Zscan4 regulates telomere elongation and genomic stability in ES cells

Exceptional genomic stability is one of the hallmarks of mouse embryonic stem (ES) cells. However, the genes contributing to this stability remain obscure. We previously identified Zscan4 as a specific marker for two-cell embryo and ES cells. Here we show that Zscan4 is involved in telomere maintenance and long-term genomic stability in ES cells. Only 5% of ES cells express Zscan4 at a given time, but nearly all ES cells activate Zscan4 at least once during nine passages. The transient Zscan4-positive state is associated with rapid telomere extension by telomere recombination and upregulation of meiosis-specific homologous recombination genes, which encode proteins that are colocalized with ZSCAN4 on telomeres. Furthermore, Zscan4 knockdown shortens telomeres, increases karyotype abnormalities and spontaneous sister chromatid exchange, and slows down cell proliferation until reaching crisis by passage eight. Together, our data show a unique mode of genome maintenance in ES cells. © 2010 Macmillan Publishers Limited. All rights reserved

Studying the spatial variability of methane flux with five eddy covariance towers of varying height

In this study, the spatial representativeness of eddy covariance (EC) methane (CH4) measurements was examined by comparing parallel CH4 fluxes from three short (6 m) towers separated by a few kilometres and from two higher levels (20 m and 60 m) at one location. The measurement campaign was held on an intensively managed grassland on peat soil in the Netherlands. The land use and land cover types are to a large degree homogeneous in the area. The CH4 fluxes exhibited significant variability between the sites on 30-min scale. The spatial coefficient of variation (CVspa) between the three short towers was 56% and it was of similar magnitude as the temporal variability, unlike for the other fluxes (friction velocity, sensible heat flux) for which the temporal variability was considerably larger than the spatial variability. The CVspa decreased with temporal averaging, although less than what could be expected for a purely random process (1/√N), and it was 14% for 26-day means of CH4 flux. This reflects the underlying heterogeneity of CH4 flux in the studied landscape at spatial scales ranging from 1 ha (flux footprint) to 10 km2 (area bounded by the short towers). This heterogeneity should be taken into account when interpreting and comparing EC measurements. On an annual scale, the flux spatial variability contributed up to 50% of the uncertainty in CH4 emissions. It was further tested whether EC flux measurements at higher levels could be used to acquire a more accurate estimate of the spatially integrated CH4 emissions. Contrarily to what was expected, flux intensity was found to both increase and decrease depending on measurement height. Using footprint modelling, 56% of the variation between 6 m and 60 m CH4 fluxes was attributed to emissions from local anthropogenic hotspots (farms). Furthermore, morning hours proved to be demanding for the tall tower EC where fluxes at 60 m were up to four-fold those at lower heights. These differences were connected with the onset of convective mixing during the morning period.Peer reviewe

The Impact of Patient Navigation on the Delivery of Diagnostic Breast Cancer Care in the National Patient Navigation Research Program: A Prospective Meta-Analysis.

Patient navigation is emerging as a standard in breast cancer care delivery, yet multi-site data on the impact of navigation at reducing delays along the continuum of care are lacking. The purpose of this study was to determine the effect of navigation on reaching diagnostic resolution at specific time points after an abnormal breast cancer screening test among a national sample. A prospective meta-analysis estimated the adjusted odds of achieving timely diagnostic resolution at 60, 180, and 365 days. Exploratory analyses were conducted on the pooled sample to identify which groups had the most benefit from navigation. Clinics from six medical centers serving vulnerable populations participated in the Patient Navigation Research Program. Women with an abnormal breast cancer screening test between 2007 and 2009 were included and received the patient navigation intervention or usual care. Patient navigators worked with patients and their care providers to address patient-specific barriers to care to prevent delays in diagnosis. A total of 4675 participants included predominantly racial/ethnic minorities (74 %) with public insurance (40 %) or no insurance (31 %). At 60 days and 180 days, there was no statistically significant effect of navigation on achieving timely diagnostic care, but a benefit of navigation was seen at 365 days (aOR 2.12, CI 1.36-3.29). We found an equal benefit of navigation across all groups, regardless of race/ethnicity, language, insurance status, and type of screening abnormality. Patient navigation resulted in more timely diagnostic resolution at 365 days among a diverse group of minority, low-income women with breast cancer screening abnormalities. Trial registrations clinicaltrials.gov Identifiers: NCT00613275, NCT00496678, NCT00375024, NCT01569672

Prevalence of obesity and abdominal obesity in the Lausanne population

Obesity can be defined using body mass index (BMI) or waist (abdominal obesity). Little information exists regarding its prevalence and determinants in Switzerland. Hence, we assessed the levels of obesity as defined by BMI or waist circumference in a Swiss population-based sample. Cross-sectional, population-based non-stratified random sample of 3,249 women and 2,937 men aged 35-75 years living in Lausanne, Switzerland. Overall participation rate was 41%. In men, the prevalences of overweight (BMI > or =25 kg/m2) and obesity (BMI > or =30 kg/m2) were 45.5% and 16.9%, respectively, higher than in women (28.3% and 14.3%, respectively). The prevalence of abdominal obesity (waist > or =102 in men and > or =88 cm in women) was higher in women than in men (30.6% vs. 23.9%). Obesity and abdominal obesity increased with age and decreased with higher educational level in both genders. In women, the prevalence of obesity was lower among former and current smokers, whereas in men the prevalence of obesity was higher in former smokers but did not differ between current and never smokers. Multivariate analysis showed age to be positively related, and education and physical activity to be negatively related with obesity and abdominal obesity in both genders, whereas differential effects of smoking were found between genders. The prevalence of abdominal obesity is higher than BMI-derived obesity in the Swiss population. Women presented with more abdominal obesity than men. The association between smoking and obesity levels appears to differ between genders

