Direct comparison of SARS-CoV-2 variant specific neutralizing antibodies in human and hamster sera

Antigenic characterization of newly emerging SARS-CoV-2 variants is important to assess their immune escape and judge the need for future vaccine updates. To bridge data obtained from animal sera with human sera, we analyzed neutralizing antibody titers in human and hamster single infection sera in a highly controlled setting using the same authentic virus neutralization assay performed in one laboratory. Using a Bayesian framework, we found that titer fold changes in hamster sera corresponded well to human sera and that hamster sera generally exhibited higher reactivity.</p

Direct comparison of SARS-CoV-2 variant specific neutralizing antibodies in human and hamster sera

Antigenic characterization of newly emerging SARS-CoV-2 variants is important to assess their immune escape and judge the need for future vaccine updates. To bridge data obtained from animal sera with human sera, we analyzed neutralizing antibody titers in human and hamster single infection sera in a highly controlled setting using the same authentic virus neutralization assay performed in one laboratory. Using a Bayesian framework, we found that titer fold changes in hamster sera corresponded well to human sera and that hamster sera generally exhibited higher reactivity.</p

Ripple Effect Mapping Outcomes of a Childhood Obesity Prevention Program From Youth and Adult Dyads Using a Qualitative Approach: iCook 4-H

Objective: To describe the impact of the iCook 4-H intervention study based on data gathered through ripple effect mapping focus groups through an explorative approach. Design: Youth–adult dyads responded about ways in which iCook had affected the individual, family, and community. Three questions were asked: (1) What were people doing differently as a result of iCook? (2) Who benefited from iCook and how? (3) Were there changes in the way community groups and institutions did things as a result of iCook?Setting: Ripple effect mapping sessions took place across 5 states (Maine, Nebraska, South Dakota, Tennessee, and West Virginia). Participants: Seventy dyad participants (n = 35 youth, n = 35 adults) from the iCook 4-H intervention. Main Outcome Measure: Three core themes of iCook 4-H were assessed: cooking, eating, and playing together. Analysis: Direct content analysis and word frequencies were used. Results: Seven categories emerged: improved health, increased community involvement, increased knowledge, increased communication, changed motivation, financial mindfulness, and increased appreciation for family. An overarching theme that was determined was that learning new skills together through trying new things (cooking, eating, and playing) leads to positive individual family and community change. Conclusions and Implications: Ripple effect mapping was effective in determining the perceived impact of iCook 4-H on oneself, family, and community

Dysregulated immunologic landscape of early host response in melioidosis

Melioidosis, a neglected tropical infection caused by Burkholderia pseudomallei, commonly presents as pneumonia or sepsis with mortality rates up to 50% despite appropriate treatment. A better understanding of the early host immune response to melioidosis may lead to new therapeutic interventions and prognostication strategies to reduce disease burden. Whole blood transcriptomic signatures in 164 melioidosis patients and 70 patients with other infections hospitalized in northeastern Thailand enrolled within 24 hours following hospital admission were studied. Key findings were validated in an independent melioidosis cohort. Melioidosis was characterized by upregulation of interferon signaling responses compared to other infections. Mortality in melioidosis was associated with excessive inflammation, up-regulated type 2 immune responses and a dramatic decrease in T cell-mediated immunity compared to survivors. We identified and independently confirmed a five-gene predictive set classifying fatal melioidosis (validation cohort: an area under the receiver operating characteristic curve 0.83, 95% CI: 0.67-0.99). In conclusion, this study highlights the intricate balance between innate and adaptive immunity during fatal melioidosis and can inform future precision medicine strategies for targeted therapies and prognostication in this severe infection

Melatonin Acts as an Antidepressant by Inhibition of the Acid Sphingomyelinase/Ceramide System

