bluuebunny/crossref_metadata_2025_split huggingface dataset:
SNVstory: A dockerized algorithm for rapid and accurate inference of sub-continental ancestry
Authors: Bollas Audrey E. , Rajkovic Andrei , Ceyhan Defne , Gaither Jeffrey B. , Mardis Elaine R. , White Peter 
Published: June 2023

AbstractKnowing a patient’s genetic ancestry is crucial in clinical settings, providing benefits such as tailored genetic testing, targeted health screening based on ancestral disease-predisposition rates, and personalized medication dosages. However, self-reported ancestry can be subjective, making it difficult to apply consistently. Moreover, existing approaches utilize genome sequencing data to infer ancestry at the continental level, creating the need for methods optimized for individual ancestry assignment. We present SNVstory, a method built upon three independent machine learning models for accurately inferring the sub-continental ancestry of individuals. SNVstory includes a feature-importance scheme, unique among open-source ancestral tools, which allows the user to track the ancestral signal broadcast by a given gene or locus. We apply SNVstory to a clinical dataset, comparing self-reported ethnicity and race to our inferred genetic ancestry. SNVstory represents a significant advance in methods to assign genetic ancestry, predicting ancestry across 36 different populations with high accuracy.
High-efficiency digitally scanned light-sheet fluorescence lifetime microscopy (DSLM-FLIM)
Authors: Nutt Kyle J. , Olesker Daniel , McGhee Ewan , Hungerford Graham , Leburn Christopher G. , Taylor Jonathan 
Published: June 2023

AbstractRecently-developed kilopixel single-photon avalanche diode (SPAD) arrays with in-pixel timing hold great promise for fluorescence lifetime imaging microscopy of dynamic samples, thanks to their widefield single-photon time-of-arrival imaging capabilities. However digitally-scanned light-sheet microscope (DSLM) and two-photon microscope systems present significant technical barriers which have to date prevented full and efficient use of the capabilities of SPAD arrays. Because the 12.4 kHz frame-rate of our array camera is faster than achievable DSLM scan rates, most pixels would be sitting idle most of the time. We present a new optical design based around astigmatic imaging optics, enabling rapid and efficient acquisition of fluorescence lifetime imaging data. We demonstrate our system with both one- and two-photon excitation sources, validate performance with lifetime reference beads, and demonstrate separation of similar fluorescence emission spectra in biological samplesvialifetime contrast.
Investigating pedigree- and SNP-associated components of heritability in a wild population of Soay sheep
Authors: James Caelinn , Pemberton Josephine M. , Navarro Pau , Knott Sara 
Published: June 2023

AbstractEstimates of narrow sense heritability derived from genomic data that contain related individuals may be biased due to the within-family effects such as dominance, epistasis and common environmental factors. However, for many wild populations, removal of related individuals from the data would result in small sample sizes. In 2013, Zaitlen et al. proposed a method to estimate heritability in populations that include close relatives by simultaneously fitting an identity-by-state genomic relatedness matrix (GRM) and an identity-by-descent GRM. The IBD GRM is identical to the IBS GRM, except relatedness estimates below a specified threshold are set to 0. We applied this method to a sample of 8557 wild Soay sheep from St. Kilda, with genotypic information for 419,281 single nucleotide polymorphisms to investigate polygenic and monogenic traits. We also implemented a variant of the model in which the IBD GRM was replaced by a GRM constructed from SNPs with low minor allele frequency to examine whether any additive genetic variance is captured by rare alleles. Each model was compared to an animal model with a single GRM based on all genotyped markers (the IBS GRM) using a log likelihood ratio test. Whilst the inclusion of the IBD GRM did not significantly improve the fit of the model for the monogenic traits, it improved the fit for some of the polygenic traits, suggesting that dominance, epistasis and/or common environment not already captured by the non-genetic random effects fitted in our models may influence these traits.
“Isolation and characterization of a novel hormone receptor positive mammary adenocarcinoma MCa-P1362 with stromal drivers of tumor growth, metastasis, and drug resistance”
Authors: Jana Samir , Li Wende , Lei Pin-Ji , Wang Zixiong , Huang Peigen , Jones Dennis 
Published: June 2023

