bluuebunny/crossref_metadata_2025_split huggingface dataset:
Along- and cross-muscle fiber shear moduli in skeletal muscle
Authors: Sahani Ridhi , Reyna William E. , Royston Thomas , Perreault Eric J. , Ludvig Daniel 
Published: August 2024

AbstractThe material properties of muscle play a central role in how muscle resists joint motion, transmits forces internally, and repairs itself. While many studies have evaluated muscle’s tensile material properties, few have investigated muscle’s shear properties. The objective of this study was to quantify the shear moduli of skeletal muscle both along (along-muscle fiber) and perpendicular (cross-muscle fiber) to the direction of muscle fibers. We collected data from the extensor digitorum longus, tibialis anterior, and soleus muscles harvested from both hindlimbs of 12 rats. These muscles were chosen to further evaluate the consistency of shear moduli across muscles with different architectures. We applied strains and measured stress in three configurations: parallel, perpendicular, and across the muscle fibers to characterize the along- and cross-muscle fiber tensile and shear material parameters. We found no significant difference between the shear modulus measured parallel to the fibers (along-muscle fiber) and the shear modulus in the plane perpendicular to the fibers (cross-muscle fiber). Although the shear moduli were not significantly different, there was a greater difference with increasing strain, suggesting that there is greater anisotropy at larger strains. We also found no significant difference in moduli between the muscles with differing muscle architecture. These results characterize the shear behavior of skeletal muscle and are relevant to understanding the role of shear in force transmission and injury.
Neutralization activity in chronic HIV infection is characterized by a distinct programming of follicular helper CD4 T cells
Authors: Moysi Eirini , Sharma Ashish A. , O’Dell Sijy , Georgakis Spiros , Del Rio Estrada Perla Mariana , Torres-Ruiz Fernanda , Navarro Mauricio González , Villalobos Yara Andrea Luna , Rios Santiago Avila , Reyes-Teran Gustavo , Beddall Margaret H. , Ko Sung-Hee , Belinky Frida , Orfanakis Michail , de Leval Laurence , Enriquez Ana B. , Buckner Clarisa M. , Moir Susan , Doria-Rose Nicole , Boritz Eli , Mascola John R. , Sekaly Rafick-Pierre , Koup Richard A. , Petrovas Constantinos 
Published: August 2024

AbstractA subset of people living with HIV (PLWH) can produce broadly neutralizing antibodies (bNAbs) against HIV, but the lymph node (LN) dynamics that promote the generation of these antibodies are poorly understood. Here, we explored LN-associated histological, immunological, and virological mechanisms of bNAb generation in a cohort of anti-retroviral therapy (ART)-naïve PLWH. We found that participants who produce bNAbs, termed neutralizers, have a superior LN-associated B cell follicle architecture compared with PLWH who do not. The latter was associated with a significantly higherin situprevalence of Bcl-6hifollicular helper CD4 T cells (TFH), expressing a molecular program that favors their differentiation and stemness, and significantly reduced IL-10 follicular suppressor CD4 T cells. Furthermore, our data reveal possible molecular targets mediating TFH-B cell interactions in neutralizers. Together, we identify cellular and molecular mechanisms that contribute to the development of bNAbs in PLWH.
Human populations with low survival at advanced ages and postponed fertility reduce long-term growth in high inflation environments
Authors: Mondal Rahul , Aburto José Manuel , Sear Rebecca , Tuljapurkar Shripad , Mishra Uday Shankar , Salguero-Gómez Roberto 
Published: August 2024

