Genetic Mapping and Functional Studies of a Natural Inhibitor of the Insulin Receptor Tyrosine Kinase: The Mouse Ortholog of Human α2-HS Glycoprotein

Fetuin/α2-HS glycoprotein (α2-HSG) homologs have been identified in several species including rat, sheep, pig, rabbit, guinea pig, cattle, mouse and human. Multiple physiological roles for these homologs have been suggested, including ability to bind to hydroxyapatite crystals and to specifically inhibit the tyrosine kinase (TK) activity of the insulin receptor (IR). In this study we report the identification, cloning, and characterization of the mouse Ahsg gene and its function as an IR-TK inhibitor. Genomic clones derived from a mouse Svj 129 genomic library were sequenced in order to characterize the intron–exon organization of the mouse Ahsg gene, including an 875 bp subclone containing 154 bp upstream from the transcription start site, the first exon, and part of the first intron. A second genomic subclone harboring a 3.45 kb Bgl II fragment contained exons 2, 3 and 4 in addition to two adjacent elements within the first intron-a repetitive element of the B1 family (92 bp) and a 271 bp tract of (T,C)n * (A,G)n. We have mapped mouse Ahsg at 16 cM adjacent to the Diacylglycerol kinase 3 (Dagk3) gene on chromosome 16 by genotyping interspecific backcross panels between C57BL/6J and Mus spretus. The position is syntenic with human chromosome 3q27, where the human AHSG gene resides. Using recombinant mouse α2-HSG expressed from a recombinant baculovirus, we demonstrate that mouse α2-HSG inhibits insulin–stimulated IR autophosphorylation and IR-TKA in vitro. In addition, mouse α2-HSG (25μg/ml) completely abolishes insulin-induced DNA synthesis in H-35 rat hepatoma cells. Based on the sequence data and functional analysis, we conclude that the mouse Ahsg gene is the true ortholog of the human AHSG gene

Sequence analysis of RNA3 of Maize stripe virus associated with stripe disease of sorghum (Sorghum bicolor) in India

Maize stripe virus (MSpV), one of the distinct species of the genus Tenuivirus, has been associated with stripe disease of sorghum in India. In this study, we report the complete sequence analysis of ambisense RNA3 of four MSpV isolates associated with this disease, to confirm its correct identity. The RNA3 of four MSpV-Sorg isolates is 2357 nucleotides in length with two ORFs, one in virion sense (594 nucleotides, non-structural protein 3, NS3) and the other in complementary sense (951 nucleotides, coat protein, CP). The intergenic region between these two ORFs is 653 nucleotides in length, which is rich in U and A residues. The deduced molecular weights of NS3 and CP are ≈22 and ≈34 kDa, respectively. RNA3 has ≈82% sequence identity at nucleotide level with RNA3 of MSpV infecting maize in Florida, USA and Reunion. NS3 and CP ORFs shared ≈94% and ≈95% identities at amino acid levels, respectively with MSpV isolates of maize from Florida and Reunion. The internal non-coding region between two ORFs has 67–68% identity at nucleotide level with the reported MSpV isolates from Florida and Reunion. The sequence identity was more than ≈98% among the four isolates of MSpV-Sorg. Compared to maize-infecting MSpV isolates in USA and Reunion, the sorghum-infecting MSpV isolates in India had more amino acid substitutions in both NS3 and CP. This is the first report of complete sequence analysis of MSpV RNA3 from Asia

Potential Impact and Study Considerations of Metabolomics in Cardiovascular Health and Disease: A Scientific Statement From the American Heart Association.

