Targeted Derepression of the Human Immunodeficiency Virus Type 1 Long Terminal Repeat by Pyrrole-Imidazole Polyamides

The host factor LSF represses the human immunodeficiency virus type 1 long terminal repeat (LTR) by mediating recruitment of histone deacetylase. We show that pyrrole-imidazole polyamides targeted to the LTR can specifically block LSF binding both in vitro and within cells via direct access to chromatin, resulting in increased LTR expression

Plasma levels of the proprotein convertase furin and incidence of diabetes and mortality

Background. Diabetes mellitus is linked to premature mortality of virtually all causes. Furin is a proprotein convertase broadly involved in the maintenance of cellular homeostasis; however, little is known about its role in the development of diabetes mellitus and risk of premature mortality. Objectives. To test if fasting plasma concentration of furin is associated with the development of diabetes mellitus and mortality. Methods. Overnight fasted plasma furin levels were measured at baseline examination in 4678 individuals from the population-based prospective Malmo Diet and Cancer Study. We studied the relation of plasma furin levels with metabolic and hemodynamic traits. We used multivariable Cox proportional hazards models to investigate the association between baseline plasma furin levels and incidence of diabetes mellitus and mortality during 21.3-21.7 years follow-up. Results. An association was observed between quartiles of furin concentration at baseline and body mass index, blood pressure and plasma concentration of glucose, insulin, LDL and HDL cholesterol (vertical bar 0.11 vertical bar Conclusion. Individuals with high plasma furin concentration have a pronounced dysmetabolic phenotype and elevated risk of diabetes mellitus and premature mortality.Peer reviewe

A Cross-Over in the Enstrophy Decay in Two-Dimensional Turbulence in a Finite Box

The numerical simulation of two-dimensional decaying turbulence in a large but finite box presented in this paper uncovered two physically different regimes of enstrophy decay. During the initial stage, the enstrophy, generated by a random Gaussian initial condition, decays as t^{-gamma} with gamma approximately 0.7-0.8. After that, the flow undergoes a transition to a gas or fluid composed of distinct vortices. Simultaneously, the magnitude of the decay exponent crosses over to gamma approximately 0.4. An exact relation for the total number of vortices, N(t), in terms of the mean circulation of an individual vortex is derived. A theory predicting that N(t) is proportional to t^{-xi} and the magnitudes of exponents gamma=2/5 and xi=4/5 is presented and the possibility of an additional very late-time cross-over to gamma=1/3 and xi=2/3 is also discussed.Comment: 11 pages, 7 figure

Fjern kvikudløbere og overvej kompostering

This article deals with aspects of destructing Elytrigia repens rhizomes after they have been uprooted and exposed on the soil surface. Removal from the field is the best practical option at present. Mechanical crushing may become possible in a few years time to erase their sprouting ability and with the prospects of reurning nutrients to the soil

Vortex line topology during vortex tube reconnection

This paper addresses reconnection of vortex tubes, with particular focus on the topology of the vortex lines (field lines of the vorticity). This analysis of vortex line topology reveals previously undiscovered features of the reconnection process, such as the generation of many small flux rings, formed when reconnection occurs in multiple locations in the vortex sheet between the tubes. Consideration of three-dimensional reconnection principles leads to a robust measurement of the reconnection rate, even once instabilities break the symmetry. It also allows us to identify internal reconnection of vortex lines within the individual vortex tubes. Finally, the introduction of a third vortex tube is shown to render the vortex reconnection process fully three-dimensional, leading to a fundamental change in the topological structure of the process. An additional interesting feature is the generation of vorticity null points.Comment: Accepted for publication in Physical Review Fluid

Waist circumference and a body shape index and prostate cancer risk and mortality.

We recently found a negative association between body mass index (BMI) and the risk of localised prostate cancer (PCa), no association with advanced PCa, and a positive association with PCa-specific mortality. In a 15% subpopulation of that study, we here investigated the measures of abdominal adiposity including waist circumference (WC) and A Body Shape Index (ABSI) in relation to PCa risk and mortality. We used data from 58,457 men from four Swedish cohorts to assess WC and ABSI in relation to PCa risk according to cancer risk category, including localised asymptomatic and symptomatic PCa and advanced PCa, and PCa-specific mortality. Cox regression models were used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs). During, on average, 10 years of follow-up, 3290 men were diagnosed with PCa and 387 died of PCa. WC was negatively associated with the risk of total PCa (HR per 10 cm, 0.95; 95% CI 0.92-0.99), localised PCa (HR per 10 cm, 0.93, 95% CI 0.88-0.96) and localised asymptomatic PCa cases detected through a prostate-specific antigen (PSA) test (HR per 10 cm, 0.87, 95% CI 0.81-0.94). WC was not associated with the risk of advanced PCa (HR per 10 cm, 1.02, 95% CI 0.93-1.14) or with PCa-specific mortality (HR per 10 cm, 1.04, 95% CI 0.92-1.19). ABSI showed no associations with the risk of PCa or PCa-specific mortality. While the negative association between WC and the risk of localised PCa was partially driven by PSA-detected PCa cases, no association was found between abdominal adiposity and clinically manifest PCa in our population

Cardiovascular risk after hospitalisation for unexplained syncope and orthostatic hypotension