AbstractTemporal variability in inflation can lead to important fluctuations in the long-term growth rate of human populations via their differential impacts on vital rates like survival and fertility. However, historically, demographic studies have overlooked this time-dependent relationship. Here, we test whether human populations have higher stochastic population growth rates when exposed to lower levels of inflation. We also examine if lower survival rates at older ages (>60 years) and fertility rates at the later reproductive years (>30 years) among populations exposed to higher inflation rates determine their expected lower long-term growth rate compared to those exposed to lower inflation rates. To explore the impact of variability in inflation on vital rates response, we develop a quantitative pipeline with four steps, and parameterise it with high-resolution economic and demographic data across 76 countries from 1971-2021. The four steps are (1) defining treatment groups based on levels of trend inflation (creeping inflation (0-3%), walking inflation (3-10%), galloping inflation (10-50%), and hyperinflation (>50%)) among which the stochastic population growth rates will be compared; (2) constructing matrix population models for each environmental state under every treatment. The environmental states for each treatment are defined on the basis of the duration of inflation (e.g., 0, 2, 4, six years or above); (3) estimating the stochastic population growth rate for each treatment by considering a Markovian environment dictated by the long-term frequency (f) and temporal autocorrelation (p) of the treatment; and (4) decomposing the differences in the population growth rate between treatments into contributions from environmental variability and vital rate differences between environments to test how vital rates impact on population growth under varying environmental scenarios. In agreement with our hypothesis, we find that the stochastic population growth rate at lower levels of inflation is systematically higher than that at a higher level of inflation at all stationary frequencies and temporal autocorrelation of the inflation environment. Moreover, the disadvantage in survival at older ages (>60 years) and fertility at ages >30 years led to the lower stochastic growth rate among populations exposed to higher level of inflation such as walking inflation compared to lower level of inflation, such as creeping inflation. Our framework explicitly links human population performance and inflation environment by describing nonlinear feedback between inflation, human survival, fertility, population growth, and its age structure. We discuss the potential of our approach to study the life-history strategies and population dynamics of a wide range of drivers of environmental variability.
Comprehensive transcription factor perturbations recapitulate fibroblast transcriptional states
Authors: Southard Kaden M. , Ardy Rico C. , Tang Anran , O’Sullivan Deirdre D. , Metzner Eli , Guruvayurappan Karthik , Norman Thomas M. 
Published: August 2024

SummaryCell atlas projects have nominated recurrent transcriptional states as drivers of biological processes and disease, but their origins, regulation, and properties remain unclear. To enable complementary functional studies, we developed a scalable approach for recapitulating cell statesin vitrousing CRISPR activation (CRISPRa) Perturb-seq. Aided by a novel multiplexing method, we activated 1,836 transcription factors in two cell types. Measuring 21,958 perturbations showed that CRISPRa activated targets within physiological ranges, that epigenetic features predicted activatable genes, and that the protospacer seed region drove an off-target effect. Perturbations recapitulatedin vivofibroblast states, including universal and inflammatory states, and identifiedKLF4andKLF5as key regulators of the universal state. Inducing the universal state suppressed disease-associated states, highlighting its therapeutic potential. Our findings cement CRISPRa as a tool for perturbing differentiated cells and indicate thatin vivostates can be elicited via perturbation, enabling studies of clinically relevant statesex vivo.
Investigating the links between trifluralin persistence in Western Australian soils and trifluralin resistance in resident annual ryegrass (Lolium rigidum) populations
Authors: Goggin Danica , Boyes Tim , Busi Roberto , Flower Ken 
Published: August 2024

AbstractThe pre-emergence herbicide trifluralin is widely used in the minimum-tillage cropping systems of Australia, with the result that resistance to trifluralin is increasing in the major weed of the region, annual ryegrass (Lolium rigidum). Repeated exposure to low herbicide rates is also known to result in the rapid evolution of resistance in weed populations. As trifluralin is highly volatile, readily photo-decomposed, metabolised by soil microbes and to bind strongly to soil organic matter, there are many factors that could result in weed populations receiving reduced (even sub-lethal) rates of the herbicide. To investigate whether trifluralin dissipation could play a role in the increasing levels of trifluralin resistance in annual ryegrass, resistance levels of populations from 18 Western Australian farms were compared with the dissipation rate of trifluralin applied to soil collected from these farms. Although there was no direct correlation between resistance level and trifluralin half-life, there were links between resistance and soil properties which suggest that higher rates of trifluralin dissipation could make a minor contribution to the development of resistance.
MOSTPLAS: A Self-correction Multi-label Learning Model for Plasmid Host Range Prediction
Authors: Zou Wei , Ji Yongxin , Guan Jiaojiao , Sun Yanni 
Published: August 2024

