bluuebunny/crossref_metadata_2025_split huggingface dataset:
Dynamics of peripheral blood flow across sleep stages
Authors: Fan Zhiwei , Suzuki Yoko , Jiang Like , Okabe Satomi , Honda Shintaro , Endo Junki , Watanabe Takahiro , Abe Takashi 
Published: November 2021

AbstractStudy ObjectivesPulse rate variability (PRV) derived from peripheral blood flow has been reported as a surrogate parameter for heart rate variability (HRV). However, there are currently no studies reporting systematic comparisons of PRV with HRV in a normal sleep state. Whether PRV can provide similar information regarding sleep stages remains unclear. Peripheral blood flow may also be modulated differently across sleep stages. Thus, we aimed to investigate blood flow dynamics and compare PRV with HRV across sleep stages to see if blood flow can provide further information about sleep stages.MethodsWe performed electrocardiography and simultaneously measured blood flow from the right index finger and ear concha of 45 healthy participants (13 women; mean age, 22.5 ± 3.4 years) during one night of sleep. Time-domain, frequency-domain, and non-linear indices of PRV/HRV, and time- and frequencydomain blood flow parameters were calculated.ResultsFinger-PRV results showed similar patterns to HRV results for most parameters. Finger-blood flow parameters in the time and frequency domains also showed information about the different sleep stages. Further, both finger- and ear-blood flow results showed 0.2–0.3 Hz oscillations that varied with sleep stages, with a significant increase in N3, suggesting a modulation (of respiration) within this frequency band.ConclusionsThese results suggest that PRV can provide as much information as HRV for different sleep stages. Furthermore, the results show that blood flow + PRV could be more advantageous than HRV alone in the assessment of the sleep state and related autonomic nervous activity.Statement of SignificanceThe research provides comprehensive information on peripheral blood flow (BF) activity across sleep stages for the first time, as the major novelty of our work. The second contribution is a systematic study comparing BF-derived pulse rate variability (PRV) with heart rate variability across sleep stages in a normal sleep state. We believe that our work makes a significant contribution to the literature because it provides comprehensive information on the potential of BF+PRV as a new biomarker for assessing the sleep state. Further, this study contributes to developing a more convenient method of assessing the sleep state in the clinical and home/work setting.
Spinal cord injury reprograms muscle fibro-adipogenic progenitors to form heterotopic bones within muscles
Authors: Tseng Hsu-Wen , Girard Dorothée , Alexander Kylie A. , Millard Susan M , Torossian Frédéric , Anginot Adrienne , Fleming Whitney , Gueguen Jules , Goriot Marie-Emmanuelle , Clay Denis , Jose Beulah , Nowlan Bianca , Pettit Allison R. , Salga Marjorie , Genêt François , Le Bousse-Kerdilès Marie-Caroline , Banzet Sébastien , Levesque Jean-Pierre 
Published: November 2021

AbstractThe cells-of-origin of neurogenic heterotopic ossifications (NHO), which develop frequently in the periarticular muscles following spinal cord injuries (SCI) and traumatic brain injuries, remain unclear because the skeletal muscle harbors two progenitor cell populations: satellite cells (SCs) which are myogenic, and fibro-adipogenic progenitors (FAPs) which are mesenchymal. Lineage-tracing experiments using the Cre recombinase /LoxP system were performed in two mouse strains with the fluorescent protein ZsGreen specifically expressed in either SCs or FAPs in the skeletal muscles under the control of the Pax7 or Prrx1 gene promotors respectively. These experiments demonstrate that following a muscle injury, SCI causes the upregulation of PDGFRα on FAPs but not SCs and the failure of SCs to regenerate myofibers in the injured muscle, with instead reduced apoptosis and continued proliferation of muscle resident FAPs enabling their osteogenic differentiation into NHO. No cells expressing ZsGreen under the Prrx1 promoter were detected in the blood after injury suggesting that the cells-of-origin of NHO are locally derived from the injured muscle. We validated these findings in the human pathology using human NHO biopsies. PDGFRα+ mesenchymal cells isolated from the muscle surrounding NHO biopsies could develop ectopic human bones when transplanted into immunocompromised mice whereas CD56+ myogenic cells had a much lower potential. Therefore, NHO is a pathology of the injured muscle in which SCI reprograms FAPs to uncontrolled proliferation and differentiation into osteoblasts.
Mapping single-cell transcriptomes to copy number evolutionary trees
Authors: Ferreira Pedro F. , Kuipers Jack , Beerenwinkel Niko 
Published: November 2021

