Multiplatform analyses reveal distinct drivers of systemic pathogenesis in adult versus pediatric severe acute COVID-19.

The pathogenesis of multi-organ dysfunction associated with severe acute SARS-CoV-2 infection remains poorly understood. Endothelial damage and microvascular thrombosis have been identified as drivers of COVID-19 severity, yet the mechanisms underlying these processes remain elusive. Here we show alterations in fluid shear stress-responsive pathways in critically ill COVID-19 adults as compared to non-COVID critically ill adults using a multiomics approach.

Dysregulated naive B cells and de novo autoreactivity in severe COVID-19.

Severe SARS-CoV-2 infection has been associated with highly inflammatory immune activation since the earliest days of the COVID-19 pandemic. More recently, these responses have been associated with the emergence of self-reactive antibodies with pathologic potential, although their origins and resolution have remained unclear. Previously, we and others have identified extrafollicular B cell activation, a pathway associated with the formation of new autoreactive antibodies in chronic autoimmunity, as a dominant feature of severe and critical COVID-19 (refs.

Descriptive analysis of seizures and comorbidities associated with fragile X syndrome.

Background: Fragile X syndrome is characterized by a myriad of physical features, behavioral features, and medical problems. Commonly found behavioral features are hyperactivity, anxiety, socialization difficulties, and ASD. There is also a higher incidence than in the general population of strabismus, otitis media, and mitral valve prolapse.

An empirical bayesian approach for testing gene expression fold change and its application in detecting global dosage effects.

We are motivated by biological studies intended to understand global gene expression fold change. Biologists have generally adopted a fixed cutoff to determine the significance of fold changes in gene expression studies (e.g.

Study of telomere length in men who carry a fragile X premutation or full mutation allele.

The fragile X premutation is defined by the expansion of the CGG trinucleotide repeat at the 5' UTR of the FMR1 gene to between 55 and 200 repeats, while repeat tracks longer than 200 are defined as full mutations. Men carrying a premutation are at increased risk for fragile X-associated tremor/ataxia syndrome (FXTAS); those with > 200 repeats have fragile X syndrome, a common genetic form of intellectual disabilities. In our study, we tested the hypothesis that men carrying a fragile X premutation or full mutation are "biologically older", as suggested by the associated age-related disorder in the presence of the fragile X premutation or the altered cellular pathology that affects both the fragile X premutation and full mutation carriers.

Analysis of the genomic expression profile in trisomy 18: insight into possible genes involved in the associated phenotypes.

Trisomy 18, sometimes called Edwards syndrome, occurs in about 1 in 6000 live births and causes multiple birth defects in affected infants. The extra copy of chromosome 18 causes the altered expression of many genes and leads to severe skeletal, cardiovascular and neurological systems malformations as well as other medical problems. Due to the low rate of survival and the massive genetic imbalance, little research has been aimed at understanding the molecular consequences of trisomy 18 or considering potential therapeutic approaches.

Author Correction: Factors of the bone marrow microniche that support human plasma cell survival and immunoglobulin secretion.

The original version of this Article omitted a declaration from the Competing Interests statement, which should have included the following: 'A patent has been applied for by Emory University with F.E.L, I.

Factors of the bone marrow microniche that support human plasma cell survival and immunoglobulin secretion.

Human antibody-secreting cells (ASC) in peripheral blood are found after vaccination or infection but rapidly apoptose unless they migrate to the bone marrow (BM). Yet, elements of the BM microenvironment required to sustain long-lived plasma cells (LLPC) remain elusive. Here, we identify BM factors that maintain human ASC > 50 days in vitro.

Women who carry a fragile X premutation are biologically older than noncarriers as measured by telomere length.

Women who carry a fragile X premutation, defined as having 55-200 unmethylated CGG repeats in the 5' UTR of the X-linked FMR1 gene, have a 20-fold increased risk for primary ovarian insufficiency (FXPOI). We tested the hypothesis that women with a premutation + FXPOI have shorter telomeres than those without FXPOI because they are "biologically older." Using linear regression, we found that women carrying a premutation (n = 172) have shorter telomeres and hence, are "biologically older" than women carrying the normal size allele (n = 81).

Long-Lived Plasma Cells Are Contained within the CD19(-)CD38(hi)CD138(+) Subset in Human Bone Marrow.

Antibody responses to viral infections are sustained for decades by long-lived plasma cells (LLPCs). However, LLPCs have yet to be characterized in humans. Here we used CD19, CD38, and CD138 to identify four PC subsets in human bone marrow (BM).

Incidence of fragile X syndrome by newborn screening for methylated FMR1 DNA.

Fragile X syndrome (FXS) results from a CGG-repeat expansion that triggers hypermethylation and silencing of the FMR1 gene. FXS is referred to as the most common form of inherited intellectual disability, yet its true incidence has never been measured directly by large population screening. Here, we developed an inexpensive and high-throughput assay to quantitatively assess FMR1 methylation in DNA isolated from the dried blood spots of 36,124 deidentified newborn males.