bluuebunny/crossref_metadata_2025_split huggingface dataset:
Sequencing analysis ofHelicobacter pyloriinfection in gastric mucosa and its progression to gastric mucosa-associated tissue (MALT) lymphoma
Authors: Yoo Seung-Joo , Koh Youngil , Byun Ja Min , Hong Junshik , Shin Dong-Yeop , Chun Jaeyoung , Chung Hyunsoo , Yoon Sung-Soo 
Published: April 2024

AbstractIntroductionThe pathogenesis of gastric mucosa-associated tissue (MALT) lymphoma is associated withHelicobacter pyloriinfection. Although treatment strategies and responsiveness according to the stage of gastric MALT lymphoma have been widely reported, a detailed study of the biological carcinogenic process is still required.MethodPaired, fresh tumor-adjacent normal and gastric mucosal tissue samples from 13 patients with gastric MALT lymphoma were prospectively collected. Whole exome sequencing (WES) and whole-transcriptome sequencing (WTS) data were generated. The analysis of mutations, gene fusion, gene expression, and the microbiome was stratified byH. pyloriinfection and disease status.ResultsSomatic mutations inTRAF3andTNFAIP3were identified inH. pylori-negative gastric MALT lymphoma. Fusions involvingBIRC3-MALT1(2 samples) andTBL1XR1-TP63(1 sample withH. pyloriinfection) were detected. Stepwise comparative analysis of RNA expression revealed upregulation of immune response, inflammatory responses, and the NF- κB signaling pathway inH. pylori-positive MALT lymphoma cases. Pathways associated with pathogens were upregulated inH. pylori-negative MALT lymphoma cases, suggesting that infections other thanH. pylorimay affect lymphomagenesis. Microbiome analysis revealed thatgenus_Rothiawas negatively correlated with alpha diversity.ConclusionA stepwise approach using diverse stages of WTS data revealed detailed pathogenic mechanisms of gastric MALT lymphoma. Chronic inflammation following infection contributes to gastric MALT lymphomagenesis in bothH. pyloripositive and negative cases.
Molecular responses of chicken embryos to maternal heat stress through DNA methylation and gene expression
Authors: Karami Keyvan , Sabban Jules , Cerutti Chloé , Devailly Guillaume , Foissac Sylvain , Gourichon David , Hubert Alexandre , Hubert Jean-Noël , Leroux Sophie , Zerjal Tatiana , Lagarrigue Sandrine , Pitel Frédérique 
Published: April 2024

AbstractClimate change, with its repercussions on agriculture, is one of the most important adaptation challenges for livestock production. Poultry production is a major source of proteins for human consumption all over the world. With a growing human population, improving poultry’s adaptation to environmental constraints becomes critical. Extensive evidence highlights the influence of environmental variations on epigenetic modifications. The aim of this paper is therefore to explore chickens’ molecular response to maternal heat stress. We employed Reduced Representation Bisulfite Sequencing (RRBS) to generate genome-wide single-base resolution DNA methylation profiling and RNA sequencing (RNA-seq) to profile the transcriptome of the brains of embryos hatched from dams reared under either heat stress (32 °C) or thermoneutrality (22°C). We detected 289 significant differentially methylated CpG sites (DMCs) and one differentially methylated region (DMR) between heat stressed and control groups. These DMCs were associated with 357 genes involved in processes such as cellular response to stimulus, developmental processes and immune function. In addition, we identified 11 genes differentially expressed between the two groups of embryos, and identified ATP9A as a target gene of maternal heat stress on offspring. This study provides a body of fundamental knowledge on adaptive mechanisms concerning heat tolerance in chickens.
A sequence- and structure-based characterization of microbial enzymes identifies P. stutzeri as a plastic-degrading species
Authors: Hong Alexander , Turner Serafina , Glazer Rita , Weishampel Zachary A. , Vispute Atharva , Huang Ashley , Holmes Zachary A. , Schleupner Beatrice , Dunphy-Daly Meagan M. , Eward William C. , Somarelli Jason A. 
Published: April 2024

