bluuebunny/crossref_metadata_2025_split huggingface dataset:
Anatomy of digital contact tracing: role of age, transmission setting, adoption and case detection
Authors: Moreno López Jesús A. , García Beatriz Arregui , Bentkowski Piotr , Bioglio Livio , Pinotti Francesco , Boëlle Pierre-Yves , Barrat Alain , Colizza Vittoria , Poletto Chiara 
Published: July 2020

AbstractThe efficacy of digital contact tracing against COVID-19 epidemic is debated: smartphone penetration is limited in many countries, non-uniform across age groups, with low coverage among elderly, the most vulnerable to SARS-CoV-2. We developed an agent-based model to precise the impact of digital contact tracing and household isolation on COVID-19 transmission. The model, calibrated on French population, integrates demographic, contact-survey and epidemiological information to describe the risk factors for exposure and transmission of COVID-19. We explored realistic levels of case detection, app adoption, population immunity and transmissibility. Assuming a reproductive ratio R = 2.6 and 50% detection of clinical cases, a ~20% app adoption reduces peak incidence by ~35%. With R = 1.7, >30% app adoption lowers the epidemic to manageable levels. Higher coverage among adults, playing a central role in COVID-19 transmission, yields an indirect benefit for elderly. These results may inform the inclusion of digital contact tracing within a COVID-19 response plan.
Theta and gamma connectivity is linked with affective and cognitive symptoms in Parkinson’s disease
Authors: Iyer Kartik K. , Au Tiffany R. , Angwin Anthony J. , Copland David A. , Dissanayaka Nadeeka N. 
Published: July 2020

AbstractBackgroundThe progression of Parkinson’s disease (PD) can often exacerbate symptoms of depression, anxiety, and/or cognitive impairment. In this study, we explore the possibility that multiple brain network responses are associated with symptoms of depression, anxiety and cognitive impairment in PD. This association is likely to provide insights into a single multivariate relationship, where common affective symptoms occurring in PD cohorts are related with alterations to electrophysiological response.Methods70 PD patients and 21 healthy age-matched controls (HC) participated in a high-density electroencephalography (EEG) study. Functional connectivity differences between PD and HC groups of oscillatory activity at rest and during completion of an emotion-cognition task were examined to identify key brain oscillatory activities. A canonical correlation analysis (CCA) was applied to identify a putative multivariate relationship between connectivity patterns and affective symptoms in PD groups.ResultsA CCA analysis identified a single mode of co-variation linking theta and gamma connectivity with affective symptoms in PD groups. Increases in frontotemporal gamma, frontal and parietal theta connectivity were related with increased anxiety and cognitive impairment. Decreases in temporal region theta and frontoparietal gamma connectivity were associated with higher depression ratings and PD patient age.LimitationsThis study only reports on optimal dosage of dopaminergic treatment (‘on’ state) in PD and didn’t investigate at “off” medication.ConclusionsTheta and gamma connectivity during rest and task-states are linked to affective and cognitive symptoms within fronto-temporo-parietal networks, suggesting a potential assessment avenue for understanding brain-behavior associations in PD with electrophysiological task paradigms.
Potential impact of individual exposure histories to endemic human coronaviruses on age-dependence in severity of COVID-19
Authors: Pinotti Francesco , Wikramaratna Paul S , Obolski Uri , Paton Robert S , Damineli Daniel S C , Alcantara Luiz C J , Giovanetti Marta , Gupta Sunetra , Lourenço José 
Published: July 2020

AbstractCross-reactivity to SARS-CoV-2 from previous exposure to endemic coronaviruses (eHCoV) is gaining increasing attention as a possible driver of both protection against infection and severity of COVID-19 disease. Here, we use a stochastic individual-based model to show that heterogeneities in individual exposure histories to endemic coronaviruses are able to explain observed age patterns of hospitalisation due to COVID-19 in EU/EEA countries and the UK, provided there is (i) a decrease in cross-protection to SARS-CoV-2 with the number of eHCoV exposures and (ii) an increase in potential disease severity with number of eHCoV exposures or as a result of immune senescence. We also show that variation in health care capacity and testing efforts is compatible with country-specific differences in hospitalisation rates. Our findings call for further research on the role of cross-reactivity to endemic coronaviruses and highlight potential challenges arising from heterogeneous health care capacity and testing.
Effect of Cholesterol vs. Ergosterol on DPPC Bilayer Properties: Insights from Atomistic Simulations
Authors: Alavizargar Azadeh , Keller Fabian , Wedlich-Söldner Roland , Heuer Andreas 
Published: July 2020

