, Barbara Conradt The mechanism(s) through which mammalian kinase MELK promotes tumorigenesis is not understood. We find that the C. elegans orthologue of MELK, PIG-1, promotes apoptosis by partitioning an anti-apoptotic factor. The C. elegans NSM neuroblast divides to produce a larger cell that differentiates into a neuron and a smaller cell that dies. We find that in this context, PIG-1 MELK is required for partitioning of CES-1...
4w
by Frank R. Wendt, Carolina Muniz Carvalho, Gita A. Pathak, Joel Gelernter, Renato Polimanti The polygenic nature and the contribution of common genetic variation to autism spectrum disorder (ASD) allude to a high degree of pleiotropy between ASD and other psychiatric and behavioral traits. In a pleiotropic system, a single genetic variant contributes small effects to several phenotypes or disorders. While analyzed broadly, there is a paucity of research studies investigating the shared genetic...
4w
by Yasuhiro Fujiwara, Yuki Horisawa-Takada, Erina Inoue, Naoki Tani, Hiroki Shibuya, Sayoko Fujimura, Ryo Kariyazono, Toyonori Sakata, Kunihiro Ohta, Kimi Araki, Yuki Okada, Kei-ichiro Ishiguro During meiotic prophase, sister chromatids are organized into axial element (AE), which underlies the structural framework for the meiotic events such as meiotic recombination and homolog synapsis. HORMA domain-containing proteins (HORMADs) localize along AE and play critical roles in the regulation of...
4w
by Daniel J. Mullen, Chunli Yan, Diane S. Kang, Beiyun Zhou, Zea Borok, Crystal N. Marconett, Peggy J. Farnham, Ite A. Offringa, Suhn Kyong Rhie Lung cancer is the leading cause of cancer-related death and lung adenocarcinoma is its most common subtype. Although genetic alterations have been identified as drivers in subsets of lung adenocarcinoma, they do not fully explain tumor development. Epigenetic alterations have been implicated in the pathogenesis of tumors. To identify epigenetic alterations...
5w
by Yan Lai, Xueqing Maggie Lu, Josquin Daron, Songqin Pan, Jianqiang Wang, Wei Wang, Tokuji Tsuchiya, Eric Holub, John M. McDowell, R. Keith Slotkin, Karine G. Le Roch, Thomas Eulgem Plant NLR-type receptors serve as sensitive triggers of host immunity. Their expression has to be well-balanced, due to their interference with various cellular processes and dose-dependency of their defense-inducing activity. A genetic “arms race” with fast-evolving pathogenic microbes requires plants to constantly...
5w
by Zong Miao, Marcus Alvarez, Arthur Ko, Yash Bhagat, Elior Rahmani, Brandon Jew, Sini Heinonen, Linda Liliana Muñoz-Hernandez, Miguel Herrera-Hernandez, Carlos Aguilar-Salinas, Teresa Tusie-Luna, Karen L. Mohlke, Markku Laakso, Kirsi H. Pietiläinen, Eran Halperin, Päivi Pajukanta Reverse causality has made it difficult to establish the causal directions between obesity and prediabetes and obesity and insulin resistance. To disentangle whether obesity causally drives prediabetes and insulin...
5w
by Aviva Levitas, Emad Muhammad, Yuan Zhang, Isaac Perea Gil, Ricardo Serrano, Nashielli Diaz, Maram Arafat, Alexandra A. Gavidia, Michael S. Kapiloff, Mark Mercola, Yoram Etzion, Ruti Parvari, Ioannis Karakikes Dilated cardiomyopathy (DCM) is a common cause of heart failure and sudden cardiac death. It has been estimated that up to half of DCM cases are hereditary. Mutations in more than 50 genes, primarily autosomal dominant, have been reported. Although rare, recessive mutations are thought...
5w
by Ojas Deshpande, Raquel Z. Lara, Oliver R. Zhang, Dorothy Concepcion, Bruce A. Hamilton Interpreting rare variants remains a challenge in personal genomics, especially for disorders with several causal genes and for genes that cause multiple disorders. ZNF423 encodes a transcriptional regulatory protein that intersects several developmental pathways. ZNF423 has been implicated in rare neurodevelopmental disorders, consistent with midline brain defects in Zfp423-mutant mice, but pathogenic...
5w
by Biaty Raymond, Loic Yengo, Roy Costilla, Chris Schrooten, Aniek C. Bouwman, Ben J. Hayes, Roel F. Veerkamp, Peter M. Visscher Genome-Wide Association Studies (GWAS) in large human cohorts have identified thousands of loci associated with complex traits and diseases. For identifying the genes and gene-associated variants that underlie complex traits in livestock, especially where sample sizes are limiting, it may help to integrate the results of GWAS for equivalent traits in humans as prior...
5w
by Marcela Montes de Oca, Fabian de Labastida Rivera, Clay Winterford, Teija C. M. Frame, Susanna S. Ng, Fiona H. Amante, Chelsea L. Edwards, Luzia Bukali, Yulin Wang, Jude E. Uzonna, Rachel D. Kuns, Ping Zhang, Agnieszka Kabat, Ramon I. Klein Geltink, Edward J. Pearce, Geoffrey R. Hill, Christian R. Engwerda Inflammation is critical for controlling pathogens, but also responsible for symptoms of infectious diseases. IL-27 is an important regulator of inflammation and can limit development of...
11h
by Yan Zhang, Tong Chen, Sajith Raghunandanan, Xuwu Xiang, Jing Yang, Qiang Liu, Diane G. Edmondson, Steven J. Norris, X. Frank Yang, Yongliang Lou Borrelia burgdorferi, the Lyme disease pathogen causes persistent infection by evading the host immune response. Differential expression of the surface-exposed lipoprotein VlsE that undergoes antigenic variation is a key immune evasion strategy employed by B. burgdorferi. Most studies focused on the mechanism of VlsE antigen variation, but little...
11h
by Jaime L. Jensen, Shavait Yamini, Arne Rietsch, Benjamin W. Spiller Type III protein secretion systems (T3SS) deliver effector proteins from the Gram-negative bacterial cytoplasm into a eukaryotic host cell through a syringe-like, multi-protein nanomachine. Cytosolic components of T3SS include a portion of the export apparatus, which traverses the inner membrane and features the opening of the secretion channel, and the sorting complex for substrate recognition and for providing the energetics...
