bluuebunny/crossref_metadata_2025_split huggingface dataset:
Surveillance for SARS-CoV-2 in Ohio’s wildlife, companion, and agricultural animals
Authors: Ehrlich Margot , Madden Christopher , McBride Dillon S. , Nolting Jaqueline M. , Huey Devra , Kenney Scott , Wang Qiuhong , Saif Linda , Vlasova Anastasia , Dennis Patricia , Lombardi Dusty , Gibson Stormy , McLaine Alexis , Lauterbach Sarah , Yaxley Page , Winston Jenessa , Diaz-Campos Dubraska , Pesapane Risa , Flint Mark , Flint Jaylene , Junge Randy , Faith Seth A. , Bowman Andrew S. , Hale Vanessa L. 
Published: December 2022

AbstractSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged in humans in late 2019 and spread rapidly to become a global pandemic. A zoonotic spillover event from animal to human was identified as the presumed origin. Subsequently, reports began emerging regarding spillback events resulting in SARS-CoV-2 infections in multiple animal species. These events highlighted critical links between animal and human health while also raising concerns about the development of new reservoir hosts and potential viral mutations that could alter virulence and transmission or evade immune responses. Characterizing susceptibility, prevalence, and transmission between animal species became a priority to help protect animal and human health. In this study, we coalesced a large team of investigators and community partners to surveil for SARS-CoV-2 in domestic and free-ranging animals around Ohio between May 2020 and August 2021. We focused on species with known or predicted susceptibility to SARS-CoV-2 infection, highly congregated or medically compromised animals (e.g. shelters, barns, veterinary hospitals), and animals that had frequent contact with humans (e.g. pets, agricultural animals, zoo animals, or animals in wildlife hospitals). This included free-ranging deer (n=76), mink (n=57), multiple species of bats (n=65), and other wildlife in addition to domestic cats (n=275) and pigs (n= 184). In total, we tested 800 animals (34 species) via rRT-PCR for SARS-CoV-2 RNA. SARS-CoV-2 viral RNA was not detected in any of the tested animals despite a major peak in human SARS-CoV-2 cases that occurred in Ohio subsequent to the peak of animal samplings. Importantly, due to lack of validated tests for animals, we did not test for SARS-CoV-2 antibodies in this study, which limited our ability to assess exposure. While the results of this study were negative, the surveillance effort was critical and remains key to understanding, predicting, and preventing re-emergence of SARS-CoV-2 in humans or animals.
Simple Models For Neuroscience Research Discoveries: How Often Are These Models Used In Africa
Authors: Hamidu S. K. , Ahmad U. , Abdulazeez R. , Muhammad Z. , Alkhamis A.I. , Umar M. , Ladan A. A. , Nasr F. E. , Ahmad A. , Musa S. , Ya’u J. , Hamman W. O. , Yoshimatsu T. , Issa S. R. , Maina M. B. 
Published: December 2022

ABSTRACTSimple animal model systems such asDrosophila, Zebrafish, andC. Eleganshave enabled numerous breakthroughs in understanding human health and disease. Their conserved biological processes, ever-expanding established procedures for handling, and amenability for molecular and genetic manipulation, in addition to the minimal ethical concerns, have made these models preferred choices in several life science disciplines globally. Owing to their cheap maintenance cost, adopting these model systems will help bridge the research gap between Africa and the Global North and contribute to advancing scientific knowledge in African universities through practical sessions. However, the extent to which these models are used across Africa is unknown. Here, we analysed the use ofDrosophila, Zebrafish, andC. elegansmodel systems in scientific publications from African laboratories from the year 2000 to 2021. Of 1851 PubMed-indexed publications in which at least one simple animal model was mentioned, 168 used at least one of these models for the actual investigation. With an average of 21 articles per country, South Africa, Nigeria, Kenya, Egypt, Morocco, and Tunisia contributed 75% of these studies. The remaining 25% were contributed by seven other countries at 2-7 articles per country. From here, we extracted and analysed information on funding and international collaboration. This revealed that 24.4 % of the studies were exclusively funded locally, 28.57 % exclusively funded internationally, 15.5% received both local and international funding, and the rest (31.5%) were unfunded, revealing that there is satisfactory access to funds for simple animal model studies, especially from external funders. By analysing the pattern of collaborations, we show that most of these studies had international collaborations, while very few collaborated within Africa. Our work provides data on the current state of research using simple model systems in African laboratories and argues that incorporating these models will advance biomedical science research in Africa.
How benthic sediment microbial communities respond to glyphosate and its metabolite: A microcosm experiment
Authors: Cornish Christine M , Bergholz Peter , Schmidt Kaycie , Sweetman Jon 
Published: December 2022

