bluuebunny/crossref_metadata_2025_split huggingface dataset:
Differences in COVID-19 Risk by Race and County-Level Social Determinants of Health Among Veterans
Authors: Abdel Magid Hoda S. , Ferguson Jacqueline M. , Cleve Raymond V. , Purnell Amanda L. , Osborne Thomas F. 
Published: October 2021

AbstractCOVID-19 disparities by area-level social determinants of health (SDH) may be impacting U.S. Veterans. This retrospective analysis utilized COVID-19 data from the U.S. Department of Veterans Affairs (VA)’s EHR and geographically linked county-level data from 18 area-based socioeconomic measures. The risk of testing positive with Veterans’ county-level SDHs adjusting for demographics, comorbidities, and facility characteristics was calculated using generalized linear models. We found an exposure-response relationship whereby individual COVID-19 infection risk increased with each increasing quartile of adverse county-level SDH such as the percentage of residents in a county without a college degree, eligible for Medicaid, and living in crowded housing.
S100A8 and S100A9, biomarkers of SARS-Cov2-infected patients, suppress HIV replication in primary macrophages
Authors: Oguariri Raphael M. , Brann Terrence W. , Adelsberger Joseph W. , Chen Qian , Goswami Suranjana , Mele Anthony R. , Imamichi Tomozumi 
Published: October 2021

AbstractS100A8 and S100A9 are members of the Alarmin family; these proteins are abundantly expressed in neutrophils and form a heterodimer complex. Recently, both proteins were identified as novel biomarkers of SARS-CoV-2 infection and were shown to play key roles in inducing an aggressive inflammatory response by mediating the release of large amounts of pro-inflammatory cytokines, called the “cytokine storm.” Although co-infection with SARS-CoV-2 in people living with HIV-1 may result in an immunocompromised status, the role of the S100A8/A9 complex in HIV-1 replication in primary T cells and macrophages is still unclear. Here, we evaluated the roles of the proteins in HIV replication to elucidate their functions. We found that the complex had no impact on virus replication in both cell types; however, the subunits of S100A8 and S100A9 inhibits HIV in macrophages. These findings provide important insights into the regulation of HIV viral loads in SARS-CoV2 co-infection.
Loss of C9orf72 perturbs the Ran-GTPase gradient and generates compositionally diverse cytoplasmic Importin β-1 granules in motor and cortical neuronsin vivo
Authors: McGoldrick Philip , Lau Agnes , You Zhipeng , Durcan Thomas M , Robertson Janice 
Published: October 2021

SummaryRepeat expansions inC9orf72cause Amyotrophic Lateral Sclerosis (ALS) and Frontotemporal Dementia (FTD) eliciting toxic effects through generation of RNA foci, dipeptide repeat proteins and/or loss of C9orf72 protein. Defects in nucleocytoplasmic transport (NCT) have been implicated as a pathogenic mechanism underlying repeat expansion toxicity. Here, we show that loss of C9orf72 causes neuronal specific phenotypes, disrupting the Ran-GTPase gradient bothin vitroandin vivo. We describe compositionally different types of cytoplasmic Importin β-1 granules that exhibit neuronal subtype-specific propertiesin vivo. We show that the abundance of Importin β-1 granules is increased in the context of C9orf72 deficiency, disrupting interactions with nuclear pore complex proteins. These granules appear to bud from the nuclear envelope and are co-immunoreactive for G3BP1 and K63-ubiquitin. These findings link loss of C9orf72 protein to gain-of-function mechanisms and defects in NCT.
What can astrocytes compute?
Authors: Peterson Erik J. 
Published: October 2021

AbstractA foundational result in neural computation was proving the firing-rate model of neurons defines a universal function approximator. In this paper I prove it is possible for astrocytes to compute anything neurons can, by extending this original proof to a model of calcium waves in astrocytes. I confirm this in a series of computer simulations. The major limit for astrocytes, it turns out, is not their ability to learn solutions but the computational complexity of their network. I suggest some initial experiments that might be used to confirm these predictions.
Single-cell Atlas Unveils Cellular Heterogeneity and Novel Markers in Human Neonatal and Adult Intervertebral Discs
Authors: Jiang Wensen , Glaeser Juliane D. , Salehi Khosrowdad , Kaneda Giselle , Mathkar Pranav , Wagner Anton , Ho Ritchie , Sheyn Dmitriy 
Published: October 2021