Through the measure of thousands of small-molecule metabolites in diverse biological systems, metabolomics now offers the potential for new insights into the factors that contribute to complex human diseases such as cardiovascular disease. Targeted metabolomics methods have already identified new molecular markers and metabolomic signatures of cardiovascular disease risk (including branched-chain amino acids, select unsaturated lipid species, and trimethylamine-N-oxide), thus in effect linking diverse exposures such as those from dietary intake and the microbiota with cardiometabolic traits. As technologies for metabolomics continue to evolve, the depth and breadth of small-molecule metabolite profiling in complex systems continue to advance rapidly, along with prospects for ongoing discovery. Current challenges facing the field of metabolomics include scaling throughput and technical capacity for metabolomics approaches, bioinformatic and chemoinformatic tools for handling large-scale metabolomics data, methods for elucidating the biochemical structure and function of novel metabolites, and strategies for determining the true clinical relevance of metabolites observed in association with cardiovascular disease outcomes. Progress made in addressing these challenges will allow metabolomics the potential to substantially affect diagnostics and therapeutics in cardiovascular medicine

Troponin T and N-Terminal Pro-B-Type Natriuretic Peptide: A Biomarker Approach to Predict Heart Failure Risk--The Atherosclerosis Risk in Communities Study

Among the various cardiovascular diseases, heart failure (HF) is projected to have the largest increases in incidence over the coming decades; therefore, improving HF prediction is of significant value. We evaluated whether cardiac troponin T (cTnT) measured with a high-sensitivity assay and N-terminal-pro-B-type natriuretic peptide (NT-proBNP), biomarkers strongly associated with incident HF, improve HF risk prediction in the Atherosclerosis Risk In Communities (ARIC) study

Perspective:Dietary Biomarkers of Intake and Exposure - Exploration with Omics Approaches

While conventional nutrition research has yielded biomarkers such as doubly labeled water for energy metabolism and 24-h urinary nitrogen for protein intake, a critical need exists for additional, equally robust biomarkers that allow for objective assessment of specific food intake and dietary exposure. Recent advances in high-throughput MS combined with improved metabolomics techniques and bioinformatic tools provide new opportunities for dietary biomarker development. In September 2018, the NIH organized a 2-d workshop to engage nutrition and omics researchers and explore the potential of multiomics approaches in nutritional biomarker research. The current Perspective summarizes key gaps and challenges identified, as well as the recommendations from the workshop that could serve as a guide for scientists interested in dietary biomarkers research. Topics addressed included study designs for biomarker development, analytical and bioinformatic considerations, and integration of dietary biomarkers with other omics techniques. Several clear needs were identified, including larger controlled feeding studies, testing a variety of foods and dietary patterns across diverse populations, improved reporting standards to support study replication, more chemical standards covering a broader range of food constituents and human metabolites, standardized approaches for biomarker validation, comprehensive and accessible food composition databases, a common ontology for dietary biomarker literature, and methodologic work on statistical procedures for intake biomarker discovery. Multidisciplinary research teams with appropriate expertise are critical to moving forward the field of dietary biomarkers and producing robust, reproducible biomarkers that can be used in public health and clinical research

The human body at cellular resolution: the NIH Human Biomolecular Atlas Program

Abstract: Transformative technologies are enabling the construction of three-dimensional maps of tissues with unprecedented spatial and molecular resolution. Over the next seven years, the NIH Common Fund Human Biomolecular Atlas Program (HuBMAP) intends to develop a widely accessible framework for comprehensively mapping the human body at single-cell resolution by supporting technology development, data acquisition, and detailed spatial mapping. HuBMAP will integrate its efforts with other funding agencies, programs, consortia, and the biomedical research community at large towards the shared vision of a comprehensive, accessible three-dimensional molecular and cellular atlas of the human body, in health and under various disease conditions

Development of duplex RT-PCR for detection of <i>Konjac mosaic virus</i> and Spathiphyllum chlorotic vein banding virus in taro and peace lily

120-122Konjac mosaic virus (KoMV) and Spathiphyllum chlorotic vein banding virus (SCVbV) infecting aroids in Andhra Pradesh, India have recently been reported as distinct potyviruses. Primers were designed based on their partial genome sequence (GenBank A/C EU979524, GQ421462) to detect above viruses by duplex-reverse transcription-polymerase chain reaction (duplex RT-PCR). Using this method, the two viruses were individually detected in limited number of filed/nursery collected Colocasia esculenta (taro) and Spathiphyllum spp. (peace lily). No co-infections with two viruses were traced among the screened samples. However, they were simultaneously detected in the simulated leaf samples of taro and peace lily (1:1, w/w). </span