AbstractSterols have been ascribed a major role in the organization of biological membranes, in particular for the formation of liquid ordered domains in complex lipid mixtures. Here, we employed molecular dynamics simulations to compare the effects of cholesterol and ergosterol as the major sterol of mammalian and fungal cells, respectively, on binary mixtures with 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) as a proxy for saturated lipids. In agreement with previous work, we observe that the addition of sterol molecules modifies the order of DPPC both in the gel phase and in the liquid phase. When disentangling the overall tilt angle and the structure of the tail imposed by trans/gauche configurations of torsion angles in the tail, respectively, a more detailed picture of the impact of sterols can be formulated, revealing, e.g., an approximate temperature-concentration superposition ranging from the liquid to the gel phase. Furthermore, a new quantitative measure to identify the presence of collective sterol effects is discussed. Moreover, when comparing both types of sterols, addition of cholesterol has a noticeably stronger impact on phospholipid properties than of ergosterol. The observed differences can be attributed to higher planarity of the cholesterol ring system. This planarity combined with an inherent asymmetry in its molecular interactions leads to better alignment and hence stronger interaction with saturated acyl chains. Our results suggest that the high order demonstrated for ergosterol in fungal plasma membranes must therefore be generated via additional mechanisms.
Spotting genome-wide pigmentation variation in a brown trout admixture context
Authors: Valette T. , Leitwein M. , Lascaux J.-M. , Desmarais E. , Berrebi P. , Guinand B. 
Published: July 2020

ABSTRACTVariation in body pigmentation attracted fish biologists for a while, but high-throughput genomic studies investigating its molecular basis remain limited to few species and associated conservation issues ignored. Using 75,684 SNPs, we explored the genomic basis of pigmentation pattern variation among individuals of the Atlantic and Mediterranean clades of the brown trout (Salmo trutta), a polytypic species in which Atlantic hatchery individuals are commonly used to supplement local wild populations. Using redundancy analyses and genome-wide association studies, a set of 337 independent “colour patterning loci” (CPLs) significantly associated with pigmentation traits such as the number of red and black spots on flanks, or the presence of a black spot on the pre-opercular bone was identified. CPLs map onto 35 out of 40 brown trout linkage groups indicating a polygenic basis to pigmentation patterns. They are mostly located in coding regions (43.4%) of 223 candidate genes, and correspond to GO-terms known to be involved in pigmentation (e.g. calcium and ion-binding, cell adhesion). Annotated candidates include genes with known pigmentation effects (e.g. SOX10, PEML, SLC45A2), but also the Gap-junction ⊗2 (GJD2) gene already shown differentially expressed in trout skin. Patterns of admixture were found significantly distinct when using either the full SNP data set or the set of CPLs, indicating that pigmentation patterns accessible to practitioners are not a reliable proxy of genome-wide admixture. Consequences for management are discussed.
No endospore formation confirmed in members of the phylum Proteobacteria
Authors: Beskrovnaya Polina , Fakih Doaa , Sexton Danielle L. , Xing Shipei , Golmohammadzadeh Mona , Morneau Isabelle , Bello Dainelys Guadarrama , Nanci Antonio , Huan Tao , Tocheva Elitza I. 
Published: July 2020