AbstractPlastic waste has accumulated rapidly in the past century and is now found throughout every ecosystem on Earth. Its ubiquitous presence means that plastic is routinely ingested by countless organisms, with potential negative consequences for organismal health. New solutions are urgently needed to combat plastic pollution. Among the many strategies required to curb the plastic pollution crisis, the bioremediation of plastic via enzymatic activity of microbial species represents a promising approach. Diverse microbes harbor enzymes capable of degrading plastic polymers and utilizing the polymers as a carbon source. Herein, we characterize the landscape of microbial protein-coding sequences with potential plastic degrading capability. Using the two enzyme systems of PETase and MHETase as a guide, we combined sequence motif analysis, phylogenetic inference, and machine learning-guided 3D protein structure prediction to pinpoint potential plastic-degrading enzymes. Our analysis platform identified hundreds of enzymes from diverse microbial taxa with similarity to known PETases, and far fewer enzymes with similarity to known MHETases. Phylogenetic reconstruction revealed that the plastic degrading enzymes formed distinct clades from the sequences of ancestral enzymes. Among the potential candidate sequences, we pinpointed both a PETase-like and MHETase-like enzyme within the bacteriumPseudomonas stutzeri. Using plate clearing assays, we demonstrated thatP. stutzeriis capable of degrading both polyurethane (Impranil®) and polycaprolactone (PCL).Pseudomonas stutzerialso grew on carbon-free agar supplemented with polystyrene, suggesting this organism can utilize synthetic polymers as a carbon source. Overall, our integrated bioinformatics and experimental approach provides a rapid and low-cost solution to identify and test novel polymer-degrading enzymes for use in the development of plastic bioremediation technologies.
Traction Force Microscopy with DNA FluoroCubes
Authors: Mortazavi Armina , Jiang Jianfei , Laric Philip , Helmerich Dominic A. , Seifert Rick , Sauer Markus , Sabass Benedikt 
Published: April 2024

AbstractFrom cell differentiation to morphogenesis and cell migration, a multitude of processes are coordinated by mechanical forces that cells generate. Among diverse techniques to assess the mechanical properties of the cell, traction force microscopy (TFM) has emerged as one of the most popular methods for quantifying cell-generated stresses. Standard TFM procedures rely on fiducial markers in the extracellular environment to measure the deformations that are caused by cellular forces. Typically, fluorescent beads are used as fiducials. However, the replacement of beads with fluorescently labeled DNA structures can have numerous advantages, including a smaller size of the markers and the possibility of customizing the DNA structures, for example to read out orthogonal information or to realize a switchable surface functionalization. Here, we develop a multi-purpose platform for combining such setups with TFM. As fiducials we employ FluoroCubes – nanometer-sized DNA constructs - for TFM. These constructs are grafted to a high refractive index polyethylene siloxane surface for the precise tracking of displacements resulting from cell-generated forces. To ensure a local transmission of traction forces from the adhesion ligands to the substrate, we also graft RGD peptides, which represent the smallest ligands of the extracellular matrix, onto our elastic substrates. To further enhance the spatial resolution of the TFM, FluoroCubes can be supplemented with densely packed fluorescent beads as fiducials. We propose a modification of the Kanade-Lucas-Tomasi (KLT) optical flow tracking (OFT) algorithm for optimal, simultaneous tracking of FluoroCubes and beads. Together, the developed experimental setup and tracking algorithm yield highly resolved maps of traction forces that correlate well with the spatial distribution of kindlin at focal adhesions.
Defining mononuclear phagocyte distribution and behaviour in the zebrafish heart
Authors: Moyse Bethany , Moss Joanna , Bevan Laura , Scott Aaron , Wittamer Valérie , Richardson Rebecca J. 
Published: April 2024

AbstractMononuclear phagocytes (MNPs) are recognised as highly plastic, multifunctional cells that influence multiple physiological and pathophysiological states. In the heart, they support homeostatic functions, contribute to disease progression and play multiple roles in reparative and regenerative processes following tissue damage. Understanding the heterogeneous populations of cells that contribute to these diverse functions is crucial to facilitating beneficial, and limiting adverse, cardiac outcomes. However, characterisation of precise populations of cardiac immune cells remains incomplete in vertebrate models capable of endogenous regeneration, such as adult zebrafish. Here, we use a combination of transgenic lines to identify distinct MNPs in the zebrafish heart. We show that larval macrophage populations have different origins and a sub-population ofcsf1raexpressing cells are maintained on the surface of the adult heart. MNPs are differently distributed in the myocardium, exhibit different behaviours and are distinguished via expression level ofcsf1raandmpeg1.1. Following injury, tissue resident macrophages rapidly proliferate potentially contributing to reduced scarring. The adult zebrafish heart contains multiple populations of MNPs that can be defined by existing tools. This new understanding of innate immune cell populations in the heart of adult zebrafish sheds light on the composition of a pro-regenerative cardiac microenvironment.
Fetal protection against bovine viral diarrhea virus types 1 and 2 after vaccination of the dam with the DIVENCE vaccine
Authors: Taberner Ester , Gibert Marta , Montbrau Carlos , Muñoz Irene , Mallorquí Joaquim , Tomas Héctor Santo , Prenafeta Antoni , March Ricard 
Published: April 2024

