bluuebunny/crossref_metadata_2025_split huggingface dataset:
Recurrent losses and rapid evolution of the condensin II complex in insectsg
Authors: King T. , Leonard C.J. , Cooper J.C. , Nguyen S. , Joyce E. , Phadnis N. 
Published: November 2018

AbstractCondensins play a crucial role in the organization of genetic material by compacting and disentangling chromosomes. The condensin I and condensin II complexes are widely considered to have distinct functions based on studies in a few model organisms, although the specific functions of each complex are yet to be fully understood. The condensin II complex is critical for genome organization in Drosophila, and is a key anti-pairing factor that separates homologous chromosomes in somatic cells. Intriguingly, the Cap-G2 subunit of condensin II is absent in Drosophila melanogaster, and this loss may be related to the high levels of homologous chromosome pairing in somatic cells seen in flies. Here, we find that this Cap-G2 loss predates the origin of Dipterans, and other CapG2 losses have occurred independently in multiple insect lineages. Furthermore, the Cap-H2 and Cap-D3 subunits have also been repeatedly and independently lost in several insect orders, and some taxa lack condensin II-specific subunits entirely. We used Oligopaint DNA-FISH to quantify pairing levels in ten species across seven orders, representing several different configurations of the condensin II complex. We find that all non-Dipteran insects display near-uniform low pairing levels, suggesting that some key aspects of genome organization are robust to condensin II subunit losses. Finally, we observe consistent signatures of positive selection in condensin II subunits across flies and mammals. These findings suggest that these ancient complexes are far more evolutionarily labile than previously suspected, and are at the crossroads of several forms of genomic conflicts. Our results raise fundamental questions about the specific functions of the two condensin complexes and the interplay between them in taxa that have experienced subunit losses, and open the door to further investigations to elucidate the diversity of molecular mechanisms that underlie genome organization across various life forms.
The Antibiotic Neomycin Enhances Coxsackievirus Plaque Formation
Authors: Woods Acevedo Mikal A. , Pfeiffer Julie K. 
Published: November 2018

AbstractCoxsackievirus typically infects humans via the gastrointestinal tract, which has a large number of microorganisms collectively referred to as the microbiota. To study how the intestinal microbiota influence enteric virus infection, several groups have used an antibiotic regimen in mice to deplete bacteria. These studies have shown that bacteria promote infection with several enteric viruses. However, very little is known about whether antibiotics influence viruses in a microbiota-independent manner. Here, we sought to determine the effects of antibiotics on coxsackievirus B3 (CVB3) using anin vitrocell culture model in the absence of bacteria. We determined that an aminoglycoside antibiotic, neomycin, enhanced plaque size of CVB3-Nancy strain. Neomycin treatment did not alter viral attachment, translation, or replication. However, we found that the positive charge of neomycin and other positively charged compounds enhanced viral diffusion by overcoming the negative inhibitory effect of sulfated polysaccharides present in agar overlays. Overall, these data lend further evidence that antibiotics can play non-canonical roles in viral infections and that this should be considered when studying enteric virus-microbiota interactions.ImportanceCoxsackieviruses primarily infect the gastrointestinal tract of humans, but they can disseminate systemically and cause severe disease. Using antibiotic treatment regimens to deplete intestinal microbes in mice, several groups have shown the bacteria promote infection with a variety of enteric viruses. However, it is possible that antibiotics have microbiota-independent effects on viruses. Here, we show that an aminoglycoside antibiotic, neomycin, can influence quantification of coxsackievirus in cultured cells in absence of bacteria.
Natural strain variation reveals diverse biofilm regulation in squid-colonizingVibrio fischeri
Authors: Rotman Ella R. , Bultman Katherine M. , Brooks John F. , Gyllborg Mattias C. , Burgos Hector L. , Wollenberg Michael S. , Mandel Mark J. 
Published: November 2018

