Genetic mechanisms underlying spermatic and testicular traits within and among cattle breeds: systematic review and prioritization of GWAS results1

[EN] Reduced bull fertility imposes economic losses in bovine herds. Specifically, testicular and spermatic traits are important indicators of reproductive efficiency. Several genome-wide association studies (GWAS) have identified genomic regions associated with these fertility traits. The aims of this study were as follows: 1) to perform a systematic review of GWAS results for spermatic and testicular traits in cattle and 2) to identify key functional candidate genes for these traits. The identification of functional candidate genes was performed using a systems biology approach, where genes shared between traits and studies were evaluated by a guilt by association gene prioritization (GUILDify and ToppGene software) in order to identify the best functional candidates. These candidate genes were integrated and analyzed breeds. Results showed that GWAS for testicular-related traits have been developed for beef breeds only, whereas the majority of GWAS for spermatic-related traits were conducted using dairy breeds. comparing traits measured within the same study, the highest number of genes shared between different traits was observed, indicating a high impact of the population genetic structure and environmental effects. Several chromosomal regions were enriched for functional candidate genes associated with fertility traits. Moreover, multiple functional candidate genes were enriched for markers in a species-specific basis, taurine (Bos taurus) or indicine (Bos indicus). For the different candidate regions identified in the GWAS in the literature, functional candidate genes were detected as follows: B. Taurus chromosome X (BTX) (TEX11, IRAK, CDK16, ATP7A, ATRX, HDAC6, FMR1, L1CAM, MECP2, etc.), BTA17 (TRPV4 and DYNLL1), and BTA14 (MOS, FABP5, ZFPM2). These genes are responsible for regulating metabolic pathways or biological processes associated with fertility, such as progression of spermatogenesis, control of ciliary activity, development of Sertoli cells, DNA integrity in spermatozoa, and homeostasis of testicular cells. This study represents the first systematic review on male fertility traits in cattle using a system biology approach to identify key candidate genes for these traits.S

Seasonal variations in the amount of isoorientin and isovitexin in cecropia glaziovii sneth. leaves over a two-year period

Cecropia glaziovii Sneth (Urticaceae) is a common tree from Southeast and South of Brazil, being widely used in traditional medicine to treat heart and respiratory conditions. C-glycosylflavonoids have being described as the major compounds for this genus, however, no seasonality studies of individual flavonoids was conducted for any Cecropia specie. In this work, the content of isoorientin and isovitexin in aqueous extract from the leaves of C glaziovii during a two-year period was determined by high-performance liquid chromatography with diode array detector (hplc-dad). Seasonal alterations in the content of these two majority C-glycosylflavonoids as well its possible correlation with the pluviosity in the period of January/2008 to January/2010 were determined. Isoorientin presented higher content in November/09 (6.04 mg/g of extract) and lower content in May/08 (1.01 mg/g of extract). The higher content of isovitexin was observed in March/09 and the lower in September/08 (11.42 and 4.47 mg/g of extract, respectively). Although they have distinct behaviors, it was not observed correlation between the values of pluviosity and the production of these C-glycosylflavonoids

Feline subcutaneous pythiosis

ABSTRACT: Pythiosis in felines is a rare disease associated with the oomycete Pythium insidiosum. The aim of this report was to describe the macroscopic, histopathological, and molecular characteristics of P. insidiosum infection in a 2-year-old cat, with a localized invasive subcutaneous mass. The feline had an increase of volume near the anal region since it was younger. The cat died just after surgery. The necropsy was performed, and samples were collected for histopathological examination. Microscopically, the skin lesion was characterized by necro-eosinophilic dermatitis, panniculitis, and myositis surrounding negatively stained hyphal structures. In the sections stained with GMS, dark brown hyphae were clearly seen inside the affected tissue. They were rarely septate and their walls were almost parallel. Immunohistochemistry using a polyclonal anti-P. insidiosum antibody showed a strongly immunostained hyphae into the lesions. The analysis based on PCR had a positive result for P. insidiosum. Pythiosis should be considered in the differential diagnosis of subcutaneous tissue disorders in felines

Modernizing Clinical Trial Eligibility Criteria: Recommendations of the American Society of Clinical Oncology-Friends of Cancer Research HIV Working Group.

