bluuebunny/crossref_metadata_2025_split huggingface dataset:
MindWatch: A Smart Cloud-based AI solution for Suicide Ideation Detection leveraging Large Language Models
Authors: Bhaumik Runa , Srivastava Vineet , Jalali Arash , Ghosh Shanta , Chandrasekharan Ranganathan 
Published: September 2023

AbstractSuicide, a serious public health concern affecting millions of individuals worldwide, refers to the intentional act of ending one’s own life. Mental health issues such as depression, frustration, and hopelessness can directly or indirectly influence the emergence of suicidal thoughts. Early identification of these thoughts is crucial for timely diagnosis. In recent years, advances in artificial intelligence (AI) and natural language processing (NLP) have paved the way for revolutionizing mental health support and education. In this proof-of-concept study, we have created MindWatch, a cutting-edge tool that harnesses the power of AI-driven language models to serve as a valuable computer-aided system for the mental health professions to achieve two important goals such asearly symptom detection, and personalized psychoeducation. We utilized ALBERT and Bio-Clinical BERT language models and fine-tuned them with the Reddit dataset to build the classifiers. We evaluated the performance of bi-LSTM, ALBERT, Bio-Clinical BERT, OpenAI GPT3.5 (via prompt engineering), and an ensembled voting classifier to detect suicide ideation. For personalized psychoeducation, we used the state-of-the-art Llama 2 foundation model leveraging prompt engineering. The tool is developed in the Amazon Web Service environment. All models performed exceptionally well, with accuracy and precision/recall greater than 92%. ALBERT performed better (AUC=.98) compared to the zero-shot classification accuracies obtained from OpenAI GPT3.5 Turbo (ChatGPT) on hidden datasets (AUC=.91). Furthermore, we observed that the inconclusiveness rate of the Llama 2 model is low while tested for few examples. This study emphasizes how transformer models can help provide customized psychoeducation to individuals dealing with mental health issues. By tailoring content to address their unique mental health conditions, treatment choices, and self-help resources, this approach empowers individuals to actively engage in their recovery journey. Additionally, these models have the potential to advance the automated detection of depressive disorders.
MRMCsamplesize: An R Package for Estimating Sample Sizes for Multi-Reader Multi-Case Studies
Authors: Robert Dennis , Sathyamurthy Saigopal , Putha Preetham 
Published: September 2023

AbstractMulti-Reader Multi-Case (MRMC) studies are typically used to evaluate improvement in diagnostic accuracy of readers (diagnosticians) when they are assisted by a computer-assisted device (CAD) such as, but not limited to, those based on Artificial Intelligence (AI) algorithms. Statistical analysis of MRMC study data is not trivial and these studies can consume a lot of resources. Optimal planning is crucial and estimation of sample size is a significant step during the study planning phase. MRMC sample size estimations require many parameter assumptions and without pilot data this is generally not intuitive. MRMCsamplesize package can help researchers to estimate sample sizes for an MRMC study in the absence of any pilot data. The program outputs the number of cases required for a given number of readers. The package can also estimate sample sizes for scenarios where intra-cluster correlation (ICC) needs to be adjusted.
RADIF(C1orf112)-FIGNL1 Complex Regulates RAD51 Chromatin Association to Promote Viability After Replication Stress
Authors: Tischler Jessica D. , Tsuchida Hiroshi , Oda Tommy T. , Park Ana , Adeyemi Richard O. 
Published: September 2023

ABSTRACTHomologous recombination (HR) plays critical roles in repairing lesions that arise during DNA replication and is thus essential for viability. RAD51 plays important roles during replication and HR, however, how RAD51 is regulated downstream of nucleofilament formation and how the varied RAD51 functions are regulated is not clear. We have investigated the poorly characterized protein c1orf112/RADIF that previously scored in genome-wide screens for mediators of DNA inter-strand crosslink (ICL) repair. Upon ICL agent exposure, RADIF loss leads to marked cell death, elevated chromosomal instability, increased micronuclei formation, altered cell cycle progression and increased DNA damage signaling. RADIF is recruited to damage foci and forms a complex with FIGNL1. Both proteins have epistatic roles in ICL repair, forming a co-stable complex. Mechanistically, RADIF loss leads to increased RAD51 amounts and foci on chromatin both with or without exogenous DNA damage, defective replication fork progression and reduced HR competency. We posit that RADIF is essential for limiting RAD51 levels on chromatin in the absence of damage and for RAD51 dissociation from nucleofilaments to properly complete HR. Failure to do so leads to replication slowing and inability to complete repair.
Bmp9 regulates Notch signaling and the temporal dynamics of angiogenesis via Lunatic Fringe
Authors: Ristori Tommaso , Thuret Raphael , Hooker Erika , Quicke Peter , Lanthier Kevin , Ntumba Kalonji , Aspalter Irene M. , Uroz Marina , Herbert Shane P. , Chen Christopher S. , Larrivée Bruno , Bentley Katie 
Published: September 2023