ABSTRACTThe aim of this study was to demonstrate the efficacy of DIVENCE, a vaccine against BVDV types 1 and 2 (BVDV-1 and BVDV-2) transplacental infection, following a booster regimen in heifers. Calves of two-to-three months of age were given two intramuscular doses three weeks apart and a booster vaccine six months later. Efficacy was evaluated by means of a challenge with virulent BVDV-1 or BVDV-2 administered via the intranasal route at 85 days of gestation. Clinical signs, serology, viral shedding, WBC count and viremia were monitored after the challenge. Sixty-six days post-challenge, the fetuses were assessed for BVDV to detect transplacental infection. The results demonstrate a reduction in hyperthermia, leukopenia, viral shedding, and viremia in vaccinated animals post-challenge with BVDV-1 and BVDV-2. Most importantly, DIVENCE administered prior to breeding protected 94% of the fetuses against BVDV transplacental infection overall across both challenge trials (BVDV-1 and BVDV-2).
Glial state changes and neuroinflammatory RIPK1 signaling are a key feature of ALS pathogenesis
Authors: Zelic Matija , Blazier Anna , Pontarelli Fabrizio , LaMorte Michael , Huang Jeremy , Tasdemir-Yilmaz Ozge E. , Ren Yi , Ryan Sean K. , Krishnaswami Pavithra , Levit Mikhail , Sood Disha , Chen Yao , Gans Joseph , Tang Xinyan , Hsiao-Nakamoto Jennifer , Huang Fen , Zhang Bailin , Gaglia Giorgio , Ofengeim Dimitry , Hammond Timothy R. 
Published: April 2024

AbstractAmyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease that causes motor neuron loss in the brain and spinal cord. Neuroinflammation driven by activated microglia and astrocytes is prominent in ALS, but an understanding of cell state dynamics and which pathways contribute to the disease remains unclear. Single nucleus RNA sequencing of ALS spinal cords demonstrated striking changes in glial cell states, including increased expression of inflammatory and glial activation markers. Many of these signals converged on RIPK1 and the necroptotic cell death pathway. Activation of the necroptosis pathway in ALS spinal cords was confirmed in a large bulk RNA sequencing dataset and at the protein level. Blocking RIPK1 kinase activity delayed symptom onset and motor impairment and modulated glial responses in SOD1G93Amice. We used a human iPSC-derived motor neuron, astrocyte, and microglia tri-culture system to identify potential biomarkers secreted upon RIPK1 activation, inhibited pharmacologicallyin vitro, and modulated in the CSF of people with ALS treated with a RIPK1 inhibitor. These data reveal ALS-enriched glial populations associated with inflammation and suggest a deleterious role for neuroinflammatory signaling in ALS pathogenesis.
In Silico Vaccine Design: Targeting Highly Epitopic Regions ofClostridium perfringensType D Epsilon Toxin andClostridium novyiType B Alpha Toxin for Optimal Immunogenicity
Authors: Ashoori Nastaran , Ranjbar Mohammad Mehdi , Schirhagl Romana 
Published: April 2024

AbstractLivestock infections caused by highly toxic bacteria pose significant challenges in veterinary medicine, often requiring complex and elusive treatment regimens. Developing effective vaccines tailored to combat these specific pathogens remains a pressing need within the field. Among the most formidable culprits areClostridium perfringenstype D andClostridium novyitype B, notorious for their extreme toxicity and the difficulty in culturing them for vaccine production. In response to this challenge, our study endeavors to engineer a vaccine candidate capable of concurrently neutralizing the virulence of both bacterial strains. Leveraging computational techniques, we meticulously identified highly epitopic regions withinC. perfringensEpsilon Toxin (ETX) andC. novyiAlpha Toxin (ATX), crucial targets for effective immunization. Through innovative fusion gene design, we integrated these epitopic regions alongside the PADRE-peptide sequence, serving as a universal adjuvant to bolster immune response. The culmination of our efforts materialized in the creation of Recombinant Fusion Protein D (rFPD), a novel vaccine construct poised to elicit robust and specific immune defenses against both bacterial species. By harnessing the power of in silico design and molecular engineering, our study heralds a promising stride towards mitigating the deleterious impact of livestock infections caused by these formidable pathogens.
Predicting chromatin conformation contact maps
Authors: Min Alan , Schreiber Jacob , Kundaje Anshul , Noble William Stafford 
Published: April 2024

