bluuebunny/crossref_metadata_2025_split huggingface dataset:
Infection of brain pericytes underlying neuropathology of COVID-19 patients
Authors: Bocci Matteo , Oudenaarden Clara , Sàenz-Sardà Xavier , Simrén Joel , Edén Arvid , Sjölund Jonas , Möller Christina , Gisslén Magnus , Zetterberg Henrik , Englund Elisabet , Pietras Kristian 
Published: May 2021

AbstractA wide range of neurological manifestations have been associated with the development of COVID-19 following SARS-CoV-2 infection. However, the etiology of the neurological symptomatology is still largely unexplored.Here, we used state-of-the-art multiplexed immunostaining of human brains (n = 6 COVID-19, median age = 69,5 years; and n = 7 control, median age = 68 years), and demonstrated that expression of the SARS-CoV-2 receptor ACE2 is restricted to a subset of neurovascular pericytes. Strikingly, neurological symptoms were exclusive to, and ubiquitous in, patients that exhibited moderate to high ACE2 expression in peri-vascular cells. Viral particles were identified in the vascular wall and paralleled by peri-vascular inflammation, as signified by T cell and macrophage infiltration. Furthermore, fibrinogen leakage indicated compromised integrity of the blood-brain barrier. Notably, cerebrospinal fluid from an additional 16 individuals (n = 8 COVID-19, median age = 67 years; and n = 8 control, median age = 69,5 years) exhibited significantly lower levels of the pericyte marker PDGFRβ in SARS-CoV-2-infected cases, indicative of disrupted pericyte homeostasis.We conclude that pericyte infection by SARS-CoV-2 underlies virus entry into the privileged central nervous system space, as well as neurological symptomatology due to peri-vascular inflammation and a locally compromised blood-brain barrier.
SARS-CoV-2 surveillance in Italy through phylogenomic inferences based on Hamming distances derived from functional annotations of SNPs, MNPs and InDels
Authors: Pasquale Adriano Di , Radomski Nicolas , Mangone Iolanda , Calistri Paolo , Lorusso Alessio , Cammà Cesare 
Published: May 2021

ABSTRACTBackgroundFaced to the ongoing global pandemic of coronavirus disease, the ‘National Reference Centre for Whole Genome Sequencing of microbial pathogens: database and bioinformatic analysis’ (GENPAT) formally established at the ‘Istituto Zooprofilattico Sperimentale dell’Abruzzo e del Molise’ (IZSAM) in Teramo (Italy) supports the genomic surveillance of the SARS-CoV-2. In a context of SARS-CoV-2 surveillance needed proper and fast assessment of epidemiological clusters from large amount of samples, the present manuscript proposes a workflow for identifying accurately the PANGOLIN lineages of SARS-CoV-2 samples and building of discriminant minimum spanning trees (MST) bypassing the usual time consuming phylogenomic inferences based on multiple sequence alignment (MSA) and substitution model.ResultsGENPAT constituted two collections of SARS-CoV-2 samples. The samples of the first collection were isolated by IZSAM in the Abruzzo region (Italy), then shotgun sequenced and analyzed in GENPAT (n = 1 592), while those of the second collection were isolated from several Italian provinces and retrieved from the reference Global Initiative on Sharing All Influenza Data (GISAID) (n = 17 201). The main outcomes of the present study showed that (i) GENPAT and GISAID identified identical PANGOLIN lineages, (ii) the PANGOLIN lineages B.1.177 (i.e. historical in Italy) and B.1.1.7 (i.e. ‘UK variant’) are major concerns today in several Italian provinces, and the new MST-based method (iii) clusters most of the PANGOLIN lineages together, (iv) with a higher dicriminatory power than PANGOLIN, (v) and faster that the usual phylogenomic methods based on MSA and substitution model.ConclusionsThe shotgun sequencing efforts of Italian provinces, combined to a structured national system of metagenomics data management, provided support for surveillance SARS-CoV-2 in Italy. We recommend to infer phylogenomic relationships of SARS-CoV-2 variants through an accurate, discriminant and fast MST-based method bypassing the usual time consuming steps related to MSA and substitution model-based phylogenomic inference.
Outpatient Portal Use in Prenatal Care: Differential Use by Race, Risk, and Area Social Determinants of Health Factors
Authors: Singh Priti , Jonnalagadda Pallavi , Morgan Evan , Fareed Naleef 
Published: May 2021

