bluuebunny/crossref_metadata_2025_split huggingface dataset:
Maternal genetic affinities of Koṅkaṇī population in the southwest coast of India
Authors: Sequeira Jaison Jeevan , Kumar Lomous , van Driem George , Thangaraj Kumarasamy , Mustak Mohammed S 
Published: September 2024

AbstractKoṅkaṇ region on the west coast of India is a hotspot of culture, folklore and ethnolinguistic diversity. The genetic landscape of this region remains understudied. The present study features Koṅkaṇī population residing along the Koṅkaṇ Malabar coast. We have sequenced complete mitogenomes of 85 and the hypervariable region of 210 Koṅkaṇī individuals to understand the maternal gene pool of this region. Comparative analysis of the over 5000 mitogenomes revealed that the Koṅkaṇī population clustered at a convergence point on the PCA plot, presumably due to a diverse maternal gene pool with both autochthonous and West Eurasian components. A distinct clustering pattern was observed within the subgroups of Sārasvata and non-Sārasvata Koṅkaṇī groups, indicating unique ancestral maternal lineages in them. This distinction is majorly due to the N macrohaplogroup lineages found in this population. We observe low haplotype and nucleotide diversity in Citrapur Sārasvata Brahmins (CSB), Rājāpur Sārasvata Brahmins (RSB), Khārvi and Kuḍubi compared to Gauḍa Sārasvata Brahmins (GSB) and Roman Catholics. The assimilation of both pre and post Last Glacial Maximum (LGM) haplogroups like M57, M36, M37, M3, M30, R8 and U2 in the Koṅkaṇī population suggests active movement and settlement along the Koṅkaṇ region on the west coast of India since the Late Pleistocene through the Holocene.
IGF2BP3 Promotes Autophagy-Mediated TNBC Metastasis via M6A-Dependent, Cap-Independent c-Met Translation
Authors: Wang Ziwen , Li Yihan , Cai Mengyuan , Zhang Xu , Xu Ruoxi , Yang Haiyan , Huang Yuzhou , Shi Liang , Wei Jifu , Ding Qiang 
Published: September 2024

AbstractTumor metastasis involves a series of complex processes and is a major challenge in clinical treatment. The cooperation of epigenetic modifications and metabolic adaptations endows tumor cells with dynamic adaptations for survival in variable environments, which is crucial for tumor metastasis and worth exploring in depth. In this study, we found IGF2BP3 could link epigenetic modification and metabolic adaptation in promoting autophagy-mediated triple-negative breast cancer (TNBC) metastasis. As a TNBC specifically high expressed N6-methyladenosine (m6A) binding protein, IGF2BP3 could bind to the m6A motif of c-Met mRNA, regulating autophagy-mediated epithelial-to-mesenchymal transition (EMT) progress by c-Met/PI3K/AKT/mTOR pathway. Moreover, through the recruitment of eIF4G2 as a collaborator, IGF2BP3 induced the changes in c-Met protein expression not by affecting mRNA stability, but by facilitating its mRNA translation initiation in an m6A-dependent and cap-independent manner. In conclusion, our study extended the role of IGF2BP3 in autophagy mediated TNBC metastasis, found IGF2BP3 could bind to the m6A motif on the 5′, 3′-UTR of c-Met mRNA to facilitate its translation in a cap-independent manner.
Characterization of motor function recovery using muscle synergies in stroke patients undergoing upper limb rehabilitation
Authors: Pregnolato Giorgia , Severini Giacomo , Maistrello Lorenza , Rimini Daniele , Lencioni Tiziana , Carpinella Ilaria , Ferrarin Maurizio , Jonsdottir Johanna , Cheung Vincent C. K. , Turolla Andrea 
Published: September 2024

