bluuebunny/crossref_metadata_2025_split huggingface dataset:
Transposon Extermination Reveals Their Adaptive Fitness Contribution
Authors: Cranz-Mileva Susanne , Reilly Eve , Chalhoub Noor , Patel Rohan , Atanassova Tania , Cao Weihuan , Ellison Christopher , Zaratiegui Mikel 
Published: November 2021

AbstractTransposable Elements are molecular parasites that persist in their host genome by generating new copies to outpace natural selection. Here we measure the parameters governing the copy number dynamics of the fission yeast Tf2 retrotransposons, using experimental and natural populations and a strain where all Tf2 copies are removed. Natural population genomes display active and persistent Tf2 colonies, but in the absence of selection mitotic recombination deletes Tf2 elements at rates that far exceed transposition. We show that Tf2 elements provide a fitness contribution to their host by dynamically rewiring the transcriptional response to metabolic stress. Therefore, Tf2 elements exhibit a mutualistic rather than parasitic behavior toward their host.
Metabolic strategies of sharing pioneer bacteria mediating fresh macroalgae breakdown
Authors: Brunet Maéva , Duff Nolwen Le , Barbeyron Tristan , Thomas François 
Published: November 2021

AbstractMacroalgae represent huge amounts of biomass worldwide, largely recycled by marine heterotrophic bacteria. We investigated the strategies of “pioneer” bacteria within the flavobacterial genusZobelliato initiate the degradation of fresh brown macroalgae, which has received little attention compared to the degradation of isolated polysaccharides.Zobellia galactanivoransDsijTcould use macroalgae as a sole carbon source and extensively degrade algal tissues without requiring physical contact,viathe secretion of extracellular enzymes. This indicated a sharing behaviour, whereby pioneers release public goods that can fuel other bacteria. Comparisons of eightZobelliastrains, and strong transcriptomic shifts inZ. galactanivoranscells using fresh macroalgae vs. isolated polysaccharides, revealed potential overlooked traits of pioneer bacteria. Besides brown algal polysaccharide degradation, they notably include stress resistance proteins, type IX secretion system proteins and novel uncharacterized Polysaccharide Utilization Loci. Overall, this work highlights the relevance of studying fresh macroalga degradation to fully understand the niche, metabolism and evolution of pioneer degraders, as well as their cooperative interactions within microbial communities, as key players in macroalgal biomass turnover.
OPTN limits herpes stromal keratitis severity and demyelination through negative regulation of IL-17 and hyperinflammatory T-cell response
Authors: Ames Joshua , Yadavalli Tejabjiram , Patil Chandrashekhar , Hopkins James , Bhattacharya Ilina , Shukla Deepak 
Published: November 2021

AbstractHerpes stromal keratitis (HSK) is a result of the inflammatory sequelae following primary and recurrent Herpes simplex virus type-1 (HSV-1) infections. This pathology is known to be mediated by immunopathogenic T cell responses against viral antigens, however most individuals infected with HSV-1 never exhibit signs of this immunopathology. Recent studies have identified the host restriction factor, optineurin (OPTN), as an inhibitor of viral spread in the central nervous system, protecting hosts from viral encephalopathy. In an HSV-1 corneal infection mouse model on OPTN knockout mice, we assess the contribution of OPTN to ameliorating the clinical manifestations of HSK. We identify that OPTN protects the host from loss of ocular and whisker sensitivity and opacification of the cornea. scRNA-seq of the trigeminal ganglion (TG) reveals that transcription changes to the peripheral neurons and immune cell populations drive the expression of Il-17A in CD4 and CD8 T cells, as well as increased infiltration of T cells into the TG. This leads to demyelination and the observed HSK pathology.
TractoInferno: A large-scale, open-source, multi-site database for machine learning dMRI tractography
Authors: Poulin Philippe , Theaud Guillaume , Rheault Francois , St-Onge Etienne , Bore Arnaud , Renauld Emmanuelle , de Beaumont Louis , Guay Samuel , Jodoin Pierre-Marc , Descoteaux Maxime 
Published: November 2021