11h
by Heverton Leandro Carneiro Dutra, Mark Anthony Deehan, Horacio Frydman Wolbachia is an intracellular bacterial symbiont of arthropods notorious for inducing many reproductive manipulations that foster its dissemination. Wolbachia affects many aspects of host biology, including metabolism, longevity and physiology, being described as a nutrient provisioning or metabolic parasite, depending on the host-microbe association. Sirtuins (SIRTs) are a family of NAD+-dependent post-translational regulatory...
11h
by Jishnu Das, Anush Devadhasan, Caitlyn Linde, Tom Broge, Jessica Sassic, Max Mangano, Sean O'Keefe, Todd Suscovich, Hendrik Streeck, Alivelu Irrinki, Chris Pohlmeyer, Gundula Min-Oo, Shu Lin, Joshua A. Weiner, Thomas Cihlar, Margaret E. Ackerman, Boris Julg, Steven Deeks, Douglas A. Lauffenburger, Galit Alter While antiretroviral therapy (ART) has effectively revolutionized HIV care, the virus is never fully eliminated. Instead, immune dysfunction, driven by persistent non-specific immune...
11h
by Zhenyu Zhang, Haili Zhang, Ling Xu, Xing Guo, Wenfei Wang, Yujie Ji, Chaohui Lin, Yujie Wang, Xiaojun Wang The influenza B virus (IBV) causes seasonal influenza and has accounted for an increasing proportion of influenza outbreaks. IBV mainly causes human infections and has not been found to spread in poultry. The replication mechanism and the determinants of interspecies transmission of IBV are largely unknown. In this study, we found that the host ANP32 proteins are required for the function...
1d
by Swarnalok De, Maija Pollari, Markku Varjosalo, Kristiina Mäkinen In this study, we investigated the significance of a conserved five-amino acid motif ‘AELPR’ in the C-terminal region of helper component–proteinase (HCPro) for potato virus A (PVA; genus Potyvirus) infection. This motif is a putative interaction site for WD40 domain-containing proteins, including VARICOSE (VCS). We abolished the interaction site in HCPro by replacing glutamic acid (E) and arginine (R) with alanines (A) to generate...
1d
by Gregory L. Sousa, Ritika Bishnoi, Richard H. G. Baxter, Michael Povelones The arthropod melanization immune response is activated by extracellular protease cascades predominantly comprised of CLIP-domain serine proteases (CLIP-SPs) and serine protease homologs (CLIP-SPHs). In the malaria vector, Anopheles gambiae, the CLIP-SPHs SPCLIP1, CLIPA8, and CLIPA28 form the core of a hierarchical cascade downstream of mosquito complement that is required for microbial melanization. However, our understanding...
1d
by Caroline Peron-Cane, José-Carlos Fernandez, Julien Leblanc, Laure Wingertsmann, Arnaud Gautier, Nicolas Desprat, Alice Lebreton Real-time imaging of bacterial virulence factor dynamics is hampered by the limited number of fluorescent tools suitable for tagging secreted effectors. Here, we demonstrated that the fluorogenic reporter FAST could be used to tag secreted proteins, and we implemented it to monitor infection dynamics in epithelial cells exposed to the human pathogen Listeria monocytogenes...
1d
by Alexander Lercher, Alexandra M. Popa, Csilla Viczenczova, Lindsay Kosack, Kristaps Klavins, Benedikt Agerer, Christiane A. Opitz, Tobias V. Lanz, Michael Platten, Andreas Bergthaler The liver is a central regulator of metabolic homeostasis and serum metabolite levels. Hepatocytes are the functional units of the liver parenchyma and not only responsible for turnover of biomolecules but also act as central immune signaling platforms. Hepatotropic viruses infect liver tissue, resulting in inflammatory...
1d
by Julia Holzerland, Lucie Fénéant, Logan Banadyga, Julia E. Hölper, Michael R. Knittler, Allison Groseth Pathogenicity often differs dramatically among even closely related arenavirus species. For instance, Junín virus (JUNV), the causative agent of Argentine hemorrhagic fever (AHF), is closely related to Tacaribe virus (TCRV), which is normally avirulent in humans. While little is known about how host cell pathways are regulated in response to arenavirus infection, or how this contributes...
1d
by Cormac M. Kinsella, Pauline Dianne Santos, Ignacio Postigo-Hidalgo, Alba Folgueiras-González, Tim Casper Passchier, Kevin P. Szillat, Joyce Odeke Akello, Beatriz Álvarez-Rodríguez, Joan Martí-Carreras The first cluster of patients suffering from coronavirus disease 2019 (COVID-19) was identified on December 21, 2019, and as of July 29, 2020, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections have been linked with 664,333 deaths and number at least 16,932,996 worldwide....
4d
by Mingming Yang, Shuangshuang Ren, Danyu Shen, Nianda Yang, Bingxin Wang, Sen Han, Xi Shen, Shan-Ho Chou, Guoliang Qian Soil bacteria possess multiple weapons to fend off microbial competitors. Currently, we poorly understand the factors guiding bacterial decisions about weapon systems deployment. In this study, we investigated how such decisions are made by the soil bacterium Lysobacter enzymogenes, used in antifungal plant protection. We found that weapons production is guided by environmental...
4d
by Cheng-Yu Wu, Peter D. Nagy Positive-stranded (+)RNA viruses greatly exploit host cells to support viral replication. However, unlike many other pathogens, (+)RNA viruses code for only a limited number of genes, making them highly dependent on numerous co-opted host factors for supporting viral replication and other viral processes during their infections. This excessive dependence on subverted host factors, however, renders (+)RNA viruses vulnerable to host restriction factors that could...
4d
by Jiachen Huang, Darren Diaz, Jarrod J. Mousa Human metapneumovirus (hMPV) is a leading cause of viral respiratory infection in children, and can cause severe lower respiratory tract infection in infants, the elderly, and immunocompromised patients. However, there remain no licensed vaccines or specific treatments for hMPV infection. Although the hMPV fusion (F) protein is the sole target of neutralizing antibodies, the immunological properties of hMPV F remain poorly understood. To further...