AbstractIn stroke rehabilitation, muscle synergies have been investigated to provide information on the level of upper limb motor impairment, but not yet for explaining motor recovery after therapy. In this study, we analysed muscle synergies parameters extracted from 62 people with stroke who underwent a specific upper limb treatment (20 sessions, 1h/day, 5d/week, 4 weeks) consisting of virtual reality, robotic or conventional treatment. Overall, participants improved upper limb motor function (Fugl-Meyer Assessment Upper Extremity-FMA-UE: Δ= 7.14 ± 7.46, p< 0.001) but the number of muscle synergies of the impaired side (N-aff) did not change after treatment (N-aff: T0= 8.8 ± 1.5; T1=8.7 ± 1.4; p=0.374). Then, we stratified the sample into Responder (No.=34) and Non-Responder (No.=28) participants, based on the Minimal Clinical Important Difference value of FMA-UE (Δ >5 points). We investigated merging and fractionation indexes in both subgroups and only the Responder subgroup significantly decreased the percentage of merged muscle synergies (p=0.004). No significant changes in the fractionation index resulted in either subgroup.Finally, we identified vocabularies of affected upper limb motor synergies, before (No. 13 synergies) and after treatment (No. 14 synergies), and in unaffected upper limb (No. 16 synergies). We identified upper limb motor functions associated with each muscle synergy in each vocabulary based on the muscles represented in the muscle synergy. There were no differences in motor functions characterizing Responder patients. However, after therapy, both Responder and Non-Responder subgroups were characterized by the same distribution of motor functions across muscle synergies observed in the unaffected limb.Trial registrationThe trial is registered in ClinicalTrial.gov, identifier numberNCT03530358(https://clinicaltrials.gov/study/NCT03530358).Key messagesRehabilitation therapy for the upper limb induces reduction of muscle synergies merging in people with stroke expressing clinically important improvement of motor function. This muscular pattern is in accordance with motor control mechanisms underpinning functional recovery.Motor function of the affected upper limb at baseline did not characterize the muscular profile of patients responding to rehabilitation treatment (Responder).After therapy, all patients regardless the amount of motor function improvement (i.e., Responder, Non-Responder) express a muscular profile of the affected upper limb like the unaffected upper limb.
Examining Age-Dependent Patterns in Academic Bullying Behaviors
Authors: Moss Sherry E. , Mahmoudi Morteza 
Published: September 2024

AbstractAcademic bullying is a pervasive and longstanding issue that negatively affects all fields of science. While influential factors such as scientific discipline, sex, and ethnicity have been investigated, the impact of perpetrators’ age on the contextual behaviors of academic bullying has not been thoroughly studied. Our cross-sectional global survey of academic bullying, involving 2,390 participants, provides evidence that age significantly influences the contextual behaviors of academic bullying. Our results revealed that the youngest perpetrators (aged 25-35) exhibit significantly less abusive behavior compared to other age categories (36 and older). Additionally, the lowest percentage of abusive behavior was observed in the youngest group, while the highest was found in the older groups (aged 56-65). Our comprehensive analysis on the potential influence of the perpetrator’s academic position, ethnicity, or sex on their age group revealed no significant impact. These findings have strong implications for the development of more customized academic bullying training, policy development, and monitoring strategies, ultimately benefiting the scientific community at large in many aspects including evolution of science and improving the mental health of the academic workforce.
Precise interpretation and prioritization of sequence variants with Onkopus for supporting molecular tumor boards
Authors: Kurz Nadine S. , Kornrumpf Kevin , Tucholski Tim , Drofenik Klara , König Alexander , Beißbarth Tim , Dönitz Jürgen 
Published: September 2024

AbstractOne of the major challenges in precision medicine is the identification of pathogenic, actionable variants and the selection of personalized treatments. We present Onkopus, a variant interpretation framework, based on a modular architecture, for interpreting and prioritizing genetic alterations in cancer patients. We show that aggregation and harmonization of clinical databases, coupled with querying of these databases to varying associated biomarkers, can increase the number of identified therapeutic options. We present a protein analysis of mutated sites and show that protein characteristics can provide potential indicators for the functional impairment of variants of unknown significance. Variant interpretation systems like Onkopus have the potential to significantly enhance the performance of personalized treatments, as they reduce the time required for variant interpretation and manual evaluation of personalized treatments, while maintaining reproducibility and traceability. We provide a free public instance of Onkopus athttps://mtb.bioinf.med.uni-goettingen.de/onkopus.
High-throughput bacterial aggregation analysis in droplets
Authors: Saar-Abroi Merili , Lindpere Karoliine , Olman Triini , Sulp Fenella Lucia , Kiir Katri , Sanka Immanuel , Bartkova Simona , Scheler Ott 
Published: September 2024