AbstractGlyphosate is the most commonly used agricultural herbicide in the world. In aquatic ecosystems, glyphosate often adsorbs to benthic substrates or is metabolized and degraded by microorganisms. The effects of glyphosate on microbial communities varies widely as microorganisms respond differently to exposure. To help understand the impacts of glyphosate on the sediment microbiome we conducted a microcosm experiment examining the responses of benthic sediment microbial communities to herbicide treatments. Sediments from a prairie pothole wetland were collected and 16S rRNA gene sequencing was used to analyze community composition 2-hours and 14-days after a single treatment of low (0.07 ppm), medium (0.7 ppm), or high (7 ppm) glyphosate, aminomethylphosphonic acid (glyphosate metabolite), or a glyphosate-based commercial formula. We found no significant differences in microbial community composition between treatments, concentration levels, or time. These findings suggest that microbial species in the Prairie Pothole Region of North America may be tolerant to glyphosate exposure.
Ventral pallidal GABAergic neuron calcium activity encodes cue-driven reward-seeking and persists in the absence of reward delivery
Authors: Scott Alexandra , Palmer Dakota , Cayton Christelle A. , Lin Iris , Richard Jocelyn M. 
Published: December 2022

AbstractReward-seeking behavior is often initiated by environmental cues that signal reward availability. This is a necessary behavioral response; however, cue reactivity and reward-seeking behavior can become maladaptive. To better understand how cue elicited reward-seeking becomes maladaptive, it is important to understand the neural circuits involved in assigning appetitive value to rewarding cues and actions. Ventral pallidum (VP) neurons are known to contribute to cue elicited reward-seeking behavior and have heterogeneous responses in a discriminative stimulus (DS) task. The VP neuronal subtypes and output pathways that encode distinct aspects of the DS task remain unknown. Here, we used an intersectional viral approach with fiber photometry to record bulk calcium activity in VP GABAergic (VP GABA) neurons in male and female rats as they learned and performed the DS task. We found that VP GABA neurons are excited by reward-predictive cues but not neutral cues, and that this response develops over time. We also found that this cue-evoked response predicts reward-seeking behavior. Additionally, we found increased VP GABA calcium activity at the time of expected reward delivery, which occurred even on trials when reward was omitted. Together, these findings suggest that VP GABA neurons encode reward expectation and calcium activity in these neurons is predictive of the vigor of cue-elicited reward-seeking.
Expanded tRNA methyltransferase family member TRMT9B regulates synaptic growth and function
Authors: Hogan C.A. , Gratz S.J. , Dumouchel J.L. , Delgado A. , Lentini J.M. , Madhwani K.R. , Thakur R.S. , Fu D. , O’Connor-Giles Kate M. 
Published: December 2022

