bluuebunny/crossref_metadata_2025_split huggingface dataset:
The association between family structure and adolescent physical activity levels: A systematic review of literature published since 2010
Authors: Mylona Elena , Kletter Maartje , Jones Helen M , Murphy Marie , Lampard Richard , Oyebode Oyinlola 
Published: July 2023

AbstractBackgroundAdolescent physical activity is influenced by biological, psychological, sociocultural, and environmental factors; however, no review has yet explored the effect of family structure (usually defined based on the relationships between people living in a household) on adolescent physical activity levels.MethodsDatabases MEDLINE, EMBASE, Web of Science, PsycINFO, CINAHL, and Sociological Abstracts were searched for peer-reviewed studies with a quantitative component published since 2010, with no restrictions on language, country, and year of data collection. Study screening, data extraction, and quality assessment occurred in duplicate. SWiM guidelines guided the narrative synthesis. PROSPERO protocol CRD42020221090.ResultsThirty studies met inclusion criteria: 17 looked at global physical activity, 13 at leisure physical activity, and sport participation. All studies used cross-sectional designs and 27 assessed outcomes through a survey. Sixteen (10 of good quality) reported a significant association between family structure and adolescent physical activity. Of these, three did not specify the direction of this association while nine found adolescents in ‘traditional’ (two-parent) families were more physically active compared with other family structures. This association was stronger in studies of leisure- time physical activity. Two studies reported that adolescents with single mothers achieve more physical activity than adolescents living with neither parent. Two studies, focused on school physical exercise classes and active transport, found adolescents in single-parent households engaged in more physical activity than those living with two parents.ConclusionHigh-quality accelerometery, time diary, and longitudinal studies are needed to investigate the effect of family structure on adolescent physical activity and health sequelae. An improved understanding of social determinants of adolescent physical activity could inform health promotion strategies.
Cortical Adaptation in the Delta Band in People with Post-Stroke Aphasia during Picture Naming
Authors: Renaud-D’Ambra Malo , Aksenov Alexandre , Mesnildrey Quentin , Hartwigsen Gesa , Volpert Vitaly , Beuter Anne 
Published: July 2023

AbstractThis study explores differences in spatiotemporal cortical dynamics between five people with chronic post-stroke aphasia and five healthy subjects. Electroencephalography was recorded during picture naming in both groups.Frequency-specific Global Field Power (GFP) results showed that the delta band has higher power to discriminate between healthy subjects and people with aphasia (PWA) than theta and alpha bands. EEG topologies computed at the time of GFP peaks in the delta band revealed strong activation oscillating between posterior and anterior areas in PWA. On the other hand, EEG topologies from healthy subjects were variable.Then, Spatial ERP (S-ERP) were developed to add spatial resolution to classical ERP analysis. S-ERP and associated analyses confirmed the previously observed oscillatory pattern in the delta frequency band among PWA during picture naming. This oscillating pattern was alternating between occipital and prefrontal areas with almost opposite phases, a characteristic not observed in healthy subjects. In addition, all PWA performed well on the picture naming task, suggesting that this oscillating pattern may be a cortical adaptation mechanism enabling them to succeed.The observation of large-scale oscillating delta activity across the scalp in all post-stroke subjects who have substantially recovered from aphasia holds the potential to inspire innovative rehabilitation methods employing non-invasive brain stimulation techniques such as transcranial alternating current stimulation (tACS).
New variants in the Chloroplast Genome Sequence of two Colombian individuals of the Cedar timber species (Cedrela odorataL.), using long read Oxford Nanopore Technology
Authors: Simbaqueba Jaime , Garzón-Martínez Gina A. , Castano Nicolas 
Published: July 2023

