bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pharmacological targeting of host chaperones protects from pertussis toxin in vitro and in vivo
Authors: Ernst Katharina , Mittler Ann-Katrin , Winkelmann Veronika , Eberhardt Nina , Anastasia Anna , Sonnabend Michael , Lochbaum Robin , Wirsching Jan , Skerry Ciaran , Carbonetti Nicholas H. , Frick Manfred , Barth Holger 
Published: September 2020

AbstractWhooping cough is caused byBordetella pertussisthat releases pertussis toxin (PT) which comprises enzyme A-subunit PTS1 and binding/transport B-subunit. After receptor-mediated endocytosis, PT reaches the endoplasmic reticulum from where unfolded PTS1 is transported to the cytosol. PTS1 ADP-ribosylates G-protein α-subunits resulting in increased cAMP signaling. Here, the role of target cell chaperones Hsp90, Hsp70, cyclophilins and FK506-binding proteins for cytosolic PTS1-uptake is characterized in detail. PTS1 specifically and directly interacts with chaperonesin vitroand in cells. Specific pharmacological chaperone inhibition protects CHO-K1, human primary airway basal cells and a fully differentiated airway epithelium from PT-intoxication by reducing cytosolic PTS1-amounts without affecting cell binding or enzyme activity. PT is internalized by human airway epithelium secretory but not ciliated cells and leads to increase of apical surface liquid. Cyclophilin-inhibitors reduced leukocytosis in infant mouse model of pertussis, indicating their promising potential for developing novel therapeutic strategies against whooping cough.
New insights into the paradoxical distribution ofIRC7inSaccharomyces cerevisiaeand its associated phenotypic and genomic landscapes
Authors: Ruiz Javier , de Celis Miguel , Martín-Santamaría María , Benito-Vázquez Iván , Pontes Ana , Lanza Val F. , Sampaio José Paulo , Santos Antonio , Belda Ignacio 
Published: September 2020

SummaryBiotic and abiotic factors of wine fermentations have led to the accumulation of numerous genomic hallmarks of domestication inSaccharomyces cerevisiaewine strains. Here we have studied the paradoxical distribution of a dominant allele ofIRC7in wine yeast strains. This gene encodes a cysteine-S-β-lyase and presents two alleles: a wild full-length allele (IRC7F) and a mutated one (IRC7S), harboring a 38bp-deletion. Interestingly,IRC7S-coding for a less active enzyme-appears in the great majority of wine strains. Studying its global distribution among phylogenetic clades, we observed thatIRC7Sallele is dominant just in wine strains, having a moderate presence in other domesticated clades (Beer, Bread and Wine-PDM), but being completely absent in wild clades, appearing as a new hallmark of domestication. To explain this paradoxical distribution, we performed anIRC7-rooted phenotypic-wide survey, demonstrating thatIRC7S-homozygous (HS) wine strains have both fitness (lower lag phases and higher growth rates) and competitive (killer toxin resistance, pseudohyphal growth) advantages. Hence, we performed a genome-wide survey across domesticated clades, finding a set of mutations that are conserved among wine strains and potentially associated toIRC7Sallele, which can help to explain the outstanding phenotype of HS strains and their dominant distribution in wines.Originality-Significance StatementS. cerevisiaeis one of the best studied microbes due to its industrial importance and its use as a eukaryotic model organism.S. cerevisiaeis also an interesting model for studying the effects of domestication in yeast genomic, phenotype and ecology. The study of how wildS. cerevisiaestrains evolved into a greatly adapted domesticated strains and changed its lifestyle drastically is still of great interest. In the case of wine populations, strains have accumulated numerous hallmarks of domestication in their genome, related with their great phenotypic adaptation to this environment. Here, we report a new hallmark of domestication in wine strains; theIRC7deleted allele (IRC7S) and present the first insights about its unexpected global distribution among phylogenetic clades, understanding the genomic context and the phenotypic implications of this allele in wine strains.
Host-interactor screens ofPhytophthora infestansRXLR proteins reveal vesicle trafficking as a major effector-targeted process
Authors: Petre Benjamin , Contreras Mauricio P. , Bozkurt Tolga O. , Schattat Martin H. , Sklenar Jan , Schornack Sebastian , Abd-El-Haliem Ahmed , Castells-Graells Roger , Lozano-Duran Rosa , Dagdas Yasin F. , Menke Frank L. H. , Jones Alexandra M. E. , Vossen Jack H. , Robatzek Silke , Kamoun Sophien , Win Joe 
Published: September 2020

