bluuebunny/crossref_metadata_2025_split huggingface dataset:
The resilience of the oral microbiome and lability of the hair microbiome across host environments in wild and captive lemurs
Authors: Burten Rachel B. , Lawler Richard R. , Ratsirarson Joelisoa , Ranaivonasy Jeannin , Leduc Rebecca , Bhagat Ankita , Lopez Amelia , Kamilar Jason M. 
Published: September 2024

AbstractMicrobiome diversity and composition in mammals is affected by the host’s environment and has been linked to important immune and physiological host functions, yet most of these data come from the gut microbiome. Research on the oral and hair microbiome in nonhuman primates has been far less common, and information from wild primates is even rarer. These overlooked patterns of environmental effects on microbial communities across the body may have important implications for a range of host functions. Therefore, in this study we characterized the gut, oral, and hair microbiomes across nine different captive and wild lemur species:Eulemur collaris,Eulemur coronatus,Eulemur mongoz,Lemur catta,Microcebus griseorufus,Microcebus murinus,Propithecus coquereli,Propithecus verreauxi, andVarecia rubra. We explored how host environment affects the microbiome diversity of these three body regions using 16S rRNA sequencing and found significant differences in microbiome composition, diversity, and environmental influence across body regions. The oral microbiome was least diverse and most resilient to different environmental effects; conversely, the hair microbiome was both most diverse and most labile. Differentially abundant bacterial taxa across oral, gut, and hair microbiota may also reflect selective regimes unique to each body region. These results emphasize the importance of accounting for body region when conducting microbiome studies.ImportanceAn organism’s microbiome plays important roles in a wide variety of the host animal’s physiological functions, yet how these microbial communities in body regions beyond the gut are affected by the host’s environment is not clearly understood. We therefore analyzed how the oral, gut, and hair microbiomes of nine lemur species (generaEulemur,Lemur,Microcebus,Propithecus, andVarecia) varied across wild and captive environments. We found that host environment affected the microbiomes of each body region in distinct ways, with the oral microbiome appearing conserved and more resilient to environmental effects, particularly compared to the diverse and widely variable hair microbiome. To our knowledge, this study is the most comprehensive multi-body-region analysis of the lemur microbiome to date. Our results demonstrate that the environment does not have a universal effect on the microbiome across body regions, but is instead mediated by body-region specific factors.
Synergistic DNA and RNA binding of the Hox transcription factor Ultrabithorax coordinates splicing and shapesin vivohomeotic functions
Authors: Blanco Constanza , Xiang Wan , Boumpas Panagiotis , Scorcelletti Maily , Hermon Ashley Suraj , Wong Jiemin , Merabet Samir , Carnesecchi Julie 
Published: September 2024

ABSTRACTThe dual interaction of many transcription factors (TFs) with both DNA and RNA is an underexplored issue that could fundamentally reshape our understanding of gene regulation. We address this central issue by investigating the RNA binding activity of theDrosophilaHox TF Ultrabithorax (Ubx) in alternative splicing and morphogenesis. Relying on molecular and genetic interactions, we uncover a homodimerization-dependent mechanism by which Ubx regulates splicing. Notably, this mechanism enables the decoupling of Ubx-DNA and -RNA binding activity in splicing. We identify a critical residue for Ubx-RNA binding and demonstrate the essential role of Ubx-RNA binding ability for its homeotic functions. Overall, we uncover a unique mechanism for Ubx-mediated splicing and underscore the critical contribution of synergistic DNA/RNA binding for its morphogenetic functions. These findings advance our understanding of co-transcriptional regulation and highlight the significance of TF-DNA/RNA synergistic function in shaping gene regulatory networks in living organisms.Graphical abstractHighlightsUbx homodimerization enables decoupling of DNA- and RNA-dependent splicing regulationThe homeodomain K58 amino acid is critical for Ubx-RNA binding abilityUbx-RNA binding ability is essential for splicing regulationDual DNA/RNA binding activities shape Ubx homeotic functions
Ethylene Modulates the Phenylpropanoid Pathway by EnhancingVvMYB14Expression via the ERF5-Melatonin-ERF104 Pathway in Grape Seeds
Authors: Gao Shiwei , Wang Fei , Wang Shengnan , Lan Shuxia , Xu Yujiao , Lyu Xinning , Kang Hui , Yao Yuxin 
Published: September 2024