AbstractThe plant speciesCedrela odoratahas been largely exploited in the timber industry due to the high demand of its wood. Therefore,C. odorata, has been considered as a vulnerable species since 1994, with the Convention on International Trade in Endangered Species of Wild Fauna and Flora (CITES).C. odoratais one of the key timber species included in the management and conservation plans in Colombia. These plans include the study of local populations by developing genetic resources for the species. In this study, two novel chloroplast (cp) genomes have been generated using the MinION long read sequencing technology. The new cp assemblies were compared with other cp genomes for the species, supporting previous hypothesis of intraspecific diversity associated to their place of origin. Furthermore, the cp genomes were screened for sequence variants (SV) and a total of 16 SNPs were identified, presumably unique to populations of the amazon region in Colombia. Here, the first cp genome sequences ofC. odoratafrom Colombian individuals represent novel and valuable genomic resources for the species suitable for DNA fingerprinting and DNA barcoding applications.
Alzheimer’s disease associated isoforms of human CD33 distinctively modulate microglial cell responses in 5XFAD mice
Authors: Eskandari-Sedighi Ghazaleh , Crichton Madeline , Zia Sameera , Gomez Erik , St. Laurent Chris D. , Cortez Leonardo M. , Patel Zain H. , Sidhu Gaurav , Sarkar Susmita , Aghanya Vivian , Sim Valerie L. , Tan Qiumin , Julien Olivier , Plemel Jason R. , Macauley Matthew S. 
Published: July 2023

AbstractMicroglia play diverse pathophysiological roles in Alzheimer’s disease (AD), with genetic susceptibility factors skewing microglial cell function to influence AD risk. CD33 is an immunomodulatory receptor associated with AD susceptibility through a single nucleotide polymorphism that modulates mRNA splicing, skewing protein expression from a long protein isoform (CD33M) to a short isoform (CD33m). Understanding how human CD33 isoforms differentially impact microglial cell functionin vivohas been challenging due to functional divergence of CD33 between mice and humans. We address this challenge by studying transgenic mice expressing either of the human CD33 isoforms crossed with the 5XFAD mouse model of amyloidosis and find that human CD33 isoforms have opposing effects on the response of microglia to amyloid-β (Aβ) deposition. Mice expressing CD33M have increased Aβ levels, mo7re diffuse plaques, fewer disease-associated microglia, and more dystrophic neurites compared to control 5XFAD mice. Conversely, CD33m promotes plaque compaction and microglia-plaque contacts, and minimizes neuritic plaque pathology, highlighting an AD protective role for this isoform. Protective phenotypes driven by CD33m are detected at an earlier timepoint compared to the more aggressive pathology in CD33M mice that appears at a later timepoint, suggesting that CD33m has a more prominent impact on microglia cell function at earlier stages of disease progression. In addition to divergent roles in modulating phagocytosis, scRNAseq and proteomics analyses demonstrate that CD33m+microglia upregulate nestin, an intermediate filament involved in cell migration, at plaque contact sites. Overall, our work provides new functional insights into how CD33, as a top genetic susceptibility factor for AD, modulates microglial cell function.
Distinct features of the regenerating heart uncovered through comparative single-cell profiling
Authors: Carey Clayton M. , Hollins Hailey L. , Schmid Alexis V. , Gagnon James A. 
Published: July 2023

ABSTRACTAdult humans respond to heart injury by forming a permanent scar, yet other vertebrates are capable of robust and complete cardiac regeneration. Despite progress towards characterizing the mechanisms of cardiac regeneration in fish and amphibians, the large evolutionary gulf between mammals and regenerating vertebrates complicates deciphering which cellular and molecular features truly enable regeneration. To better define these features, we compared cardiac injury responses in zebrafish and medaka, two fish species that share similar heart anatomy and common teleost ancestry but differ in regenerative capability. We used single-cell transcriptional profiling to create a time-resolved comparative cell atlas of injury responses in all major cardiac cell types across both species. With this approach, we identified several key features that distinguish cardiac injury response in the non-regenerating medaka heart. By comparing immune responses to injury, we found altered cell recruitment and a distinct pro-inflammatory gene program in medaka leukocytes, and an absence of the injury-induced interferon response seen in zebrafish. In addition, we found a lack of pro-regenerative signals, including nrg1 and retinoic acid, from medaka endothelial and epicardial cells. Finally, we identified alterations in the myocardial structure in medaka, where they lack embryonic-like primordial layer cardiomyocytes, and fail to employ a cardioprotective gene program shared by regenerating vertebrates. Our findings reveal notable variation in injury response across nearly all major cardiac cell types in zebrafish and medaka, demonstrating how evolutionary divergence influences the hidden cellular features underpinning regenerative potential in these seemingly similar vertebrates.
ColabSeg: An interactive tool for editing, processing, and visualizing membrane segmentations from cryo-ET data
Authors: Siggel Marc , Jensen Rasmus K. , Mahamid Julia , Kosinski Jan 
Published: July 2023