SummaryIn briefThe mechanisms regulating the signaling pathways involved in angiogenesis are not fully known. Ristori et al. show that Lunatic Fringe (LFng) mediates the crosstalk between Bone Morphogenic Protein 9 (Bmp9) and Notch signaling, thereby regulating the endothelial cell behavior and temporal dynamics of their identity during sprouting angiogenesis.HighlightsBmp9 upregulates the expression of LFng in endothelial cells.LFng regulates the temporal dynamics of tip/stalk selection and rearrangement.LFng indicated to play a role in hereditary hemorrhagic telangiectasia.Bmp9 and LFng mediate the endothelial cell-pericyte crosstalk.Bone Morphogenic Protein 9 (Bmp9), whose signaling through Activin receptor-like kinase 1 (Alk1) is involved in several diseases, has been shown to independently activate Notch target genes in an additive fashion with canonical Notch signaling. Here, by integrating predictive computational modeling validated with experiments, we uncover that Bmp9 upregulates Lunatic Fringe (LFng) in endothelial cells (ECs), and thereby also regulates Notch activity in an inter-dependent, multiplicative fashion. Specifically, the Bmp9-upregulated LFng enhances Notch receptor activity creating a much stronger effect when Dll4 ligands are also present. During sprouting, this LFng regulation alters vessel branching by modulating the timing of EC phenotype selection and rearrangement. Our results further indicate that LFng can play a role in Bmp9-related diseases and in pericyte-driven vessel stabilization, since we find LFng contributes to Jag1 upregulation in Bmp9-stimulated ECs; thus, Bmp9-upregulated LFng results in not only enhanced EC Dll4-Notch1 activation, but also Jag1-Notch3 activation in pericytes.
Untargeted proteomics identifies plant substrates of the bacterial-derived ADP-ribosyltransferase AvrRpm1
Authors: Kaur Simranjit , Colby Thomas , Thieme Domenika , Proksch Carsten , Matschi Susanne , Matić Ivan , Wirthmueller Lennart 
Published: September 2023

AbstractOne class of enzymes that plant pathogens employ to manipulate innate immunity and physiology of the infected cells are host-targeted ADP-ribosyltransferases. The bacterial pathogenPseudomonas syringaeuses its type III secretion system to inject several effector proteins with ADP-ribosyltransferase activity into plant cells. One of them, AvrRpm1, ADP-ribosylates the plasma membrane-associated RPM1-INTERACTING PROTEIN 4 (RIN4) inGlycine maxandArabidopsis thalianato attenuate targeted secretion of defense-promoting compounds. Substrate identification of host-targeted ADP-ribosyltransferases is complicated by the biochemical lability of the protein modification during plant protein extraction and in several cases required prior knowledge on plant immune signaling pathways that are impaired by the ADP-ribosylating type III effector. Using the AvrRpm1-RIN4 pair as a proof-of-concept, we present an untargeted proteomics workflow for enrichment and detection of ADP-ribosylated proteins and peptides from plant cell extracts that in several cases provides site-resolution for the modification.
Cellular RNA Interacts with MAVS to Promote Antiviral Signaling
Authors: Gokhale Nandan S. , Somfleth Kim , Thompson Matthew G. , Sam Russell K. , Marciniak Daphnée M. , Chu Lan H. , Park Moonhee , Dvorkin Steve , Oberst Andrew , Horner Stacy M. , Ong Shao-En , Gale Michael , Savan Ram 
Published: September 2023