AbstractObjectiveTo report the relationship of Outpatient Patient Portal (OPP) use with clinical risk, area social determinants of health (SDoH), and race/ethnicity among pregnant women.MethodsRegression models predicting overall and individual portal feature use (main effects and interactions) based on key variables were specified using logfiles and clinical data.ResultsOverall OPP use among non-Hispanic Black women or patients who lived in lower SDoH neighborhoods were significantly less. High-risk pregnancy patients were likely to use the OPP more than those with normal-risk pregnancy. We found similar associations with individual OPP features, like the Visit (scheduling) and My Record (test results). We also found significant interactive associations between race, clinical risk, and SDoH. Non-Hispanic Black women living in lower SDoH areas used OPP less than non-Hispanic White women from similar or affluent areas.ConclusionMore research must be conducted to learn of OPP implications for pregnant women with specific clinical diagnoses.
SARS-CoV-2 Antibody Testing in Healthcare Workers: a comparison of the clinical performance of three commercially available antibody assays
Authors: Allen Niamh , Brady Melissa , Martin Antonio Isidro Carrion , Domegan Lisa , Walsh Cathal , Houlihan Elaine , Kerr Colm , Doherty Lorraine , King Joanne , Doheny Martina , Griffin Damian , Molloy Maria , Dunne Jean , Crowley Vivion , Holmes Philip , Keogh Evan , Naughton Sean , Kelly Martina , O’Rourke Fiona , Lynagh Yvonne , Crowley Brendan , de Gascun Cillian , Holder Paul ,   PRECISE Study Steering Group, Bergin Colm , Fleming Catherine , Ni Riain Una , Conlon Niall 
Published: May 2021

AbstractSARS-CoV-2 antibodies are an excellent indicator of past COVID-19 infection. As the COVID-19 pandemic progresses, retained sensitivity over time is an important quality in an antibody assay that is to be used for the purpose of population seroprevalence studies.We compared 5788 healthcare worker (HCW) serum samples on two serological assays (Abbott SARS-CoV-2 anti-nucleocapsid IgG and Roche Anti-SARS-CoV-2 anti-nucleocapsid Total Antibody) and a subset of samples (all Abbott assay positive or grayzone, n=485) on Wantai SARS-CoV-2 anti-spike Antibody ELISA. For 367 samples from HCW with previous PCR-confirmed SARS-CoV-2 infection we correlated the timing of infection with assay results.Overall seroprevalence was 4.2% on Abbott, 9.5% on Roche. Of those with previously confirmed infection, 41% (150/367) and 95% (348/367) tested positive on Abbott and Roche respectively. At 21 weeks (150 days) after confirmed infection, positivity on Abbott started to decline. Roche positivity was retained for the entire study period (33 weeks). Factors associated (P≤ 0.050) with Abbott seronegativity in those with previous PCR-confirmed infection included sex (male OR0.30;95%CI0.15-0.60), symptom severity (OR0.19 severe symptoms;95%CI0.05-0.61), ethnicity (OR0.28 Asian ethnicity;95%CI0.12-0.60) and time since PCR diagnosis (OR2.06 for infection 6 months previously;95%CI1.01-4.30. Wantai detected all previously confirmed infections.In our population, Roche detected antibodies up to at least seven months after natural infection with SARS-CoV-2. This may indicate that Roche is better suited than Abbott to population-based studies. Wantai demonstrated high sensitivity but sample selection was biased. The relationship between serological response and functional immunity to SARS-CoV-2 infection needs to be delineated.
Probing DNA-protein interactions using single-molecule diffusivity contrast
Authors: Wilson Hugh , Lee Miles , Wang Quan 
Published: May 2021

