bluuebunny/crossref_metadata_2025_split huggingface dataset:
Investigating trait variability of gene co-expression network architecture in brain by manipulating genomic signatures of schizophrenia risk
Authors: Radulescu Eugenia , Chen Qiang , Pergola Giulio , Eagles Nicholas J , Stolz Joshua M , Shin Joo Heon , Hyde Thomas M , Kleinman Joel E , Weinberger Daniel R 
Published: May 2021

ABSTRACTWhile the role of genomic risk for schizophrenia on brain gene co-expression networks has been described, the patterns of its manifestations are varied and complex. To acquire a deeper understanding of this issue, we implemented a novel approach to network construction by manipulating the RNA-Seq expression input to “integrate” or “remove” the “modulatory” effects of genomic risk for schizophrenia. We created co-expression networks in DLPFC from the adjusted expression input and compared them in terms of gene overlap and connectivity. We used linear regression models to remove variance explained by RNA quality, cell type proportion, age, sex and genetic ancestry. We also created co-expression networks based on the genomic profile of a normative trait, height, as a “negative control”; we also applied the same analytical approach in two independent samples: LIBD Human Brain Repository (HBR) (N=78 brains, European ancestry) and Common Mind Consortium (CMC) (N=116 brains, European ancestry). In addition to direct comparisons, we explored the biological plausibility of the differential gene clusters between co-expression networks by testing them for enrichment in relevant gene ontologies and gene sets of interest (PGC2-CLOZUK GWAS significant loci genes, height GWAS significant loci genes, genes in synaptic ontologies-SynGO and genes of the “druggable genome”). We identify several key aspects of the role of genomic risk for schizophrenia in brain co-expression networks: 1) Variability of co-expression modules with “integration” or “removal” of genomic profiles of complex traits (normal or pathological); 2) Biological plausibility of gene sets represented in the differential co-expression contrasts and potential relevance for illness etiopathogenesis; 3) Non-preferential mapping of schizophrenia GWAS loci genes to network areas apparently influenced by the genomic risk score. Overall, our study supports the notion that genomic risk for schizophrenia has an extensive and non-linear effect on brain gene co-expression networks that possibly manifests as a molecular background for gene-gene, gene-environment interactions that affect various biological pathways.
Are the Items of the Starkstein Apathy Scale Fit for the Purpose of Measuring Apathy Post-Stroke?
Authors: Hum Stanley , Fellows Lesley K. , Lourenco Christiane , Mayo Nancy E. 
Published: May 2021

AbstractGiven the importance of apathy for stroke, we felt it was time to scrutinize the commonly used Starkstein Apathy Scale (SAS) for psychometric evidence that it is fit for this purpose. The objectives were to: (i) estimate the extent to which the SAS items fit a hierarchical continuum of the Rasch Model; and (ii) estimate the strength of the relationships between the Rasch analysed SAS and converging constructs related to stroke outcomes.MethodsData on 238 people with stroke (mean age=63.1 years (SD=12.1) women=37.4%) from a clinical trial of a community-based intervention targeting participation were available at 5 time points yielding 856 SAS questionnaires. SAS has 14 items, rated on a 4-point scale with higher values indicating more apathy. Psychometric properties were tested using Rasch partial-credit model, correlation, and regression. The construct was modeled as motivation with items rescored as high is better.ResultsRasch analysis indicated that the response options were disordered for 8/14 items, pointing to unreliability in the interpretation of the response options; they were consequently reduced from 4 to 3. Only 9/14 items fit the Rasch model and therefore suitable for creating a total score. The new rSAS was deemed unidimensional (residual correlations: < 0.3), reasonably reliable (person separation index: 0.74), with item-locations uniform across time, age, sex, and education. However, 30% of scores were >2 SD above the standardized mean but only 2/9 items covered this range (construct mistargeting).Apathy (rSAS/SAS) was correlated weakly with anxiety/depression and uncorrelated with physical capacity. Regression showed that the effect of apathy on participation and health perception was similar for rSAS/SAS versions: R2 participation measures ranged from 0.11 to 0.29; R2 for health perception was ∼0.25.When placed on the same scale (0-42), rSAS value was 6.5 units lower than SAS value with minimal floor/ceiling effects. Estimated change over time was identical (0.12 units/month) which was not substantial (1.44 units/year) but greater than expected assuming no change (t: 3.6 and 2.4).ConclusionThe retained items of the rSAS targeted behaviours more than beliefs and results support the rSAS as a robust measure of apathy in people with chronic stroke.
How can risk of COVID-19 transmission be minimised in domiciliary care for older people: development, parameterisation and initial results of a simple mathematical model
Authors: Kiss István Z. , Blyuss Konstantin B. , Kyrychko Yuliya N. , Middleton Jo , Roland Daniel , Bertini Lavinia , Bogen-Johnston Leanne , Wood Wendy , Sharp Rebecca , Forder Julien , Cassell Jackie 
Published: May 2021