ABSTRACTPathogens modulate plant cell structure and function by secreting effectors into host tissues. Effectors typically function by associating with host molecules and modulating their activities. This study aimed to identify the host processes targeted by the RXLR class of host-translocated effectors of the potato blight pathogenPhytophthora infestans.To this end, we performed anin plantaprotein-protein interaction screen by transiently expressingP. infestansRXLR effectors inNicotiana benthamianaleaves followed by co-immunoprecipitation (co-IP) and liquid chromatography tandem mass spectrometry (LC-MS/MS). This screen generated an effector-host protein interactome matrix of 59P. infestansRXLR effectors x 586N. benthamianaproteins. Classification of the host interactors into putative functional categories revealed over 35 biological processes possibly targeted byP. infestans.We further characterized the PexRD12/31 family of RXLR-WY effectors, which associate and co-localize with components of the vesicle trafficking machinery. One member of this family, PexRD31, increased the number of FYVE positive vesicles inN. benthamianacells. FYVE positive vesicles also accumulated in leaf cells nearP. infestanshyphae, indicating that the pathogen may enhance endosomal trafficking during infection. We anticipate that the interactome dataset we generated will serve as a useful community resource for functional studies ofP. infestanseffectors and of effector-targeted host processes.
Peripheral sgp130-mediatedtrans-signaling blockade induces obesity and insulin resistance in mice via PPARα suppression
Authors: Lanton Tali , Levkovitch-Siany Orr , Udi Shiran , Tam Joseph , Abramovitch Rinat , Perles Sharon , Williams Evan , Rachmilewitz Jacob , Mor Uria , Elinav Eran , Schmidt-Arras Dirk , Rehman Ateequr , Rosenstiel Philip , Giannou Anastasios , Huber Samuel , Rose-John Stefan , Galun Eithan , Axelrod Jonathan H. 
Published: September 2020

AbstractIL-6 signaling via its receptor (IL-6R) and co-receptor (gp130) performs multiple roles in regulating metabolic homeostasis. However, gp130 is also expressed systemically in a soluble form (sgp130), which limits soluble IL-6 receptor (sIL-6R)-mediated signaling – also calledtrans-signaling. Here we find that transgenic peripheral sgp130-mediatedtrans-signaling blockade induces mature-onset obesity, while differentially affecting age-dependent behavioral determinants of energy expenditure. In youth,trans-signaling blockade increases feeding associated with reduced leptin sensitivity but increases energy expenditure to maintain metabolic balance. In aging, reduced physical activity predisposes mice to adiposity, adipose tissue macrophage recruitment, hepatosteatosis, hyperglycemia, and insulin resistance. Mechanistically,trans-signaling blockade reduces hepatic Stat3 phosphorylation and suppresses PPARα, associated with miR-21 upregulation, while pharmacological activation of PPARα prevents obesity and hepatosteatosis, and rescues insulin sensitivity. Together these experiments reveal a role for peripheral IL-6trans-signaling in metabolic homeostasis and provide clinical significance to elevated sgp130 levels found in some obese and diabetic patients.
Synaptonemal Complex dimerization regulates chromosome alignment and crossover patterning in meiosis
Authors: Gordon Spencer G. , Kursel Lisa E. , Xu Kewei , Rog Ofer 
Published: September 2020

AbstractDuring sexual reproduction the parental homologous chromosomes find each other (pair) and align along their lengths by integrating local sequence homology with large-scale contiguity, thereby allowing for precise exchange of genetic information. The Synaptonemal Complex (SC) is a conserved zipper-like structure that assembles between the homologous chromosomes. This phase-separated interface brings chromosomes together and regulates exchanges between them. However, the molecular mechanisms by which the SC carries out these functions remain poorly understood. Here we isolated and characterized two mutations in the dimerization interface in the middle of the SC zipper inC. elegans. The mutations perturb both chromosome alignment and the regulation of genetic exchanges. Underlying the chromosome-scale phenotypes are distinct alterations to the way SC subunits interact with one another. We propose that the SC brings homologous chromosomes together through two biophysical activities: obligate dimerization that prevents assembly on unpaired chromosomes; and a tendency to phase-separate that extends pairing interactions along the entire length of the chromosomes.
Evolution of fungal community associated with ready-to-eat pineapple during storage under different temperature conditions
Authors: Manthou Evanthia , Coeuret Gwendoline , Chaillou Stephane , Nychas George-John E. 
Published: September 2020

