bluuebunny/crossref_metadata_2025_split huggingface dataset:
Systematic investigation of interindividual variation of DNA methylation in human whole blood
Authors: Grant Olivia A. , Kumari Meena , Schalkwyk Leonard , Zabet Nicolae Radu 
Published: January 2024

AbstractInterindividual genetic variability is well characterised, but we still lack a complete catalogue of loci displaying variable and stable epigenetic patterns. Here, we report a catalogue of stable and variable interindividual DNA methylation in human whole blood by analysing the DNA methylation patterns in 3642 individuals using the IlluminaEPIC array. Our results showed that 41,216 CpGs display stable methylation (SMPs) and 34,972 CpGs display variable methylation levels (VMPs). This catalogue will be a useful resource for interpretation of results when associating epigenetic signals to phenotypes. We observed that SMPs are highly enriched in CpG islands, depleted at CpG shelves and open sea regions of the genome. In addition, we found that the VMPs were under higher genetic control than the SMPs and that trans mQTL pairs are often located in the same TAD or connected by chromatin loops. A subset of these VMPs (784) were classified as putative epialleles and our results demonstrate that these loci located in regulatory regions exhibit a link with gene expression.
Lead in the head: persistent lead poisoning of waterfowl in the Camargue (southern France) ten years after the ban on the use of lead shot in wetlands
Authors: Béchet Arnaud , Olivier Anthony , Cavallo François , Sauvajon Lou , Champagnon Jocelyn , Defos du Rau Pierre , Mondain-Monval Jean-Yves 
Published: January 2024

AbstractLead pollution remains a worldwide environmental and health issue with persistent detrimental effects on human and wildlife. Despite having been identified as an issue for wildlife a long time ago, the use of lead shot for hunting in wetlands was banned only in 2006 in France. Here, we took advantage of a long-term monitoring of waterfowl lead shot contamination in the Camargue (southern France) to (1) assess the local effectiveness of the French regulation in reducing waterfowl contamination and to (2) assess local compliance regarding the use of nontoxic shots in wetlands from 2007 onwards. We collected waterfowl gizzard from 38 hunters in the Camargue during 20 hunting seasons (1998 to 2017) for a total of 2306 gizzards from 28 different species. From 2008 to 2019, we also systematically collected the cartridge casings at three sites of communal wetland hunting. Ratio of lead vs nontoxic cartridges found in the field allowed monitoring hunter compliance with the new regulation. Despite a ten-year long ban on lead shot our results do not show any significant reduction in waterfowl exposure to lead through shot ingestion in the Camargue over the 20-year monitoring period. Indeed, gizzards of harvested waterfowl were as likely to contain at least one lead shot before the ban as after with a mean prevalence of 12% over the 13 species considered across the study period. Cartridge casings showed the persistence of use of lead shots by hunters in the Camargue wetlands despite a slow increase in the use of nontoxic cartridges. This unequivocally indicates that the law is far from being strictly applied, pointing to an insufficient policy enforcement. Our results support the need for a complete ban of lead ammunition for both wetland and terrestrial wildfowl which will facilitate policy enforcement and compliance.
Immunomodulatory Porous Regenerative Scaffolds forin situVascular Engineering
Authors: Zhen Le , Quiroga Elina , Creason Sharon A. , Chen Ningjing , Sapre Tanmay R. , Snyder Jessica M. , Lindhartsen Sarah L. , Fountaine Brendy S. , Barbour Michael C. , Faisal Syed , Aliseda Alberto , Johnson Brian W. , Himmelfarb Jonathan , Ratner Buddy D. 
Published: January 2024