AbstractNervous system function relies on the formation and function of synaptic connections between neurons. Through a genetic screen inDrosophilafor new conserved synaptic genes, we identified CG42261/Fid/ TRMT9B as a negative regulator of synaptogenesis. TRMT9B has been studied for its role as a tumor suppressor in multiple carcinomas and is one of two metazoan homologs of yeast tRNA methyltransferase 9 (Trm9), which methylates tRNA wobble uridines. Members of the expanded family of tRNA methyltransferases are increasingly being associated with neurological disorders and new biochemical functions. Interestingly, whereas Trm9 homolog ALKBH8/CG17807 is ubiquitously expressed, we find that TRMT9B is enriched in the nervous system, including at synapses. However, in the absence of animal models the role of TRMT9B in the nervous system has remained unknown. Here, we generated null alleles ofTRMT9BandALKBH8, and through liquid chromatography-mass spectrometry find that ALKBH8 is responsible for canonical tRNA wobble uridine methylation under basal conditions. In the nervous system, we find that TRMT9B negatively regulates synaptogenesis through a methyltransferase-dependent mechanism in agreement with our modeling studies. Finally, we find that neurotransmitter release is impaired inTRMT9Bmutants. Our findings reveal a role for TRMT9B in regulating synapse formation and function, and highlight the importance of the expanded family of tRNA methyltransferases in the nervous system.
Androgen-mediated TGFβ expression suppresses anti-tumor neutrophil response in bone metastatic prostate cancer
Authors: Alsamraae Massar , Costanzo-Garvey Diane , Teply Benjamin A. , Boyle Shawna , Sommerville Gary , Herbert Zach , Morrissey Colm , Dafferner Alicia J. , Abdalla Maher Y. , Fallet Rachel W. , Kielian Tammy , Jensen-Smith Heather , deOliveira Edson I. , Chen Keqiang , Bettencourt Ian A. , Wang Ji Ming , McVicar Daniel W. , Keeley Tyler , Yu Fang , Cook Leah M. 
Published: December 2022

AbstractProstate Cancer (PCa) bone metastases are associated with spinal cord compression, fracture, bone pain and death. Despite advances in the medical therapy for localized disease, metastatic disease is incurable and osseous progression is largely dictated by tumor-stromal interactions in the bone microenvironment. We showed previously that tumor bone neutrophils are tumoricidal to PCa but lose their cytotoxic potential as the tumor progresses. However, there have been no studies to date to clinically define and characterize neutrophils throughout the prostate cancer disease spectrum to determine their biomarker potential. Using patient peripheral blood polymorphonuclear neutrophils (PMNs), we identify that PCa progression dictates PMN properties, including viability, cell surface markers and gene expression. However, the majority of PMNs elicited an anti-tumor responseex vivodemonstrating that PMN cytotoxicity is cell autonomous and independent of PCa disease stage. In fact, we identify a novel role for androgen regulation, i.e., androgen deprivation therapy (ADT), in suppressing PMN cytotoxicity via altered transforming growth factor beta receptor I (TβRI). Using preclinical models, we found that high dose testosterone/bipolar androgen therapy (BAT) and genetic or pharmacologic TβRI inhibition combined with standard ADT rescued the androgen-associated suppression and restored PMN anti-tumor immune response. This combination provided a therapeutic strategy more impactful than ADT alone, in bone metastatic prostate cancer (BM-PCa). These studies: 1) highlight a necessity for both molecular and functional characterization of PMNs per cancer type and 2) reveals the ability to program PMN immune response for successful targeting of BM-PCa.
Improving Therapeutic Protein Secretion in the Probiotic YeastSaccharomyces boulardiiusing a Multifactorial Engineering Approach
Authors: Durmusoglu Deniz , Al’Abri Ibrahim , Williams Taufika Islam , Collins Leonard B. , Martínez José L. , Crook Nathan 
Published: December 2022

AbstractThe probiotic yeastSaccharomyces boulardii(Sb) is a promising chassis to deliver therapeutic proteins to the gut due toSb’s innate therapeutic properties, resistance to phage and antibiotics, and high protein secretion capacity. To maintain therapeutic efficacy in the context of challenges such as washout, low rates of diffusion, weak target binding, and/or high rates of proteolysis, it is desirable to engineerSbstrains with enhanced levels of protein secretion. In this work, we explored genetic modifications in bothcis- (i.e., to the expression cassette of the secreted protein) andtrans- (i.e., to theSbgenome) that enhanceSb’s ability to secrete proteins, taking aClostridioides difficileToxin A neutralizing peptide (NPA) as our model therapeutic. First, by modulating the copy number of the NPA expression cassette, we found NPA concentrations in the supernatant could be varied by 6-fold (76-458 mg/L) in microbioreactor fermentations. In the context of high NPA copy number, we found a previously-developed collection of native and synthetic secretion signals could further tune NPA secretion between 121 - 463 mg/L. Then, guided by prior knowledge ofS. cerevisiae’s secretion mechanisms, we generated a library of homozygous single gene deletion strains, the most productive of which achieved 2297 mg/L secretory production of NPA. We then expanded on this library by performing combinatorial gene deletions, supplemented by proteomics experiments. We ultimately constructed a quadruple protease-deficientSbstrain that produces 5045 mg/L secretory NPA, an improvement of >10-fold over wild-typeSb. Overall, this work systematically explores a broad collection of engineering strategies to improve protein secretion inSband highlights the ability of proteomics to highlight under-explored mediators of this process. In doing so, we created a set of probiotic strains that are capable of delivering a wide range of protein titers and therefore furthers the ability ofSbto deliver therapeutics to the gut and other settings to which it is adapted.
Kinase-modulated bioluminescent indicators enable noninvasive imaging of drug activity in the brain
Authors: Wu Yan , Walker Joel R. , Westberg Michael , Ning Lin , Monje Michelle , Kirkland Thomas A. , Lin Michael Z. , Su Yichi 
Published: December 2022

