bluuebunny/crossref_metadata_2025_split huggingface dataset:
Inflammation biomarkers and neurobehavioral performance in rural adolescents
Authors: Amdemicael Beemnet , Yang Kun , Chronister Briana N.C. , Mackey Caroline , Tu Xin , Gahagan Sheila , Martinez Danilo , Checkoway Harvey , Jacobs David R , Suarez-Torres Jose , Hong Suzi , Suarez-Lopez Jose R. 
Published: October 2024

AbstractBackgroundSystemic inflammation has been associated with lower neurobehavioral performance in diverse populations, yet the evidence in adolescents remains lacking. Cytokines can alter neural network activity to induce neurocognitive changes. This work seeks to investigate the association between inflammation and neurobehavior in adolescents living in a rural region of Ecuador.MethodsWe examined 535 adolescents in rural communities of Ecuador (ESPINA study), 508 of which had neurobehavioral assessments (NEPSY-II) and circulating plasma levels of inflammatory markers (CRP, IL-6, TNF-⍺, sICAM-1, sVCAM-1, SAA, and sCD14). Associations between inflammatory biomarker concentrations and neurobehavioral scores were examined using adjusted bivariate semi-parametric models with generalized estimating equations. A partial least square regression approach was used to create composite variables from multiple inflammation biomarkers and model their association with cognitive outcomes.ResultsHigher sCD14 and TNF-α concentrations were significantly associated with lower social perception scores, by −0.47 units (95% CI: −0.80, −0.13) and −0.42 (−0.72, −0.12) for every 50% increase in inflammatory marker concentration, respectively. Similarly, every 50% increase in the inflammation summary score was associated with a significantly lower Social Perception score by −0.11 units (−0.19, −0.03). A unit increase in inflammatory composites of seven markers were associated with lower scores in language (−0.11 units, p=0.04), visuospatial processing (−0.15, p= 0.09), and social perception (−0.22, p=0.005) domains.ConclusionsHigher levels of inflammation were associated with lower neurobehavioral performance in adolescents, especially with social perception. In addition, using a robust analytic method to examine an association between a composite inflammatory variable integrating seven markers led to additional findings, including the domains of language and visuospatial processing. A longitudinal follow-up of such investigations could unveil potential changes in inflammation-neurobehavior performance links through developmental stages and intervention opportunities.
Prospective validation of mean metacarpophalangeal joint extension as a measure of flexor compartment fibrotic inflammation in diabetes-related hand manifestations
Authors: Phatak Sanat , Jadhav Sarita , Wagh Rucha , Ladha Parth , Nalkande Rishi , Tope Rutvij , Balbudhe Harsh , Shah Rohan , Dhadge Smita , Goel Pranay , Ingram Jennifer L. , Yajnik Chittaranjan 
Published: October 2024

AbstractIntroductionHand conditions in diabetes, namely limited joint mobility (LJM), flexor tenosynovitis (FT), carpal tunnel syndrome (CTS), and Dupuytren disease (DD), share a common pathophysiological process involving pro-fibrotic inflammation in flexor structures. A unified, quantitative measure of disease severity across these conditions is lacking, limiting correlational research. We evaluated mean metacarpophalangeal (MCP) joint extension as a potential measure of severity.MethodsWe assessed 2405 adults, including individuals with type 1 diabetes (n=291), type 2 diabetes (n=877), prediabetes (n=326), and non-diabetic controls (n=911). MCP extension was calculated as the average maximum passive extension of the 2nd-5th fingers, measured with a protractor. Validity was determined by correlating MCP extension with physician-rated severity (convergent) and hand grip strength and the Duruoz Hand Index (DHI, both divergent). Inter-rater reliability was tested in 128 individuals, and sensitivity to change was evaluated in 143 participants over time and in 21 rheumatology patients with subacute noninfectious FT.ResultsMean MCP extension was significantly lower in individuals with all hand conditions (42.4° LJM, 42.8° FT, 39.9° DD, 51.7° CTS) than in those without (58.6°, all p<0.05). MCP extension correlated with physician-rated severity (−0.5, p<0.01) and weakly with DHI (R2=0.03) and grip strength (R2=0.07). Inter-rater reliability was strong (ICC 0.72), and MCP extension demonstrated sensitivity to change, worsening over eight months (SRM -0.61) and improving after treatment in subacute FT (SRM 0.69).ConclusionMean MCP extension is a valid, reliable, and responsive measure for assessing fibro-inflammatory hand conditions in diabetes, suitable for use in research studies.
Practices, perceptions, and ethical concerns of antimicrobial use among poultry farmers in Kiambu County, Kenya. One-Health context
Authors: Munene Ann , Majiwa Hamilton , Bukusi Elizabeth 
Published: October 2024

