bluuebunny/crossref_metadata_2025_split huggingface dataset:
The “Proxitome” of Arabidopsis Processing Bodies Reveals a Condensate-Membrane Interface Instructing Actin-Driven Directional Growth
Authors: Liu Chen , Mentzelopoulou Andriani , Muhammad Amna , Volkov Andriy , Weijers Dolf , Gutierrez-Beltran Emilio , Moschou Panagiotis N. 
Published: June 2022

ABSTRACTCellular condensates can comprise membrane-less ribonucleoprotein assemblies with liquid-like properties. These cellular condensates influence various biological outcomes, but their liquidity hampers their isolation and characterization. Here, we investigated the composition of the condensates known as processing bodies (PBs) in the model plant Arabidopsis through a proximity-biotinylation pipeline. Using in situ protein–protein interaction approaches, genetics and high-resolution imaging, we show that PBs comprise networks that interface with membranes. Surprisingly, the conserved component of PBs, DECAPPING PROTEIN 1 (DCP1), can interface with unique plasma membrane subdomains that include cell edges and vertices. We characterized these plasma membrane interfaces and discovered a developmental module that can control cell shape. This module is modulated by the liquid-like properties of DCP1 and the actin-nucleating SCAR–WAVE complex, whereby the DCP1-SCAR–WAVE interaction confines actin nucleation. This study reveals an unexpected repertoire for a conserved condensate at unique membrane-condensate interfaces.
Male sex hormone and reduced plakoglobin jointly impair atrial conduction and cardiac sodium currents
Authors: Sommerfeld Laura C. , Holmes Andrew P. , Yu Ting Y. , O’Shea Christopher , Kavanagh Deirdre M. , Pike Jeremy M. , Wright Thomas , Syeda Fahima , Aljehani Areej , Kew Tania , Cardoso Victor R. , Kabir S. Nashitha , Hepburn Claire , Menon Priyanka M. , Broadway-Stringer Sophie , O’Reilly Molly , Witten Anika , Fortmueller Lisa , Lutz Susanne , Kulle Alexandra , Gkoutos Georgios V. , Pavlovic Davor , Arlt Wiebke , Lavery Gareth G. , Steeds Richard , Gehmlich Katja , Stoll Monika , Kirchhof Paulus , Fabritz Larissa 
Published: June 2022

AbstractAndrogenic anabolic steroids (AAS) are commonly abused by young men. Male sex associates with earlier manifestation of common and rare cardiac conditions including atrial fibrillation and arrhythmogenic right ventricular cardiomyopathy (ARVC). Clinical data suggest an atrial involvement in ARVC. The disease is caused by desmosomal gene defects such as reduced plakoglobin expression. Analysis of clinical records from 146 ARVC patients identified male preponderance and increased prevalence of atrial arrhythmias in patients with definite ARVC. Definite patients displayed ECG changes suggesting atrial remodelling. To study mechanisms of atrial remodelling due to desmosomal vulnerability and AAS, young adult male mice, heterozygously deficient for plakoglobin (Plako+/-) and wildtype (WT) littermates, were chronically exposed to 5α-dihydrotestosterone (DHT) or placebo. DHT increased atrial expression of pro-hypertrophic, fibrotic and inflammatory transcripts. DHT caused atrial conduction slowing, decreased peak sodium current density, reduced action potential amplitude and lowered the peak depolarisation rate in Plako+/- but not WT atria. Super-resolution microscopy revealed a reduction in Nav1.5 clustering in Plako+/- atrial cardiomyocytes following DHT exposure. These data reveal that AAS combined with plakoglobin deficiency cause pathological atrial electrical remodelling in young male hearts. AAS abuse may increase the risk of atrial myopathy in males with desmosomal gene variants.
Systemic Calcitonin Gene-Related Peptide (CGRP) modifies auditory and vestibular end organ electrical potentials, and increases sensory hypersensitivities
Authors: Rahman Shafaqat M. , Faucher Stefanie , Jonnala Raajan , Holt Joseph C. , Lee Choongheon , Luebke Anne E. 
Published: June 2022