AbstractThis paper proposes and analyses a stochastic model for the spread of an infectious disease that is transmitted between clients and care workers in the UK domiciliary care setting. Interactions between clients and care workers are modelled using specially generated networks, with network parameters reflecting realistic patterns of care needs and visit allocation. These networks are then used to simulate and SEIR-type epidemic dynamics with different numbers of infectious and recovery stages. The results indicate that with the same overall capacity provided by care workers, the minimum peak proportion of infection, and the smallest overall size of infection are achieved for the highest proportion of overlap between visit allocation, i.e. when care workers have the highest chances of being allocated a visit to the same client they have visited before. An intuitive explanation of this is that while providing the required care coverage, maximising overlap in visit allocation reduces the possibility of an infectious care worker inadvertently spreading the infection to other clients. The model is quite generic and can be adapted to any particular directly transmitted infectious disease, such as, more recently, COVID-19, provided accurate estimates of disease parameters can be obtained from real data.
Circadian Regulation of Vertebrate Cone Photoreceptor Function
Authors: Zang Jingjing , Gesemann Matthias , Keim Jennifer , Samardzija Marijana , Grimm Christian , Neuhauss Stephan C.F. 
Published: May 2021

AbstractEukaryotes generally display a circadian rhythm as an adaption to the reoccurring day/night cycle. This is particularly true for visual physiology that is directly affected by changing light conditions. Here we investigate the influence of the circadian rhythm on the expression and function of visual transduction cascade regulators in diurnal zebrafish and nocturnal mice. We focused on regulators of shut-off kinetics such asrecoverins, arrestins, opsin kinases, andGTPase-accelerating proteinthat have direct effects on temporal vision. Transcript as well as protein levels of most analyzed genes show a robust circadian rhythm dependent regulation, which correlates with changes in photoresponse kinetics. Electroretinography demonstrates that photoresponse recovery in zebrafish is delayed in the evening and accelerated in the morning. This physiological rhythmicity is mirrored in visual behaviors, such as optokinetic and optomotor responses. Functional rhythmicity persists in continuous darkness, it is reversed by an inverted light cycle and disrupted by constant light. This is in line with our finding that orthologous gene transcripts from diurnal zebrafish and nocturnal mice are often expressed in an anti-phasic daily rhythm.
Targeting Integrated Stress Response by ISRIB combined with imatinib attenuates STAT5 signaling and eradicates therapy-resistant Chronic Myeloid Leukemia cells
Authors: Dudka Wioleta , Hoser Grażyna , Mondal Shamba S. , Turos-Korgul Laura , Swatler Julian , Kusio-Kobiałka Monika , Wołczyk Magdalena , Klejman Agata , Brewińska-Olchowik Marta , Kominek Agata , Wiech Milena , Machnicki Marcin M , Seferyńska Ilona , Stokłosa Tomasz , Piwocka Katarzyna 
Published: May 2021

