bluuebunny/crossref_metadata_2025_split huggingface dataset:
“Technical Note: DeepLabCut-Display: open-source desktop application for visualizing and analyzing two-dimensional locomotor data in livestock”
Authors: Shirey Jacob , Smythe Madelyn P. , Dewberry L. Savannah , Allen Kyle , Jain Eakta , Brooks Samantha A. 
Published: November 2023

AbstractGait assessments are a key part of determining the wellbeing of livestock. Techniques for gait assessment have traditionally involved human-eye inspections or reflective markers, but markerless computer vision methods have been developed in recent years. Despite many computer vision tools providing high-quality pose estimations in an efficient manner, they lack post-processing functionality. A review of model performance and calculation of gait parameters is a necessary step to fully harness the capability of this new technology. Thus, this study developed DeepLabCut-Display, an open-source desktop software application. DeepLabCut-Display allows a user to upload the video and coordinate data associated with the output of DeepLabCut, a prominent pose-estimation software tool. A user can review the video and coordinate data in parallel, filter points by a likelihood threshold, and automatically calculate gait parameters. Specific video frames, filtered data, and gait parameters can be exported from the application for further usage. The source code is publicly hosted on GitHub alongside installation and usage instructions. DeepLabCut-Display, the product of interdisciplinary and collaborative design between software developers and animal scientists, will alleviate a critical bottleneck in processing of data for locomotor analysis in livestock.Summary StatementDeepLabCut-Display is a utility to dynamically visualize raw marker coordinates, and to automatically produce gait parameters for locomotion analysis of horses and other livestock.Lay SummaryArtificial intelligence systems that can predict and track the positions of objects are now being applied in many fields, including animal science. Veterinarians and animal scientists use these systems to create pose estimations, a digital label of anatomical landmarks overlaid on a video of an animal in motion. They are used to quantify the subject’s motion and detect anomalies that may be indicative of disease or injury. Pose estimation systems are efficient and accurate, but they lack features like data visualization and post-processing analysis that are necessary to make determinations about the animal’s motion. This study developed DeepLabCut-Display, a software application that can visualize the data from a pose estimation system and provides a set of tools for further analysis. After a user is done with analysis, they can save the results to their computer. The application was made by a collaboration between software developers and animal scientists, highlighting how interdisciplinary teams are effective at producing useful software.
Physical performance and telomere length in older adults
Authors: Martínez-Ezquerro José Darío , Ortiz-Ramírez Mauricio , García-delaTorre Paola , González-Covarrubias Vanessa , Sánchez-García Sergio 
Published: November 2023

AbstractBackgroundThe fast-paced aging demographic prompts studying risk factors and markers that could predict healthy aging. Telomere length shows promise for assessing a broad spectrum of aging-related phenotypes.Aim of the studyTo assess the association between physical performance and telomere length in Mexican older adults.MethodsIn this observational cross-sectional study, we recruited 323 older adults affiliated with the Instituto Mexicano del Seguro Social (IMSS) and members of the “Cohort of Obesity, Sarcopenia, and Frailty of Older Mexican Adults’’ (COSFOMA). To assess physical performance, we used the Short Physical Performance Battery (SPPB) and stratified individuals into two groups according to their SPPB score into low ≤7 (L-SPPB) and high >7 (H-SPPB). Absolute telomere length (aTL) was determined by using qPCR. Next, we classified individuals according to their aTL into short ≤4.22 kb (S-TL) and long >4.22 kb (L-TL). For both SPPB and aTL categories, we calculated the mean and adjusted mean by sex, age, marital status, education, remunerated work, smoking, drinking, cognitive decline, depression, and polypharmacy with 95% CI, including the lower and upper CI (LCImeanUCI). We estimated the effect size between physical performance and telomere length with Cohen’s d for unequal group sizes. Also, we calculated the odds ratio with 95% confidence intervals, including the lower and upper CI (LCIORUCI) for physical performance according to telomere length categories.ResultsParticipants in the low physical performance category had significantly shorter telomeres (4.14.44.7mean and3.54.04.5kb adjusted mean, p<0.001), in opposition to the high physical performance category (score >7) with longer telomeres (5.55.75.9mean and4.75.35.8kb adjusted mean, p<0.001), with a medium-to-high telomere length effect size (d= 0.762). Finally, the odds of being classified in the low physical activity category increased2.13.66.1times per kb of telomere (adjOR1.73.36.3, p<0.001) compared to the high physical activity group (p<0.001).ConclusionDecreased physical functioning is associated with lower telomere length. Absolute telomere length (aTL) as a possible biomarker for differential diagnosis of healthy and unhealthy aging should be explored further.
Fortune may favor the flexible: Environment-dependent behavioral shifts in invasive coquí frogs
Authors: Soto Katharina M , Edmonds Devin , Colton Andrea L , Hardin Faith O , Fischer Eva K 
Published: November 2023