Statistical epistasis between candidate gene alleles for complex tuber traits in an association mapping population of tetraploid potato

Association mapping using DNA-based markers is a novel tool in plant genetics for the analysis of complex traits. Potato tuber yield, starch content, starch yield and chip color are complex traits of agronomic relevance, for which carbohydrate metabolism plays an important role. At the functional level, the genes and biochemical pathways involved in carbohydrate metabolism are among the best studied in plants. Quantitative traits such as tuber starch and sugar content are therefore models for association genetics in potato based on candidate genes. In an association mapping experiment conducted with a population of 243 tetraploid potato varieties and breeding clones, we previously identified associations between individual candidate gene alleles and tuber starch content, starch yield and chip quality. In the present paper, we tested 190 DNA markers at 36 loci scored in the same association mapping population for pairwise statistical epistatic interactions. Fifty marker pairs were associated mainly with tuber starch content and/or starch yield, at a cut-off value of q ≤ 0.20 for the experiment-wide false discovery rate (FDR). Thirteen marker pairs had an FDR of q ≤ 0.10. Alleles at loci encoding ribulose-bisphosphate carboxylase/oxygenase activase (Rca), sucrose phosphate synthase (Sps) and vacuolar invertase (Pain1) were most frequently involved in statistical epistatic interactions. The largest effect on tuber starch content and starch yield was observed for the paired alleles Pain1-8c and Rca-1a, explaining 9 and 10% of the total variance, respectively. The combination of these two alleles increased the means of tuber starch content and starch yield. Biological models to explain the observed statistical epistatic interactions are discussed

Expression and Function of Macrophage Migration Inhibitory Factor (MIF) in Melioidosis

Melioidosis is a severe tropical infection caused by the bacterium Burkholderia pseudomallei. B. pseudomallei is the major cause of community-acquired septicemia in northeast Thailand with a mortality rate in severe cases of around 40% Little is known, however, about the mechanisms of the host defense to B. pseudomallei infection. Macrophage migration inhibitory factor (MIF) is a proinflammatory cytokine that has emerged as an important mediator of the host defense in severe bacterial infections. In this article, we studied the expression and function of MIF both in patients with melioidosis and in mice during experimental melioidosis. We found that MIF concentrations were elevated in patients with melioidosis. Furthermore, high MIF concentrations are associated with poor outcome in patients with melioidosis. Also, in mice with experimentally induced melioidosis, we observed an upregulation of MIF concentrations. Furthermore, mice with melioidosis that were treated with a MIF blocking treatment showed lower bacterial counts in their lungs during infection. In conclusion, MIF seems to impair host defense mechanisms during melioidosis

A Fear-Inducing Odor Alters PER2 and c-Fos Expression in Brain Regions Involved in Fear Memory

Evidence demonstrates that rodents learn to associate a foot shock with time of day, indicating the formation of a fear related time-stamp memory, even in the absence of a functioning SCN. In addition, mice acquire and retain fear memory better during the early day compared to the early night. This type of memory may be regulated by circadian pacemakers outside of the SCN. As a first step in testing the hypothesis that clock genes are involved in the formation of a time-stamp fear memory, we exposed one group of mice to fox feces derived odor (TMT) at ZT 0 and one group at ZT 12 for 4 successive days. A separate group with no exposure to TMT was also included as a control. Animals were sacrificed one day after the last exposure to TMT, and PER2 and c-Fos protein were quantified in the SCN, amygdala, hippocampus, and piriform cortex. Exposure to TMT had a strong effect at ZT 0, decreasing PER2 expression at this time point in most regions except the SCN, and reversing the normal rhythm of PER2 expression in the amygdala and piriform cortex. These changes were accompanied by increased c-Fos expression at ZT0. In contrast, exposure to TMT at ZT 12 abolished the rhythm of PER2 expression in the amygdala. In addition, increased c-Fos expression at ZT 12 was only detected in the central nucleus of the amygdala in the TMT12 group. TMT exposure at either time point did not affect PER2 or c-Fos in the SCN, indicating that under a light-dark cycle, the SCN rhythm is stable in the presence of repeated exposure to a fear-inducing stimulus. Taken together, these results indicate that entrainment to a fear-inducing stimulus leads to changes in PER2 and c-Fos expression that are detected 24 hours following the last exposure to TMT, indicating entrainment of endogenous oscillators in these regions. The observed effects on PER2 expression and c-Fos were stronger during the early day than during the early night, possibly to prepare appropriate systems at ZT 0 to respond to a fear-inducing stimulus