4d
by Satoshi Ikegame, Shannon M. Beaty, Christian Stevens, Sohui T. Won, Arnold Park, David Sachs, Patrick Hong, Benhur Lee, Patricia A. Thibault The antigenic and genomic stability of paramyxoviruses remains a mystery. Here, we evaluate the genetic plasticity of Sendai virus (SeV) and mumps virus (MuV), sialic acid-using paramyxoviruses that infect mammals from two Paramyxoviridae subfamilies (Orthoparamyxovirinae and Rubulavirinae). We performed saturating whole-genome transposon insertional...
4d
by Emmeline L. Blanchard, Molly R. Braun, Aaron W. Lifland, Barbara Ludeke, Sarah L. Noton, Daryll Vanover, Chiara Zurla, Rachel Fearns, Philip J. Santangelo The ribonucleocapsid complex of respiratory syncytial virus (RSV) is responsible for both viral mRNA transcription and viral replication during infection, though little is known about how this dual function is achieved. Here, we report the use of a recombinant RSV virus with a FLAG-tagged large polymerase protein, L, to characterize and...
5d
by Ujjaldeep Jaggi, Mingjie Yang, Harry H. Matundan, Satoshi Hirose, Prediman K. Shah, Behrooz G. Sharifi, Homayon Ghiasi After HSV-1 infection, macrophages infiltrate early into the cornea, where they play an important role in HSV-1 infection. Macrophages are divided into M1 or M2 groups based on their activation. M1 macrophages are pro-inflammatory, while M2 macrophages are anti-inflammatory. Macrophage phenotypes can shift between M1 or M2 in vitro and in vivo following treatment with specific...
5d
by Olha Puhach, Eleonore Ostermann, Christoph Krisp, Giada Frascaroli, Hartmut Schlüter, Melanie M. Brinkmann, Wolfram Brune Cytomegaloviruses (CMV) infect many different cell types and tissues in their respective hosts. Monocytes and macrophages play an important role in CMV dissemination from the site of infection to target organs. Moreover, macrophages are specialized in pathogen sensing and respond to infection by secreting cytokines and interferons. In murine cytomegalovirus (MCMV), a model...
5d
The potyviral silencing suppressor HCPro recruits and employs host ARGONAUTE1 in pro-viral functions
by Maija Pollari, Swarnalok De, Aiming Wang, Kristiina Mäkinen In this study, we demonstrate a novel pro-viral role for the Nicotiana benthamiana ARGONAUTE 1 (AGO1) in potyvirus infection. AGO1 strongly enhanced potato virus A (PVA) particle production and benefited the infection when supplied in excess. We subsequently identified the potyviral silencing suppressor, helper-component protease (HCPro), as the recruiter of host AGO1. After the identification of a conserved AGO1-binding GW/WG motif...
5d
by Fernando Cantu, Shuai Cao, Candy Hernandez, Pragyesh Dhungel, Joshua Spradlin, Zhilong Yang Cellular decapping enzymes negatively regulate gene expression by removing the methylguanosine cap at the 5’ end of eukaryotic mRNA, rendering mRNA susceptible to degradation and repressing mRNA translation. Vaccinia virus (VACV), the prototype poxvirus, encodes two decapping enzymes, D9 and D10, that induce the degradation of both cellular and viral mRNAs. Using a genome-wide survey of translation...
5d
by Brigitta M. Laksono, Paola Fortugno, Bernadien M. Nijmeijer, Rory D. de Vries, Sonia Cordisco, Thijs Kuiken, Teunis B. H. Geijtenbeek, W. Paul Duprex, Francesco Brancati, Rik L. de Swart Measles is characterized by fever and a maculopapular skin rash, which is accompanied by immune clearance of measles virus (MV)-infected cells. Histopathological analyses of skin biopsies from humans and non-human primates (NHPs) with measles rash have identified MV-infected keratinocytes and mononuclear...
5d
by Masashi Ohno, Mizuho Hasegawa, Atsushi Hayashi, Gustavo Caballero-Flores, Christopher J. Alteri, Trevor D. Lawley, Nobuhiko Kamada, Gabriel Núñez, Naohiro Inohara Gut dysbiosis associated with intestinal inflammation is characterized by the blooming of particular bacteria such as adherent-invasive E. coli (AIEC). However, the precise mechanisms by which AIEC impact on colitis remain largely unknown. Here we show that antibiotic-induced dysbiosis worsened chemically-induced colitis in IL-22-deficient...
6d
by Crispin Zavala-Alvarado, Odile Sismeiro, Rachel Legendre, Hugo Varet, Giovanni Bussotti, Jan Bayram, Samuel G. Huete, Guillaume Rey, Jean-Yves Coppée, Mathieu Picardeau, Nadia Benaroudj Pathogenic Leptospira spp. are the causative agents of the waterborne zoonotic disease leptospirosis. Leptospira are challenged by numerous adverse conditions, including deadly reactive oxygen species (ROS), when infecting their hosts. Withstanding ROS produced by the host innate immunity is an important strategy...
1w
by Hassan Hakimi, Thomas J. Templeton, Miako Sakaguchi, Junya Yamagishi, Shinya Miyazaki, Kazuhide Yahata, Takayuki Uchihashi, Shin-ichiro Kawazu, Osamu Kaneko, Masahito Asada Babesia bovis causes a pathogenic form of babesiosis in cattle. Following invasion of red blood cells (RBCs) the parasite extensively modifies host cell structural and mechanical properties via the export of numerous proteins. Despite their crucial role in virulence and pathogenesis, such proteins have not been comprehensively...
2w
by Anna Crisford, Fernando Calahorro, Elizabeth Ludlow, Jessica M. C. Marvin, Jennifer K. Hibbard, Catherine J. Lilley, James Kearn, Francesca Keefe, Peter Johnson, Rachael Harmer, Peter E. Urwin, Vincent O’Connor, Lindy Holden-Dye Plant parasitic nematodes are microscopic pathogens that invade plant roots and cause extensive damage to crops. We have used a chemical biology approach to define mechanisms underpinning their parasitic behaviour: We discovered that reserpine, a plant alkaloid that...