AbstractCellular cryo-electron tomography (cryo-ET) has emerged as a key method to unravel the spatial and structural complexity of cells in their near-native state at unprecedented molecular resolution. To enable quantitative analysis of the complex shapes and morphologies of lipid membranes, the noisy three-dimensional (3D) volumes must be segmented. Despite recent advances, this task often requires considerable user intervention to curate the resulting seg-mentations. Here, we present ColabSeg, a Python-based tool for processing, visualizing, cleaning, and fitting membrane segmentations from cryo-ET data for downstream analysis. ColabSeg makes many well-established algorithms for point-cloud processing easily available to the broad community of structural biologists for applications in cryo-ET through its graphical user interface (GUI). We demonstrate the usefulness of the tool with a range of use cases and biological examples. Finally, for a largeMycoplasma pneumoniaedataset of 50 tomograms, we show how ColabSeg enables high-throughput membrane segmentation, which can be used as valuable training dataset for fully automated convolutional neural network (CNN)-based segmentation.
Spontaneous single-nucleotide substitutions and microsatellite mutations have distinct distributions of fitness effects
Authors: Plavskin Yevgeniy , de Biase Maria Stella , Ziv Naomi , Janská Libuše , Zhu Yuan O. , Hall David W. , Schwarz Roland F. , Tranchina Daniel , Siegal Mark L. 
Published: July 2023

AbstractThe fitness effects of new mutations determine key properties of evolutionary processes. Beneficial mutations drive evolution, yet selection is also shaped by the frequency of small-effect deleterious mutations, whose combined effect can burden otherwise adaptive lineages and alter evolutionary trajectories and outcomes in clonally evolving organisms such as viruses, microbes, and tumors. The small effect sizes of these important mutations have made accurate measurements of their rates difficult. In microbes, assessing the effect of mutations on growth can be especially instructive, as this complex phenotype is closely linked to fitness in clonally evolving organisms. Here, we perform high-throughput time-lapse microscopy on cells from mutation-accumulation strains to precisely infer the distribution of mutational effects on growth rate in the budding yeast,Saccharomyces cerevisiae. We show that mutational effects on growth rate are overwhelmingly negative, highly skewed towards very small effect sizes, and frequent enough to suggest that deleterious hitchhikers may impose a significant burden on evolving lineages. By using lines that accumulated mutations in either wild-type or slippage repair-defective backgrounds, we further disentangle the effects of two common types of mutations, single-nucleotide substitutions and simple sequence repeat indels, and show that they have distinct effects on yeast growth rate. Although the average effect of a simple sequence repeat mutation is very small (∼0.3%), many do alter growth rate, implying that this class of frequent mutations has an important evolutionary impact.
Systemic Lupus Erythematosus Serum Stimulation of Human Intestinal Organoids Induces Changes in Goblet Cell Differentiation and Mitochondrial Fitness
Authors: Hensel Inga Viktoria , Éliás Szabolcs , Steinhauer Michelle , Stoll Bilgenaz , Benfatto Salvatore , Merkt Wolfgang , Krienke Stefan , Lorenz Hanns-Martin , Haas Jürgen , Wildeman Brigitte , Resnik-Docampo Martin 
Published: July 2023

AbstractHuman intestinal epithelial cells are the interface between potentially harmful luminal content and basally residing immune cells. Their role is not only nutrient absorption but also the formation of a tight monolayer that constantly secrets mucus creating a multi-layered protective barrier. Alterations in this barrier can lead to increased gut permeability which is frequently seen in individuals with chronic extraintestinal autoimmune diseases, such as Systemic Lupus Erythematosus (SLE). Despite recent advances in identifying alterations in gut microbiota composition in SLE patients, not much attention has been given to the epithelial barrier itself. To date, it remains largely unexplored which role and function intestinal epithelial cells have in SLE pathology. Here, we present a unique near-physiologicin vitromodel specifically designed to examine the effects of SLE on the epithelial cells. We utilize human colon organoids that are stimulated with serum obtained from SLE patients. Combining bulk and scRNA transcriptomic analysis with functional assays revealed that SLE serum stimulation induced a unique expression profile marked by a type I interferon gene signature. Additionally, organoids exhibited decreased mitochondrial fitness, alterations in mucus composition and imbalanced cellular composition. Similarly, transcriptomic analysis of SLE human colon biopsies revealed a downregulation of epithelial secretory markers. Our work uncovers a crucial connection between SLE and intestinal homeostasis that might be promotedin vivothrough the blood, offering insights into the causal connection of barrier dysfunction and autoimmune diseases.
Mimicking of tau hyperphosphorylation in GABAergic motoneurons ofC. elegansinduces severe peripheral and neuronal alterations
Authors: Labarre Audrey , Schramm Émilien , Pilliod Julie , Boyer Samuel , Lapointe Marianne , Maios Claudia , Leclerc Nicole , Parker J. Alex 
Published: July 2023