AbstractOver the past 15 years, a variety of next-generation sequencing assays have been developed for measuring the 3D conformation of DNA in the nucleus. Each of these assays gives, for a particular cell or tissue type, a distinct picture of 3D chromatin architecture. Accordingly, making sense of the relationship between genome structure and function requires teasing apart two closely related questions: how does chromatin 3D structure change from one cell type to the next, and how do different measurements of that structure differ from one another, even when the two assays are carried out in the same cell type? In this work, we assemble a collection of chromatin 3D datasets—each represented as a 2D contact map— spanning multiple assay types and cell types. We then build a machine learning model that predicts missing contact maps in this collection. We use the model to systematically explore how genome 3D architecture changes, at the level of compartments, domains, and loops, between cell type and between assay types.
Excitatory neurons of the anterior cingulate cortex encode chosen actions and their outcomes rather than cognitive state
Authors: Jendryka Martin M. , Lewin Uwe , Kapanaiah Sampath K.T. , Dermutz Hartmut , Liss Birgit , Pekcec Anton , Akam Thomas , Grewe Benjamin F. , Kätzel Dennis 
Published: April 2024

AbstractThe anterior cingulate cortex (ACC) causally influences cognitive control of goal-directed behaviour. However, it is unclear whether ACC directly encodes cognitive variables like attention or impulsivity, or implements goal-directed action selection mechanisms that are modulated by them. We recorded ACC activity with miniature endoscopic microscopes in mice performing the 5-choice-serial-reaction time task, and applied decoding and encoding analyses. ACC pyramidal cells represented specific actions before and during the behavioural response, whereas the response type (e.g. correct/incorrect/premature) – indicating the state of attentional and impulse control – could only be decoded during and after the response with high reliability. Devaluation and extinction experiments further revealed that action encoding depended on reward expectation. Our findings support a role for ACC in goal-directed action selection and monitoring, that is modulated by cognitive state, rather than in tracking levels of attention or impulsivity directly in individual trials.
Carbon Dioxide Controls Fungal Fitness and Skin Tropism ofCandida auris
Authors: Phan-Canh Trinh , Penninger Philipp , Seiser Saskia , Khunweeraphong Narakorn , Moser Doris , Bitencourt Tamires , Arzani Hossein , Chen Weiqiang , Zenz Lisa-Maria , Knarr Andrej , Cerbu Diana , Jenull Sabrina , Müller Christoph , Lackner Michaela , Ianiri Giuseppe , Chowdhary Anuradha , Hartl Markus , Elbe-Bürger Adelheid , Kuchler Karl 
Published: April 2024

AbstractThe pronounced skin tropism and pan-antifungal resistance traits of the fungal pathogenCandida aurisstand out as a serious health threat. Here, we show that a carbonic sensing pathway (CSP) promotes development of resistance to amphotericin B through a reactive oxygen species (ROS) response, as well as ectopic cell wall and membrane lipid homeostasis. Mechanistically, the transcription factor Rca1 acts in cooperation with Efg1 to control the expression and activity of the carbonic anhydrase Nce103 as a key effector component. The conversion of carbon dioxide to bicarbonate provides a direct link to energy metabolism, facilitating colonization and growth on skin tissues. Native mouse and human skin models unequivocally show that the CSP is essential for maintaining skin tropism as well as fungal fitness. Curiously, upon ablation of Rca1 and Efg1,C. aurisdebilitates efficient growth on native skin. Collectively, our findings highlight critical roles of the CSP inC. aurisskin tropism and antifungal drug resistance. The work suggests therapeutic options for disrupting skin colonization and thus preventing infections.Highlights✓Proteo-transcriptomics links a carbonic sensing pathway (CSP) toC. aurismultidrug resistance✓The Nce103 carbonic anhydrase controls drug resistance as a key component of the CSP✓The transcription factors Rca1 and Efg1 control Nce103 and link CSP withC. aurisskin tropism✓CSP acts through ectopic ROS response, cell wall architecture and membrane lipid function✓CSP is required forC. aurisfitness and efficient growth and colonization of skin tissuesResult contents✓Integrated omics reveals multidrug-resistant mechanisms inC. auris✓CO2-sensing controls amphotericin B resistance (AMBR) traits through Rca1 and Efg1✓The carbonic anhydrase Nce103 governs susceptibility to amphotericin B✓The CSP influences AMBRby maintaining reactive oxygen species homeostasis✓The CSP controls AMBRvia cell membrane and cell wall remodelling✓The CSP regulates fungal fitness through controlling energy metabolism✓C. aurisrequires the CSP for skin colonization
Alignments between cortical neurochemical systems, proteinopathy and neurophysiological alterations along the Alzheimer’s disease continuum
Authors: Wiesman Alex I. , Gallego-Rudolf Jonathan , Villeneuve Sylvia , Baillet Sylvain , Wilson Tony W. ,   the PREVENT-AD Research Group
Published: April 2024

