bluuebunny/crossref_metadata_2025_split huggingface dataset:
Intestinal inflammation reversibly alters the microbiota to drive susceptibility to Clostridioides difficile colonization in a mouse model of colitis
Authors: Barron Madeline R. , Sovacool Kelly L. , Abernathy-Close Lisa , Vendrov Kimberly C. , Standke Alexandra K. , Bergin Ingrid L. , Schloss Patrick D. , Young Vincent B. 
Published: April 2022

AbstractSusceptibility to Clostridioides difficile infection (CDI) typically follows the administration of antibiotics. Patients with inflammatory bowel disease (IBD) have increased incidence of CDI, even in the absence of antibiotic treatment. However, the mechanisms underlying this susceptibility are not well understood. To explore the intersection between CDI and IBD, we recently described a mouse model where colitis triggered by the murine gut bacterium, Helicobacter hepaticus, in IL-10-/- mice led to susceptibility to C. difficile colonization without antibiotic administration. The current work disentangles the relative contributions of inflammation and gut microbiota in colonization resistance to C. difficile in this model. We show that inflammation drives changes in microbiota composition, which leads to CDI susceptibility. Decreasing inflammation with an anti-p40 monoclonal antibody promotes a shift of the microbiota back toward a colonization-resistant state. Transferring microbiota from susceptible and resistant mice to germ-free animals transfers the susceptibility phenotype, supporting the primacy of the microbiota in colonization resistance. These findings shine light on the complex interactions between the host, microbiota, and C. difficile in the context of intestinal inflammation, and may form a basis for the development of strategies to prevent or treat CDI in IBD patients.ImportancePatients with inflammatory bowel disease (IBD) have an increased risk of developing C. difficile infection (CDI), even in the absence of antibiotic treatment. Yet, mechanisms regulating C. difficile colonization in IBD patients remain unclear. Here, we use an antibiotic-independent mouse model to demonstrate that intestinal inflammation alters microbiota composition to permit C. difficile colonization in mice with colitis. Notably, treating inflammation with an anti-p40 monoclonal antibody, a clinically relevant IBD therapeutic, restores microbiota-mediated colonization resistance to the pathogen. Through microbiota transfer experiments in germ-free mice, we confirm that the microbiota shaped in the setting of IBD is the primary driver of susceptibility to C. diffiicile colonization. Collectively, our findings provide insight into CDI pathogenesis in the context of intestinal inflammation, which may inform methods to manage infection in IBD patients. More broadly, this work advances our understanding of mechanisms by which the host-microbiota interface modulates colonization resistance to C. difficile.
Can neurogenesis act as a neural regularizer?
Authors: Tran Lina M. , Santoro Adam , Liu Lulu , Josselyn Sheena A. , Richards Blake A. , Frankland Paul W. 
Published: April 2022

AbstractNew neurons are continuously generated in the subgranular zone of the dentate gyrus throughout adulthood. These new neurons gradually integrate into hippocampal circuits, forming new naïve synapses. Viewed from this perspective, these new neurons may represent a significant source of ‘wiring’ noise in hippocampal networks. In machine learning, such noise injection is commonly used as a regularization technique. Regularization techniques help prevent overfitting training data, and allow models to generalize learning to new, unseen data. Using a computational modeling approach, here we ask whether a neurogenesis-like process similarly acts as a regularizer, facilitating generalization in a category learning task. In a convolutional neural network (CNN) trained on the CIFAR-10 object recognition dataset, we modeled neurogenesis as a replacement/turnover mechanism, where weights for a randomly chosen small subset of neurons in a chosen hidden layer were re-initialized to new values as the model learned to categorize 10 different classes of objects. We found that neurogenesis enhanced generalization on unseen test data compared to networks with no neurogenesis. Moreover, neurogenic networks either outperformed or performed similarly to networks with conventional noise injection (i.e., dropout, weight decay, and neural noise). These results suggest that neurogenesis can enhance generalization in hippocampal learning through noise-injection, expanding on the roles that neurogenesis may have in cognition.Author SummaryIn deep neural networks, various forms of noise injection are used as regularization techniques to prevent overfitting and promote generalization on unseen test data. Here, we were interested in whether adult neurogenesis– the lifelong production of new neurons in the hippocampus– might similarly function as a regularizer in the brain. We explored this question computationally, assessing whether implementing a neurogenesis-like process in a hidden layer within a convolutional neural network trained in a category learning task would prevent overfitting and promote generalization. We found that neurogenesis regularization was as least as effective as, or more effective than, conventional regularizers (i.e., dropout, weight decay and neural noise) in improving model performance. These results suggest that optimal levels of hippocampal neurogenesis may improve memory-guided decision making by preventing overfitting, thereby promoting the formation of more generalized memories that can be applied in a broader range of circumstances. We outline how these predictions may be evaluated behaviorally in rodents with altered hippocampal neurogenesis.
The multi-BRCT domain protein DDRM2 is required for homologous recombination in plants
Authors: Wang Lili , Yu Chen , Hou Longhui , Huang Yongchi , Cui Xiaoyu , Xu Shijun , Yan Shunping 
Published: April 2022

