bluuebunny/crossref_metadata_2025_split huggingface dataset:
Insights into Dentatorubral-Pallidoluysian Atrophy from a newDrosophilamodel of disease
Authors: Prifti Matthew V. , Nuga Oluwademilade , Dulay Ryan O. , Patel Nikhil C. , Kula Truman , Libohova Kozeta , Jackson-Butler Autumn , Tsou Wei-Ling , Richardson Kristin , Todi Sokol V. 
Published: December 2024

ABSTRACTDentatorubral-pallidoluysian atrophy (DRPLA) is a neurodegenerative disorder that presents with ataxia, dementia and epilepsy. As a member of the polyglutamine family of diseases, DRPLA is caused by abnormal CAG triplet expansion beyond 48 repeats in the protein-coding region ofATROPHIN 1(ATN1), a transcriptional co-repressor. To better understand DRPLA, we generated newDrosophilalines that express full-length, human ATN1 with a normal (Q7) or pathogenic (Q88) repeat. Expression of ATN1 is toxic, with the polyglutamine-expanded version being consistently more problematic than wild-type ATN1. Fly motility, longevity and internal structures are negatively impacted by pathogenic ATN1. RNA-seq identified altered protein quality control and immune pathways in the presence of pathogenic ATN1. Based on these data, we conducted genetic experiments that confirmed the role of protein quality control components that ameliorate or exacerbate ATN1 toxicity. Hsc70-3, a chaperone, arose as a likely suppressor of toxicity. VCP (a proteasome-related AAA ATPase), Rpn11 (a proteasome-related deubiquitinase) and select DnaJ proteins (co-chaperones) were inconsistently protective, depending on the tissues where they were expressed. Lastly, informed by RNA-seq data that exercise-related genes may also be involved in this model of DRPLA, we conducted short-term exercise, which improved overall fly motility. This new model of DRPLA will prove important to understanding this understudied disease and will help to identify therapeutic targets for it.
An Unsupervised Approach to Identify Patient-Specific EMG Detector to Trigger Robot-Assisted Therapy
Authors: Yuvaraj Monisha , Prabakar A.T. , S.K.M Varadhan , Burdet Etienne , Ramos-Murgialday Ander , Balasubramanian Sivakumar 
Published: December 2024

AbstractIn severely impaired stroke patients, implementing EMG-driven robot-assisted therapy requires the presence of sufficient residual EMG and a patient-specific detector for accurate and low-latency EMG detection. However, identifying such a detector is challenging, especially when the level of residual EMG in a given patient is unknown . This paper proposes an unsupervised approach to distinguish between EMG data when the patient is relaxed versus attempting a movement – themaximally separating detector. We investigated six different detector types and separation measures using EMG data from a previous randomized controlled trial. The results indicate that the approximate generalized likelihood ratio detector, along with the modified Hodges and modified Lidierth detectors, achieved the best separation. Using a subset of clinician annotated data to evaluate the detection performance, the modified Hodges detector employing the probability difference-sum ratio measure had the best detection performance in terms of detection accuracy and latency. Using the data from 30 participants, we propose a probability difference-sum ratio threshold of 0.7 for the modified Hodges detector to identify patients with sufficient residual EMG to trigger robotic assistance. From the results, we propose the use of modified Hodges detector along with a probability difference-sum ratio measure to learn the maximally separating detector for a given patient, which will screen the patient for sufficient residual EMG and provide a detector to trigger robotic assistance if sufficient EMG is present. The validation of this approach using a large dataset and investigating the quality of the human-machine interaction implemented with such a detector is warranted.
NucleoSeeker: Precision Filtering of RNA Databases to Curate High-Quality Datasets
Authors: Upadhyay Utkarsh , Pucci Fabrizio , Herold Julian , Schug Alexander 
Published: December 2024

