bluuebunny/crossref_metadata_2025_split huggingface dataset:
Clinical severity prediction of COVID-19 admitted patients in Spain: SEMI and REDISSEC cohorts
Authors: Martínez-García Mario , García-Gutierrez Susana , Barreñada Taleb Lasai , Armañanzas Rubén , Inza Inaki , Lozano Jose A. 
Published: February 2023

AbstractThis report addresses, from a machine learning perspective, a multi-class classification problem to predict the first deterioration level of a COVID-19 positive patient at the time of hospital admission. Socio-demographic features, laboratory tests and other measures are taken into account to learn the models. Our output is divided into 4 categories ranging from healthy patients, followed by patients requiring some form of ventilation (divided in 2 cate-gories) and finally patients expected to die. The study is conducted thanks to data provided bySociedad Española de Medicina Interna(SEMI) andRed de Investigación en Servicios de Salud de Enfermedades Crónicas(REDISSEC). Results show that logistic regression is the best method for identifying patients with clinical deterioration.
TheE. colipathobiont LF82 encodes a unique variant of σ70that results in specific gene expression changes and altered phenotypes
Authors: Arroyo-Mendoza Melissa , Proctor Alexandra , Correa-Medina Abraham , Brand Meghan Wymore , Rosas Virginia , Wannemuehler Michael J. , Phillips Gregory J. , Hinton Deborah M. 
Published: February 2023

AbstractLF82, an adherent invasiveEscherichia colipathobiont, is associated with ileal Crohn’s disease, an inflammatory bowel disease of unknown etiology. Although LF82 contains no virulence genes, it carries several genetic differences, including single nucleotide polymorphisms (SNPs), that distinguish it from nonpathogenicE. coli. We have identified and investigated an extremely rare SNP that is within the highly conservedrpoDgene, encoding σ70, the primary sigma factor for RNA polymerase. We demonstrate that this single residue change (D445V) results in specific transcriptome and phenotypic changes that are consistent with multiple phenotypes observed in LF82, including increased antibiotic resistance and biofilm formation, modulation of motility, and increased capacity for methionine biosynthesis. Our work demonstrates that a single residue change within the bacterial primary sigma factor can lead to multiple alterations in gene expression and phenotypic changes, suggesting an underrecognized mechanism by which pathobionts and other strain variants with new phenotypes can emerge.
Testing the predictive performance of comparative extinction risk models to support the global amphibian assessment
Authors: Lucas P.M. , Di Marco M. , Cazalis V. , Luedtke J. , Neam K. , Brown M.H. , Langhammer P. , Mancini G. , Santini L. 
Published: February 2023

ABSTRACTAssessing the extinction risk of species through the IUCN Red List is key to guiding conservation policies and reducing biodiversity loss. This process is resource-demanding, however, and requires a continuous update which becomes increasingly difficult as new species are added to the IUCN Red List. The use of automatic methods, such as comparative analyses to predict species extinction risk, can be an efficient alternative to maintaining up to date assessments. Using amphibians as a study group, we predict which species were more likely to change status, in order to suggest species that should be prioritized for reassessment. We used species traits, environmental variables, and proxies of climate and land-use change as predictors of the IUCN Red List category of species. We produced an ensemble prediction of IUCN Red List categories by combining four different model algorithms: Cumulative Link Models (CLM), phylogenetic Generalized Least Squares (PGLS), Random Forests (RF), Neural Networks (NN). By comparing IUCN Red List categories with the ensemble prediction, and accounting for uncertainty among model algorithms, we identified species that should be prioritized for future reassessments due to high prediction versus observation mismatch. We found that CLM and RF performed better than PGLS and NN, but there was not a clear best algorithm. The most important predicting variables across models were species range size, climate change, and landuse change. We propose ensemble modelling of extinction risk as a promising tool for prioritizing species for reassessment while accounting for inherent models’ uncertainty.
Inflammation induces bitter taste oversensitization via epigenetic changes inTas2rgene clusters
Authors: Lin Cailu , Jyotaki Masafumi , Quinlan John , Feng Shan , Zhou Minliang , Jiang Peihua , Matsumoto Ichiro , Huang Liquan , Ninomiya Yuzo , Margolskee Robert F. , Reed Danielle R. , Wang Hong 
Published: February 2023