AbstractCancer arises and evolves by the accumulation of somatic mutations that provide a selective advantage. The interplay of mutations and their functional consequences shape the evolutionary dynamics of tumors and contribute to different clinical outcomes. In the absence of scalable methods to jointly assay genomic and transcriptomic profiles of the same individual cell, the two data modalities are usually measured separately and need to be integrated computationally. Here, we introduce SCATrEx, a statistical model to map single-cell gene expression data onto the evolutionary history of copy number alterations of the tumor. SCATrEx jointly assigns cancer cells assayed with scRNA-seq to copy number profiles arranged in a copy number aberration tree and augments the tree with clone-specific clusters. Our simulations show that SCATrEx improves over both state-of-the-art unsupervised clustering methods and cell-to-clone assignment methods. In an application to real data, we observe that SCATrEx finds inter-clone and intra-clone gene expression heterogeneity not detectable using other integration methods. SCATrEx will allow for a better understanding of tumor evolution by jointly analysing the genomic and transcriptomic changes that drive it.
CDK1 and PLK1 cooperate to regulate BICD2, dynein activation and recruitment to the nucleus as well as centrosome separation in G2/M
Authors: Gallisà-Suñé Núria , Sànchez-Fernàndez-de-Landa Paula , Zimmermann Fabian , Serna Marina , Paz Joel , Regué Laura , Llorca Oscar , Lüders Jens , Roig Joan 
Published: November 2021

SummaryThe activity of dynein is regulated by a number of adaptors that mediate its interaction with dynactin, effectively activating the motor complex while also connecting it to different cargos. The regulation of adaptors is consequently central to dynein physiology, but remains largely unexplored. We now describe that one of the best-known dynein adaptors, BICD2, is effectively activated through phosphorylation. In G2 phosphorylation of BICD2 by CDK1 promotes its interaction with PLK1. In turn, PLK1 phosphorylation of a single residue in the N-terminus of BICD2 results in a conformational change that facilitates interaction with dynein and dynactin, allowing the formation of active motor complexes. BICD2 phosphorylation is central for dynein recruitment to the nuclear envelope, centrosome tethering to the nucleus and centrosome separation in G2/M. This work reveals adaptor activation through phosphorylation as crucial for the spatiotemporal regulation of dynein activity.
Genome-wide association study of cerebellar volume
Authors: Tissink E.P. , de Lange S.C. , Savage J.E. , Wightman D.P. , Kelly K.M. , Nagel M. , van den Heuvel M.P. , Posthuma D. 
Published: November 2021

AbstractCerebellar volume is highly heritable and associated with neurodevelopmental and neurodegenerative disorders. Understanding the genetic architecture of cerebellar volume may improve our insight into these disorders. This study aims to investigate the convergence of cerebellar volume genetic associations in close detail. A genome-wide associations study for cerebellar volume was performed in a sample of 27,486 individuals from UK Biobank, resulting in 29 genome-wide significant loci and a SNP heritability of 39.82%. We pinpoint variants that have effects on amino acid sequence or cerebellar gene-expression. Additionally, 85 genome-wide significant genes were detected and tested for convergence onto biological pathways, cerebellar cell types or developmental stages. Local genetic correlations between cerebellar volume and neurodevelopmental and neurodegenerative disorders reveal shared loci with Parkinson’s disease, Alzheimer’s disease and schizophrenia. These results provide insights into the heritable mechanisms that contribute to developing a brain structure important for cognitive functioning and mental health.
Pronounced uptake and metabolism of organic substrates by diatoms revealed by pulse-labeling metabolomics
Authors: Meyer Nils , Rydzyk Aljoscha , Pohnert Georg 
Published: November 2021