AbstractThe 70-year quest for synthetic vascular graft (sVG) endothelialization has not led to completely healed endothelium in clinically used sVGs. In humans, healing is limited to the vicinity of anastomotic regions (pannus ingrowth) and does not reach the middle regions of sVGs. Here, we conducted proof-of-concept implantation ofimmunomodulatory porous regenerative scaffolds for in situ vascular engineering(IMPRESSIVE) as interposition grafts in sheep carotid arteries. These scaffolds are based on a new polyurethane (PU) material featuring a 40 µm precision porous structure optimized for angiogenesis. The modulus of the PU was adjusted to match that of natural arteries. The implantation study revealed rapid healing in IMPRESSIVE sVGs. In side-by-side comparison with standard polytetrafluoroethylene (PTFE) grafts, the luminal surfaces of PU grafts were almost completely covered with nucleated cells, while healing in PTFE grafts was limited to several millimeters within anastomotic regions. Endothelialization was observed in the middle regions of PU grafts and overall endothelialization increased significantly compared to PTFE grafts. Densities of mononuclear cells, foreign body giant cells (FBGCs), and endothelial cells within graft walls of PU grafts were also significantly higher than those in PTFE grafts, suggesting transmural cellular infiltration may play a key role in overall improved healing. High percentages of macrophages in pores of PU grafts show Type 1 (CCR7+) and Type 2 (mannose receptor, MR+) characteristics. We also discovered that FBGCs exist in a diverse spectrum of phenotypes. Dually activated FBGCs (CCR7+MR+, G1/2) dominate the population of FBGCs associated with pro-healing PU grafts. These observations suggest a complex, balanced pro-healing response from macrophages and FBGCs. The IMPRESSIVE approach may enable complete endothelialization in pro-healing sVGs and have wide applications in implantable devices and tissue engineering.
Characterizing substructure via mixture modeling in large-scale genetic summary statistics
Authors: Stoneman Hayley R , Price Adelle , Scribner Trout Nikole , Lamont Riley , Tifour Souha , Pozdeyev Nikita ,   Colorado Center for Personalized Medicine, Crooks Kristy , Lin Meng , Rafaels Nicholas , Gignoux Christopher R , Marker Katie M , Hendricks Audrey E 
Published: January 2024

AbstractGenetic summary data are broadly accessible and highly useful including for risk prediction, causal inference, fine mapping, and incorporation of external controls. However, collapsing individual-level data into groups masks intra- and inter-sample heterogeneity, leading to confounding, reduced power, and bias. Ultimately, unaccounted substructure limits summary data usability, especially for understudied or admixed populations. Here, we presentSummix2, a comprehensive set of methods and software based on a computationally efficient mixture model to estimate and adjust for substructure in genetic summary data. In extensive simulations and application to public data,Summix2characterizes finer-scale population structure, identifies ascertainment bias, and identifies potential regions of selection due to local substructure deviation.Summix2increases the robust use of diverse publicly available summary data resulting in improved and more equitable research.
SCFFBXL5ubiquitin ligase regulates stability of von-Hippel Lindau protein and the HIF1α-dependent response to hypoxia
Authors: Mayank Adarsh K , Pandey Vijaya , Lien Kyle , Li Lu , Jami-Alahmadi Yasaman , Kassem Ahmad Mohammad , Wohlschlegel James A 
Published: January 2024

SummaryThe canonical response to changes in cellular oxygen levels consists of the ubiquitin-dependent degradation of hypoxia-inducible transcription factors (HIFs) in a prolyl hydroxylase (PHD) and von-Hippel Lindau-ElonginB-ElonginC (VHL-ElonginBC) E3 ubiquitin ligase complex-dependent manner. This regulated degradation event is oxygen-dependent and results in activation of a transcriptional program that mediates the cellular adaptation to changes in oxygen tension. Here, we show that a distinct Cullin-RING ligase complex, SKP1-CUL1-FBXL5 (SCFFBXL5), physically associates with VHL and promotes its ubiquitin-dependent degradation during hypoxia. The regulation of VHL protein stability by FBXL5 influences HIF1α expression levels and the transcriptional activation of downstream hypoxia-responsive target genes. This work identifies a novel mechanism for VHL regulation which contributes to the HIF1α-mediated cellular response to hypoxia and provides an additional layer of crosstalk between iron and oxygen homeostasis.
The Primate Cortical LFP Exhibits Multiple Spectral and Temporal Gradients and Widespread Task-Dependence During Visual Short-Term Memory
Authors: Hoffman Steven J. , Dotson Nicholas M. , Lima Vinicius , Gray Charles M. 
Published: January 2024

