Use of high throughput sequencing to observe genome dynamics at a single cell level

With the development of high throughput sequencing technology, it becomes possible to directly analyze mutation distribution in a genome-wide fashion, dissociating mutation rate measurements from the traditional underlying assumptions. Here, we sequenced several genomes of Escherichia coli from colonies obtained after chemical mutagenesis and observed a strikingly nonrandom distribution of the induced mutations. These include long stretches of exclusively G to A or C to T transitions along the genome and orders of magnitude intra- and inter-genomic differences in mutation density. Whereas most of these observations can be explained by the known features of enzymatic processes, the others could reflect stochasticity in the molecular processes at the single-cell level. Our results demonstrate how analysis of the molecular records left in the genomes of the descendants of an individual mutagenized cell allows for genome-scale observations of fixation and segregation of mutations, as well as recombination events, in the single genome of their progenitor.Comment: 22 pages, 9 figures (including 5 supplementary), one tabl

Event Organizer sebagai Peluang Wirausaha

The article discusses business chance in event organizer that could be conducted by anybody. Less employment in this country is not balanced with the amount of college graduates every year, which is getting bigger. Government ability to create new jobs does not give a credible chance for new graduates to work. However, there are still chances in building new jobs by being entrepreneurs in event organizer sector. Event organizer service is a business that gives chances in effective employment for society; especially new college graduates so instead of competing to get jobs, they will create a self-employment and also for others. Beginning business in event organizer is not hard as we thought. In the article, it is attached several tips to begin event organizer business

Estimating Health-State Utility Values in Kidney Transplant Recipients and Waiting-List Patients Using the EQ-5D-5L.

OBJECTIVES: To report health-state utility values measured using the five-level EuroQol five-dimensional questionnaire (EQ-5D-5L) in a large sample of patients with end-stage renal disease and to explore how these values vary in relation to patient characteristics and treatment factors. METHODS: As part of the prospective observational study entitled "Access to Transplantation and Transplant Outcome Measures," we captured information on patient characteristics and treatment factors in a cohort of incident kidney transplant recipients and a cohort of prevalent patients on the transplant waiting list in the United Kingdom. We assessed patients' health status using the EQ-5D-5L and conducted multivariable regression analyses of index scores. RESULTS: EQ-5D-5L responses were available for 512 transplant recipients and 1704 waiting-list patients. Mean index scores were higher in transplant recipients at 6 months after transplant surgery (0.83) compared with patients on the waiting list (0.77). In combined regression analyses, a primary renal diagnosis of diabetes was associated with the largest decrement in utility scores. When separate regression models were fitted to each cohort, female gender and Asian ethnicity were associated with lower utility scores among waiting-list patients but not among transplant recipients. Among waiting-list patients, longer time spent on dialysis was also associated with poorer utility scores. When comorbidities were included, the presence of mental illness resulted in a utility decrement of 0.12 in both cohorts. CONCLUSIONS: This study provides new insights into variations in health-state utility values from a single source that can be used to inform cost-effectiveness evaluations in patients with end-stage renal disease

Barriers to living donor kidney transplantation in the United Kingdom: a national observational study.

BACKGROUND: Living donor kidney transplantation (LDKT) provides more timely access to transplantation and better clinical outcomes than deceased donor kidney transplantation (DDKT). This study investigated disparities in the utilization of LDKT in the UK. METHODS: A total of 2055 adults undergoing kidney transplantation between November 2011 and March 2013 were prospectively recruited from all 23 UK transplant centres as part of the Access to Transplantation and Transplant Outcome Measures (ATTOM) study. Recipient variables independently associated with receipt of LDKT versus DDKT were identified. RESULTS: Of the 2055 patients, 807 (39.3%) received LDKT and 1248 (60.7%) received DDKT. Multivariable modelling demonstrated a significant reduction in the likelihood of LDKT for older age {odds ratio [OR] 0.11 [95% confidence interval (CI) 0.08-0.17], P < 0.0001 for 65-75 years versus 18-34 years}; Asian ethnicity [OR 0.55 (95% CI 0.39-0.77), P = 0.0006 versus White]; Black ethnicity [OR 0.64 (95% CI 0.42-0.99), P = 0.047 versus White]; divorced, separated or widowed [OR 0.63 (95% CI 0.46-0.88), P = 0.030 versus married]; no qualifications [OR 0.55 (95% CI 0.42-0.74), P < 0.0001 versus higher education qualifications]; no car ownership [OR 0.51 (95% CI 0.37-0.72), P = 0.0001] and no home ownership [OR 0.65 (95% CI 0.85-0.79), P = 0.002]. The odds of LDKT varied significantly between countries in the UK. CONCLUSIONS: Among patients undergoing kidney transplantation in the UK, there are significant age, ethnic, socio-economic and geographic disparities in the utilization of LDKT. Further work is needed to explore the potential for targeted interventions to improve equity in living donor transplantation