AbstractDiatoms contribute as a dominant group of microalgae to approximately 20% of the global carbon fixation. In the plankton, these photosynthetic algae are exposed to a plethora of metabolites, especially when competing algae are lysed. It is well established that diatoms can take up specific metabolites, such as vitamins, amino acids as nitrogen source, or dimethylsulfoniopropoionate to compensate for changes in water salinity. It is, however, unclear to which extent diatoms take up other organic resources and if these are incorporated into the cell’s metabolism. Here, we ask about the general scope of uptake of metabolites from competitors. Using labeled metabolites released during lysis of algae grown under a 13CO2 atmosphere, we show that the cosmopolitan diatom Chaetoceros didymus takes up organic substrates with little bias and remarkable efficiency. The newly developed pulse label/ mass spectrometry metabolomics approach reveals that polarity and molecular weight has no detectable influence on uptake efficiency. We also reveal that the taken-up pool of metabolites is partly maintained unaltered within the cells but is also subject to catabolic and anabolic transformation. One of the most dominant phytoplankton groups is thus substantially competing with other heterotrophs for organic material, suggesting that the observed absorbotrophy may substantially impact organic material fluxes in the oceans. Our findings call for the refinement of our understanding of competition in the plankton.SignificanceThis study demonstrates a remarkably universal uptake of organic substrates by diatoms. The extent to which one of the most dominant phytoplankton groups is competing for organic material in the plankton is documented by novel pulse labeling metabolomics studies. Our results show that uptake of organic material by the photosynthetic microalgae occurs with remarkably little bias. Taken-up metabolites are further transformed by the diatoms or directly incorporated into the algal metabolome. Our study calls for a re-consideration of organic material fluxes in the oceans. Also, our understanding of competition in the plankton will have to be refined. The broader implications for the cycling of resources in plankton communities are discussed within this work.
A lateral protrusion latticework connects neuroepithelial cells and is regulated during neurogenesis
Authors: Kasioulis Ioannis , Dady Alwyn , James John , Prescott Alan , Halley Pamela A. , Storey Kate G. 
Published: November 2021

AbstractDynamic contacts between cells within the developing neuroepithelium are poorly understood but play important roles in cell and tissue morphology and cell signalling. Here, using live-cell imaging and electron microscopy we reveal multiple protrusive structures in neuroepithelial apical endfeet of the chick embryonic spinal cord, including sub-apical protrusions that extend laterally within the tissue, and observe similar structures in human neuroepithelium. We characterise the dynamics, shape, and cytoskeleton of these lateral protrusions and distinguish these structures from cytonemes/filopodia and tunnelling nanotubes. We demonstrate that lateral protrusions form a latticework of membrane contacts between non-adjacent cells, depend on actin but not microtubule dynamics and provide a lamellipodial-like platform for further extending fine actin-dependent filipodia. We find that lateral protrusions depend on the actin-binding protein WAVE1: mutant-WAVE1 misexpression attenuated protrusion and generated a round-ended apical endfoot morphology. However, this did not alter apico-basal cell polarity nor reduce tissue integrity. During normal neuronal delamination sub-apical protrusions were withdrawn, but mutant-WAVE1-induced precocious protrusion loss was insufficient to trigger neurogenesis. This study uncovers a new form of cell-cell contact within the developing neuroepithelium regulation of which prefigures neuronal delamination.
Rapid ecological and evolutionary divergence during a poleward range expansion
Authors: Sheffer Monica M. , Schulze Brian , Zander Linda , Mouginot Pierick , Naef Thomas , Lalk Michael , Wurster Martina , Ahrend Clara , Kreyling Jürgen , Gillespie Rosemary G. , Hoff Katharina J. , Prost Stefan , Krehenwinkel Henrik , Uhl Gabriele 
Published: November 2021