AbstractEthylene plays a crucial role in regulating polyphenol metabolism, however the underlying mechanism remains largely unknown. This work demonstrated that ethylene release occurred earlier than melatonin during seed ripening. Ethylene treatment increased theVvASMTexpression and melatonin content.VvERF5was elucidated to bind to the ERE element in theVvASMTpromoter.VvERF5overexpression increased ASMT expression and melatonin content while its suppression generated the opposite results in grape seeds, calli and/or Arabidopsis seeds. Using the promoter ofVvMYB14, which was strongly induced by melatonin, a melatonin responsive element (MTRE) was identified.VvERF104was revealed not only to be strongly induced by melatonin but to bind to the MTRE of theVvMYB14.VvERF104overexpression and suppression largely increased and decreased the MYB14 expression, respectively, in grape seeds, calli and/or Arabidopsis seeds.VvMYB14overexpression widely modified the expression of genes in phenylpropanoid pathway and phenolic compound content in grape seeds. DAP-seq revealed that the MEME-1 motif was the most likely binding sites ofVvMYB14.VvPAL,VvC4HandVvCHSwere verified to be the target genes ofVvMYB14. Additionally, the roles ofVvERF5,VvASMTandVvERF104in mediating ethylene-induced changes in phenylpropanoid pathway were elucidated using their suppressing seeds. Collectively, ethylene increased theVvMYB14expression via the pathway of ERF5-melatonin-ERF104 and thereby modified phenylpropanoid pathway.
Screening of histone mutants reveals a domain within the N-terminal tail of histone H3 that regulates the Tup1-independent repressive role of Cyc8 at the activeFLO1
Authors: Singh Ranu , Tomar Raghuvir Singh 
Published: September 2024

AbstractYeast flocculation relies on cell surface flocculin proteins encoded by theFLO1gene. The expression ofFLO1is antagonistically regulated by the Tup1-Cyc8 and the Swi-Snf complexes. The Post translational modifications of core histones regulate the transcription of Tup1-Cyc8-regulated genes. However, the mechanisms by which the physical presence of tail residues regulateFLO1transcription process and flocculation is yet to be completely understood. Through screening we have identified a new region within the N-terminal tail of histone H3 regulating the transcription ofFLO1andFLO5. One of the histone H3 N-terminal truncation mutants H3Δ(17–24) showed higherFLO1expression compared to wild-type H3. Results revealed that in absence of 17-24 stretch the occupancy of Cyc8 decreases from the upstream regions ofFLO1. Additionally, analysis suggests that Hda1 is required for the Cyc8-mediated repression ofFLO1. Altogether we demonstrate that 17–24 stretch is essential for the Tup1 independent binding of Cyc8 at the promoters assisted by Hda1, leading to the strong repression ofFLO1transcription. In the absence of the 17–24 stretch, Cyc8 cannot bind, resulting in uncontrolled transcription ofFLO1.
A novelUNC93B1gain-of-function mutation leads to TLR7 and TLR8 hyperactivation and systemic lupus erythematosus
Authors: Han Xu , Wang Ruoran , Ozen Seza , Wang Qintao , Dong Wei , Zeng Yi , Xu Ouyuan , Şener Seher , Guo Li , Gu Ying , Yang Huanming , Yu Xiaomin , Tao Panfeng , Zhou Qing 
Published: September 2024

