Regional genome transcriptional response of adult mouse brain to hypoxia

<p>Abstract</p> <p>Background</p> <p>Since normal brain function depends upon continuous oxygen delivery and short periods of hypoxia can precondition the brain against subsequent ischemia, this study examined the effects of brief hypoxia on the whole genome transcriptional response in adult mouse brain.</p> <p>Result</p> <p>Pronounced changes of gene expression occurred after 3 hours of hypoxia (8% O₂) and after 1 hour of re-oxygenation in all brain regions. The hypoxia-responsive genes were predominantly up-regulated in hindbrain and predominantly down-regulated in forebrain - possibly to support hindbrain survival functions at the expense of forebrain cognitive functions. The up-regulated genes had a significant role in cell survival and involved both shared and unshared signaling pathways among different brain regions. Up-regulation of transcriptional signaling including hypoxia inducible factor, insulin growth factor (IGF), the vitamin D3 receptor/retinoid X nuclear receptor, and glucocorticoid signaling was common to many brain regions. However, many of the hypoxia-regulated target genes were specific for one or a few brain regions. Cerebellum, for example, had 1241 transcripts regulated by hypoxia only in cerebellum but not in hippocampus; and, 642 (54%) had at least one hepatic nuclear receptor 4A (HNF4A) binding site and 381 had at least two HNF4A binding sites in their promoters. The data point to HNF4A as a major hypoxia-responsive transcription factor in cerebellum in addition to its known role in regulating erythropoietin transcription. The genes unique to hindbrain may play critical roles in survival during hypoxia.</p> <p>Conclusion</p> <p>Differences of forebrain and hindbrain hypoxia-responsive genes may relate to suppression of forebrain cognitive functions and activation of hindbrain survival functions, which may coordinately mediate the neuroprotection afforded by hypoxia preconditioning.</p

CsMYB60 is a key regulator of flavonols and proanthocyanidans that determine the colour of fruit spines in cucumber

Spine colour is an important fruit quality trait that influences the commercial value of cucumber (Cucumis sativus). However, little is known about the metabolites and the regulatory mechanisms of their biosynthesis in black spine varieties. In this study, we determined that the pigments of black spines are flavonoids, including flavonols and proanthocyanidins (PAs). We identified CsMYB60 as the best candidate for the previously identified B (Black spine) locus. Expression levels of CsMYB60 and the key genes involved in flavonoid biosynthesis were higher in black-spine inbred lines than that in white-spine lines at different developmental stages. The insertion of a Mutator-like element (CsMULE) in the second intron of CsMYB60 decreased its expression in a white-spine line. Transient overexpression assays indicated that CsMYB60 is a key regulatory gene and Cs4CL is a key structural gene in the pigmentation of black spines. In addition, the DNA methylation level in the CsMYB60 promoter was much lower in the black-spine line compared with white-spine line. The CsMULE insert may decrease the expression level of CsMYB60, causing hindered synthesis of flavonols and PAs in cucumber fruit spines

Hemorrhagic transformation after ischemic stroke in animals and humans.

Hemorrhagic transformation (HT) is a common complication of ischemic stroke that is exacerbated by thrombolytic therapy. Methods to better prevent, predict, and treat HT are needed. In this review, we summarize studies of HT in both animals and humans. We propose that early HT (&lt;18 to 24 hours after stroke onset) relates to leukocyte-derived matrix metalloproteinase-9 (MMP-9) and brain-derived MMP-2 that damage the neurovascular unit and promote blood-brain barrier (BBB) disruption. This contrasts to delayed HT (&gt;18 to 24 hours after stroke) that relates to ischemia activation of brain proteases (MMP-2, MMP-3, MMP-9, and endogenous tissue plasminogen activator), neuroinflammation, and factors that promote vascular remodeling (vascular endothelial growth factor and high-moblity-group-box-1). Processes that mediate BBB repair and reduce HT risk are discussed, including transforming growth factor beta signaling in monocytes, Src kinase signaling, MMP inhibitors, and inhibitors of reactive oxygen species. Finally, clinical features associated with HT in patients with stroke are reviewed, including approaches to predict HT by clinical factors, brain imaging, and blood biomarkers. Though remarkable advances in our understanding of HT have been made, additional efforts are needed to translate these discoveries to the clinic and reduce the impact of HT on patients with ischemic stroke