AbstractBiological invasions are a major driver of global biodiversity loss, impacting endemic species, ecosystems, and economies. While the influence of life history traits on invasive success is well-established, the role of behavior in the invasive potential of animals is less studied. The common coquí frog,Eleutherodactylus coqui, is a highly successful invader in Hawaii. We build on previous research characterizing changes in physiology and morphology to explore behavioral variation across the invasive range of coquí in Hawaii. We hypothesized that behavioral traits contributing to invasion expansion would be reflected in behavioral differences at the invasive center versus invasive edge. To investigate whether differences in the field represent local adaptation or behavioral plasticity, we additionally evaluated behavior following acclimation to a shared laboratory environment. While we identified only subtle behavioral variation among populations in the field, we found that individuals from all populations became less bold, active, and exploratory in the laboratory, converging on a similar behavioral phenotype. Alongside previous work, our results suggest that coquí adjust their behavior to local environmental conditions across their invasive range, and that behavioral flexibility may contribute to invasive success.
Towards robust and generalizable representations of extracellular data using contrastive learning
Authors: Vishnubhotla Ankit , Loh Charlotte , Paninski Liam , Srivastava Akash , Hurwitz Cole 
Published: November 2023

AbstractContrastive learning is quickly becoming an essential tool in neuroscience for extracting robust and meaningful representations of neural activity. Despite numerous applications to neuronal population data, there has been little exploration of how these methods can be adapted to key primary data analysis tasks such as spike sorting or cell-type classification. In this work, we propose a novel contrastive learning framework,CEED(ContrastiveEmbeddings forExtracellularData), for high-density extracellular recordings. We demonstrate that through careful design of the network architecture and data augmentations, it is possible to generically extract representations that far outperform current specialized approaches. We validate our method across multiple high-density extracellular recordings. All code used to run CEED can be found athttps://github.com/ankitvishnu23/CEED.
Intrinsic p53 Activation Restricts Gammaherpesvirus-Driven Germinal Center B Cell Expansion during Latency Establishment
Authors: Owens Shana M. , Sifford Jeffrey M. , Li Gang , Murdock Steven J. , Salinas Eduardo , Manzano Mark , Ghosh Debopam , Stumhofer Jason S. , Forrest J. Craig 
Published: November 2023