AbstractDNA double-strand breaks (DSBs) are the most toxic DNA damage for cells. Homologous recombination (HR) is a precise DSB repair mechanism as well as a basis for gene targeting using genome-editing techniques. Despite the importance of HR, the HR mechanism in plants is poorly understood. In a genetic screen for DNA Damage Response Mutants (DDRMs), we find that the Arabidopsisddrm2mutant is hypersensitive to DSB-inducing reagents. DDRM2 encodes a protein with four BRCA1 C-terminal (BRCT) domains and is highly conserved in plants including the earliest land plant linage, bryophytes. The plant-specific transcription factor SOG1 binds to the promoter ofDDRM2and activates its expression, suggesting thatDDRM2is a direct target of SOG1. In consistence, the expression ofDDRM2is induced by DSBs in a SOG1-dependent manner. Epistasis analysis indicates that DDRM2 functions downstream of SOG1. Similar to thesog1mutant, theddrm2mutant shows dramatically reduced HR efficiency. Our study suggests that the SOG1-DDRM2 module is required for HR, providing new insights into the HR mechanisms in plants and a potential target for improving the efficiency of gene targeting.One Sentence SummaryA genetic screen in Arabidopsis reveals that the multi-BRCT domain protein DDRM2 is required for homologous recombination and is targeted by the master DNA damage response regulator SOG1.
Traits of soil bacteria predict plant responses to soil moisture
Authors: Bolin Lana G. , Lennon Jay T. , Lau Jennifer A. 
Published: April 2022

ABSTRACTMicrobes can promote beneficial plant and animal responses to abiotic environments, but the ecological drivers of this benefit remain elusive. Here we investigated byproduct benefits, which occur when traits that increase the fitness of one species provide incidental benefits to another species with no direct cost to the provider species. In experimental mesocosms, microbial traits predicted plant responses to soil moisture such that bacteria with self-beneficial traits in drought increased plant early growth, size at reproduction, and chlorophyll concentration under drought, while bacteria with self-beneficial traits in well-watered environments increased these same plant traits in well-watered environments. Thus, microbial traits that promote microbial success in different soil moisture environments also promote plant success in these same environments. Our results show that the concept of byproduct benefits, originally conceived to explain the evolution of cooperation in pairwise mutualisms, also applies to interactions between plants and non-symbiotic soil microbes.
Liver-secreted fluorescent blood plasma markers enable chronic imaging of microcirculation
Authors: Wang Xiaowen , Delle Christine , Asiminas Antonis , Akther Sonam , Vittani Marta , Brøgger Peter , Kusk Peter , Vo Camilla Trang , Konno Ayumu , Hirai Hirokazu , Fukuda Masahiro , Weikop Pia , Goldman Steven A , Nedergaard Maiken , Hirase Hajime 
Published: April 2022

AbstractStudying blood microcirculation is vital for gaining insights into vascular diseases. Acute administration of fluorescent tracers is currently used for deep tissue blood flow imaging. This is invasive, and the plasma fluorescence decreases within an hour of administration. We report a novel approach for the longitudinal study of vasculature. Using a single systemic administration of viral vectors, we express fluorescent secretory albumin-fusion proteins in the liver to label the blood in mice. All segments of the vasculature in brain and peripheral tissue are observable by two-photon microscopy within two weeks of vector administration. This approach allows for observation of circulation without the need for repeated administration for several months. We demonstrate the chronic assessment of vascular functions at micro-and mesoscopic scales. This genetic plasma labeling approach represents a versatile and cost-effective method for the chronic investigation of vasculature functions across the body in health and disease.
Functionally and structurally distinct fusiform face area(s) in over 1000 participants
Authors: Chen Xiayu , Liu Xingyu , Parker Benjamin J. , Zhen Zonglei , Weiner Kevin S. 
Published: April 2022

