bluuebunny/crossref_metadata_2025_split huggingface dataset:
The European Neolithic Expansion: A Model Revealing Intense Assortative Mating and Restricted Cultural Transmission
Authors: LaPolice Troy M. , Williams Matthew P. , Huber Christian D. 
Published: May 2024

AbstractThe Neolithic revolution initiated a pivotal change in human society, marking the shift from foraging to farming. The underlying mechanisms of agricultural expansion are debated, primarily between cultural diffusion (knowledge and practices transfer) and demic diffusion, or people migration and replacement. Ancient DNA analyses reveal significant ancestry changes during Europe’s Neolithic transition, suggesting primarily demic expansion. However, the presence of 10-15% hunter-gatherer ancestry in modern Europeans indicates cultural transmission and non-assortative mating were additional contributing factors. We integrate mathematical models, agent-based simulations, and ancient DNA analysis to dissect and quantify the roles of cultural diffusion and assortative mating in farming’s expansion. Our findings indicate limited cultural transmission and predominantly within-group mating. Additionally, we challenge the assumption that demic spread always leads to ancestry turnover. This underscores the need to reassess prehistoric cultural expansions and offers new insights into early agricultural society through the integration of ancient DNA with archaeological models.
Human CD29+/CD56+ myogenic progenitors display tenogenic differentiation potential and facilitate tendon regeneration
Authors: Shao Xiexiang , Lin Xingzuan , Zhou Hao , Wang Minhui , Han Lili , Fu Xin , Li Sheng , Zhu Siyuan , Zhou Shenao , Yang Wenjun , Wang Jianhua , Hu Ping 
Published: May 2024

AbstractTendon injury occurs at high frequency and is difficult to repair. Identification of human stem cells being able to regenerate tendon will greatly facilitate the development of regenerative medicine for tendon injury. We identified human CD29+/CD56+ myogenic progenitors having tendon differentiation potential both in vitro and in vivo. Transplantation of human CD29+/CD56+ myogenic progenitors contributes to injured tendon repair and thus improves locomotor function. Interestingly, the tendon differentiation potential in mouse muscle stem cells is minimal and the higher TGFβ signaling level may be the key for the distinct feature of human CD29+/CD56+ myogenic progenitors. These findings reveal that human CD29+/CD56+ myogenic progenitors are bi-potential adult stem cells and can serve as a new source for tendon regeneration.
Distinct anatomical and functional corticospinal inputs innervate different spinal neuron types
Authors: Fageiry Samaher , Warriner Claire L. , Loper Jackson , Pianski Liam , Reardon Thomas , Jessell Thomas M. , Costa Rui M. , Miri Andrew 
Published: May 2024

SUMMARYThe corticospinal tract exerts its influence on movement through spinal neurons, which can be divided into types that exhibit distinct functions. However, it remains unknown whether these functional distinctions are reflected in the corticospinal inputs that different types of spinal neurons receive. Using rabies monosynaptic tracing from individual neuron types in the cervical cord and 3D histological reconstruction in mice, we discovered that different types receive inputs distinctly distributed across cortex, and aligned with cell type function. This included a distinct, sparse distribution of direct inputs from cortex onto motor neurons. Coupling rabies tracing with activity measurement during motor behavior revealed different interneuron types receive different input activity patterns, primarily due to the topographical distribution of the corticospinal neurons contacting them. Our results establish that different spinal neuron types get distinct anatomical and functional inputs from the cortex, and reveal functionally relevant homology to primate corticospinal organization.
High-plex Digital Spatial Profiling Identifies Subregion-Dependent Directed Proteome Changes Across Multiple Variants of Dementia
Authors: Bolen MacKenzie L. , Menees Kelly B. , Merchak Andrea R. , Gearing Marla , Gong Jingjing , Ren Yuqi , Murray Melissa , McEachin Zachary T. , Tansey Malú Gámez 
Published: May 2024

