Synthesis and X-ray diffraction structure of a novel steroid-pyrrolidinoisoquinoline alkaloid hybrid

1575-1578A novel steroid – pyrrolidinoisoquinoline alkaloid hybrid has been successfully synthesized by Diels-Alder reaction N-acyliminium ion cyclization sequence

SARS-CoV-2 susceptibility and COVID-19 disease severity are associated with genetic variants affecting gene expression in a variety of tissues

Variability in SARS-CoV-2 susceptibility and COVID-19 disease severity between individuals is partly due to genetic factors. Here, we identify 4 genomic loci with suggestive associations for SARS-CoV-2 susceptibility and 19 for COVID-19 disease severity. Four of these 23 loci likely have an ethnicity-specific component. Genome-wide association study (GWAS) signals in 11 loci colocalize with expression quantitative trait loci (eQTLs) associated with the expression of 20 genes in 62 tissues/cell types (range: 1:43 tissues/gene), including lung, brain, heart, muscle, and skin as well as the digestive system and immune system. We perform genetic fine mapping to compute 99% credible SNP sets, which identify 10 GWAS loci that have eight or fewer SNPs in the credible set, including three loci with one single likely causal SNP. Our study suggests that the diverse symptoms and disease severity of COVID-19 observed between individuals is associated with variants across the genome, affecting gene expression levels in a wide variety of tissue types

Trans-ethnic and Ancestry-Specific Blood-Cell Genetics in 746,667 Individuals from 5 Global Populations

Most loci identified by GWASs have been found in populations of European ancestry (EUR). In trans-ethnic meta-analyses for 15 hematological traits in 746,667 participants, including 184,535 non-EUR individuals, we identified 5,552 trait-variant associations at p < 5 × 10−9, including 71 novel associations not found in EUR populations. We also identified 28 additional novel variants in ancestry-specific, non-EUR meta-analyses, including an IL7 missense variant in South Asians associated with lymphocyte count in vivo and IL-7 secretion levels in vitro. Fine-mapping prioritized variants annotated as functional and generated 95% credible sets that were 30% smaller when using the trans-ethnic as opposed to the EUR-only results. We explored the clinical significance and predictive value of trans-ethnic variants in multiple populations and compared genetic architecture and the effect of natural selection on these blood phenotypes between populations. Altogether, our results for hematological traits highlight the value of a more global representation of populations in genetic studies. Delineation of the genetic architecture of hematological traits in a multi-ethnic dataset allows identification of rare variants with strong effects specific to non-European populations and improved fine mapping of GWAS variants using the trans-ethnic approach

A first update on mapping the human genetic architecture of COVID-19

peer reviewe

A new membrane probing steroidal spin label: Synthesis and applications

45-50The applicability of a new steroidal spin label, <span style="font-size:14.0pt;font-family:HiddenHorzOCR; mso-bidi-font-family:HiddenHorzOCR">3-oxo-androstan-17β-yl-(2",2",6",6"-tetramethyl-N-oxyl) piperidyl butan- 1', 4'-dioate, in studying the phase transition properties of model membrane L-α-dipalmitoyl  phosphatidyl choline (DPPC) in the presence and absence of drugs has been explored. Its synthesis and characterization has  been described, herein. Besides, the localization of this spin label in lipid liposomes has been studied using electron spin resonance (ESR), differential scanning calorimetry (DSC) and 1H and 31P NMR spectroscopic techniques. The label has also been used to study the permeability of <span style="font-size:14.0pt;font-family: HiddenHorzOCR;mso-bidi-font-family:HiddenHorzOCR">epinephrine into membrane. The results show that the spin label has a good potential as a spin probe in the study of biomembranes. </span

Cycloaddition of oxidopyrylium species in organic synthesis

In the current survey, to highlight the cycloaddition of oxidopyrylium ylides and their application in organic synthesis. Cycloaddition of the related carbonyl ylides, generated by rhodium-catalyzed addition of diazo ketones, has recently been reviewed and hence, only the recent developments are covered here.© Elsevie

1,3-Dipolar cycloaddition reaction of ?,?-unsaturated esters and lactones with diazomethane

1,3-Dipolar cycloaddition of diazomethane to the alpha,beta-unsaturated esters and lactones such as 2-4, 6-8, 10 and 13 occurs in a stereoselective manner affording conjugated Delta(2)-pyrazolines. E and Z isomers of D-mannitol lead to identical product which was cyclised to investigate the absolute stereochemistry of the product. The regiospecificities of all the reactions are consistent with FMO coefficients obtained through AM1 calculations

Synthesis and X-ray diffraction structure of a novel steroid-pyrrolidinoisoquinoline alkaloid hybrid

A novel steroid – pyrrolidinoisoquinoline alkaloid hybrid has been successfully synthesized by Diels-Alder reaction N-acyliminium ion cyclization sequence.

Significance of TNF-α and the Adhesion Molecules: L-Selectin and VCAM-1 in Papillary Thyroid Carcinoma

Circulating levels of TNF-α and the adhesion molecules L-Selectin and VCAM-1 as well as their expression in the primary tumors of patients with benign thyroid diseases and papillary thyroid carcinoma (PTC) have been determined in this study. The serum levels of TNF-α, L-Selectin, and VCAM-1 were significantly higher in patients with both benign thyroid diseases and PTC as compared to the healthy individuals. However, the levels of only TNF-α and L-Selectin, and not VCAM-1, were significantly higher in patients with PTC in comparison to those observed in patients with benign thyroid diseases. Further the expression of TNF-α and L-Selectin was also significantly higher in the primary tumors of PTC patients, relative to the benign thyroid diseases. The expression of L-Selectin and VCAM-1 significantly correlated with aggressive tumor behavior. In PTC patients, the circulating TNF-α levels significantly positively correlated with the levels of L-Selectin, while TNF-α immunoreactivity was significantly associated with VCAM-1 expression. Serum TNF-α was found to be a significant prognosticator for OS in PTC patients. Overall the results signify that the interaction between TNF-α and the adhesion molecules may have a role in thyroid carcinogenesis and understanding this complexity may offer potential therapeutic targets for better management of thyroid cancer