bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cenozoic evolutionary history obscures the Mesozoic origins of acanthopterygian fishes
Authors: Brownstein Chase D. , Dornburg Alex , Near Thomas J. 
Published: October 2024

AbstractSister lineage comparisons provide a valuable tool for understanding evolutionary origins of species-rich clades.Percomorpha, comprising over 18,900 species, represents one of the most species-rich vertebrate clades. However, the phylogenetic resolution of its sister lineage remains unclear, obscuring whether contrasts in histories of diversification provide insights into the factors that gave rise to this clade’s diversity. Using 887 ultraconserved element loci and Sanger-sequenced nuclear genes, we resolve the phylogenetic relationships of the three closest relatives ofPercomorpha-the roughies, flashlightfishes, porcupinefishes and fangtooths (Trachichthyiformes), the squirrelfishes and soldierfishes (Holocentridae), and the whalefishes, bigscales, and alfonsinos (Berycoidei)-and the placement of percomorphs among them. Contrary to expectations from the fossil record, we demonstrate that living lineages ofBerycoidei,Holocentridae, andTrachichthyiformesall diversified after the Cretaceous-Paleogene mass extinction. Our findings show that multiple clades inTrachichthyiformesandBerycoideiindependently colonized deep ocean habitats during the climatically unstable Eocene and Oligocene and shallow-water reefs during the extensive hotspot migration and faunal turnover of the Early Miocene. Due to their complex evolutionary history, the closest relatives ofPercomorphaare not ideal for understanding the origins of this exceptionally species-rich clade.
Genetic Association of Glutathione S-Transferase Omega 2(GSTO2)Gene Variant (rs156697) with Chronic Kidney Disease Patients of Pakistani Origin
Authors: Afzal Abeer , Saif Rashid , Atta Asia , Jafri Saghir Ahmad , Naqvi Syeda Komal Abbas 
Published: October 2024

AbstractChronic Kidney Disease (CKD) poses a significant global health challenge. The kidneys can be compromised by internal diseases, environmental influences and various genetic factors. Among the genetic factors, particularly,GSTO2gene plays a crucial role in cellular processes and enzyme performance, which can lead to interstitial kidney damage and contribute to CKD. The current study investigates the genetic association between theGSTO2gene variation (rs156697) and CKD in the Punjabi community. This study examined the association between theGSTO2gene locus (c.424A>T) and CKD in a Punjabi population using ARMS-PCR genotyping. A total of 50 samples were analyzed, revealing 19 homozygous wild-type, 25 heterozygous and 6 homozygous mutants. PLINK data analysis toolset indicated an insignificant genotypic association with CKD phenotype with observedp-valueof 0.7177 and an odds ratio of 0.85. Similarly, the alternative allele frequency of 0.34 and 0.375 was also observed in CKD and normal controls respectively. In the future, further studies with more genetic markers along with functional studies with large sample data may be performed for robust statistical evidence of the association of subject gene with CKD patients in Pakistan.
Prevalence of dementia risk factors in a memory clinic setting: The Oxford Brain Health Clinic
Authors: Blane J. , Gillis G. , Griffanti L. , Mitchell R. , Pretorius P.M. , Forster S. , Shabir S. , Maffei L. , O’Donoghue M.C. , Fossey J. , Raymont V. , Martos L. , Mackay C.E . 
Published: October 2024

AbstractWith promising disease-modifying therapies (DMTs) emerging and good evidence to support risk reduction in the delay of dementia onset and progression, it is important to understand the profile of patients attending memory assessment services to estimate what proportion of patients might benefit from different types of interventions. The Oxford Brain Health Clinic (OBHC) is a psychiatry-led, clinical-research service that offers memory clinic patients detailed clinical assessments and equal access to research opportunities as part of their secondary care pathway. In this work, we describe the characteristics of OBHC patients in terms of demographics, diagnoses and prevalence of potentially modifiable risk factors compared with a cohort of healthy volunteers and the average memory clinic population. Our results suggest that high research consent rates (91.5%) in the OBHC resulted in a highly representative cohort of the clinical population. Based on Lecanemab trial inclusion criteria, 24.6% of the OBHC population may be suitable for further investigation into DMTs. Furthermore, 67.4% of OBHC patients have at least one potentially modifiable risk factor that may benefit from lifestyle interventions, particularly those focused on depression, sleep and physical activity.
Quantifying the Trainability of Peripheral Nerve Function in Young and Older Adults
Authors: Shields JoCarol E. , Smith Claire M. , Reese Shawn M. , Santos Marcel L. Dos , Parodi Maria , DeFreitas Jason M. 
Published: October 2024