SUMMARYThe origin, composition, distribution, and function of cells in the human intervertebral disc (IVD) has not been fully understood. Here, cell atlases of both human neonatal and adult IVDs have been generated and further assessed by gene ontology pathway enrichment, pseudo-time trajectory, histology, and immunofluorescence. Comparison of cell atlases revealed the presence of two sub-populations of notochordal cells (NCs) and their associated markers in both the neonatal and adult IVDs. Developmental trajectories predicted 7 different cell states that describe the developmental process from neonatal to adult cells in IVD and analyzed the NC’s role in the IVD development. A high heterogeneity and gradual transition of annulus fibrosus cells (AFCs) in the neonatal IVD was detected and their potential relevance in IVD development assessed. Collectively, comparing single-cell atlases between neonatal and adult IVDs delineates the landscape of IVD cell biology and may help discovering novel therapeutic targets for IVD degeneration.
Unravelling the role of thyroid hormones in seasonal neuroplasticity in European Starlings (Sturnus vulgaris)
Authors: Orije Jasmien , Raymaekers Sander R. , Majumadar Gaurav , De Groof Geert , Jonckers Elisabeth , Ball Gregory F. , Verhoye Marleen , Darras Veerle M. , Van der Linden Annemie 
Published: October 2021

1AbstractThyroid hormones clearly play a role in the seasonal regulation of reproduction, but any role they might play in song behavior and the associated seasonal neuroplasticity in songbirds remains to be elucidated. To pursue this question, we first established seasonal patterns in the expression of thyroid hormone regulating genes in male European starlings employing in situ hybridization methods. Thyroid hormone transporter LAT1 expression in the song nucleus HVC was elevated during the photosensitive phase, pointing towards an active role of thyroid hormones during this window of possible neuroplasticity. In contrast DIO3 expression was high in HVC during the photostimulated phase, limiting the possible effect of thyroid hormones to maintain song stability during the breeding season. Next, we studied the effect of hypothyroidism on song behavior and neuroplasticity using in vivo MRI. Hypothyroidism inhibited the photostimulation-induced increase in testosterone, confirming the role of thyroid hormones in activating the hypothalamic–pituitary–gonadal (HPG) axis. Surprisingly, apart from the myelination of several tracts during the photostimulated phase, most neuroplasticity related to song production was unaffected by hypothyroidism. Remarkably, T3 plasma concentrations were negatively correlated to the microstructural changes in several song control nuclei. Potentially, a global reduction of circulating thyroid hormones during the photosensitive period is necessary to lift the brake imposed by the photorefractory period, whereas local fine-tuning of thyroid hormone concentrations through LAT1 could activate underlying neuroplasticity mechanisms. Given the complexity of thyroid hormone effects, this study is a steppingstone to disentangle the influence of thyroid hormones on seasonal neuroplasticity.
Engineering transcription factor BmoR mutants for constructing multifunctional alcohol biosensors
Authors: Wu Tong , Chen Zhenya , Guo Shuyuan , Zhang Cuiying , Huo Yi-Xin 
Published: October 2021

AbstractNative transcription factor-based biosensors (TFBs) have the potential for in situ detection of value-added chemicals or byproducts. However, their industrial application is limited by their ligand promiscuity, low sensitivity, and narrow detection range. Alcohols exhibit similar structures, and no reported TFB can distinguish a specific alcohol from its analogs. Here, we engineered an alcohol-regulated transcription factor, BmoR, and obtained various mutants with remarkable properties. For example, the generated signal-molecule-specific BmoRs could distinguish the constitutional isomers n-butanol and isobutanol, with insensitivity up to an ethanol concentration of 800 mM (36.9 g/L). Linear detection of 0–60 mM of a specific higher alcohol could be achieved in the presence of up to 500 mM (23.0 g/L) ethanol as background noise. Notably, two mutants with raised outputs and over 1.0 × 107-fold higher sensitivity, and one mutant with an increased upper detection limit (14.8 g/L n-butanol or isobutanol) were screened out. Using BmoR as an example, this study systematically explored the ultimate detection limit of a TFB towards its small-molecule ligands, paving the way for in situ detection in the biofuel and wine industries.
The response to drought-stressed host plants varies among herbivorous mite populations from a climate gradient
Authors: Migeon Alain , Auger Philippe , Fossati-Gaschignard Odile , Hufbauer Ruth A. , Miranda Maëva , Zriki Ghais , Navajas Maria 
Published: October 2021