AbstractThe international market of fresh-cut products has witnessed dramatic growth in recent years, stimulated by consumer’s demand for healthy, nutritious and convenient foods. One of the main challenging issues for the quality and safety of these products is the potential microbial spoilage that can significantly reduce their shelf-life. The complete identification of fresh-cut product microbiota together with the evaluation of environmental factors impact on microbial composition is of primary importance. We therefore assessed the fungal communities associated with the spoilage of ready-to-eat (RTE) pineapple using a metagenetic amplicon sequencing approach, based on the ITS2 region. Our results revealed a significant variability on fungal species composition between the different batches of RTE pineapple. The initial microbiota composition was the main influencing factor and determined the progress of spoilage. Temperature and storage time were the secondary factors influencing spoilage and their impact was depending on the initial prevalent fungal species, which showed different responses to the various modifications. Our results strongly suggest that further large-scale sampling of RTE pineapple production should be conducted in order to assess the full biodiversity range of fungal community involved in the spoilage process and for unravelling the impact of important environmental factors shaping the initial microbiota.
Unique features of stimulus-based probabilistic reversal learning
Authors: Harris Carl , Aguirre Claudia , Kolli Saisriya , Das Kanak , Izquierdo Alicia , Soltani Alireza 
Published: September 2020

AbstractReversal learning paradigms are widely-used assays of behavioral flexibility with their probabilistic versions being more amenable to studying integration of reward outcomes over time. Prior research suggests differences between initial and reversal learning, including higher learning rates, a greater need for inhibitory control, and more perseveration after reversals. However, it is not well-understood what aspects of stimulus-based reversal learning are unique to reversals, and whether and how observed differences depend on reward probability. Here, we used a visual probabilistic discrimination and reversal learning paradigm where male and female rats selected between a pair of stimuli associated with different reward probabilities. We compared accuracy, rewards collected, omissions, latencies, win-stay/lose-shift strategies, and indices of perseveration across two different reward probability schedules. We found that discrimination and reversal learning are behaviorally more unique than similar: latencies to select the better option, win-stay strategies, and perseveration were of a different pattern in reversal learning compared to discrimination learning. Additionally, fit of choice behavior using reinforcement learning models revealed a lower sensitivity to the difference in subjective reward values (greater exploration) and higher learning rates for the reversal phase. Interestingly, a consistent reward probability group difference emerged with a richer environment associated with longer reward collection latencies than a leaner environment. We also replicated previous reports on sex differences in reversal learning. Future studies should systematically compare the neural correlates of fine-grained behavioral measures to reveal possible dissociations in how the circuitry is recruited in each phase.
IF1 connects obesity and insulin resistance through mitochondrial reprogramming in association with ANT2
Authors: Wang Ying , Guan Yaya , Zhang Jiaojiao , Cao Xinyu , Shen Shuang , Zhong Genshen , Xong Xiwen , Xu Yanhong , Zhang Xiaoying , Wang Hui , Ye Jianping 
Published: September 2020

