19 research outputs found

    Who are you, Griselda? A replacement name for a new genus of the Asiatic short-tailed shrews (Mammalia, Eulipotyphla, Soricidae): molecular and morphological analyses with the discussion of tribal affinities

    Get PDF
    The first genetic study of the holotype of the Gansu short-tailed shrew, Blarinella griselda Thomas, 1912, is presented. The mitochondrial analysis demonstrated that the type specimen of B. griselda is close to several recently collected specimens from southern Gansu, northern Sichuan and Shaanxi, which are highly distinct from the two species of Asiatic short-tailed shrews of southern Sichuan, Yunnan, and Vietnam, >B. quadraticauda and B. wardi. Our analysis of four nuclear genes supported the placement of B. griselda as sister to B. quadraticauda / B. wardi, with the level of divergence between these two clades corresponding to that among genera of Soricinae. A new generic name, Parablarinella, is proposed for the Gansu short-tailed shrew. Karyotypes of Parablarinella griselda(2n = 49, NFa = 50) and B. quadraticauda (2n = 49, NFa = 62) from southern Gansu are described. The tribal affinities of Blarinellini and Blarinini are discussed.Copyright Anna A. Bannikova et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. The attached file is the published version of the article

    What are new opportunities for clinical practice the VERIFY study opens and which values for native diabetes patients? Joint conclusion on the advisory board results. November 6, 2019

    Get PDF
    According to key diabetic studies, the early use of metformin glucose lowering therapy is associated with a reduced risk of developing micro- and, in the long term, 10-year follow-up, macrovascular complications and cardiovascular mortality. Short-term studies results on combined glucose lowering therapy with metformin suggests that combination therapy can have several advantages on the one side from the effectiveness of glycemic control and on another side from positive effect on the development of complications of type 2 diabetes. The question of the start time of combined hypoglycemic therapy remains open. According to the results of recent large-scale studies, real world evidence data, careful glycemic control during the first year from the moment of diagnosis of type 2 diabetes is crucial for further management of the disease and slow the progression of complications. However, due to the fact that the clinical benefits of early combination therapy were not demonstrated in randomized clinical trials, this approach, despite the theoretical background, was not recommended for widespread use in international guidelines for the treatment diabetes patients. Russian algorithms on the treatment diabetes patients recommend combined glucose lowering therapy at the start of treatment at a HbA1c level of 1% higher than the target. A 5-year VERIFY study results were demonstrated long-term sustained glycemic control in combination with vildagliptin + metformin prescribed for native diabetes patients with relatively low HbA1c values, as well as the advantages of this approach in comparison with the standard strategy for phased intensification of monotherapy. The results of the VERIFY study provided a wealth of information to discuss early treatment intensification, the clinical benefits of this approach and a possible review of the treatment strategy for native diabetes patients

    Candidate Variants in DNA Replication and Repair Genes in Early-Onset Renal Cell Carcinoma Patients Referred for Germline Testing

    Get PDF
    Background: Early-onset renal cell carcinoma (eoRCC) is typically associated with pathogenic germline variants (PGVs) in RCC familial syndrome genes. However, most eoRCC patients lack PGVs in familial RCC genes and their genetic risk remains undefined. Methods: Here, we analyzed biospecimens from 22 eoRCC patients that were seen at our institution for genetic counseling and tested negative for PGVs in RCC familial syndrome genes. Results: Analysis of whole-exome sequencing (WES) data found enrichment of candidate pathogenic germline variants in DNA repair and replication genes, including multiple DNA polymerases. Induction of DNA damage in peripheral blood monocytes (PBMCs) significantly elevated numbers of [Formula: see text]H2AX foci, a marker of double-stranded breaks, in PBMCs from eoRCC patients versus PBMCs from matched cancer-free controls. Knockdown of candidate variant genes in Caki RCC cells increased [Formula: see text]H2AX foci. Immortalized patient-derived B cell lines bearing the candidate variants in DNA polymerase genes (POLD1, POLH, POLE, POLK) had DNA replication defects compared to control cells. Renal tumors carrying these DNA polymerase variants were microsatellite stable but had a high mutational burden. Direct biochemical analysis of the variant Pol δ and Pol η polymerases revealed defective enzymatic activities. Conclusions: Together, these results suggest that constitutional defects in DNA repair underlie a subset of eoRCC cases. Screening patient lymphocytes to identify these defects may provide insight into mechanisms of carcinogenesis in a subset of genetically undefined eoRCCs. Evaluation of DNA repair defects may also provide insight into the cancer initiation mechanisms for subsets of eoRCCs and lay the foundation for targeting DNA repair vulnerabilities in eoRCC

    Biological Earth observation with animal sensors

    Get PDF
    Space-based tracking technology using low-cost miniature tags is now delivering data on fine-scale animal movement at near-global scale. Linked with remotely sensed environmental data, this offers a biological lens on habitat integrity and connectivity for conservation and human health; a global network of animal sentinels of environmen-tal change
    corecore