AbstractIn several neurodegenerative diseases including Alzheimer’s disease (AD), tau, a microtubule-associated protein (MAP) enriched in the axon, becomes hyperphosphorylated, detaches from microtubules, redistributes to the somato-dendritic compartment and self-aggregates. The mechanisms leading to neuronal dysfunction and death by tau pathology remain to be fully elucidated.C. eleganshas been successfully used by several groups including ours to identify mechanisms involved in neurodegeneration. We generated three strains, one overexpressing wild-type human tau (WT Tau), one a tau mutant mimicking hyperphosphorylation (hyperP Tau) and one preventing phosphorylation (hypoP Tau) in GABA motor neurons. A significant reduction of body size and egg laying was noted in these tau strains. Starting at day 1, we found that the worms overexpressing hyperP Tau were smaller than the N2 control strain and the worms either overexpressing WT Tau or hypoP Tau. Starting at day 5, the worms overexpressing WT Tau were smaller than control and the worms overexpressing hypoP Tau. Egg laying was reduced in both hyperP Tau and WT Tau worms. Survival was only decreased in WT Tau worms. Motility deficits were also observed. For age-dependent paralysis, a difference was noted between control and hyperP Tau. Swimming activity and speed were increased in hypoP Tau and decreased in hyperP Tau strains. Axonal integrity was altered in all tau strains. In the case of synaptic activity, at day 1, it was increased in the hypoP Tau strain and decreased in the hyperP Tau one. Collectively, our data revealed that overexpression of tau exerted neuronal and peripheral defects indicating that tau dysfunction could affect cell-cell communication.
Mapping interactions between disordered regions reveals promiscuity in biomolecular condensate formation
Authors: Gilat Atar , Dubrueil Benjamin , Levy Emmanuel D. 
Published: July 2023

ABSTRACTIntrinsically-disordered regions (IDRs) promote intracellular phase separation and the formation of biomolecular condensates through interactions encoded in their primary sequence. While these condensates form spatially distinct assemblies in cells, it is unclear whether such specificity can be conferred by IDRs alone. Indeed, IDRs exhibit high conformational flexibility whereas specificity in protein recognition is generally associated with well-defined 3D structures. To characterize IDR-IDR interactions and assess their ability to mediate self-specific partitioning, we developed a synthetic system of Multivalent IDRs forming Constitutive DROPlets (micDROP). We investigated ten natural IDRs that underwent phase separation inmicDROP. These IDRs exhibited a wide range of saturation concentrationsin vivo, which correlated well with their total sequence stickiness. We then probed IDR-IDR specificity by co-expressing pairs of IDRs fused to homologous scaffolds that did not co-assemble. We observed a high degree of promiscuity, particularly among IDRs from the proteins Ddx4, DYRK3, ERα, FUS, hnRNPA1, HspB8, RBM14 and TAF15, whereas TDP43 and UBQ2 formed spatially distinct condensates regardless of their partner. Further investigation revealed the short and conserved α-helical segment of TDP43’s IDR was governing its specific self-recognition. Our findings imply that IDRs can tune their phase separation propensity through sequence composition, while their formation of discrete condensates likely requires additional cellular or structural determinants.Abstract Figure
Strengthening E-cadherin adhesion via antibody mediated binding stabilization
Authors: Xie Bin , Xu Shipeng , Schecterson Leslayann , Gumbiner Barry M. , Sivasankar Sanjeevi 
Published: July 2023