AbstractIt is well known that the natural progression of age can result in motor neuron degeneration. Consequently, this leads to slowing of nerve conduction, denervation, and reduced motor function. Slower neural conduction can negatively alter an individual’s response time, which could increase the risk of falls. Further investigation is needed to determine the potential role exercise interventions may afford in mitigating age-related nerve deterioration. The purpose was two-fold: first, to determine the effects of resistance training on nerve conduction velocity (NCV), and second, to determine if changes in NCV are dependent on age. We hypothesized that training would result in faster nerves in both young and older adults, albeit to a lesser extent in older adults. Forty-eight subjects (18-84 yrs) completed this study (n = 26 younger, 22 older). Motor NCV and maximal strength were recorded before and after 4-weeks of handgrip training in both limbs. Training was conducted 3×/week with the use of a grip training kit. Mixed-factorial ANOVAs revealed significant increases in NCV for both the young (p< 0.001) and older training groups (p< 0.001), but neither control groups (p > 0.05). The young training group showed increased handgrip strength after four weeks (p= 0.004), while the other groups did not. The results of this study suggest that resistance training may be a viable method to counteract age-related nerve deterioration. These outcomes have the potential to improve quality of life and generate greater independence for our older populations.NEW & NOTEWORTHYAging is characterized by a slowing in nerve conduction speed, which could potentially affect how quickly an individual responds to unexpected incidents. Consequently, this slowing could increase the risk of falls and injuries. This study utilized resistance training as an intervention to mitigate age-related nerve deterioration. We show that motor nerve conduction velocity significantly increases in both young and older adults after 4-weeks of training.
A novel modelling framework to simulate the effects of HIV stigma on HIV transmission dynamics
Authors: Bisanzio Donal , Roberts Sarah T. , Stelmach Rachel D. , McClellan Kendall N. , Bobashev Georgiy , Adams Joella , Karriker-Jaffe Katherine , Endres-Dighe Stacy M. , Saalim Khalida , Blackburn Natalie , Nyblade Laura 
Published: October 2024

ABSTRACTIntroductionHIV remains a global public health challenge, with social determinants such as stigma influencing transmission dynamics, access to testing, and treatment. HIV stigma shapes both individual behaviour and community responses to HIV. However, modelling approaches have rarely represented the complex role of stigma in HIV epidemics. Our study introduces an innovative modelling framework designed to capture the interplay between stigma and HIV transmission dynamics.MethodsWe modelled effects of anticipated, internalised, and experienced HIV stigma on HIV testing, antiretroviral treatment initiation, and treatment adherence. We built an individual-based model representing the HIV epidemic (HIV-IBM) in a USA-like population of 3 million individuals that accounts for community demography, behaviour, and healthcare access. Stigma parameters were based on a scoping review focused on the prevalence and effects of stigma in people living with and without HIV. HIV-IBM was used to assess effects of interventions targeting different types of stigma. We tested reductions of stigma by 50% and 100% across the simulated population and performed a sensitivity analysis to identify effects of each type of stigma on the simulated HIV epidemic.ResultsWithout reduced stigma, the HIV-IBM had an annual incidence rate of 12.6 (95% credible interval [CI]: 11.4-13.5) new cases per 100,000 people. Reducing the overall level of stigma in the population by 50% resulted in an annual incidence rate of 9.6 (95% CI: 8.6-10.3) per 100,000, and a 100% reduction in stigma resulted in an annual incidence rate of just 6.8 (95% CI: 6.1-7.3) per 100,000. In addition to reducing HIV incidence, reducing stigma resulted in a substantial increase of viral suppression among people living with HIV (50% stigma reduction: +10.5%; 100% stigma reduction: +16.4%). Sensitivity analysis showed that outcomes resulting from interventions targeting each type of stigma were highly heterogeneous.ConclusionSimulation results suggest that reducing HIV stigma could have a large effect on HIV incidence and viral suppression. Our model framework provides a dynamic approach to understanding the role of stigma in HIV outcomes that facilitates exploration of stigma reduction strategies and offers insights to inform evidence-based policies and interventions for reducing stigma and curtailing HIV.
Identification of novel associations of candidate loci with Alzheimer’s disease by leveraging the shared genetic basis with hippocampal volume
Authors: Jiang Chenyang , van der Lee Sven J. , Tesi Niccolo , van der Flier Wiesje M. , Tijms Betty M. , Reus Lianne M. 
Published: October 2024