AbstractPreclinical models that display spontaneous metastasis are necessary to improve therapeutic options for hormone receptor positive breast cancers. In this study, we conducted a detailed cellular and molecular characterization of MCa-P1362, a novel syngeneic Balb/c mouse model of metastatic breast cancer. MCa-P1362 cancer cells expressed estrogen receptors (ER), progesterone receptors (PR), and HER-2 receptors. MCa-P1362 cells proliferate in vitro and in vivo in response to estrogen, yet do not depend on steroid hormones for tumor progression. Further characterization of MCa-P1362 tumor explants shows that they contain a mixture of epithelial cancer cells and stromal cells. Based on transcriptomic and functional analyses of cancer and stromal cells, stem cells are present in both populations. Functional studies demonstrate that crosstalk between cancer and stromal cells promotes tumor growth, metastasis, and drug resistance. MCa-P1362 may serve as a useful preclinical model to investigate the cellular and molecular basis of hormone receptor positive tumor progression and therapeutic resistance.
Benchmarking DIA data analysis workflows
Authors: Staes An , Maia Teresa , Dufour Sara , Bouwmeester Robbin , Gabriels Ralf , Martens Lennart , Impens Francis , Devos Simon 
Published: June 2023

AbstractData independent acquisition (DIA) has become a well-established method in LC-MS driven proteomics. Nonetheless, there are still a lot of possibilities at the data analysis level. By benchmarking different DIA analysis workflows using a ground-truth sample, consisting of a differential spike-in of UPS2 in a constant yeast background, we provide a roadmap for DIA data analysis of shotgun samples based on whether sensitivity, precision or accuracy is of the essence. Three different commonly used DIA software tools (DIA-NN, EncyclopeDIA and SpectronautTM) were tested in both spectral library mode and spectral library-free mode. In spectral library mode we used the independent spectral library prediction tools PROSIT and MS2PIP together with DeepLC, next to the classical DDA-based spectral libraries. In total we benchmarked 12 DIA workflows. DIA-NN in library-free mode or usingin silicopredicted libraries, together with Spectronaut in library-free mode, shows the highest sensitivity maintaining a high reproducibility and accuracy. In general, DIA-NN shows the best reproducibility, while the accuracy is comparable for all DIA workflows.
Anti-NMDAR and non-anti-NMDAR antibodies promptly modulate NMDAR through p38 and flux-independent signaling: implications for anti-NMDAR encephalitis
Authors: Montes de Oca-B Pavel , Gómora-García Juan Carlos , Massieu Lourdes , Hernández-Cruz Arturo 
Published: June 2023

ABSTRACTAnti-N-methyl D-aspartic acid receptor (anti-NMDAR) encephalitis is caused by anti-NMDAR antibodies (Abs) that induce neurologic and psychiatric symptoms, explained mainly by NMDAR hypofunction. In the long-term, these Abs decrease surface NMDAR and NMDAR-mediated intracellular Ca2+([Ca2+]i) influx. However, there are contradictory findings regarding short-term mechanisms. We investigated NMDAR function in cultured neurons after 60 min treatment with three commercial, rabbit, anti-NMDAR Abs (anti-GluN1 extracellular (EC) domain; anti-GluN2B EC domain; and anti-GluN1 intracellular (IC) domain). The anti-GluN2B and anti-GluN1 IC Abs were previously reported to mimic patientś Ab effects in a rodentin vivomodel and decreased NMDAR-mediated [Ca2+]i entry after 24 h treatment in our cells. After 60 min incubation with anti-GluN2B or anti-GluN1 IC decreased the NMDAR-mediated [Ca2+]i rise, whereas anti-GluN1 EC slightly increased it. Interestingly, all Abs induced p38 phosphorylation (p-p38). However, surprisingly, it was also elicited by a rabbit Ab directed against a non-NMDAR intracellular epitope, which also reduced NMDAR-mediated [Ca2+]i entry. We further investigated the cellular mechanisms regulated by the anti-GluN2B Ab after 60 min. This Ab did not reduce surface NMDAR and p38 inhibition partially prevented its effect on NMDAR function. This Ab did not elicitper sean [Ca2+]i rise, whereas NMDAR inhibitors 7DCK and MK-801 did not prevent p-p38. Nonetheless, 7DCK prevented NMDAR-mediated [Ca2+]i reduction by the Ab, suggesting a role of GluN1 flux-independent signaling. These data indicate that anti-NMDAR and non-anti-NMDAR Ab modulate NMDAR function distinctly and p38 signaling in the short-term, and a role of a third-party mediator. Finally, our results suggest the involvement of NMDAR flux-independent signaling.
Potential involvement of protein phosphatase PP2CA on protein synthesis and cell cycle during SARS-CoV-2 infection. A meta analysis investigation
Authors: Otvos Luca P. , Garrito Giulia I.M. , Machado Luciana E.S.F. 
Published: June 2023

