Abstract Background West Africa has recorded a relatively higher proportion of asymptomatic coronavirus disease 2019 (COVID-19) cases than the rest of the world, and West Africa-specific host factors could play a role in this discrepancy. Here, we assessed the association between COVID-19 severity among Ghanaians with their immune profiles and ABO blood groups. Methods Plasma samples were obtained from Ghanaians PCR-confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-positive individuals. The participants were categorized into symptomatic and asymptomatic cases. Cytokine profiling and antibody quantification were performed using Luminex™ multiplex assay whereas antigen-driven agglutination assay was used to assess the ABO blood groups. Immune profile levels between symptomatic and asymptomatic groups were compared using the two-tailed Mann-Whitney U test. Multiple comparisons of cytokine levels among and between days were tested using Kruskal-Wallis with Dunn’s post hoc test. Correlations within ABO blood grouping (O’s and non-O’s) and between cytokines were determined using Spearman correlations. Logistic regression analysis was performed to assess the association of various cytokines with asymptomatic phenotype. Results There was a trend linking blood group O to reduced disease severity, but this association was not statistically significant. Generally, symptomatic patients displayed significantly (p < 0.05) higher cytokine levels compared to asymptomatic cases with exception of Eotaxin, which was positively associated with asymptomatic cases. There were also significant (p < 0.05) associations between other immune markers (IL-6, IL-8 and IL-1Ra) and disease severity. Cytokines’ clustering patterns differ between symptomatic and asymptomatic cases. We observed a steady decrease in the concentration of most cytokines over time, while anti-SARS-CoV-2 antibody levels were stable for at least a month, regardless of the COVID-19 status. Conclusions The findings suggest that genetic background and pre-existing immune response patterns may in part shape the nature of the symptomatic response against COVID-19 in a West African population. This study offers clear directions to be explored further in larger studies.
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Raw scores for KBIT-2 and total scores for informant questionnaires
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Female lethality data for C. hominivorax FL11 and FL12 heterozygous lines. (XLSX 36 kb)
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Additional file 6. Tal1 expression in an E7.75 embryo rotating around its proximal distal axis A = anterior, P = posterior, YS = yolk sac, ECs = endothelial cells. Tal1 expression in an E7.75, fixed, non-cleared embryo, imaged by light sheet microscopy, rotating around the vertical axis.
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Additional file 10: Table S9. Classification of eQTLs detected by AD Model (Table S9-1, F2 pigs liver tissue; Table S9-2, F2 pigs muscle tissue; Table S9-3, HS rats amygdala genes expression; Table S9-4, HS rats heart genes expression; Table S9-5, amygdala transcripts expression; Table S9-6, heart transcripts expression; Table S9-7, HS mice hippocampus gene expression; Table S9-8, HS mice liver gene expression; Table S9-9, HS mice lung gene expression). Rows with -log10(P)values of ADvsA Model > 6 are in red, remaining rows with -log10(P)values of AD Model> 10 are in blue.
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Abstract Introduction Conditionally immortalised human neural progenitor cells (hNPCs) represent a robust source of native neural cells to investigate physiological mechanisms in both health and disease. However, in order to recognise the utility of such cells, it is critical to determine whether they retain characteristics of their tissue of origin and generate appropriate neural cell types upon differentiation. To this end, we have characterised the conditionally immortalised, cortically-derived, human NPC line, CTX0E16, investigating the molecular and cellular phenotype of differentiated neurons to determine whether they possess characteristics of cortical glutamatergic neurons. Methods Differentiated CTX0E16 cells were characterised by assessing expression of several neural fates markers, and examination of developing neuronal morphology. Expression of neurotransmitter receptors, signalling proteins and related proteins were assessed by q- and RT-PCR and complemented by Ca2+ imaging, electrophysiology and assessment of ERK signalling in response to neurotransmitter ligand application. Finally, differentiated neurons were assessed for their ability to form putative synapses and to respond to activity-dependent stimulation. Results Differentiation of CTX0E16 hNPCs predominately resulted in the generation of neurons expressing markers of cortical and glutamatergic (excitatory) fate, and with a typical polarized neuronal morphology. Gene expression analysis confirmed an upregulation in the expression of cortical, glutamatergic and signalling proteins following differentiation. CTX0E16 neurons demonstrated Ca2+ and ERK1/2 responses following exogenous neurotransmitter application, and after 6 weeks displayed spontaneous Ca2+ transients and electrophysiological properties consistent with that of immature neurons. Differentiated CTX0E16 neurons also expressed a range of pre- and post-synaptic proteins that co-localized along distal dendrites, and moreover, displayed structural plasticity in response to modulation of neuronal activity. Conclusions Taken together, these findings demonstrate that the CTX0E16 hNPC line is a robust source of cortical neurons, which display functional properties consistent with a glutamatergic phenotype. Thus CTX0E16 neurons can be used to study cortical cell function, and furthermore, as these neurons express a range of disease-associated genes, they represent an ideal platform with which to investigate neurodevelopmental mechanisms in native human cells in health and disease.