2w
by Daniele Veggi, Federica Bianchi, Laura Santini, Paola Lo Surdo, Chelsy C. Chesterman, Werner Pansegrau, Nicoletta Bechi, Ying Huang, Vega Masignani, Mariagrazia Pizza, Rino Rappuoli, Matthew J. Bottomley, Roberta Cozzi, Domenico Maione Neisseria meningitidis serogroup B (MenB) is the leading cause of meningococcal meningitis and sepsis in industrialized countries, with the highest incidence in infants and adolescents. Two recombinant protein vaccines that protect against MenB are now available...
2w
by Li-hui He, Hao Wang, Yang Liu, Mei Kang, Tao Li, Chang-cheng Li, Ai-ping Tong, Yi-bo Zhu, Ying-jie Song, Stephen J. Savarino, Michael G. Prouty, Di Xia, Rui Bao Colonization factor CFA/I defines the major adhesive fimbriae of enterotoxigenic Escherichia coli and mediates bacterial attachment to host intestinal epithelial cells. The CFA/I fimbria consists of a tip-localized minor adhesive subunit, CfaE, and thousands of copies of the major subunit CfaB polymerized into an ordered helical rod....
2w
by Emily R. Bowman, Cheryl M. Cameron, Brian Richardson, Manjusha Kulkarni, Janelle Gabriel, Morgan J. Cichon, Kenneth M. Riedl, Yousef Mustafa, Michael Cartwright, Brandon Snyder, Subha V. Raman, David A. Zidar, Susan L. Koletar, Martin P. Playford, Nehal N. Mehta, Scott F. Sieg, Michael L. Freeman, Michael M. Lederman, Mark J. Cameron, Nicholas T. Funderburg People with HIV (PWH) are at increased risk for atherosclerotic cardiovascular disease (ASCVD). Proportions of vascular homing monocytes...
2w
by Melanie Genoula, José Luis Marín Franco, Mariano Maio, Belén Dolotowicz, Malena Ferreyra, M. Ayelén Milillo, Rémi Mascarau, Eduardo José Moraña, Domingo Palmero, Mario Matteo, Federico Fuentes, Beatriz López, Paula Barrionuevo, Olivier Neyrolles, Céline Cougoule, Geanncarlo Lugo-Villarino, Christel Vérollet, María del Carmen Sasiain, Luciana Balboa The ability of Mycobacterium tuberculosis (Mtb) to persist inside host cells relies on metabolic adaptation, like the accumulation of lipid bodies...
2w
by Yijuan Ding, Jiaqin Mei, Yaru Chai, Wenjing Yang, Yi Mao, Baoqin Yan, Yang Yu, Joseph Onwusemu Disi, Kusum Rana, Jiana Li, Wei Qian Necrotrophic plant pathogen induces host reactive oxygen species (ROS) production, which leads to necrosis in the host, allowing the pathogen to absorb nutrients from the dead tissues. Sclerotinia sclerotiorum is a typical necrotrophic pathogen that causes Sclerotinia stem rot in more than 400 species, resulting in serious economic losses. Here, we found that...
2w
by Katharina Robichon, Tim Maiwald, Marcel Schilling, Annette Schneider, Joschka Willemsen, Florian Salopiata, Melissa Teusel, Clemens Kreutz, Christian Ehlting, Jun Huang, Sajib Chakraborty, Xiaoyun Huang, Georg Damm, Daniel Seehofer, Philipp A. Lang, Johannes G. Bode, Marco Binder, Ralf Bartenschlager, Jens Timmer, Ursula Klingmüller The induction of an interferon-mediated response is the first line of defense against pathogens such as viruses. Yet, the dynamics and extent of interferon alpha...
2w
by Pachiyappan Kamarajan, Islam Ateia, Jae M. Shin, J. Christopher Fenno, Charles Le, Ling Zhan, Ana Chang, Richard Darveau, Yvonne L. Kapila Epidemiological studies reveal significant associations between periodontitis and oral cancer. However, knowledge about the contribution of periodontal pathogens to oral cancer and potential regulatory mechanisms involved is limited. Previously, we showed that nisin, a bacteriocin and commonly used food preservative, reduced oral cancer tumorigenesis and...
2w
by Michael T. McIntosh, Siva Koganti, J. Lucas Boatwright, Xiaofan Li, Salvatore V. Spadaro, Alexis C. Brantly, Jasmine B. Ayers, Ramon D. Perez, Eric M. Burton, Sandeepta Burgula, Thomas MacCarthy, Sumita Bhaduri-McIntosh Epstein-Barr virus (EBV) causes lymphomas and epithelial cell cancers. Though generally silent in B lymphocytes, this widely prevalent virus can cause endemic Burkitt lymphoma and post-transplant lymphoproliferative disorders/lymphomas in immunocompromised hosts. By learning...
2w
by Yuzhen Mei, Yaqin Wang, Fangfang Li, Xueping Zhou In plants, cytosine DNA methylation is an efficient defense mechanism against geminiviruses, since methylation of the viral genome results in transcriptional gene silencing (TGS). As a counter-defense mechanism, geminiviruses encode viral proteins to suppress viral DNA methylation and TGS. However, the molecular mechanisms by which viral proteins contribute to TGS suppression remain incompletely understood. In this study, we found that the...
2w
by Mohsan Saeed, Sebastian Kapell, Nicholas T. Hertz, Xianfang Wu, Kierstin Bell, Alison W. Ashbrook, Milica Tesic Mark, Henry A. Zebroski, Maxwell L. Neal, Malin Flodström-Tullberg, Margaret R. MacDonald, John D. Aitchison, Henrik Molina, Charles M. Rice Viruses cleave cellular proteins to remodel the host proteome. The study of these cleavages has revealed mechanisms of immune evasion, resource exploitation, and pathogenesis. However, the full extent of virus-induced proteolysis in infected...
2w
by Pranav N. M. Shah, David J. Filman, Krishanthi S. Karunatilaka, Emma L. Hesketh, Elisabetta Groppelli, Mike Strauss, James M. Hogle The virions of enteroviruses such as poliovirus undergo a global conformational change after binding to the cellular receptor, characterized by a 4% expansion, and by the opening of holes at the two and quasi-three-fold symmetry axes of the capsid. The resultant particle is called a 135S particle or A-particle and is thought to be on the pathway to a productive...