AbstractGlobally, the poultry sector is one of the primary animal protein sources for human consumption. The poultry sector enhances both food and economic security in Kenya. This has led to adaptations in the poultry sector to respond to the growing demand for animal protein. Practices such as antimicrobial use for disease management, growth promotion, and product improvement within the poultry industry have led to public health, environmental, and ethical concerns. A predominant poultry-producing region in Kenya, Kiambu County was chosen for this study. In-depth interviews (n=21) were conducted until saturation among both small- and large-scale poultry farmers of layers, broiler, and indigenous chicken breeds. The farmers revealed overuse and misuse of antimicrobials, use of antimicrobials for growth promotion and product improvement, and non-adherence to withdrawal periods. They also use poultry waste in other animal feeds and improperly dispose of antimicrobial dilutions. These practices are all likely to contribute to the development and spread of antimicrobial resistance (AMR), which is a global threat to human, animal, and environmental health. The lack of awareness of the potential harm caused by the practices and disregard of instructions, demonstrates the need for increased awareness among poultry farmers on rational use of antimicrobials in poultry farming. Poultry farmers’ ignorance and lack of adherence to regulations of antimicrobial use in poultry farming raises ethical concerns about the threat to human, animal, and environmental health. We conclude that a multifaceted One Health approach is required to evaluate the different ethical, social, and biological factors that contribute to the development and spread of antibiotic resistance arising from poultry production to safeguard public and environmental health.
Targeting the 3D genome by anthracyclines for chemotherapeutic effects
Authors: Tan Minkang , Sun Shengnan , Liu Yuchen , Perreault Andrea A. , Phanstiel Douglas H. , Dou Liping , Pang Baoxu 
Published: October 2024

AbstractThe chromatins are folded into three-dimensional (3D) structures inside cells, which coordinates the regulation of gene transcription by the non-coding regulatory elements. Aberrant chromatin 3D folding has been shown in many diseases, such as acute myeloid leukemia (AML), and may contribute to tumorigenesis. The anthracycline topoisomerase II inhibitors can induce histone eviction and DNA damage. We performed genome-wide high-resolution mapping of the chemotherapeutic effects of various clinically used anthracycline drugs. ATAC-seq was used to profile the histone eviction effects of different anthracyclines. TOP2A ChIP-seq was used to profile the potential DNA damage regions. Integrated analyses show that different anthracyclines have distinct target selectivity on epigenomic regions, based on their respective ATAC-seq and ChIP-seq profiles. We identified the underlying molecular mechanism that unique anthracycline variants selectively target chromatin looping anchors via disrupting CTCF binding, suggesting an additional potential therapeutic effect on the 3D genome. We further performed Hi-C experiments, and data from K562 cells treated with the selective anthracycline drugs indicate that the 3D chromatin organization is disrupted. Furthermore, AML patients receiving anthracycline drugs showed altered chromatin structures around potential looping anchors, which linked to distinct clinical outcomes. Our data indicate that anthracyclines are potent and selective epigenomic targeting drugs and can target the 3D genome for anticancer therapy, which could be used for personalized medicine to treat tumors with aberrant 3D chromatin structures.
Spatial frequency channels mediate a visual metric for human spatial perception
Authors: Zhang Shijia , Mo Ce , Mo Lei , Fang Fang 
Published: October 2024