AbstractCoronavirus disease 2019 is a multi-systemic syndrome that caused a pandemic. Proteomic studies demonstrate changes in protein expression and interaction involved in signaling pathways related to SARS-CoV-2 infections. Protein phosphatases are important for cell signaling regulation. Here we aimed to understand the involvement of protein phosphatases and the signaling pathways that may be involved during SARS-CoV-2 infection. Then, we carried out a metanalysis of protein phosphatase interaction directly or indirectly with viral proteins. Additionally, we analyzed the expression degree of protein phosphatases, and phosphorylation degree of intermediate proteins. Our analyses revealed that PP2CA and PTEN were the key protein involved in the cell cycle and apoptosis regulation, during SARS-CoV-2 infection. Showing it as potential target for COVID-19 control.
Rapid and sensitive detection of genome contamination at scale with FCS-GX
Authors: Astashyn Alexander , Tvedte Eric S. , Sweeney Deacon , Sapojnikov Victor , Bouk Nathan , Joukov Victor , Mozes Eyal , Strope Pooja K. , Sylla Pape M. , Wagner Lukas , Bidwell Shelby L. , Clark Karen , Davis Emily W. , Smith-White Brian , Hlavina Wratko , Pruitt Kim D. , Schneider Valerie A. , Murphy Terence D. 
Published: June 2023

AbstractAssembled genome sequences are being generated at an exponential rate. Here we present FCS-GX, part of NCBI’s Foreign Contamination Screen (FCS) tool suite, optimized to identify and remove contaminant sequences in new genomes. FCS-GX screens most genomes in 0.1-10 minutes. Testing FCS-GX on artificially fragmented genomes demonstrates sensitivity >95% for diverse contaminant species and specificity >99.93%. We used FCS-GX to screen 1.6 million GenBank assemblies and identified 36.8 Gbp of contamination (0.16% of total bases), with half from 161 assemblies. We updated assemblies in NCBI RefSeq to reduce detected contamination to 0.01% of bases. FCS-GX is available athttps://github.com/ncbi/fcs/.
An exploratory study of gastrointestinal redox biomarkers in the presymptomatic and symptomatic Tg2576 mouse model of familial Alzheimer’s disease – phenotypic correlates and the effects of chronic oral D-galactose
Authors: Homolak Jan , Babic Perhoc Ana , Knezovic Ana , Osmanovic Barilar Jelena , Virag Davor , Salkovic-Petrisic Melita 
Published: June 2023