AbstractDrought associated with climate change can stress plants, altering their interactions with phytophagous arthropods. Drought not only impacts cultivated plants but also their parasites, which in some cases are favored by drought. Herbivorous arthropods feeding on drought-stressed plants typically produce bigger offspring and develop faster. However, it is unclear how much responses to drought stress differ among populations of herbivore species. Here, we evaluate variability among populations of a major agricultural pest, the two spotted spider mite,Tetranychus urticae, in response to drought stress. We compare key life history parameters of twelve populations that originate from climates ranging from wet and cool Atlantic locations to medium to dry hot Mediterranean locations. We evaluated how plant drought stress affects four life history traits: development time, fecundity, sex-ratio and emigration rate in an experiment comparing well-watered and drought-stressed bean plants. Mites feeding on drought-stressed plants developed faster and attempted to leave leaves less often, and young females were more fecund. The mites from wet temperate climates exhibited greater plasticity between the two water regimes than mites originating from dryer and hot climates, suggesting that the climate in the area of origin influences mite response to drought.
Habitat loss exacerbates pathogen spread: An Agent-based model of avian influenza infection in migratory waterfowl
Authors: Yin Shenglai , Xu Yanjie , de Jong Mart C.M. , Huisman Mees R.S. , Contina Andrea , Prins Herbert H. T. , Huang Zheng Y. X. , de Boer Willem F. 
Published: October 2021

AbstractHabitat availability determines the distribution of migratory waterfowl along their flyway, which further influences the transmission and spatial spread of avian influenza viruses (AIVs). The extensive habitat loss in the East Asian-Australasian Flyway (EAAF) may have potentially altered the virus transmission and spread, but those consequences are rarely studied. We constructed 6 fall migration networks that differed in their level of habitat loss, wherein an increase in habitat loss resulted in smaller networks with fewer sites. The networks were integrated with an agent-based model and a susceptible-infected-recovered model to simulate waterfowl migration and AIV transmission. We found that extensive habitat loss in the EAAF can 1) relocate the outbreaks northwards responding to the distribution changes of wintering waterfowl geese, 2) increase the outbreak risk in remaining sites due to larger bird congregations, and 3) facilitate AIV transmission among wintering geese. Our modelling output suggested that there was a certain system resilience of migration network to confront the site removal. In addition, the outputs were in line with the predictions from the concept of “migratory escape”, affecting the pattern of infection prevalence in the waterfowl population. Our modelling shed light on the potential consequences of habitat loss in transmitting and spreading AIV at the flyway scale, and suggested the driving mechanisms behind these effects, advocating the importance of nature conservation in changing spatial and temporal patterns of AIV outbreak.Author summaryWhat are the possible consequences of extensive habitat loss on the transmission and spread of avian influenza viruses (AIVs)? We used a logistic regression model to select the suitable habitats of Greater white-fronted goose in the East Asian-Australasian Flyway and treated these habitats as sites to construct 6 fall migration networks that differed in their level of habitat loss (i.e., site removal). We then simulate geese migration in these networks, and explore the impacts of habitat loss on habitat connectivity and AIV transmission. We found the extensive habitat loss can cause relocation of the outbreaks and increase the outbreak risk and AIV transmission. Our modelling outputs suggested a certain network resilience to confront the site loss, and a “migratory escape” to change the spatial and temporal pattern of infection prevalence in the population. Overall, our study showed that land use changes and habitat loss can affect disease distribution and prevalence, suggested the importance of habitat conservation in changing the spatial and temporal pattern of AIVs transmission and spread.
The 2D Ising model, criticality and AIT
Authors: Ruffini G. , Deco G. 
Published: October 2021

