Rif1 S-acylation mediates DNA double-strand break repair at the inner nuclear membrane

Rif1 is involved in telomere homeostasis, DNA replication timing, and DNA double-strand break (DSB) repair pathway choice from yeast to human. The molecular mechanisms that enable Rif1 to fulfill its diverse roles remain to be determined. Here, we demonstrate that Rif1 is S-acylated within its conserved N-terminal domain at cysteine residues C466 and C473 by the DHHC family palmitoyl acyltransferase Pfa4. Rif1 S-acylation facilitates the accumulation of Rif1 at DSBs, the attenuation of DNA end-resection, and DSB repair by non-homologous end-joining (NHEJ). These findings identify S-acylation as a posttranslational modification regulating DNA repair. S-acylated Rif1 mounts a localized DNA-damage response proximal to the inner nuclear membrane, revealing a mechanism of compartmentalized DSB repair pathway choice by sequestration of a fatty acylated repair factor at the inner nuclear membrane

Rif1 maintains telomeres and mediates DNA repair by encasing DNA ends

In yeast, Rif1 is part of the telosome, where it inhibits telomerase and checkpoint signaling at chromosome ends. In mammalian cells, Rif1 is not telomeric, but it suppresses DNA end resection at chromosomal breaks, promoting repair by nonhomologous end joining (NHEJ). Here, we describe crystal structures for the uncharacterized and conserved ∼125-kDa N-terminal domain of Rif1 from Saccharomyces cerevisiae (Rif1-NTD), revealing an α-helical fold shaped like a shepherd's crook. We identify a high-affinity DNA-binding site in the Rif1-NTD that fully encases DNA as a head-to-tail dimer. Engagement of the Rif1-NTD with telomeres proved essential for checkpoint control and telomere length regulation. Unexpectedly, Rif1-NTD also promoted NHEJ at DNA breaks in yeast, revealing a conserved role of Rif1 in DNA repair. We propose that tight associations between the Rif1-NTD and DNA gate access of processing factors to DNA ends, enabling Rif1 to mediate diverse telomere maintenance and DNA repair functions

Biodiversity conservation: history, protected areas and hotspots

Angola is a large country of great physiographic, climatic and habitat diversity, with a corresponding richness in animal and plant species. Legally protected areas (National Parks and Game Reserves) were established from the 1930s and occupied 6% of the country’s terrestrial area at the time of independence in 1975. As a consequence of an extended war, the Protected Areas were exposed to serious neglect, poaching and land invasions. Many habitats of biogeographic importance, and many rare and endemic species came under threat. The recently strengthened administration gives cause for optimism that a new era for biodiversity conservation is at hand. The Protected Areas system was greatly expanded in 2011, and increasing resources are being made available towards achieving management effectivenessinfo:eu-repo/semantics/publishedVersio

Evaluation of prognostic risk models for postoperative pulmonary complications in adult patients undergoing major abdominal surgery: a systematic review and international external validation cohort study

Background Stratifying risk of postoperative pulmonary complications after major abdominal surgery allows clinicians to modify risk through targeted interventions and enhanced monitoring. In this study, we aimed to identify and validate prognostic models against a new consensus definition of postoperative pulmonary complications. Methods We did a systematic review and international external validation cohort study. The systematic review was done in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. We searched MEDLINE and Embase on March 1, 2020, for articles published in English that reported on risk prediction models for postoperative pulmonary complications following abdominal surgery. External validation of existing models was done within a prospective international cohort study of adult patients (≥18 years) undergoing major abdominal surgery. Data were collected between Jan 1, 2019, and April 30, 2019, in the UK, Ireland, and Australia. Discriminative ability and prognostic accuracy summary statistics were compared between models for the 30-day postoperative pulmonary complication rate as defined by the Standardised Endpoints in Perioperative Medicine Core Outcome Measures in Perioperative and Anaesthetic Care (StEP-COMPAC). Model performance was compared using the area under the receiver operating characteristic curve (AUROCC). Findings In total, we identified 2903 records from our literature search; of which, 2514 (86·6%) unique records were screened, 121 (4·8%) of 2514 full texts were assessed for eligibility, and 29 unique prognostic models were identified. Nine (31·0%) of 29 models had score development reported only, 19 (65·5%) had undergone internal validation, and only four (13·8%) had been externally validated. Data to validate six eligible models were collected in the international external validation cohort study. Data from 11 591 patients were available, with an overall postoperative pulmonary complication rate of 7·8% (n=903). None of the six models showed good discrimination (defined as AUROCC ≥0·70) for identifying postoperative pulmonary complications, with the Assess Respiratory Risk in Surgical Patients in Catalonia score showing the best discrimination (AUROCC 0·700 [95% CI 0·683–0·717]). Interpretation In the pre-COVID-19 pandemic data, variability in the risk of pulmonary complications (StEP-COMPAC definition) following major abdominal surgery was poorly described by existing prognostication tools. To improve surgical safety during the COVID-19 pandemic recovery and beyond, novel risk stratification tools are required. Funding British Journal of Surgery Society

Optimization of welding parameters of hot plate welded PC/ABS blends by using the Taguchi experimental design method

WOS: 000429869000006This study aims to investigate the influence of welding parameters in hot plate welding (HPW) process of polycarbonate (PC)/acrylonitrile-butadiene-styrene (ABS) blends using Taguchi method. Three welding parameters, namely the plate temperature, heating time, and welding displacement, were optimized in terms of joint strength using the results of tensile tests. Taguchi experimental design method is implemented as a statistical design of experiment technique so as to set the optimum welding parameters and determine the optimal levels. For HPW of the specimens, the combination of process parameters based on three levels of L-9 orthogonal array was utilized. The signal to noise ratio and the analysis of variance were employed to find the optimum levels and to indicate the impact of the welding parameters on joint strength after tensile tests of the welded joints were carried out. It was shown that it might achieve the improved joint strength using 290 degrees C of plate temperature, 1.25 mm of welding displacement, and 25 s of heating time. For the optimized parameters, it was verified that the most effective factor on joint strength is plate temperature and second effective factor is welding displacement and heating time only slightly influenced on joint strength. After the optimum levels of process parameters are set, in order to demonstrate the effectiveness of Taguchi method, a confirmation run is also performed. An improvement by about 70% from initial welding parameters was observed, and joint efficiency has increased from 22.5% to 38.2% regarding base material properties