AbstractIF1 (ATPIF1) is a nuclear DNA-encoded protein with an activity in the inhibition of catalytic activity of F1Fo-ATP synthase (ATPase), an enzyme for ATP synthesis in mitochondria. A role of IF1 remains unknown in the metabolic disorder in obesity. In this study, IF1 was examined in the diet-induced obese (DIO) mice and a decrease in IF1 protein was observed in several tissues including the skeletal muscle, liver and intestine in the absence of mRNA alteration. Significance of the reduction was investigated in the IF1-KO mice, in which insulin sensitivity was improved in the absence of body weight alteration on Chow diet. On a high fat diet (HFD), the IF1-KO mice gain more body weight as a result of enhanced fat tissue growth. The energy expenditure and locomotion activity were decreased in the KO mice without an alteration in food intake. The increase in insulin sensitivity remained in the obese KO mice. The colon tissue exhibited a resistance to the HFD-induced atrophy with less cell apoptosis and more secretion of GLP-1. Mitochondria exhibited an enhanced ATP production and maximal oxygen consumption without an alteration in the respiratory chain proteins. However, the ATP level was reduced in the fasting condition in the muscle as well as the liver. Mitophagy was enhanced with elevated accumulation of PINK1 and Parkin proteins in the mitochondria. The protein abundance of ADP/ATP translocase 2 (ANT2) was decreased in the inner membrane of mitochondria to account for the reduced apoptosis and enhanced mitophagy. The data suggest that the IF1 reduction in obesity leads to reprogramming of mitochondrial metabolism in a compensatory response to maintain the insulin sensitivity through down-regulation of ANT2 protein.
Evolutionary study of the412/mdg1lineage of theTy3/gypsygroup of LTR retrotransposons in Diptera
Authors: Bertocchi Natasha Avila , Torres Fabiano Pimentel , Deprá Maríndia , da Silva Valente Vera Lúcia 
Published: September 2020

AbstractLTR-retrotransposons are structurally similar to retroviruses, as they possess the enzymes reverse transcriptase, Ribonuclease H, integrase, proteinase, and thegaggene and are flanked by long terminal repeats (LTRs). The412/mdg1lineage, belonging to theTy3/Gypsygroup, consists of the TEs412, mdg1, stalker, pilgrim, andblood. The412/mdg1lineage is distinguished from the others in thegypsygroup in that it has small ORFs at the beginning of the TE and is highly similar to thepolORF among the TEs that make up the lineage. In this study, our aim was to elucidate the evolutionary history of the412/mdg1lineage in the 127 dipteran genomes available to date, and the characteristics of the sequences in each genome. We used the canonical TE412probe described inDrosophila melanogasteras the query. We found sequences homologous to the412/mdg1lineage restricted to the suborder Brachycera. These sequences are widely distributed in drosophilids but are also present in other groups of flies. We note the presence of the412/mg1lineage in tsetse flies (Glossina). Furthermore, our results showed an elaborate evolutionary history for thepolORF in the412/mdg1lineage of the LTR-Retrotransposon.
QuickFigures: a tool to quickly transform microscope images into quality figures
Authors: Mazo Gregory 
Published: September 2020

AbstractPublications involving fluorescent microscopy generally contain many panels with split channels, merged images, scale bars and label text. Assembling and editing these figures with even spacing, consistent font, text position, accurate scale bars and other features can be tedious and time consuming. In order to save time and streamline the process I have created a toolset called QuickFigures.
Introduction of a precocious metamorphosis BmNPV infection in the latter half of the fifth instar silkworm larvae
Authors: Xu Pingzhen , Zhang Meirong , Wang Xueyang , Wu Yangchun 
Published: September 2020

AbstractThe silkworm,Bombyx mori, is a complete metamorphosis insect, the model to study insect physiology and biochemistry.Bombyx morinucleopolyhedrovirus (BmNPV) is a principal pathogen of the silkworm and its host range is restricted to silkworm larvae, requiring interaction with larvae to accomplish virus replication. Prothoracic glands (PGs) are a model for synthetic ecdysone with regulating insect growth and development. This study performed a transcriptome analysis of silkworm PGs after BmNPV infection. Transcriptome data were annotated with KEGG, GO, and shown to be of high quality by RT-qPCR. The spatial expression profiles ofBmJingandBmArylindicate that they may be specifically expressed in silkworm PGs. The RT-qPCR results of the DEGs in the PGs of BmNPV-infected larvae at 24, 48, and 72 h and at the developmental stages of days-6 and 7, comparing to day-3, reveal that the DEGs may be related to the BmNPV infection via promoting early maturation in the latter half of the silkworm fifth instar. This study is the first report on the identification of possible genes in PGs correlating with the precocious molting and metamorphosis of silkworm larvae under BmNPV infection in the latter half of the fifth instar. Our findings will help to address the interactions between BmNPV infection and host developmental response. This work provides a new perspective on BmNPV infection and host developmental response, as well as suggesting candidate genes for further research.
Ribosomal protein S7 ubiquitination during ER stress in yeast is associated with selective mRNA translation and stress outcome
Authors: Matsuki Yasuko , Matsuo Yoshitaka , Nakano Yu , Iwasaki Shintaro , Yoko Hideyuki , Udagawa Tsuyoshi , Li Sihan , Saeki Yasushi , Yoshihisa Tohru , Tanaka Keiji , Ingolia Nicholas T. , Inada Toshifumi 
Published: September 2020