ABSTRACTThe Fusiform Face Area (FFA) is a widely studied region causally involved in face perception. Even though cognitive neuroscientists have been studying the FFA for over two decades, answers to foundational questions regarding the structure, function, and connectivity of the FFA from a large (N>1000) group of participants are still lacking. To fill this gap, we quantified structural, functional, and connectivity features of fusiform face-selective regions in 1080 participants in the Human Connectome Project (HCP). After manually defining over 4,000 fusiform face-selective regions, we report five main findings. First, 68.94% of hemispheres have two cortically separate regions (pFus-faces/FFA-1 and mFus-faces/FFA-2). Second, in 26.48% of hemispheres, pFus-faces/FFA-1 and mFus-faces/FFA-2 are spatially contiguous, yet functionally and structurally distinct. Third, pFus-faces/FFA-1 is more face-selective than mFus-faces/FFA-2, and the two regions have distinct functional connectivity fingerprints. Fourth, pFus-faces/FFA-1 is cortically thinner and more heavily myelinated than mFus-faces/FFA-2. Fifth, face-selective patterns and functional connectivity fingerprints of each region were more similar in monozygotic than dizygotic twins and more so than structural gradients. As we share our areal definitions with the field, future studies can explore how structural and functional features of these regions will inform theories regarding how visual categories are represented in the brain.
NEUROeSTIMator: Using Deep Learning to Quantify Neuronal Activation from Single-Cell and Spatial Transcriptomic Data
Authors: Bahl Ethan , Chatterjee Snehajyoti , Mukherjee Utsav , Elsadany Muhammad , Vanrobaeys Yann , Lin Li-Chun , McDonough Miriam , Resch Jon , Giese K Peter , Abel Ted , Michaelson Jacob J. 
Published: April 2022

ABSTRACTNeuronal activity-dependent transcription directs molecular processes that regulate synaptic plasticity, brain circuit development, behavioral adaptation, and long-term memory. Single cell RNA-sequencing technologies (scRNAseq) are rapidly developing and allow for the interrogation of activity-dependent transcription at cellular resolution. Here, we present NEUROeSTIMator, a deep learning model that integrates transcriptomic signals to estimate neuronal activation in a way that we demonstrate is associated with Patch-seq electrophysiological features and that is robust against differences in species, cell type, and brain region. We demonstrate this method’s ability to accurately detect neuronal activity in previously published studies of single cell activity-induced gene expression. Further, we applied our model in a spatial transcriptomic study to identify unique patterns of learning-induced activity across different brain regions. Altogether, our findings establish NEUROeSTIMator as a powerful and broadly applicable tool for measuring neuronal activation, whether as a critical covariate or a primary readout of interest.
Acquired resistance to anti-PD1 therapy in patients with NSCLC reveals changes in T cell phenotypes and MET amplification
Authors: Hiltbrunner Stefanie , Cords Lena , Kasser Sabrina , Freiberger Sandra N. , Kreutzer Susanne , Toussaint Nora C. , Grob Linda , Opitz Isabelle , Messerli Michael , Zoche Martin , Soltermann Alex , Rechsteiner Markus , van den Broek Maries , Bodenmiller Bernd , Curioni-Fontecedro Alessandra 
Published: April 2022

AbstractThe treatment of non-small cell lung cancer (NSCLC) patients with immune checkpoint inhibitors has prolonged their survival dramatically. However, some patients develop resistance after initial response. Here, we used imaging mass cytometry and whole exome and RNA sequencing to analyze matching tumor samples from a cohort of NSCLC patients who initially responded to immune checkpoint inhibitor therapy and later developed acquired resistance. We detected two patterns of resistance: One group of patients had reduced numbers of tumor-infiltrating CD8+ T cells and reduced expression of PD-L1 after development of resistance, whereas the other group showed high CD8+ T cell infiltration and high expression of PD-L1 and markedly elevated expression of other immune-inhibitory molecules. In two cases, we detected downregulation of type I and II IFN pathways after resistance developed, which could lead to an impaired anti-tumor immune response. This study adds to our knowledge of the mechanisms that cause resistance to immunotherapy in NSCLC patients.
Pneumococcus suppresses host inflammatory response through COMMD2 mediated NF-κB degradation by aggrephagy
Authors: Connor Michael G. , Sanchez Lisa , Chevalier Christine , Carvalho Filipe , Eldridge Matthew G. , Chaze Thibault , Matondo Mariette , Weight Caroline M. , Dufour Sara , Impens Francis , Baumgarten Sebastian , Enninga Jost , Hamon Melanie A. 
Published: April 2022