SummaryT2R bitter receptors, encoded byTas2rgenes, are not only critical for bitter taste signal transduction but also important for defense against bacteria and parasites. However, little is known about whether and howTas2rgene expression are regulated. Here we show that, in an inflammation model mimicking bacterial infection, the expression of manyTas2rsare significantly up-regulated and mice displayed markedly increased neural and behavioral responses to bitter compounds. Using single-cell assays for transposase-accessible chromatin with sequencing (scATAC-seq), we found that the chromatin accessibility ofTas2rswas highly cell type specific and inflammation increased the accessibility of manyTas2rs. scATAC-seq also revealed substantial chromatin remodeling in immune response genes in taste tissue stem cells, suggesting potential long-term effects. Together, our results suggest an epigenetic mechanism connecting inflammation,Tas2rgene regulation, and altered bitter taste, which may explain heightened bitter taste that can occur with infections and cancer treatments.
BAG3 regulates the specificity of the recognition of specific MAPT species by NBR1 and SQSTM1
Authors: Lin Heng , Sandkuhler Sarah , Dunlea Colleen , King Darron H , Johnson Gail V. W. 
Published: February 2023

AbstractAutophagy receptors are essential for the recognition and clearance of specific cargos by selective autophagy, which is essential for maintaining MAPT proteostasis. Previous studies have implicated different autophagy receptors in directing distinct species of MAPT to autophagy, but the underlying mechanisms have not been fully investigated. Here we examine how the autophagy receptors NBR1 and SQSTM1 differentially engage specific forms of MAPT and facilitate their clearance. In primary neurons depletion of NBR1, unlike depletion of SQSTM1, significantly increased phosphorylated MAPT levels. The specificity of the interactions were confirmed using in vitro binding assays with purified proteins. We provide direct evidence that NBR1 preferentially binds to monomeric MAPT, while SQSTM1 interacts predominantly with oligomeric MAPT, and that the co-chaperone BAG3 regulates the specificity of these interactions. Using an in vitro pulldown assay, we show that SQSTM1 only binds to monomeric MAPT when BAG3 is absent and fails to bind when BAG3 is present. The opposite is true of NBR1; its binding to monomeric MAPT was dependent on the presence of BAG3. Interestingly, in Alzheimer’s disease brain the association of NBR1 with BAG3 was significantly decreased. In a mouse model, ablation of BAG3 in neural cells disrupted the association of NBR1 with phosphorylated MAPT and lead to increased levels of phosphorylated and oligomeric MAPT. Overall, our results uncover a novel role for BAG3 in regulating the specificity of selective autophagy receptors in targeting different species of MAPT and provide compelling evidence that BAG3 plays a key role in maintaining MAPT proteostasis.HighlightsFirst direct evidence of the district role of NBR1 and SQSTM1 in binding with monomeric and oligomeric MAPT, respectively.Demonstration of a novel mechanism by which BAG3 regulates the specificity of the recognition of monomeric MAPT by NBR1 and oligomeric MAPT by SQSTM1.Conditional knockout of BAG3 in the brain disrupted the association of NBR1 with phosphorylated MAPT and lead to increased levels of phosphorylated and oligomeric MAPT.
Self-stabilization mechanism encoded by a bacterial toxin facilitates reproductive parasitism
Authors: Harumoto Toshiyuki 
Published: February 2023

ABSTRACTA wide variety of bacterial endosymbionts in insects are associated with reproductive parasitism, whereby they interfere with host reproductive systems to spread within populations. Recent successes in identifying bacterial factors responsible for reproductive parasitism have highlighted the common appearance of deubiquitinase domains, although their functional roles remain unknown. For example,Spiroplasmasymbionts inDrosophilaselectively kill male progeny with a male-killing toxin Spaid that encodes an OTU deubiquitinase domain. Here I show that without the function of OTU, the male-killing activity of Spaid is attenuated, though not eliminated, since it is polyubiquitinated and degraded through the host ubiquitin-proteasome pathway. Furthermore, I find that Spaid utilizes its OTU domain to deubiquitinate itself in an intermolecular manner. Collectively, the deubiquitinase domain of Spaid serves as a self-stabilization mechanism to facilitate male killing in flies, optimizing a molecular strategy of endosymbionts that enables the efficient manipulation of the host at low-cost.
Extracellular proteases are an essential public good supportingBacillus subtilisgrowth through exogenous protein degradation
Authors: Rosazza Thibault , Eigentler Lukas , Earl Chris , Davidson Fordyce , Stanley-Wall Nicola 
Published: February 2023