AbstractMigraine is a severe and chronic neurological disorder that affects ∼18% of people worldwide, the majority being female (3:1). It is characterized by recurrent, debilitating headaches and heightened sensory sensitivities. People with migraine may develop vestibular migraine (VM), characterized by a heightened motion sensitivity and preponderance for spontaneous vertigo attacks and balance problems such as postural instability. Calcitonin gene-related peptide (CGRP) is implicated in migraine and is believed to act on brain meninges or in subcortical central nervous system (CNS) structures, and CGRP-based antagonists have shown efficacy for migraine treatment. CGRP also signals at efferent synapses of the cochlea and vestibular end organs, but it is unclear if exogenous CGRP can modulate inner ear function at the end organ level and cause heightened behavioral responses consistent with VM. We tested if intraperitoneally (IP) delivered CGRP to wildtype mice can modulate end organ potentials to sound [via auditory brainstem responses (ABRs)] and jerk stimuli [via vestibular sensory evoked potentials (VsEPs)]. We also assessed behavioral measures of phonophobia [acoustic startle reflex (ASR)] and static imbalance [postural sway-center of pressure (CoP)] after IP CGRP, and observed female mice exhibited heightened sensitivities to IP CGRP in all assays. Male mice showed similar auditory sensitivity and end organ effects to CGRP, but systemic CGRP did not modify male postural sway as it did in females. In conclusion, we show that intraperitoneally delivered CGRP affects ABRs and VsEPs, and elicits behaviors suggestive of auditory hypersensitivity and postural instability in mice related to the phonophobia and postural instability seen in VM patients.Significance StatementCalcitonin Gene-Related Peptide (CGRP) has been implicated in migraine, and CGRP-based therapeutics have shown efficacy in the treatment of migraine headaches. CGRP is also present in efferent synapses of the inner ear, so we questioned if increases in systemic CGRP can act directly on inner ear end organs and modify corresponding behavioral responses. In this study, we determined systemic CGRP changes cochlear and vestibular end organ potentials and produces migraine behaviors similar to phonophobia and postural control deficits. Peripheral changes in auditory and vestibular compound action potentials following systemic CGRP administration suggest CGRP can act directly on the inner ear, which provides one site of action for CGRP’s involvement in hypersensitivity to sound and movement in migraine.
Network preservation analysis reveals dysregulated metabolic pathways in human vascular smooth muscle cell phenotypic switching
Authors: Perry R. Noah , Albarracin Diana , Aherrahrou Redouane , Civelek Mete 
Published: June 2022

AbstractVascular smooth muscle cells (VSMCs) are key players involved in atherosclerosis, the underlying cause of coronary artery disease (CAD). They can play either beneficial or detrimental roles in lesion pathogenesis, depending on the nature of their phenotypic changes. An in-depth characterization of their gene regulatory networks can help better understand how their dysfunction may impact disease progression. We conducted a gene expression network preservation analysis in aortic SMCs isolated from 151 multi-ethnic heart transplant donors cultured under quiescent or proliferative conditions. We identified 86 groups of co-expressed genes (modules) across the two conditions and focused on the 18 modules that are least preserved between the phenotypic conditions. Three of these modules were significantly enriched for genes belonging to proliferation, migration, cell adhesion, and cell differentiation pathways, characteristic of phenotypically modulated proliferative VSMCs. The majority of the modules, however, were enriched for metabolic pathways consisting of both nitrogen-related and glycolysis-related processes. Therefore, we explored correlations between nitrogen metabolism-related genes and CAD-associated genes and found significant correlations, suggesting the involvement of the nitrogen metabolism pathway in CAD pathogenesis. for six genes in the nitrogen metabolism pathway. We also created gene regulatory networks enriched for genes in glycolysis and predicted key regulatory genes driving glycolysis dysregulation. Our work suggests that dysregulation of VSMC metabolism participates in phenotypic transitioning, which may contribute to disease progression and suggests that AMT and MPI may play an important role in regulating nitrogen and glycolysis related metabolism in SMCs.
Population genomics of an emergent tri-species hybrid zone
Authors: Natola Libby , Seneviratne Sampath S. , Irwin Darren 
Published: June 2022