ABSTRACTFrontotemporal lobar degeneration (FTLD) is the leading cause of dementia in patients under the age of 65. Even in a single anatomical region, there is variance within pathological protein deposition as a result of FTLD. This spectrum of pathology leads to difficulty in identification of the disease during its progression and consequential varied post mortem clinicopathological diagnoses. NanoString GeoMx™ Digital Spatial Profiling (DSP) is a novel method that leverages the ability to spatially multiplex protein biomarkers of interest. We utilized NanoString DSP to investigate the proteome geography at two levels of the cortex and the subcortical white matter in patients with various types of dementia (Alzheimer’s disease, FTLD-c9ALS, FTLD-17, FTLD-TDP, FTLD-GRN; n=6 per syndrome) and neurologically healthy controls (NHC). Analysis of 75 different protein biomarkers of interest revealed both a disease and cortical subregion specific biomarker profile. Layers II-V of the cortex from diseased individuals displayed the greatest protein dysregulation as compared to NHC. Additionally, out of all disease groups within cortical layer 1, II-V and white matter, the FTLD-17 group had the most significant protein dysregulation as compared to NHC--specifically associated with immune cell pathways. Traditional biomarkers of dementia, such as various phosphorylated tau proteins and amyloid-β 42 displayed dysregulation, however our data suggest spatial enrichment in distinct to cortical sublayers. In conclusion, we observed that depending on the variant of disease, specific protein deposits either span multiple levels of cortical geography or only a single layer. Thus, the specific localization of these deposits could potentially be used to elucidate region-specific pathologic biomarkers unique to individual variants of dementia.
Layer-specific control of inhibition by NDNF interneurons
Authors: Naumann Laura Bella , Hertäg Loreen , Müller Jennifer , Letzkus Johannes J. , Sprekeler Henning 
Published: May 2024

AbstractNeuronal processing of external sensory input is shaped by internally-generated top-down information. In the neocortex, top-down projections predominantly target layer 1, which contains NDNF-expressing interneurons, nestled between the dendrites of pyramidal cells (PCs). Here, we propose that NDNF interneurons shape cortical computations by presynap-tically inhibiting the outputs of somatostatin-expressing (SOM) interneurons via GABAergic volume transmission in layer 1. Whole-cell patch clamp recordings from genetically identified NDNF INs in layer 1 of the auditory cortex show that SOM-to-NDNF synapses are indeed modulated by ambient GABA. In a cortical microcircuit model, we then demonstrate that this mechanism can control inhibition in a layer-specific way and introduces a competition for dendritic inhibition between NDNF and SOM interneurons. This competition is mediated by a unique mutual inhibition motif between NDNF interneurons and the synaptic outputs of SOM interneurons, which can dynamically prioritise different inhibitory signals to the PC dendrite. NDNF interneurons can thereby control information flow in pyramidal cells by redistributing dendritic inhibition from fast to slow timescales and by gating different sources of dendritic inhibition, as exemplified in a predictive coding application. This work corroborates that NDNF interneurons are ideally suited to control information flow within cortical layer 1.
SOP-MULTI: A self-organized polymer based coarse-grained model for multi-domain and intrinsically disordered proteins with conformation ensemble consistent with experimental scattering data
Authors: Baratam Krishnakanth , Srivastava Anand 
Published: May 2024

AbstractMultidomain proteins with long flexible linkers and full-length intrinsically disordered proteins (IDPs) are best defined as an ensemble of conformations rather than a single structure. Determining high-resolution ensemble structures of such proteins poses various challenges using tools from experimental structural biophysics. Integrative approaches combining available low-resolution ensemble-averaged experimental data andin silicobiomolecular reconstructions are now often used for the purpose. However, an exhaustive Boltzmann weighted conformation sampling for large proteins, especially for ones where both the folded and disordered domains exist in the same polypeptide chain, remains a challenge. In this work, we present a 2-site per amino-acid resolution SOP-MULTI force field for simulating coarse-grained models of multidomain proteins. SOP-MULTI combines two well-established self-organized polymer (SOP) models —: (i) SOP-SC models for folded systems and (ii) SOP-IDP for IDPs. For the SOP-MULTI, we train the cross-interaction terms between the beads belonging to the folded and disordered regions to generate experimentally-consistent conformation ensembles for full-length multi-domain proteins such as hnRNPA1, TDP-43, G3BP1, hGHR-ECD, TIA1, HIV-1 Gag, Poly-Ubiquitin and FUS. When back-mapped to all-atom resolution, SOP-MULTI trajectories faithfully recapitulate the scattering data over the range of the reciprocal space. We also show that individual folded domains preserve native contacts with respect to solved folded structures, and root mean square fluctuations of residues in folded domains match those obtained from all-atom molecular dynamics simulations trajectories of the same folded systems. SOP-MULTI Force Field is made available as a LAMMPS-compatible user package along with setup codes for generating the required files for any full-length protein with folded and disordered regions.
Comparison between EEG and MEG of static and dynamic resting-state networks
Authors: Cho SungJun , van Es Mats , Woolrich Mark , Gohil Chetan 
Published: May 2024