AbstractThe structural prediction of biomolecules via computational methods complements the often involved wet-lab experiments. Un-like protein structure prediction, RNA structure prediction remains a significant challenge in bioinformatics, primarily due to the scarcity of annotated RNA structure data and its varying quality. Many methods have used this limited data to train deep learning models but redundancy, data leakage and bad data quality hampers their performance. In this work, we present NucleoSeeker, a tool designed to curate high-quality, tailored datasets from the Protein Data Bank (PDB) database. It is a unified framework that combines multiple tools and streamlines an otherwise complicated process of data curation. It offers multiple filters at structure, sequence and annotation levels, giving researchers full control over data curation. Further, we present several use cases. In particular, we demonstrate how NucleoSeeker allows the creation of a non-redundant RNA structure dataset to assess AlphaFold3’s performance for RNA structure prediction. This demonstrates NucleoSeeker’s effectiveness in curating valuable non-redundant tailored datasets to both train novel and judge existing methods. NucleoSeeker is very easy to use, highly flexible and can significantly increase the quality of RNA structure datasets.
Extreme lead tolerance in an urban lizard
Authors: Blanchette A , Su KJ , Frick AJ , Karubian J , Gunderson AR 
Published: December 2024

AbstractLead (Pb) is an extremely toxic heavy metal pollutant pervasive in many environments with serious health consequences for humans and wildlife. Identifying organisms that can serve as biomonitors of lead contamination and models to understand mechanisms of lead tolerance is therefore an important goal. We used the Cuban brown anole lizard (Anolis sagrei) in New Orleans, USA, to investigate the consequences of variation in environmental lead exposure at the physiological and gene regulatory levels. We found that brown anole blood lead levels are associated with soil lead contamination, and that their blood lead levels are extreme. At our most contaminated site, the mean and highest individual blood lead levels were over two times higher than the next highest values reported in free-living vertebrates. However, this lead exposure did not decrease performance in whole-organism traits commonly affected by lead (balance, sprint speed, endurance). A 60-day lead dosing experiment demonstrated that the brown anole blood lead threshold for decreased whole-organism performance is actually an order of magnitude higher than the highest mean field concentration. Transcriptomic analysis of brain and liver from lizards in high and low lead sites revealed relatively minor effects of lead exposure. However, several of the differentially expressed genes function in metal ion homeostasis and oxygen carrying capacity, pointing to cellular mechanisms that may contribute to high lead tolerance. The brown anole may be the most lead-tolerant vertebrate known to date and has the potential to be a powerful model system to help us better understand how organisms cope with heavy metal exposure.
Leaving Science: Attrition of Biologists in 38 OECD Countries
Authors: Kwiek Marek , Szymula Lukasz 
Published: December 2024

AbstractThis study examines biologists leaving science in 38 OECD countries in the past two decades. We use publication metadata from a global bibliometric database (raw Scopus data at the micro-level of individual scientists). In a cohort-based and longitudinal fashion, we follow individual men and women scientists over time, from their first to their last publication (N=86,178). We examine four academic disciplines: AGRI (agricultural and biological sciences), BIO (biochemistry, genetics, and molecular biology), IMMU (immunology and microbiology), and NEURO (neuroscience). We apply survival analysis, conceptualizing scientific life as a sequence of scholarly publishing events. Our Kaplan–Meier survival analysis shows how women disappear from science: in BIO, about 60% are still in science after 5 years, 40% after 10 years, and only 20% by the end of the period examined (i.e., after 19 years). The percentages are substantially higher for men: approximately 70%, 50%, and 30%, respectively. Kaplan–Meier estimations indicate that women in the largest discipline (BIO) are 23.26% more likely to leave science after 10 years and 39.74% more likely to leave science at the end of the study period. Gender difference in attrition, slightly visible after 5 years, increase consistently in later career stages. The probability of surviving for women after 15 years varies considerably, from 47.8% in AGRI to 27.6% in IMMU; for men, the probability is about a fifth higher. Our data show that with the passage of time, women disappear from science in ever-larger proportions compared to men. Gender differences in attrition in the four disciplines have been and continue to be high, but comparing the 2000 and 2010 cohorts, have slightly decreased over time.
Honest signalling in predator-prey interactions: testing the resource allocation hypothesis
Authors: Burdfield-Steel Emily , Ottocento Cristina , Furlanetto Miriam , Rojas Bibiana , Nokelainen Ossi , Mappes Johanna 
Published: December 2024