AbstractThe gut might play an important role in the etiopathogenesis of Alzheimer’s disease (AD) as gastrointestinal alterations often precede the development of neuropathological changes in the brain and correlate with disease progression in animal models. The gut has an immense capacity to generate free radicals whose role in the etiopathogenesis of AD is well known; however, it remains to be clarified whether gastrointestinal redox homeostasis is associated with the development of AD. The aim was to i) examine gastrointestinal redox homeostasis in the presymptomatic and symptomatic Tg2576 mouse model of AD; ii) investigate the effects of chronic oral D-galactose previously shown to alleviate cognitive deficits and metabolic changes in animal models of AD; iii) investigate the association between gastrointestinal redox biomarkers and behavioral alterations in Tg2576 mice. Presymptomatic Tg2576 have a heightened gastrointestinal electrophilic tone reflected in increased lipid peroxidation and activity of Mn/Fe-SOD. Chronic oral D-galactose treatment was associated with detrimental effects on redox homeostasis only in the wild-type controls. In the symptomatic stage, Tg2576 mice demonstrate compensated redox disbalance characterized by normalized lipid peroxidation and increased hydrogen peroxide dissociation capacity but diminished total antioxidant reserve alleviated with chronic oral D-galactose treatment. Conversely, D-galactose reduced antioxidant capacity and increased lipid peroxidation in the controls. Total antioxidant capacity was associated with greater spatial memory, while other biomarkers had a complex relationship with exploration, nesting, and grooming. Gut redox homeostasis might be involved in the development and progression of AD pathophysiology and should be further explored in this context.
Cryo-EM structures of the human G-protein coupled receptor 1 (GPR1) – Gi protein complexes bound to the full-length chemerin and to its C-terminal nonapeptide
Authors: Liu Aijun , Liu Yezhou , Chen Geng , Lyu Wenping , Ye Fang , Wang Junlin , Liao Qiwen , Zhu Lizhe , Du Yang , Ye Richard D. 
Published: June 2023

ABSTRACTChemerin is an adipokine with chemotactic activity to a subset of leukocytes. Chemerin mainly acts through its C-terminal nonapeptide (YFPGQFAFS, C9) that bind to three G protein-coupled receptors including chemokine-like receptor 1 (CMKLR1), G-protein coupled receptor 1 (GPR1) and C-C chemokine receptor-like 2 (CCRL2). We examined C9 signaling through GPR1 and found this receptor capable of Gi signaling but very weak β-arrestin signaling. Here we report high-resolution cryo-EM structures of GPR1-Gi complexes bound to full-length chemerin and to C9, respectively. Unlike C9 that inserts directly into a transmembrane binding pocket, full-length chemerin uses its N-terminal globular core for extensive interaction with the N terminus of GPR1. Within the binding pocket, the C terminal loop containing the nonapeptide takes the same “S-shape” pose as synthetic C9 nonapeptide. These findings explain why the nonapeptide is a full agonist of GPR1, and demonstrate that chemerin uses a “two-site” model for interaction with GPR1. An analysis of the GPR1-Gi protein interface found high similarities to the CMKLR1-Gi complex, as confirmed by site-directed mutagenesis with functional verifications. Our structural analysis demonstrates shared features with chemokines in that chemerin acts as a “reverse chemokine” with switched functions of its N and C termini in the interaction with GPR1.
A Quantitative Analysis of Locomotor Patterns in DevelopingC. elegans
Authors: Hassinan Cera W. , Sterrett Scott C. , Summy Brennan , Khera Arnav , Wang Angie , Bai Jihong 
Published: June 2023

AbstractAdult animals display robust locomotion, yet the timeline and mechanisms of how juvenile animals acquire coordinated movements and how these movements evolve during development are not well understood. Recent advances in quantitative behavioral analyses have paved the way for investigating complex natural behaviors like locomotion. In this study, we tracked the swimming and crawling behaviors of the nematodeCaenorhabditis elegansfrom postembryonic development through to adulthood. Our principal component analyses revealed that adultC. elegansswimming is low dimensional, suggesting that a small number of distinct postures, or eigenworms, account for most of the variance in the body shapes that constitute swimming behavior. Additionally, we found that crawling behavior in adultC. elegansis similarly low dimensional, corroborating previous studies. However, our analysis revealed that swimming and crawling are distinct gaits in adult animals, clearly distinguishable within the eigenworm space. Remarkably, young L1 larvae are capable of producing the postural shapes for swimming and crawling seen in adults, despite frequent instances of uncoordinated body movements. In contrast, late L1 larvae exhibit robust coordination of locomotion, while many neurons crucial for adult locomotion are still under development. In conclusion, this study establishes a comprehensive quantitative behavioral framework for understanding the neural basis of locomotor development, including distinct gaits such as swimming and crawling inC. elegans.
Contrasting responses to aridity by different-sized decomposers cause similar decomposition rates across a precipitation gradient
Authors: Torsekar Viraj R. , Sagi Nevo , Alfred Daniel J , Hawlena Yael , Gavish-Regev Efrat , Hawlena Dror 
Published: June 2023

