Characterization and conservation of indigenous sheep genetic resources: A practical framework for developing countries

Livestock characterization projects in developing regions are characterized by a mere physical description of traditionally recognized populations or a purely academic genetic description of populations. However, characterization of livestock resources is meant to serve the purpose of developing conservation and utilization programs. A national characterization project should be geared to the specific national livestock production objectives. Thus there is a need to adopt a more practical characterization approach to assist in the development of national conservation and utilization strategies. This report provides a practical methodological framework suited for characterization and conservation of sheep resources in developing regions. The report highlights current approaches and tools for characterization and conservation of sheep resources and presents a model approach synthesising results of a study on characterization and conservation of sheep resources of Ethiopia. The study is a collaborative project between Wageningen University and the International Livestock Research Institute. The methodological framework can be applied elsewhere in developing countries with similar characterization and conservation objectives. This report largely dwelt on the technical aspects of sheep genetic resource characterization and conservation in developing regions. Operational aspects of setting up national programs for characterization and conservation action may be country specific. However, some general aspects such as institutional setups and breeding policy and strategy formulation could be similar across countries. A proposed scheme for setting up a national livestock characterization and conservation program is presented, taking Ethiopia as a case study

Impact of Androgen Deprivation Therapy on Cardiovascular Outcomes in Prostate Cancer

PurposeSubstantial evidence indicates that men with prostate cancer are at an increased risk for cardiovascular disease, and medical and surgical androgen deprivation therapy is associated with further increased cardiovascular risk. There are conflicting reports of differences in cardiovascular safety between gonadotropin-releasing hormone (GnRH) agonists and antagonists. The purpose of this narrative review is to compare data on the cardiovascular risks and safety outcomes associated with different hormonal treatment options in prostate cancer patients and to provide guidance on how to manage the increased risk associated with the condition.MethodsA PubMed search was conducted for papers published in the last 15 years using the following MeSH terms: “prostate neoplasms,” “gonadotropin-releasing hormone,” “androgen agonist,” “androgen antagonists,” “cardiovascular disease,” “epidemiology.”ResultsEvidence regarding the risk of cardiovascular events during treatment with GnRH agonists and antagonists is conflicting. Some retrospective studies have shown that agonists are associated with a greater risk of cardiovascular disease and cardiovascular mortality and morbidity, and a similar risk with agonists and combined androgen blockade. Some studies have reported that antagonists are associated with a decreased risk of cardiovascular mortality and morbidity compared with agonists. With respect to coronary heart disease, ischemic heart disease, myocardial infarction, stroke, or sudden cardiac death, current evidence has failed to demonstrate a significant difference between antagonists and agonists. Cardiovascular risks in patients should be mitigated by regular monitoring of blood pressure, blood glucose, and lipids, as well as counseling patients to abstain from alcohol and improve their diet and exercise. Statins, metformin, and aspirin should also be considered

Rad54p is a chromatin remodeling enzyme required for heteroduplex DNA joint formation with chromatin

In eukaryotic cells, the repair of DNA double-strand breaks by homologous recombination requires a RecA-like recombinase, Rad51p, and a Swi2p/Snf2p-like ATPase, Rad54p. Here we find that yeast Rad51p and Rad54p support robust homologous pairing between single-stranded DNA and a chromatin donor. In contrast, bacterial RecA is incapable of catalyzing homologous pairing with a chromatin donor. We also show that Rad54p possesses many of the biochemical properties of bona fide ATP-dependent chromatin-remodeling enzymes, such as ySWI/SNF. Rad54p can enhance the accessibility of DNA within nucleosomal arrays, but it does not seem to disrupt nucleosome positioning. Taken together, our results indicate that Rad54p is a chromatin-remodeling enzyme that promotes homologous DNA pairing events within the context of chromatin

Werner Protein Protects Nonproliferating Cells from Oxidative DNA Damage

Werner syndrome, caused by mutations of the WRN gene, mimics many changes of normal aging. Although roles for WRN protein in DNA replication, recombination, and telomere maintenance have been suggested, the pathology of rapidly dividing cells is not a feature of Werner syndrome. To identify cellular events that are specifically vulnerable to WRN deficiency, we used RNA interference (RNAi) to knockdown WRN or BLM (the RecQ helicase mutated in Bloom syndrome) expression in primary human fibroblasts. Withdrawal of WRN or BLM produced accelerated cellular senescence phenotype and DNA damage response in normal fibroblasts, as evidenced by induction of γH2AX and 53BP1 nuclear foci. After WRN depletion, the induction of these foci was seen most prominently in nondividing cells. Growth in physiological (3%) oxygen or in the presence of an antioxidant prevented the development of the DNA damage foci in WRN-depleted cells, whereas acute oxidative stress led to inefficient repair of the lesions. Furthermore, WRN RNAi-induced DNA damage was suppressed by overexpression of the telomere-binding protein TRF2. These conditions, however, did not prevent the DNA damage response in BLM-ablated cells, suggesting a distinct role for WRN in DNA homeostasis in vivo. Thus, manifestations of Werner syndrome may reflect an impaired ability of slowly dividing cells to limit oxidative DNA damage

Using change in predicted adult height during GnRH agonist treatment for individualized treatment decisions in girls with central precocious puberty

ObjectivesIt is important to understand what variables influence change in predicted adult height (PAH) throughout GnRHa treatment for central precocious puberty (CPP) to individualize treatment decisions and optimize care.MethodsChanges in PAH, chronological age (CA), bone age (BA), BA/CA, and height velocity (HV) were evaluated in girls with CPP throughout treatment with leuprolide acetate (n=77). A second analysis focused on changes in the 3 years preceding the first observed BA of ≥12 years. Relationships were characterized using plot inspection and linear mixed-effects analyses. Association between treatment duration and last assessed PAH was examined using multiple linear regression models.ResultsBA/CA and HV showed a nonlinear change during treatment, with the largest changes and improvement in PAH observed in the first 6-18 months. Rate of BA advancement tended to decrease more slowly in girls initiating treatment at a younger BA. On-treatment change in PAH was predicted by concurrent BA/CA change, HV, and BA, as well as CA at treatment initiation. Last assessed PAH was positively associated with longer treatment durations (primary/exploratory models cut-offs of ≥33/≥55 months).ConclusionsThese findings support individualized monitoring during GnRHa treatment. Initial response should be interpreted with caution until 6-18 months after treatment initiation and failure should not be assumed based on continued bone maturation in girls starting therapy at a younger age. Treatment cessation should not be automatically based on a diminishing change in PAH or HV, as ongoing treatment may result in continued increase or maintenance of PAH