AbstractEndospore formation is used by members of the phylum Firmicutes to withstand extreme environmental conditions. Several recent studies have documented endospore formation in species outside of Firmicutes, particularly inRhodobacter johriiandSerratia marcescens, members of the phylum Proteobacteria. Here, we aimed to investigate endospore formation in these two species by using advanced imaging and analytical approaches. Examination of the phase-bright structures observed inR. johriiandS. marcescensusing cryo-electron tomography failed to identify endospores or stages of endospore formation. We determined that the phase-bright objects inR. johriicells were triacylglycerol storage granules and those inS. marcescenswere aggregates of cellular debris. In addition,R. johriiandS. marcescenscontaining phase-bright objects do not possess phenotypic and genetic features of endospores, including enhanced resistance to heat, presence of dipicolinic acid, or the presence of many of the genes associated with endospore formation. Our results support the hypothesis that endospore formation is restricted to the phylum Firmicutes.ImportanceEndospore formation is a mechanism that allows bacteria to generate resilient dormant spores under harsh environmental conditions. Although this process has been traditionally restricted to the largely Gram-positive bacteria of the phylum Firmicutes, recent studies have also described endospores in some Proteobacteria. High complexity of endosporulation, reflected in extensive morphological transformations governed by hundreds of conserved genes, hinders its facile acquisition via horizontal gene transfer. Therefore, ability of distantly related bacteria to produce endospores would imply an ancient nature of this mechanism and potentially a pivotal role in species diversification and outer membrane biogenesis.
Dynamics of SARS-CoV-2 with Waning Immunity in the UK Population
Authors: Crellen Thomas , Pi Li , Davis Emma L. , Pollington Timothy M. , Lucas Tim C. D. , Ayabina Diepreye , Borlase Anna , Toor Jaspreet , Prem Kiesha , Medley Graham F. , Klepac Petra , Hollingsworth T. Déirdre 
Published: July 2020

AbstractThe dynamics of immunity are crucial to understanding the long-term patterns of the SARS-CoV-2 pandemic. Several cases of reinfection with SARS-CoV-2 have been documented 48–142 days after the initial infection and immunity to seasonal circulating coronaviruses is estimated to be shorter than one year. Using an age-structured, deterministic model, we explore potential immunity dynamics using contact data from the UK population. In the scenario where immunity to SARS-CoV-2 lasts an average of three months for non-hospitalised individuals, a year for hospitalised individuals, and the effective reproduction number after lockdown ends is 1.2 (our worst case scenario), we find that the secondary peak occurs in winter 2020 with a daily maximum of 387,000 infectious individuals and 125,000 daily new cases; three-fold greater than in a scenario with permanent immunity. Our models suggests that longitudinal serological surveys to determine if immunity in the population is waning will be most informative when sampling takes place from the end of the lockdown in June until autumn 2020. After this period, the proportion of the population with antibodies to SARS-CoV-2 is expected to increase due to the secondary wave. Overall, our analysis presents considerations for policy makers on the longer term dynamics of SARS-CoV-2 in the UK and suggests that strategies designed to achieve herd immunity may lead to repeated waves of infection as immunity to reinfection is not permanent.
Data-independent acquisition method for ubiquitinome analysis reveals regulation of circadian biology
Authors: Hansen Fynn M. , Tanzer Maria C. , Brüning Franziska , Bludau Isabell , Schulman Brenda A. , Robles Maria S. , Karayel Ozge , Mann Matthias 
Published: July 2020

SUMMARYProtein ubiquitination is involved in virtually all cellular processes. Enrichment strategies employing antibodies targeting ubiquitin-derived diGly remnants combined with mass spectrometry (MS) have enabled investigations of ubiquitin signaling at a large scale. However, so far the power of data independent acquisition (DIA) with regards to sensitivity in single run analysis and data completeness have not yet been explored. We developed a sensitive workflow combining diGly antibody-based enrichment and optimized Orbitrap-based DIA with comprehensive spectral libraries together containing more than 90,000 diGly peptides. This approach identified 35,000 diGly peptides in single measurements of proteasome inhibitor-treated cells – double the number and quantitative accuracy of data dependent acquisition. Applied to TNF-alpha signaling, the workflow comprehensively captured known sites while adding many novel ones. A first systems-wide investigation of ubiquitination of the circadian cycle uncovered hundreds of cycling ubiquitination sites and dozens of cycling ubiquitin clusters within individual membrane protein receptors and transporters, highlighting novel connections between metabolism and circadian regulation.
Neurodegeneration induces a developmental RNA processing program by calpain-mediated MBNL2 degradation
Authors: Wang Lee-Hsin , Lin Yu-Mei , Lin Chien-Yu , Chern Yijuang , Wang Guey-Shin 
Published: July 2020