AbstractAn intriguing and ubiquitous phenomenon in vision is the perception of spatial property information (e.g. separation, size, shape etc.) that departs from the raw physical inputs yet conforms to the visual context. While it has been postulated that visual system employs an internal adaptable metric by which the signals conveying the spatial property information are scaled, it remains unknown whether and how such putative visual metric is represented in the brain. Here, we hypothesized the putative visual metric is mediated by the joint responses of differently-tuned spatial frequency (SF) channels, and investigated this idea by combining the use of psychophysics, fMRI-based population receptive field (pRF) mapping and computation modeling. We found that reweighting of spatial frequency (SF) channels, either by adaption or presentation of the corresponding SF background, led to systematic distortions of the perceived spatial property information. Moreover, the pRFs in V1 were more concentrated towards the fovea under the high SF stimulation regardless of their positions in the visual field. Importantly, both the perceptual distortions and the global-scale pRF displacement were functionally coupled with the changes in the population SF response induced by SF channel reweighting. Our findings revealed, for the first time, the neural apparatus signaling the putative visual metric that constrains spatial vision by establishing the comprehensive three-way connection between SF channel reweighting, pRF position displacement and perceptual distortions of spatial property information.
Small-molecule Activation of TFEB Alleviates Niemann-Pick Disease Type C via Promoting Lysosomal Exocytosis and Biogenesis
Authors: Du Kaili , Chen Hongyu , Pan Zhaonan , Zhao Mengli , Cheng Shixue , Luo Yu , Zhang Wenhe , Li Dan 
Published: October 2024

AbstractNiemann–Pick disease type C (NPC) is a devastating lysosomal storage disease characterized by abnormal cholesterol accumulation in lysosomes. Currently, there is no treatment for NPC. Transcription factor EB (TFEB), a member of the microphthalmia transcription factors (MiTF), has emerged as a master regulator of lysosomal function and promoted the clearance of substrates stored in cells. However, it is not known whether TFEB plays a role in cholesterol clearance in NPC disease. Here, we show that transgenic overexpression of TFEB, but not TFE3 (another member of MiTF family) facilitates cholesterol clearance in various NPC1 cell models. Pharmacological activation of TFEB by sulforaphane (SFN), a previously identified natural small-molecule TFEB agonist by us, can dramatically ameliorate cholesterol accumulation in human and mouse NPC1 cell models. In NPC1 cells, SFN induces TFEB nuclear translocation via a ROS-Ca2+-calcineurin dependent but MTOR-independent pathway and upregulates the expression of TFEB-downstream genes, promoting lysosomal exocytosis and biogenesis. While genetic inhibition of TFEB abolishes the cholesterol clearance and exocytosis effect by SFN. In the NPC1 mouse model, SFN dephosphorylates/activates TFEB in brain and exhibits potent efficacy of rescuing the loss of Purkinje cells and body weight. Hence, pharmacological upregulating lysosome machinery via targeting TFEB represents a promising approach to treat NPC and related lysosomal storage diseases, and provides the possibility of TFEB agonists ie SFN as potential NPC therapeutic candidates.
Nrf2 orchestrates epigenetic regulations and serves as the master regulator of KLF4 expression and activity during arsenic-induced transformation
Authors: Wang Ziwei , Bi Zhuoyue , Bamrah Jessica , Qiu Yiran , Zhang Wenxuan , Ji Haoyan , Haley John D. , Thakur Chitra , Chen Fei 
Published: October 2024

AbstractEmerging evidence suggests that Nrf2 plays a pro-carcinogenic role in cancer. Our previous study showed that arsenic-induced Nrf2 activation triggers metabolic reprogramming, leading to the formation of cancer stem-like cells. Here, we further demonstrated that KLF4, a key pluripotency factor, is a direct transcriptional target of Nrf2 in arsenic-exposed human bronchial epithelial cells. ChIP-seq analysis identified multiple Nrf2 binding peaks at the Klf4 gene locus, which overlap with the enhancer markers H3K4me1 and H3K27Ac. Nrf2 knockout reduced both KLF4 expression and enhancer marker enrichment, accompanied by a global decrease in KLF4 binding across the genome. In wild-type (WT) cells, arsenic treatment increased KLF4 binding on genes involved in oncogenic pathways such as STAT3, SOX2, Nrf2, cell growth, Hedgehog, and EMT. We also found that KLF4 engages in a self-feedback loop in response to Nrf2 signaling. Lastly, our data showed that the co-occupancy of Nrf2 and KLF4 is crucial for establishing active enhancer hubs in the genome. These findings suggest that Nrf2’s oncogenic effects are, in part, mediated by Nrf2 dependent self-amplification of KLF4 expression and function. Thus, targeting both Nrf2 and KLF4 could be a promising therapeutic strategy for eliminating cancer stem-like cells.
Genetic compatibility and ecological connectivity drive the dissemination of antibiotic resistance genes
Authors: Lund David , Parras-Moltó Marcos , Inda-Díaz Juan S. , Ebmeyer Stefan , Larsson D.G. Joakim , Johnning Anna , Kristiansson Erik 
Published: October 2024