ABSTRACTThe communal lifestyle of bacteria manifested as bacterial aggregation and potential biofilm formation is posing as a significant contributor to antimicrobial resistance. A key approach to adress the emerging pandemic is to implement novel techniques that enhance the precision and speed of analysis in various microbiological experiments.Droplet-based platforms coupled with image analysis techniques exhibit great potential in advancing the precision of investigating bacterial behaviour and increasing the speed of microbiological experiments. As most of the image analysis techniques require advanced programming skills or implement high-priced fees, open-source software interweaving user-friendly interface is in great demand.In this paper, we introduce two image analysis pipelines constructed in CellProfiler™ to quantify bacterial aggregation responding to a presence of microplastics as well as suboptimal concentrations of antibiotics in droplets.
Respiratory shedding of infectious SARS-CoV-2 Omicron XBB.1.41.1 lineage with increased evolutionary rate among captive white-tailed deer
Authors: Ferreira Francisco C. , Pervin Tahmina , Tang Wendy , Hediger Joseph , Thomas Logan , Cook Walter , Cherry Michael , Neuman Benjamin W. , Hamer Gabriel L. , Hamer Sarah A. 
Published: September 2024

AbstractWhite-tailed deer (Odocoileus virginianus) have high value for research, conservation, agriculture and recreation, and may be important SARS-CoV-2 reservoirs with unknown human health implications. In November 2023, we sampled 15 female deer in a captive facility in central Texas, USA. All individuals had neutralizing antibodies against SARS-CoV-2 and 11 had RT-qPCR-positive respiratory swabs; one also had a positive rectal swab. Six of 11 respiratory swabs yielded infectious virus with replication kinetics of most samples displaying lower growth 24-48 h post infectionin vitrowhen compared to Omicron lineages isolated from humans in Texas in the same period. However, virus growth was similar between groups by 72 h, suggesting no strong attenuation of deer-derived virus. All deer viruses clustered in XBB Omicron clade, with more mutations than expected compared to contemporaneous viruses in humans, suggesting that crossing the species barrier to deer was accompanied by a high substitution rate.
Sedentary life accelerates epigenetic ageing in King penguins
Authors: Cristofari Robin , Davis Leyla , Bardon Gaël , Nitta Fernandes Flávia A. , Figueroa Maria Elena , Franzenburg Sören , Gauthier-Clerc Michel , Grande Francesco , Heidrich Richard , Hukkanen Mikaela , Le Maho Yvon , Ollikainen Miina , Paciello Elodie , Rampal Patrick , Stenseth Nils C , Trucchi Emiliano , Zahn Sandrine , Le Bohec Céline , Meyer Britta S. 
Published: September 2024

Introductory paragraphAdvances in medicine and food security have contributed to an increase in human lifespan1. Yet, the associated rise in sedentary behaviour and in obesity2,3already threatens these gains4. Indeed, a growing body of evidence supports the central role of nutrient sensing and energy management pathways in regulating ageing rate and healthspan5,6, but the diversity of human lifestyles challenges our ability to identify the genetic and epigenetic drivers of this age acceleration. Here, we examine how the transition of wild King penguins to zoo husbandry can closely mimic the shift to a Western lifestyle in humans, and shed light on evolutionarily conserved epigenetic changes in responses to sedentary conditions. We show that, just like modern humans, zoo-housed King penguins experience an extended lifespan, but this comes at the cost of accelerated epigenetic ageing throughout life. This accelerated ageing is associated with differential methylation in key growth and maintenance pathways including the mTOR and PI3K/Akt networks, as well as in specific pathways of lipid-rich diet adaptation and heart-function. Our results demonstrate the deeply conserved link between sedentary behaviour and food availability on the one hand, and age acceleration on the other. Such evolutionary evidence may in turn help us to improve risk detection and, ultimately, therapeutics for lifestyle-induced age acceleration in humans7.
Exploring the Biological Mechanisms of Severe COVID-19 in the Elderly: Insights from an Aged Mouse Model
Authors: Ma Li , Lin Xian , Xu Meng , Ke Xianliang , Liu Di , Chen Quanjiao 
Published: September 2024

AbstractCoronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has resulted in a global health crisis, particularly affecting the elderly, who are more susceptible to severe outcomes. However, definitive parameters or mechanisms underlying the severity of COVID-19 in elderly people remain confused. Thus, this study seeks to elucidate the mechanism behind the increased vulnerability of elderly individuals to severe COVID-19. We employed an aged mouse model with a mouse-adapted SARS-CoV-2 strain to mimic the severe symptoms observed in elderly patients with COVID-19. Comprehensive analyses of the whole lung were performed using transcriptome and proteome sequencing, comparing data from aged and young mice. For transcriptome analysis, bulk RNA sequencing was conducted using an Illumina sequencing platform. Proteomic analysis was performed using mass spectrometry following protein extraction, digestion, and peptide labeling. We analyzed the transcriptome and proteome profiles of young and aged mice and discovered that aged mice exhibited elevated baseline levels of inflammation and tissue damage repair. After SARS-CoV-2 infection, aged mice showed increased antiviral and inflammatory responses; however, these responses were weaker than those in young mice, with significant complement and coagulation cascade responses. In summary, our study demonstrates that the increased vulnerability of the elderly to severe COVID-19 can be attributed to an attenuated antiviral response and the overactivation of complement and coagulation cascades.
Transcriptomic and histological characterization of telocytes in the human dorsal root ganglion
Authors: Haberberger Rainer V , Matusica Dusan , Shiers Stephanie , Sankaranarayanan Ishwarya , Price Theodore J 
Published: September 2024

AbstractTelocytes are interstitial cells with long processes that cover distances in tissues and likely coordinate interacts with other cell types. Though present in central and peripheral neuronal tissues, their role remains unclear. Dorsal root ganglia (DRG) house pseudounipolar afferent neurons responsible for signals such as temperature, proprioception and nociception. This study aimed to investigate the presence and function of telocytes in human DRG by investigating their transcriptional profile, location and ultrastructure.Sequencing data revealed CD34 and PDGFRA expressing cells comprise roughly 1.5-3% of DRG cells. Combined expression ofCD34andPDGFRAis a putative marker gene set for telocytes. Further analysis identified nine subclusters with enriched cluster-specific genes. KEGG and GO pathway analysis suggested vascular, immune and connective tissue associated putative telocyte subtypes. Over 3000 potential receptor-ligand interactions between sensory neurons and theseCD34andPDGFRAexpressing putative telocytes were identified using a ligand-receptors interactome platform. Immunohisto-chemistry showed CD34+ telocytes in the endoneural space of DRGs, next to neuron-satellite complexes, in perivascular spaces and in the endoneural space between nerve fibre bundles, consistent with pathway analysis. Transmission electron microscopy (TEM) confirmed their location identifying characteristic elongated nucleus, long and thin telopods containing vesicles, surrounded by a basal lamina. This is the first study that provides gene expression analysis of telocytes in complex human tissue such as the DRG, highlighting functional differences based on tissue location with no significant ultrastructural variation.Key pointsuman DRGs containCD34/PDGFRA+ putative telocytes that can be subgrouped in nine clusters based on gene expressionThe DRGs contain CD34+ telocytes in close proximity to neuron-satellite complexes, blood vessels and nerve fibre bundles.The basic features of telocytes with elongated nuclei and thin telopods do not differ between locations.
Tumor microenvironment distinctions between esophageal cancer subtypes explain varied immunotherapy responses
Authors: Baek Seungbyn , Cha Junha , Hong Min-Hee , Kim Gamin , Koh Yoon Woo , Kim Dahee , Hemberg Martin , Park Seong Yong , Kim Hye Ryun , Lee Insuk 
Published: September 2024

AbstractEsophageal cancer comprises two main subtypes: esophageal squamous cell carcinoma (ESCC) and esophageal adenocarcinoma (EAC). Previous studies have revealed distinct genomic characteristics between these subtypes, with ESCC sharing similarities with head and neck squamous cell carcinoma (HNSCC), and EAC aligning with gastric adenocarcinoma (GAC). Additionally, recent immunotherapy clinical trials have shown a higher response rate in ESCC and HNSCC compared to EAC and GAC. However, how the tumor microenvironment contributes to these varied immunotherapy responses remains unclear. In this study, through a comparative analysis of single-cell tumor transcriptomes from 35 patients with ESCC, EAC, HNSCC, or GAC, we identified two groups with tumor microenvironment distinctions: ESCC and HNSCC versus EAC and GAC, consistent with their genomic classifications. Malignant epithelial cells displayed distinct separations based on histological origin. In the tumor immune microenvironment, we observed an enrichment of CXCL13+CD8+T cells and CXCL9+CXCL10+tumor-associated macrophages (TAMs) in ESCC and HNSCC, which activate cellular immunity through interferon-γ. In contrast, EAC and GAC exhibited a high presence of heat-shock protein-expressing CD8+T cells and MARCO+TAMs. These immune signatures help explain the varied immunotherapy responses among these cancer subtypes and successfully predict immunotherapy outcomes across diverse cancer types, underscoring their clinical significance.
ADrosophilaholidic diet optimised for growth and development
Authors: Sorge Sebastian , Girard Victor , Lampe Lena , Tixier Vanessa , Weaver Alexandra , Higgins Theresa , Gould Alex P. 
Published: September 2024