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Background: There is increasing emphasis in medical research on modelling growth across the life course and identifying factors associated with growth. Here, we demonstrate multilevel models for childhood growth either as a smooth function (using fractional polynomials) or a set of connected linear phases (using linear splines). Methods: We related parental social class to height from birth to 10 years of age in 5,588 girls from the Avon Longitudinal Study of Parents and Children (ALSPAC). Multilevel fractional polynomial modelling identified the best-fitting model as being of degree 2 with powers of the square root of age, and the square root of age multiplied by the log of age. The multilevel linear spline model identified knot points at 3, 12 and 36 months of age. Results: Both the fractional polynomial and linear spline models show an initially fast rate of growth, which slowed over time. Both models also showed that there was a disparity in length between manual and non-manual social class infants at birth, which decreased in magnitude until approximately 1 year of age and then increased. Conclusions: Multilevel fractional polynomials give a more realistic smooth function, and linear spline models are easily interpretable. Each can be used to summarise individual growth trajectories and their relationships with individual-level exposures.
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Additional file 3. CpG DNA does not stimulate STAT1 phosphorylation or ISG expression. HeLa cells were stimulated with TLR ligands for 5 h. TLR3 was targeted with 0.1, 1, 10 μg/ml polyIC, TLR7 with 0.3, 3, 30 nM Gardiquimod (Gard), TLR8/7 with 0.3, 3, 30 nM CL075, TLR7/8 with 0.01, 0.1, 1 μg/ml R848, TLR9 with 0.01, 0.1, 1 μg/ml CpG DNA, TLR13 with 0.01, 0.1, 1 μg/ml 23S ribosomal RNA (rRNA). TLR 4, 2 and 5 were targeted with 0.1 μg/ml LPS, Pam3Cys (P3C) or Flagellin (FliC), respectively. As controls for pattern recognition receptor signaling and JAK-STAT signaling, cells were infected with 50 HAU/ml Sendai virus (SeV) for 5 h or stimulated with 0.01 μg/ml IFN-β for 1 h, respectively. Activation of IFN signaling was monitored by western immunoblotting against phosphorylated STAT1 (pSTAT1) or expression of the ISG IFIT1. Actin was used as a loading control. (* Denotes the molecular weight marker).
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Abstract Background West Africa has recorded a relatively higher proportion of asymptomatic coronavirus disease 2019 (COVID-19) cases than the rest of the world, and West Africa-specific host factors could play a role in this discrepancy. Here, we assessed the association between COVID-19 severity among Ghanaians with their immune profiles and ABO blood groups. Methods Plasma samples were obtained from Ghanaians PCR-confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-positive individuals. The participants were categorized into symptomatic and asymptomatic cases. Cytokine profiling and antibody quantification were performed using Luminex™ multiplex assay whereas antigen-driven agglutination assay was used to assess the ABO blood groups. Immune profile levels between symptomatic and asymptomatic groups were compared using the two-tailed Mann-Whitney U test. Multiple comparisons of cytokine levels among and between days were tested using Kruskal-Wallis with Dunn’s post hoc test. Correlations within ABO blood grouping (O’s and non-O’s) and between cytokines were determined using Spearman correlations. Logistic regression analysis was performed to assess the association of various cytokines with asymptomatic phenotype. Results There was a trend linking blood group O to reduced disease severity, but this association was not statistically significant. Generally, symptomatic patients displayed significantly (p < 0.05) higher cytokine levels compared to asymptomatic cases with exception of Eotaxin, which was positively associated with asymptomatic cases. There were also significant (p < 0.05) associations between other immune markers (IL-6, IL-8 and IL-1Ra) and disease severity. Cytokines’ clustering patterns differ between symptomatic and asymptomatic cases. We observed a steady decrease in the concentration of most cytokines over time, while anti-SARS-CoV-2 antibody levels were stable for at least a month, regardless of the COVID-19 status. Conclusions The findings suggest that genetic background and pre-existing immune response patterns may in part shape the nature of the symptomatic response against COVID-19 in a West African population. This study offers clear directions to be explored further in larger studies.
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Raw scores for KBIT-2 and total scores for informant questionnaires
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Female lethality data for C. hominivorax FL11 and FL12 heterozygous lines. (XLSX 36 kb)
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