AbstractIn this short note we study the 2D Ising model, a universal computational model which reflects phase transitions and critical phenomena, as a framework for establishing links between systems that exhibit criticality with the notions of complexity. This is motivated in the context of neuroscience applications stemming from algorithmic information theory (AIT). Starting with the original 2D Ising model, we show that — together with correlation length of the spin lattice, susceptibility to a uniform external field — the correlation time of the magnetization time series, the compression ratio of the spin lattice, the complexity of the magnetization time series — as derived from Lempel-Ziv-Welch compression—, and the rate of information transmission in the lattice, all reflect the effects of the phase transition, which results in spacetime pockets of uniform magnetization at all scales. We also show that in the Ising model the insertion of sparse long-range couplings has a direct effect on the critical temperature and other parameters. The addition of positive links extends the ordered regime to higher critical temperatures, while negative links have a stronger, disordering influence at the global scale. We discuss some implications for the study of long-range (e.g., ephaptic) interactions in the human brain and the effects of weak perturbations in neural dynamics.
A comprehensive benchmark for structural assessment in bipartite networks
Authors: Palazzi María J. , Lampo Aniello , Solé-Ribalta Albert , Borge-Holthoefer Javier 
Published: October 2021

AbstractThe use of null models has been a cornerstone to assess the emergence of many network properties at different levels of organization (micro-, meso- and macroscale). Notwithstanding, the debate around which is the most appropriate randomization procedure for a given problem is far from being over. Within the ecological community, for example, the discussion around whether nestedness is –or is not– a frequent pattern in natural systems, and under which assumptions, remains open. For this particular problem, efforts have been devoted to exploring to what extent current models are vulnerable to statistical errors, or to introduce new models that employ different randomization procedures. However, few or no attention has been devoted to the performance of those null models against other architectures. Here, we show that assessing alternative structures under a single null model may produce ambiguous results, which difficult the comparison regarding the joint emergence of different arrangements within a single network. To this aim, we analyze the statistical significance –in terms ofz-scores– of nestedness, modularity, and in-block nestedness scores, employing five different null models on a benchmark of ∼ 2.5 × 104synthetic bipartite networks with prescribed levels of the mentioned patterns. We show that some null models systematically over- or underestimate the presence of one or another structural pattern. In light of these ambiguities, we introduce an alternative model (termed Corrected Probabilistic model) that reduces the observed biases towards under- and overestimation, and highlight the need for the development of new frameworks that take into account those biases.
fcfdr: an R package to leverage continuous and binary functional genomic data in GWAS
Authors: Hutchinson Anna , Liley James , Wallace Chris 
Published: October 2021

AbstractSummaryGWAS discovery is limited in power to detect associations that exceed the stringent genome-wide significance threshold, but this limitation can be alleviated by leveraging relevant auxiliary data. Frameworks utilising the conditional false discovery rate (cFDR) can be used to leverage continuous auxiliary data (including GWAS and functional genomic data) with GWAS test statistics and have been shown to increase power for GWAS discovery whilst controlling the FDR. Here, we describe an extension to the cFDR framework for binary auxiliary data (such as whether SNPs reside in regions of the genome with specific activity states) and introduce an all-encompassing R package to implement the cFDR approach, fcfdr, demonstrating its utility in an application to type 1 diabetes.Availability and implementationThe fcfdr R package is freely available at: https://github.com/annahutch/fcfdr. Scripts and data to reproduce the analysis in this paper are freely available at: https://annahutch.github.io/fcfdr/articles/t1d_app.html
Mimicked synthetic ribosomal protein complex for benchmarking crosslinking mass spectrometry workflows
Authors: Matzinger Manuel , Vasiu Adrian , Madalinski Mathias , Müller Fränze , Stanek Florian , Mechtler Karl 
Published: October 2021