ABSTRACTImmune signaling needs to be well-regulated to promote clearance of pathogens, while preventing aberrant inflammation. Interferons (IFNs) and antiviral genes are activated by the detection of viral RNA by RIG-I-like receptors (RLRs). Signal transduction downstream of RLRs proceeds through a multi-protein complex organized around the central adaptor protein MAVS. Recent work has shown that protein complex function can be modulated by RNA molecules providing allosteric regulation or acting as molecular guides or scaffolds. Thus, we hypothesized that RNA plays a role in organizing MAVS signaling platforms. Here, we show that MAVS, through its central intrinsically disordered domain, directly interacts with the 3′ untranslated regions of cellular mRNAs. Importantly, elimination of RNA by RNase treatment disrupts the MAVS signalosome, including newly identified regulators of RLR signaling, and inhibits phosphorylation of the transcription factor IRF3. This supports the hypothesis that RNA molecules scaffold proteins in the MAVS signalosome to induce IFNs. Together, this work uncovers a function for cellular RNA in promoting signaling through MAVS and highlights a generalizable principle of RNA regulatory control of cytoplasmic immune signaling complexes.
Neuroanatomical, electrophysiological, and morphological characterization of melanin-concentrating hormone cells coexpressing cocaine- and amphetamine-regulated transcript
Authors: Miller Persephone A , Williams-Ikhenoba Jesukhogie G , Sankhe Aditi S , Hoffe Brendan H , Chee Melissa J 
Published: September 2023

ABSTRACTMelanin-concentrating hormone (MCH) cells in the hypothalamus regulate fundamental physiological functions like energy balance, sleep, and reproduction. This diversity may be ascribed to the neurochemical heterogeneity among MCH cells. One prominent subpopulation of MCH cells coexpresses cocaine- and amphetamine-regulated transcript (CART), and as MCH and CART can have opposing actions, MCH/CART+ and MCH/CART− cells may differentially modulate behavioural outcomes. However, it is not known if there are differences in cellular properties underlying their functional differences, thus we compared the neuroanatomical, electrophysiological, and morphological properties of MCH cells in male and femaleMch-cre;L10-Egfpreporter mice. Half of MCH cells expressed CART and were most prominent in the medial hypothalamus. Whole-cell patch-clamp recordings revealed differences in their passive and active membrane properties in a sex-dependent manner. Female MCH/CART+ cells had lower input resistances, but male cells largely differed in their firing properties. All MCH cells increased firing when stimulated, but their firing frequency decreases with sustained stimulation. MCH/CART+ cells showed stronger spike rate adaptation than MCH/CART− cells. The kinetics of excitatory events at MCH cells also differed by cell type, as the rising rate of excitatory events was slower at MCH/CART+ cells. By reconstructing the dendritic arborization of our recorded cells, we found no sex differences, but male MCH/CART+ cells had less dendritic length and fewer branch points. Overall, distinctions in topographical division and cellular properties between MCH cells add to their heterogeneity and help elucidate their response to stimuli or effect on modulating their respective neural networks.
A morphogenic cascade emerges from the co-evolution of spheroid fluidization and fracturing of multicellular barriers
Authors: Wu Selwin K. , Ho Celestine Z. , Sun Fuqiang , Lou Yuting , Huang Christina Bao-Xian , Xiao Jingwei , Shagirov Murat , Yow Ivan , Chin Jasmine Fei Li , Verma Suzie , Yap Alpha S. , Lin Yuan , Hiraiwa Tetsuya , Low Boon Chuan 
Published: September 2023

AbstractCell collectives migrate and undergo morphological transitions during development and diseases. How cells collectively invade a tissue barrier and its immediate consequence remains elusive. An outstanding challenge is to achieve a comprehensive understanding of the invasion cascade by integrating and applying principles from material science, biophysics, and cell biology. Using a three-dimensional model system of cancer spheroids invading the mesothelium, we show that collective cell invasion emerges from an interplay between spheroid fluidization and fracturing of the multicellular barrier. We found that mesothelial cell- cell contacts undergo tensile fracturing due to spheroid invasion. At the subcellular level, force transmission via intercellular integrin complexes between spheroid and mesothelial cells induces mesothelial cell apical constriction that leads to fracturing. Concurrently, fluidization and directed spheroid cells motility expand the mesothelial fracture. In response, the deformed mesothelium retards spheroid spreading, leading to spheroid cells crowding with contact inhibition of locomotion and proliferation. Our results demonstrate that collective invasion is a morphogenic cascade, revealing that the multicellular barrier undergoing invasion-induced fracture can subsequently force the invaded cells into a dormant state of reduced proliferative potential. Thus, our conclusion may help explain why cancer cells that have invaded a foreign microenvironment tend to enter dormancy.
Unveiling the ultrastructural landscape of native extracellular matrix via lift-out cryo-FIBSEM and cryo-ET
Authors: Zens Bettina , Fäßler Florian , Hansen Jesse M , Hauschild Robert , Datler Julia , Hodirnau Victor-Valentin , Zheden Vanessa , Alanko Jonna , Sixt Michael , Schur Florian KM 
Published: September 2023