AbstractAlthough cognitive functions are hypothesized to be mediated by synchronous neuronal interactions in multiple frequency bands among widely distributed cortical areas, we still lack a basic understanding of the distribution and task dependence of oscillatory activity across the cortical map. Here, we ask how the spectral and temporal properties of the local field potential (LFP) vary across the primate cerebral cortex, and how they are modulated during visual short-term memory. We measured the LFP from 55 cortical areas in two macaque monkeys while they performed a visual delayed match to sample task. Analysis of peak frequencies in the LFP power spectra reveals multiple discrete frequency bands between 3-80 Hz that differ between the two monkeys. The LFP power in each band, as well as the Sample Entropy, a measure of signal complexity, display distinct spatial gradients across the cortex, some of which correlate with reported spine counts in layer 3 pyramidal neurons. Cortical areas can be robustly decoded using a small number of spectral and temporal parameters, and significant task dependent increases and decreases in spectral power occur in all cortical areas. These findings reveal pronounced, widespread and spatially organized gradients in the spectral and temporal activity of cortical areas. Task-dependent changes in cortical activity are globally distributed, even for a simple cognitive task.
Werner syndrome RECQ helicase participates in and directs maintenance of the protein complexes of constitutive heterochromatin in proliferating human cells
Authors: Lazarchuk Pavlo , Nguyen Matthew Manh , Curca Crina M. , Pavlova Maria N. , Oshima Junko , Sidorova Julia M. 
Published: January 2024

AbstractThe WRN RECQ helicase is responsible for the Werner syndrome of premature aging and cancer predisposition. Substantial progress has been made in delineating WRN functions in multiple aspects of DNA metabolism, including DNA replication, repair, transcription, and telomere maintenance. Nevertheless, a complete mechanistic understanding of how loss of WRN accelerates aging in humans has not been achieved yet. Here we show that WRN is involved in the maintenance of constitutive heterochromatin, CH, in proliferating, immortalized human fibroblasts. WRN is found within a complex with histone deacetylase 2, HDAC2, and WRN/HDAC2 association is mediated by heterochromatin protein alpha, HP1α. WRN deficiency derepresses SATII pericentromeric satellite repeats and reduces a subset of protein-protein interactions that participate in the organization of CH in the nucleus. In particular, WRN deficiency reduces the complexes involving Lamin B1 and Lamin B receptor, LBR. Both mRNA level and subcellular distribution of LBR are affected by WRN deficiency, and the latter phenotype does not require WRN catalytic activities. At the mRNA level, WRN supports complete maturation of the LBR mRNA. All signs of heterochromatin disruption seen in WRN-deficient proliferating fibroblasts are also observed in WRN-proficient fibroblasts undergoing replicative or oncogene-induced senescence, and WRN complexes with HP1α and HDAC2 are also markedly downregulated in these senescing cells. The data suggest that WRN loss affects heterochromatin independently of the senescence program but can mimic aspects of it and thus sensitize cells to triggers of senescence.
FtsZ-mediated spatial-temporal control over septal cell wall synthesis
Authors: Hu Longhua , Perez Amilcar , Nesterova Tanya , Lyu Zhixin , Yahashiri Atsuhi , Weisss David S. , Xiao Jie , Liu Jian 
Published: January 2024