AbstractDysfunctions in nucleic acid-sensing Toll-like receptors (TLRs) disrupt nucleic acid tolerance, leading to systemic lupus erythematosus (SLE). Here, we report a novel homozygous gain-of-function p.R95L mutation in the TLR chaperone protein UNC93B1 in an SLE patient. Bulk and single-cell transcriptional analysis of the patient’s peripheral blood mononuclear cells (PBMCs) revealed significantly elevated inflammation in T cells and myeloid cells due to enhanced dendritic cells function. TheUNC93B1R95L mutation leads to hyperactivation of TLR7/8, but not TLR3/9, upon stimulation with specific agonistsin vitro. TransgenicUnc93b1R95L/R95Lmice develop inflammatory and autoimmune phenotypes, and the upregulation of inflammatory signaling differs among organs, with a specific contribution of malfunctioned T cells and B cells. In human and mouse cell lines, theUNC93B1R95L mutation promotes TLR7/8 signaling by enhancing its binding to ssRNA, without affecting TLR7/8 translocation. Overall, our results elucidate the pathology of organs and the immunological profiles of immune cell populations in the development of SLE caused by theUNC93B1R95L mutation through the TLR7/8 axis.
The association between malnutrition and cognitive development in infancy as manifest in EEG functional connectivity and power spectral density
Authors: Hartjen Berit , Kakon Shahria , Rahman Navin , Greaves Garrett , Xie Wanze , Tofail Fahmida , Haque Rashidul , Nelson Charles A. 
Published: September 2024

ABSTRACTMalnutrition, particularly undernutrition, is a critical global health challenge, contributing to nearly half of all deaths among children under 5 and severely impacting physical and mental health, along with neural and cognitive development. Prior research by Xie et al. (2019a) linked growth faltering to altered EEG functional connectivity (FC) at 36 months and poorer cognitive outcomes at 48 months; however, no associations were found at 6 months for EEG measures or at 27 months for cognitive outcomes. Our study investigates these relationships in a sample of 12-month-old infants in Dhaka, Bangladesh, using various growth measurements (height/length-for-age, weight-for-age, weight-for-height/length, head-circumference-for-age, and mid-upper-arm-circumference-for-age z-scores) as indicators of nutritional status. Brain development was assessed through EEG, focusing on power spectral density (PSD) and FC, while cognitive development was evaluated with the Bayley Scales of Infant and Toddler Development, Fourth Edition. Our findings reveal that, at 12 months, growth faltering, indicative of undernutrition, was associated with reduced PSD, while initial correlations with increased FC did not remain significant after false discovery rate (FDR) correction. PSD was further positively linked to cognitive development, but associations with FC were not significant post-correction. Notably, EEG PSD in the theta and alpha bands mediated the relationship between malnutrition and behavioral outcomes. These results underscore the early impact of malnutrition on brain development, highlighting the importance of PSD in understanding neural development in this context. Our study emphasizes the need for early intervention and continuous monitoring to mitigate the adverse effects of malnutrition on infant brain and cognitive development.RESEARCH HIGHLIGHTS-EEG power spectral density (PSD) in the theta and alpha frequency bands at 12 months sheds light on undernutrition’s impact on cognitive development.-Better nutritional health, indicated by higher height/length-for-age (HAZ), leads to increased theta and alpha PSD, contributing to better cognitive outcomes.-Initial correlations between undernutrition, increased EEG functional connectivity (FC), and poorer cognitive outcomes did not remain significant after FDR correction.-Findings highlight the critical role of nutritional interventions in early childhood to support optimal neural and cognitive development.
Characterizing the Longitudinal Impact of Backward Locomotor Treadmill Training on Walking and Balance Outcomes in Chronic Stroke Survivors: A Randomized Single Center Clinical Trial
Authors: Awosika Oluwole O. , Drury Colin , Garver Amanda , Boyne Pierce , Sucharew Heidi J. , Wasik Emily , Bhattacharya Amit , Dunning Kari , Khatri Pooja , Kissela Brett M. 
Published: September 2024

