RNA Helicase DDX5 Regulates MicroRNA Expression and Contributes to Cytoskeletal Reorganization in Basal Breast Cancer Cells

RNA helicase DDX5 (also p68) is involved in all aspects of RNA metabolism and serves as a transcriptional co-regulator, but its functional role in breast cancer remains elusive. Here, we report an integrative biology study of DDX5 in breast cancer, encompassing quantitative proteomics, global MicroRNA profiling, and detailed biochemical characterization of cell lines and human tissues. We showed that protein expression of DDX5 increased progressively from the luminal to basal breast cancer cell lines, and correlated positively with that of CD44 in the basal subtypes. Through immunohistochemistry analyses of tissue microarrays containing over 200 invasive human ductal carcinomas, we observed that DDX5 was upregulated in the majority of malignant tissues, and its expression correlated strongly with those of Ki67 and EGFR in the triple-negative tumors. We demonstrated that DDX5 regulated a subset of MicroRNAs including miR-21 and miR-182 in basal breast cancer cells. Knockdown of DDX5 resulted in reorganization of actin cytoskeleton and reduction of cellular proliferation. The effects were accompanied by upregulation of tumor suppressor PDCD4 (a known miR-21 target); as well as upregulation of cofilin and profilin, two key proteins involved in actin polymerization and cytoskeleton maintenance, as a consequence of miR-182 downregulation. Treatment with miR-182 inhibitors resulted in morphologic phenotypes resembling those induced by DDX5 knockdown. Using bioinformatics tools for pathway and network analyses, we confirmed that the network for regulation of actin cytoskeleton was predominantly enriched for the predicted downstream targets of miR-182. Our results reveal a new functional role of DDX5 in breast cancer via the DDX5→miR-182→actin cytoskeleton pathway, and suggest the potential clinical utility of DDX5 and its downstream MicroRNAs in the theranostics of breast cancer

Optical System and Detection Range Analysis of Synthetic Aperture Ladar

Optical system and detection range of Synthetic Aperture Ladar (SAL) are analyzed. According to the imaging characteristics of SAL, the concept that SAL uses non-imaging diffractive optical system are proposed, meanwhile, the phased array model is introduced to analyze its performance. In the condition of using binary optical element on the feeder and primary mirror, the phaser parameters and beam pattern are presented using simulation. The signal of 2° view field is introduced into fiber with the 300 mm aperture telescope and compressed optical path. The radar detection range equation of SAL is introduced, coherent detection and signal accumulation gain are analyzed, the conclusion is SAL has good ability of detecting weak signal. Aiming at application requirement, system parameters and working modes of airborne SAL are given with high resolution and long detection range. With 5 cm resolution, the airborne SAL can achieve 5 km detection range with 1.5 km swath in strip-map imaging mode and 10 km detection range with 1 km swath in sliding spotlight imaging mode

Long-term vegetation changes in the four mega-sandy lands in Inner Mongolia, China.

Desertification in China has become one of the most serious ecological and social problems. The four mega-sandy lands (Hulunbeir, Horqin, Otindag, and Mu Us) in Inner Mongolia are reported to be the most widespread and seriously desertified areas in China. To explore changes of vegetation activity and the possible driving forces in the four mega-sandy lands over the last three decades. We investigated spatiotemporal variations in the growing-season (May-September) normalized difference vegetation index (NDVI) and their relationships with climate factors and human activities during 1982-2011, using two NDVI datasets from Global Inventory Modelling and Mapping Studies (GIMMS) and Moderate Resolution Imaging Spectroradiometer (MODIS). We found a significant overall NDVI increase in Mu Us, but no such trends in the other three. A significant increase was in south and northeast Mu Us and southeast Horqin, and a decrease in south Hulunbeir, northwest Horqin, and central Otindag. NDVI trends were positively correlated with precipitation and uncorrelated with temperature and wind speed in all sandy lands except Mu Us. NDVI trends showed a large spatial heterogeneity in the four sandy lands. Precipitation was a major determiner for the interannual variations and spatial patterns of NDVI at regional scale, whereas human activities were the cause of NDVI variations at local scale. The consistent interannual variations between two NDVI datasets of GIMMS and MODIS for all four sandy lands suggested that GIMMS NDVI was appropriate for investigating long-term vegetation changes in sandy lands.National Natural Science Foundation of China [31330012, 31021001]; Strategic Priority Research Program of the Chinese Academy of Sciences [XDA05050300]SCI(E)[email protected]

Long-term vegetation changes in the four mega-sandy lands in Inner Mongolia, China

Desertification in China has become one of the most serious ecological and social problems. The four mega-sandy lands (Hulunbeir, Horqin, Otindag, and Mu Us) in Inner Mongolia are reported to be the most widespread and seriously desertified areas in China. To explore changes of vegetation activity and the possible driving forces in the four mega-sandy lands over the last three decades. We investigated spatiotemporal variations in the growing-season (May-September) normalized difference vegetation index (NDVI) and their relationships with climate factors and human activities during 1982-2011, using two NDVI datasets from Global Inventory Modelling and Mapping Studies (GIMMS) and Moderate Resolution Imaging Spectroradiometer (MODIS). We found a significant overall NDVI increase in Mu Us, but no such trends in the other three. A significant increase was in south and northeast Mu Us and southeast Horqin, and a decrease in south Hulunbeir, northwest Horqin, and central Otindag. NDVI trends were positively correlated with precipitation and uncorrelated with temperature and wind speed in all sandy lands except Mu Us. NDVI trends showed a large spatial heterogeneity in the four sandy lands. Precipitation was a major determiner for the interannual variations and spatial patterns of NDVI at regional scale, whereas human activities were the cause of NDVI variations at local scale. The consistent interannual variations between two NDVI datasets of GIMMS and MODIS for all four sandy lands suggested that GIMMS NDVI was appropriate for investigating long-term vegetation changes in sandy lands