AbstractTractoInferno is the world’s largest open-source multi-site tractography database, including both research- and clinical-like human acquisitions, aimed specifically at machine learning tractography approaches and related ML algorithms. It provides 284 datasets acquired from 3T scanners across 6 different sites. Available data includes T1-weighted images, single-shell diffusion MRI (dMRI) acquisitions, spherical harmonics fitted to the dMRI signal, fiber ODFs, and reference streamlines for 30 delineated bundles generated using 4 tractography algorithms, as well as masks needed to run tractography algorithms. Manual quality control was additionally performed at multiple steps of the pipeline. We showcase TractoInferno by benchmarking the learn2track algorithm and 5 variations of the same recurrent neural network architecture. Creating the TractoInferno database required approximately 20,000 CPU-hours of processing power, 200 man-hours of manual QC, 3,000 GPU-hours of training baseline models, and 4 Tb of storage, to produce a final database of 350 Gb. By providing a standardized training dataset and evaluation protocol, TractoInferno is an excellent tool to address common issues in machine learning tractography.
Non-uniform distribution of dendritic nonlinearities differentially engages thalamostriatal and corticostriatal inputs onto cholinergic interneurons
Authors: Oz Osnat , Matityahu Lior , Mizrahi-Kliger Aviv , Kaplan Alexander , Berkowitz Noa , Tiroshi Lior , Bergman Hagai , Goldberg Joshua A. 
Published: November 2021

AbstractThe tonic activity of striatal cholinergic interneurons (CINs) is modified differentially by their afferent inputs. Although their unitary synaptic currents are identical, in most CINs cortical inputs onto distal dendrites only weakly entrain them, whereas proximal thalamic inputs trigger abrupt pauses in discharge in response to salient external stimuli. To test whether the dendritic expression of the active conductances that drive autonomous discharge contribute to the CINs’ capacity to dissociate cortical from thalamic inputs, we used an optogenetics-based method to quantify dendritic excitability. We found that the persistent sodium (NaP) current gave rise to dendritic boosting, and that the hyperpolarization-activated cyclic nucleotide-gated (HCN) current gave rise to a subhertz membrane resonance. This resonance may underlie our novel finding of an association between CIN pauses and internally-generated slow wave events in sleeping non-human primates. Moreover, our method indicated that dendritic NaP and HCN currents were preferentially expressed in proximal dendrites. We validated the non-uniform distribution of NaP currents pharmacologically; with two-photon imaging of dendritic back-propagating action potentials; and by demonstrating boosting of thalamic, but not cortical, inputs by NaP currents. Thus, the localization of active dendritic conductances in CIN dendrites mirrors the spatial distribution of afferent terminals and may promote their differential responses to thalamic vs. cortical inputs.
Differential EDS1 requirement for cell death activities of plant TIR-domain proteins
Authors: Johanndrees Oliver , Baggs Erin L. , Uhlmann Charles , Locci Federica , Läßle Henriette L. , Melkonian Katharina , Käufer Kiara , Dongus Joram A. , Nakagami Hirofumi , Krasileva Ksenia V. , Parker Jane E. , Lapin Dmitry 
Published: November 2021

AbstractToll/interleukin-1 Receptor (TIR) domains are integral to immune systems across all domains of life. TIRs exist as single-domain and as larger receptor or adaptor proteins. In plants, TIRs constitute N-terminal domains of nucleotide-binding leucine-rich repeat (NLR) immune receptors. Although TIR-NLR and TIR signaling requires the Enhanced disease susceptibility 1 (EDS1) protein family, TIR domains persist in species that have incomplete or no EDS1 members. To assess whether particular TIR groups appear with EDS1, we searched for TIR-EDS1 co-occurrence patterns. Using a large-scale phylogenetic analysis of TIR domains from 39 algae and land plant species, we identify four conserved TIR groups, two of which are TIR-NLRs present in eudicots and two are more widespread. Presence of one TIR-only protein group is highly correlated with EDS1 and members of this group elicit EDS1-dependent cell death. By contrast, a more widely represented TIR group of TIR-NB-WD40/TPR (TNP) proteins (formerly called XTNX) has at least one member which can induce EDS1-independent cell death. Our data provide a new phylogeny-based plant TIR classification and identify TIR groups that appear to have evolved with and are dependent on EDS1, while others have EDS1-independent activity.One sentence summaryLand plants have evolved four conserved TIR groups
Bet-hedging antimicrobial strategies in macrophage phagosome acidification drive the dynamics ofCryptococcus neoformansintracellular escape mechanisms
Authors: Dragotakes Quigly , Jacobs Ella , Ramirez Lia Sanchez , Yoon Insun , Perez-Stable Caitlin , Eden Hope , Pagnotta Jenlu , Vij Raghav , Bergman Aviv , D’Alessio Franco , Casadevall Arturo 
Published: November 2021