ABSTRACTBackground and PurposeWalking and balance impairments after stroke are a global health concern, causing significant morbidity and mortality. However, effective strategies for achieving meaningful recovery in the chronic stages are limited. Backward locomotor treadmill training (BLTT) is a novel walking rehabilitation protocol that is safe, feasible, and likely beneficial in stroke survivors; however, its efficacy has not been tested. This single-center, randomized, assessor-blind clinical trial aims to test the preliminary efficacy of BLTT compared to forward locomotor treadmill training (FLTT) on walking speed, symmetry, and postural stability.MethodsForty stroke survivors [BLTT (N=19), FLTT (N=21); mean age= 56.3 ± 8.6 years; 53% Female; 30% Non-Hispanic Black] with mild-moderate walking impairment were enrolled. Participants underwent nine 30-minute BLTT or FLTT sessions over three weeks. The primary outcome was the mean change in the 10-meter walk test (10 MWT) at 24 hours post-training (24 hr POST). Secondary outcome measures were changes in spatiotemporal walking symmetry and postural stability during quiet standing at 24 hr POST. Retention was explored at Days 30- and 90 POST.ResultsWe report clinically meaningful (≥ 0.16 m/s) improvements in overground walking speed at 24 hr POST, with retention up to Day 90 POST with BLTT and FLTT. However, contrary to our working hypothesis, no between-group differences in walking speed were observed. Nonetheless, we found that BLTT resulted in offline improvements in spatial symmetry and retention of subcomponents of the modified clinical test of sensory interaction on balance (mCTSIB), including the testing of proprio-vestibular integration up to Day 30 POST.ConclusionAmong chronic stroke patients with mild-moderate walking impairment, BLTT and FLTT both resulted in long-lasting and clinically meaningful improvement in walking speed. However, preliminary findings suggest that BLTT may better comprehensively target walking asymmetry and sensory systems processing and integration.
The beginnings of light-dependent nuclear relocation in land plants
Authors: Iwabuchi Kosei , Yagi Hiroki , Moriya Kenta C. , Komatsu Aino , Sakai Yuuki , Shimada Tomoo , Nishihama Ryuichi , Kohchi Takayuki , Harada Akiko , Watanabe Yo-hei , Ueda Haruko , Hara-Nishimura Ikuko 
Published: September 2024

The terrestrialization of plants was accompanied by exposure to several environmental stresses. Adaptation to these stresses required numerous changes at the cellular and molecular level. One such adaptation in the leaves ofArabidopsis thalianais the movement of cell nuclei to avoid UV damage. In the dark, the nuclei locate to the bottom walls of leaf cells to distance genetic material from external stresses, but in response to intense blue light (an indication of the presence of UV), they move to the side walls to escape UV-induced DNA damage1. The movement is driven by the photoreceptor phototropin and the actin cytoskeleton2. However, how this protective mechanism evolved in land plants remains unclear. Here, we show that in the liverwortMarchantia polymorpha, nuclei show a similar, but less stable movement in response to intense blue light. In the dark,M. polymorphapositioned nuclei on the upper walls of epidermal cells in young thalli, but in response to intense blue light, the nuclei immediately moved to the side walls, similar toA. thaliana. However, the movement was transient and the nuclei returned to the upper walls through both the actin and microtubule cytoskeletons.UnlikeA. thaliana,M. polymorpharesponded to prolonged (> 1 day) exposure to low light by moving nuclei from the upper to the side walls through both the actin and microtubule cytoskeletons and two photoreceptors (phototropin and phytochrome). However, no light-dependent nuclear relocation was observed in charophyte algae, suggesting that light-dependent nuclear relocation was initially established in the common ancestor of land plants as a result of terrestrialization and then diverged during land plant evolution.
Integrative Molecular Dynamics Simulations Untangle Cross-Linking Data to Unveil Mitochondrial Protein Distributions
Authors: Schuhmann Fabian , Akkaya Kerem Can , Puchkov Dmytro , Lehmann Martin , Liu Fan , Pezeshkian Weria 
Published: September 2024

