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

Evolution of Surface Hydrology in the Sahelo-Sudanian Strip: An Updated Review

In the West African Sahel, two paradoxical hydrological behaviors have occurred during the last five decades. The first paradox was observed during the 1968–1990s ‘Great Drought’ period, during which runoff significantly increased. The second paradox appeared during the subsequent period of rainfall recovery (i.e., since the 1990s), during which the runoff coefficient continued to increase despite the general re-greening of the Sahel. This paper reviews and synthesizes the literature on the drivers of these paradoxical behaviors, focusing on recent works in the West African Sahelo/Sudanian strip, and upscaling the hydrological processes through an analysis of recent data from two representative areas of this region. This paper helps better determine the respective roles played by Land Use/Land Cover Changes (LULCC), the evolution of rainfall intensity and the occurrence of extreme rainfall events in these hydrological paradoxes. Both the literature review and recent data converge in indicating that the first Sahelian hydrological paradox was mostly driven by LULCC, while the second paradox has been caused by both LULCC and climate evolution, mainly the recent increase in rainfall intensity

The Acute Phase Protein Serum Amyloid A Induces Lipolysis and Inflammation in Human Adipocytes through Distinct Pathways

Background: The acute phase response (APR) is characterized by alterations in lipid and glucose metabolism leading to an increased delivery of energy substrates. In adipocytes, there is a coordinated decrease in Free Fatty acids (FFAs) and glucose storage, in addition to an increase in FFAs mobilization. Serum Amyloid A (SAA) is an acute phase protein mainly associated with High Density Lipoproteins (HDL). We hypothesized that enrichment of HDL with SAA, during the APR, could be implicated in the metabolic changes occurring in adipocytes. Methodology/Principal Findings: In vitro differentiated human adipocytes (hMADS) were treated with SAA enriched HDL or recombinant SAA and the metabolic phenotype of the cells analyzed. In hMADS, SAA induces an increased lipolysis through an ERK dependent pathway. At the molecular level, SAA represses PPARc2, C/EBPa and SREBP-1c gene expression, three transcription factors involved in adipocyte differentiation or lipid synthesis. In addition, the activation of the NF-kB pathway by SAA leads to the induction of pro-inflammatory cytokines and chemokines, as in the case of immune cells. These latter findings were replicated in freshly isolated mature human adipocytes. Conclusions/Significance: Besides its well-characterized role in cholesterol metabolism, SAA has direct metabolic effects on human adipocytes. These metabolic changes could be at least partly responsible for alterations of adipocyte metabolism observed during the APR as well as during pathophysiological conditions such as obesity and conditions leading to insuli

Assessing use of the WHO surgical safety checklist for pediatric surgery in Senegal: A nationwide survey

ABSTRACT Introduction The World Health Organization (WHO) introduced the surgical safety checklist (SSC) to reduce postoperative morbidity and mortality; however, its use in low- and middle-income countries is still low. Methods We conducted a survey from January 2 to 22, 2024, in public hospitals’ pediatric surgery departments and units in Senegal to assess the use of the WHO SSC or an adapted version. Results The participation rate was 100% (23 hospitals), with 11 second-level hospitals (47.8%) and 10 (43.5%) having at least two pediatric surgeons. All hospitals had an anesthetist nurse, and 18 hospitals (78.3%) had at least two scrub nurses. For the surgical workload, 14 hospitals (60.9%) had five to 10 surgical interventions weekly. Eleven hospitals (47.8%) had training on use of the SSC, and 8 of the 23 hospitals (34.8%) used the SSC. The WHO SSC nonutilization was mainly due to a lack of training in nine hospitals (60%) and SSC unavailability in five hospitals (33.3%). Members of 22 hospitals (95.6%) were available for training on use of the SSC. Conclusion The WHO SSC is poorly used in pediatric operating rooms of public hospitals in Senegal. The main reasons for nonutilization are remediable

Investigations on the corrosion of constructional steels in different aqueous and simulated atmospheric environments

The corrosion behavior of three constructional steels used in Senegal, S235, S275 and S355, was studied in simulated atmospheric conditions in an exposure chamber above distilled water and above 3% NaCl solution representing marine atmosphere by comparing the ratio of rusted to unrusted area. Electrochemical test methods (potentiodynamic tests and electrochemical impedance spectroscopy) were employed to study the steels fully immersed in acidic, near neutral and basic conditions in 0.5 M HCl, NaCl, and NaOH solutions, respectively. Results indicate that S355 and S235 steels have comparable corrosion resistance, which are much lower than that of S275

The baculovirus promoter OpIE2 sequence has inhibitory effect on the activity of the Cytomegalovirus (CMV) promoter in HeLa and HEK-293T cells

ABSTRACTUnderstanding how promoters work in non-host cells is complex. Nonetheless, understanding this process is crucial while performing gene expression modulation studies. In this study, inhibitory regions in the 5’ end of the OpIE2 insect viral promoter were found to be blocking the activity of the CMV promoter in mammalian cells. This finding was reached in the process of constructing a shuttle vector with CMV and OpIE2 promoters in a tandem arrangement to achieve gene expression in both mammalian and insect cells, respectively. OpIE2 promoter was cloned downstream of the CMV promoter and upstream of the EGFP reporter gene. After introducing the constructed shuttle vector to insect and mammalian cells, a significant drop in the CMV promoter activity in mammalian cells was observed. To enhance the CMV promoter activity, several modification were made to the shuttle vector including site-directed mutagenesis to remove all ATG codons from the downstream promoter (OpIE2), separating the two promoters to eliminate the effect of transcription interference between them, and finally, identifying some inhibitory regions in the OpIE2 promoter sequence. When these inhibitory regions were removed, high expression levels in insect and mammalian cells were restored. In conclusion, a shuttle vector was constructed that works efficiently in both mammalian and insect cell lines. This study showed that inserting 261 to 313 bp from the 3’ end of the OpIE2 promoter downstream of the CMV promoter maintains efficient gene expression in both Sf9 and mammalian cells.</jats:p