2w
by Norbert Donhauser, Eileen Socher, Sebastian Millen, Stefanie Heym, Heinrich Sticht, Andrea K. Thoma-Kress The Human T-cell leukemia virus type 1 (HTLV-1) orf I-encoded accessory protein p8 is cleaved from its precursor p12, and both proteins contribute to viral persistence. p8 induces cellular protrusions, which are thought to facilitate transfer of p8 to target cells and virus transmission. Host factors interacting with p8 and mediating p8 transfer are unknown. Here, we report that vasodilator-stimulated...
2w
by Siraje Arif Mahmud, Mohammed Adnan Qureshi, Madhab Sapkota, Mark W. Pellegrino The mitochondrial unfolded protein response (UPRmt) is a stress-activated pathway promoting mitochondrial recovery and defense against infection. In C. elegans, the UPRmt is activated during infection with the pathogen Pseudomonas aeruginosa—but only transiently. As this may reflect a pathogenic strategy to target a pathway required for host survival, we conducted a P. aeruginosa genetic screen to uncover mechanisms...
2w
by Jonathan D. Edgeworth, Rahul Batra, Gaia Nebbia, Karen Bisnauthsing, Eithne MacMahon, Malur Sudhanva, Sam Douthwaite, Simon Goldenberg, Geraldine O’Hara, Manu Shankar-Hari, Katie J. Doores, Rocio Martinez-Nunez, Carolyn Hemsley, Nicholas M. Price, Jill Lockett, Robert I. Lechler, Stuart J. D. Neil, Michael H. Malim
2w
by Wenwen Wang, Guijie Wang, Xiaorong Zhuo, Yu Liu, Lin Tang, Xusheng Liu, Jialin Wang The immune system of a host functions critically in shaping the composition of the microbiota, and some microbes are involved in regulating host endocrine system and development. However, whether the immune system acts on endocrine and development by shaping the composition of the microbiota remains unclear, and few molecular players or microbes involved in this process have been identified. In the current...
2w
by Maxime Godfroid, Tal Dagan, Matthias Merker, Thomas A. Kohl, Roland Diel, Florian P. Maurer, Stefan Niemann, Anne Kupczok In genome evolution, genetic variants are the source of diversity, which natural selection acts upon. Treatment of human tuberculosis (TB) induces a strong selection pressure for the emergence of antibiotic resistance-conferring variants in the infecting Mycobacterium tuberculosis (MTB) strains. MTB evolution in response to treatment has been intensively studied and mainly...
2w
by Jonas Fixemer, Jonas F. Hummel, Frederic Arnold, Christoph S. N. Klose, Alexis Hofherr, Kristoffer Weissert, Tamara Kögl, Michael Köttgen, Sebastian J. Arnold, Peter Aichele, Yakup Tanriver The two T-box transcription factors T-bet and Eomesodermin (Eomes) are important regulators of cytotoxic lymphocytes (CTLs), such as activated CD8 T cells, which are essential in the fight against intracellular pathogens and tumors. Both transcription factors share a great degree of homology based on sequence...
2w
by Melanie Chitray, Abhay Kotecha, Peninah Nsamba, Jingshan Ren, Sonja Maree, Tovhowani Ramulongo, Guntram Paul, Jacques Theron, Elizabeth E. Fry, David I. Stuart, Francois F. Maree Field isolates of foot-and-mouth disease viruses (FMDVs) utilize integrin-mediated cell entry but many, including Southern African Territories (SAT) viruses, are difficult to adapt to BHK-21 cells, thus hampering large-scale propagation of vaccine antigen. However, FMDVs acquire the ability to bind to cell surface...
2w
by Simone De Meo, Valentina Dell’Oste, Rosa Molfetta, Valentina Tassinari, Lavinia Vittoria Lotti, Simone Vespa, Benedetta Pignoloni, Daniela Angela Covino, Laura Fantuzzi, Roberta Bona, Alessandra Zingoni, Ilaria Nardone, Matteo Biolatti, Alessandra Coscia, Rossella Paolini, Monsef Benkirane, Fredrik Edfors, Tatyana Sandalova, Adnane Achour, John Hiscott, Santo Landolfo, Angela Santoni, Cristina Cerboni SAMHD1 is a host restriction factor that functions to restrict both retroviruses and DNA...
3w
by Anubama Rajan, Matthew J. Robertson, Hannah E. Carter, Nina M. Poole, Justin R. Clark, Sabrina I. Green, Zachary K. Criss, Boyang Zhao, Umesh Karandikar, Yikun Xing, Mar Margalef-Català, Nikhil Jain, Reid L. Wilson, Fan Bai, Joseph M. Hyser, Joseph Petrosino, Noah F. Shroyer, Sarah E. Blutt, Cristian Coarfa, Xuezheng Song, BV Venkataram Prasad, Manuel R. Amieva, Jane Grande-Allen, Mary K. Estes, Pablo C. Okhuysen, Anthony W. Maresso Enteroaggregative Escherichia coli (EAEC) is a significant...
3w
by Gang Yu, Liu Xian, Hao Xue, Wenjia Yu, Jose S. Rufian, Yuying Sang, Rafael J. L. Morcillo, Yaru Wang, Alberto P. Macho Nucleotide-binding domain and leucine-rich repeat-containing (NLR) proteins function as sensors that perceive pathogen molecules and activate immunity. In plants, the accumulation and activation of NLRs is regulated by SUPPRESSOR OF G2 ALLELE OF skp1 (SGT1). In this work, we found that an effector protein named RipAC, secreted by the plant pathogen Ralstonia solanacearum,...
3w
by Soumya Panigrahi, Bonnie Chen, Mike Fang, Daria Potashnikova, Alexey A. Komissarov, Anna Lebedeva, Gillian M. Michaelson, Jonathan M. Wyrick, Stephen R. Morris, Scott F. Sieg, Mirko Paiardini, Francois J. Villinger, Karem Harth, Vikram S. Kashyap, Mark J. Cameron, Cheryl M. Cameron, Elena Vasilieva, Leonid Margolis, Souheil-Antoine Younes, Nicholas T. Funderburg, David A. Zidar, Michael M. Lederman, Michael L. Freeman Atherosclerotic cardiovascular disease (ASCVD) remains an important cause...