OBJECTIVE: To investigate the relationship of hospital admissions due to unexplained syncope and orthostatic hypotension (OH) with subsequent cardiovascular events and mortality. METHODS: We analysed a population-based prospective cohort of 30 528 middle-aged individuals (age 58±8 years; males, 40%). Adjusted Cox regression models were applied to assess the impact of unexplained syncope/OH hospitalisations on cardiovascular events and mortality, excluding subjects with prevalent cardiovascular disease. RESULTS: After a median follow-up of 15±4 years, 524 (1.7%) and 504 (1.7%) participants were hospitalised for syncope or OH, respectively, yielding 1.2 hospital admissions per 1000 person-years for each diagnosis. Syncope hospitalisations increased with age (HR, per 1 year: 1.07, 95% CI 1.05 to 1.09), higher systolic blood pressure (HR, per 10 mm Hg: 1.06, 95% CI 1.01 to 1.12), antihypertensive treatment (HR: 1.26, 95% CI 1.00 to 1.59), use of diuretics (HR: 1.77, 95% CI 1.31 to 2.38) and prevalent cardiovascular disease (HR: 1.59, 95% CI 1.14 to 2.23), whereas OH hospitalisations increased with age (HR: 1.11, 95% CI 1.08 to 1.12) and prevalent diabetes (HR: 1.82, 95% CI 1.23 to 2.70). After exclusion of 1399 patients with prevalent cardiovascular disease, a total of 473/464 patients were hospitalised for unexplained syncope/OH before any cardiovascular event. Hospitalisation for unexplained syncope predicted coronary events (HR: 1.85, 95% CI 1.49 to 2.30), heart failure (HR: 2.24, 95% CI 1.65 to 3.04), atrial fibrillation (HR: 1.84, 95% CI 1.50 to 2.26), aortic valve stenosis (HR: 2.06, 95% CI 1.28 to 3.32), all-cause mortality (HR: 1.22, 95% CI 1.09 to 1.37) and cardiovascular death (HR: 1.72, 95% CI 1.23 to 2.42). OH-hospitalisation predicted stroke (HR: 1.66, 95% CI 1.24 to 2.23), heart failure (HR: 1.78, 95% CI 1.21 to 2.62), atrial fibrillation (HR: 1.89, 95% CI 1.48 to 2.41) and all-cause mortality (HR: 1.14, 95% CI 1.01 to 1.30). CONCLUSIONS: Patients discharged with the diagnosis of unexplained syncope or OH show higher incidence of cardiovascular disease and mortality with only partial overlap between these two conditions

A genome-wide association study for blood lipid phenotypes in the Framingham Heart Study

<p>Abstract</p> <p>Background</p> <p>Blood lipid levels including low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and triglycerides (TG) are highly heritable. Genome-wide association is a promising approach to map genetic loci related to these heritable phenotypes.</p> <p>Methods</p> <p>In 1087 Framingham Heart Study Offspring cohort participants (mean age 47 years, 52% women), we conducted genome-wide analyses (Affymetrix 100K GeneChip) for fasting blood lipid traits. Total cholesterol, HDL-C, and TG were measured by standard enzymatic methods and LDL-C was calculated using the Friedewald formula. The long-term averages of up to seven measurements of LDL-C, HDL-C, and TG over a ~30 year span were the primary phenotypes. We used generalized estimating equations (GEE), family-based association tests (FBAT) and variance components linkage to investigate the relationships between SNPs (on autosomes, with minor allele frequency ≥10%, genotypic call rate ≥80%, and Hardy-Weinberg equilibrium p ≥ 0.001) and multivariable-adjusted residuals. We pursued a three-stage replication strategy of the GEE association results with 287 SNPs (P < 0.001 in Stage I) tested in Stage II (n ~1450 individuals) and 40 SNPs (P < 0.001 in joint analysis of Stages I and II) tested in Stage III (n~6650 individuals).</p> <p>Results</p> <p>Long-term averages of LDL-C, HDL-C, and TG were highly heritable (h²= 0.66, 0.69, 0.58, respectively; each P < 0.0001). Of 70,987 tests for each of the phenotypes, two SNPs had p < 10^-5in GEE results for LDL-C, four for HDL-C, and one for TG. For each multivariable-adjusted phenotype, the number of SNPs with association p < 10^-4ranged from 13 to 18 and with p < 10^-3, from 94 to 149. Some results confirmed previously reported associations with candidate genes including variation in the lipoprotein lipase gene (<it>LPL</it>) and HDL-C and TG (rs7007797; P = 0.0005 for HDL-C and 0.002 for TG). The full set of GEE, FBAT and linkage results are posted at the <b>d</b>ata<b>b</b>ase of <b>G</b>enotype <b>a</b>nd <b>P</b>henotype (dbGaP). After three stages of replication, there was no convincing statistical evidence for association (i.e., combined P < 10^-5across all three stages) between any of the tested SNPs and lipid phenotypes.</p> <p>Conclusion</p> <p>Using a 100K genome-wide scan, we have generated a set of putative associations for common sequence variants and lipid phenotypes. Validation of selected hypotheses in additional samples did not identify any new loci underlying variability in blood lipids. Lack of replication may be due to inadequate statistical power to detect modest quantitative trait locus effects (i.e., <1% of trait variance explained) or reduced genomic coverage of the 100K array. GWAS in FHS using a denser genome-wide genotyping platform and a better-powered replication strategy may identify novel loci underlying blood lipids.</p