AbstractIsolating barriers that drive speciation are commonly studied in the context of two-species hybrid zones. There is however evidence that more complex introgressive relationships are common in nature. Here, we use field observations and genomic analysis, including the sequencing and assembly of a novel reference genome, to study an emergent hybrid zone involving two colliding hybrid zones of three woodpecker species: Red-breasted, Red-naped, and Yellow-bellied Sapsuckers (Sphyrapicus ruber, S. nuchalis, and S. varius). Surveys of the area surrounding Prince George, British Columbia, Canada, show that all three species are sympatric, and Genotyping-by-Sequencing identifies hybrids from each species pair and birds with ancestry from all three species. Observations of mate pair phenotypes and genotypes provide evidence for assortative mating, though there is some heterospecific pairing. Hybridization is more extensive in this tri-species hybrid zone than in two di-species hybrid zones. However, there is no evidence of a hybrid swarm and admixture is constrained to contact zones, so we classify this region as a tension zone and invoke selection against hybrids as a likely mechanism maintaining species boundaries. Analysis of sapsucker age classes does not show disadvantages in hybrid survival to adulthood, so we speculate the selection upholding the tension zone may involve hybrid fecundity. Gene flow among all sapsuckers in di-species hybrid zones suggests introgression likely occurred before the formation of this tri-species hybrid zone, and might result from bridge hybridization, vagrancies, or other three-species interactions.
Cyclin B3 implements timely vertebrate oocyte arrest for fertilization
Authors: Bouftas Nora , Schneider Lena , Halder Marc , Demmig Rebecca , Baack Martina , Cladière Damien , Walter Melanie , Abdallah Hiba Al , Kleinhempel Camilla , Müller Janina , Passarelli Francesca , Wehrle Patrick , Heim Andreas , Wassmann Katja , Mayer Thomas U. 
Published: June 2022

SummaryTo ensure successful offspring ploidy, vertebrate oocytes must halt the cell cycle in meiosis II until sperm entry. Emi2 is essential to keep oocytes arrested until fertilization. Yet, how this arrest is implemented exclusively in meiosis II and not prematurely in meiosis I remained enigmatic. Using mouse and frog oocytes, we show here that cyclin B3, an understudied B- type cyclin, is essential to keep Emi2 levels low in meiosis I. Direct phosphorylation of Emi2 at an evolutionarily highly conserved site by Cdk1/cyclin B3 targets Emi2 for degradation. In contrast, Cdk1/cyclin B1 is inefficient in Emi2 phosphorylation providing a molecular explanation for the requirement of different B-type cyclins for oocyte maturation. Cyclin B3 degradation at exit from meiosis I enables Emi2 accumulation and thus, timely arrest in meiosis II. Our findings illuminate the evolutionarily conserved mechanisms controlling oocyte arrest for fertilization at the correct cell cycle stage, essential for embryo viability.
Saturated cell lysing is critical for high sensitivity microbiome analysis
Authors: Wang Ying , Zhao Cuiping , Lam Yan Y. , Zhao Liping , Wu Guojun 
Published: June 2022

Introductory paragraphFor robust DNA-based gut microbiome analysis, all cells in the stool samples need to be lysed. However, no standards have been developed to evaluate a DNA extraction protocol’s capability of lysing all cells and its sensitivity on detecting microbial structural differences among samples. In this study, we incrementally increased the intensity of mechanical lysis and integrated lysozyme pretreatment to Protocol Q (PQ), which was recommended as the best from 21 protocols1. A new protocol (LPQ) was optimized when DNA yield, Gram-positive bacteria ratio, and beta diversity all reached to a plateau with no further significant changes, indicating the achievement of saturated lysing. LPQ detected significant differences among three groups of fiber-treated human stool samples and identified 64 responsive ASVs, while a commercial kit failed to detect any significant treatment effects and PQ only detected 17 responsive ASVs. Therefore, saturated lysing as defined in this study should be adopted for evaluating microbiome DNA extraction protocols.
Summer dynamics of microbial diversity on a mountain glacier
Authors: Hotaling Scott , Price Taylor L. , Hamilton Trinity L. 
Published: June 2022