3w
by Suzanne Pickering, Gilberto Betancor, Rui Pedro Galão, Blair Merrick, Adrian W. Signell, Harry D. Wilson, Mark Tan Kia Ik, Jeffrey Seow, Carl Graham, Sam Acors, Neophytos Kouphou, Kathryn J. A. Steel, Oliver Hemmings, Amita Patel, Gaia Nebbia, Sam Douthwaite, Lorcan O’Connell, Jakub Luptak, Laura E. McCoy, Philip Brouwer, Marit J. van Gils, Rogier W. Sanders, Rocio Martinez Nunez, Karen Bisnauthsing, Geraldine O’Hara, Eithne MacMahon, Rahul Batra, Michael H. Malim, Stuart J. D. Neil, Katie J....
3w
by Wenzhi Liu, Yecheng Zhang, Jie Ma, Nan Jiang, Yuding Fan, Yong Zhou, Kenneth Cain, Meisheng Yi, Kuntong Jia, Hua Wen, Wei Liu, Wuxiang Guan, Lingbing Zeng Tilapia is one of the most important economic and fastest-growing species in aquaculture worldwide. In 2015, an epidemic associated with severe mortality occurred in adult tilapia in Hubei, China. The causative pathogen was identified as Tilapia parvovirus (TiPV) by virus isolation, electron microscopy, experimental challenge, In situ hybridization...
3w
by Cécile Viboud, Katelyn Gostic, Martha I. Nelson, Graeme E. Price, Amanda Perofsky, Kaiyuan Sun, Nídia Sequeira Trovão, Benjamin J. Cowling, Suzanne L. Epstein, David J. Spiro The prospect of universal influenza vaccines is generating much interest and research at the intersection of immunology, epidemiology, and viral evolution. While the current focus is on developing a vaccine that elicits a broadly cross-reactive immune response in clinical trials, there are important downstream questions...
3w
by Alejandra Zárate-Potes, Wentao Yang, Barbara Pees, Rebecca Schalkowski, Philipp Segler, Bentje Andresen, Daniela Haase, Rania Nakad, Philip Rosenstiel, Guillaume Tetreau, Jacques-Philippe Colletier, Hinrich Schulenburg, Katja Dierking The nematode Caenorhabditis elegans has been extensively used as a model for the study of innate immune responses against bacterial pathogens. While it is well established that the worm mounts distinct transcriptional responses to different bacterial species,...
3w
by Vanessa Knittel, Pooja Sadana, Stephanie Seekircher, Anne-Sophie Stolle, Britta Körner, Marcel Volk, Cy M. Jeffries, Dmitri I. Svergun, Ann Kathrin Heroven, Andrea Scrima, Petra Dersch Type VI secretion systems (T6SSs) are complex macromolecular injection machines which are widespread in Gram-negative bacteria. They are involved in host-cell interactions and pathogenesis, required to eliminate competing bacteria, or are important for the adaptation to environmental stress conditions. Here...
3w
by Swagata Ghosh, Laura Farr, Aditya Singh, Laura-Ann Leaton, Jay Padalia, Debbie-Ann Shirley, David Sullivan, Shannon Moonah Understanding how the protozoan protein degradation pathway is regulated could uncover new parasite biology for drug discovery. We found the COP9 signalosome (CSN) conserved in multiple pathogens such as Leishmania, Trypanosoma, Toxoplasma, and used the severe diarrhea-causing Entamoeba histolytica to study its function in medically significant protozoa. We show that...
3w
The glucosyltransferase activity of <i>C. difficile</i> Toxin B is required for disease pathogenesis
by Terry W. Bilverstone, Megan Garland, Rory J. Cave, Michelle L. Kelly, Martina Tholen, Donna M. Bouley, Philip Kaye, Nigel P. Minton, Matthew Bogyo, Sarah A. Kuehne, Roman A. Melnyk Enzymatic inactivation of Rho-family GTPases by the glucosyltransferase domain of Clostridioides difficile Toxin B (TcdB) gives rise to various pathogenic effects in cells that are classically thought to be responsible for the disease symptoms associated with C. difficile infection (CDI). Recent in vitro studies...
3w
by Tara C. Marcink, Tong Wang, Amedee des Georges, Matteo Porotto, Anne Moscona Infection by human parainfluenza viruses (HPIVs) causes widespread lower respiratory diseases, including croup, bronchiolitis, and pneumonia, and there are no vaccines or effective treatments for these viruses. HPIV3 is a member of the Respirovirus species of the Paramyxoviridae family. These viruses are pleomorphic, enveloped viruses with genomes composed of single-stranded negative-sense RNA. During viral entry,...
4w
by Natalia Freitas, Margot Enguehard, Solène Denolly, Camille Levy, Gregory Neveu, Solène Lerolle, Stephanie Devignot, Friedemann Weber, Eric Bergeron, Vincent Legros, François-Loïc Cosset Crimean-Congo hemorrhagic fever virus (CCHFV) is a tick-borne orthonairovirus that has become a serious threat to the public health. CCHFV has a single-stranded, tripartite RNA genome composed of L, M, and S segments. Cleavage of the M polyprotein precursor generates the two envelope glycoproteins (GPs) as...
4w
by Dhiraj Kumar Singh, Ved Prakash Dwivedi, Shashi Prakash Singh, Anjna Kumari, Saurabh Kumar Sharma, Anand Ranganathan, Luc Van Kaer, Gobardhan Das Despite the availability of multiple antibiotics, tuberculosis (TB) remains a major health problem worldwide, with one third of the population latently infected and ~2 million deaths annually. The only available vaccine for TB, Bacillus Calmette Guérin (BCG), is ineffective against adult pulmonary TB. Therefore, alternate strategies that enhance...
4w
by Bridget Kastelberg, Nuria Tubau-Juni, Tariq Ayubi, Austin Leung, Andrew Leber, Raquel Hontecillas, Josep Bassaganya-Riera, Shiv D. Kale Aspergillus fumigatus is an opportunistic fungal pathogen of immunocompromised patient populations. Mortality is thought to be context-specific and occurs via both enhanced fungal growth and immuno-pathogenesis. NLRX1 is a negative regulator of immune signaling and metabolic pathways implicated in host responses to microbes, cancers, and autoimmune diseases....
