bluuebunny/crossref_metadata_2025_split huggingface dataset:
Genetic diversity and demographic history of the largest remaining migratory population of blue wildebeest (Connochaetes taurinus taurinus) in southern Africa
Authors: Szarmach Stephanie J. , Teeter Katherine C. , M’soka Jassiel , Dröge Egil , Ndakala Hellen , Chifunte Clive , Becker Matthew S. , Lindsay Alec R. 
Published: September 2024

ABSTRACTThe blue wildebeest (Connochaetes taurinus taurinus) is a keystone species in the savannahs of southern Africa, where it maintains shortgrass plains and serves as an important prey source for large carnivores. Despite being the second largest migratory wildebeest population, the wildebeest of the Greater Liuwa Ecosystem (GLE) of western Zambia have remained largely unstudied, until recently. While studies have increased understanding of recent demography, migration, and population limiting factors, the level of genetic diversity, patterns of gene flow, and long-term demographic history of blue wildebeest in the GLE remains unknown. Most genetic studies of wildebeest have focused on small, heavily-managed populations, rather than large, migratory populations of high conservation significance. We used restriction-site associated DNA sequencing (RAD-seq) to assess genetic diversity, population structure, and demographic history of blue wildebeest in the GLE. Using SNPs from 1,730 loci genotyped across 75 individuals, we found moderate levels of genetic diversity in GLE blue wildebeest (He = 0.210), no evidence of inbreeding (FIS = 0.033), and an effective population size of about one tenth the estimated population size. No genetic population structure was evident within the GLE. Analyses of the site frequency spectrum found signatures of expansion during the Middle Pleistocene followed by population decline in the Late Pleistocene and early Holocene, a pattern previously observed in other African ungulates. These results will supplement field studies in developing effective conservation plans for wildebeest as they face continued and increasing threats of habitat loss, poaching, and other human impacts across their remaining range.
Stopping Speed as State, Not Trait: Exploring Within-Animal Varying Stopping Speeds in a Multi-Session Stop-Signal Task
Authors: ter Horst Jordi , Cohen Michael X , Englitz Bernhard 
Published: September 2024

AbstractBeing able to reactively stop ongoing movements is important for safe navigation through the environment. Reactive stopping is typically studied using the stop-signal task, where participants are occasionally instructed to stop initiated movements. The speed of stopping, also referred to as the stop-signal reaction time (SSRT), is not observable because successful stopping lacks a response, but can be estimated. Researchers most often acquire one session of data per participant to estimate the speed of stopping, but sometimes more sessions of data are acquired to maximize the signal-to-noise ratio, for example when the task is combined with neural recordings such as electrophysiology. However, it is unknown whether the estimated stopping speed is a fixed trait or a state that can vary under identical experimental conditions. In this study, we investigate whether a separately estimated SSRT for each acquired session is statistically meaningful compared to estimating an across-session SSRT, by collecting many sessions in which male rats performed a stop-signal task. Results revealed that within-animal stopping speeds meaningfully changed from session to session and were not following a trend over time (e.g., due to task learning). Single-session SSRT estimates with lower reliabilities were associated with higher go trial response time variabilities, lower skewness levels of the go trial response time distribution, and lower stop accuracies. We also explored which factors explained changing SSRTs, and showed that motivation, shared motor dynamics, and attention could play a role. In conclusion, we encourage researchers to treat SSRTs as state-like variables when collecting multi-session stop-signal task data, as our results have convincingly shown that stopping speeds are far from trait-like under identical experimental conditions. This session-by-session approach will help future research in which neural signatures of reactive stopping need to be extracted in a time-precise manner, because time-locking stop-related neural activity to session-specific SSRTs is expected to capture the signature more precisely as opposed to an across-session SSRT.
A 15-Gene prognostic signature with TFAP2B functioning in Platinum Resistance of Ovarian Carcinoma
Authors: Hu Yang , Wang Ping , Xiang Jian , Han Lu , Zhang Biyun , Liu Xiaohua , Nie Hua , Chen Guobing , Qin Weibing 
Published: September 2024