Purpose People with HIV are living longer as a result of effective antiretroviral therapy. Cancer has become a leading cause of morbidity and mortality in this patient population. However, studies of novel cancer therapeutics have historically excluded patients with HIV. Critical review of eligibility criteria related to HIV is required to accelerate development of and access to effective therapeutics for HIV-infected patients with cancer and make studies more generalizable to this patient population. Methods From January through April 2016, the HIV Working Group conducted a series of teleconferences; a review of 46 New Drug Applications from registration studies of unique agents studied in adults with cancer that led to the initial US Food and Drug Administration approval of that agent from 2011 to 2015; and a review of HIV-related eligibility criteria from National Cancer Institute–sponsored studies. Results were discussed and refined at a multistakeholder workshop held May 12, 2016. The HIV Working Group developed recommendations for eligibility criteria that focus on pharmacologic and immunologic considerations in this patient population and that balance patient safety, access to appropriate investigational agents, and study integrity. Results Exclusion of patients with HIV remains common in most studies of novel cancer agents. Models for HIV-related eligibility criteria in National Cancer Institute–sponsored studies are instructive. HIV infection itself should no longer be an exclusion criterion for most studies. Eligibility criteria related to HIV infection that address concurrent antiretroviral therapy and immune status should be designed in a manner that is appropriate for a given cancer. Conclusion Expanding clinical trial eligibility to be more inclusive of patients with HIV is justified in most cases and may accelerate the development of effective therapies in this area of unmet clinical need. </jats:sec

Pronounced thrombocytosis in transgenic mice expressing reduced levels of Mpl in platelets and terminally differentiated megakaryocytes

We generated mice expressing a full-length Mpl transgene under the control of a 2-kb Mpl promoter in an Mpl(-/-) background, effectively obtaining mice that express full-length Mpl in the absence of other Mpl isoforms. These mice developed thrombocytosis with platelet levels approximately 5-fold higher than wild-type controls and markedly increased megakaryocyte numbers. The reintroduction of one wild-type Mpl allele restored normal platelet counts. We excluded the deletion of Mpl-tr, a dominant-negative isoform, as the underlying molecular cause for thrombocytosis. Instead, we found that transgene expression driven by the 2-kb Mpl promoter fragment was decreased during late megakaryocyte maturation, resulting in strongly diminished Mpl protein expression in platelets. Because platelets exert a negative feedback on thrombopoiesis by binding and consuming Tpo in the circulation through Mpl, we propose that the severe reduction of Mpl protein in platelets in Mpl-transgenic Mpl(-/-) mice shifts the equilibrium of this feedback loop, resulting in markedly elevated levels of megakaryocytes and platelets at steady state. Although the mechanism causing decreased expression of Mpl protein in platelets from patients with myeloproliferative disorders differs from this transgenic model, our results suggest that lowering Mpl protein in platelets could contribute to raising the platelet count

Sexual Orientation and Gender Identity Data Collection in Oncology Practice: Findings of an ASCO Survey

PURPOSE: Lack of collection of sexual orientation and gender identity (SOGI) data in oncology practices limits assessment of sexual and gender minority (SGM) cancer patients\u27 experiences and restricts opportunities to improve health outcomes of SGM patients. Despite national calls for routine SOGI data collection, individual-level and institutional barriers hinder progress. This study aimed to identify these barriers in oncology. METHODS: An online survey of ASCO members and others assessed SOGI data collection in oncology practices, institutional characteristics related to SOGI data collection, respondents\u27 attitudes about SOGI data and SGM patients, and respondent demographics. Logistic regression calculated adjusted odds ratios (ORs) and 95% CIs for factors associated with sexual orientation (SO) and gender identity (GI) data collection. RESULTS: Less than half of 257 respondents reported institutional SO and GI data collection (40% and 46%, respectively), whereas over a third reported no institutional data collection (34% and 32%, respectively) and the remainder were unsure (21% and 17%, respectively). Most respondents felt that knowing both SO and GI was important for quality care (77% and 85%, respectively). Collection of SO and GI was significantly associated in separate models with leadership support (ORs = 8.01 and 6.02, respectively), having resources for SOGI data collection (ORs = 10.6 and 18.7, respectively), and respondents\u27 belief that knowing patient SO and GI is important (ORs = 4.28 and 2.76, respectively). Themes from qualitative comments mirrored the key factors identified in our quantitative analysis. CONCLUSION: Three self-reinforcing factors emerged as critical drivers for collecting SOGI data: leadership support, dedicated resources, and individual respondents\u27 attitudes. Policy mandates, implementation science, and clinical reimbursement are strategies to advance meaningful data collection and use in clinical practice