AbstractLitter decomposition is expected to be positively associated with precipitation despite evidence that decomposers of varying sizes have different moisture dependencies. We hypothesized that higher tolerance of macro-decomposers to aridity may counterbalance the effect of smaller decomposers, leading to similar decomposition rates across climatic gradients. We tested this hypothesis by placing plant litter baskets of different mesh sizes in seven sites along a sharp precipitation gradient, and by characterizing the macro-decomposer assemblages using pitfall trapping. We found that decomposers responded differently to precipitation levels based on their size. Microbial decomposition increased with precipitation in the winter while macro-decomposition peaked in arid sites during the summer. This led to similar overall decomposition rates across the gradient except in hyper-arid sites. Macro-decomposer richness, abundance and biomass peaked in arid environments. Our findings highlight the importance of macro-decomposition in arid-lands, possibly resolving the dryland decomposition conundrum, and emphasizing the need to contemplate decomposer size when investigating zoogeochemical processes.
Monocyte production of C1q potentiates CD8+T cell effector function following respiratory viral infection
Authors: Eddens Taylor , Parks Olivia B. , Lou Dequan , Fan Li , Sojati Jorna , Ramsey Manda Jo , Schmitt Lori , Salgado Claudia M. , Reyes-Mugica Miguel , Oury Tim D. , Byersdorfer Craig , Chen Kong , Williams John V. 
Published: June 2023

SummaryRespiratory viral infections remain a leading cause of morbidity and mortality. Using a murine model of human metapneumovirus (HMPV), we identified recruitment of a C1q-producing inflammatory monocyte population concomitant with viral clearance by adaptive immune cells. Genetic ablation of C1q led to reduced CD8+T cell function. Production of C1q by a myeloid lineage was sufficient to enhance CD8+T cell function. Activated and dividing CD8+T cells expressed a putative C1q receptor, gC1qR. Perturbation of gC1qR signaling led to altered CD8+T cell IFN-γ production and metabolic capacity. Autopsy specimens from fatal respiratory viral infections in children demonstrated diffuse production of C1q by an interstitial population. Humans with severe COVID-19 infection also demonstrated upregulation of gC1qR on activated and rapidly dividing CD8+T cells. Collectively, these studies implicate C1q production from monocytes as a critical regulator of CD8+T cell function following respiratory viral infection.
Clustering temporal step-counting patterns for 24 hours with machine learning revealed potential heterogeneity in the categorization by a traditional tertile procedure
Authors: Nawrin Saida Salima , Inada Hitoshi , Momma Haruki , nagatomi Ryoichi 
Published: June 2023

AbstractObjectivesPhysical activity is a crucial aspect of health benefits in the public society. Although studies on the temporal physical activity patterns might lead to the protocol for efficient intervention/program, a standardized procedure to determine and analyze the temporal physical activity patterns remains to be developed. Here, we attempted to develop a procedure to cluster 24-hour patterns of physical activity as step counts measured with an accelerometer-based wearable sensor.MethodsData was collected from 42 healthy participants, comprising 35 males and 7 females, at the Sendai Oroshisho center in 2008. Using unsupervised machine learning, specifically the kernel k-means algorithm with the global alignment kernel was applied on a total of 815 days from 42 participants, and 6 activity patterns were identified. Further, the probability of each 24-hour step-counting pattern was calculated for every participant., and was used in MATLAB to apply spectral clustering, and 5 activity behaviors were identified.ResultsWe could identify six 24-hour step-counting patterns and five daily step-behavioral clusters. When the amount of physical activity was categorized into tertile groups reflecting highly active, moderately active, and low active, each tertile group consisted of different proportions of six 24-hour step-counting patterns.ConclusionsOur study introduces a novel approach using an unsupervised machine learning method to categorize daily hourly activity, revealing six distinct step counting patterns and five clusters representing daily step behaviors. Our procedure would be reliable for finding and clustering physical activity patterns/behaviors and reveal heterogeneity in the categorization by a traditional tertile procedure using total step amount.