AbstractThe Muscleblind-like (MBNL) protein family plays an important role in regulating developmental RNA processing transition. Loss of MBNL2 function has been implicated in the neurodegeneration of myotonic dystrophy type 1 (DM1). However, the causal mechanism of neurodegeneration-induced MBNL2 loss of function remains elusive. Here, we show that neurodegenerative conditions including NMDAR-mediated excitotoxicity and dysregulated calcium homeostasis triggered nuclear translocation of calpain-2 resulting in MBNL2 degradation and reversion of MBNL2-regulated RNA processing to developmental patterns. The developmental stage featured nucleus-enriched distribution of calpain-2 and low expression of MBNL2. Increased MBNL2 expression during development is required for promoting developmental RNA processing transition and neuronal maturation. Knockdown of calpain-2 expression inhibited neurodegeneration-induced MBNL2 reduction and dysregulated RNA processing. Neurodegenerative disease mouse models including DM1 and Alzheimer’s disease showed nuclear translocation of calpain-2 associated with MBNL2 degradation and reversion of MBNL2-regulated RNA processing to the developmental pattern. Our results identify a novel regulatory mechanism for MBNL2 downregulation and suggest that reduced MBNL2 expression accompanied by the re-induction of a developmental RNA processing program may be a common feature of neurodegeneration.
Gradual centriole maturation associates with the mitotic surveillance pathway in mouse development
Authors: Xiao Cally , Grzonka Marta , Gerards Charlotte , Mack Miriam , Figge Rebecca , Bazzi Hisham 
Published: July 2020

AbstractCentrosomes, composed of two centrioles and pericentriolar material, organize mitotic spindles during cell division and template cilia during interphase. The first few divisions during mouse development occur without centrioles, which form around embryonic day (E) 3. However, disruption of centriole biogenesis inSas-4null mice leads to embryonic arrest around E9. Centriole loss inSas-4−/−embryos causes prolonged mitosis and p53-dependent cell death. Studiesin vitrodiscovered a similar USP28-, 53BP1-, and p53-dependent mitotic surveillance pathway that leads to cell cycle arrest. In this study, we show that an analogous pathway is conservedin vivowhere 53BP1 and USP28 are upstream of p53 inSas-4−/−embryos. The data indicates that the pathway is established around E7 of development, four days after the centrioles appear. Our data suggest that the newly formed centrioles gradually mature to participate in mitosis and cilia formation around the beginning of gastrulation, coinciding with the activation of mitotic surveillance pathway upon centriole loss.
Interplay between medial nuclear stalling and lateral cellular flow underlies cochlear duct spiral morphogenesis
Authors: Ishii Mamoru , Tateya Tomoko , Matsuda Michiyuki , Hirashima Tsuyoshi 
Published: July 2020

AbstractA notable example of spiral architecture in organs is the mammalian cochlear duct, where the duct morphology is critical for hearing function. Molecular genetics has revealed the necessary signaling molecules for the formation of spirals in organs, but it remains unclear how cellular dynamics generate bending and coiling of the cochlear duct during development. Here we show two modes of multicellular dynamics underlying the morphogenetic process by combining deep tissue live-cell imaging, Förster resonance energy transfer (FRET)-based quantitation, and mathematical modeling. First, surgical separation of the cochlear duct revealed that bending forces reside primarily in the medial side of the duct. In the medial pseudostratified epithelium, we found that nuclei stall at the luminal side during interkinetic nuclear migration, which would cause the extension of the luminal side, thereby bending the duct. Second, long-term organ-scale FRET imaging of extracellular signal-regulated kinase (ERK) activity showed that helical ERK activation waves propagate from the duct tip concomitant with the reverse multicellular flow in the lateral side of the duct, resulting in advection-based duct elongation. We propose an interplay of distinct multicellular behaviors underpinning spiral morphogenesis in the developing cochlear duct.
Adaptive divergence of meiotic recombination rate in ecological speciation
Authors: Neupane Swatantra , Xu Sen 
Published: July 2020