AbstractBacteria encounter polymeric nutrient sources that need to be processed to support growth.Bacillus subtilisis a bacterium known for its adaptability and resilience within the rhizosphere and broader soil environment. Here we explore the role that a suite of extracellular proteases plays in supporting growth ofB. subtiliswhen an extracellular heterologous protein (BSA) provides an abundant, but polymeric, food source. We confirm the essential role of extracellular proteases in this context and note the influence of the polymeric nutrient concentration on the yield of growth, but not on the relative level of extracellular proteases. We demonstrate the collective action of the extracellular proteases in supportingB. subtilisgrowth and evidence their use as a shared public good. Furthermore, we show thatB. subtilisis subjected to a public good dilemma, but only in the context of using a polymeric food source. Using mathematical simulations, we uncover that this dilemma is driven by therelativecost of producing the public good. Collectively, our findings reveal howB. subtiliscan survive in environments that vary significantly in terms of immediate nutrient accessibility. This information should inform steps to improve its efficacy as a biofertilizer in agricultural settings.
Ts-Biotag, a multimodal reporter of Tie2 expression, labels microglia in a model of neuro injury
Authors: Brodsky Jennifer , Tashi Zeinab , Christopher Sharon K. , Cerna Gabriella , Gohsman Simone , Bartelle Benjamin B. 
Published: February 2023

AbstractThe Ts-Biotag transgenic mouse reports the expression of receptor tyrosine kinase Tie2, a known marker of angiogenic states for both vascular endothelial cells and macrophages. We demonstrate Ts-Biotag labeling and Tie2 expression in a neural injury model to find the majority of labeling occurs in the myeloid derived and brain resident cell type, microglia. Additionally the ligand of Tie2, Ang1, is dynamically expressed, first in astrocytes then neural progenitor during wound signaling and healing. These results offer a Tie2 specific, in vivo view of a neuroimmune response to injury, suggesting a microglia/neural progenitor intercellular interaction guides recovery from a brain lesion.Graphical AbstractThe Ts-Biotag mouse reports expression of Tie2 for any imaging modality compatible with avidinated agents. Mice were given a transcranial cryo-injury and Ts-Biotag activity was followed for 7 days with MRI and histology, showing local and systemic Ts-Biotag labeling. Histology of WT and labeled bone marrow chimeras showed the protein Tie2 expressed in microglia, which assembled at the border of the lesion 1-2d post injury before invading by day 7. The main ligand of Tie2, Ang1, was first expressed systemically by astrocytes, then by neural progenitor cells proximal to and within the lesion. These results elucidate an axis of intercellular signaling involved in the resolution of inflammation and partial healing of a CNS injury.
Posterior parietal cortex is causally involved in reward valuation but not probability weighting during risky choice
Authors: Panidi Ksenia , Vorobiova Alicia Nunez , Feurra Matteo , Klucharev Vasily 
Published: February 2023

AbstractThis study provides evidence that the posterior parietal cortex (PPC) is causally involved in risky decision making via the processing of reward values but not reward probabilities. In the within-group experimental design, participants performed a binary lottery choice task following transcranial magnetic stimulation of the right PPC, left PPC and a right PPC sham (placebo) stimulation. Both, mean-variance and the prospect theory approach to risky choice showed that the PPC stimulation changed participants’ preferences towards greater risk aversion compared to sham. On the behavioral level, after the PPC stimulation the likelihood of choosing a safer option became more sensitive to the difference in standard deviations between lotteries, compared to sham, indicating greater risk avoidance within the meanvariance framework. We also estimated the shift in prospect theory parameters of risk preferences after PPC stimulation. The hierarchical Bayesian approach showed moderate evidence (BF = 7.44 and 5.41 for right and left PPC respectively) for a credible change in risk aversion parameter towards lower marginal reward value (and, hence, lower risk tolerance), while no credible change in probability weighting was observed. Additionally, we observed anecdotal evidence (BF = 2.9) for a credible increase in the consistency of responses after the left PPC stimulation compared to sham.
HMMSTRTM: A hidden Markov model for local structure prediction in globular and membrane associated proteins
Authors: Benavides Tiburon , Bystroff Christopher 
Published: February 2023