AbstractPlasmids play an essential role in horizontal gene transfer among diverse microorganisms, aiding their host bacteria in acquiring beneficial traits like antibiotic and metal resistance. Identifying the host bacteria where a plasmid can transfer, replicate or persist provides insights into how plasmids promote bacterial evolution. Plasmid host range prediction tools can be categorized as alignment-based and learning-based. Alignment-based tools have high precision but fail to align many newly sequenced plasmids with characterized ones in reference databases. In contrast, learning-based tools help predict the host range of these newly discovered plasmids. Although previous researches have demonstrated the existence of broad-host-range (BHR) plasmids, there is no database providing their detailed and complete host labels. Without adequate well-annotated training samples, learning-based tools fail to extract discriminative feature representations and obtain limited performance. To address this problem, we propose a self-correction multi-label learning model called MOSTPLAS. We design a pseudo label learning algorithm and a self-correction asymmetric loss to facilitate the training of multi-label learning model with samples containing some unknown missing positive labels. Experimental results on multi-host plasmids generated from the NCBI RefSeq database, metagenomic data, and real-world plasmid sequences with experimentally determined host range demonstrate the superiority of MOSTPLAS.
Lack of pathogenic involvement of CCL4 and its receptor CCR5 in arthritogenic alphavirus disease
Authors: Hameed Muddassar , Solomon Norman A. , Weger-Lucarelli James 
Published: August 2024

AbstractArthritogenic alphaviruses, including chikungunya virus (CHIKV), Mayaro virus (MAYV), Ross River virus (RRV), and O’nyong nyong virus (ONNV) are emerging and reemerging viruses that cause disease characterized by fever, rash, and incapacitating joint swelling. Alphavirus infection induces robust immune responses in infected hosts, leading to the upregulation of several cytokines and chemokines, including chemokine C ligand 4 (CCL4). CCL4 is a chemoattractant for immune cells such as T cells, natural killer cells, monocytes/macrophages, and dendritic cells, recruiting these cells to the site of infection, stimulating the release of proinflammatory mediators, and inducing T cell differentiation. CCL4 has been found at high levels in both the acute and chronic phases of chikungunya disease; however, the role of CCL4 in arthritogenic alphavirus disease development remains unexplored. Here, we tested the effect of CCL4 on MAYV infection in mice through antibody depletion and treatment with recombinant mouse CCL4. We observed no differences in mice depleted of CCL4 or treated with recombinant CCL4 in terms of disease progression such as weight loss and footpad swelling or the development of viremia. CCL4 uses the G protein-coupled receptor C-C chemokine receptor type 5 (CCR5). To determine whether CCR5 deficiency would alter disease outcomes or virus replication in mice, we inoculated CCR5 knockout (CCR5-/-) mice with MAYV and observed no effect on disease development and immune cell profile of blood and footpads between CCR5-/-and wild type mice. These studies failed to identify a clear role for CCL4 or its receptor CCR5 in MAYV infection.
Target enrichment phylogenomics and biogeographic analyses unravel rapid radiation and reticulate evolution between Hainan-South China mainland -Vietnam in SectionNintooa(Lonicera, Caprifoliaceae)
Authors: Zuo Shi-You , Sun Qing-Hui , Morales-Briones Diego F. , Wang Hong-Xin , Landis Jacob B. , Li Hong-Yang , Dong Hong-Jin , Wen Jun , Wang Hua-Feng 
Published: August 2024

AbstractThe South China mainland and nearby islands are biodiversity hotspots. SectionNintooa, widely distributed across mainland China, Vietnam, and Hainan Island, exhibits a typical disjunct distribution pattern. However, the origins of the flora of Hainan Island and the phylogenetic relationships within SectionNintooaremain contentious. In this study, we collected 81 samples encompassing all recognized species of SectionNintooa, along with samples from other sections ofLonicera. We reconstructed the phylogenetic relationships using 491 orthologous nuclear genes and complete plastomes generated by target enrichment and genome skimming sequencing. Our nuclear gene-based species and concatenated trees support the monophyly of SectionNintooa. The species tree indicates that the Vietnamese and Hainan populations form sister clades. However, the plastome results indicate that SectionNintooais polyphyletic, with subsectionVolubilisforming a monophyletic group and subsectionCalcarataeforming a sister clade with other members of subgenusChamaecerasus. Our hybridization network analysis reveals extensive gene flow within SectionNintooa, whereas subsectionCalcarataeshows no gene flow with subsectionVolubilis, leaving the origin ofCalcarataeunclear.Loniceraspecies from Hainan Island exhibit unstable phylogenetic positions and underwent a rapid radiation during the Miocene. Biogeographical results indicate that populations from Vietnam and Hainan both originated from mainland China. Overall, our findings enhance the understanding of the evolutionary diversification history ofLonicera.
Targeting mechanistic target of rapamycin complex 2 attenuates immunopathology in Systemic Lupus Erythematosus
Authors: Ai Minji , Zhou Xian , Carrer Michele , Jafar-nejad Paymaan , Li Yanfeng , Gades D.V.M. Naomi , Alexander Mariam , Bautista Mario A. , Duarte Garcia Ali A. , Zeng Hu 
Published: August 2024