AbstractTheories predict that directional selection during adaptation to a novel habitat results in elevated meiotic recombination rate. Yet the lack of population-level recombination rate data leaves this hypothesis untested in natural populations. Here we examine the population-level recombination rate variation in two incipient ecological species, the microcrustaceanDaphnia pulex(an ephemeral-pond species) andD. pulicaria(a permanent-lake species). The divergence ofD. pulicariafromD. pulexinvolved habitat shifts from pond to lake habitats as well as strong local adaptation due to directional selection. Using a novel single-sperm genotyping approach, we estimated the male-specific recombination rate of two linkage groups in multiple populations of each species in common garden experiments and identified a significantly elevated recombination rate inD. pulicaria. Most importantly, population genetic analyses show that the divergence in recombination rate between these two species is most likely due to divergent selection in distinct ecological habitats rather than neutral evolution.Significance statementWhether directional selection during adaptation to a novel habitat results in elevated meiotic recombination remains largely untested in natural populations. This work examines the population-level recombination rate in two closely related microcructacean speciesDaphnia pulexandD. pulicariausing single-sperm genotyping approach. Recombination rate data from two linkage groups show elevated recombination rates inD. pulicariawhose divergence fromD. pulexis accompanied by a habitat shift. Importantly, population genetic analysis suggests that this divergence of recombination is likely adaptive rather than neutral.
A nutrient-responsive hormonal circuit controls energy and water homeostasis inDrosophila
Authors: Koyama Takashi , Terhzaz Selim , Naseem Muhammad T. , Nagy Stanislav , Rewitz Kim , Dow Julian A. T. , Davies Shireen A. , Halberg Kenneth A. 
Published: July 2020

ABSTRACTThe regulation of systemic energy balance involves the coordinated activity of specialized organs, which control nutrient uptake, utilization and storage to promote metabolic homeostasis during environmental challenges. The humoral signals that drive such homeostatic programs are largely unidentified. Here we show that three pairs of central neurons in adultDrosophilarespond to internal water and nutrient availability by releasing Capa-1 and -2 hormones that signal through the Capa receptor (CapaR) to exert systemic metabolic control. Loss of Capa/CapaR signaling leads to intestinal hypomotility and impaired nutrient absorption, which gradually deplete internal nutrient stores and reduce organismal lifespan. Conversely, hyperactivation of the Capa circuitry stimulates fluid and waste excretion. Furthermore, we demonstrate that Capa/CapaR regulates energy metabolism by modulating the release of the glucagon-like adipokinetic hormone, which governs lipolysis in adipose tissue to stabilize circulating energy levels. Altogether, our results uncover a novel inter-tissue program that plays a central role in coordinating post-prandial responses that are essential to maintain adult viability.
A twofold strategy for the protection of therapeutic peptides by attachment to the protease-resistant and fusogenic protein, saposin C
Authors: Sandin Suzanne I. , Randolph Christopher J. , de Alba Eva 
Published: July 2020

ABSTRACTA great challenge of therapeutic peptides (biologics) is their short half-life. However, biologics can be protected by encapsulation in liposomes used as drug-delivery platforms. Liposomes are typically incorporated into cells by endocytic pathways, which eventually expose therapeutics to favorable proteolytic conditions. To enhance biologics protection, we report the design and characterization of a liposome-protein chimera combining the liposome fusogenic properties of peripheral-membrane protein saposin C, covalently linked to a proapoptotic peptide (the active domain of Bcl-2 protein PUMA). We show by NMR that the saposin C component of the chimera is capable of binding liposomes and that the peptide binds prosurvival Bcl-xL, thus following known PUMA’s mechanism to induce cell death. These results indicate that the function of the individual components is preserved in the chimera. Our results point to a promising twofold strategy for drug delivery to; 1) avoid endocytosis by promoting liposome-membrane fusion, 2) provide additional protection by attachment to a stable, protease-resistant protein, which is a well-known method commonly used to prolong biologics half-life.