AbstractMotivationWe present HMMSTRTM, a Hidden Markov Model (HMM) that is useful for predicting topology of trans-membrane (TM) proteins. HMMSTRTM provides additional prediction categories of TM regions provided by the PDBTM corpus such as transmembrane beta sheets, coils, and reentrant loops.ResultsHMMSTRTM is competitive with existing TM protein topology predictors like TMHMM, it correctly predicts at least half the residues in 96.18% of all transmembrane helices in a cross validation dataset.AvailabilityModel architecture, source code, and supplementary figures are made available on github:github.com/TiburonB/HMMSTRTM.Contactbystrc@rpi.edu
Delineating regional vulnerability in the neurodegenerative disease SCA1 using a conditional mutant ATXN1 mouse
Authors: Duvick Lisa , Southern W. Michael , Benzow Kellie , Burch Zoe N. , Handler Hillary P. , Mitchell Jason S. , Kuivinen Hannah , Gadiparthi Udaya Keerthy , Yang Praseuth , Soles Alyssa , Scheeler Carrie , Rainwater Orion , Serres Shannah , Lind Erin , Nichols-Meade Tessa , O’Callaghan Brennon , Zoghbi Huda Y. , Cvetanovic Marija , Wheeler Vanessa C. , Ervasti James M. , Koob Michael D. , Orr Harry T. 
Published: February 2023

ABSTRACTSpinocerebellar ataxia type 1 (SCA1) is a fatal neurodegenerative disease caused by an expanded polyglutamine tract in the widely expressed ATXN1 protein. To elucidate anatomical regions and cell types that underlie mutant ATXN1-induced disease phenotypes, we developed a floxed conditional knockout mouse model (f-ATXN1146Q/2Q) having mouseAtxn1coding exons replaced by human exons encoding 146 glutamines.F-ATXN1146Q/2Qmice manifest SCA1-like phenotypes including motor and cognitive deficits, wasting, and decreased survival. CNS contributions to disease were revealed usingATXN1146Q/2Q;Nestin-Cremice, that showed improved rotarod, open field and Barnes maze performances. Striatal contributions to motor deficits were examined usingf-ATXN1146Q/2Q;Rgs9-Cremice. Mice lacking striatalATXN1146Q/2Qhad improved rotarod performance late in disease. Muscle contributions to disease were revealed inf-ATXN1146Q/2Q;ACTA1-Cremice which lacked muscle pathology and kyphosis seen inf-ATXN1146Q/2Qmice. Kyphosis was not improved inf-ATXN1146Q/2Q;Nestin-Cremice. Thus, optimal SCA1 therapeutics will require targeting mutant ATXN1 toxic actions in multiple brain regions and muscle.
Size and locomotor ecology have differing effects on the external and internal morphologies of squirrel (Rodentia: Sciuridae) limb bones
Authors: Rickman Johannah , Burtner Abigail E , Linden Tate J , Santana Sharlene E , Law Chris J 
Published: February 2023

AbstractMammals exhibit a diverse range of limb morphologies that are associated with different locomotor ecologies and structural mechanics. Much remains to be investigated, however, about the combined effects of locomotor modes and scaling on the external shape and structural properties of limb bones. Here, we used squirrels (Sciuridae) as a model clade to examine the effects of locomotor mode and scaling on the external shape and structure of the two major limb bones, the humerus and femur. We quantified humeral and femoral morphologies using 3D geometric morphometrics and bone structure analyses on a sample of 76 squirrel species across their four major ecotypes. We then used phylogenetic generalized linear models to test how locomotor ecology, size, and their interaction influenced morphological traits. We found that size and locomotor mode exhibit different relationships with the external shape and structure of the limb bones, and that these relationships differ between the humerus and femur. External shapes of the humerus and, to a lesser extent, the femur are best explained by locomotor ecology rather than by size, whereas structures of both bones are best explained by interactions between locomotor ecology and scaling. Interestingly, the statistical relationships between limb morphologies and ecotype were lost when accounting for phylogenetic relationships among species under Brownian motion. That assuming Brownian motion confounded these relationships is not surprising considering squirrel ecotypes are phylogenetically clustered; our results suggest that humeral and femoral variation partitioned early between clades and their ecomorphologies were maintained to the present. Overall, our results show how mechanical constraints, locomotor ecology, and evolutionary history may enact different pressures on the shape and structure of limb bones in mammals.
Ciliary ARL13B inhibits developmental kidney cystogenesis in mouse
Authors: Van Sciver Robert E. , Long Alyssa B. , Katz Harrison G. , Gigante Eduardo D. , Caspary Tamara 
Published: February 2023