AbstractAberrant kinase activity contributes to the pathogenesis of brain cancers, neurodegeneration, and neuropsychiatric diseases, but identifying kinase inhibitors that function in the brain is challenging. Drug levels in blood do not predict efficacy in the brain because the blood-brain barrier prevents entry of most compounds. Rather, assessing kinase inhibition in the brain requires tissue dissection and biochemical analysis, a time-consuming and resource-intensive process. Here, we report kinase-modulated bioluminescent indicators (KiMBIs) for non-invasive longitudinal imaging of drug activity in the brain based on a recently optimized luciferase-luciferin system. We develop an ERK KiMBI to report inhibitors of the Ras-Raf-MEK-ERK pathway, for which no bioluminescent indicators previously existed. ERK KiMBI discriminates between brain-penetrant and non-penetrant MEK inhibitors, reveals blood-tumor barrier leakiness in xenograft models, and reports MEK inhibitor pharmacodynamics in native brain tissues and intracranial xenografts. Finally, we use ERK KiMBI to screen ERK inhibitors for brain efficacy, identifying temuterkib as a promising brain-active ERK inhibitor, a result not predicted from chemical characteristics alone. Thus, KiMBIs enable the rapid identification and pharmacodynamic characterization of kinase inhibitors suitable for treating brain diseases.
Differential roles of positive and negative supercoiling in organizing theE. coligenome
Authors: Fu Ziqi , Guo Monica S. , Zhou Weiqiang , Xiao Jie 
Published: December 2022

ABSTRACTThis study aims to explore whether and how positive and negative supercoiling contribute to the three-dimensional (3D) organization of the bacterial genome. We used recently publishedEscherichia coliGapR ChIP-seq and TopoI ChIP-seq (also called EcTopoI-seq) data, which marks positive and negative supercoiling sites, respectively, to study how positive and negative supercoiling correlates with the corresponding contact frequencies obtained from chromosome conformation capture sequencing (Hi-C and 5C). We found that supercoiled chromosomal loci have overall higher Hi-C contact frequencies than sites that are not supercoiled, with positive supercoiling surprisingly corresponding to higher spatial contacts than negative supercoiling. Additionally, Hi-C contact frequencies alone could identify positive, but not negative, supercoiling with high accuracy. The majority of positive and negative supercoils coincide with highly active transcription units, with a minor group likely associated with replication and other genomic processes. Our results suggest that both positive and negative supercoiling enhance chromosome interactions, but positive supercoils contribute more than negative supercoils to bring distant chromosomal loci closer in space. Based on these results, we propose new physical models of how theE. colichromosome is organized differentially by positive and negative supercoils.
Increased intracellular crowding during hyperosmotic stress
Authors: Kitamura Akira , Oasa Sho , Kawaguchi Haruka , Osaka Misato , Vukojević Vladana , Kinjo Masataka 
Published: December 2022