ABSTRACTThe field of cross-linking mass spectrometry has matured to a frequently used tool for the investigation of protein structures as well as interactome studies up to a system wide level. The growing community generated a broad spectrum of applications, linker types, acquisition strategies and specialized data analysis tools, which makes it challenging, especially for newcomers, to decide for an appropriate analysis workflow. Therefore, we here present a large and flexible synthetic peptide library as reliable instrument to benchmark crosslinkers with different reactive sites as well as acquisition techniques and data analysis algorithms. Additionally, we provide a tool, IMP-X-FDR, that calculates the real, experimentally validated, FDR, compares results across search engine platforms and analyses crosslink properties in an automated manner. The library was used with the reagents DSSO, DSBU, CDI, ADH, DHSO and azide-a-DSBSO and data were analysed using the algorithms MeroX, MS Annika, XlinkX, pLink 2, MaxLynx and xiSearch. We thereby show that the correct algorithm and search setting choice is highly important to improve ID rate and FDR in combination with software and sample-complexity specific score cut-offs. When analysing DSSO data with MS Annika, we reach high identification rates of up to ∼70 % of the theoretical maximum (i.e. 700 unique lysine-lysine cross-links) while maintaining a low real FDR of < 3 % at cross-link level and with high reproducibility, representatively showing that our test system delivers valuable and statistically solid results.Graphical abstract
PI4P and BLOC-1 remodel endosomal membranes into tubules
Authors: Jani Riddhi Atul , Cicco Aurélie Di , Keren-Kaplan Tal , Vale-Costa Silvia , Hamaoui Daniel , Hurbain Ilse , Tsai Feng-Ching , Dimarco Mathilde , Macé Anne-Sophie , Zhu Yueyao , Amorim Maria João , Bassereau Patricia , Bonifacino Juan S. , Subtil Agathe , Marks Michael S. , Lévy Daniel , Raposo Graça , Delevoye Cédric 
Published: October 2021

ABSTRACTIntracellular trafficking is mediated by transport carriers that originate by membrane remodeling from donor organelles. Tubular carriers play major roles in the flux of membrane lipids and proteins to acceptor organelles. However, how lipids and proteins impose a tubular geometry on the carriers is incompletely understood. By exploiting imaging approaches at different scales on cells and in vitro membrane systems, we show that phosphatidylinositol-4-phosphate (PI4P) and biogenesis of lysosome-related organelles complex 1 (BLOC-1) govern the formation, stability and functions of recycling endosomal tubules. Endosomal PI4P production by type II PI4-kinases is needed to form nascent curved tubules through binding of BLOC-1 that stabilize and elongate them. Membrane remodeling by the PI4P/ BLOC-1 module functions not only in the recycling of endosomal cargoes, but also in the lifecycles of intracellular pathogens such as Chlamydia bacteria and influenza virus. This study demonstrates how a phospholipid and a protein complex coordinate as a minimal machinery to remodel cellular membranes into functional tubes.
Potassium-chelating drug sodium polystyrene sulfonate enhances lysosomal function and suppresses proteotoxicity
Authors: Arputhasamy Cyrene , Lucanic Mark , Rane Anand , Schmidt Minna , Garett Theo , Foulger Anna C. , Broussalian Michael , Battistoni Elena , Brem Rachel B. , Lithgow Gordon J. , Chamoli Manish , Andersen Julie K. 
Published: October 2021

ABSTRACTLysosomes are crucial for degradation and recycling of damaged proteins and cellular components. Therapeutic strategies enhancing lysosomal function are a promising approach for aging and age-related neurodegenerative diseases. Here, we show that an FDA approved drug sodium polystyrene sulfonate (SPS), used to reduce high blood potassium in humans, enhances lysosomal function both in C.elegans and in human neuronal cells. Enhanced lysosomal function following SPS treatment is accompanied by the suppression of proteotoxicity caused by expression of the neurotoxic peptides Aβ and TAU. Additionaly, treatment with SPS imparts health benefits as it significantly increases lifespan in C.elegans. Overall our work supports the potential use of SPS as a prospective geroprotective intervention.HIGHLIGHTSSodium polystyrene sulfonate improves pH-dependent processing of lysosomal cargo, enhances proteotoxic stress resistance and extends lifespan in C. elegansSodium polystyrene sulfonate boosts lysosomal function in human neuronal cells and reduces level of aggregation-associated phosphorylated-TAU