ABSTRACTGammaherpesviruses (GHV) are DNA tumor viruses that establish lifelong latent infections in lymphocytes. For viruses such as Epstein-Barr virus (EBV) and murine gammaherpesvirus 68 (MHV68), this is accomplished through a viral gene-expression program that promotes cellular proliferation and differentiation, especially of germinal center (GC) B cells. Intrinsic host mechanisms that control virus-driven cellular expansion are incompletely defined. Using a small-animal model of GHV pathogenesis, we demonstratein vivothat tumor suppressor p53 is activated specifically in B cells that are latently infected by MHV68. In the absence of p53, the early expansion of MHV68 latency was greatly increased, especially in GC B cells, a cell-type whose proliferation was conversely restricted by p53. We identify the B cell-specific latency gene M2, a viral promoter of GC B cell differentiation, as a viral protein sufficient to elicit a p53-dependent anti-proliferative response caused by Src-family kinase activation. We further demonstrate that EBV-encoded latent membrane protein 1 (LMP1) similarly triggers a p53 response in primary B cells. Our data highlight a model in which GHV latency gene-expression programs that promote B cell proliferation and differentiation to facilitate viral colonization of the host trigger aberrant cellular proliferation that is controlled by p53.IMPORTANCEGammaherpesviruses cause lifelong infections of their hosts, commonly referred to as latency, that can lead to cancer. Latency establishment benefits from the functions of viral proteins that augment and amplify B cell activation, proliferation, and differentiation signals. In uninfected cells, off-schedule cellular differentiation would typically trigger anti-proliferative responses by effector proteins known as tumor suppressors. However, tumor suppressor responses to gammaherpesvirus manipulation of cellular processes remain understudied, especially those that occur during latency establishment in a living organism. Here we identify p53, a tumor suppressor commonly mutated in cancer, as a host factor that limits virus-driven B cell proliferation and differentiation, and thus, viral colonization of a host. We demonstrate that p53 activation occurs in response to viral latency proteins that induce B cell activation. This work informs a gap in our understanding of intrinsic cellular defense mechanisms that restrict lifelong GHV infection.
Small but significant genetic differentiation among populations ofPhyllachora maydisin the midwestern United States revealed by microsatellite (SSR) markers
Authors: Ross Tiffanna. J. , Jumbam Blaise , Bonkowski John , Chaky Jennifer L. , Chilvers Martin I. , Goodwin Stephen B. , Kleczewski Nathan. M. , Mueller Daren. S. , Robertson Alison. E. , Smith Damon. L. , Telenko Darcy. E. P. 
Published: November 2023

AbstractPhyllachora maydisMaubl, the causal pathogen of tar spot of corn (Zea maysL.), has emerged recently in the United States and Canada. Studies related to its genetic diversity and population structure are limited and are necessary to improve our understanding of this pathogen’s biology, ecology, epidemiology, and evolutionary potential within this region. This study developed and used 13 microsatellites (SSR markers) to assess the genetic population structure, diversity, gene flow and reproductive mode of 181P. maydissamples across five states in the Midwest U.S. The polymorphic information content (PIC) of loci ranged from 0.32 to 0.72 per locus, indicating their high utility for assessing the dynamics ofP. maydispopulations. Analysis of molecular variance (AMOVA) detected a significantly low, but statistically significant genetic differentiation (FST= 0.15) among populations, where 85% of the variance resided within populations.P. maydispopulations were highly diverse (He = 0.55), with moderate gene flow (Nm = 2.80), and showed evidence of sexual recombination (r̄d;p = > 0.001). Structure analysis showed the samples were not geographically structured but rather grouped into two genetic clusters (k =2) of severe genetic admixture suggesting possible long-distance dispersal of aerial spores or infected corn materials among the five Midwest states. Both principal coordinate analysis (PCoA) and discriminate analysis of principal component (DAPC) supported the STRUCTURE analysis of the two clusters. These 13 highly polymorphic molecular markers could be used for future investigations of this pathogen’s population dynamics within the U.S., and possibly populations outside.
Hierarchical encoding of reward, effort and choice across the cortex and basal ganglia during cost-benefit decision making
Authors: Härmson Oliver , Grennan Isaac , Perry Brook , Toth Robert , McNamara Colin G. , Denison Timothy , Cagnan Hayriye , Manohar Sanjay G. , Walton Mark E. , Sharott Andrew 
Published: November 2023

AbstractAdaptive value-guided decision-making requires weighing up the costs and benefits of pursuing an available opportunity. Though neurons across frontal cortical-basal ganglia circuits have been repeatedly shown to represent decision-related parameters, it is unclear whether and how this information is coordinated. To address this question, we performed large-scale single unit recordings simultaneously across 5 medial/orbital frontal and basal ganglia regions as rats decided whether to pursue varying reward payoffs available at different effort costs. We found that single neurons encoding combinations of the canonical decision variables (reward, effort and choice) were represented within all recorded brain regions. Co-active cell assemblies - ensembles of neurons that repeatedly co-activated within short time windows (<25ms) within and across structures - were able to provide representations of the same decision variables through the synchronisation of individual neurons with different coding properties. Together, these findings demonstrate a hierarchical encoding structure for cost-benefit computations, where individual neurons with diverse encoding properties are coordinated into larger, low-dimensional spaces within and across brain regions that can signal decision parameters on the millisecond timescale.
Kidney single-cell transcriptomes uncover SGLT2i-induced metabolic reprogramming via restoring glycolysis and fatty acid oxidation
Authors: Shi Ying , Bhalla Vivek 
Published: November 2023