AbstractThe dissemination of mobile antibiotic resistance genes (ARGs) via horizontal gene transfer is a significant threat to public health globally. The flow of ARGs into and between pathogens, however, remains poorly understood, limiting our ability to develop strategies for managing the antibiotic resistance crisis. Therefore, we aimed to identify genetic and ecological factors that are fundamental for successful horizontal ARG transfer. From the analysis of ∼1 million bacterial genomes and >20,000 metagenomes, we developed random forest models that could reliably predict horizontal ARG transfer between bacteria. Our results suggest that genetic incompatibility, measured as nucleotide composition dissimilarity, negatively influences the likelihood of transfer of ARGs between evolutionarily divergent bacteria. Conversely, environmental co-occurrence increased the likelihood, especially in humans and wastewater, in which several environment-specific dissemination patterns were observed. This study provides new ways to predict the spread of ARGs and provides new insights into the mechanisms governing this evolutionary process.
Aβ-targeting synNotch Receptor for Alzheimer’s Disease: Expanding Applications to Extracellular Protein Aggregates
Authors: Bergo Nicholas J. , Lee Suckwon , Siebrand Cynthia J. , Andersen Julie K. , Walton Chaska C. 
Published: October 2024

SummaryThe synthetic Notch receptor (synNotch) system is a versatile platform that induces gene transcription in response to extracellular signals. However, its application has been largely confined to membrane-bound targets due to specific activation requirements. Whether synNotch can also target extracellular protein aggregates, such as amyloid beta (Aβ) in Alzheimer’s disease (AD), is unclear. To address this, we engineered an Aβ-targeting synNotch receptor controlling the production of chimeric human-mouse versions of Lecanemab (Leqembi®) or Aducanumab (Aduhelm®), both FDA-approved antibodies for AD. We demonstrate that NIH 3T3 cells expressing this synNotch system detect and respond to extracellular Aβ aggregates by synthesizing and secreting Aducanumab or Lecanemab. These findings broaden the potential applications of synNotch, extending its targets beyond membrane-bound proteins to extracellular protein aggregates, providing obvious benefits to research in this scientific arena.
Are protected areas tracking threats to terrestrial biodiversity?
Authors: Pulido Chadid Katherine , Rahbek Carsten , Geldmann Jonas 
Published: October 2024

1AbstractProtected areas (PAs) are vital for nature conservation, yet evidence shows that pressure on biodiversity is increasing despite their global expansion. Using threat probability maps based on the IUCN Red List and PA data, we analyzed the relationship between PA coverage and the major threats—agriculture, hunting, logging, pollution, invasive species, and urbanization—affecting amphibians, birds, mammals, and reptiles. Our analysis includes data on 33,379 species and 255,848 protected sites. Our results reveal a potential disconnect between global PAs and threat tracking, often leaving high-threat areas insufficiently protected. Over half of the mapped area for amphibians and mammals faces high threat impact probability and insufficient PA cover. Amphibians face the highest proportion of high-simultaneous threats and lack sufficient cover. Areas facing a high probability of impact lacking sufficient PA cover also harbor the highest proportion of threatened species across all taxonomic groups. Our research provides crucial insights into the current state of terrestrial PAs concerning threats, highlighting areas requiring immediate attention and guiding strategic conservation planning.
An Extensive Atlas of Proteome and Phosphoproteome Turnover Across Mouse Tissues and Brain Regions
Authors: Li Wenxue , Dasgupta Abhijit , Yang Ka , Wang Shisheng , Hemandhar-Kumar Nisha , Yarbro Jay M. , Hu Zhenyi , Salovska Barbora , Fornasiero Eugenio F. , Peng Junmin , Liu Yansheng 
Published: October 2024