AbstractThe characterisation of resting state networks (RSNs) using neuroimaging techniques has significantly contributed to our understanding of the organisation of brain activity. Prior work has demonstrated the electrophysiological basis of RSNs and their dynamic nature, revealing transient activations of brain networks with millisecond timescales. While previous research has confirmed the comparability of RSNs identified by electroencephalography (EEG) to those identified by magnetoencephalography (MEG) and functional magnetic resonance imaging (fMRI), most studies have utilised static analysis techniques, ignoring the dynamic nature of brain activity. Often, these studies use high-density EEG systems, which limit their applicability in clinical settings. Addressing these gaps, our research studies RSNs using medium-density EEG systems (61 sensors), comparing both static and dynamic brain network features to those obtained from a high-density MEG system (306 sensors). We assess the qualitative and quantitative comparability of EEG-derived RSNs to those from MEG, including their ability to capture age-related effects, and explore the reproducibility of dynamic RSNs within and across the modalities. Our findings suggest that both MEG and EEG offer comparable static and dynamic network descriptions, albeit with MEG offering some increased sensitivity and reproducibility. Such RSNs and their comparability across the two modalities remained consistent qualitatively but not quantitatively when the data were reconstructed without subject-specific structural MRI images.
High glucose treatment induced nuclei aggregation of microvascular endothelial cells via foxo1a-klf2a pathway
Authors: Wang Xiaoning , Kang Xinyi , Li Bowen , Chen Changshen , Chen Liping , Liu Dong 
Published: May 2024

AbstractBACKGROUNDHyperglycemia is a major contributor to endothelial dysfunction and blood vessel damage, leading to severe diabetic microvascular complications. Despite the growing body of research on the underlying mechanisms of endothelial cell dysfunction, the available drugs based on current knowledge fall short of effectively alleviating these complications. Therefore, our endeavor to explore novel insights into the cellular and molecular mechanisms of endothelial dysfunction is crucial for the field.METHODSIn this study, we carried out a high-resolution imaging and time-lapse imaging analysis of the behavior of endothelial cellsin Tg(kdrl:ras-mCherry::fli1a:nEGFP)zebrafish embryos upon high glucose treatment. Genetic manipulation and chemical biology approaches were utilized to analyze the underlying mechanism of high-glucose-induced nuclei aggregation and aberrant migration of zebrafish endothelial cells and cultured human endothelial cells. Bioinformatical analysis of single-cell RNA sequencing data and molecular biological techniques to identify the target genes of Foxo1a.RESULTSIn this study, we observed that the high glucose treatment resulted in nuclei aggregation of endothelial cells in zebrafish intersegmental vessels (ISVs). Additionally, the aberrant migration of microvascular endothelial cells in high glucose-treated embryos, which might be a cause of nuclei aggregation, was discovered. High glucose-induced aggregation of vascular endothelial nuclei via foxo1a downregulation in zebrafish embryos. Then, we revealed that high glucose resulted in the downregulation of foxo1a expression and increased the expression of its direct downstream effector, klf2a, through which the aberrant migration and aggregation of vascular endothelial nuclei were caused.CONCLUSIONSHigh glucose treatment caused the nuclei of endothelial cells to aggregatein vivo, which resembles the crowded nuclei of endothelial cells in microaneurysms. High glucose suppresses foxo1a expression and increases the expression of its downstream effector, klf2a, thereby causing the aberrant migration and aggregation of vascular endothelial nuclei. Our findings provide a novel insight into the mechanism of microvascular complications in hyperglycemia.
Sex-dependant differences in the ability of nicotine to modulate discrimination learning and cognitive flexibility in mice
Authors: Aomine Yoshiatsu , Shimo Yuto , Sakurai Koki , Abe Mayuka , Macpherson Tom , Ozawa Takaaki , Hikida Takatoshi 
Published: May 2024