AbstractThe fungusCryptococcus neoformansis a major human pathogen with a remarkable intracellular survival strategy that includes exiting macrophages through non-lytic exocytosis (Vomocytosis) and transferring between macrophages (Dragotcytosis) by a mechanism that involves sequential events of non-lytic exocytosis and phagocytosis. Vomocytosis and Dragotcytosis are fungal driven processes, but their triggers are not understood. We hypothesized that the dynamics of Dragotcytosis could inherit the stochasticity of phagolysosome acidification and that Dragotcytosis was triggered by fungal cell stress. Consistent with this view, fungal cells involved in Dragotcytosis reside in phagolysosomes characterized by low pH and/or high oxidative stress. Using fluorescent microscopy, qPCR, live cell video microscopy, and fungal growth assays we found that the that mitigating pH or oxidative stress abrogated Dragotcytosis frequency, that ROS susceptible mutants ofC. neoformansunderwent Dragotcytosis more frequently. Dragotcytosis initiation was linked to phagolysosomal pH and oxidative stresses and correlated with the macrophage polarization state. Dragotcytosis manifested stochastic dynamics thus paralleling the dynamics of phagosomal acidification, which correlated with the inhospitality of phagolysosomes in differently polarized macrophages. Hence, randomness in phagosomal acidification randomly created a population of inhospitable phagosomes where fungal cell stress triggered stochasticC. neoformansnon-lytic exocytosis dynamics to escape a non-permissive intracellular macrophage environment.
Structured connectivity in the cerebellum enables noise-resilient pattern separation
Authors: Nguyen Tri M. , Thomas Logan A. , Rhoades Jeff L. , Ricchi Ilaria , Yuan Xintong Cindy , Sheridan Arlo , Hildebrand David G. C. , Funke Jan , Regehr Wade G. , Lee Wei-Chung Allen 
Published: November 2021

SummaryThe cerebellum is thought to detect and correct errors between intended and executed commands1–3 and is critical for social behaviors, cognition and emotion4–6. Computations for motor control must be performed quickly to correct errors in real time and should be sensitive to small differences between patterns for fine error correction while being resilient to noise7. Influential theories of cerebellar information processing have largely assumed random network connectivity, which increases the encoding capacity of the network’s first layer8–13. However, maximizing encoding capacity reduces resiliency to noise7. To understand how neuronal circuits address this fundamental tradeoff, we mapped the feedforward connectivity in the mouse cerebellar cortex using automated large-scale transmission electron microscopy (EM) and convolutional neural network-based image segmentation. We found that both the input and output layers of the circuit exhibit redundant and selective connectivity motifs, which contrast with prevailing models. Numerical simulations suggest these redundant, non-random connectivity motifs increase discriminability of similar input patterns at a minimal cost to the network’s overall encoding capacity. This work reveals how neuronal network structure can balance encoding capacity and redundancy, unveiling principles of biological network architecture with implications for artificial neural network design.
Modeling Alternate Conformations with Alphafold2 via Modification of the Multiple Sequence Alignment
Authors: Stein Richard A. , Mchaourab Hassane S. 
Published: November 2021

ABSTRACTThe unprecedented performance of Deepmind’s Alphafold2 in predicting protein structure in CASP XIV and the creation of a database of structures for multiple proteomes is reshaping structural biology. Moreover, the availability of Alphafold2’s architecture and code has stimulated a number of questions on how to harness the capabilities of this remarkable tool. A question of central importance is whether Alphafold2’s architecture is amenable to predict the intrinsic conformational heterogeneity of proteins. A general approach presented here builds on a simple manipulation of the multiple sequence alignment, via in silico mutagenesis, and subsequent modeling by Alphafold2. The approach is based in the concept that the multiple sequence alignment encodes for the structural heterogeneity, thus its rational manipulation will enable Alphafold2 to sample alternate conformations and potentially structural alterations due to point mutations. This modeling pipeline is benchmarked against canonical examples of protein conformational flexibility and applied to interrogate the conformational landscape of membrane proteins. This work broadens the applicability of Alphafold2 by generating multiple protein conformations to be tested biologically, biochemically, biophysically, and for use in structure-based drug design.
TRPA1: A Potential Prognostic Indicator for Oral Squamous Cell Carcinoma
Authors: Chakraborty Rajdeep , Jabeen Amara , Hu Honghua , Darido Charbel , Vickery Karen , Ranganathan Shoba 
Published: November 2021