AbstractObjectiveAlzheimer’s disease (AD) is a complex neurodegenerative disorder with a considerable genetic contribution that remains not fully understood. The hippocampus plays a critical role in learning and memory, with its volume loss being a core hallmark of AD. Hippocampal volume also has a strong heritable component and its genetic underpinnings may help us to understand the complex biological mechanism underlying AD.MethodsWe performed cross-trait analysis of exisiting GWAS data on late-onset AD and Hippocampal volumes using the conjunctional false discovery rate (conjFDR) framework to identify the specific shared genetic basis.For identified SNPs, we performed functional annotation and phenome-wide association studies (PheWAS).ResultsOur cross-trait analyses identified 11 non-APOE lead genetic loci, of which 7 loci showed discordant directional effects (loci associated with decreased risk for AD and smaller hippocampal volumes, and vice versa). We found thatSHARPINandTNIP1genes play a role in AD by affecting the hippocampal volumes. In addition, we observed 9 novel AD-hippocampus loci in genes previously implicated in AD (IGIPandACE) and novel AD-genes (KCTD13, HINT1, SH3TC2, FAM53B, TPM1, IL34andSSH2). Phenome-wide association study highlighted varying degrees of pleiotropy, including brain imaging measurements, white blood cell markers, red blood cell markers, and lipids in multiple shared loci.ConclusionsOur integrating GWAS study reveals a shared genetic basis between AD and hippocampal volumes. By integrating GWAS summary statistics for these two traits, we identified both novel and previously reported AD-hippocampus loci. Functional analysis highlights the roles of immune cells and lipid markers in the shared loci and traits, suggesting a shared neurobiological basis for both traits.
PHLOWER - Single cell trajectory analysis using Decomposition of the Hodge Laplacian
Authors: Cheng Mingbo , Jansen Jitske , Reimer Katharina , Nagai James Shiniti , Li Zhijian , Kießling Paul , Grasshoff Martin , Kuppe Christoph , Schaub Michael T. , Kramann Rafael , Costa Ivan G. 
Published: October 2024

ABSTRACTMulti-modal single-cell sequencing, which captures changes in chromatin and gene expression in the same cells, is a game changer in the study of gene regulation in cellular differentiation processes. Computational trajectory analysis is a key computational task for inferring differentiation trees from this single-cell data, though current methods struggle with complex, multi-branching trees and multi-modal data. To address this, PHLOWER leverages simplicial complexes and Hodge Laplacian decomposition to infer trajectory embeddings. These natural representations of cell differentiation facilitate the estimation of their underlying differentiation trees. We evaluate PHLOWER through benchmarking with multi-branching differentiation trees and using novel kidney organoid multi-modal and spatial single-cell data. These demonstrate the power of PHLOWER in both the inference of complex trees and the identification of transcription factors regulating off-target cells in kidney organoids.
Controllability and cause in human collaboration
Authors: Spiering Lisa , Trier Hailey A , O’Reilly Jill , Kolling Nils , Wittmann Marco K , Rushworth Matthew F S , Scholl Jacqueline 
Published: October 2024

