Background-Cardiovascular events occur most frequently in the morning hours. We prospectively studied the association between the morning blood pressure (BP) surge and stroke in elderly hypertensives. Methods and Results-We studied stroke prognosis in 519 older hypertensives in whom ambulatory BP monitoring was performed and silent cerebral infarct was assessed by brain MRI and who were followed up prospectively. The morning BP surge (MS) was calculated as follows: mean systolic BP during the 2 hours after awakening minus mean systolic BP during the 1 hour that included the lowest sleep BP. During an average duration of 41 months (range 1 to 68 months), 44 stroke events occurred. When the patients were divided into 2 groups according to MS, those in the top decile (MS group; MS Ն55 mm Hg, nϭ53) had a higher baseline prevalence of multiple infarcts (57% versus 33%, Pϭ0.001) and a higher stroke incidence (19% versus 7.3%, Pϭ0.004) during the follow-up period than the others (non-MS group; MS Ͻ55 mm Hg, nϭ466). After they were matched for age and 24-hour BP, the relative risk of the MS group versus the non-MS group remained significant (relative riskϭ2.7, Pϭ0.04). The MS was associated with stroke events independently of 24-hour BP, nocturnal BP dipping status, and baseline prevalence of silent infarct (Pϭ0.008). Conclusions-In older hypertensives, a higher morning BP surge is associated with stroke risk independently of ambulatory BP, nocturnal BP falls, and silent infarct. Reduction of the MS could thus be a new therapeutic target for preventing target organ damage and subsequent cardiovascular events in

The pluripotential cell-specific gene Nanog encodes a homeodomain-bearing transcription factor required for maintaining the undifferentiated state of stem cells. However, the molecular mechanisms that regulate Nanog gene expression are largely unknown. To address this important issue, we used luciferase assays to monitor the relative activities of deletion fragments from the 5-flanking region of the gene. An adjacent pair of highly conserved Octamer-and Sox-binding sites was found to be essential for activating pluripotential state-specific gene expression. Furthermore, the 5-end fragment encompassing the Octamer/Sox element was sufficient for inducing the proper expression of a green fluorescent protein reporter gene even in human embryonic stem (ES) cells. The potential of OCT4 and SOX2 to bind to this element was verified by electrophoretic mobility shift assays with extracts from F9 embryonal carcinoma cells and embryonic germ cells derived from embryonic day 12.5 embryos. However, in ES cell extracts, a complex of OCT4 with an undefined factor preferentially bound to the Octamer/Sox element. Thus, Nanog transcription may be regulated through an interaction between Oct4 and Sox2 or a novel pluripotential cell-specific Sox element-binding factor which is prominent in ES cells.

Intracellular energy balance is important for cell survival. In eukaryotic cells, the most energy-consuming process is ribosome biosynthesis, which adapts to changes in intracellular energy status. However, the mechanism that links energy status and ribosome biosynthesis is largely unknown. Here, we describe eNoSC, a protein complex that senses energy status and controls rRNA transcription. eNoSC contains Nucleomethylin, which binds histone H3 dimethylated Lys9 in the rDNA locus, in a complex with SIRT1 and SUV39H1. Both SIRT1 and SUV39H1 are required for energy-dependent transcriptional repression, suggesting that a change in the NAD(+)/NADH ratio induced by reduction of energy status could activate SIRT1, leading to deacetylation of histone H3 and dimethylation at Lys9 by SUV39H1, thus establishing silent chromatin in the rDNA locus. Furthermore, eNoSC promotes restoration of energy balance by limiting rRNA transcription, thus protecting cells from energy deprivation-dependent apoptosis. These findings provide key insight into the mechanisms of energy homeostasis in cells.

These results suggest that galectin-3 is involved in the pathogenesis of human IPF and CVD-IP by activating macrophages and fibroblasts.