AbstractApproximately 40% of individuals with chronic kidney disease have type 2 diabetes mellitus, and diabetic kidney disease is the leading cause of end-stage kidney disease worldwide. Inhibitors of sodium-glucose cotransporter 2 (SGLT2) have been demonstrated to be effective in glucose control, improving cardiovascular outcomes and the progression of kidney disease. However, the protective role of SGLT2 inhibition on kidney metabolism is not fully understood. To explore these mechanisms further, we conducted analysis of publicly available single-cell RNA sequencing data of db/db mice treated with an SGLT2 inhibitor(dapagliflozin) and accompanying controls. We found that proximal tubule cells exhibited impaired glycolysis and high fatty acid oxidation in diabetes compared with control mice. SGLT2 inhibition reversed this metabolic dysfunction by reducing glycolysis and its substrate accumulation. SGLT2 inhibition also upregulates high fatty oxidation without increasing the uptake of fatty acids and elongation, along with low lipotoxicity. Surprisingly, both SGLT2(+) and SGLT2(-) cells show gene consistent changes in expression of metabolic genes, consistent with a non-cell autonomous effect of dapagliflozin treatment. This study demonstrates the protective role of SGLT2 inhibition via restoring metabolic dysfunction.
CryoSTAR: Leveraging Structural Prior and Constraints for Cryo-EM Heterogeneous Reconstruction
Authors: Li Yilai , Zhou Yi , Yuan Jing , Ye Fei , Gu Quanquan 
Published: November 2023

AbstractResolving conformational heterogeneity in cryo-electron microscopy (cryo-EM) datasets remains a significant challenge in structural biology. Previous methods have often been restricted to working exclusively on volumetric densities, neglecting the potential of incorporating any pre-existing structural knowledge as prior or constraints. In this paper, we present a novel methodology, cryoSTAR, that harnesses atomic model information as structural regularization to elucidate such heterogeneity. Our method uniquely outputs both coarse-grained models and density maps, showcasing the molecular conformational changes at different levels. Validated against four diverse experimental datasets, spanning large complexes, a membrane protein, and a small single-chain protein, our results consistently demonstrate an efficient and effective solution to conformational heterogeneity with minimal human bias. By integrating atomic model insights with cryo-EM data, cryoSTAR represents a meaningful step forward, paving the way for a deeper understanding of dynamic biological processes.1
Early Steps of Protein Disaggregation by Hsp70 Chaperone and Class B J-Domain Proteins are Shaped by Hsp110
Authors: Sztangierska Wiktoria , Wyszkowski Hubert , Pokornowska Maria , Kochanowicz Klaudia , Rychłowski Michał , Liberek Krzysztof , Kłosowska Agnieszka 
Published: November 2023

AbstractHsp70 is a key cellular system counteracting protein misfolding and aggregation, associated with stress, ageing and disease. Hsp70 solubilizes aggregates and aids protein refolding through substrate binding and release cycles regulated by co-chaperones: J-domain proteins (JDPs) and Nucleotide Exchange Factors (NEFs). Here, we elucidate the collaborative impact of Hsp110 NEFs and different JDP classes throughout Hsp70-dependent aggregate processing. We show that Hsp110 plays a major role at initial stages of disaggregation, determining its final efficacy. The NEF catalyses the recruitment of thick Hsp70 assemblies onto aggregate surface, which modifies aggregates into smaller species more readily processed by chaperones. Hsp70 stimulation by Hsp110 is much stronger with Class B than Class A JDPs and requires the auxiliary interaction between Class B JDP and the Hsp70 EEVD motif. Furthermore, we demonstrate for the first time that Hsp110 disrupts the JDP-Hsp70 interaction. Such destabilisation of chaperone complexes at the aggregate surface might improve disaggregation, but also lead to the inhibition above the substoichiometric Hsp110 optimum. Thus, balanced interplay between the co-chaperones and Hsp70 is critical to unlock its disaggregating potential.
Cryo-EM structure of the Spo11 core complex bound to DNA
Authors: Yu You , Wang Juncheng , Liu Kaixian , Zheng Zhi , Arter Meret , Bouuaert Corentin Claeys , Pu Stephen , Patel Dinshaw J. , Keeney Scott 
Published: November 2023