Cross-linking mass spectrometry (XL-MS) enables the mapping of protein-protein interactions on the cellular level. When applied to all compartments of mitochondria, the sheer number of cross-links and connections can be over-whelming, rendering simple cluster analyses convoluted and uninformative. To address this limitation, we integrate the XL-MS data, 3D electron microscopy data, and localization annotations with a supra coarse-grained molecular dynamics simulation to sort all data, making clusters more accessible and interpretable. In the context of mitochondria, this method, through a total of 6.9 milliseconds of simulations, successfully identifies known, suggests unknown protein clusters, and reveals the distribution of inner mitochondrial membrane proteins allowing a more precise localization within compartments. Our integrative approach suggests, that two so-far ambigiously placed proteins FAM162A and TMEM126A are localized in the cristae, which is validated through super resolution microscopy. Together, this demonstrates the strong potential of the presented approach.Entry for the Table of ContentsThe approach combines cross-linking mass spectrometry, electron microscopy, and coarse-grained molecular dynamics simulations to map protein-protein interactions in mitochondria. This integration makes complex data clusters accessible, revealing protein distributions and localizations. Notably, it allows the localization of FAM162A and TMEM126A through super-resolution microscopy, showcasing the synergy of experimental and computational methods.
Mutations in legume symbiosis genes create a complex selective landscape for natural genetic variation in rhizobia during multi-strain inoculations
Authors: Guha Sohini , Bledsoe Regina B. , Sutherland Jeremy , Epstein Brendan , Fry Gwendolyn M. , Young Nevin D. , Tiffin Peter , Burghardt Liana T. 
Published: September 2024

AbstractIn the mutualism between leguminous plants and rhizobia bacteria, rhizobia live inside root nodules, creating the potential for host genes to shape the rhizobial selective environment. Single-strain screens have identified many host genes influencing symbiosis. However, it’s unknown whether these genes influence which rhizobial strains colonize and thrive inside nodules during multi-strain inoculations. In this study, we inoculated 18Medicago truncatulasymbiotic mutants (including mutations that alter NCR peptide production, plant defence, and nodule number regulation) with a mixture of 86Sinorhizobium melilotistrains. In multi-strain inoculations, most mutations led to reduced host benefits but widely varying effects on host investment and rhizobial benefit (i.e., strain relative fitness), revealing widespread host gene by strain fitness interactions. Genome-wide association studies identify genetic variants on rhizobial replicons pSymA and pSymB as important in mediating strain fitness responses to host mutations. While most top variants only affected rhizobial fitness when one host gene was disrupted, we identified ten variant groups with pervasive effects across six or more host mutations. These variants occurred primarily on pSymA, the symbiotic replicon, and includefixLand a few metabolic genes. In contrast to the limited-effect variants, variants with pervasive positive effects in mutants tended to adversely affect strain fitness in wild-type hosts. Our results reveal how host symbiosis genes perturb the selective landscape and symbiotic outcomes for rhizobia and set the stage for improving rhizobial inoculants and breeding legume hosts better adapted for multi-strain environments.
Apparent timescaling of fossil diversification rates is caused by sampling bias
Authors: Reijenga Bouwe R. , Close Roger A. 
Published: September 2024

SummaryNegative scaling relationships between both speciation and extinction rates on the one hand, and the age or duration of organismal groups on the other, are pervasive, and recovered in both molecular phylogenetic and fossil time series. The agreement between molecular and fossil data hints at a universal cause, and potentially to incongruence between micro- and macroevolution. However, the existence of negative rate scaling in fossil time series has not undergone the same level of scrutiny as in molecular data. Here, we analyse the marine fossil record across the last ~538.8 Ma of the Phanerozoic to investigate the presence and strength of negative rate scaling. We find that negative rate scaling arises under commonly applied age range-based per-capita rates, which do not control for sampling bias, but are severely reduced or absent when metrics are used that do correct for sampling. We further show by simulation that even moderately-incomplete sampling of species occurrences through time may induce rate scaling. We thus conclude that there are no significant scaling relationships present in these fossil clades, and that any apparent trend is caused by sampling artefacts and taxonomic practices. If rate scaling in molecular phylogenies is genuine, the absence of such a relationship in the fossil record will provide a valuable benchmark and constraint on what processes can cause it.HighlightsStudies have found that fossil and molecular diversification rates scale with timeSuch rate scaling hints at a disconnect between micro- and macroevolutionThese trends are absent from the fossil record when controlling for sampling biasesRate scaling in general may be artefactual, or fossils could show distinct patterns