Activation regions in a yeast transposon have homology to mating type control sequences and to mammalian enhancers.

The DNA sequence of the Ty1 activating region from the CYC7-H2 mutant of Saccharomyces cerevisiae is presented. Analysis of the data revealed the presence of four simian virus 40-type enhancer core sequences. Two of the Ty1 enhancer cores are contiguous with sequences also homologous to the diploid control site at MAT alpha. We postulate that these two Ty1 regions of approximately equal to 30 base pairs are regulatory blocks, and we have analyzed deletions to ascertain whether they are necessary for effects of Ty1 on adjacent gene expression. We found that activation is lost when a restriction fragment encompassing both postulated regulatory blocks is deleted. Deletion of restriction fragments that remove only one of the two regulatory blocks has little or no effect on Ty1 activating ability in haploid yeast cells or on repression of this function in diploid yeast cells. Because the most significant internal homologies in the restriction fragments analyzed are the putative regulatory blocks, these observations suggest that enhancer-like sequences are involved in cell-type control of Ty1 effects on gene expression

Factors Affecting the Amount of Puffing in Tomatoes.

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Peak positions and shapes in neutron pair correlation functions from powders of highly anisotropic crystals

The effect of the powder average on the peak shapes and positions in neutron pair distribution functions of polycrystalline materials is examined. It is shown that for highly anisotropic crystals, the powder average leads to shifts in peak positions and to non-Gaussian peak shapes. The peak shifts can be as large as several percent of the lattice spacing

Ecologists need robust survey designs, sampling and analytical methods

1. Research that yields conflicting results rightly causes controversy. Where methodological weaknesses are apparent, there is ready opportunity for discord within the scientific community, which may undermine the entire study. 2. We use the debate about the role of dingoes Canis dingo in conservation in Australia as a case study for a phenomenon that is relevant to all applied ecologists, where conflicting results have been published in high-quality journals and yet the problems with the methods used in these studies have led to significant controversy. 3. To alleviate such controversies, scientists need to use robust methods to ensure that their results are repeatable and defendable. To date, this has not occurred in Australia’s dingo debate due to the use of unvalidated indices that rely on unsupported assumptions. 4. We highlight the problems that poor methods have caused in this debate. We also reiterate our recommendations for practitioners, statisticians and researchers to work together to develop long-term, multi-site experimental research programmes using robust methods to understand the impacts of dingoes on mesopredators. 5. Synthesis and applications. Incorporating robust methods and appropriate experimental designs is needed to ensure that conservation actions are appropriately focused and are supported with robust results. Such actions will go a long way towards resolving the debate about the role of dingoes in conservation in Australia, and other, ecological debates.http://onlinelibrary.wiley.com/journal/10.1111/(ISSN)1365-2664hb201

Fibrinogen, viscosity, and white blood cell count are major risk factors for ischemic heart disease. The Caerphilly and Speedwell collaborative heart disease studies.

BACKGROUND Recent studies have suggested that hemostatic factors and white blood cell count are predictive of ischemic heart disease (IHD). The relations of fibrinogen, viscosity, and white blood cell count to the incidence of IHD in the Caerphilly and Speedwell prospective studies are described. METHODS AND RESULTS The two studies have a common core protocol and are based on a combined cohort of 4,860 middle-aged men from the general population. The first follow-up was at a nearly constant interval of 5.1 years in Caerphilly and 3.2 years in Speedwell; 251 major IHD events had occurred. Age-adjusted relative odds of IHD for men in the top 20% of the distribution compared with the bottom 20% were 4.1 (95% confidence interval, 2.6-6.5) for fibrinogen, 4.5 (95% confidence interval, 2.8-7.4) for viscosity, and 3.2 (95% confidence interval, 2.0-4.9) for white blood cell count. Associations with IHD were similar in men who had never smoked, exsmokers, and current smokers, and the results suggest that at least part of the effect of smoking on IHD is mediated through fibrinogen, viscosity, and white blood cell count. Multivariate analysis shows that white blood cell count is an independent risk factor for IHD as is either fibrinogen or viscosity, or possibly both. Jointly, these three variables significantly improve the fit of a logistic regression model containing all the main conventional risk factors. Further, a model including age, smoking habits, fibrinogen, viscosity, and white blood cell count predicts IHD as well as one in which the three hemostatic/rheological variables are replaced by total cholesterol, diastolic pressure, and body mass index. CONCLUSION Jointly, fibrinogen, viscosity, and white blood cell count are important risk factors for IHD