AbstractNF-κB driven cellular immunity is essential for both pro- and anti-inflammatory responses to microbes, which makes it one of the most frequently targeted pathways by bacteria during pathogenesis. How NF-κB tunes the epithelial response toStreptococcus pneumoniaeacross the spectrum of commensal to pathogenic outcomes is not fully understood. In this study, we compare a commensal-like 6B ST90 strain to an invasive TIGR4 isolate and demonstrate that TIGR4 both blunts and antagonizes NF-κB activation. We identified, through comparative mass spectrometry of the p65 interactome, that the 6B ST90 isolate drives a non-canonical NF-κB RelB cascade, whereas TIGR4 induces p65 degradation though aggrephagy. Mechanistically, TIGR4 challenge triggers a novel interaction of COMMD2 with p65 and p62. This complex mediates export of p65 for degradation and is necessary for repressing host inflammatory transcription. With these results, we reveal for the first time a new bacterial pathogenesis mechanism to repress host inflammatory response though COMMD2 mediated turnover of p65, and present a paradigm for diverging NF-κB responses to pneumococcus.
RetroSnake: a Modular End-to-End Pipeline for Detection of Human Endogenous Retrovirus (HERV) Transposable Elements in Next Generation Sequencing (NGS) Data
Authors: Kabiljo Renata , Bowles Harry , Marriott Heather , Jones Ashley R. , Dobson Richard JB , Quinn John P , Swanson Chad M , Al-Chalabi Ammar , Iacoangeli Alfredo 
Published: April 2022

AbstractHuman Endogenous Retroviruses (HERVs) integrated into the genome of vertebrates as a result of ancient exogenous infections and currently comprise ∼8% of our genome. The majority of these elements have accumulated mutations rendering them inactive. The most recently acquired members, HERV-K have potential to produce viral particles and have been linked to a wide range of diseases including cancer and neurodegeneration. Although a range of tools for HERV discovery exist, most of them lack wet-lab validation of their results and are not end-to-end as they do not cover all steps of the analysis. These factors greatly limit their use. Here we describe RetroSnake, an end-to-end, modular, computationally efficient and customisable pipeline for the discovery of HERVs in short-read NGS data. RetroSnake presents important advantages with respect to other available tools. For instance, it is the only pipeline based on an extensively wet-lab validated protocol, and it is the most complete transposable elements detection pipeline, producing annotated insertions presented as an interactive html file, easy enough to use by life scientists without substantial computational training.Availability and implementationThe Pipeline and an extensive documentation are available at https://github.com/KHP-Informatics/RetroSnakeContactalfredo.iacoangeli@kcl.ac.uk
Multitrait diversification in marine diatoms in constant and warmed environments
Authors: Hinners Jana , Argyle Phoebe A. , Walworth Nathan G. , Doblin Martina A. , Levine Naomi M. , Collins Sinéad 
Published: April 2022

AbstractPhytoplankton are photosynthetic marine microbes that affect food webs, nutrient cycles, and climate regulation. Their roles are determined by a correlated set of phytoplankton functional traits including cell size, chlorophyll content, and cellular composition. Here, we explore how interrelated trait values and correlations evolve. Because both chance events and natural selection contribute to phytoplankton trait evolution, we used population bottlenecks to diversify six genotypes of Thalassiosirid diatoms. We then evolved them in two environments where natural selection could act on this diversity. Interspecific variation and within-species evolution were visualized for nine traits and their correlations using reduced axes (a trait-scape). Shifts in both trait values and correlations, resulting in movement of evolving populations on the trait-scape, occurred in both environments, and were more frequent under environmental change. Which trait correlations evolved was strain-specific, but greater departures from ancestral trait correlations were associated with lower population growth rates. There was no single master trait that could be used to understand multitrait evolution. Instead, repeatable multitrait evolution occurred along a major axis of variation defined by several diatom functional traits and trait relationships. Because trait-scapes capture changes in trait correlations and values together, they offer an insightful way to study multitrait variation.
The GUN mutants: new weapons to unravel ascospore germination regulation in the model fungus Podospora anserina
Authors: Demoor Alexander , Lacaze Isabelle , Ferrari Roselyne , Lalanne Christophe , Silar Philippe , Brun Sylvain 
Published: April 2022