ABSTRACTThe mutualistic symbiontVibrio fischeribuilds a symbiotic biofilm during colonization of squid hosts. Regulation of the exopolysaccharide component, termed Syp, has been examined in strain ES114, where production is controlled by a phosphorelay that includes the inner membrane hybrid histidine kinase RscS. Most strains that lack RscS or encode divergent RscS proteins cannot colonize a squid host unless RscS from a squid symbiont is heterologously expressed. In this study, we examineV. fischeriisolates worldwide to understand the landscape of biofilm regulation during beneficial colonization. We provide a detailed study of three distinct evolutionary groups ofV. fischeriand find that while the RscS-Syp biofilm pathway is required in one of the groups, two other groups of squid symbionts require Syp independent of RscS. Mediterranean squid symbionts, includingV. fischeriSR5, colonize without an RscS homolog encoded in their genome. Additionally, Group AV. fischeristrains, which form a tightly-related clade of Hawaii isolates, have a frameshift inrscSand do not require the gene for squid colonization or competitive fitness. These same strains have a frameshift insypE, and we provide evidence that this Group AsypEallele leads to an upregulation in biofilm activity. This work thus describes the central importance of Syp biofilm in colonization of diverse isolates, and demonstrates that significant evolutionary transitions correspond to regulatory changes in thesyppathway.IMPORTANCEBiofilms are surface-associated, matrix-encased bacterial aggregates that exhibit enhanced protection to antimicrobial agents. Previous work has established the importance of biofilm formation by a strain of luminousVibrio fischeribacteria as the bacteria colonize their host, the Hawaiian bobtail squid. In this study, expansion of this work to many natural isolates revealed that biofilm genes are universally required, yet there has been a shuffling of the regulators of those genes. This work provides evidence that even when bacterial behaviors are conserved, dynamic regulation of those behaviors can underlie evolution of the host colonization phenotype. Furthermore, this work emphasizes the importance of investigating natural diversity as we seek to understand molecular mechanisms in bacteria.
TNF-α differentially regulates cell cycle genes in promyelocytic and granulocytic HL-60/S4 cells
Authors: Jacobson Elsie C. , Jain Lekha , Perry Jo K. , Vickers Mark H. , Olins Ada L. , Olins Donald E. , O’Sullivan Justin M. 
Published: November 2018

AbstractTumor necrosis factor alpha (TNF-α) is a potent cytokine involved in systemic inflammation and immune modulation. Signaling responses that involve TNF-α are context dependent and capable of stimulating pathways promoting both cell death and survival. TNF-α treatment has been investigated as part of a combined therapy for acute myeloid leukemia due to its modifying effects on all-trans retinoic acid (ATRA) mediated differentiation into granulocytes.To investigate the interaction between cellular differentiation and TNF-α, we performed RNA-sequencing on two forms of the human HL-60/S4 promyelocytic leukemia cell line treated with TNF-α. The ATRA-differentiated granulocytic form of HL-60/S4 cells had an enhanced transcriptional response to TNF-α treatment compared to the undifferentiated promyelocytes. The observed TNF-α responses included differential expression of cell cycle gene sets, which were generally upregulated in TNF-α treated promyelocytes, and downregulated in TNF-α treated granulocytes. This is consistent with TNF-α induced cell cycle repression in granulocytes and cell cycle progression in promyelocytes. Moreover, comparisons with gene expression changes associated with differentiation indicated that TNF-α treatment of granulocytes shifts the transcriptome towards that of a macrophage.We conclude that TNF-α treatment promotes a divergent transcriptional program in promyelocytes and granulocytes. TNF-α promotes cell cycle associated gene expression in promyelocytes. In contrast, TNF-α stimulated granulocytes have reduced cell cycle gene expression, and a macrophage-like transcriptional program.
Immuno-proteomic interrogation of dengue infection reveals novel HLA haplotype-specific MHC-I antigens
Authors: Swaminathan Kavya , Olsson Niclas , Lund Peder J. , Marceau Caleb D. , Wagar Lisa E. , Tian Yuan , Sidney John , Weiskopf Daniela , Majzoub Karim , de Silva Aruna D. , Harris Eva , Davis Mark M. , Sette Alessandro , Carette Jan E. , Elias Joshua E. 
Published: November 2018