SUMMARYUnderstanding how proteins in different mammalian tissues are regulated is central to biology. Protein abundance, turnover, and post-translational modifications like phosphorylation, are key factors that determine tissue-specific proteome properties. However, these properties are challenging to study across tissues and remain poorly understood. Here, we presentTurnover-PPT, a comprehensive resource mapping the abundance and lifetime of 11,000 proteins and 40,000 phosphosites across eight mouse tissues and various brain regions, using advanced proteomics and stable isotope labeling. We revealed tissue-specific short- and long-lived proteins, strong correlations between interacting protein lifetimes, and distinct impacts of phosphorylation on protein turnover. Notably, we discovered that peroxisomes are regulated by protein turnover across tissues, and that phosphorylation regulates the stability of neurodegeneration-related proteins, such as Tau and α-synuclein. Thus,Turnover-PPTprovides new fundamental insights into protein stability, tissue dynamic proteotypes, and the role of protein phosphorylation, and is accessible via an interactive web-based portal athttps://yslproteomics.shinyapps.io/tissuePPT.
Fusobacterium necrophorumandFusobacterium variumare commensal members of the bovine reproductive microbiota and may colonize calf prenatally
Authors: Kilama Justine , Dahlen Carl R , Abbasi Mina , Shi Xiaorong , Nagaraja T. G. , Crouse Matthew S. , Cushman Robert A. , Snider Alexandria P. , McCarthy Kacie L. , Caton Joel S. , Amat Samat 
Published: October 2024

ABSTRACTFusobacterium necrophorumis an important pathogen associated with several infectious diseases in cattle. However, recent sequencing-based studies have indicated thatF. necrophorumis positively associated with pregnancy in beef cows and thatFusobacteriumis the most abundant genus in the bull seminal microbiota, suggesting the potential role ofFusobacteriumin reproductive health and fertility. Here, we performed a comprehensive screening to 1) determine whetherFusobacterium necrophorum(subspeciesnecrophorum[FNN] andfunduliforme[FNF]), andFusobacterium varium(FV) are part of the commensal members of the reproductive microbiota in cattle; 2) to explore whether theseFusobacteriumspp. are colonized in calf prenatally. For this, we screened 11 different sample types including bovine and ram semen, bovine vaginal and uterine swabs, and bull fecal samples, as well as samples from 180- and 260-days old calf fetuses and their respective dams using both quantitative PCR (514 samples) and targeted culturing (499 samples). By qPCR, all the targetedFusobacteriumspp. were detected across all sample types, with FNF being the highly prevalent in the bull semen (66.7%) and maternal ruminal fluids (87.1%), which was confirmed by culturing. All the targetedFusobacteriumwere identified in vaginal and uterine (3.1%-9.4%) as well as placental caruncles, and fetal fluids, ruminal and meconium samples (2.7% - 26.3%) by qPCR and were not isolated by culture method. Overall, our results suggest thatF. necrophorumis a commensal member of healthy male reproductive microbiota, and that FNF, FNN and FV are present in bovine vagino-uterine microbiota, and calf intestine prenatally.
Commensal virome regulate intestinal nutrient sensing via Th17 cells
Authors: Lin Fengqing 
Published: October 2024

AbstractOur study explores the influence of gut virome on nutrient sensing via T cells in the small intestine. We discovered that the gut virome can independently affect the digestion and absorption of carbohydrates in the small intestine, and this effect is contingent upon T cell surveillance. Additionally, our research reveals heterogeneous responses elicited by virome components across different small intestinal cell types. Stimulation of intestinal epithelial cells is dependent on intact viral particles, while the stimulation of T cells and antigen-presenting cells relies on viral capsids. In the normal murine gut, the virome stimulates antigen-presenting cells to recruit T cells and induce IL22 expression. These findings are significant for developing therapeutic and nutritional strategies targeting metabolic diseases, underscoring the importance of incorporating the gut virome as a key element in interventions.