AbstractResistance to platinum is the main challenge in the chemotherapy of ovarian cancer (OV). Therefore, developing a response signature to platinum is essential for the precision therapy of OV. Existing quantitative signatures of platinum are susceptible to batch effects and sequencing platform variations. To address this, we developed a transcriptome-based platinum signature, named PRSM, consisting of 15 genes, based on within-sample prognostic and relative expression ordering of genes, to predict individual responses to platinum in OV. The PRSM model demonstrated superior classification accuracy compared to previous quantitative signatures. Resistant samples classified by PRSM exhibited poorer overall survival, lower SNV neoantigen load, tumor mutational burden, and distinct methylation patterns compared to sensitive samples. Pathway analysis revealed the activation of MYC targets V2 and oxidative phosphorylation in resistant tumors. Single-cell analysis highlighted the roles of NK and epithelial cells in resistance. Among the 15 core genes, five (TFAP2B, KRT81, PAGE1, CRNN, UGT2B17) were linked to poor prognosis, with TFAP2B having the highest contribution to PRSM. Overexpression of TFAP2B in A2780 cells enhanced cisplatin sensitivity, while in A2780cis cells, it inhibited growth. In brief, our findings provide a multi-dimensional view of platinum resistance in ovarian cancer, introducing a robust predictive model and identifying potential therapeutic targets.
Deep mutational scanning of the human insulin receptor ectodomain to inform precision therapy for insulin resistance
Authors: Aslanzadeh Vahid , Brierley Gemma V. , Kumar Rupa , Çubuk Hasan , Vigouroux Corinne , Matreyek Kenneth A. , Kudla Grzegorz , Semple Robert K. 
Published: September 2024

SummaryThe insulin receptor (INSR) entrains tissue growth and metabolism to nutritional conditions. Complete loss of function in humans leads to extreme insulin resistance and infantile mortality, while loss of 80-90% function permits longevity of decades. Even low-level activation of severely compromised receptors, for example by anti-receptor monoclonal antibodies, thus offers the potential for decisive clinical benefit. A barrier to genetic diagnosis and translational research is the increasing identification ofINSRvariants of uncertain significance. We employed saturation mutagenesis coupled to multidimensional flow-based assays to stratify approximately 14,000 INSR extracellular domain missense variants by cell surface expression, insulin binding, and insulin- or monoclonal antibody-stimulated signaling. The resulting function scores correlate strongly with clinical syndromes, offer insights into dynamics of insulin binding, and reveal novel potential gain-of-function variants. This INSR sequence-function map has high biochemical, diagnostic and translational utility, aiding rapid identification of variants amenable to activation by non-canonical INSR agonists.
Adapting COVID-19 research infrastructure to capture influenza and RSV alongside SARS-CoV-2 in UK healthcare workers winter 2022/23: Evaluation of the SIREN Winter Pressures pilot study
Authors: Russell Sophie , Munro Katie , Foulkes Sarah , Broad Jonathan , Sparkes Dominic , Atti Ana , Islam Jasmin , Hopkins Susan , Hall Victoria ,   SIREN study group
Published: September 2024

AbstractBackgroundIn 2022, with high early winter respiratory virus circulation, SIREN, a prospective healthcare worker cohort study monitoring SARS-CoV-2, ran a pilot study introducing multiplex PCR testing for SARS-CoV-2, influenza A/B, and RSV to investigate winter pressures. Three pathways were trialled: (A) on-site swabbing with local laboratory testing, (B) on-site swabbing with UKHSA-commissioned laboratory testing, and (C) postal swabbing with UKHSA-commissioned laboratory testing. Here, we compare pathways in relation to recruitment, testing coverage, participant acceptability, and UKHSA SIREN research team feedback.MethodsWe conducted a mixed methods evaluation using metrics of quality assurance and study fidelity (participant recruitment and retention; multiplex PCR testing timing and coverage), an adapted NIHR ‘participant in research’ feedback questionnaire, and thematic analysis of a UKHSA SIREN research team workshop.ResultsWith 7,774 participants recruited, target recruitment (N=7,500) was achieved. Thirty-nine sites took part in the sub-study (4,289 participants). Thirty-three used pathway A, and six used pathway B. 3,485 participants enrolled to pathway C (27.8% of invitees). The median number of tests per participant was similar across pathways (6; 4; 5). However, sites using local laboratories showed a wide variation in the date they switched to multiplex testing (28thNovember 2022 to 16thMarch 2023). Consequently, influenza and RSV testing coverage was higher for pathways using UKHSA-commissioned laboratories (100.0% vs 45.6% at local laboratories). 1,204/7,774 (15.5%) participants completed the feedback survey. All pathways were acceptable to participants; 98.9% of postal and 97.5% of site-based participants ‘would consider taking part again’.ConclusionTransitioning SARS-CoV-2 PCR testing to include influenza and RSV was challenging to achieve rapidly across multiple sites. The postal testing pathway proved more agile, and UKHSA-commissioned laboratory testing provided more comprehensive data collection than local laboratory testing. This sub-study indicates that postal protocols are effective, adaptable at pace, and acceptable to participants.
Cross-species interactome analysis uncovers a conserved selective autophagy mechanism for protein quality control in plants
Authors: Hernández Víctor Sánchez de Medina , García Marintia Mayola Nava , Clavel Marion , Papareddy Ranjith K. , Andreev Veselin I. , Mathur Varsha , Mohseni Azadeh , García-León Marta , Gao Peng , de la Concepción Juan Carlos , Picchianti Lorenzo , Grujic Nenad , Kobylinska Roksolana , Abdrakhmanov Alibek , Duvergé Héloïse , Anand Gaurav , Leibrock Nils , Bianchi Anita , Raffeiner Margot , Crawford Timothy Scott , Argirò Luca , Matuszkiewicz Mateusz , Wun Cheuk-Ling , Kanne Jakob Valdbjørn , Meinhart Anton , Roitinger Elisabeth , Bäurle Isabel , Kang Byung Ho , Petersen Morten , Üstün Suayib , Kulathu Yogesh , Clausen Tim , Ramundo Silvia , Dagdas Yasin 
Published: September 2024