AbstractBroadly effective vaccines against dengue virus (DENV) infection have remained elusive, despite rising infection rates in the developing world. Infection-specific peptide ligands presented on Major Histocompatibility Complexes (MHC) open new avenues for developing T-cell-based interventions. Past efforts towards mapping viral MHC epitopes were based on computational predictions that only partially reflected actual antigen presentation. To empirically identify DENV-specific MHC ligands, we developed an immuno-proteomics approach for interrogating DENV- and self-derived MHC ligands from infected B-lymphocytes. Here, we report four fundamental findings: First, over 700 infection-specific MHC-ligands reflected host cellular responses to DENV that were not apparent from the proteome. Second, we report 121 viral MHC-I ligands (108 novel) which clustered into discrete hotspots across the DENV polyprotein, some of which spanned DENV polyprotein components, described here as MHC ligands for the first time. Third, we found DENV ligands which were distinctly presented by MHC alleles previously associated with either high or low anti-DENV response. Fourth, we demonstrate that while ourin vitroassay only overlapped with a small fraction of previously described DENV T-cell epitopes, several novel MHC ligands identified here were recognized by T-cells from DENV-infected patients despite having low binding affinities. Together, these discoveries suggest that virus and host-derived MHC ligands have under-exploited potential for describing the cell biology of DENV infection, and as candidates for designing effective DENV vaccines.
Selection, linkage, and population structure interact to shape genetic variation among threespine stickleback genomes
Authors: Nelson Thomas C. , Crandall Johnathan G. , Ituarte Catherine M. , Catchen Julian M , Cresko William A. 
Published: November 2018

AbstractThe outcome of selection on genetic variation depends on the geographic organization of individuals and populations as well as the syntenic organization of loci within the genome. Spatially variable selection between marine and freshwater habitats has had a significant and heterogeneous impact on patterns of genetic variation across the genome of threespine stickleback fish. When marine stickleback invade freshwater habitats, more than a quarter of the genome can respond to divergent selection, even in as little as 50 years. This process largely uses standing genetic variation that can be found ubiquitously at low frequency in marine populations, can be millions of years old, and is likely maintained by significant bidirectional gene flow. Here, we combine population genomic data of marine and freshwater stickleback from Cook Inlet, Alaska, with genetic maps of stickleback fish derived from those same populations to examine how linkage to loci under selection affects genetic variation across the stickleback genome. Divergent selection has had opposing effects on linked genetic variation on chromosomes from marine and freshwater stickleback populations: near loci under selection, marine chromosomes are depauperate of variation while these same regions among freshwater genomes are the most genetically diverse. Forward genetic simulations recapitulate this pattern when different selective environments also differ in population structure. Lastly, dense genetic maps demonstrate that the interaction between selection and population structure may impact large stretches of the stickleback genome. These findings advance our understanding of how the structuring of populations across geography influences the outcomes of selection, and how the recombination landscape broadens the genomic reach of selection.
Inherited defects in natural killer cells shape tumor immune microenvironment, clinical outcome and immunotherapy response
Authors: Xu Xue , Li Jianqiang , Zou Jinfeng , Feng Xiaowen , Zhang Chao , Zheng Ruiqing , Duanmu Weixiang , Saha-Mandal Arnab , Ming Zhong , Wang Edwin 
Published: November 2018