ABSTRACTSingle-molecule fluorescence investigations of protein-nucleic acid interactions require robust means to identify the binding state of individual substrate molecules in real time. Here we show that diffusivity contrast, widely used in fluorescence correlation spectroscopy at the ensemble level and in single-particle tracking on individual (but slowly diffusing) species, can be used as a general readout to determine the binding state of single DNA molecules with unlabeled proteins in solution. We first describe the technical basis of drift-free single-molecule diffusivity measurements in an Anti-Brownian ELetrokinetic (ABEL) trap. We then cross-validate our method with protein-induced fluorescence enhancement (PIFE), a popular technique to detect protein binding on nucleic acid substrates with single-molecule sensitivity. We extend an existing hydrodynamic modeling framework to link measured diffusivity to particular DNA-protein structures and obtain good agreement between the measured and predicted diffusivity values. Finally, we show that combining diffusivity contrast with PIFE allows simultaneous mapping of binding stoichiometry and location on individual DNA-protein complexes, potentially enhancing single-molecule views of relevant biophysical processes.
Subcellular micropatterning for visual immunoprecipitation reveals differences in cytosolic protein complexes downstream the EGFR
Authors: Hager Roland , Müller Ulrike , Ollinger Nicole , Weghuber Julian , Lanzerstorfer Peter 
Published: May 2021

AbstractAnalysis of protein-protein interactions in living cells by protein micropatterning is currently limited to the spatial arrangement of transmembrane proteins and their corresponding downstream molecules. Here we present a robust method for visual immunoprecipitation of cytosolic protein complexes by use of an artificial transmembrane bait construct in combination with micropatterned antibody arrays on cyclic olefin polymer (COP) substrates. The method was used to characterize Grb2-mediated signalling pathways downstream the epidermal growth factor receptor (EGFR). Ternary protein complexes (Shc1:Grb2:SOS1 and Grb2:Gab1:PI3K) were identified and we found that EGFR downstream signalling is based on constitutively bound (Grb2:SOS1 and Grb2:Gab1) as well as on agonist-dependent protein associations with transient interaction properties (Grb2:Shc1 and Grb2:PI3K). Spatiotemporal analysis further revealed significant differences in stability and exchange kinetics of protein interactions. Furthermore, we could show that this approach is well suited to study the efficacy and specificity of SH2 and SH3 protein domain inhibitors in a live cell context. Altogether, this method represents a significant enhancement of quantitative subcellular micropatterning approaches as an alternative to standard biochemical analyses.
Purification of functional Plasmodium falciparum tubulin allows for the identification of parasite-specific microtubule inhibitors
Authors: Hirst William Graham , Fachet Dominik , Kuropka Benno , Weise Christoph , Saliba Kevin , Reber Simone 
Published: May 2021

ABSTRACTCytoskeletal proteins are essential for parasite proliferation, growth, and transmission, and therefore represent promising drug targets. While αβ-tubulin, the molecular building block of microtubules, is an established drug target in a variety of cancers, we still lack substantial knowledge of the biochemistry of parasite tubulins, which would allow us to exploit the structural divergence between parasite and human tubulins. Indeed, mechanistic insights have been limited by the lack of purified, functional parasite tubulin. In this study, we isolated Plasmodium falciparum tubulin that is assembly-competent and shows specific microtubule dynamics in vitro. We further present mechanistic evidence that two compounds selectively interact with parasite over host microtubules and inhibit Plasmodium microtubule polymerization at substoichiometric compound concentrations. The ability of compounds to selectively disrupt protozoan microtubule growth without affecting human microtubules provides the exciting possibility for the targeted development of novel antimalarials.
An Issue of Concern: Unique Truncated ORF8 Protein Variants of SARS-CoV-2
Authors: Hassan Sk. Sarif , Kodakandla Vaishnavi , Redwan Elrashdy M. , Lundstrom Kenneth , Choudhury Pabitra Pal , El-Aziz Tarek Mohamed Abd , Takayama Kazuo , Kandimalla Ramesh , Lal Amos , Serrano-Aroca Ángel , Azad Gajendra Kumar , Aljabali Alaa A. A. , Palu Giorgio , Chauhan Gaurav , Adadi Parise , Tambuwala Murtaza , Brufsky Adam M. , Baetas-da-Cruz Wagner , Barh Debmalya , Bazan Nicolas G , Uversky Vladimir N. 
Published: May 2021