Background: Melatonin has been shown to have antidepressive effects. We tested whether melatonin inhibits the acid sphingomyelinase/ceramide system and mediates its antidepressive effects via inhibition of the acid sphingomyelinase and a reduction of ceramide in the hippocampus. Antidepressants such as amitriptyline and fluoxetine were previously shown to inhibit the acid sphingomyelinase/ceramide system, which mediates neurogenesis and behavioral changes induced by these drugs. Methods: The effect of melatonin on the activity of the acid sphingomyelinase prior to and after treatment with melatonin was determined in cultured neurons and in vivo in the hippocampus of mice by measuring the consumption of [14C] sphingomyelin. Ceramide was measured by DAG kinase assay and fluorescence microscopy of the hippocampus and of cultured neurons. Neurogenesis in the hippocampus was analyzed by in vivo labeling with bromodeoxyuridine. Behavior was assessed in standardized tests. Results: Melatonin treatment inhibited acid sphingomyelinase in vitro in cultured pheochromocytoma cells and in vivo in the hippocampus, which resulted in a reduction of ceramide in vitro and in vivo. The inhibition of the acid sphingomyelinase/ceramide system translated into increased neurogenesis in glucocorticosterone-stressed mice after treatment with melatonin, an effect that is abrogated in acid sphingomyelinase-deficient mice. Likewise, melatonin improved the depressive behavior of stressed mice, a therapeutic effect that was again absent in acid sphingomyelinase-deficient animals. Conclusion: These data indicate that the antidepressive effects of melatonin as well as the induction of neurogenesis triggered by this drug are mediated by an inhibition of the acid sphingomyelinase/ceramide system. This is the first study to identify melatonin as an inhibitor of the acid sphingomyelinase

Investigation of previously implicated genetic variants in chronic tic disorders: a transmission disequilibrium test approach

Genetic studies in Tourette syndrome (TS) are characterized by scattered and poorly replicated findings. We aimed to replicate findings from candidate gene and genome-wide association studies (GWAS). Our cohort included 465 probands with chronic tic disorder (93% TS) and both parents from 412 families (some probands were siblings). We assessed 75 single nucleotide polymorphisms (SNPs) in 465 parent–child trios; 117 additional SNPs in 211 trios; and 4 additional SNPs in 254 trios. We performed SNP and gene-based transmission disequilibrium tests and compared nominally significant SNP results with those from a large independent case–control cohort. After quality control 71 SNPs were available in 371 trios; 112 SNPs in 179 trios; and 3 SNPs in 192 trios. 17 were candidate SNPs implicated in TS and 2 were implicated in obsessive–compulsive disorder (OCD) or autism spectrum disorder (ASD); 142 were tagging SNPs from eight monoamine neurotransmitter-related genes (including dopamine and serotonin); 10 were top SNPs from TS GWAS; and 13 top SNPs from attention-deficit/hyperactivity disorder, OCD, or ASD GWAS. None of the SNPs or genes reached significance after adjustment for multiple testing. We observed nominal significance for the candidate SNPs rs3744161 (TBCD) and rs4565946 (TPH2) and for five tagging SNPs; none of these showed significance in the independent cohort. Also, SLC1A1 in our gene-based analysis and two TS GWAS SNPs showed nominal significance, rs11603305 (intergenic) and rs621942 (PICALM). We found no convincing support for previously implicated genetic polymorphisms. Targeted re-sequencing should fully appreciate the relevance of candidate genes

Genomic Relationships, Novel Loci, and Pleiotropic Mechanisms across Eight Psychiatric Disorders

Genetic influences on psychiatric disorders transcend diagnostic boundaries, suggesting substantial pleiotropy of contributing loci. However, the nature and mechanisms of these pleiotropic effects remain unclear. We performed analyses of 232,964 cases and 494,162 controls from genome-wide studies of anorexia nervosa, attention-deficit/hyper-activity disorder, autism spectrum disorder, bipolar disorder, major depression, obsessive-compulsive disorder, schizophrenia, and Tourette syndrome. Genetic correlation analyses revealed a meaningful structure within the eight disorders, identifying three groups of inter-related disorders. Meta-analysis across these eight disorders detected 109 loci associated with at least two psychiatric disorders, including 23 loci with pleiotropic effects on four or more disorders and 11 loci with antagonistic effects on multiple disorders. The pleiotropic loci are located within genes that show heightened expression in the brain throughout the lifespan, beginning prenatally in the second trimester, and play prominent roles in neurodevelopmental processes. These findings have important implications for psychiatric nosology, drug development, and risk prediction.Peer reviewe

Study of ordered hadron chains with the ATLAS detector

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