Activation of Ventral Tegmental Area 5-HT2C Receptors Reduces Incentive Motivation

FUNDING AND DISCLOSURE The research was funded by Wellcome Trust (WT098012) to LKH; and National Institute of Health (DK056731) and the Marilyn H. Vincent Foundation to MGM. The University of Michigan Transgenic Core facility is partially supported by the NIH-funded University of Michigan Center for Gastrointestinal Research (DK034933). The remaining authors declare no conflict of interest. ACKNOWLEDGMENTS We thank Dr Celine Cansell, Ms Raffaella Chianese and the staff of the Medical Research Facility for technical assistance. We thank Dr Vladimir Orduña for the scientific advice and technical assistance.Peer reviewedPublisher PD

Troponin I and cardiovascular risk prediction in the general population: the BiomarCaRE consortium

Our aims were to evaluate the distribution of troponin I concentrations in population cohorts across Europe, to characterize the association with cardiovascular outcomes, to determine the predictive value beyond the variables used in the ESC SCORE, to test a potentially clinically relevant cut-off value, and to evaluate the improved eligibility for statin therapy based on elevated troponin I concentrations retrospectively

The Association of C-Reactive Protein and CRP Genotype with Coronary Heart Disease: Findings from Five Studies with 4,610 Cases amongst 18,637 Participants

Background: It is unclear whether C-reactive protein (CRP) is causally related to coronary heart disease (CHD). Genetic variants that are known to be associated with CRP levels can be used to provide causal inference of the effect of CRP on CHD. Our objective was to examine the association between CRP genetic variant +1444C>T (rs1130864) and CHD risk in the largest study to date of this association.Methods and Results: We estimated the association of CRP genetic variant +1444C>T (rs1130864) with CRP levels and with CHD in five studies and then pooled these analyses (N= 18,637 participants amongst whom there were 4,610 cases). CRP was associated with potential confounding factors (socioeconomic position, physical activity, smoking and body mass) whereas genotype (rs1130864) was not associated with these confounders. The pooled odds ratio of CHD per doubling of circulating CRP level after adjustment for age and sex was 1.13 (95% CI: 1.06, 1.21), and after further adjustment for confounding factors it was 1.07 (95% CI: 1.02, 1.13). Genotype (rs1130864) was associated with circulating CRP; the pooled ratio of geometric means of CRP level among individuals with the TT genotype compared to those with the CT/CC genotype was 1.21 (95% CI: 1.15, 1.28) and the pooled ratio of geometric means of CRP level per additional T allele was 1.14 (95% CI: 1.11, 1.18), with no strong evidence in either analyses of between study heterogeneity (I-2 = 0%, p>0.9 for both analyses). There was no association of genotype (rs1130864) with CHD: pooled odds ratio 1.01 (95% CI: 0.88, 1.16) comparing individuals with TT genotype to those with CT/CC genotype and 0.96 (95% CI: 0.90, 1.03) per additional T allele (I-2<7.5%, p. 0.6 for both meta-analyses). An instrumental variables analysis (in which the proportion of CRP levels explained by rs1130864 was related to CHD) suggested that circulating CRP was not associated with CHD: the odds ratio for a doubling of CRP level was 1.04 (95% CI: 0.61, 1.80).Conclusions: We found no association of a genetic variant, which is known to be related to CRP levels, (rs1130864) and having CHD. These findings do not support a causal association between circulating CRP and CHD risk, but very large, extended, genetic association studies would be required to rule this out