AbstractOpen reading frame 8 (ORF8) protein is one of the most evolving accessory proteins in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of coronavirus disease 2019 (COVID-19). It was previously reported that the ORF8 protein inhibits presentation of viral antigens by the major histocompatibility complex class I (MHC-I) and interacts with host factors involved in pulmonary inflammation. The ORF8 protein assists SARS-CoV-2 to evade immunity and replication. Among many contributing mutations, Q27STOP, a mutation in the ORF8 protein defines the B.1.1.7 lineage of SARS-CoV-2, which is engendering the second wave of COVID-19. In the present study, 47 unique truncated ORF8 proteins (T-ORF8) due to the Q27STOP mutations were identified among 49055 available B.1.1.7 SARS-CoV-2 sequences. The results show that only one of the 47 T-ORF8 variants spread to over 57 geo-locations in North America, and other continents which includes Africa, Asia, Europe and South America. Based on various quantitative features such as amino acid homology, polar/non-polar sequence homology, Shannon entropy conservation, and other physicochemical properties of all specific 47 T-ORF8 protein variants, a collection of nine possible T-ORF8 unique variants were defined. The question of whether T-ORF8 variants work similarly to ORF8 has yet to be investigated. A positive response to the question could exacerbate future COVID-19 waves, necessitating severe containment measures.
Sexual selection in females across the animal tree of life
Authors: Fromonteil Salomé , Winkler Lennart , Marie-Orleach Lucas , Janicke Tim 
Published: May 2021

AbstractThe pioneers of sexual selection theory proposed that males are generally ‘eager’ whereas females are rather ‘coy’ with respect to mating. This male-centred perspective on sexual selection continues to permeate our perception of sex differences across disciplines. Despite an increased awareness that females also compete for mating partners, we still tend to consider sexual selection in females a rare peculiarity. Here we present meta-analytic evidence from 72 species across a broad range of animal taxa to show that sexual selection in females is widespread and should be considered the norm rather than the exception. Thereby, our results extend our general understanding of sexual reproduction and may contribute to a more balanced perspective of how sexual selection operates in both males and females.
Correcting differential gene expression analysis for cyto-architectural alterations in substantia nigra of Parkinson’s disease patients reveals known and potential novel disease-associated genes and pathways
Authors: Federico Ferraro , Christina Fevga , Vincenzo Bonifati , Wim Mandemakers , Ahmed Mahfouz , Marcel Reinders 
Published: May 2021

AbstractSeveral studies have analyzed gene expression profiles in the substantia nigra to better understand the pathological mechanisms causing Parkinson’s disease (PD). However, the concordance between the identified gene signatures in these individual studies was generally low. This might be caused by a change in cell type composition as loss of dopaminergic neurons in the substantia nigra pars compacta is a hallmark of PD. Through an extensive meta-analysis of nine previously published microarray studies, we demonstrated that a big proportion of the detected differentially expressed genes was indeed caused by cyto-architectural alterations due to the heterogeneity in the neurodegenerative stage and/or technical artifacts. After correcting for cell composition, we identified a common signature that deregulated the previously unreported ammonium transport, as well as known biological processes including bioenergetic pathways, response to proteotoxic stress, and immune response. By integrating with protein-interaction data, we shortlisted a set of key genes, such as LRRK2, PINK1, and PRKN known to be related to PD; others with compelling evidence for their role in neurodegeneration, such as GSK3β, WWOX, and VPC; as well as novel potential players in the PD pathogenesis, including NTRK1, TRIM25, ELAVL1. Together, these data showed the importance of accounting for cyto-architecture in these analyses and highlight the contribution of multiple cell types and novel processes to PD pathology providing potential new targets for drug development.Significance StatementThe exploration of the transcriptomic landscape in PD is pivotal for the understanding of the pathological mechanisms of this disease. Nonetheless, little attention has been paid to the influence of cell composition on the transcriptome even though it is known that cyto-architecture undergoes major alterations in neurodegenerative diseases such as PD. Our study signifies that changes in cellular architecture of human substantia nigra in PD have a strong effect on the set of detected differentially expressed genes. By reanalyzing the data and accounting for cell composition, we provide an updated description of deregulated biological processes in PD and nominate a shortlist of PD-associated genes for further investigations.
Long lasting anxiety following early life stress is dependent on glucocorticoid signaling in zebrafish
Authors: Chin Jacqueline S.R. , Phan Tram-Anh N. , Albert Lydia T. , Keene Alex C. , Duboué Erik R. 
Published: May 2021