AbstractHyperosmotic stress activates in live cells numerous processes and also promotes intracellular protein/RNA aggregation and phase separation. However, the time course and the extent of these changes remain largely uncharacterized. To investigate dynamic changes in intracellular macromolecular crowding (MMC) induced by hyperosmotic stress in live cells, we used Fluorescence Lifetime Imaging Microscopy (FLIM) and Fluorescence Correlation Spectroscopy (FCS) to quantify changes in the local environment by measuring the fluorescence lifetime and the diffusion of the monomeric enhanced Green Fluorescent Protein (eGFP), respectively. Real-time monitoring of eGFP fluorescence lifetime showed that a faster response to environmental changes due to MMC is observed than when measuring the acceptor/donor emission ratio using the MMC-sensitive Förster Resonance Energy Transfer sensor (GimRET). This suggests that eGFP molecular electronic states and/or collision frequency are affected by changes in the immediate surroundings due to MMC without requiring conformational changes as is the case for the GimRET sensor. Furthermore, eGFP diffusion assessed by FCS indicated higher intracellular viscosity due to increased MMC during hyperosmotic stress. Our findings reveal that changes in eGFP fluorescence lifetime and diffusion are early indicators of elevated intracellular MMC. These variables can therefore be used for quantitative characterization of MMC in live cells.
A stochastic world model on gravity for stability inference
Authors: Huang Taicheng , Liu Jia 
Published: December 2022

AbstractThe fact that objects without proper support will fall to the ground is not only a natural phenomenon, but also common sense in mind. Previous studies suggest that humans may infer objects’ stability through a world model that performs mental simulations witha prioriknowledge of gravity acting upon the objects. Here we measured participants’ sensitivity to gravity to investigate how the world model works. We found that the world model on gravity was not a faithful replica of the physical laws, but instead encoded gravity’s vertical direction as a Gaussian distribution. The world model with this stochastic feature fit nicely with participants’ subjective sense of objects’ stability and explained the illusion that taller objects are perceived as more likely to fall. Furthermore, a computational model with reinforcement learning revealed that the stochastic characteristic likely originated from experience-dependent comparisons between predictions formed by internal simulations and the realities observed in the external world, which illustrated the ecological advantage of stochastic representation in balancing accuracy and speed for efficient stability inference. The stochastic world model on gravity provides an example of howa prioriknowledge of the physical world is implemented in mind that helps humans operate flexibly in open-ended environments.Significance StatementHumans possess an exceptional capacity for inferring the stability of objects, a skill that has been crucial to the survival of our predecessors and continues to facilitate our daily interactions with the natural world. The present study elucidates that our representation of gravitational direction adheres to a Gaussian distribution, with the vertical orientation as the maximum likelihood. This stochastic representation is likely to have originated from our interactions with the physical world, conferring an ecological advantage of balancing accuracy with speed. Therefore, the world model on gravity in the mind is a distorted replica of the natural world, enabling adaptive functionality in open-ended environments and thus shedding light on developing machines imbued with embodied intelligence.
Flexible and scalable control of T cell memory by a reversible epigenetic switch
Authors: Abadie Kathleen , Clark Elisa C. , Ukogu Obinna , Yang Wei , Daza Riza M. , Ng Kenneth K.H. , Fathima Jumana , Wang Allan L. , Bhandoola Avinash , Nourmohammad Armita , Shendure Jay , Cao Junyue , Kueh Hao Yuan 
Published: December 2022

AbstractThe immune system encodes information about the severity of a pathogenic threat in the quantity and type of memory cell populations formed in response. This encoding emerges from the decisions of lymphocytes to maintain or lose self-renewal and memory potential during a challenge. By tracking responding CD8 T cells at the single-cell and clonal lineage level using time-resolved transcriptomics and quantitative live imaging, we identify a remarkably flexible decision-making strategy, whereby T cells initially choose whether to maintain or lose memory potential early after antigen recognition, but following pathogen clearance may regain memory potential if initially lost. Mechanistically, this flexibility is implemented by acis-epigenetic switch that silences the memory regulator TCF1 in a stochastic and reversible manner in response to stimulatory inputs. Mathematical modeling shows how this strategy allows memory T cell numbers to scale robustly with pathogen virulence and immune response magnitudes. We propose that flexibility and stochasticity in cellular decision making ensures optimal immune responses against diverse threats.