ABSTRACTThe DNA double-strand breaks that initiate meiotic recombination are formed by topoisomerase relative Spo11, supported by conserved auxiliary factors. Because high-resolution structural data are lacking, many questions remain about the architecture of Spo11 and its partners and how they engage with DNA. We report cryo-EM structures at up to 3.3 Å resolution of DNA-bound core complexes ofSaccharomyces cerevisiaeSpo11 with Rec102, Rec104, and Ski8. In these structures, monomeric core complexes make extensive contacts with the DNA backbone and with the recessed 3’-OH and first 5’ overhanging nucleotide, definitively establishing the molecular determinants of DNA end-binding specificity and providing insight into DNA cleavage preferences in vivo. The structures of individual subunits and their interfaces, supported by functional data in yeast, provide insight into the role of metal ions in DNA binding and uncover unexpected structural variation in homologs of the Top6BL component of the core complex.
Genome evolution and introgression in the New Zealand mud snailsPotamopyrgus estuarinusandPotamopyrgus kaitunuparaoa
Authors: Fields Peter D. , Jalinsky Joseph R. , Bankers Laura , McElroy Kyle E. , Sharbrough Joel , Higgins Chelsea , Morgan-Richards Mary , Boore Jeffrey L. , Neiman Maurine , Logsdon John M. 
Published: November 2023

AbstractWe have sequenced, assembled, and analyzed the nuclear and mitochondrial genomes and transcriptomes ofPotamopyrgus estuarinusandPotamopyrgus kaitunuparaoa, two prosobranch snail species native to New Zealand that together span the continuum from estuary to freshwater. These two species are the closest known relatives of the freshwater speciesP. antipodarum—a model for studying the evolution of sex, host-parasite coevolution, and biological invasiveness—and thus provide key evolutionary context for understanding its unusual biology. TheP. estuarinusandP. kaitunuparaoagenomes are very similar in size and overall gene content. Comparative analyses of genome content indicate that these two species harbor a near-identical set of genes involved in meiosis and sperm functions, including seven genes with meiosis-specific functions. These results are consistent with obligate sexual reproduction in these two species and provide a framework for future analyses ofP. antipodarum—a species comprising both obligately sexual and obligately asexual lineages, each separately derived from a sexual ancestor. Genome-wide multigene phylogenetic analyses indicate thatP. kaitunuparaoais likely the closest relative toP. antipodarum.We nevertheless show that there has been considerable introgression betweenP. estuarinusandP. kaitunuparaoa.That introgression does not extend to the mitochondrial genome, which appears to serve as a barrier to hybridization betweenP. estuarinusandP. kaitunuparaoa.Nuclear-encoded genes whose products function in joint mitochondrial-nuclear enzyme complexes exhibit similar patterns of non-introgression, indicating that incompatibilities between the mitochondrial and the nuclear genome may have prevented more extensive gene flow between these two species.Significance StatementNo whole-nuclear genome sequences are currently available for snails of the genusPotamopyrgus, best known forPotamopyrgus antipodarum, an invasive species of rivers and lakes worldwide, and a famous model for the study of the evolution of sex. We have sequenced and analyzed the genome of sexualP. estuarinusandP. kaitunuparaoa, the closest known relatives ofP. antipodarum. We show that 1) the genomes are very similar in gene content and size, 2)P. kaitunuparaoais the closest relative toP. antipodarum, 3) significant introgression has occurred betweenP. estuarinusandP. kaitunuparaoa; these genomes set the stage for powerful direct analyses of the genomic features,e.g., sex to asexual transitions and invasive success, that makeP. antipodarumunique.