AbstractIntegrated Stress Response (ISR) facilitates cellular adaptation to variable environmental conditions by reprogramming cellular response. Activation of ISR was reported in neurological disorders and solid tumours, but its function in hematological malignancies remains largely unknown. Previously we showed that ISR is activated in chronic myeloid leukemia (CML) CD34+ cells, and its activity correlates with disease progression and imatinib resistance. Here we demonstrate that inhibition of ISR by small molecule ISRIB, but not by PERK inhibitor GSK2656157, restores sensitivity to imatinib and eliminates CM Blast Crisis (BC) D34+ resistant cells. We found that in Patient Derived Xenograft (PDX) mouse model bearing CD34+ imatinib/dasatinib-resistant CML blasts withPTPN11gain-of-function mutation, combination of imatinib and ISRIB decreases leukemia engraftment. Furthermore, genes related to SGK3, RAS/RAF/MAPK, JAK2 and IFNγ pathways were downregulated upon combined treatment. Remarkably, we confirmed that ISRIB and imatinib combination decreases STAT5 phosphorylation and inhibits expression of STAT5-target genes responsible for proliferation, viability and stress response. Thus, our data point to a substantial effect of imatinib and ISRIB combination, that results in transcriptomic deregulation and eradication of imatinib-resistant cells. Our findings suggest such drug combination might improve therapeutic outcome of TKI-resistant leukemia patients exhibiting constitutive STAT5 activation.
Predicting the presence and abundance of bacterial taxa in environmental communities through flow cytometric fingerprinting
Authors: Heyse Jasmine , Schattenberg Florian , Rubbens Peter , Müller Susann , Waegeman Willem , Boon Nico , Props Ruben 
Published: May 2021

AbstractMicrobiome management research and applications rely on temporally-resolved measurements of community composition. Current technologies to assess community composition either make use of cultivation or sequencing of genomic material, which can become time consuming and/or laborious in case high-throughput measurements are required. Here, using data from a shrimp hatchery as an economically relevant case study, we combined 16S rRNA gene amplicon sequencing and flow cytometry data to develop a computational workflow that allows the prediction of taxon abundances based on flow cytometry measurements. The first stage of our pipeline consists of a classifier to predict the presence or absence of the taxon of interest, with yields an average accuracy of 88.13±4.78 % across the top 50 OTUs of our dataset. In the second stage, this classifier was combined with a regression model to predict the relative abundances of the taxon of interest, which yields an average R2of 0.35±0.24 across the top 50 OTUs of our dataset. Application of the models on flow cytometry time series data showed that the generated models can predict the temporal dynamics of a large fraction of the investigated taxa. Using cell-sorting we validated that the model correctly associates taxa to regions in the cytometric fingerprint where they are detected using 16S rRNA gene amplicon sequencing. Finally, we applied the approach of our pipeline on two other datasets of microbial ecosystems. This pipeline represents an addition to the expanding toolbox for flow cytometry-based monitoring of bacterial communities and complements the current plating- and marker gene-based methods.ImportanceMonitoring of microbial community composition is crucial for both microbiome management research and applications. Existing technologies, such as plating and amplicon sequencing, can become laborious and expensive when high-throughput measurements are required. Over the recent years, flow cytometry-based measurements of community diversity have been shown to correlate well to those derived from 16S rRNA gene amplicon sequencing in several aquatic ecosystems, suggesting there is a link between the taxonomic community composition and phenotypic properties as derived through flow cytometry. Here, we further integrated 16S rRNA gene amplicon sequencing and flow cytometry survey data in order to construct models that enable the prediction of both the presence and the abundance of individual bacterial taxa in mixed communities using flow cytometric fingerprinting. The developed pipeline holds great potential to be integrated in routine monitoring schemes and early warning systems for biotechnological applications.
Detection of persistent SARS-CoV-2 IgG antibodies in oral mucosal fluid and upper respiratory tract specimens following COVID-19 mRNA vaccination
Authors: Mades Aubree , Chellamathu Prithivi , Lopez Lauren , Kojima Noah , MacMullan Melanie A. , Denny Nicholas , Angel Aaron N. , Casian Joseph G. , Brobeck Matthew , Nirema Nina , Klausner Jeffrey D , Turner Frederick , Slepnev Vladimir I. , Ibrayeva Albina 
Published: May 2021