Isolation, small population size, and management influence inbreeding and reduced genetic variation in K’gari dingoes

Small island populations are vulnerable to genetic decline via demographic and environmental stochasticity. In the absence of immigration, founder effects, inbreeding and genetic drift are likely to contribute to local extinction risk. Management actions may also have a greater impact on small, closed populations. The demographic and social characteristics of a species can, however, delay the impact of threats. K’gari, a ~ 1 660 km2 island off the Australian east coast and UNESCO World Heritage Site (Fraser Island 1842–2023), supports an isolated population of approximately 70–200 dingoes that represent an ideal opportunity to explore the small island paradigm. To examine temporal and spatial patterns of genetic diversity in this population we analysed single nucleotide polymorphism (SNP) genotype data (72 454 SNPS) for 112 K’gari dingoes collected over a 25-year period (1996 to 2020). Genetic diversity was lower in K’gari dingoes than mainland dingoes at the earliest time point in our study and declined significantly following a management cull in 2001. We did not find any spatial genetic patterns on the island, suggesting high levels of genetic connectivity between socially discrete packs. This connectivity, combined with the social structure and behaviour of dingoes, may act in concert to buffer the population from the impacts of genetic drift in the short term. Nevertheless, a general decline in genetic variation via inbreeding and drift has occurred over the past 20 years which we suggest should be considered in any future management planning for the population. Monitoring patterns of genetic variation, together with a clearer understanding of the social ecology of K’gari dingoes, will aid in the development of measurable genetic targets set over ecologically meaningful timelines, and help ensure continued survival of this culturally important population

The Cohesin loading factor NIPBL recruits histone deacetylases to mediate local chromatin modifications

Cornelia de Lange Syndrome (CdLS) is a rare congenital malformation disorder. About half of the patients with CdLS carry mutations in the NIPBL gene encoding the NIPBL protein, a subunit of the Cohesin loading complex. Recent studies show association of Cohesin with chromatin-remodeling complexes, either by establishing cohesion or by recruiting Cohesin to specific chromosome locations. In yeast two-hybrid assays, we identified an interaction of NIPBL with the histone deacetylases -1 and -3. These interactions were confirmed in mammalian cells by coimmunoprecipitation and a critical region for interaction was defined to a stretch of 163 amino acids of a highly conserved region of NIPBL, which is mutated in patients with CdLS. Utilizing reporter gene assays, we could show that NIPBL fused to the GAL4-DNA-binding domain (GAL4-DBD) represses promoter activity via the recruitment of histone deacetylases. Interestingly, this effect is dramatically reduced by both NIPBL missense mutations identified in CdLS and by chemical inhibition of the histone deacetylases. Our data are the first to indicate a molecular and functional connection of NIPBL with chromatin-remodeling processes via the direct interaction with histone deacetylases

Reporting of harm in randomized controlled trials evaluating stents for percutaneous coronary intervention

<p>Abstract</p> <p>Background</p> <p>The aim of this study was to assess the reporting of harm in randomized controlled trials evaluating stents for percutaneous coronary intervention.</p> <p>Methods</p> <p>The study design was a methodological systematic review of randomized controlled trials. The data sources were MEDLINE and the Cochrane Central Register of Controlled Trials. All reports of randomized controlled trials assessing stent treatment for coronary disease published between January 1, 2003, and September 30, 2008 were selected.</p> <p>A standardized abstraction form was used to extract data.</p> <p>Results</p> <p>132 articles were analyzed. Major cardiac adverse events (death, cardiac death, myocardial infarction or stroke) were reported as primary or secondary outcomes in 107 reports (81%). However, 19% of the articles contained no data on cardiac events. The mode of data collection of adverse events was given in 29 reports (22%) and a definition of expected adverse events was provided in 47 (36%). The length of follow-up was reported in 95 reports (72%). Assessment of adverse events by an adjudication committee was described in 46 reports (35%), and adverse events were described as being followed up for 6 months in 24% of reports (n = 32), between 7 to 12 months in 42% (n = 55) and for more than 1 year in 4% (n = 5). In 115 reports (87%), numerical data on the nature of the adverse events were reported per treatment arm. Procedural complications were described in 30 articles (23%). The causality of adverse events was reported in only 4 articles.</p> <p>Conclusion</p> <p>Several harm-related data were not adequately accounted for in articles of randomized controlled trials assessing stents for percutaneous coronary intervention.</p> <p>Trials Registration</p> <p>Trials manuscript: 5534201182098351 (T80802P)</p