1AbstractNicotine, an addictive compound found in tobacco, functions as an agonist of nicotinic acetylcholine receptors (nAChRs) in the brain. Interestingly, nicotine has been reported to act as a cognitive enhancer in both human subjects and experimental animals. However, its effects in animal studies have not always been consistent, and sex differences have been identified in the effects of nicotine on several behaviors. Specifically, the role that sex plays in modulating the effects of nicotine on discrimination learning and cognitive flexibility in rodents is still unclear. Here, we evaluated sex-dependent differences in the effect of daily nicotine administration at various doses (0.125, 0.25, and 0.5 mg/kg) on visual discrimination (VD) learning and reversal (VDR) learning in mice. In male mice, nicotine significantly improved performance in VDR, but not VD, task, while, in female mice, nicotine significantly worsened performance in the VD, but not VDR, task. Next, to investigate the cellular mechanisms that underlie the sex differences in the effects of nicotine on cognition, transcriptomic analyses were performed on prefrontal cortex tissue samples from male and female mice that had undergone VD and VDR tasks. Pathway enrichment analysis and Protein-protein interaction (P-PI) analysis using gene sets with altered gene expression found three types of effects of nicotine: those common to both sexes, those in males only, and those in females only. Decreased expression of postsynaptic-related genes in males and increased expression of innate immunity-related genes in females were identified as possible molecular mechanisms related to sex differences in the effects of nicotine on cognition in discrimination learning and cognitive flexibility.
Data Resource Profile: Whole Blood DNA Methylation Resource in Generation Scotland (MeGS)
Authors: Walker Rosie M. , McCartney Daniel L. , Carr Kevin , Barber Michael , Shen Xueyi , Campbell Archie , Bernabeu Elena , Aitken Emma , Fawkes Angie , Wrobel Nicola , Murphy Lee , Whalley Heather C. , Howard David M. , Adams Mark J. , Rawlik Konrad , Navarro Pau , Tenesa Albert , Sudlow Cathie L , Porteous David J , Marioni Riccardo , McIntosh Andrew M. , Evans Kathryn L. 
Published: May 2024

AbstractWe have generated whole-blood DNA methylation profiles from 18,869 Generation Scotland Scottish Family Health Study (GS) participants, resulting in, at the time of writing, the largest single-cohort DNA methylation resource for basic biological and medical research: Methylation in Generation Scotland (MeGS). GS is a community- and family-based cohort, which recruited over 24,000 participants from Scotland between 2006 and 2011. Comprehensive phenotype information, including detailed data on cognitive function, personality traits, and mental health, is available for all participants. The majority (83%) have genome-wide SNP genotype data (Illumina HumanOmniExpressExome-8 array v1.0 and v1.2), and over 97% of GS participants have given consent for health record linkage and re-contact. At baseline, blood-based DNA methylation was characterised at ∼850,000 sites across four batches using the Illumina EPICv1 array. MeGS participants were aged between 17 and 99 years at the time of enrolment to GS. Blood-based DNA methylation EPICv1 array profiles collected at a follow-up appointment that took place 4.3-12.2 years (mean=7.1 years) after baseline are also available for 796 MeGS participants. Access to MeGS for researchers in the UK and international collaborators is via application to the GS Access Committee (access@generationscotland.org).
Hepatic Toxicity Assessment in HIV’s Interaction with Reverse Transcriptase and Integrase Strand Transfer Inhibitors at a Military Hospital, Southsouth Nigeria
Authors: Odegbemi Odekunle Bola , Olaniyan Mathew Folaranmi , Muhibi Musa Abidemi 
Published: May 2024