AbstractSelective autophagy is a fundamental protein quality control pathway that safeguards proteostasis by degrading damaged or surplus cellular components, particularly under stress. This process is orchestrated by selective autophagy receptors (SARs) that direct specific cargo for degradation. While significant strides have been made in understanding the molecular framework of selective autophagy, the diversity of SAR repertoires across species remain largely unexplored. Through a comparative interactome analysis across five model organisms, we identified a suite of conserved and lineage-specific SAR candidates. Among these, we validated CESAR as a conserved SAR critical for proteostasis under heat stress. CESAR specifically facilitates the degradation of hydrophobic, ubiquitinated protein aggregates and is indispensable for heat stress tolerance. Our study offers a rich resource for SAR discovery and positions CESAR as a pivotal regulator of proteostasis, with broad implications for improving stress resilience in plants.
Bioactivity Analysis of Secondary Metabolites from Actinomycetes’ Isolated from Coastal Sediments
Authors: Shubhro Kumar , Rimi Arifa Afrose , Islam Md. Emdadul , Islam Kazi Didarul , Billah Md. Morsaline , Mia Mijan , Rahman SM Mahbubur 
Published: September 2024

AbstractThe rising threat of antibiotic resistance underscores the need for new antibiotics. Marine actinomycetes have emerged as promising sources of bioactive compounds. In this study, 22 isolates from marine sediments were morphologically identified, with nine confirmed as actinomycetes through 16S rRNA gene sequencing. Five strains-Streptomyces olivoverticillatus(T-2),Streptomyces cyaneus(T-4),Nocardiopsis synnemataformans(T-7),Streptomyces albogriseolus(T-8), andStreptomyces atrovirens(T-9)- exhibited significant antibacterial activity. Cultured in Starch Casein Broth, their metabolites were tested for antibacterial, antioxidant, anticoagulation, and anti-inflammatory activities. T-4 and T-8 demonstrated notable antimicrobial action, T-8 showing potent DPPH radical scavenging (372.09 ± 11.05 µg/mL). T-9 inhibited trypsin (IC50435.12 ± 15.88 µg/mL) and had a prothrombin time of 12.08 ± 1.46 minutes. T-8 enhanced RBC membrane stabilization (IC50140.08 ± 2.30 µg/mL). These findings suggest that marine sediment-derived actinomycetes hold significant therapeutic potential and warrant further study.
CSF pressure in fetal micein utero: External factors pressurize the intraventricular space
Authors: Tsujikawa Koichiro , Muramatsu Reina , Miyata Takaki 
Published: September 2024