AbstractTumor immune microenvironment (TIME) plays an important role in metastasis and immunotherapy. However, it has been not much known how to classify TIMEs and how TIMEs are genetically regulated. Here we showed that tumors were classified into TIME-rich, -intermediate and -poor subtypes which had significant differences in clinical outcomes, abundances of tumor-infiltrating lymphocytes (TILs), the degree of key immune programs’ activation, and immunotherapy response across 13 common cancer types (n= ∼6,000). Furthermore, TIME-intermediate/-poor patients had significantly more inherited genetic defects (i.e., functional germline variants) in natural killer (NK) cells, antigen processing and presentation (APP) and Wnt signaling pathways than TIME-rich patients, and so did cancer patients than non-cancer individuals (n=4,500). These results suggested that individuals who had more inherited defects in NK cells, APP and Wnt pathways had a higher risk of developing cancers. Moreover, in the 13 common cancers the number of inheritably defected genes of NK cells was significantly negative-correlated with patients’ survival, TILs’ abundance in TIMEs and immunotherapy response, suggesting that inherited defects in NK cells alone were sufficient to shape TILs’ recruitment, clinical outcome, and immunotherapy response, highlighting that NK cell activation was required in the 13 cancer types to drive the recruitment of immune troops into TIMEs. Thus, we proposed that cancer was a disease of NK cell inherited deficiencies. These results had implications in identifying of high-risk individuals based on germline genomes, implementing precision cancer prevention by adoptive transfer of healthy NK cells, and improving existing immunotherapies by combining of adoptive NK cell transfer (i.e., converting TIME-intermediate/-poor tumors into TIME-rich tumors) and anti-PD-1 or CAR-T therapy.ContactEW (edwin.wang@ucalgary.ca)
Chemo-mechanical Coupling in the Transport Cycle of a Type II ABC Transporter
Authors: Tamura Koichi , Sugimoto Hiroshi , Shiro Yoshitsugu , Sugita Yuji 
Published: November 2018

AbstractAT P -binding cassette (ABC) transporters are integral membrane proteins that translocate a wide range of substrates across biological membranes, harnessing free energy from the binding and hydrolysis of ATP. To understand the mechanism of the inward- to outward-facing transition that could be achieved by tight regulation of ATPase activity through extensive conformational changes of the protein, we applied template-based iterative all-atom molecular dynamics (MD) simulation to the heme ABC transporter BhuUV-T. The simulations, together with biased MDs, predict two new conformations of the protein, namely, occluded (Occ) and outward-facing (OF) conformations. The comparison between the inward-facing crystal structure and the predicted two structures shows atomic details of the gating motions at the transmembrane helices and dimerization of the nucleotide-binding domains (NBDs). The MD simulations further reveal a novel role of the ABC signature motifs (LSGG[Q/E]) at the NBDs in decelerating ATPase activity in the Occ form through sporadic flipping of the side chains of the LSGG[Q/E] catalytic serine residues. The orientational changes are coupled to loose NBD dimerization in the Occ state, whereas they are blocked in the OF form where the NBDs are tightly dimerized. The chemo-mechanical coupling mechanism may apply to other types of ABC transporters having the conserved LSGG[Q/E] signature motifs.
Insights into the microbiota of Asian seabass (Lates calcarifer) with tenacibaculosis symptoms and description ofsp. nov. Tenacibaculum singaporense
Authors: Miyake Sou , Soh Melissa , Azman Muhamad Nursyafiq , Ngoh Si Yan , Orbán László , Seedorf Henning 
Published: November 2018