AbstractThe extracellular matrix (ECM) is a highly hydrated, three-dimensional network composed of various macromolecules and signaling factors. It serves as a structural scaffold for cells and plays an essential role in the regulation of numerous cellular processes, including cell migration, adhesion, and proliferation. Despite its importance in metazoans, structural knowledge is rudimentary on how the components of the matrisome are secreted, remodeled, and interact with each other and with surrounding cells. Specifically, the exact molecular assembly of important ECM fibers, such as fibronectin fibrils, fibrillin microfibrils, or Collagen-VI filaments has remained enigmatic. This is largely due to methodological limitations in specimen preparation for conventional room-temperature electron microscopy (EM).To overcome these limitations, we have developed a cell culture-based 3D-ECM platform compatible with sample thinning by cryo-lift out focused ion beam (FIB) milling and cryo-electron tomography (cryo-ET). Our workflow involves the implementation of cell-derived matrices (CDMs) grown on EM grids, resulting in a highly adaptable and versatile tool to closely mimic ECM environments. This allows us to visualize native ECM and its components for the first time in their fully hydrated, cellular context. Our data reveals an intricate network of ECM fibers and their positioning with respect to matrix-secreting cells. In addition to D-spaced collagen fibers, we visualize previously unresolved fibrous structures, and an amorphous matrix co-assembling in proximity to ECM fibers and delineating the boundary between ECM and empty extra-cellular space. Intra- and extracellular granules presumably represent assembly intermediates of the ECM. Our results add to the structural atlas of the ECM and provide novel insights into ECM secretion, assembly and maintenance.
Automatic learning mechanisms for flexible human locomotion
Authors: Rossi Cristina , Leech Kristan A. , Roemmich Ryan T. , Bastian Amy J. 
Published: September 2023

AbstractMovement flexibility and automaticity are necessary to successfully navigate different environments. When encountering difficult terrains such as a muddy trail, we can change how we step almost immediately so that we can continue walking. This flexibility comes at a cost since we initially must pay deliberate attention to how we are moving. Gradually, after a few minutes on the trail, stepping becomes automatic so that we do not need to think about our movements. Canonical theory indicates that different adaptive motor learning mechanisms confer these essential properties to movement: explicit control confers rapid flexibility, while forward model recalibration confers automaticity. Here we uncover a distinct mechanism of treadmill walking adaptation – an automatic stimulus-response mapping – that confers both properties to movement. The mechanism is flexible as it learns stepping patterns that can be rapidly changed to suit a range of treadmill configurations. It is also automatic as it can operate without deliberate control or explicit awareness by the participants. Our findings reveal a tandem architecture of forward model recalibration and automatic stimulus-response mapping mechanisms for walking, reconciling different findings of motor adaptation and perceptual realignment.
NatB-dependent acetylation protects procaspase-8 from UBR4-mediated degradation and is required for full induction of the extrinsic apoptosis pathway
Authors: Guedes Joana P. , Boyer Jean Baptiste , Elurbide Jasmine , Carte Beatriz , Redeker Virginie , Sago Laila , Meinnel Thierry , Côrte-Real Manuela , Giglione Carmela , Aldabe Rafael 
Published: September 2023