AbstractWarning signals are honest if they reliably deliver information about prey unprofitability to predators. One potential mechanism that may create and maintain a positive relationship between the strength of signals and defence is the resource allocation between these costly traits. Here, we test this hypothesis using the wood tiger mothArctia plantaginis, whose females’ red hindwings are a warning signal to predators but show considerable variation in colouration within populations. These moths also produce a defensive chemical that is known to influence avian predator attack risk. Using dietary manipulations, image and chemical analyses, and experiments with ecologically relevant predators we demonstrate that protein availability during development can influence the strength of both the primary warning signal and the secondary defence. Our results show that females raised on a high-protein orad libitumnatural diet produced more distasteful defensive fluids than those raised on a low-protein diet or subjected to periodic food deprivation. While the patterning of the warning signal was unaffected by food deprivation, its efficacy was diminished in moths raised on a low-protein diet. However, this change was imperceptible to avian predators. Critically, resource availability influenced the relationship between signal strength and defence: moths on a high-protein diet displayed a positive correlation between warning signal strength and unpalatability, whereas this correlation was absent in moths raised on a natural diet. These findings show that resource availability can weaken the reliability of warning signals as an indicator of an individual’s defensive capabilities, highlighting the complex interplay between ecological conditions and the evolution of honest signalling.
Deep analysis of the Major Histocompatibility Complex associations using covariate analysis and haploblocks unravels new mechanisms for the molecular etiology of Elite Control in AIDS
Authors: Rahmouni Myriam , Clerc Sigrid Le , Spadoni Jean-Louis , Labib Taoufik , Tison Maxime , Medina-Santos Raissa , Bensussan Armand , Tamouza Ryad , Deleuze Jean-François , Zagury Jean-François 
Published: December 2024

AbstractIntroductionWe have reanalyzed the genomic data from the International Collaboration for the Genomics of HIV (ICGH), focusing on HIV-1 Elite Controllers (EC).MethodsA genome-wide association study (GWAS) was performed, comparing 543 HIV-1 EC individuals with 3,272 uninfected controls (CTR) of European ancestry. 8 million single nucleotide polymorphisms (SNPs) and HLA class I and class II gene alleles were imputed to compare EC and CTR.Results2,626 SNPs were associated with EC (p<5.10-8), all located within the Major Histocompatibility Complex (MHC) region. Stepwise regression analysis narrowed this list to 17 SNPs. In parallel, 22 HLA class I and II alleles were associated with EC. Through meticulous mapping of the LD between all identified signals and employing reciprocal covariate analyses, we delineated a final set of 6 independent SNPs and 3 HLA class I gene alleles that accounted for most of the associations observed with EC. Our study revealed the presence of cumulative haploblock effects (SNP rs9264942 contributing to the HLA-B*57:01 effect) and that several HLA allele associations were in fact caused by SNPs in linkage disequilibrium (LD). Upon investigating SNPs in LD with the selected 6 SNPs and 3 HLA class I alleles for their impact on protein function (either damaging or differential expression), we identified several compelling mechanisms potentially explaining EC among which: a multi-action mechanism of HLA-B*57:01 involving MICA mutations and MICB differential expression overcoming the HIV-1 blockade of NK cell response, and overexpression of ZBTB12 with a possible anti-HIV-1 effect through HERV-K interference; a deleterious mutation in PPP1R18 favoring viral budding associated with rs1233396.ConclusionOur results show that MHC influence on EC likely extends beyond traditional HLA class I or class II allele associations, encompassing other MHC SNPs with various biological impacts. They point to the key role of NK cells in preventing HIV-1 infection. Our analysis shows that HLA-B*57:01 is indeed associated with a partially functional NK cell response which could also explain this marker’s involvement in other diseases such as psoriasis. More broadly, our findings suggest that within any HLA class I and II association in diseases, there may exist distinct causal SNPs within this crucial, gene-rich, and LD-rich MHC region.
GABAergic neurons from the ventral tegmental area represent and regulate force vectors
Authors: Jiang Qiaochu , Bakhurin Konstantin I. , Hughes Ryan N. , Lu Bryan , Ruan Shaolin , Yin Henry H. 
Published: December 2024