AbstractPrevious studies have shown that mRNA COVID-19 vaccines are highly effective at preventing SAR-CoV-2 infection by generating an immune response, which in part produces SARS-CoV-2 IgG antibodies in serum. In this study, we hypothesized that COVID-19 vaccines may elicit production of SARS-CoV-2 IgG antibodies in the upper respiratory tract, such as in oral and nasal mucosal fluid. To test that hypothesis, we enrolled 114 participants within 3-7 days of receiving the first dose of the Moderna mRNA COVID-19 vaccine and collected oral mucosal fluid samples on days 5, 10, 15, and 20 after each vaccine dose. Of participants naive to SARS-CoV-2 (n = 89), 79 (85.4%) tested positive for SARS-CoV-2 IgG antibodies by time point 2 (10 days +/-2 days after first vaccine dose), and 100% tested positive for SARS-CoV-2 IgG by time point 3 (15 days +/-2 days after first vaccine dose). Additionally, we collected paired oral mucosal fluid and anterior nares samples from 10 participants who had received both vaccine doses. We found that participants had an average SARS-CoV-2 IgG antibody concentration of 2496.0 +/-2698.0ng/mL in nasal mucosal fluid versus 153.4 +/-141.0ng/mL in oral mucosal fluid. Here, we demonstrate detection and longitudinal persistence of SARS-CoV-2 IgG antibodies in upper respiratory tract specimens following COVID-19 mRNA vaccination.
Short-term effects of BNT162b2 mRNA COVID-19 vaccination on physiological measures: a prospective study
Authors: Gepner Yftach , Mofaz Merav , Oved Shay , Yechezkel Matan , Constantini Keren , Goldstein Nir , Shmueli Erez , Yamin Dan 
Published: May 2021

AbstractBackgroundClinical trial guidelines for assessing the safety of vaccines, including the FDA criteria, are primarily based on subjective, self-reported questionnaires. Despite the tremendous technological advances in recent years, objective, continuous assessment of physiological measures post-vaccination is rarely performed.MethodsTo evaluate the short-term effects of the BNT162b2 COVID-19 vaccine on physiological measures, we conducted a prospective observational study during the mass vaccination campaign in Israel. 160 individuals >18 years who were not previously found to be COVID-19 positive and who received the second dose of the COVID-19 vaccine between 1 January, 2021, and 13 March, 2021 were equipped with a chest-patch sensor and a dedicated mobile application. The chest-patch sensor continuously measured 13 physiological vitals one day before the inoculation (baseline), for four days: heart rate, blood oxygen saturation, respiratory rate, systolic and diastolic blood pressure, pulse pressure, mean arterial pressure, heart rate variability, stroke volume, cardiac output, cardiac index, systemic vascular resistance, and body temperature. The mobile application collected daily self-reported questionnaires starting one day before the inoculation, for 15 days on local and systemic reactions, sleep quality, stress levels, physical activity, and mood levels.FindingsWithin the first 48 hours post-vaccination, we identified significant changes (p-value <0.05) in nearly all 13 chest-patch indicators compared to their baseline levels. 48.5% (n=78) reported no local or systemic reaction. Nevertheless, we identified considerable changes in chest-patch indicators during the first 48 hours post-vaccination also in this group of presumably asymptomatic participants. Within three days from vaccination, these measures returned to baseline levels in both groups, further supporting the safety of the vaccine.InterpretationOur work underscores the importance of obtaining objective physiological data in addition to self-reported questionnaires when performing clinical trials, particularly in ones conducted in very short time frames.FundingThe European Research Council (ERC) project #949850.
Relationships of diversity and evenness in adaptation strategies of the effect of protective coloration of animals
Authors: Bespalov Yu. , Kabalyants P. , Zuev S. 
Published: May 2021

AbstractThis study aims to investigate the relationship between the diversity and uniformity of the protective coloration of animals. The protective coloration of animals is the result of the formation of adaptation strategies. The aim of this study is to identify the colorimetric parameters that characterize the adaptive properties of the protective coloration of animals in relation to their natural habitat. The relevance of this study is related to the importance of the tasks of remote collection of information about various biological species; in particular, animals that carry dangerous infections. This is all the more important in light of the current epidemic problems facing humanity. The revealed colorimetric characteristics can be used to describe digital images and their further recognition. They can be classifying features in machine learning algorithms. We give an example of digital image processing of a duck (Anas platyrhynchos). The analysis of the distribution of the found colorimetric parameter makes it possible to identify the image segments corresponding to theAnas platyrhynchos. The results thus obtained are also of interest from the point of view of the problem of the adaptive role of the diversity of biological systems in relation to the problem of the mechanisms of functioning of the protective coloration of animals.
The transcription factor EGR2 is indispensable for tissue-specific imprinting of alveolar macrophages in health and tissue repair
Authors: McCowan Jack , Kirkwood Phoebe M. , Fercoq Frédéric , T’Jonck Wouter , Mawer Connar M. , Cunningham Richard , Mirchandani Ananda S. , Hoy Anna , Jones Gareth-Rhys , Hansen Carsten G. , Hirani Nik , Jenkins Stephen J. , Henri Sandrine , Malissen Bernard , Walmsley Sarah R. , Dockrell David H. , Saunders Philippa T. K. , Carlin Leo M. , Bain Calum C. 
Published: May 2021