AbstractPrevious experiments inducing leakage of embryonic cerebrospinal fluid (CSF) suggest the necessity of intraventricular CSF pressure (PCSF) for brain morphogenesis. Nevertheless, how embryonic PCSFoccurs is unclear, especiallyin utero. Using a Landis water manometer, we measured PCSFin fetal mice isolated from the amniotic cavity (PCSF-ISO). At embryonic day (E) 13, PCSF-ISOwas 82.7 Pa. Intraventricular injections of ≥2 μl of saline elevated PCSF-ISOby ∼30%. Intraventricularly injecting inhibitors of CSF secretion decreased PCSF-ISOby ∼30%. Shh-mediated cerebral-wall expansion and the resulting ventricular narrowing did not significantly increase PCSF-ISO. Removal of the brain-surrounding contractile tissues decreased PCSF-ISOby 80-90%. The intraamniotic pressure measuredin utero(PAF-IU) was 1030.7 Pa. Our direct measurement revealed that the PCSFin utero(PCSF-IU) was 1076.4 Pa, confirming the susceptibility of PCSFto external factors. Subsequent PCSFmeasurements under hydrostatic pressure loading suggested that PCSF-IU= PCSF-ISO+ PAF-IU, a relationship further used to estimate PCSF-IUat other ages when direct measurement was not possible. The estimated PCSF-IUdecreased almost constantly from E10 to E16 (2000 ➔ 500 Pa).
Bidirectional Upregulation of Klotho by Triiodothyronine and Baicalein: Mitigating Chronic Kidney Disease and Associated Complications in Aged BALB/c Mice
Authors: Mohanty Saswat Kumar , Sahu Vikas Kumar , Singh Bhanu Pratap , Suchiang Kitlangki 
Published: September 2024

AbstractChronic kidney disease (CKD) is a global health challenge marked by progressive renal decline and increased mortality. The interplay between CKD and hypothyroidism, particularly nonthyroidal low-triiodothyronine (T3) syndrome, exacerbates disease progression, driven by HPT axis dysfunction and reduced Klotho levels due to Wnt–β-catenin pathway activation. This study explored Klotho as a link between CKD and hypothyroidism using an adenine-induced CKD aged mouse model. Exogenous T3 and baicalein (BAI), targeting the Wnt pathway, were used to upregulate Klotho expression. Combined T3 and BAI treatment significantly increased Klotho levels, surpassing individual effects, and suppressed key signaling molecules (TGF, NFκB, GSK3), mitigating renal fibrosis and CKD complications, including cardiovascular disorders and dyslipidemia. This bidirectional approach, enhancing Klotho via T3 and sustained Wnt pathway inhibition, offers a novel and effective strategy for CKD management, particularly in elderly patients with hypothyroidism.
The antimicrobial potential of traditional remedies of Indigenous Peoples from Canada against MRSA planktonic and biofilm bacteria in wound-infection mimetic conditions
Authors: Rieger Colin D. , Soliman Ahmed M. , Kaplia Kateryna , Ghosh Nilrup , Lopez Alexa Cervantes , Venkatesan Surya Arcot , Flores Abraham Gildaro Guevara , Belin Matheus Antônio Filiol , Allen Florence , Reynolds Margaret , McKenna Betty , Lavallee Harold , Weenie Archie , Favel Thomas , Gendron Fidji , Ziffle Vincent E. , El-Halfawy Omar M. 
Published: September 2024

AbstractMethicillin-resistantStaphylococcus aureus(MRSA) is the leading cause of wound infections, often progressing into serious invasive bloodstream infections. MRSA disproportionately affects Indigenous peoples in Canada with higher rates of skin and wound infections, an example of persistent gaps in health outcomes between Indigenous and non-Indigenous peoples precipitated by the legacy of colonialism. Conversely, Indigenous peoples have long used natural remedies for infections and other diseases; however, their knowledge was rarely considered for modern medicine. The stagnant antibiotic discovery pipeline and alarming rise of resistance to current antibiotics prompted us to turn to Indigenous medicine as an untapped source of antimicrobials. As such, we collected and prepared 85 extracts of medicinal plants of value to Indigenous Peoples spanning the Canadian Prairies. We explored the antimicrobial potential of these extracts against MRSA under wound infection-mimetic conditions compared to culture media typically used to study bacterial antibiotic responses and biofilms but not adequately representative of infection sites. We identified extracts with MRSA growth inhibitory [e.g., bergamot, dock, gaillardia, and dandelion extracts] and biofilm prevention and eradication [e.g., gumweed extracts] activities. Extracts, including those of chokecherry, hoary puccoon, and Northern bedstraw, were only active under wound infection-mimetic conditions, highlighting the relevance of antibiotic discovery under host-relevant conditions. Testing growth inhibitory extracts against anS. aureuscross-resistance platform suggested that they act through mechanisms likely distinct from known antibiotic classes. Together, through an interdisciplinary partnership leveraging Western approaches and traditional Indigenous knowledge, we identified plant extracts with promising antimicrobial potential for drug-resistant MRSA wound infections.
Dimerization-dependent gel-like condensation with dsDNA underpins the activation of human cGAS
Authors: Lueck Jacob , Strom Alexander , Wu Shuai , Wendorff Hannah , Sohn Jungsan 
Published: September 2024