SummaryThe ventral tegmental area (VTA), a midbrain region associated with motivated behaviors, consists predominantly of dopaminergic (DA) neurons and GABAergic (GABA) neurons. Previous work has suggested that VTA GABA neurons provide a reward prediction, which is used in computing a reward prediction error. In this study, using in vivo electrophysiology and continuous quantification of force exertion in head-fixed mice, we discovered distinct populations of VTA GABA neurons that exhibited precise force tuning independently of learning, reward prediction, and outcome valence. Their activity usually preceded force exertion, and selective optogenetic manipulations of these neurons systematically modulated force exertion without influencing reward prediction. Together, these findings show that VTA GABA neurons continuously regulate force vectors during motivated behavior.
Chitin soil amendment triggers systemic plant disease resistance through enhanced pattern-triggered immunity
Authors: Makechemu Moffat , Goto Yukihisa , Zbinden Helen , Widrig Victoria , Keller Beat , Zipfel Cyril 
Published: December 2024

SummaryChitin triggers localised and systemic plant immune responses, making it a promising treatment for sustainable disease resistance. However, the precise molecular mechanisms underlying chitin-induced systemic effects in plants remain unknown. In this study, we investigated the effects of soil amendment with crab chitin flakes (hereafter chitin) on pattern-triggered immunity (PTI) and systemic disease resistance in various plant species. We found that soil amendment with chitin potentiates PTI and disease resistance against the bacterial pathogenPseudomonas syringaepv. tomato DC3000 in lettuce, tomato, and Arabidopsis as well as against the fungal pathogenBlumeria graminiscausing powdery mildew in wheat. Using micrografting in Arabidopsis, we demonstrated that this systemic effect is dependent on active chitin perception in the roots. We also showed that induced systemic resistance (ISR) and pattern-recognition receptors (PRRs)/co-receptors, but not systemic acquired resistance (SAR), are involved in the systemic effects triggered by chitin soil amendment. This systemic effect correlated with the transcriptional up-regulation of key PTI components in distal leaves upon chitin soil amendment. Notably, chitin-triggered systemic immunity was independent of microbes present in soil or chitin flakes. Together, these findings contribute to a better understanding of chitin-triggered systemic immunity, from active chitin perception in roots to the potentiation of PTI in the leaves, ultimately priming plants to mount enhanced defense responses against pathogen attacks. Our study provides valuable insights into the molecular mechanisms of chitin soil amendment and resulting induced immunity, and highlights its potential use for sustainable crop protection strategies.
Orchestration of SARS-CoV-2 Nsp4 and host-cell ESCRT proteins induces morphological changes of the endoplasmic reticulum
Authors: Kifer Allison , Pina Franciso , Codallos Nicholas , Herman Anita , Ziegler Lauren , Niwa Maho 
Published: December 2024

AbstractUpon entry into the host cell, the non-structural proteins 3, 4, and 6 (Nsp3, Nsp 4, and Nsp6) of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) facilitate the formation of double- membrane vesicles (DMVs) through extensive rearrangement of the host cell endoplasmic reticulum (ER) to replicate the viral genome and translate viral proteins. To dissect the functional roles of each Nsp and the molecular mechanisms underlying the ER changes, we exploited both yeastS. cerevisiaeand human cell experimental systems. Our results demonstrate that Nsp4 alone is sufficient to induce ER structural changes. Nsp4 expression led to robust activation of both the unfolded protein response (UPR) and the ER surveillance (ERSU) cell cycle checkpoint, resulting in cortical ER inheritance block and septin ring mislocalization. Interestingly, these ER morphological changes occurred independently of the canonical UPR and ERSU components but were mediated by the endosomal sorting complex for transport (ESCRT) proteins Vps4 and Vps24 in yeast. Similarly, ER structural changes occurred in human cells upon Nsp4 expression, providing a basis for a minimal experimental system for testing the involvement of human ESCRT proteins and ultimately advancing our understanding of DMV formation.
Unconventional structure and function of PHD domains from Additional Sex Combs-like proteins
Authors: Reddington CJ , Walsh AR , Göbl C , Mace PD 
Published: December 2024

