Chromosome movements and licensing of synapsis must be tightly regulated during early meiosis to ensure accurate chromosome segregation and avoid aneuploidy, although how these steps are coordinated ...is not fully understood. Here we show that GRAS-1, the worm homolog of mammalian GRASP/Tamalin and CYTIP, coordinates early meiotic events with cytoskeletal forces outside the nucleus. GRAS-1 localizes close to the nuclear envelope (NE) in early prophase I and interacts with NE and cytoskeleton proteins. Delayed homologous chromosome pairing, synaptonemal complex (SC) assembly, and DNA double-strand break repair progression are partially rescued by the expression of human CYTIP in gras-1 mutants, supporting functional conservation. However, Tamalin, Cytip double knockout mice do not exhibit obvious fertility or meiotic defects, suggesting evolutionary differences between mammals. gras-1 mutants show accelerated chromosome movement during early prophase I, implicating GRAS-1 in regulating chromosome dynamics. GRAS-1-mediated regulation of chromosome movement is DHC-1-dependent, placing it acting within the LINC-controlled pathway, and depends on GRAS-1 phosphorylation at a C-terminal S/T cluster. We propose that GRAS-1 coordinates the early steps of homology search and licensing of SC assembly by regulating the pace of chromosome movement in early prophase I.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
The impact of carbohydrate quality, measured by the carbohydrate quality index (CQI), on gut microbiota and health has been scarcely investigated. The aim of this study was to cross-sectionally and ...longitudinally explore the relationships between CQI, fecal microbiota, and cardiometabolic risk factors in an elderly Mediterranean population at high cardiovascular risk. At baseline and 1-year, CQI was assessed from food frequency questionnaires data, cardiometabolic risk factors were measured, and fecal microbiota profiled from 16S sequencing. Multivariable-adjusted linear regression models were fitted to assess the associations between tertiles of baseline CQI, fecal microbiota, and cardiometabolic risk factors at baseline, and between tertiles of 1-year change in CQI, 1-year change in fecal microbiota and cardiometabolic risk factors. Cross-sectionally, higher CQI was positively associated with Shannon alpha diversity index, and abundance of genera Faecalibacterium and Christensenellaceae R7 group, and negatively associated with the abundance of Odoribacter, and uncultured Rhodospirillales genera. Some of these genera were associated with higher glycated hemoglobin and lower body mass index. In addition, we observed a positive association between CQI, and some pathways related with the metabolism of butyrate precursors and plants-origin molecules. Longitudinally, 1-year improvement in CQI was associated with a concurrent increase in the abundance of genera Butyrivibrio. Increased abundance of this genera was associated with 1-year improvement in insulin status. These observations suggest that a better quality of carbohydrate intake is associated with improved metabolic health, and this improvement could be modulated by greater alpha diversity and abundance of specific genera linked to beneficial metabolic outcomes.
Inflammation is known to be related to the leading causes of death including cardiovascular disease, several types of cancer, obesity, type 2 diabetes, depression-suicide and other chronic diseases. ...In the context of whole dietary patterns, the Dietary Inflammatory Index (DII®) was developed to appraise the inflammatory potential of the diet.
We prospectively assessed the association between DII scores and all-cause mortality in two large Spanish cohorts and valuated the consistency of findings across these two cohorts and results published based on other cohorts.
We assessed 18,566 participants in the “Seguimiento Universidad de Navarra” (SUN) cohort followed-up during 188,891 person-years and 6790 participants in the “PREvencion con DIeta MEDiterránea” (PREDIMED) randomized trial representing 30,233 person-years of follow-up. DII scores were calculated in both cohorts from validated FFQs. Higher DII scores corresponded to more proinflammatory diets. A total of 230 and 302 deaths occurred in SUN and PREDIMED, respectively. In a random-effect meta-analysis we included 12 prospective studies (SUN, PREDIMED and 10 additional studies) that assessed the association between DII scores and all-cause mortality.
After adjusting for a wide array of potential confounders, the comparison between extreme quartiles of the DII showed a positive and significant association with all-cause mortality in both the SUN (hazard ratio HR = 1.85; 95% CI: 1.15, 2.98; P-trend = 0.004) and the PREDIMED cohort (HR = 1.42; 95% CI: 1.00, 2.02; P-trend = 0.009). In the meta-analysis of 12 cohorts, the DII was significantly associated with an increase of 23% in all-cause mortality (95% CI: 16%–32%, for the highest vs lowest category of DII).
Our results provide strong and consistent support for the hypothesis that a pro-inflammatory diet is associated with increased all-cause mortality.
The SUN cohort and PREDIMED trial were registered at clinicaltrials.gov as NCT02669602 and at isrctn.com as ISRCTN35739639, respectively.
To examine associations between intake of simple sugars and cancer incidence, cancer mortality, and total mortality in a prospective cohort study based on the PREDIMED trial conducted from 2003 to ...2010.
Participants were older individuals at high cardiovascular risk. Exposures were total sugar, glucose and fructose from solid or liquid sources, and fructose from fruit and 100% fruit juice. Cancer incidence was the primary outcome; cancer mortality and all-cause mortality were secondary outcomes. Multivariable-adjusted, time-dependent Cox proportional hazard models were used.
Of 7447 individuals enrolled, 7056 (94.7%) were included (57.6% women, aged 67.0 ± 6.2 years). 534 incident cancers with 152 cancer deaths and 409 all-cause deaths were recorded after a median follow-up of 6 years. Intake of simple sugars in solid form was unrelated to outcomes. Higher cancer incidence was found per 5 g/day increase in intake of liquid sugars, with multivariable-adjusted HR of 1.08 (95% CI, 1.03–1.13) for total liquid sugar, 1.19 (95% CI, 1.07–1.31) for liquid glucose, 1.14 (95% CI, 1.05–1.23) for liquid fructose, and 1.39 (95% CI, 1.10–1.74) for fructose from fruit juice. Cancer and all-cause mortality increased to a similar extent with intake of all sugars in liquid form. In categorical models, cancer risk was dose-related for all liquid sugars.
Simple sugar intake in drinks and fruit juice was associated with an increased risk of overall cancer incidence and mortality and all-cause mortality. This suggests that sugary beverages are a modifiable risk factor for cancer and all-cause mortality.
Background
The Coronavirus disease 2019(COVID‐19) pandemic has negatively impacted worldwide organ transplantation. However, there is limited information on recipients transplanted after SARS‐CoV‐2 ...infection. A full understanding of this scenario is required, as transplantation is a life‐saving procedure and COVID‐19 remains an ongoing threat.
Methods
Abdominal organ transplant recipients diagnosed with COVID‐19 prior to transplantation were identified by chart review and clinical data were collected. The primary outcome was the transplant outcome including graft loss, rejection and death, and reactivation of infection post‐transplant.
Results
We identified 14 patients who received abdominal organ transplants after symptomatic PCR confirmed SARS‐CoV‐2 infection; four patients had a positive PCR at the time of admission for transplantation. The median time of follow‐up was 79 (22‐190) days. One recipient with negative PCR before transplant tested positive 9 days after transplant. One of 14 transplanted patients developed disseminated mold infection and died 86 days after transplant. During the follow‐up, only one patient developed rejection; thirteen patients had favorable graft outcomes.
Conclusions
We were able to perform abdominal transplantation for patients with COVID‐19 before transplant, even with positive PCR at the time of transplant. Larger studies are needed to determine the time to safe transplant after SARS‐CoV‐2 infection.
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