AbstractIntroductionTransient receptors are related to oral cancer pain. Previously capsaicin (TRPV1 agonist) was shown to induce cell death in oral cancer cells. We hypothesised that these receptors are present in oral cancer.MethodWe examined the presence of cannabinoid receptors (CB1 and CB2) and targets (TRPV1, TRPA1, CaV 3.1, CaV 3.2, CaV 3.3) via quantitative polymerase chain reaction (qPCR) in oral cancer cells SCC4, SCC9, SCC25, Cal27, and normal oral cell line OKF6.ResultCannabinoid receptors are absent in all the cell lines, while TRPA1 is only present in normal cells, but absent in all the oral cancer cell lines. Voltage-gated calcium channels are present in all the cell lines.Conclusion and Future AspectsTRPA1 could be the possible future prognostic indicator of oral squamous cell carcinoma. Future functionality assays could use precancerous cell lines to follow the loss of TRPA1.
Coping with COVID-19 Stressors: Adverse and Protective Factors Responding to Emotions in a Chinese Sample
Authors: Xu Rui , Zhang Xinfeng , Liu Danni , Li Qiang , Wang Yanping , Jiao Rong , Gong Ximei , Hou Xueyan , Xu Tao , Qing Xuemei , Song Kangxing , Kavcic Voyko , Yan Shiyan , Gu Ruolei , Stratton Terry , Jiang Yang 
Published: November 2021

AbstractBackgroundThe potential roles of affective responses to environmental stressors in individuals’ physical and mental health are complex and multi-faceted. This study, then, explores Chinese citizens’ emotional responses to COVID-19-related stressors and influence factors which may boost or buffer such effects.MethodsFrom late March to early June (2020), a cross-sectional study was conducted using an anonymous online questionnaire included demographic characteristics, COVID-19-related stressors related to individuals’ daily functioning, and the self-assessed impact of protective and adverse internal factors on emotions.Results1,662 questionnaires were received from residents in 32 Chinese provinces classified by prevalence level according to COVID-19 infections. Among the 17 positive and negative emotional responses, agglomerative hierarchical clustering revealed four subclassifications: (1) stress relations; (2) missing someone relations; (3) individual relations; and (4) social relations. Additionally, heightened regional prevalence levels positively corresponded to intensity of stress relations. Lowest intensity of social relations was found in the areas surrounding Wuhan and coastal areas. Specially, economic- and work-related stressors as well as negative self-perceptions (e.g., suppression, emotionally unstable, self-denial) implicated in negative emotions. While positive emotions were tied to demographic characteristics (e.g., high education, young age and male) and protective traits (e.g., creativity, sympathy, social responsibility), and inversely linked to relationships- and pandemic-related stressors, etc.ConclusionAssociations were clearly noted among Chinese residents’ emotions to specific stressors during pandemic. Providing appropriate psychological resources/supports during future or extended public health crises may help offset the cognitive burden of individuals striving to regain an adequate level of normalcy and emotional well-being.
The ulcerative colitis associated gene FUT8 regulates the quantity and quality of secreted mucins
Authors: Cantero-Recasens Gerard , Burballa Carla , Ohkawa Yuki , Fukuda Tomohiko , Harada Yoichiro ,   IBD Character Consortium, Curwin Amy , Brouwers Nathalie , Thun Gian A. , Gu Jianguo , Gut Ivo , Taniguchi Naoyuki , Malhotra Vivek 
Published: November 2021