Hemorrhagic Transformation after Ischemic Stroke in Animals and Humans

Hemorrhagic transformation (HT) is a common complication of ischemic stroke that is exacerbated by thrombolytic therapy. Methods to better prevent, predict, and treat HT are needed. In this review, we summarize studies of HT in both animals and humans. We propose that early HT (<18 to 24 hours after stroke onset) relates to leukocyte-derived matrix metalloproteinase-9 (MMP-9) and brain-derived MMP-2 that damage the neurovascular unit and promote blood–brain barrier (BBB) disruption. This contrasts to delayed HT (>18 to 24 hours after stroke) that relates to ischemia activation of brain proteases (MMP-2, MMP-3, MMP-9, and endogenous tissue plasminogen activator), neuroinflammation, and factors that promote vascular remodeling (vascular endothelial growth factor and high-moblity-group-box-1). Processes that mediate BBB repair and reduce HT risk are discussed, including transforming growth factor beta signaling in monocytes, Src kinase signaling, MMP inhibitors, and inhibitors of reactive oxygen species. Finally, clinical features associated with HT in patients with stroke are reviewed, including approaches to predict HT by clinical factors, brain imaging, and blood biomarkers. Though remarkable advances in our understanding of HT have been made, additional efforts are needed to translate these discoveries to the clinic and reduce the impact of HT on patients with ischemic stroke

Recycled moisture in an enclosed basin, Guanzhong Basin of Northern China, in the summer: Contribution to precipitation based on a stable isotope approach

Recycled moisture, mainly originated from evapotranspiration (surface evaporation and transpiration), is the main sources of precipitation. Influenced on the different regional/local environments, the contributions of recycled moisture to precipitation present as different proportions. Recycled moisture has an important impact on the hydrological cycle, further occurred a series of environmental effect for regional/local. Aimed to estimate the contribution of recycled moisture to precipitation in an enclosed basin, Guanzhong Basin of northern China, precipitation and lake/reservoir samples were collected. The isotope ratio analysis was done for the summer season, and a three-component mixing model based on the stable hydrogen and oxygen isotopes was applied. The results indicated that the averaged contribution of recycled moisture to precipitation was 17.44% in Guanzhong Basin of northern China, while the mean proportions of surface evaporation moisture and transpiration moisture were found to be 0.38% and 16.97%, respectively. Comparatively, most of the recycled moisture mainly comes from transpiration moisture rather than evaporation moisture, suggesting that transpiration moisture from cropland, vegetation, and plants instead of evaporation is dominant in moisture recycling of the Guanzhong Basin

Nitrosporeusines A and B, Unprecedented Thioester-Bearing Alkaloids from the Arctic <i>Streptomyces nitrosporeus</i>

Chemical examination of an arctic actinomycete <i>Streptomyces nitrosporeus</i> resulted in the isolation of two new alkaloids named nitrosporeusines A (<b>1</b>) and B (<b>2</b>), an unprecedented skeleton containing benzenecarbothioc cyclopenta[<i>c</i>]pyrrole-1,3-dione. Their structures were determined through extensive spectroscopic analyses in association with X-ray single crystal diffraction. Both <b>1</b> and <b>2</b> exhibited inhibitory activities against the H1N1 virus in MDCK cells

Nitrosporeusines A and B, Unprecedented Thioester-Bearing Alkaloids from the Arctic <i>Streptomyces nitrosporeus</i>

Chemical examination of an arctic actinomycete <i>Streptomyces nitrosporeus</i> resulted in the isolation of two new alkaloids named nitrosporeusines A (<b>1</b>) and B (<b>2</b>), an unprecedented skeleton containing benzenecarbothioc cyclopenta[<i>c</i>]pyrrole-1,3-dione. Their structures were determined through extensive spectroscopic analyses in association with X-ray single crystal diffraction. Both <b>1</b> and <b>2</b> exhibited inhibitory activities against the H1N1 virus in MDCK cells