AbstractThere has been considerable interest in how we ascertain whether an environment is controllable and the neural mechanisms mediating this process. An especially acute version of this problem occurs when multiple people collaborate towards a joint outcome. Here we demonstrate that in such ambiguous social contexts, people engage in specific patterns of behaviour that we refer to as active disambiguation. This process helps individuals establish what they themselves, as opposed to others, control and what consequence they themselves cause or that another person causes. People identify when active disambiguation is needed and engage in it at that time. A pattern of activity in the supramarginal gyrus that emerges during and after active disambiguation is linked to establishing controllability and tracking the outcomes from which control is inferred. Activity in this brain region also signals a second learning mechanism, by which individuals attribute outcomes to themselves versus others, in proportion to their perceived control.
A previously reported bottleneck in human ancestry 900 kya is likely a statistical artifact
Authors: Deng Yun , Nielsen Rasmus , Song Yun S. 
Published: October 2024

AbstractIt was recently reported that a severe ancient bottleneck occurred around 900 thousand years ago in the ancestry of African populations, while this signal is absent in non-African populations. Here, we present evidence to show that this finding is likely a statistical artifact.
Mitigation of Reproductive Function in Sodium Fluoride-administered Wistar Rats byTamarindus indicaFruit Pulp Ethanol Extract
Authors: Usman Lutfat A. , Ajani Emmanuel O. , Ishiaku Muhammed A. , Bankole Taofeeq A. , Ibrahim Rasheed B. , Saka Dauda K. 
Published: October 2024

ABSTRACTInfertility is a stigmatized and emotionally challenging issue for affected individuals, often compounded by the high costs of conventional fertility treatments. This study investigated the prophylactic and therapeutic effects of an ethanolic extract of Tamarindus indica fruit pulp on sodium fluoride-induced sexual and reproductive dysfunction in Wistar rats. The extract was prepared via ethanol maceration, followed by filtration and drying. Seventy Wistar rats were used, with an initial acute toxicity study indicating no adverse effects at 5000 mg/kg of the extract.Following toxicity assessment, rats were divided into seven groups, with varying treatments involving Tamarindus indica extract, sodium fluoride, and clomid. After the treatment period, biochemical analyses revealed that rats treated with 400 mg/kg of Tamarindus indica extract showed significant improvements (p < 0.05) in sperm count, luteinizing hormone (in males), testosterone, estrogen, along with reduced levels of follicle-stimulating hormone (in males), and luteinizing hormone (in females). Histopathological examination revealed normal histomorphology in certain groups treated with the extract. Phytochemical analysis identified the presence of tannins and steroids in the extract.The study concluded that Tamarindus indica fruit pulp extract exhibits both prophylactic and therapeutic effects on sodium fluoride-induced sexual and reproductive dysfunction in rats, with the most significant effects observed at a 400 mg/kg dosage. These findings suggest that Tamarindus indica extract could serve as an alternative to conventional treatments for infertility.
Exploring the effect of Hydrocarbon Cross-linkers on the Structure and Binding of Stapled p53 Peptides
Authors: Choudhury Asha Rani , Gaikwad Vikram , Maity Atanu , Chakrabarti Rajarshi 
Published: October 2024

AbstractShort-length peptides are used as therapeutics due to their high target specificity and low toxicity, for example, peptides designed for targeting the interaction between oncogenic protein p53 and E3 ubiquitin ligase MDM2. These peptide therapeutics form a class of successful inhibitors. To design such peptide-based inhibitors, stapling is one of the methods in which amino acid side chains are stitched together to get conformationally rigid peptides, ensuring effective binding to their partners. In the current work, we use computer simulations to investigate p53 peptides stapled with hydrocarbon chains of different lengths and positions of attachment to the peptide. We subsequently analyze their binding efficiency with MDM2. The introduction of stapling agents restricts the conformational dynamics of peptides, resulting in higher persistence of helicity. The efficiency of the stapling agents has also been verified imposing these stapled peptides to adverse conditions viz. thermal and chemical denaturation. In addition, the conformational exploration of peptides has been investigated using Temperature replica exchange molecular dynamics (T-REMD) simulations. From both the unbiased and T-REMD simulations, p53 with a long hydrocarbon cross-linker shows a more conformationally rigid structure having high helicity compared to other stapled peptides. The rigidity gained due to cross-linking reduces the entropy of the peptide in the free state and thereby facilitates the complexation process. From the binding studies, we have shown that the peptide having multiple short staples has shown a larger enthalpy change during binding free energy, resulting from its orientation and interactions of residues in the binding interface. On the other hand, a peptide with a single long stapling agent shows less entropic penalty than other systems. Our studies suggest a plausible rationale for the relation between the length and the position of attachment of cross-linkers to peptides and the binding free energies between the peptides and their target partners.
Rho-dependent termination and RNase E-mediated cleavage: Dual pathways for RNA 3’ end processing in polycistronic mRNA
Authors: Jeon Heung Jin , N Monford Paul Abishek , Wang Xun , Lim Heon M. 
Published: October 2024