AbstractTwo neuropathological hallmarks of Alzheimer’s disease (AD) are the accumulation of amyloid-β (Aβ) proteins and alterations in cortical neurophysiological signaling. Despite parallel research indicating disruption of multiple neurotransmitter systems in AD, it has been unclear whether these two phenomena are related to the neurochemical organization of the cortex. We leveraged task-free magnetoencephalography and positron emission tomography, with a cortical atlas of 19 neurotransmitters to study the alignment and interactions between alterations of neurophysiological signaling, Aβ deposition, and the neurochemical gradients of the human cortex. In patients with amnestic mild cognitive impairment (N = 18) and probable AD (N = 20), we found that changes in rhythmic, but not arrhythmic, cortical neurophysiological signaling relative to healthy controls (N = 20) are topographically aligned with cholinergic, serotonergic, and dopaminergic neurochemical systems. These neuro-physio-chemical alignments are related to the severity of cognitive and behavioral impairments. We also found that cortical Aβ plaques are preferentially deposited along neurochemical boundaries, and mediate how beta-band rhythmic cortical activity maps align with muscarinic acetylcholine receptors. Finally, we show in an independent dataset that many of these alignments manifest in the asymptomatic stages of cortical Aβ accumulation (N = 33; N = 71 healthy controls), particularly the Aβ-neurochemical alignments (57.1%) and neuro-physio-chemical alignments in the alpha frequency band (62.5%). Overall, the present study demonstrates that the expression of pathology in pre-clinical and clinical AD aligns topographically with the cortical distribution of chemical neuromodulator systems, scaling with clinical severity and with implications for potential pharmacotherapeutic pathways.
KIF2C-induced nuclear condensation concentrates PLK1 and phosphorylated BRCA2 at the kinetochore microtubules in mitosis
Authors: Skobelkina Anastasiia , Julien Manon , Jeannin Sylvain , Miron Simona , Egger Tom , Chaaban Rady , Bouvignies Guillaume , Ghouil Rania , Friel Claire , Busso Didier , Theillet François-Xavier , Le Bars Romain , Carreira Aura , Constantinou Angelos , Basbous Jihane , Zinn-Justin Sophie 
Published: April 2024

SUMMARYDuring mitosis, the human microtubule depolymerase KIF2C increases the turnover of kinetochore-microtubule attachments. This facilitates the correction of attachment errors. Moreover, BRCA2 phosphorylated at Thr207 by PLK1 (BRCA2-pT207) assembles a complex including PLK1, PP2A and BUBR1 that contributes to the stability of the kinetochore-microtubule attachments. PLK1, together with Aurora B, critically regulate the accurate segregation of chromosomes. Here we demonstrate that KIF2C contains an N-terminal domain that binds directly to several phosphorylated peptides, including BRCA2-pT207. Using an optogenetic platform, we reveal that KIF2C assembles into membrane-less compartments or biomolecular condensates that are located next to microtubules. We provide evidence that condensate assembly depends on the presence of the newly defined N-terminal phospho-binding domain of KIF2C and on the kinase activities of Aurora B and PLK1. Moreover, KIF2C condensates concentrate active PLK1 and colocalize with BRCA2-pT207. We propose that, because of its phospho-dependent binding and oligomerization capacities, KIF2C forms biomolecular condensates that partition PLK1 and locally amplify its kinase activity during mitosis.Graphical Abstract