AbstractObjectiveWe aim to explore the role of mechanistic target of rapamycin complex (mTORC) 2 in systemic lupus erythematosus (SLE) development, the invivoregulation of mTORC2 by type I interferon (IFN) signaling in autoimmunity, and to use mTORC2 targeting therapy to ameliorate lupus-like symptoms in anin vivolupus mouse model and anin vitrococulture model using human PBMCs.MethodWe first induced lupus-like disease in T cell specificRictor, a key component of mTORC2, deficient mice by topical application of imiquimod (IMQ) and monitored disease development. Next, we investigated the changes of mTORC2 signaling and immunological phenotypes in type I IFNAR deficient Lpr mice. We then tested the beneficial effects of anti-Rictorantisense oligonucleotide (Rictor-ASO) in a mouse model of lupus: MRL/lprmice. Finally, we examined the beneficial effects ofRICTOR-ASO on SLE patients’ PBMCs using anin vitroT-B cell coculture assay.ResultsT cell specificRictordeficient mice have reduced age-associated B cells, plasma cells and germinal center B cells, and less autoantibody production than WT mice following IMQ treatment. IFNAR1 deficient Lpr mice have reduced mTORC2 activity in CD4+T cells accompanied by restored CD4+T cell glucose metabolism, partially recovered T cell trafficking, and reduced systemic inflammation.In vivo Rictor-ASO treatment improves renal function and pathology in MRL/lprmice, along with improved immunopathology. In human SLE (N = 5) PBMCs derived T-B coculture assay,RICTOR-ASO significantly reduce immunoglobulin and autoantibodies production (P < 0.05).ConclusionTargeting mTORC2 could be a promising therapeutic for SLE.
Exploration of the Metabolomic Mechanisms of Postmenopausal Hypertension Induced by Low Estrogen State
Authors: Li Yao , Xin Hui , Lian Zhexun , Zhang Wei 
Published: August 2024

AbstractBackgroundEstrogen significantly impacts women’s health, and postmenopausal hypertension is a common issue characterized by blood pressure fluctuations. Current control strategies for this condition are limited in efficacy, necessitating further research into the underlying mechanisms. Although metabolomics has been applied to study various diseases, its use in understanding postmenopausal hypertension is scarce.MethodsAn ovariectomized rat model was used to simulate postmenopausal conditions. Estrogen levels, blood pressure, and aortic tissue metabolomics were analyzed. Animal models were divided into Sham, OVX, and OVX+E groups. Serum estrogen levels, blood pressure measurements, and aortic tissue metabolomics analyses were performed using radioimmunoassay, UHPLC-Q-TOF, and bioinformatics techniques.ResultsThe study successfully established a correlation between low estrogen levels and postmenopausal hypertension in rats. Notable differences in blood pressure parameters and aortic tissue metabolites were observed across the experimental groups. Specifically, metabolites that were differentially expressed, particularly L-alpha-aminobutyric acid (L-AABA), showed potential as a biomarker for postmenopausal hypertension, potentially exerting a protective function through macrophage activation and vascular remodeling. Enrichment analysis revealed alterations in sugar metabolism pathways, such as the Warburg effect and glycolysis, indicating their involvement in postmenopausal hypertension.ConclusionThis research provides insights into the metabolic changes associated with postmenopausal hypertension, highlighting the role of AABA and sugar metabolism reprogramming in aortic tissue. The findings suggest a potential link between low estrogen levels, macrophage function, and vascular remodeling in the pathogenesis of postmenopausal hypertension. Further investigations are needed to validate these findings and explore their clinical implications for postmenopausal women.
A map of integrated cis-regulatory elements enhances gene regulatory analysis in maize
Authors: Manosalva Pérez Nicolás , Staut Jasper , Ferrando Andrés Matres , Dissanayake Indeewari , Vandepoele Klaas 
Published: August 2024