SummaryE-cadherins (Ecads) are a crucial cell-cell adhesion protein with tumor suppression properties. Ecad adhesion can be enhanced by the monoclonal antibody 66E8, which has potential applications in inhibiting cancer metastasis. However, the biophysical mechanisms underlying 66E8 mediated adhesion strengthening are unknown. Here, we use molecular dynamics simulations, site directed mutagenesis and single molecule atomic force microscopy experiments to demonstrate that 66E8 strengthens Ecad binding by stabilizing the primary Ecad adhesive conformation: the strand-swap dimer. By forming electrostatic interactions with Ecad, 66E8 stabilizes the swapped β-strand and its hydrophobic pocket and impedes Ecad conformational changes, which are necessary for rupture of the strand-swap dimer. Our findings identify fundamental mechanistic principles for strengthening of Ecad binding using monoclonal antibodies.
Modeling the Correlation betweenZandBin an X-ray Crystal Structure Refinement
Authors: Buscagan Trixia M. , Rees Douglas C. 
Published: July 2023

AbstractWe have examined how the refinedB-factor changes as a function ofZ(the atomic number of a scatterer) at the sulfur site of the [4Fe:4S] cluster of the nitrogenase iron protein by refinement. A simple model is developed that quantitatively captures the observed relationship betweenZandB, based on a Gaussian electron density distribution with a constant electron density at the position of the scatterer. From this analysis, the fractional changes inBandZare found to be similar. The utility ofB-factor refinement to potentially distinguish atom types reflects theZdependence of X-ray atomic scattering factors; the weaker dependence of electron atomic scattering factors onZimplies that distinctions between refined values ofBin an electron scattering structure will be less sensitive to the atomic identity of a scatterer than for the case with X-ray-diffraction. This behavior provides an example of the complementary information that can be extracted from different types of scattering studies.
Replication Protein A1 is essential for DNA damage repair during mammalian oogenesis
Authors: Miao Xiaosu , Guo Rui , Williams Andrea , Lee Catherine , Ma Jun , Wang P. Jeremy , Cui Wei 
Published: July 2023

AbstractPersistence of unrepaired DNA damage in oocytes is detrimental and may cause genetic aberrations, miscarriage, and infertility. RPA, an ssDNA-binding complex, is essential for various DNA-related processes. Here we report that RPA plays a novel role in DNA damage repair during postnatal oocyte development after meiotic recombination. To investigate the role of RPA during oogenesis, we inactivated RPA1 (replication protein A1), the largest subunit of the heterotrimeric RPA complex, specifically in oocytes using two germline-specificCredrivers (Ddx4-CreandZp3-Cre). We find that depletion of RPA1 leads to the disassembly of the RPA complex, as evidenced by the absence of RPA2 and RPA3 in RPA1-deficient oocytes. Strikingly, severe DNA damage occurs in RPA1-deficient GV-stage oocytes. Loss of RPA in oocytes triggered the canonical DNA damage response mechanisms and pathways, such as activation of ATM, ATR, DNA-PK, and p53. In addition, the RPA deficiency causes chromosome misalignment at metaphase I and metaphase II stages of oocytes, which is consistent with altered transcript levels of genes involved in cytoskeleton organization in RPA1-deficient oocytes. Absence of the RPA complex in oocytes severely impairs folliculogenesis and leads to a significant reduction in oocyte number and female infertility. Our results demonstrate that RPA plays an unexpected role in DNA damage repair during mammalian folliculogenesis.
MEILB2-BRME1 forms a V-shaped DNA clamp upon BRCA2-binding in meiotic recombination
Authors: Gurusaran Manickam , Zhang Jingjing , Zhang Kexin , Shibuya Hiroki , Davies Owen R. 
Published: July 2023

AbstractDNA double-strand break repair by homologous recombination has a specialised role in meiosis by generating crossovers that enable the formation of haploid germ cells. This requires meiosis-specific MEILB2-BRME1, which interacts with BRCA2 to facilitate loading of recombinases onto resected DNA ends. Here, we report the crystal structure of the MEILB2-BRME1 2:2 core complex, revealing a parallel four-helical assembly that recruits BRME1 to meiotic double-strand breaksin vivo. It forms an N-terminal β-cap that binds to DNA, and a MEILB2 coiled-coil that bridges to C-terminal ARM domains. Upon BRCA2-binding, MEILB2-BRME1 2:2 complexes dimerize into a V-shaped 2:4:4 complex, with rod-like MEILB2-BRME1 components arranged at right-angles. The β-caps located at the tips of the MEILB2-BRME1 limbs are separated by 25 nm, allowing them to bridge between DNA molecules. Thus, we propose that BRCA2 induces MEILB2-BRME1 to function as a DNA clamp, connecting resected DNA ends or homologous chromosomes to facilitate meiotic recombination.