4w
by Simona Krasnopolsky, Alona Kuzmina, Ran Taube Despite the widespread use of anti-retroviral therapy, human immunodeficiency virus (HIV) still persists in an infected cell reservoir that harbors transcriptionally silent yet replication-competent proviruses. While significant progress has been made in understanding how the HIV reservoir is established, transcription repression mechanisms that are enforced on the integrated viral promoter have not been fully revealed. In this study, we performed...
4w
by Adil Mohamed, Prathyusha Konda, Heather E. Eaton, Shashi Gujar, James R. Smiley, Maya Shmulevitz The Dearing isolate of Mammalian orthoreovirus (T3D) is a prominent model of virus-host relationships and a candidate oncolytic virotherapy. Closely related laboratory strains of T3D, originating from the same ancestral T3D isolate, were recently found to exhibit significantly different oncolytic properties. Specifically, the T3DPL strain had faster replication kinetics in a panel of cancer cells...
4w
by Elyzana Dewi Putrianti, Anja Schmidt-Christensen, Volker Heussler, Kai Matuschewski, Alyssa Ingmundson The transitions between developmental stages are critical points in the Plasmodium life cycle. The development of Plasmodium in the livers of their mammalian hosts bridges malaria transmission and the onset of clinical symptoms elicited by red blood cell infection. The egress of Plasmodium parasites from the liver must be a carefully orchestrated process to ensure a successful switch to...
4w
by Gloria Volohonsky, Perrine Paul-Gilloteaux, Jitka Štáfková, Julien Soichot, Jean Salamero, Elena A. Levashina Malaria-causing Plasmodium parasites traverse the mosquito midgut cells to establish infection at the basal side of the midgut. This dynamic process is a determinant of mosquito vector competence, yet the kinetics of the parasite migration is not well understood. Here we used transgenic mosquitoes of two Anopheles species and a Plasmodium berghei fluorescence reporter line to track...
4w
by Robert Faris, Alix McCullough, Shelby E. Andersen, Thomas O. Moninger, Mary M. Weber As an obligate intracellular pathogen, host cell invasion is paramount to Chlamydia trachomatis proliferation. While the mechanistic underpinnings of this essential process remain ill-defined, it is predicted to involve delivery of prepackaged effector proteins into the host cell that trigger plasma membrane remodeling and cytoskeletal reorganization. The secreted effector proteins TmeA and TarP, have risen...
4w
by Amy L. Hartman, Sham Nambulli, Cynthia M. McMillen, Alexander G. White, Natasha L. Tilston-Lunel, Joseph R. Albe, Emily Cottle, Matthew D. Dunn, L. James Frye, Theron H. Gilliland, Emily L. Olsen, Katherine J. O’Malley, Madeline M. Schwarz, Jaime A. Tomko, Reagan C. Walker, Mengying Xia, Matthew S. Hartman, Edwin Klein, Charles A. Scanga, JoAnne L. Flynn, William B. Klimstra, Anita K. McElroy, Douglas S. Reed, W. Paul Duprex Vaccines are urgently needed to combat the global coronavirus disease...
4w
by Mradul Mohan, Jerin Jose Cherian, Amit Sharma Coronavirus Disease 2019 (COVID-19) pandemic remains a major public health threat in most countries. The causative severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus can lead to acute respiratory distress syndrome and result in mortality in COVID-19 patients. Vitamin D is an immunomodulator hormone with established effectiveness against various upper respiratory infections. Vitamin D can stall hyper-inflammatory responses and expedite...
4w
by Pattana Jaroenlak, Michael Cammer, Alina Davydov, Joseph Sall, Mahrukh Usmani, Feng-Xia Liang, Damian C. Ekiert, Gira Bhabha Microsporidia, a divergent group of single-celled eukaryotic parasites, harness a specialized harpoon-like invasion apparatus called the polar tube (PT) to gain entry into host cells. The PT is tightly coiled within the transmissible extracellular spore, and is about 20 times the length of the spore. Once triggered, the PT is rapidly ejected and is thought to penetrate...
4w
by Michelle Zanoni, David Palesch, Claudia Pinacchio, Maura Statzu, Gregory K. Tharp, Mirko Paiardini, Ann Chahroudi, Steven E. Bosinger, Jack Yoon, Bryan Cox, Guido Silvestri, Deanna A. Kulpa MHC-I-restricted, virus-specific cytotoxic CD8+ T cells (CTLs) may control human immunodeficiency virus (HIV) and simian immunodeficiency virus (SIV) replication via the recognition and killing of productively infected CD4+ T cells. Several studies in SIV-infected macaques suggest that CD8+ T cells may...
4w
by Omoshola Aleru, Matthew F. Barber
4w
by Amit Luthra, Jairo M. Montezuma-Rusca, Carson J. La Vake, Morgan LeDoyt, Kristina N. Delgado, Timothy C. Davenport, Mary Fiel-Gan, Melissa J. Caimano, Justin D. Radolf, Kelly L. Hawley Deconvolution of syphilis pathogenesis and selection of candidate syphilis vaccinogens requires detailed knowledge of the molecular architecture of the Treponema pallidum outer membrane (OM). The T. pallidum OM contains a low density of integral OM proteins, while the spirochete’s many lipoprotein immunogens...
4w
by Kuan-Ying A. Huang, Peng-Nien Huang, Yhu-Chering Huang, Shu-Li Yang, Kuo-Chien Tsao, Cheng-Hsun Chiu, Shin-Ru Shih, Tzou-Yien Lin An outbreak of the hand-foot-mouth disease with severe neurological cases, mainly caused by the genotype C1 enterovirus A71 (EV-A71), occurred in Taiwan between 2018 and early 2019. In the recent decade, the most dominant EV-A71 genotypes in Taiwan were B5 and C4 but changed to C1 in 2018. Antibody-mediated immunity plays a key role in limiting the EV-A71 illness...