AbstractUnder climate change, glaciers are rapidly receding worldwide. A melting cryosphere will dramatically alter global sea levels, carbon cycling, and water resource availability. Glaciers also host rich biotic communities that are dominated by microbial diversity and this biodiversity can impact surface albedo, thereby driving a feedback loop between biodiversity and cryosphere melt. However, the microbial diversity of glacier ecosystems remains largely unknown outside of major ice sheets, particularly from a temporal perspective. Here, we characterized temporal dynamics of bacteria, eukaryotes, and algae on the Paradise Glacier, Mount Rainier, USA, over the summer melt season. During our study, the glacier surface steadily darkened as seasonal snow melted and darkening agents accumulated until new snow fell in late September. From a community-wide perspective, the bacterial community remained generally constant and eukaryotes exhibited a clear temporal progression of community change while fungal diversity was intermediate. Individual taxonomic groups, however, exhibited considerable stochasticity. We found little support for our a priori prediction that autotroph abundance would peak before heterotrophs. Notably, two different trends in snow algae emerged—an abundant early-and late-season OTU with a different mid-summer OTU that peaked in August. Overall, our results highlight the need for temporal sampling to clarify microbial diversity on glaciers and that caution should be exercised when interpreting results from single or few timepoints.
A novel Wnt pathway orients Par complex-dependent cell polarity
Authors: Yoshiura Shigeki , Matsuzaki Fumio 
Published: June 2022

AbstractThe Par-complex is a highly conserved cell polarization machinery, playing critical roles in tissue development and homeostasis. However, how extracellular signals globally orient Par-dependent cell polarity in tissues remains poorly understood. We show here that four of seven Drosophila Wnts redundantly serve as directional cues for the Par-dependent cell polarity of neural stem cells, neuroblasts, through a novel pathway. Wnt2/5/6/D proteins, expressed in ectodermal cells, act via frizzled receptors on underlying neuroblasts to localize armadillo/β-catenin to neuroblast cytocortex facing the Wnt signal source. The localized armadillo recruits the Par complex and Pins complex to the neuroblast apical side, through the association of arm with Par3 and Inscuteable. Wnts consequently orient the cell polarity and asymmetric divisions of neuroblasts perpendicular to the epithelium, allowing nerve tissue to grow inward along the central-peripheral axis in Drosophila embryos. This novel non-canonical Wnt signaling pathway may regulate Par-dependent polarity in various biological contexts.
hnRNP R is a regulator of stress granule formation
Authors: Ji Changhe 
Published: June 2022

ABSTRACThnRNP R (Heterogeneous nuclear ribonucleoproteins R) is one member of RNA-binding proteins (RBPs) in hnRNP family, it plays important role in nucleic acid metabolism including alternative splicing, mRNA stabilization, transcriptional and translational regulation, and mRNA transport. Mostly hnRNP R is localized in nuclear and extensively binds with RNA and chromatin, but still some part of it exports to cytosol. We found that long and short isoform hnRNP R can located in stress granules, depletion hnRNP R can facilitate the stress granule formation and accelerate mRNA in the stress granules. Meanwhile we found that depletion hnRNP R can alter the stress granule phenotype and impair stress granule resolving. Additionally, we also found that depletion hnRNP R also induce TDP43 granules formation. Furthermore, depletion hnRNP R can impair TDP43 binding with ribosome. Altogether, hnRNP R plays important role in the stress granule formation.
Efficient reconciliation of genomic datasets of high similarity
Authors: Shibuya Yoshihiro , Belazzougui Djamal , Kucherov Gregory 
Published: June 2022

AbstractWe apply Invertible Bloom Lookup Tables (IBLTs) to the comparison of k-mer sets originated from large DNA sequence datasets. We show that for similar datasets, IBLTs provide a more space-efficient and, at the same time, more accurate method for estimating Jaccard similarity of underlying k-mer sets, compared to MinHash which is a go-to sketching technique for efficient pairwise similarity estimation. This is achieved by combining IBLTs with k-mer sampling based on syncmers, which constitute a context-independent alternative to minimizers and provide an unbiased estimator of Jaccard similarity. A key property of our method is that involved data structures require space proportional to the difference of k-mer sets and are independent of the size of sets themselves. As another application, we show how our ideas can be applied in order to efficiently compute (an approximation of) k-mers that differ between two datasets, still using space only proportional to their number. We experimentally illustrate our results on both simulated and real data (SARS-CoV-2 and Streptococcus Pneumoniae genomes).Available at: https://github.com/yhhshb/km-peeler.git
Rapid evolution of the fine-scale recombination landscape in wild house mouse (Mus musculus) populations
Authors: Wooldridge Lydia K. , Dumont Beth L. 
Published: June 2022