AbstractIn response to climate change, a northward range expansion has been observed in many species. The wasp spider,Argiope bruennichi, has expanded from its historic range in the Mediterranean (“core”), now reaching as far as the Baltic States and Scandinavia (“edge”), even faster than the pace of climate change. We explored life history traits, adult phenotypes, offspring cold tolerance, and genomic patterns across the European range ofA. bruennichi, and found origin-, environment- and life stage-specific responses to the cold northern climate. Wasp spiders have shifted their phenology at the edge, with females maturing earlier and at a smaller size, but maintaining similar pigmentation, clutch sizes, and hatching success compared to the core region. Using a reciprocal common garden experiment on overwintering offspring from the core and edge, we found evidence for genetic adaptation and considerable phenotypic plasticity. Overwintering survival was lower under the cold winter treatment for spiderlings from both origins. However, the edge-origin spiderlings that survived the winter had lower lethal temperatures and enhanced supercooling ability with reduced phenotypic plasticity in supercooling points compared to core spiderlings, while the chill coma recovery time was similar. Metabolomic analysis revealed accumulations of amino acids and myo-inositol in the cold winter treatment, particularly in spiderlings from the edge population, suggesting a role of these metabolites in improving cold tolerance. Genotype-environment tests showed strong genetic association across the genome to seasonality and minimum winter temperature. The population genomic analysis across the European range splitsA. bruennichiinto two distinct genetic clusters through the center of Germany, which roughly aligns with turnover from an oceanic to continental climate zone, complementing the genotype-environment test results. Overall, our study highlights the importance of integrating data on phenological shifts, changes in life-history, and life stage-specific phenotypic plasticity and genetic adaptation to understand the impacts of range expansions and shifts. The nuanced processes of acclimation and adaptation we uncovered advocate for holistic investigations of evolutionary fitness and fitness-related traits in the context of organismal responses to novel and changing environments.
Microthrombocytopenia caused by impaired microtubule stability in RhoB-deficient mice
Authors: Englert Maximilian , Aurbach Katja , Gerber Annika , Heib Tobias , Becker Isabelle C. , Wackerbarth Lou M. , Kusch Charly , Baig Ayesha A. , Dütting Sebastian , Knaus Ulla G. , Stigloher Christian , Nieswandt Bernhard , Pleines Irina , Nagy Zoltan 
Published: November 2021

ABSTRACTMegakaryocytes are large cells in the bone marrow, which give rise to blood platelets. Platelet biogenesis involves megakaryocyte maturation, the localization of mature cells in close proximity to bone marrow sinusoids and the formation of protrusions, which are shed into the circulation. Rho GTPases play important roles in platelet biogenesis and function. RhoA-deficient mice display macrothrombocytopenia and a striking mislocalization of megakaryocytes into bone marrow sinusoids and a specific defect in G-protein signaling in platelets. However, the role of the closely related protein RhoB in megakaryocytes or platelets remains unknown. In this study, we show that, in contrast to RhoA deficiency, genetic ablation of RhoB in mice results in microthrombocytopenia (decreased platelet count and size). RhoB-deficient platelets displayed mild functional defects predominantly upon induction of the collagen/glycoprotein VI pathway. Megakaryocyte maturation and localization within the bone marrow, as well as actin dynamics were not affected in the absence of RhoB. However, in vitro generated proplatelets revealed pronouncedly impaired microtubule organization. Furthermore, RhoB-deficient platelets and megakaryocytes displayed selective defects in microtubule dynamics/stability, correlating with pronouncedly reduced levels of acetylated α-tubulin. Our findings imply that absence of this tubulin posttranslational modification results in decreased microtubule stability leading to microthrombocytopenia in RhoB-deficient mice. Our data thus points to specifically impaired microtubule - but not actin - dynamics as a general mechanism underlying the manifestation of microthrombocytopenia in vivo. We furthermore demonstrate that RhoA and RhoB have specific, non-redundant functions in the megakaryocyte lineage.KEY POINTSRhoB-deficient mice display microthrombocytopeniaRhoB has different functions in the megakaryocyte lineage than RhoA and regulates microtubule dynamics
Prolonged and extended impacts of SARS-CoV-2 on the olfactory neurocircuit
Authors: Kishimoto-Urata Megumi , Urata Shinji , Kagoya Ryoji , Imamura Fumiaki , Nagayama Shin , Reyna Rachel A. , Maruyama Junki , Yamasoba Tatsuya , Kondo Kenji , Hasegawa-Ishii Sanae , Paessler Slobodan 
Published: November 2021

