Disease-associated SNPs at the 9p21 locus predominantly affect the expression of ANRIL. Overall, our results suggest that several CVD-associated SNPs in the 9p21 locus affect the expression of ANRIL, which, in turn modulate cell growth, possibly via CDKN2A/B regulation.

Defective glucose-stimulated insulin secretion is the main cause of hyperglycemia in type 2 diabetes mellitus. Mutations in HNF-1alpha cause a monogenic form of type 2 diabetes, maturity-onset diabetes of the young (MODY), characterized by impaired insulin secretion. Here we report that collectrin, a recently cloned kidney-specific gene of unknown function, is a target of HNF-1alpha in pancreatic beta cells. Expression of collectrin was decreased in the islets of HNF-1alpha (-/-) mice, but was increased in obese hyperglycemic mice. Overexpression of collectrin in rat insulinoma INS-1 cells or in the beta cells of transgenic mice enhanced glucose-stimulated insulin exocytosis, without affecting Ca(2+) influx. Conversely, suppression of collectrin attenuated insulin secretion. Collectrin bound to SNARE complexes by interacting with snapin, a SNAP-25 binding protein, and facilitated SNARE complex formation. Therefore, collectrin is a regulator of SNARE complex function, which thereby controls insulin exocytosis.

No abstract

We present the thermal evolution and emergent spectra of solidifying terrestrial planets along with the formation of steam atmospheres. The lifetime of a magma ocean and its spectra through a steam atmosphere depends on the orbital distance of the planet from the host star. For a type-I planet, which is formed beyond a certain critical distance from the host star, the thermal emission declines on a timescale shorter than approximately 10 6 years. Therefore, young stars should be targets when searching for molten planets in this orbital region. In contrast, a type-II planet, which is formed inside the critical distance, will emit significant thermal radiation from near-infrared atmospheric windows during the entire lifetime of the magma ocean. The Ks and L bands will be favorable for future direct imaging because the planet-to-star contrasts of these bands are higher than approximately 10 −7 -10 −8 . Our model predicts that, in the type-II orbital region, molten planets would be present over the main sequence of the G-type host star if the initial bulk content of water exceeds approximately 1 wt%. In visible atmospheric windows, the contrasts of the thermal emission drop below 10 −10 in less than 10 5 years, whereas those of the reflected light remain 10 −10 for both types of planets. Since the contrast level is comparable to those of reflected light from Earth-sized planets in the habitable zone, the visible reflected light from molten planets also provides a promising target for direct imaging with future ground-and space-based telescopes.

Hypertension is an important risk factor for cardiovascular diseases such as chronic kidney disease. It is still not fully understood how blood pressure impacts the kidneys. In this study, we aimed to establish the significance of visit-to-visit variability in blood pressure for renal function. We analyzed 143 consecutive patients undergoing renal Doppler ultrasonography in our hospital ward and measured blood pressure at outpatient visits six or more times. We analyzed the correlation between visit-to-visit variability in blood pressure and multiple clinical parameters, including albuminuria and resistive index evaluated by renal Doppler ultrasonography, which is thought to be a good indicator of renal vascular resistance. Subjects with higher variability in systolic blood pressure showed a significantly higher prevalence rate of clinical albuminuria and microalbuminuria, and showed significantly higher resistive index. Stepwise multiple regression analysis showed that variability in systolic blood pressure was a significant risk factor for higher resistive index, independent of other renal risk factors. Visit-to-visit variability in blood pressure correlates significantly with renal function and renal arteriosclerotic change. This parameter could provide additional information about renal arteriosclerotic change independent of estimated glomerular filtration rate and albuminuria, and should be considered a therapeutic target for renal protection.

The present study indicated that RI might be very useful for the evaluation of very early renal damage more effectively than eGFR and that diurnal BP change might be partly due to the progression of atherosclerotic change in the kidney evaluated by RI.

Aim: Arterial stiffness has been reported to correlate with cardiovascular disease (CVD). Brachialankle pulse wave velocity (baPWV) is easy to measure and has been used as a marker to evaluate arterial stiffness. The objective of the present study was to determine the cut-off value of baPWV for predicting cardiovascular prognosis in a prospective cohort study. Methods: Four hundred forty patients with essential hypertension were analyzed in study 1 with a mean follow-up of 6.3±0.1 years. Four hundred patients from study 1 who did not have a past history of CVD and/or stroke were analyzed in study 2 with a mean follow-up of 6.4±0.1 years. Stroke, CVD, and death were the primary endpoints. Results: Receiver operating characteristic (ROC) curve analysis revealed that 1750.0 cm/sec is an appropriate cut-off value for baPWV to predict the onset of stroke, CVD, stroke＋CVD, and total mortality (area under curve: 0.576-0.719). A baPWV higher than 1750.0 may also be a significant and independent risk factor for the onset of CVD＋stroke (relative risk: 2.048 (1.176-3.616), p= 0.0113 in study 1; relative risk: 1.920 (1.028-3.634), p = 0.0408 in study 2). Conclusions: The present study indicates that 1750.0 cm/sec could be a useful cut-off value for baPWV to predict cardiovascular prognosis. J Atheroscler Thromb, 2013; 20:391-400.

No abstract