AbstractFtsZ, the tubulin-like GTPase, is the central organizer of the bacterial divisome, a macromolecular complex that synthesizes new septal cell wall and degrades old septal cell wall (made of septal peptidoglycan, sPG) to allow cell wall constriction and cytokinesis. InE. coli, it is well accepted that 1) FtsZ recruits all essential divisome proteins to the septum, including the core sPG synthase complex, FtsWI/QLB and its activator, FtsN; 2) FtsWI/QLB must complex with FtsN to produce sPG under the wild-type background; and 3) the Brownian ratcheting by treadmilling FtsZ polymers drives the directional movements of sPG synthase proteins along the septum circumference; and 4) FtsZ is essential for the early stage, but dispensable for the late stage of cell wall constriction. However, it remains unclear how FtsZ spatial-temporally organizes the divisome for robust bacterial cytokinesis throughout cell wall constriction process. Combining theoretical modeling with experiments inE. coli, we show that at the early stage during cell division, the Brownian ratcheting by FtsZ treadmilling acts both as a template to corral FtsWI/QLB and FtsN into close contacts for FtsWI/QLB-FtsN complex formation and as a conveyor to maximally homologize the septal distribution of sPG synthesis activities to avoid uneven cell wall constriction. When the septum constricts progressively, the FtsN septal density increases via binding to denuded sPG; consequently, the denuded PG-bound FtsN serves as the template to activate FtsWI/QLB for continued sPG synthesis, rendering FtsZ dispensable. Our work establishes an overarching framework that FtsZ spatial-temporally controls over septal cell wall constriction.SignificanceBacteria utilize FtsZ, the tubulin-like GTPase, to organize cell wall enzymes during cell division. FtsZ forms treadmilling polymers along the septum circumference and drives the directional movement of cell wall enzymes for robust cell wall constriction. How this role is achieved is unclear. We show that FtsZ treadmilling acts both as a template to corral cell wall enzymes into close contacts for priming and as a conveyor to homologize the septal distribution of cell wall synthesis activities for even septum constriction. These roles evolve at different stages of cell division and are modulated differentially by different bacteria; they likely define an overarching principle for robust cell division across the microbial world.
Stimulating the medial prefrontal cortex disrupts inhibitory control over memory by modulating frontal and parietal brain regions
Authors: Khan Ahsan , Eden Ti Chun Hang , Yuan Kai , Garcia Maite Crespo , Anderson Michael C. , Tong Raymond Kai-Yu 
Published: January 2024

SummaryThe act of recalling memories can paradoxically lead to the forgetting of other associated memories, a phenomenon known as retrieval-induced forgetting (RIF). This effect is thought to be mediated by inhibitory control mechanisms in the prefrontal cortex of the brain. Here we investigated whether stimulation of the medial prefrontal cortex (mPFC) with transcranial direct current stimulation modulates inhibitory control during memory retrieval in a RIF paradigm. In a randomized study, fifty participants received either real or sham stimulation, before performing retrieval practice on target memories. After retrieval practice, a final test was administered to measure the impact of stimulation on RIF. We found that stimulation selectively increased the retrieval accuracy of non-target memories and thus decreased RIF, suggesting a disruption of inhibitory control. Meanwhile, no change arose for the retrieval accuracy of target memories. The reduction in RIF was caused by a more pronounced beta desynchronization within the left dorsolateral prefrontal cortex (left-DLPFC), in an early time window (<500 msec) after the onset of the cue during retrieval practice. This, in turn, led to a stronger beta desynchronization within the parietal cortex in a later time window, an established marker for successful memory retrieval. Together, our results establish the causal involvement of the mPFC in actively suppressing competing memories and we demonstrate that while forgetting arises as a consequence of retrieving specific memories, these two processes are functionally independent. Finally, we demonstrate that beta desynchronization in the fronto-parietal brain regions indicates the disruption of inhibitory control.
Macrophages protect against sensory axon degeneration in diabetic neuropathy
Authors: Hakim Sara , Jain Aakanksha , Petrova Veselina , Indajang Jonathan , Kawaguchi Riki , Wang Qing , Duran Elif Sude , Nelson Drew , Adamson Stuart S. , Greene Caitlin , Woolf Clifford J. 
Published: January 2024

AbstractDiabetic peripheral neuropathy (DPN) is a common complication of diabetes, causing sensory loss and debilitating neuropathic pain1,2. Although the onset and progression of DPN have been linked with dyslipidemia and hyperglycemia3, the contribution of inflammation in the pathogenesis of DPN has not been investigated. Here, we use a High Fat High Fructose Diet (HFHFD) to model DPN and the diabetic metabolic syndrome in mice. Diabetic mice develop persistent heat hypoalgesia after three months, but a reduction in epidermal skin innervation only manifests at 6 months. Using single-cell sequencing, we find that CCR2+ macrophages infiltrate the sciatic nerves of diabetic mice well before axonal degeneration is detectable. We show that these infiltrating macrophages share gene expression similarities with nerve crush-induced macrophages4and express neurodegeneration-associated microglia marker genes5although there is no axon loss or demyelination. Inhibiting this macrophage recruitment in diabetic mice by genetically or pharmacologically blocking CCR2 signaling results in a more severe heat hypoalgesia and accelerated skin denervation. These findings reveal a novel neuroprotective recruitment of macrophages into peripheral nerves of diabetic mice that delays the onset of terminal axonal degeneration, thereby reducing sensory loss. Potentiating and sustaining this early neuroprotective immune response in patients represents, therefore, a potential means to reduce or prevent DPN.
A deep-learning strategy to identify cell types across species from high-density extracellular recordings
Authors: Beau Maxime , Herzfeld David J. , Naveros Francisco , Hemelt Marie E. , D’Agostino Federico , Oostland Marlies , Sánchez-López Alvaro , Chung Young Yoon , Maibach Michael , Kyranakis Stephen , Stabb Hannah N. , Martínez Lopera M. Gabriela , Lajko Agoston , Zedler Marie , Ohmae Shogo , Hall Nathan J. , Clark Beverley A. , Cohen Dana , Lisberger Stephen G. , Kostadinov Dimitar , Hull Court , Häusser Michael , Medina Javier F. 
Published: January 2024