AbstractCis-regulatory elements (CREs) are non-coding DNA sequences that modulate gene expression. Their identification is critical to study the transcriptional regulation of genes controlling key traits that govern plant growth and development. They are also crucial components for the delineation of gene regulatory networks, which represent regulatory interactions between transcription factors (TFs) and target genes. In maize, CREs have been profiled using different computational and experimental methods, but the extent to which these methods complement each other in identifying functional CREs is unclear. Here, we report the data-driven integration of different maize CRE profiling methods to optimize the capture of experimentally-confirmed TF binding sites, resulting in maps of integrated CREs (iCREs) showing increased levels of completeness and precision. We combined the iCREs with a wide diversity of gene expression data under drought conditions to perform motif enrichment and infer drought-specific GRNs. Mining these organ-specific GRNs revealed previously characterized and novel candidate regulators of maize drought response. Furthermore, by studying the transposable elements (TEs) overlapping with iCREs, we identified few TE superfamilies displaying typical epigenetic features of regulatory DNA that are potentially involved in wiring specific TF-target gene regulatory interactions. Overall, our study showcases the integration of different omics data sources to generate a high-quality collection of CREs, together with their applicability to better characterize gene regulation in the complex maize genome.
A causative SNP in the promoter of myogenin is essential for myogenic differentiation
Authors: Lin Zhuhu , Wang Xiaoyu , Liang Ziyun , Xu Rong , Chen Meilin , Tong Xian , Li Chenggan , Xiong Yanyun , Yuan Renqiang , Chen Yaosheng , Zhao Yunxiang , Liu Xiaohong , Mo Delin 
Published: August 2024

AbstractSingle nucleotide polymorphisms (SNPs) widely existing in different breeds genome represent population-specific. Under the influence of long-term evolution and artificial selection, there are a large number of SNPs between western lean-type pig breeds and Chinese indigenous pig breeds, but until now, little is known about their roles in inter-breed differences. Our study revealed SNP rs3471653254 C>T generated from the two types of pigs mentioned above, located in the promoter shared by MyoG and Myoparr, played an important role in the differentiation of myoblast by influencing the enrichment of HOXA5 to regulate the transcription of MyoG and Myoparr. Meanwhile, Myoparr could be used as the sponge of mir-30b-3p which repressed myogenic differentiation and muscle regeneration through targeting MyoD. Our results indicated that SNP rs3471653254 C>T is essential for myogenic differentiation and regeneration and could be used as an ideal site for increasing lean meat production in pigs.
Loss function of tumor suppressor FRMD8 confers resistance to tamoxifen therapy via a dual mechanism
Authors: Wu Weijie , Yu Miao , Li Qianchen , Zhao Yiqian , Zhang Lei , Sun Yi , Wang Zhenbin , Gong Yuqing , Wang Wenjing , Liu Chenying , Zhang Jing , Tang Yan , Xu Xiaojie , Guo Xiaojing , Zhan Jun , Zhang Hongquan 
Published: August 2024

AbstractApproximately 40% ERα-positive breast cancer patients suffer from therapeutic resistance to tamoxifen. Although reduced ERα level is the major cause of tamoxifen resistance, the underlying mechanisms remain elusive. Here, we report that FRMD8 raises the level of ERα at both transcriptional and post-translational layers. FRMD8 deficiency inMMTV-Cre+;Frmd8fl/fl;PyMTmice accelerates mammary tumor growth and loss of luminal phenotype, and confers tamoxifen resistance. Single-cell RNA profiling reveals that Frmd8 loss decreases the proportion of hormone-sensing differentiated epithelial cells and downregulates the levels of ERα. Mechanically, on one hand, loss of FRMD8 inhibitsESR1transcription via suppressing the expression of FOXO3A, a transcription factor ofESR1. On the other hand, FRMD8 interacts both with ERα and UBE3A, and disrupts the interaction of UBE3A with ERα, thereby blocking UBE3A-mediated ERα degradation. In breast cancer patients,FRMD8gene promoter is found hypermethylated and low level of FRMD8 predicts poor prognosis. Therefore, FRMD8 is an important regulator of ERα and may control therapeutic sensitivity to tamoxifen in ERα-positive breast cancer patients.Impact StatementTumor suppressive protein FRMD8 inhibits breast cancer progression by regulating the level of ERα and has the possibility to be a potential target for overcoming tamoxifen treatment resistance.