ABSTRACTN-terminal acetyltransferase B (NatB) is a major contributor to the N-terminal acetylome and is implicated in several key cellular processes including apoptosis and proteostasis. However, the molecular mechanisms linking NatB-mediated N-terminal acetylation to apoptosis and its relationship with protein homeostasis remain elusive. In this study, we generated mouse embryonic fibroblasts (MEFs) with an inactivated catalytic subunit of NatB (Naa20-/-) to investigate the impact of NatB deficiency on apoptosis regulation. Through quantitative N-terminomics, label-free quantification, and targeted proteomics, we demonstrated that NatB does not influence the proteostasis of all its substrates. Instead, our focus on putative NatB-dependent apoptotic factors revealed that NatB-mediated acetylation serves as a protective shield against UBR4 and UBR1 Arg/N-recognin-mediated degradation. Notably,Naa20-/-MEFs exhibited reduced responsiveness to extrinsic pro-apoptotic stimuli, a phenotype that was partially reversible upon UBR4 Arg/N-recognin silencing and consequent inhibition of procaspase-8 degradation. Collectively, our results shed light on how the interplay between NatB-mediated acetylation and the Arg/N-degron pathway impacts apoptosis regulation, providing new perspectives in the field including in therapeutic interventions.
Nutritional condition drives spatial variation in physiology of Antarctic lipid-storing copepods
Authors: Berger Cory A. , Steinberg Deborah K. , Tarrant Ann M. 
Published: September 2023

AbstractLipid-rich copepods form an essential link between primary producers and higher trophic levels in high-latitude oceans. These zooplankton can take advantage of ephemeral phytoplankton blooms to fuel development and reproduction. However, we have limited understanding of how the physiological condition of these animals varies in relation to environmental factors such as food availability. Due to high advection, it is likely that physiological plasticity, rather than local adaptation, is primarily responsible for physiological differences within a region. We use transcriptomics and other physiological metrics to understand how two species of copepods (Calanoides acutusandCalanus propinquus) vary across environmental gradients along the West Antarctic Peninsula. For the primarily herbivorousC. acutus, physiological separation between sampling locations appears to be driven by feeding status, and gene expression differences indicate differential expression of genes regulating lipid metabolism, reproduction, aerobic metabolism, and protein translation. For the more omnivorousC. propinquus,physiology and gene expression did not segregate as clearly by location, showed minimal signs of food deprivation at any location, and had a weaker relationship with chlorophyll compared toC. acutus. By comparing these results with concurrent starvation experiments, we find thatspatial variation in gene expression reflects short-term differences in food availability (particularly forC. acutus,), and we identify genes whose expression indicates recent feeding status. Further examination of the relationships between food availability, copepod physiology, and population dynamics will ultimately improve our capacity to predict how copepod populations will respond to rapidly changing environmental conditions in the West Antarctic Peninsula ecosystem.
Affinity-tagged SMAD1 and SMAD5 mouse lines reveal transcriptional reprogramming mechanisms during early pregnancy
Authors: Liao Zian , Tang Suni , Nozawa Kaori , Shimada Keisuke , Ikawa Masahito , Monsivais Diana , Matzuk Martin M. 
Published: September 2023

ABSTRACTEndometrial decidualization, a prerequisite for successful pregnancies, relies on transcriptional reprogramming driven by progesterone receptor (PR) and bone morphogenetic protein (BMP)-SMAD1/SMAD5 signaling pathways. Despite their critical roles in early pregnancy, how these pathways intersect in reprogramming the endometrium into a receptive state remains unclear. To define how SMAD1 and/or SMAD5 integrate BMP signaling in the uterus during early pregnancy, we generated two novel transgenic mouse lines with affinity tags inserted into the endogenous SMAD1 and SMAD5 loci (Smad1HA/HAandSmad5PA/PA). By profiling the genome-wide distribution of SMAD1, SMAD5, and PR in the mouse uterus, we demonstrated the unique and shared roles of SMAD1 and SMAD5 during the window of implantation. We also showed the presence of a conserved SMAD1, SMAD5, and PR genomic binding signature in the uterus during early pregnancy. To functionally characterize the translational aspects of our findings, we demonstrated that SMAD1/5 knockdown in human endometrial stromal cells suppressed expressions of canonical decidual markers (IGFBP1, PRL, FOXO1)and PR-responsive genes (RORB,KLF15). Here, our studies provide novel tools to study BMP signaling pathways and highlight the fundamental roles of SMAD1/5 in mediating both BMP signaling pathways and the transcriptional response to progesterone (P4) during early pregnancy.