Long-term vegetation changes in the four mega-sandy lands in Inner Mongolia, China

Desertification in China has become one of the most serious ecological and social problems. The four mega-sandy lands (Hulunbeir, Horqin, Otindag, and Mu Us) in Inner Mongolia are reported to be the most widespread and seriously desertified areas in China. To explore changes of vegetation activity and the possible driving forces in the four mega-sandy lands over the last three decades. We investigated spatiotemporal variations in the growing-season (May-September) normalized difference vegetation index (NDVI) and their relationships with climate factors and human activities during 1982-2011, using two NDVI datasets from Global Inventory Modelling and Mapping Studies (GIMMS) and Moderate Resolution Imaging Spectroradiometer (MODIS). We found a significant overall NDVI increase in Mu Us, but no such trends in the other three. A significant increase was in south and northeast Mu Us and southeast Horqin, and a decrease in south Hulunbeir, northwest Horqin, and central Otindag. NDVI trends were positively correlated with precipitation and uncorrelated with temperature and wind speed in all sandy lands except Mu Us. NDVI trends showed a large spatial heterogeneity in the four sandy lands. Precipitation was a major determiner for the interannual variations and spatial patterns of NDVI at regional scale, whereas human activities were the cause of NDVI variations at local scale. The consistent interannual variations between two NDVI datasets of GIMMS and MODIS for all four sandy lands suggested that GIMMS NDVI was appropriate for investigating long-term vegetation changes in sandy lands

Satellite-indicated long-term vegetation changes and their drivers on the Mongolian Plateau

The Mongolian Plateau, comprising the nation of Mongolia and the Inner Mongolia Autonomous Region of China, has been influenced by significant climatic changes and intensive human activities. Previous satellite-based analyses have suggested an increasing tendency in the vegetation cover over recent decades. However, several ground-based observations have indicated a decline in vegetation production. This study aimed to explore long-term changes in vegetation greenness and land surface phenology in relation to changes in temperature and precipitation on the Plateau between 1982 and 2011 using the normalized difference vegetation index (NDVI). Across the Plateau, a significantly positive trend in the growing season (May-September) NDVI was observed from 1982 to 1998, but since that time, the NDVI has not shown a persistent increase, thus causing an insignificant trend over the entire study period. For the steppe vegetation (a major vegetation type on the Plateau), the NDVI increased significantly in spring but decreased in summer. Precipitation was the dominant factor related to changes in steppe vegetation. Warming in spring contributed to earlier vegetation green-up only in meadow steppe vegetation, implying that water deficiency in typical and desert steppe vegetation may eliminate the effect of warming. Our results also suggest a combined effect of climatic and non-climatic factors and highlight the need to examine the role of regional human activities in the control of vegetation dynamics.National Natural Science Foundation of China [31330012, 31321061]; National Basic Research Program of China on Global Change [2010CB950600]; Strategic Priority Research Program of the Chinese Academy of Sciences [XDA05050300]SCI(E)[email protected]

α-Ketoglutarate improves cardiac insufficiency through NAD+-SIRT1 signaling-mediated mitophagy and ferroptosis in pressure overload-induced mice

Abstract Background In heart failure (HF), mitochondrial dysfunction and metabolic remodeling lead to a reduction in energy productivity and aggravate cardiomyocyte injury. Supplementation with α-ketoglutarate (AKG) alleviated myocardial hypertrophy and fibrosis in mice with HF and improved cardiac insufficiency. However, the myocardial protective mechanism of AKG remains unclear. We verified the hypothesis that AKG improves mitochondrial function by upregulating NAD+ levels and activating silent information regulator 2 homolog 1 (SIRT1) in cardiomyocytes. Methods In vivo, 2% AKG was added to the drinking water of mice undergoing transverse aortic constriction (TAC) surgery. Echocardiography and biopsy were performed to evaluate cardiac function and pathological changes. Myocardial metabolomics was analyzed by liquid chromatography‒mass spectrometry (LC‒MS/MS) at 8 weeks after surgery. In vitro, the expression of SIRT1 or PINK1 proteins was inhibited by selective inhibitors and siRNA in cardiomyocytes stimulated with angiotensin II (AngII) and AKG. NAD+ levels were detected using an NAD test kit. Mitophagy and ferroptosis levels were evaluated by Western blotting, qPCR, JC-1 staining and lipid peroxidation analysis. Results AKG supplementation after TAC surgery could alleviate myocardial hypertrophy and fibrosis and improve cardiac function in mice. Metabolites of the malate-aspartate shuttle (MAS) were increased, but the TCA cycle and fatty acid metabolism pathway could be inhibited in the myocardium of TAC mice after AKG supplementation. Decreased NAD+ levels and SIRT1 protein expression were observed in heart of mice and AngII-treated cardiomyocytes. After AKG treatment, these changes were reversed, and increased mitophagy, inhibited ferroptosis, and alleviated damage in cardiomyocytes were observed. When the expression of SIRT1 was inhibited by a selective inhibitor and siRNA, the protective effect of AKG was suppressed. Conclusion Supplementation with AKG can improve myocardial hypertrophy, fibrosis and chronic cardiac insufficiency caused by pressure overload. By increasing the level of NAD+, the SIRT-PINK1 and SIRT1-GPX4 signaling pathways are activated to promote mitophagy and inhibit ferroptosis in cardiomyocytes, which ultimately alleviates cardiomyocyte damage