AbstractARL13B is a small GTPase enriched in cilia. Deletion ofArl13bin mouse kidney results in renal cysts and an associated absence of primary cilia. Similarly, ablation of cilia leads to kidney cysts. To investigate whether ARL13B functions from within cilia to direct kidney development, we examined kidneys of mice expressing an engineered cilia-excluded ARL13B variant, ARL13BV358A. These mice retained renal cilia and developed cystic kidneys. Because ARL13B functions as a guanine nucleotide exchange factor (GEF) for ARL3, we examined kidneys of mice expressing an ARL13B variant that lacks ARL3 GEF activity, ARL13BR79Q. We found normal kidney development with no evidence of cysts in these mice. Taken together, our results show that ARL13B functions within cilia to inhibit renal cystogenesis during mouse development, and that this function does not depend on its role as a GEF for ARL3.
Modulation of Retinal Inflammation Delays Degeneration in a Mouse Model of Geographic Atrophy
Authors: Ridley Raela B , Bowman Brianna M , Lee Jieun , Walsh Erin , Massengill Michael T , Lewin Alfred S , Ildefonso Cristhian J 
Published: February 2023

ABSTRACTThe advanced form of AMD, geographic atrophy, is associated with increased RPE oxidative stress and chronic inflammation. Here we evaluated the effects of delivering an anti-inflammatory viral gene by an AAV-vector in a mouse model of geographic atrophy. We measured changes in retinal function, structure, and morphology over nine months with electroretinography, optical coherence tomography, and fundoscopy, respectively. In addition, we used retinal tissue to quantify changes in markers of inflammation by multiplex ELISA, RT-qPCR, and immunofluorescence staining. Our AAV significantly delayed the loss of retinal function and structure and decreased retinal inflammation compared to the control AAV treatment. Our results suggest that modulating retinal inflammation could significantly slow the progression of geographic atrophy.
Impact of experimental bias on compositional analysis of microbiome data
Authors: Hu Yingtian , Satten Glen A. , Hu Yi-Juan 
Published: February 2023

AbstractMicrobiome data are subject to experimental bias that is caused by DNA extraction, PCR amplification among other sources, but this important feature is often ignored when developing statistical methods for analyzing microbiome data. McLaren, Willis and Callahan (2019) proposed a model for how such bias affects the observed taxonomic profiles, which assumes main effects of bias without taxon-taxon interactions. Our newly developed method, LOCOM (logistic regression for compositional analysis) for testing differential abundance of taxa, is the first method that accounted for experimental bias and is robust to the main effect biases. However, there is also evidence for taxon-taxon interactions. In this report, we formulated a model for interaction biases and used simulations based on this model to evaluate the impact of interaction biases on the performance of LOCOM as well as other available compositional analysis methods. Our simulation results indicated that LOCOM remained robust to a reasonable range of interaction biases. The other methods tended to have inflated FDR even when there were only main effect biases. LOCOM maintained the highest sensitivity even when the other methods cannot control the FDR. We thus conclude that LOCOM outperforms the other methods for compositional analysis of microbiome data considered here.
Massively parallel protein-protein interaction measurement by sequencing (MP3-seq) enables rapid screening of protein heterodimers
Authors: Baryshev Alexander , La Fleur Alyssa , Groves Benjamin , Michel Cirstyn , Baker David , Ljubetič Ajasja , Seelig Georg 
Published: February 2023

AbstractProtein-protein interactions (PPIs) regulate many cellular processes, and engineered PPIs have cell and gene therapy applications. Here we introduce massively parallel protein-protein interaction measurement by sequencing (MP3-seq), an easy-to-use and highly scalable yeast-two-hybrid approach for measuring PPIs. In MP3-seq, DNA barcodes are associated with specific protein pairs, and barcode enrichment can be read by sequencing to provide a direct measure of interaction strength. We show that MP3-seq is highly quantitative and scales to over 100,000 interactions. We apply MP3-seq to characterize interactions between families of rationally designed heterodimers and to investigate elements conferring specificity to coiled-coil interactions. Finally, we predict coiled heterodimer structures using AlphaFold-Multimer (AF-M) and train linear models on physics simulation energy terms to predict MP3-seq values. We find that AF-M and AF-M complex prediction-based models could be valuable for pre-screening interactions, but that measuring interactions experimentally remains necessary to rank their strengths quantitatively.