AbstractHigh-density probes allow electrophysiological recordings from many neurons simultaneously across entire brain circuits but don’t reveal cell type. Here, we develop a strategy to identify cell types from extracellular recordings in awake animals, revealing the computational roles of neurons with distinct functional, molecular, and anatomical properties. We combine optogenetic activation and pharmacology using the cerebellum as a testbed to generate a curated ground-truth library of electrophysiological properties for Purkinje cells, molecular layer interneurons, Golgi cells, and mossy fibers. We train a semi-supervised deep-learning classifier that predicts cell types with greater than 95% accuracy based on waveform, discharge statistics, and layer of the recorded neuron. The classifier’s predictions agree with expert classification on recordings using different probes, in different laboratories, from functionally distinct cerebellar regions, and across animal species. Our classifier extends the power of modern dynamical systems analyses by revealing the unique contributions of simultaneously-recorded cell types during behavior.
Can we trace the social affiliation of rooks (Corvus frugilegus) through their vocal signature?
Authors: Martin Killian , Cornero Francesa M. , Danby Emily , Daunay Virgile , Nervet Louise , Clayton Nicola S. , Obin Nicolas , Dufour Valérie 
Published: January 2024

AbstractInter-individual recognition is crucial for stable social relationships and it is frequently mediated through vocal signatures. In socially complex species, recognition may additionally require additional levels corresponding to other layers of social organisation such as the pair, family, social group or colony. Additional vocal signatures may encode these different levels of social organisations for recognition. We investigated this hypothesis in the calls of the rook (Corvus frugilegus), a highly social corvid. Rooks form large breeding colonies where multiple pairs nest in clusters. We recorded the calls of five colonies located in France and in Great Britain, including both wild and captive colonies. To exclude variations due to different call types, we focused on the loud nest call produced exclusively by nesting females during the breeding season. We compared the acoustic distance of calls from each individual and between individuals at various levels of nest proximity, i.e. from the same nest cluster, from different nest clusters, from colonies within the same country, and from colonies in different countries. The only vocal signatures we found were at the individual level, but not at the nest cluster or colony level. This suggests a lack of vocal convergence in this species, at least for the nest call, which may be important for pair recognition in large colonies. Further studies should now evaluate if types of calls other than the nest call better carry vocal signatures as markers of different layers of sociality in this species, or if vocal divergence is a more general vocal phenomenon. In that case, applying new methods of monitoring vocal signatures in wild individuals should help understand the cognitive, social and environmental mechanisms underlying this vocal singularisation.1.Significance statementInter-individual recognition is crucial for social relationships in animals, and is often mediated by individual-specific acoustic characteristics in vocalisations, called a vocal signature. High levels of social organisations, such as a social group of familiar conspecifics or a breeding colony, may likewise be signalled by vocal signatures shared by multiple individuals. We used machine-learning techniques to investigate vocal signatures at multiple social levels in the nest call of brooding female rooks, a corvid species that breeds colonially but lives year-round in social groups. We find evidence of a strong individual vocal signature, but no common vocal signature even in females that nest close together, or in the same colony. A strong individual vocal signature may be a potent tool to monitor populations in this species with minimal disturbance and minimal material, especially as corvids are frequently targeted by human-fauna conflicts in continental Europe.