4w
by Fitz Gerald S. Silao, Kicki Ryman, Tong Jiang, Meliza Ward, Nicolas Hansmann, Chris Molenaar, Ning-Ning Liu, Changbin Chen, Per O. Ljungdahl Candida albicans cells depend on the energy derived from amino acid catabolism to induce and sustain hyphal growth inside phagosomes of engulfing macrophages. The concomitant deamination of amino acids is thought to neutralize the acidic microenvironment of phagosomes, a presumed requisite for survival and initiation of hyphal growth. Here, in contrast...
4w
by Doron Teper, Jin Xu, Jinyun Li, Nian Wang Citrus canker caused by Xanthomonas citri subsp. citri (Xcc) is one of the most devastating diseases in citrus. Meiwa kumquat (Fortunella crassifolia) has shown a durable resistance against Xcc. Here, we aimed to characterize the mechanisms responsible for such a durable resistance by characterizing the transcriptional and physiological responses of Meiwa kumquat to Xcc. Inoculation of Meiwa kumquat with Xcc promoted immune responses such as upregulation...
4w
by Geoffrey D. Vrla, Mark Esposito, Chen Zhang, Yibin Kang, Mohammad R. Seyedsayamdost, Zemer Gitai Surface attachment, an early step in the colonization of multiple host environments, activates the virulence of the human pathogen P. aeruginosa. However, the downstream toxins that mediate surface-dependent P. aeruginosa virulence remain unclear, as do the signaling pathways that lead to their activation. Here, we demonstrate that alkyl-quinolone (AQ) secondary metabolites are rapidly induced...
5w
by Steven W. Jin, Francis M. Mwimanzi, Jaclyn K. Mann, Mwebesa Bosco Bwana, Guinevere Q. Lee, Chanson J. Brumme, Peter W. Hunt, Jeff N. Martin, David R. Bangsberg, Thumbi Ndung’u, Zabrina L. Brumme, Mark A. Brockman HIV Nef counteracts cellular host restriction factors SERINC3 and SERINC5, but our understanding of how naturally occurring global Nef sequence diversity impacts these activities is limited. Here, we quantify SERINC3 and SERINC5 internalization function for 339 Nef clones, representing...
5w
PHOENIX, Ariz. — Oct. 12, 2020 — The Translational Genomics Research Institute (TGen) , an affiliate of City of Hope , is bringing together thousands of supporters of the institute’s world-class pancreatic cancer research in ways never envisioned before the advent of COVID-19. “While the pandemic makes it impossible for thousands to join safely in one place, as we did the past 14 years, technology enables our 15 th annual Step-N-Out 5K, now a virtual event , to engage more people from throughout...
21h
PHOENIX and TUCSON, Ariz. — Oct. 5, 2020 — Avery Therapeutics Inc. of Tucson has developed an engineered heart tissue, a lab-grown cardiac membrane that can help heal the heart, either following a heart attack or as a result of progressive heart disease. The heart tissue, called MyCardia™, could revolutionize the treatment of cardiovascular disease, and someday might be applied to other failing organs. To better understand how MyCardia works — at the infinitesimally small molecular level — Avery...
21h
PHOENIX, Ariz. — Oct. 1, 2020 — As ventilator use in hospitals skyrockets during the COVID-19 pandemic, results of a study by the Translational Genomics Research Institute (TGen) , City of Hope , HonorHealth Research and Innovation Institute , and the University of Arizona suggests there may be a better way to diagnose ventilator-associated pneumonia (VAP). The findings of this study, which was supervised by Patrick Pirrotte , Ph.D., Director of TGen’s Collaborative Center for Translational Mass...
21h
SCOTTSDALE, Ariz. — Sept. 29, 2020 — Led by the Translational Genomics Research Institute (TGen) , an affiliate of City of Hope , and by HonorHealth Research and Innovation Institute , an international team of researchers have described in detail the individual cells that comprise the pancreatic cancer microenvironment, a critical step in devising new treatment options for patients with this aggressive and difficult-to-treat disease. The study results were published today in the scientific journal...
21h
PHOENIX, Ariz. — Sept. (28), 2020 — After more than a decade of pioneering the study of naturally occurring cancer in pet dogs, the Translational Genomics Research Institute (TGen) , an affiliate of City of Hope , announced today the commercial launch of Vidium Animal Health , providing genomic-based precision-medicine to veterinary oncologists and pet parents. As a veterinarian, Vidium President Dr. David Haworth has seen first-hand the pain and concern that veterinarians and pet parents experience...
21h
PHOENIX, Ariz. — Sept. 21, 2020 — Adult cancer can be like a punch to the gut, but childhood cancer is not only devastating and heartbreaking for the child and their family, but also for neighbors, friends and sometimes the entire community. That is the story of little Hollis Doherty, whose amazing fight against a particularly aggressive and deadly form of childhood brain cancer brought together thousands of Arizonans, including some of the state’s most iconic sports celebrities, to root for this...
21h
PHOENIX, Ariz. — Sept. 17, 2020 — The Translational Genomics Research Institute (TGen) , an affiliate of City of Hope , will employ two relatively new technologies in a study led by Cleveland Clinic Lerner Research Institute and Case Western Reserve University School of Medicine into why men are stricken with glioblastoma brain cancer far more often than women, and why women survive the disease almost twice as long as men. As part of a five-year $10.4 million grant announced today from the National...
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See a recording of the ACGU press conference by clicking here . FLAGSTAFF, Ariz. — Sept. 15, 2020 — Initial findings reported by the Arizona COVID-19 Genomics Union (ACGU) suggest that following Arizona’s first reported case of COVID-19 in late January, the state experienced no cases that went undetected and was COVID-free until at least 11 distinct incursions occurred between mid-February and early April. The published results appear in the scientific journal mBio . Faculty at the Translational...
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PHOENIX and SCOTTSDALE, Ariz. — Sept. 14, 2020 — A team of researchers led by Mayo Clinic and the Translational Genomics Research Institute (TGen) , an affiliate of City of Hope , has identified specific potential therapeutic targets for the most aggressive and lethal form of pancreatic cancer. In what is believed to be the most comprehensive analysis of adenosquamous cancer of the pancreas (ASCP), the Mayo Clinic and TGen team identified, in preclinical models, therapeutic targets for this extremely...
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