SummaryChronic adversity in early childhood is associated with increased anxiety and a propensity for substance abuse later in adulthood, yet the effects of early life stress (ELS) on brain development remains poorly understood. The zebrafish, Danio rerio, is a powerful model for studying neurodevelopment and stress. Here, we describe a zebrafish model of ELS and identify a role for glucocorticoid signaling during a critical window in development that leads to long-term changes in brain function. Larval fish subjected to chronic stress in early development exhibited increased anxiety-like behavior and elevated glucocorticoid levels later in life. Increased stress-like behavior was only observed when fish were subjected to ELS within a precise time window in early development, revealing a temporal critical window of sensitivity. Moreover, enhanced anxiety-like behavior only emerges after two months post-ELS, revealing a developmentally specified delay in the effects of ELS. ELS leads to increased levels of baseline cortisol, and resulted in a dysregulation of cortisol receptors, suggesting long-term effects on cortisol signaling. Together, these findings reveal a ‘critical window’ for ELS to affect developmental reprogramming of the glucocorticoid receptor pathway, resulting in chronic elevated stress.
Temporal Progression: A case study in Porcine Survivability through Hemostatic Nanoparticles
Authors: Kulkarni Chhaya , Maisha Nuzhat , Schaub Leasha J , Glaser Jacob , Lavik Erin , Janeja Vandana P. 
Published: May 2021

ABSTRACTThis paper focuses on the analysis of time series representation of blood loss and cytokines in animals experiencing trauma to understand the temporal progression of factors affecting survivability of the animal. Trauma related grave injuries cause exsanguination and lead to death. 50% of deaths especially in the armed forces are due to trauma injuries. Restricting blood loss usually requires the presence of first responders, which is not feasible in certain cases. Hemostatic nanoparticles have been developed to tackle these kinds of situations to help achieve efficient blood coagulation. Hemostatic nanoparticles were administered into trauma induced porcine animals (pigs) to observe impact on the cytokine and blood loss experienced by them. In this paper we present temporal models to study the impact of the hemostatic nanoparticles and provide snapshots about the trend in cytokines and blood loss in the porcine data to study their progression over time. We utilized Piecewise Aggregate Approximation, Similarity based Merging and clustering to evaluate the impact of the different hemostatic nanoparticles administered. In some cases the fluctuations in the cytokines may be too small. So in addition we highlight situations where temporal modelling that produces a smoothed time series may not be useful as it may remove out the noise and miss the overall fluctuations resulting from the nanoparticles. Our results indicate certain nanoparticles stand out and lead to novel hypothesis formation.
Smell what you hardly see: Odors assist categorization in the human visual cortex
Authors: Rekow Diane , Baudouin Jean-Yves , Durand Karine , Leleu Arnaud 
Published: May 2021

AbstractVisual categorization is the brain ability to rapidly and automatically respond to widely variable visual inputs in a category-selective manner (i.e., distinct responses between categories and similar responses within categories). Whether category-selective neural responses are purely visual or can be influenced by other sensory modalities remains unclear. Here, we test whether odors modulate visual categorization, expecting that odors facilitate the neural categorization of congruent visual objects, especially when the visual category is ambiguous. Scalp electroencephalogram (EEG) was recorded while natural images depicting various objects were displayed in rapid 12-Hz streams (i.e., 12 images / second) and variable exemplars of a target category (either human faces, cars, or facelike objects in dedicated sequences) were interleaved every 9thstimulus to tag category-selective responses at 12/9 = 1.33 Hz in the EEG frequency spectrum. During visual stimulation, participants (N = 26) were implicitly exposed to odor contexts (either body, gasoline or baseline odors) and performed an orthogonal cross-detection task. We identify clear category-selective responses to every category over the occipito-temporal cortex, with the largest response for human faces and the lowest for facelike objects. Critically, body odor boosts the response to the ambiguous facelike objects (i.e., either perceived as nonface objects or faces) over the right hemisphere, especially for participants reporting their presence post-stimulation. By contrast, odors do not significantly modulate other category-selective responses, nor the general visual response recorded at 12 Hz, revealing a specific influence on the categorization of congruent ambiguous stimuli. Overall, these findings support the view that the brain actively uses cues from the different senses to readily categorize visual inputs, and that olfaction, which is generally considered as poorly functional in humans, is well placed to disambiguate visual information.