Abstract“Pre-full-length” transcripts are produced at the end of the polycistronic galactose (gal)operon, 5’galE-galT-galK-galM3’, via Rho-dependent (RDT) and -independent transcription termination (RIT). The full-lengthgalETKMmRNA’s 3’ end is acquired by exo-nucleolytic processing of the 3’-OH ends of the pre-full-length transcripts. However, thegaloperon produces an mRNA namedgalEwhose 3’ end forms at ∼120 nucleotides from thegalEstop codon, thus in the following gene,galT, establishing polarity in gene expression. In this study, we investigated the molecular processes that generate the 3’ end ofgalEmRNA. We discovered that the 3’ ends of pre-galE mRNA are produced in the middle of thegalTgene as a result of the combination of two separate molecular processes - one previously reported as RDT and the other as unreported RNase E-mediated transcript cleavage. The 3’ ends of the pre-galEmRNA are exo-nucleolytically processed to the current 3’ end of thegalEmRNA. A hairpin structure of 8 base-pair stems and 4 nucleotide-loop formed 5-10 nucleotides upstream of the 3’ ends of thegalEmRNA blocks the exoribonuclease digestion and renders stability. These findings showed that RNase E produces RNA 3’end establishing polarity in gene expression, in contrast to the general role of mRNA degradation.Significance statementHere, we show the findings of two molecular mechanisms that generate the pre-galEmRNA 3’ends in thegaloperon: Rho-dependent termination (RDT) and RNase E-mediated cleavage. These 3’ ends are subsequently processed to produce stablegalEmRNA with a hairpin structure that prevents exoribonuclease degradation. This mechanism establishes gene expression polarity by generating the 3’ end ofgalEmRNA within thegalTgene, contrasting with the usual mRNA degradation role of RNase E. The study reveals a unique role of RNase E in mRNA processing and stability.
FB5P-seq-mAbs: monoclonal antibody production from FB5P-seq libraries for integrative single-cell analysis of B cells
Authors: Ado Sakina , Dong Chuang , Attaf Noudjoud , Moussa Myriam , Carrier Agathe , Milpied Pierre , Navarro Jean-Marc 
Published: October 2024

ABSTRACTParallel analysis of phenotype, transcriptome and antigen receptor sequence in single B cells is a useful method for tracking B cell activation and maturation during immune responses. However, in most cases, the specificity and affinity of the B cell antigen receptor cannot be inferred from its sequence. Antibody cloning and expression from single B cells is then required for functional assays. Here we propose a method that integrates FACS-based 5’-end single-cell RNA sequencing (FB5P-seq) and monoclonal antibody cloning for integrative analysis of single B cells. Starting from a cell suspension, single B cells are FACS-sorted into 96-well plates for reverse transcription, cDNA barcoding and amplification. A fraction of the single-cell cDNA is used for preparing 5’-end RNA-seq libraries that are sequenced for retrieving transcriptome-wide gene expression and paired BCR sequences. The archived cDNA of selected cells of interest is used as input for cloning heavy and light chain variable regions into antibody expression plasmid vectors. The corresponding monoclonal antibodies are produced by transient transfection of a eukaryotic producing cell line and purified for functional assays. We provide detailed step-by-step instructions and describe results obtained on ovalbumin-specific murine germinal center B cells after immunization. Our method is robust, flexible, cost-effective, and applicable to different B cell types and species. We anticipate it will be useful for mapping antigen specificity and affinity of rare B cell subsets characterized by defined gene expression and/or antigen receptor sequence.