AbstractThe impact of SARS-CoV-2 on the olfactory pathway was studied over several time points using Syrian golden hamsters. We found an incomplete recovery of the olfactory sensory neurons, prolonged activation of glial cells in the olfactory bulb, and a decrease in the density of dendritic spines within the hippocampus. These data may be useful for elucidating the mechanism underlying long-lasting olfactory dysfunction and cognitive impairment as a post-acute COVID-19 syndrome.
Diverse pathogens activate the host RIDD pathway to subvert BLOS1-directed immune defense
Authors: Wells Kelsey , He Kai , Pandey Aseem , Cabello Ana , Zhang Dong-Mei , Yang Jing , Gomez Gabriel , Liu Yue , Chang Hao-Wu , Li Xue-Qing , Zhang Hao , da Costa Luciana Fachini , Metz Richard P. , Johnson Charles D. , Martin Cameron , Skrobarczyk Jill , Berghman Luc R. , Patrick Kristin , Leibowitz Julian , Rice-Ficht Allison , Sze Sing-Hoi , Qian Xiaoning , Qin Qing-Ming , Ficht Thomas A. , de Figueiredo Paul 
Published: November 2021

AbstractThe phagocytosis and destruction of pathogens in lysosomes constitute central elements of innate immune defense. Here, we show that Brucella, the causative agent of brucellosis, the most prevalent bacterial zoonosis globally, subverts this immune defense pathway by activating regulated IRE1α-dependent decay (RIDD) of mRNAs encoding BLOS1, a protein that promotes endosome-lysosome fusion. RIDD-deficient cells and mice harboring a RIDD-incompetent variant of IRE1α were resistant to infection. Non-functional Blos1 struggled to assemble the BLOC-1-related complex (BORC), resulting in differential recruitment of BORC-related lysosome trafficking components, perinuclear trafficking of Brucella-containing vacuoles (BCVs), and enhanced susceptibility to infection. The RIDD-resistant Blos1 variant maintains the integrity of BORC and a higher-level association of BORC-related components that promote centrifugal lysosome trafficking, resulting in enhanced BCV peripheral trafficking and lysosomal-destruction, and resistance to infection. These findings demonstrate that host RIDD activity on BLOS1 regulates Brucella intracellular parasitism by disrupting BORC-directed lysosomal trafficking. Notably, coronavirus MHV also subverted the RIDD-BLOS1 axis to promote intracellular replication. Our work therefore establishes BLOS1 as a novel immune defense factor whose activity is hijacked by diverse pathogens.
A Trypanosoma brucei orphan kinesin employs a convergent microtubule organization strategy to complete cytokinesis
Authors: Sladewski Thomas E. , Campbell Paul C. , Billington Neil , D’Ordine Alexandra , de Graffenried Christopher L. 
Published: November 2021

AbstractMany single-celled eukaryotes have complex cell morphologies defined by cytoskeletal elements comprising microtubules arranged into higher-order structures. Trypanosoma brucei (T. brucei) cell polarity is mediated by a parallel array of microtubules that underlie the plasma membrane and define the auger-like shape of the parasite. The subpellicular array must be partitioned and segregated using a microtubule-based mechanism during cell division. We previously identified an orphan kinesin, KLIF, that localizes to the division plane and is essential for the completion of cytokinesis. To gain mechanistic insight into how this novel kinesin functions to complete cleavage furrow ingression, we characterized the biophysical properties of the KLIF motor domain in vitro. We found that KLIF is a non-processive dimeric kinesin that dynamically crosslinks microtubules. Microtubules crosslinked in an antiparallel orientation are translocated relative to one another by KLIF, while microtubules crosslinked parallel to one another remain static, resulting in the formation of organized parallel bundles. In addition, we found that KLIF stabilizes the alignment of microtubule plus ends. These features provide a mechanistic understanding for how KLIF functions to form a new pole of aligned microtubule plus ends that defines the shape of the new posterior, which is a unique requirement for the completion of cytokinesis in T. brucei.