SummaryDiets composed of chemically pure components (holidic diets) are useful for determining the metabolic roles of individual nutrients. For the model organismDrosophila melanogaster,existing holidic diets are unable to support rapid growth characteristic of the larval stage. Here, we use a nutrient co-optimisation strategy across more than 50 diet variants to design HoldFast, a holidic medium tailored to fast larval growth and development. We identify dietary amino acid ratios optimal for developmental speed but show that they compromise survival unless vitamins and sterols are co-optimised. Rapid development on HoldFast is not improved by adding fatty acids but it is dependent upon theirde novosynthesis in the fat body viafatty acid synthase(FASN). HoldFast outperforms other holidic diets, supporting rates of growth and development close to those of yeast-based diets and, under germ-free conditions, identical. HoldFast provides new opportunities for studying growth and metabolism duringDrosophiladevelopment.
Structural and Functional Glycosylation of the Abdala COVID-19 Vaccine
Authors: Burnap Sean A. , Calvaresi Valeria , Cabrera Gleysin , Pousa Satomy , Limonta Miladys , Ramos Yassel , González Luis Javier , Harvey David J. , Struwe Weston B. 
Published: September 2024

ABSTRACTAbdala is a COVID-19 vaccine produced inPichia pastorisand is based on the receptor-binding domain (RBD) of the SARS-CoV-2 spike. Abdala is currently approved for use in multiple countries with clinical trials confirming its safety and efficacy in preventing severe illness and death. AlthoughP. pastorisis used as an expression system for protein-based vaccines, yeast glycosylation remains largely uncharacterised across immunogens. Here, we characterise N-glycan structures and their site of attachment on Abdala and show how yeast-specific glycosylation decreases binding to the ACE2 receptor and a receptor-binding motif (RBM) targeting antibody compared to the equivalent mammalian-derived RBD. Reduced receptor and antibody binding is attributed to changes in conformational dynamics resulting from N-glycosylation. These data highlight the critical importance of glycosylation in vaccine design and demonstrate how individual glycans can influence host interactions and immune recognition via protein structural dynamics.
Phonological decoding ability is associated with fiber density of the left arcuate fasciculus longitudinally across reading development
Authors: Perdue Meaghan V. , Geeraert Bryce L. , Manning Kathryn Y. , Dewey Deborah , Lebel Catherine 
Published: September 2024

AbstractNumerous studies have linked reading ability to white matter microstructure using diffusion tensor imaging, but recent large studies have failed to show consistency. Fiber-specific diffusion-weighted magnetic resonance imaging (dMRI) models offer enhanced precision to measure specific features of white matter structure and may be more sensitive to individual differences in reading skills. However, fiber-specific models have not yet been applied to examine associations between reading ability and white matter microstructure over the course of reading acquisition. In this accelerated longitudinal study, we applied constrained spherical deconvolution (CSD) and fiber-specific modelling to characterize developmental changes in fiber density of key white matter tracts of the reading network bilaterally, and investigated associations between tract-wise fiber density and children’s phonological decoding abilities. Fiber density was measured from ages 2-13 years, and decoding ability (pseudoword reading) was assessed at ages 6 years and older. Higher decoding ability was associated with greater fiber density in the left arcuate fasciculus, and effects remained consistent over time. Follow-up analysis revealed that asymmetry changes in the arcuate fasciculus were moderated by decoding ability: good decoders showed leftward asymmetry from early childhood onward, while poorer decoders shifted toward leftward asymmetry over time. These results suggest that densely organized fibers in the left arcuate fasciculus serve as a foundation for the development of reading skills from the pre-reading stage through fluent reading. Ongoing developmental changes in fiber density and microstructural asymmetry throughout childhood may reflect a reciprocal relationship in which reading experience continues to refine and strengthen these pathways.