ddRAD sequencing based genotyping of six indigenous dairy cattle breeds of India to infer existing genetic diversity and population structure

Abstract The present investigation aimed to identify genome wide SNPs and to carry out diversity and population structure study using ddRAD-seq based genotyping of 58 individuals of six indigenous milch cattle breeds (Bos indicus) such as Sahiwal, Gir, Rathi, Tharparkar, Red Sindhi and Kankrej of India. A high percentage of reads (94.53%) were mapped to the Bos taurus (ARS-UCD1.2) reference genome assembly. Following filtration criteria, a total of 84,027 high quality SNPs were identified across the genome of 6 cattle breeds with the highest number of SNPs observed in Gir (34,743), followed by Red Sindhi (13,092), Kankrej (12,812), Sahiwal (8956), Tharparkar (7356) and Rathi (7068). Most of these SNPs were distributed in the intronic regions (53.87%) followed by intergenic regions (34.94%) while only 1.23% were located in the exonic regions. Together with analysis of nucleotide diversity (π = 0.373), Tajima’s D (D value ranging from − 0.295 to 0.214), observed heterozygosity (HO ranging from 0.464 to 0.551), inbreeding coefficient (FIS ranging from − 0.253 to 0.0513) suggested for the presence of sufficient within breed diversity in the 6 major milch breeds of India. The phylogenetic based structuring, principal component and admixture analysis revealed genetic distinctness as well as purity of almost all of the 6 cattle breeds. Overall, our strategy has successfully identified thousands of high-quality genome wide SNPs that will further enrich the Bos indicus representation basic information about genetic diversity and structure of 6 major Indian milch cattle breeds which should have implications for better management and conservation of valuable indicine cattle diversity

Psiguanol, a novel <i>α</i>-pyrone derivative from <i>Psidium guajava</i> leaves and vasorelaxant activity in rat aorta cells through intracellular cGMP-dependent opening of calcium channels

The phytochemical investigation of Psidium guajava leaves led to the isolation of total nineteen compounds which belongs to meroterpenoids, flavonoid, phenolics, and triterpenoids. The compounds were isolated using extensive chromatography techniques and identified as psiguanol (4), as new compound along with guajadial (1), psidial A (2), β-caryophyllene (3), quercetin (5), avicularin (6), guaijaverin (7), hyperin (8), rutin (9), ursolic acid (10), corosolic acid (11), asiatic acid (12), β-sitosterol (13), β-sitosterol-D-glucoside (14), ellagic acid (15), 3,3',4'-trimethylellagic acid 4-O-glucoside (16), protocatechuic acid (17), gallic acid (18), and tricosanoic acid (19) as known molecules. The compound 16 was isolated for the first time from this plant. The isolated compounds were evaluated for vasorelaxation activity in rat aorta cells and it was observed that compound 4 exhibited the most potent vasorelaxation response in the ex-vivo model in isolated rat aorta cells. Mechanistically, the vasorelaxation activity of 4 was mediated through cGMP-dependent BKCa channel opening.</p

Spatial transcriptomics reveals distinct and conserved tumor core and edge architectures that predict survival and targeted therapy response

Abstract The spatial organization of the tumor microenvironment has a profound impact on biology and therapy response. Here, we perform an integrative single-cell and spatial transcriptomic analysis on HPV-negative oral squamous cell carcinoma (OSCC) to comprehensively characterize malignant cells in tumor core (TC) and leading edge (LE) transcriptional architectures. We show that the TC and LE are characterized by unique transcriptional profiles, neighboring cellular compositions, and ligand-receptor interactions. We demonstrate that the gene expression profile associated with the LE is conserved across different cancers while the TC is tissue specific, highlighting common mechanisms underlying tumor progression and invasion. Additionally, we find our LE gene signature is associated with worse clinical outcomes while TC gene signature is associated with improved prognosis across multiple cancer types. Finally, using an in silico modeling approach, we describe spatially-regulated patterns of cell development in OSCC that are predictably associated with drug response. Our work provides pan-cancer insights into TC and LE biology and interactive spatial atlases ( http://www.pboselab.ca/spatial_OSCC/ ; http://www.pboselab.ca/dynamo_OSCC/ ) that can be foundational for developing novel targeted therapies