AbstractAlveolar macrophages are the most abundant macrophages in the healthy lung where they play key roles in homeostasis and immune surveillance against air-borne pathogens. Tissue-specific differentiation and survival of alveolar macrophages relies on niche-derived factors, such as colony stimulating factor 2 (CSF-2) and transforming growth factor beta (TGF-β). However, the nature of the downstream molecular pathways that regulate the identity and function of alveolar macrophages and their response to injury remains poorly understood. Here, we identify that the transcriptional factor EGR2 is an evolutionarily conserved feature of lung alveolar macrophages and show that cell-intrinsic EGR2 is indispensable for the tissue-specific identity of alveolar macrophages. Mechanistically, we show that EGR2 is driven by TGF-β and CSF-2 in a PPAR-γ-dependent manner to control alveolar macrophage differentiation. Functionally, EGR2 was dispensable for lipid handling, but crucial for the effective elimination of the respiratory pathogenStreptococcus pneumoniae. Finally, we show that EGR2 is required for repopulation of the alveolar niche following sterile, bleomycin-induced lung injury and demonstrate that EGR2-dependent, monocyte-derived alveolar macrophages are vital for effective tissue repair following injury. Collectively, we demonstrate that EGR2 is an indispensable component of the transcriptional network controlling the identity and function of alveolar macrophages in health and disease.One Sentence SummaryEGR2 controls alveolar macrophage function in health and disease
Reinforcement alone does not explain increased reproductive isolation in sympatry
Authors: Matute Daniel R. , Cooper Brandon S. 
Published: May 2021

AbstractComparative studies of reproductive isolation (RI) by Coyne and Orr (1, 2) and others indicate a significant role for reinforcing natural selection inDrosophilaspeciation. The reinforcement hypothesis predicts increased prezygotic, but not postzygotic, RI between sympatric species pairs in response to maladaptive hybridization. We revisit this hypothesis and others using additionalDrosophila, Lepidopteran, and toad(Bufo)data. In contrast to the predictions of reinforcement, we find increased premating and postzygotic RI between sympatricDrosophilaspecies, including between recently diverged species pairs, as defined by Coyne and Orr (1) and others (i.e.,DNei< 0.5). However, at slightly lower divergence thresholds increased postzygotic RI in sympatry is not statistically significant, while increased premating RI is, generally in agreement with the predictions of reinforcement. While premating data are unavailable, postzygotic RI is also increased between sympatric Lepidopteran and toad (Bufo) species. We find only modest support for “concordant asymmetries” in premating and postzygotic RI between sympatricDrosophila, described by others as uniquely supporting reinforcement. Finally, the proportion of geographic range overlap shared by species is positively associated with the magnitude of premating RI as predicted by reinforcement, but it is also positively associated with postzygotic RI, which cannot be explained by reinforcement. Taken together, our results demonstrate that comparisons of premating and postzygotic RI in sympatry depend greatly on divergence time, and suggest that fusion, extinction, and/or other mechanisms must combine with reinforcement to generate these patterns.Significance StatementUnderstanding mechanisms underlying the origin of species remains a central goal of biology. By combining laboratory estimates of premating and postzygotic reproductive isolation (RI) with phylogenetic hypotheses, geographic range data, and genetic divergence estimates, the fundamental meta-analyses of Coyne and Orr provided compelling support that reinforcement contributes significantly toDrosophilaspeciation. Using additionalDrosophiladata, we demonstrate increased premating and postzygotic RI in sympatry. Postzygotic RI is also increased in sympatry between Lepidopteran and toad species. We also find only modest support for patterns previously described as uniquely supporting reinforcement. Together, our analyses demonstrate that comparisons of premating and postzygotic RI depend on divergence time, and suggest that fusion, extinction, and/or other mechanisms combine with reinforcement to produce these patterns.