AbstractMeiotic recombination is an important evolutionary force and essential meiotic process. In many species, recombination events concentrate into “hotspots” defined by the site-specific binding of PRMD9. Rapid evolution of PRDM9’s zinc finger DNA-binding array leads to remarkably abrupt shifts in the genomic distribution of hotspots between species, but the question of how Prdm9 allelic variation shapes the landscape of recombination between populations remains less well understood. Wild house mice (Mus musculus) harbor exceptional Prdm9 diversity, with >100 alleles identified to date, and pose a particularly powerful system for addressing this open question. We employed a coalescent-based approach to construct fine-scale, sex-averaged recombination maps from contemporary patterns of linkage disequilibrium in nine geographically isolated wild house mouse populations, including multiple populations from each of three subspecies. Comparing maps between wild mouse populations and subspecies reveals several themes. First, we report weak fine- and broad-scale recombination map conservation across subspecies and populations, with genetic divergence offering no clear prediction for recombination map divergence. Second, most hotspots are unique to one population, an outcome consistent with minimal sharing of Prdm9 alleles between surveyed populations. Finally, by contrasting aggregate hotspot activity on the X versus autosomes, we uncover evidence for population-specific differences in the degree and direction of sex-dimorphism for recombination. Overall, our findings illuminate the variability of both the broad- and fine-scale recombination landscape in Mus musculus and underscore the functional impact of Prdm9 allelic variation in wild mouse populations.
Species existence and coexistence under nutrient enrichment in the Park Grass
Authors: Yao Qi , Feng Yanhao 
Published: June 2022

AbstractNumerous studies have shown that nutrient enrichment causes the loss of plant diversity in different grasslands across the globe. Thus far, three main hypotheses (niche dimension, competitive asymmetry, and soil acidification) have been proposed to account for this general phenomenon, but our knowledge of the underlying mechanisms remains rather vague. To reveal the cryptic mechanisms, we analyzed the famous long-term Park Grass Experiment (1856-) under modern coexistence theory by fitting Lotka-Volterra competition models with time-series data from the different treatments (15 different combinations of nutrient addition fully crossed with four levels of soil pH) to quantitatively test the three competing hypotheses. Supportive of the competitive asymmetry and soil acidification hypotheses, both nutrient addition and soil acidification overall decreased intrinsic population growth rates (r) and intensified competitive differences or asymmetries dramatically, which mostly favored grasses over forbs and legumes (and also forbs over legumes). These changes in r and competitive differences or asymmetries are generally consistent with the abundance changes of different functional groups following the various treatments. Moreover, the altered r (determining species existence) and competitive differences (affecting species coexistence) effectively explained the diversity loss and recovery (after nitrogen addition was withheld). However, while nutrient addition significantly decreased per-capita intra- and inter-specific competition (which indicates that belowground competition becomes less intense when soil nutrients are more abundant), it did not decrease niche differences as predicted, poorly supporting the niche dimension hypothesis. These findings advance our understanding of fundamental mechanisms driving the response of plant communities to nutrient deposition in nature.Significance StatementAn unresolved fundamental scientific mystery with the crucial applied value in ecology is what causes the general loss of biodiversity following nutrient enrichment in the Anthropocene. In this study, we combined the recent advance in coexistence theory with the longest-running fertilization experiment existing in the world to wrestle with this conundrum. Our major results, which highlight the critical role of both existence and coexistence, could help settle the debate between the three popular hypotheses and also, for the first time, provide quantitative explanations for the general findings in numerous nutrient-addition experiments. Our study shows the importance of applying modern coexistence theory to more quantitatively explain, predict and cope with the responses of ecological communities to global change factors in nature.