ABSTRACTFucosylation of mucins, the main macrocomponents of the mucus layer that protects the digestive tract from pathogens, increases their viscoelasticity and shear stress resistance. These properties are altered in patients with ulcerative colitis (UC), which is marked by a chronic inflammation of the distal part of the colon. Here we show that the levels of Fucosyltransferase 8 (FUT8) and specific mucins are increased in the distal inflamed colon of UC patients compared to normal individuals. Overexpressing FUT8, as observed in UC, in mucin-producing HT29-18N2 colonic cell line increases trafficking of MUC1 to plasma membrane and secretion of MUC2/MUC5AC. FUT8 depletion (FUT8 KD), instead, causes intracellular accumulation of MUC1 and alters the ratio of secreted MUC2 to MUC5AC. Mucins secreted by FUT8 overexpressing cells are more resistant to shear stress compared to mucins secreted by FUT8 KD cells. These data fit well with the Fut8−/− mice phenotype, which are protected against UC. Fut8−/− mice exhibit a thinner proximal colon mucus layer with an altered ratio of neutral to acidic mucins compared to Fut8+/+ mice. Together, these data reveal that FUT8 optimizes the viscoelastic properties of the extracellular mucous by controlling the quantities of mucins secreted.SIGNIFICANCE STATEMENTMucins, the major components of the mucous barrier that protects our body from pathogens, are heavily glycosylated proteins. Changes their amounts and properties will alter the viscosity of mucous. Here we show that FUT8, a glycosylation enzyme of the Golgi apparatus, can control the viscosity of secreted mucins. Mucin secreting cells of the distal colon express FUT8, but their levels are altered in Ulcerative colitis patients. As a result, mucous produced by these cells is easily washed away, which exposes them to pathogens. We suggest that a defective mucous production is the main cause of initial inflammation observed in disease. Our findings help in understanding how cells control the quality of mucins and provide a means to prevent Ulcerative colitis.
Comparison of the somatic TADs and lampbrush chromomere-loop complexes in transcriptionally active prophase I oocytes
Authors: Kulikova Tatiana , Maslova Antonina , Starshova Polina , Rodriguez Sebastian Juan , Krasikova Alla 
Published: November 2021

AbstractIn diplotene oocyte nuclei of all vertebrate species, except mammals, chromosomes lack interchromosomal contacts and chromatin is linearly compartmentalized into distinct chromomere-loop complexes forming lampbrush chromosomes. However, the mechanisms underlying the formation of chromomere-loop complexes remain unexplored. Here we aimed to juxtapose somatic topologically associating domains (TADs), recently identified in chicken embryonic fibroblasts, with chromomere-loop complexes in lampbrush meiotic chromosomes. By measuring 3D-distances and colocalization between linear equidistantly located genomic loci, positioned within one TAD or separated by a TAD border, we confirmed the presence of predicted TADs in chicken embryonic fibroblast nuclei. Using three-colored FISH with BAC probes we mapped equidistant genomic regions included in several sequential somatic TADs on isolated chicken lampbrush chromosomes. Eight genomic regions, each comprising two or three somatic TADs, were mapped to non-overlapping neighboring lampbrush chromatin domains – lateral loops, chromomeres or chromomere-loop complexes. Genomic loci from the neighboring somatic TADs could localize in one lampbrush chromomere-loop complex, while genomic loci belonging to the same somatic TAD could be localized in neighboring lampbrush chromomere- loop domains. In addition, FISH-mapping of BAC probes to the nascent transcripts on the lateral loops indicates transcription of at least 17 protein-coding genes and 2 non-coding RNA genes during the lampbrush stage of chicken oogenesis, including genes involved in oocyte maturation and early embryo development.
Hypothesis: Colony-forming activity of pluripotent stem cell-derived hepatocyte-like cells for stem cell assay
Authors: Ite Kenta , Toyoda Masashi , Akiyama Saeko , Enosawa Shin , Yoshioka Saeko , Yukitake Takaaki , Yamazaki-Inoue Mayu , Tatsumi Kuniko , Akutsu Hidenori , Nishina Hiroshi , Kimura Toru , Otani Naoko , Nakazawa Atsuko , Fukuda Akinari , Kasahara Mureo , Umezawa Akihiro 
Published: November 2021

ABSTRACTHepatocyte-like cells (HLCs) generated from human pluripotent stem cells (PSCs) exhibit hepatocytic properties in vitro; however, their engraftment and functionality in vivo remain unsatisfactory. Despite optimization of differentiation protocols, HLCs did not engraft in a mouse model of liver injury. In contrast, organ-derived hepatocytes reproducibly formed colonies in the liver injury mouse model. As an extension of the phenomenon observed in hematopoietic stem cells giving rise to colonies within the spleen, commonly referred to as “colony-forming units in spleen (CFU-s“, we hypothesize that “colony-forming units in liver (CFU-L)“ serves as a reliable indicator of stemness, engraftment, and functionality of hepatocytes. The uniform expression of the randomly inactivated gene in a single colony, as reported by Sugahara et al. 2022, suggests that the colonies generated by isolated hepatocytes likely originate from a single cell. We, therefore, propose that CFU-L can be used to quantify the number of “hepatocytes that engraft and proliferate in vivo“ as a quantitative assay for stem cells that utilize colony-forming ability, similar to that observed in hematopoietic stem cells.