Complete revascularization with multivessel PCI for myocardial infarction

BACKGROUND In patients with ST-segment elevation myocardial infarction (STEMI), percutaneous coronary intervention (PCI) of the culprit lesion reduces the risk of cardiovascular death or myocardial infarction. Whether PCI of nonculprit lesions further reduces the risk of such events is unclear. METHODS We randomly assigned patients with STEMI and multivessel coronary artery disease who had undergone successful culprit-lesion PCI to a strategy of either complete revascularization with PCI of angiographically significant nonculprit lesions or no further revascularization. Randomization was stratified according to the intended timing of nonculprit-lesion PCI (either during or after the index hospitalization). The first coprimary outcome was the composite of cardiovascular death or myocardial infarction; the second coprimary outcome was the composite of cardiovascular death, myocardial infarction, or ischemia-driven revascularization. RESULTS At a median follow-up of 3 years, the first coprimary outcome had occurred in 158 of the 2016 patients (7.8%) in the complete-revascularization group as compared with 213 of the 2025 patients (10.5%) in the culprit-lesion-only PCI group (hazard ratio, 0.74; 95% confidence interval [CI], 0.60 to 0.91; P=0.004). The second coprimary outcome had occurred in 179 patients (8.9%) in the complete-revascularization group as compared with 339 patients (16.7%) in the culprit-lesion-only PCI group (hazard ratio, 0.51; 95% CI, 0.43 to 0.61; P<0.001). For both coprimary outcomes, the benefit of complete revascularization was consistently observed regardless of the intended timing of nonculprit-lesion PCI (P=0.62 and P=0.27 for interaction for the first and second coprimary outcomes, respectively). CONCLUSIONS Among patients with STEMI and multivessel coronary artery disease, complete revascularization was superior to culprit-lesion-only PCI in reducing the risk of cardiovascular death or myocardial infarction, as well as the risk of cardiovascular death, myocardial infarction, or ischemia-driven revascularization. (Funded by the Canadian Institutes of Health Research and others; COMPLETE ClinicalTrials.gov number, NCT01740479. opens in new tab.

Adolescentes y drogas : su relación con la delincuencia

Esta investigación describe la relación con las drogas de una muestra de 286 Adolescentes en Conflicto con la Ley de la ciudad de Valencia (España). Tiene por objeto analizar relación entre trayectoria delictiva y consumo de drogas. Los resultados informan que a mayor incidencia delictiva, mayor dependencia. En cuanto a patrones de consumo por tipo de sustancia, el cannabis se asocia a trayectorias delictivas iniciales y la cocaína a trayectorias consolidadas. El consumo se produce en escenarios habituales diurnos, se extiende a otros de ocio nocturno, y particularmente forma parte de la vida cotidiana de los adolescentes en conflicto con la ley de trayectoria consolidada

Site Fidelity in Space Use by Spider Monkeys (Ateles geoffroyi) in the Yucatan Peninsula, Mexico

Animal home ranges may vary little in their size and location in the short term but nevertheless show more variability in the long term. We evaluated the degree of site fidelity of two groups of spider monkeys (Ateles geoffroyi) over a 10- and 13-year period, respectively, in the northeastern Yucatan peninsula, Mexico. We used the Local Convex Hull method to estimate yearly home ranges and core areas (defined as the 60% probability contour) for the two groups. Home ranges varied from 7.7 to 49.6 ha and core areas varied from 3.1 to 9.2 ha. We evaluated the degree of site fidelity by quantifying the number of years in which different areas were used as either home ranges or core areas. Large tracts were used only as home ranges and only for a few years, whereas small areas were used as either core area or home range for the duration of the study. The sum of the yearly core areas coincided partially with the yearly home ranges, indicating that home ranges contain areas used intermittently. Home ranges, and especially core areas, contained a higher proportion of mature forest than the larger study site as a whole. Across years and only in one group, the size of core areas was positively correlated with the proportion of adult males in the group, while the size of home ranges was positively correlated with both the proportion of males and the number of tree species included in the diet. Our findings suggest that spider monkey home ranges are the result of a combination of long-term site fidelity and year-to-year use variation to enable exploration of new resources