AbstractIn Podospora anserina as in many other ascomycetes, ascospore germination is a regulated process that requires breaking of dormancy. Despite its importance in survival and dispersal, ascospore germination in filamentous fungi has been poorly investigated and little is known about its regulation and genetic control. We have designed a positive genetic screen that led to the isolation of mutants showing uncontrolled germination, the GUN mutants. In this paper, we report on the characterization of GUN1SG. We show that GUN1SG is mutated in Pa_6_1340, the ortholog of Magnaporthe oryzae Pth2, which encodes a Carnitine-acetyltransferase (CAT) involved in the shuttling of acetyl-CoA between peroxisomes and mitochondria and which is required for appressorium-development. Bioinformatic analysis revealed that the mutated residue (I441) is highly conserved among the Fungi, and that the mutation has a deleterious impact on the protein function. We show that GUN1 is essential for ascospore germination and that the protein is localized both in mitochondria and in peroxisomes. Finally, epistasis studies allowed us to place GUN1 upstream of the PaMpk2 MAPK pathway and the PaNox2/PaPls1 complex in the regulation of ascospore germination. The identification of GUN1, the ortholog of Pth2, in ascospore germination, strengthens the idea of a common genetic regulation governing both appressorium development and melanized ascospore germination. In addition, we characterize the second CAT encoded in P. anserina genome, Pa_3_7660/GUP1, and we show that the function of both CATs is conserved in P. anserina.
Wax worm saliva and the enzymes therein are the key to polyethylene degradation by Galleria mellonella
Authors: Sanluis-Verdes A. , Colomer-Vidal P. , Rodríguez-Ventura F. , Bello-Villarino M. , Spinola-Amilibia M. , Ruiz-López E. , Illanes-Vicioso R. , Castroviejo P. , Cigliano R. Aiese , Montoya M. , Falabella P. , Pesquera C. , González-Legarreta L. , Arias-Palomo E. , Solà M. , Torroba T. , Arias C.F. , Bertocchini F. 
Published: April 2022

ABSTRACTPlastic degradation by biological systems with re-utilization of the by-products can be the future solution to the global threat of plastic waste accumulation. We report that the saliva of Galleria mellonella larvae (wax worms) is capable of oxidizing and depolymerizing polyethylene (PE), one of the most produced and sturdy polyolefin-derived plastics. This effect is achieved after a few hours’ exposure at room temperature and physiological conditions (neutral pH). The wax worm saliva can indeed overcome the bottleneck step in PE biodegradation, that is the initial oxidation step. Within the saliva, we identified two enzymes that can reproduce the same effect. This is the first report of enzymes with this capability, opening up the way to new ground-breaking solutions for plastic waste management through bio-recycling/up-cycling.
Dietary and Reproductive Traits of Two Brachyuran Crab Species
Authors: Potter Ben , Cannizzo Zachary J. , Griffen Blaine D. 
Published: April 2022

AbstractMany animals have flexible morphological traits that allow them to succeed in differing circumstances with differing diets available to them. For brachyuran crabs, claw height and gut size are diet-specific and largely reflect foraging strategies, while abdomen width reflects relative levels of fecundity. However, the link between claw size and diet has largely been documented only for primarily carnivorous crabs, while the link between diet and fecundity is strong in herbivorous crabs. We sought to determine the nature of the intraspecific relationship between claw size, dietary habits, and fecundity for two primarily herbivorous crab species, Hemigrapsus sanguineus and Aratus pisonii. Specifically, we examined whether claw size and/or abdomen width can be used as reliable measures of individual diet strategy. To test these hypotheses, we collected crabs and measured the dimensions of their claws, abdomens, and guts. By comparing these dimensions for each individual, we found that strongly predictive relationships do not exist between these traits for the primarily herbivorous species in our study. Thus, identifying external morphological features that can be used to assess diets of primarily herbivorous crabs remains elusive.