AbstractOutbreaks of diseases in farmed fish remain a recurring problem despite the development of vaccines and improved hygiene standards on aquaculture farms. One commonly observed bacterial disease in tropical aquaculture of the South-East Asian region is tenacibaculosis, which is attributed to members of the Bacteroidetes genusTenacibaculum, most notablyT. maritimum. The impact of tenacibaculosis on fish microbiota remains poorly understood. In this study, we analysed the microbiota of different tissue types of commercially reared Asian seabass (Lates calcarifer) that showed symptoms of tenacibaculosis and compared the microbial communities to those of healthy and experimentally infected fish that were exposed to diseased farm fish. The microbiota of diseased farm fish was dominated by Proteobacteria (relative abundance±standard deviation, 74.5%±22.8%) and Bacteroidetes (18.07%±21.7%), the latter mainly comprised by a high abundance ofTenacibaculumspecies (17.6%±20.7%). In healthy seabass Proteobacteria had also highest relative abundance (48.04%±0.02%), but Firmicutes (34.2%±0.02%) and Fusobacteria (12.0%±0.03%) were the next two major constituents. Experimentally infected fish developed lesions characteristic for tenacibaculosis, but the microbiota was primarily dominated by Proteobacteria (90.4%±0.2%) and Firmicutes (6.2%±0.1%). The relative abundance ofTenacibaculumspecies in experimentally infected fish was significantly lower than in the commercially reared diseased fish and revealed a higher prevalence of differentTenacibaculumspecies. One strain was isolated and is described here assp. nov. Tenacibaculum singaporenseTLL-A1T(=DSM 106434T, KCTC 62393T). The genome ofT. singaporensewas sequenced and compared to those ofT. maritimumDSM 17995Tand the newly sequencedT. mesophilumDSM 13764T.ImportanceFish production from aquaculture facility has become a major source of protein for human consumption and is expected to further grow to meet the growing demands. Devastating fish diseases, such as tenacibaculosis, can eradicate entire stocks of aquaculture fish in a short time and pose a serious threat to individual fish farmers and overall fish production. Understanding the disease processes and the individual microbial players involved has the potential to develop methods to prevent or mitigate infections on aquaculture farms. This study provides important insights into the microbial ecology of tenacibaculosis from an aquaculture facility in Singapore and highlights the complexity of this fish disease at two different disease stages. Furthermore, the isolation of a novelTenacibaculumspecies and comparative genome analysis of three differentTenacibaculumspecies enhance our view of this economically and environmentally important bacterial genus.
Light remote control of alternative splicing in roots through TOR kinase
Authors: Riegler Stefan , Servi Lucas , Fuchs Armin , Herz Micaela A. Godoy , Kubaczka María G. , Venhuizen Peter , Schweighofer Alois , Simpson Craig , Brown John W.S. , Meyer Christian , Kalyna Maria , Barta Andrea , Petrillo Ezequiel 
Published: November 2018

SummaryFor plants, light is the source of energy and the most relevant regulator of growth and adaptations to the environment by inducing changes in gene expression at various levels, including alternative splicing. Chloroplasts trigger retrograde signals that control alternative splicing in leaves and roots in response to light. Here we provide evidence suggesting that sugars, derived from photosynthesis, act as mobile signals controlling alternative splicing in roots. The inhibition of TOR kinase activity diminishes the alternative splicing response to light and/or sugars in roots, showing the relevance of the TOR pathway in this signaling mechanism. Furthermore, disrupting the function of the mitochondria abolishes alternative splicing changes supporting a key role for these organelles in this signaling axis. We conclude that sugars can act as mobile signals coordinating alternative splicing responses to light throughout the whole plant, exerting this function in roots by activating the TOR pathway.Graphical AbstractArt by Dr. Luciana Giono.
Revealing dynamic protein acetylation across subcellular compartments
Authors: Baeza Josue , Lawton Alexis J. , Fan Jing , Smallegan Michael J. , Lienert Ian , Gandhi Tejas , Bernhardt Oliver M. , Reiter Lukas , Denu John M. 
Published: November 2018

ABSTRACTProtein acetylation is a widespread post-translational modification implicated in many cellular processes. Recent advances in mass spectrometry have enabled the cataloging of thousands of sites throughout the cell, however identifying regulatory acetylation marks have proven to be a daunting task. Knowledge of the kinetics and stoichiometry of site-specific acetylation are important factors to uncover function. Here, an improved method of quantifying acetylation stoichiometry was developed and validated, providing a detailed landscape of dynamic acetylation stoichiometry within cellular compartments. The dynamic nature of site-specific acetylation in response to serum stimulation was revealed. In two distinct human cell lines, growth factor stimulation led to site-specific, temporal acetylation changes, revealing diverse kinetic profiles that clustered into several groups. Overlap of dynamic acetylation sites among two different human cell lines suggested similar regulatory control points across major cellular pathways that include splicing, translation, and protein homeostasis. Rapid increases in acetylation on protein translational machinery suggest a positive regulatory role under pro-growth conditions. Lastly, higher median stoichiometry was observed in cellular compartments where active acetyltransferases are well-described.