AbstractIntroductionThe use of Anti-retroviral therapy (ART) has made HIV a manageable condition, but there are risks associated with medications like Reverse Transcriptase Inhibitors (RTIs) and Integrase Strand Transfer Inhibitors (INSTIs), such as liver and renal toxicity. It is essential to understand these risks for effective treatment and case management. Investigating liver toxicity related to RTIs and INSTIs in Nigeria is crucial for optimizing HIV treatment. This study aimed to assess the impact of Tenofovir Lamivudine Dolutegravir (TLD) on the liver function of HIV patients at Nigerian Navy Hospital (NNH) Warri.MethodsThe liver function of 170 participants was assessed, with 120 on ART and the remainder being HIV-negative attendees at NNH Warri. The study used a cross-sectional design and selected participants through random sampling. We collected data using a semi-structured questionnaire. Blood samples were taken through venipuncture and stored at –20°C before analysis. Ethical approval was obtained, and data analysis was conducted using SPSS Statistical Software Version 23, with significance set at p < 0.05.ResultsThe study found significant differences in AST, TP, Alb, and GST levels between HIV-positive subjects receiving TLD and HIV-negative individuals. HIV-positive subjects had lower AST and Alb levels but higher TP and GST levels. Further analysis revealed correlations between age, gender, and liver enzymes, highlighting the complex relationship between HIV, liver function, and treatment outcomes.ConclusionThe study suggests that decreased AST levels may have a protective effect, while ALT activity had minimal impact. Changes in TP, Alb, and GSTs emphasize the importance of monitoring hepatic synthetic function and detoxification pathways in HIV patients taking TLD.
Dynamics of the blood plasma proteome during hyperacute HIV-1 infection
Authors: Nazziwa Jamirah , Freyhult Eva , Hong Mun-Gwan , Johansson Emil , Årman Filip , Hare Jonathan , Gounder Kamini , Rezeli Melinda , Mohanty Tirthankar , Kjellström Sven , Kamali Anatoli , Karita Etienne , Kilembe William , Price Matt A , Kaleebu Pontiano , Allen Susan , Hunter Eric , Ndung’u Thumbi , Gilmour Jill , Rowland-Jones Sarah L. , Sanders Eduard , Hassan Amin S. , Esbjörnsson Joakim 
Published: May 2024

ABSTRACTHIV-1 remains incurable and there is no effective vaccine towards the infection. A main challenge for this is the lack of a holistic understanding of the myriad of complex virus-host interactions during hyperacute HIV-1 infection (hAHI), and how these contribute to tissue damage and pathogenesis. Here, 1293 blood plasma proteins were quantified from 157 linked plasma samples collected before, during, and after hAHI of 54 volunteers from four sub-Saharan African countries. Six distinct longitudinal expression profiles were identified, of which four demonstrated a consistent decrease in protein levels following HIV-1 infection. Differentially expressed proteins were involved in inflammation, innate immunity, cell motility, and actin cytoskeleton reorganisation. Specifically, decreased levels of Zyxin, Secretoglobin family 1A member 1, and Pro-platelet basic protein were associated with acute retroviral syndrome; Rho GTPase activating protein 18, Annexin A1, and Lipopolysaccharide binding protein with viral load; and Hepsin, Protein kinase C beta, and Integrin subunit beta 3 with disease progression. This is the first holistic characterisation of within-patient blood plasma proteome dynamics during the first weeks of HIV-1 infection and presents multiple potential blood biomarkers and targets for prophylactic and therapeutic HIV-1 interventions.
Holistic antenatal care during pregnancy: A systematic review
Authors: Chewe Violet Manonyana , Mathibe-Neke Johanna Mmabojalwa 
Published: May 2024

AbstractBackgroundPregnancy outcomes are determined by the type of antenatal care a woman receives. The purpose of this review was to conduct a critical analysis of the literature on the provision of holistic antenatal care to pregnant women.DesignA systematic research review was employed for the study.Data SourcesA search of EBSCO Host, Google Scholar, Sabinet, and Science Direct databases was performed. After reviewing 150 paper titles and abstracts, 14 studies were found to meet the final criteria for quality assessment. Included were only English-language papers published from 2020 to 2023.Eligibility Criteria for Selecting StudiesQuantitative, Qualitative, Review studies, Quasi-experimental, and cohort studies. Papers had to include adults (>18 years old), and pregnant women attending antenatal care at different health facilities worldwide and published in peer-reviewed journals from 2020 onwards.ResultsFour of the fourteen analysed articles focused on socioeconomic status, three on staff attitudes, age, parity, and religion, and one on infrastructure. Six studies focused on midwives ’role in providing holistic antenatal care. These factors impacted pregnant women’s ability to receive comprehensive antenatal care. Three studies on woman-centered care and three on focused antenatal care have also come to light to enhance midwives’ capacity to deliver comprehensive prenatal care.ConclusionHealthcare facilities should offer an environment where communities may learn about the importance of antenatal care visits and how to ensure pregnant women obtain acceptable treatments.ImplicationsThis study demonstrates the necessity for healthcare providers to be resourceful about offering holistic antenatal care to pregnant women to enhance outcomes for both mothers and newborns.