The tumor suppressor complex BRCA1-BARD1 functions in DNA double-strand break repair by homologous recombination. Therein, BRCA1-BARD1 facilitates the nucleolytic resection of DNA ends to generate a single-stranded template for the recruitment of another tumor suppressor complex BRCA2-PALB2 and the recombinase RAD51. By examining purified BRCA1-BARD1 and mutants, we show that BRCA1 and BARD1 both bind DNA and interact with RAD51, and that BRCA1-BARD1 enhances the recombinase activity of RAD51. Mechanistically, BRCA1-BARD1 promotes the assembly of the synaptic complex, an essential intermediate in RAD51-mediated DNA joint formation. Evidence is provided that BRCA1 and BARD1 are both indispensable for RAD51 stimulation. Importantly, BRCA1-BARD1 mutants weakened for RAD51 interaction are compromised for DNA joint formation and for the mediation of homologous recombination and DNA repair in cells. Our results identify a late role of BRCA1-BARD1 in homologous recombination, a novel attribute of the tumor suppressor complex that could be targeted in cancer therapy.

objective. To evaluate antimicrobial utilization and prescription practices in a neonatal intensive care unit (NICU) after implementation of an antimicrobial stewardship program (ASP).design. Quasi-experimental, interrupted time-series study.setting. A 54-bed, level IV NICU in a regional academic and tertiary referral center.patients and participants. All neonates prescribed antimicrobials from January 1, 2011, to June 30, 2016, were eligible for inclusion.intervention. Implementation of a NICU-specific ASP beginning July 2012.methods. We convened a multidisciplinary team and developed guidelines for common infections, with a focus on prescriber audit and feedback. We conducted an interrupted time-series analysis to evaluate the effects of our ASP. Our primary outcome measure was days of antibiotic therapy (DOT) per 1,000 patient days for all and for select antimicrobials. Secondary outcomes included provider-specific antimicrobial prescription events for suspected late-onset sepsis (blood or cerebrospinal fluid infection at >72 hours of life) and guideline compliance.results. Antibiotic utilization decreased by 14.7 DOT per 1,000 patient days during the stewardship period, although this decrease was not statistically significant (P = .669). Use of ampicillin, the most commonly antimicrobial prescribed in our NICU, decreased significantly, declining by 22.5 DOT per 1,000 patient days (P = .037). Late-onset sepsis evaluation and prescription events per 100 NICU days of clinical service decreased significantly (P < .0001), with an average reduction of 2.65 evaluations per year per provider. Clinical guidelines were adhered to 98.75% of the time.conclusions. Implementation of a NICU-specific antimicrobial stewardship program is feasible and can improve antibiotic prescribing practices.

tRNA-derived fragments (tRFs) are a new category of regulatory noncoding RNAs with distinct biological functions in cancers and stress-induced diseases. Herein, we first summarize the classification and biogenesis of tRFs. tRFs are produced from pre-tRNAs or mature tRNAs. Based on the incision loci, tRFs are classified into several types: tRF-1, tRF-2, tRF-3, tRF-5, and i-tRF. Some tRFs participate in posttranscriptional regulation through microRNA-like actions or by displacing RNA binding proteins and regulating protein translation by promoting ribosome biogenesis or interfering with translation initiation. Other tRFs prevent cell apoptosis by binding to cytochrome c or promoting virus replication. More importantly, the dysregulation of tRFs has important clinical implications. They are potential diagnostic and prognostic biomarkers of gastric cancer, liver cancer, breast cancer, prostate cancer, and chronic lymphocytic leukemia. tRFs may become new therapeutic targets for the treatment of diseases such as hepatocellular carcinoma and respiratory syncytial virus infection. Finally, we point out the existing problems and future research directions associated with tRFs. In conclusion, the current progress in the research of tRFs reveals that they have important clinical implications and may constitute novel molecular therapeutic targets for modulating pathological processes.

A study was conducted to evaluate effects of alfalfa meal on growth performance and gastrointestinal tract development of growing layer ducks to provide evidence for application of alfalfa meal in the duck industry. Two hundred and fifty-six healthy Shaoxing 7-wk old growing layer ducks were selected and randomly allocated to 1 of 4 dietary treatments based on corn and soybean meal and containing 0, 3, 6, and 9% of alfalfa meal for 8 wks. Each treatment consisted of 4 replicates of 16 ducks each. Briefly, birds were raised in separate compartments, and each compartment consisted of three parts: indoor floor house, adjacent open area and a connecting water area. The results showed: i) Growing ducks fed alfalfa meal diet were not significantly different in average daily gain, feed intake and gain-to-feed ratio from those fed no alfalfa diet (p>0.05). ii) Alfalfa meal increased the ratio crop, gizzard to live weight, caecum to live weight, the caecum index of growing ducks (p<0.05). iii) Villus height in duodenum and jejunum of growing ducks increased significantly with the increase of alfalfa meal levels (p<0.05). Crypt depth in duodenum and jejunum of growing ducks decreased significantly with the increase of alfalfa meal levels (p<0.05). This experiment showed that feeding of alfalfa meal to growing layer ducks could improve gastrointestinal tract growth and small intestinal morphology without effect on performance. This experiment provides evidence that alfalfa meal is a very valuable feedstuff for growing layer ducks.

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