ABSTRACTeIF2α phosphorylation-mediated translational regulation is crucial for global translation repression by various stresses, including the unfolded protein response (UPR). However, translational control during UPR has not been demonstrated in yeast. This study investigated ribosome ubiquitination-mediated translational controls during UPR. Tunicamycin-induced ER stress enhanced the levels of ubiquitination of the ribosomal proteins uS10, uS3 and eS7. Not4-mediated monoubiquitination of eS7A was required for resistance to tunicamycin, whereas E3 ligase Hel2-mediated ubiquitination of uS10 was not. Ribosome profiling showed that the monoubiquitination of eS7A was crucial for translational regulation, including the upregulation of the spliced form of HAC1 (HAC1i) mRNA and the downregulation of Histidine triad NucleoTide-binding 1 (HNT1) mRNA. Downregulation of the deubiquitinating enzyme complex Upb3-Bre5 increased the levels of ubiquitinated eS7A during UPR in an Ire1-independent manner. These findings suggest that the monoubiquitination of ribosomal protein eS7A plays a crucial role in translational controls during the ER stress response in yeast.
Human marginal zone B cell development from early T2 progenitors
Authors: Tull Thomas J. , Pitcher Michael J. , Guesdon William , Siu Jacqueline H. , Lebrero-Fernández Cristina , Zhao Yuan , Petrov Nedyalko , Heck Susanne , Ellis Richard , Dhami Pawan , Kadolsky Ulrich D. , Kleeman Michelle , Kamra Yogesh , Fear David J. , John Susan , Jassem Wayel , Groves Richard W. , Sanderson Jeremy D. , Robson Michael D. , D’Cruz David , Bemark Mats , Spencer Jo 
Published: September 2020

AbstractB cells emerge from the bone marrow as transitional (TS) B cells that differentiate through T1, T2 and T3 stages to become naïve B cells. We have identified a bifurcation of human B cell maturation from the T1 stage forming IgMhiand IgMlodevelopmental trajectories. IgMhiT2 cells have higher expression of α4β7 integrin and lower expression of IL4 receptor (IL4R) compared to the IgMlobranch and are selectively recruited into gut-associated lymphoid tissue. IgMhiT2 cells also share transcriptomic features with marginal zone B cells (MZB). Lineage progression from T1 cells to MZB via an IgMhitrajectory is identified by pseudotime analysis of scRNA-sequencing data. Reduced frequency of IgMhigut homing T2 cells is observed in severe SLE and is associated with reduction of MZB and their putative IgMhiprecursors. The collapse of the gut-associated MZB maturational axis in severe SLE affirms its existence and importance for maintaining health.
Robust Self-Regeneratable Stiff Living Materials
Authors: Manjula-Basavanna Avinash , Duraj-Thatte Anna , Joshi Neel S. 
Published: September 2020

AbstractLiving systems have not only the exemplary capability to fabricate materials (e.g.wood, bone) under ambient conditions but they also consist of living cells that imbue them with properties like growth and self-regeneration. Like a seed that can grow into a sturdy living wood, we wondered: can living cells alone serve as the primary building block to fabricate stiff materials? Here we report the fabrication of stiff living materials (SLMs) produced entirely from microbial cells, without the incorporation of any structural biopolymers (e.g.cellulose, chitin, collagen) or biominerals (e.g.hydroxyapatite, calcium carbonate) that are known to impart stiffness to biological materials. Remarkably, SLMs are also lightweight, strong, resistant to organic solvents and can self-regenerate. This living materials technology can serve as a powerful biomanufacturing platform to design and develop sustainable structural materials, biosensors, self-regulators, self-healing and environment-responsive smart materials.