AbstractCyclic G/AMP Synthase (cGAS) initiates inflammatory responses against pathogenic double-stranded (ds)DNA. Although it is well established that cGAS forms phase-separated condensates with dsDNA, their function remains poorly defined. We report here that the dimerization of cGAS on dsDNA creates a mesh-like network, leading to gel-like condensate formation. Although cGAS binds to and forms condensates with various nucleic acids, only dsDNA permits the dimerization necessary for activation and gelation. cGAS co-condenses dsDNA and other nucleic acids but retains a distinct dsDNA-mediated gel-like substate, which single-stranded RNA can dissolve and deactivate the enzyme. Moreover, gel-like, but not liquid-like, condensation not only protects bound dsDNA from exonucleases, but also limits the mobility of NTPs and the dinucleotide intermediate for efficient cGAMP synthesis. Together, our results show that enzymes can finetune surrounding microenvironments to regulate their signaling activities.
Stress response of membrane-based cell organelles in budding yeast
Authors: Peng Sheng , Li-zhe Bai , Hong Cao , Dan Li 
Published: September 2024

AbstractThe organelles of yeast demonstrate diverse morphological traits in response to different stress stimuli. However, there is a lack of systematic reports on the structural changes induced by stress stimuli in all membrane-based organelles. Here, we utilized a set of fluorescent protein-based organelle markers to highlight the distinct characteristics of yeast under various stress triggers, including high temperature, hydrogen peroxide, acetic acid, and ethyl alcohol. We found that all of these organelles undergo alterations in structure or function in response to the four stress triggers we tested. Specifically, filamentous mitochondria rupture into smaller segments when exposed to the above four stress conditions. The structure of the endoplasmic reticulum (ER) remains relatively unchanged, but its function is affected. Additionally, high temperature and hydrogen peroxide can induce the Ire1p-mediated ER unfolded protein response (UPR). The translocation of most nuclear-localized proteins to the cytosol is dependent on the specific stress conditions employed. Under the above stress conditions, the vacuole undergoes fusion, resulting in the formation of a larger vacuole from multiple smaller ones. Meanwhile, acetic acid-induced stress leads to the translocation of vacuole-localized proteins Prc1p and Pep4p to unknown puncta, while Ybh3p relocates from the inner vacuole to the vacuole membrane. Proteins localized in the early Golgi, late Golgi, and late endosomes exhibit distinct traits, such as fading away or mis-localization. The structure and function of peroxisomes, lipid droplets, and autophagosomes also undergo modifications. Furthermore, upon exposure to high temperature and ethanol, apoptosis-related proteins Yca1, Aif1, and Mmi1 aggregate instead of remaining dispersed.
Tcc+
and
χc1(3872)
with the complex scaling method and
DD(D¯)π
three-body effect
Authors: Lin Zi-Yang , Cheng Jian-Bo , Zhu Shi-Lin 
Published: September 2024

We use the leading-order contact interactions and one-pion-exchange potentials to investigate the newly observed double-charm state Tcc+. We employ the complex scaling method to search for the poles on the first Riemann sheet with respect to the DD* threshold and the second Riemann sheet with respect to the DDπ threshold. The DDπ three-body effect is important in this system since the intermediate states can go on shell. We involve the three-body effect through an energy-dependent one-pion-exchange potential, which results in a unitary cut at the DDπ three-body threshold. We find a pole corresponding to the Tcc+ on the physical Riemann sheet. Its width is around 80 keV and nearly independent of the choice of the cutoff. Assuming the DD¯π and DD¯* channels as the main decay channels, we apply the similar calculations to the χc1(3872), and find its width is even smaller. The isospin breaking effect is so significant for the χc1(3872) that it is mainly a molecular state of D0D¯*0. Furthermore, we introduce a revised Schrödinger equation for unstable particles to include the contribution of the D* width, which is also revised by the three-body effect.

Published by the American Physical Society
2024