AbstractThe Polycomb Repressive-Deubiquitinase (PR-DUB) complex removes ubiquitin from Lysine residue 119 on histone H2A (H2AK119Ub) in humans. The PR-DUB is composed of two central protein factors, the catalytic Breast Cancer type 1 susceptibility protein (BRCA1)-activating protein 1 (BAP1), and one of Additional Sex Combs-like 1–3 (ASXL1–3). A Plant Homeodomain (PHD) at the C-terminus of ASXL proteins is recurrently truncated in cancer, and was previously proposed to recognise epigenetic modifications on the N-terminal tail of histone H3. Here we demonstrate that the ASXL PHD domain lacks features required for histone tail recognition and is unable to bind histone H3 epigenetic marks. Modelling the structure of the ASXL PHD using AlphaFold3 suggests that the domain has an atypical fold and that the isolated ASXL PHD can chelate a single Zinc ionin vitro, compared to the two ions conventionally bound by PHD domains. Recently, the ASXL PHD was shown to bind an auxiliary set of PR-DUB interactors, named methyl CpG-binding domain proteins 5 (MBD5) and 6 (MBD6). We show that the ASXL PHD-MBD5 and -MBD6 complexes are stablein vitro,and surprisingly contain a composite Zinc-binding site at the interface between the two proteins. Overall, this data suggests an unconventional pairing of domains coordinate key functions of the PR-DUB — a non-canonical PHD domain from ASXL proteins obligately partners with MBD5 and 6, which were themselves misannotated because they cannot bind to methylated DNA.
Impact of Mass Distribution of Long-Lasting Insecticide Nets on Malaria Prevention in Lindi Region, Tanzania: A quasi experimental study
Authors: Mwanja Epafra Luka , Mwalyanzi Scola Anilozi , Khalfan Seif S. , Ambikile Ezekia Jasson , Mkama Mgole Eliud , Kisendi Dotto Daniel 
Published: December 2024

AbstractBackgroundMalaria is a major public health issue with high rates of morbidity and mortality in the United Republic of Tanzania. To ensure that all households remain protected, national malaria control programs and partners in 2022 implemented free mass distribution of long-lasting insecticides nets to population at risk and high prevalent regions with malaria including Lindi region. The present study aimed to assess the effectiveness of free long-lasting insecticide-treated nets in reducing malaria burden among the population.Methodswe conducted a quasi-experimental study from September 2021 to August 2022 and September 2022 to August 2023. The data were collected on District Health Information System version two in Lindi region and analysed with T-tests to compare the malaria positive rate before (September 2021 to August 2022) and after the distribution of long-lasting insecticides nets (September 2022 to August 2023). Malaria positive rate in the general population who attended outpatient department was reduced by 7.6% after distribution of long-lasting insecticides nets. A comparison of malaria cases recorded between September 2021 and August 2023 in the different area showed disparities. Before long lasting insecticides nets implementation, the malaria positive rate in all area combined was 20.6%. Whereas malaria positive rate in all area combined was 13% after implementation. The mean difference is 6.60, with a standard deviation of 2.47. The t-value is 6.55, with 5 degrees of freedom. The significance (2-tailed) value is <0.001, indicating a statistically significant difference between the malaria positive rate before and after long lasting insecticides nets implementation.Conclusionthe long-lasting insectides nets distribution campaign synergy with other preventive interventions has had a significant impact on reducing the malaria positive rate in the population.