135 research outputs found
High Glucose Induces Reactivation of Latent Kaposi’s Sarcoma-Associated Herpesvirus
High prevalence of Kaposi’s sarcoma (KS) is seen in diabetic patients. It is unknown if the physiological condition of diabetes contributes to KS development. We found elevated levels of viral lytic gene expression when Kaposi’s sarcoma-associated herpesvirus (KSHV) infected cells were cultured in high glucose medium. To demonstrate the association between high glucose and KSHV replication, we xeno29
grafted telomerase-immortalized human umbilical vein endothelial cells that are infected with KSHV (TIVE-KSHV) into hyperglycemic and normal nude mice. The injected cells expressed significantly higher levels of KSHV lytic genes in hyperglycemic mice than in normal mice. We further demonstrated that high glucose induced production of hydrogen peroxide (H2O2), which down regulated silent information regulator 1 (SIRT1), a class-III histone deacetylase (HDAC), resulting in epigenetic transactivation of KSHV lytic genes.These results suggest that high blood glucose in diabetic patients contributes to development of KS by promoting KSHV lytic replication and infection
Polycystin-1 inhibits eIF2α phosphorylation and cell apoptosis through a PKR-eIF2α pathway.
Autosomal dominant polycystic kidney disease (ADPKD) is caused by mutations in PKD1 or PKD2 which encodes polycystin-1 (PC1) and polycystin-2, respectively. PC1 was previously shown to slow cell proliferation and inhibit apoptosis but the underlying mechanisms remain elusive or controversial. Here we showed in cultured mammalian cells and Pkd1 knockout mouse kidney epithelial cells that PC1 and its truncation mutant comprising the last five transmembrane segments and the intracellular C-terminus (PC1-5TMC) down-regulate the phosphorylation of protein kinase R (PKR) and its substrate eukaryotic translation initiation factor 2 alpha (eIF2α). PKR is known to be activated by interferons and dsRNAs, inhibits protein synthesis and induces apoptosis. By co-immunoprecipitation experiments we found that PC1 truncation mutants associate with PKR, or with PKR and its activator PACT. Further experiments showed that PC1 and PC1-5TMC reduce phosphorylation of eIF2α through inhibiting PKR phosphorylation. Our TUNEL experiments using tunicamycin, an apoptosis inducer, and GADD34, an inhibitor of eIF2α phosphorylation, demonstrated that PC1-5TMC inhibits apoptosis of HEK293T cells in a PKR-eIF2α-dependent manner, with concurrent up- and down-regulation of Bcl-2 and Bax, respectively, revealed by Western blotting. Involvement of PC1-regulated eIF2α phosphorylation and a PKR-eIF2α pathway in cell apoptosis may be an important part of the mechanism underlying ADPKD pathogenesis
Measuring value-added-oriented BIM climate in construction projects: dimensions and indicators
A value-added-oriented (VAO) BIM climate is the organizational climate of BIM value-added. However, a lack of research on VAO BIM climate has thwarted progress on BIM knowledge systems. By using the socio-technical systems approach and the competing value approach, 12 dimensions and 39 indicators of a VAO BIM climate are proposed and tested using 306 questionnaires collected from workers engaged in BIM construction projects across China. Data was analyzed by confirmatory factor analysis. The results show that the proposed dimensions and indicators are highly reliable and valid. The VAO BIM climate is heavily influenced by autonomy, career development, and task orientation. The top 10 indicators were mainly related to participation, task orientation, and goal effectiveness. And the MWD-BIM, RCS-BIM, CDMT-BIM, and SMD-BIM were mistaken as key indicators of participation, autonomy, peer relations, and organizational adaptability, respectively. The proposed dimensions and indicators can be used to advance scholarly understanding and theory on BIM climate in construction projects through directing resource allocation, enhancing the understanding of human–BIM interactions, improving the BIM knowledge system and facilitating decision framework of BIM adoption. Practical implications for managers in construction projects are provided in the end
Mapping crop phenology using NDVI time-series derived from HJ-1 A/B data
With the availability of high frequent satellite data, crop phenology could be accurately mapped using time-series remote sensing data. Vegetation index time-series data derived from AVHRR, MODIS, and SPOT-VEGETATION images usually have coarse spatial resolution. Mapping crop phenology parameters using higher spatial resolution images (e.g., Landsat TM-like) is unprecedented. Recently launched HJ-1 A/B CCD sensors boarded on China Environment Satellite provided a feasible and ideal data source for the construction of high spatio-temporal resolution vegetation index time-series. This paper presented a comprehensive method to construct NDVI time-series dataset derived from HJ-1 A/B CCD and demonstrated its application in cropland areas. The procedures of time-series data construction included image preprocessing, signal filtering, and interpolation for daily NDVI images then the NDVI time-series could present a smooth and complete phenological cycle. To demonstrate its application, TIMESAT program was employed to extract phenology parameters of crop lands located in Guanzhong Plain, China. The small-scale test showed that the crop season start/end derived from HJ-1 A/B NDVI time-series was comparable with local agro-metrological observation. The methodology for reconstructing time-series remote sensing data had been proved feasible, though forgoing researches will improve this a lot in mapping crop phenology. Last but not least, further studies should be focused on field-data collection, smoothing method and phenology definitions using time-series remote sensing data
Resource utilization of high-salinity mine water through the membrane-integrated process based on bipolar membrane electrodialysis
In the context of “zero discharge” of mine water and the reverse distribution of coal and water resources in the western mining areas, the direct discharge of high-salinity mine water without proper treatment not only causes immeasurable damage to the local ecological environment, but also leads to serious water resource waste, ultimately constraining the green development of coal industry and the development of ecological civilization. The traditional zero discharge technology for high-salinity wastewater mainly relies on evaporation and crystallization to transform inorganic salts from a solution state to a crystalline state for recovery. From an economic perspective, this technology faces issues such as high investment, high operating costs, and low added value of inorganic salts. Based on this, this paper takes the mine water from a western mine as the raw water, aiming to achieve the resource utilization and desalination of mine water through the membrane integration technology, and focuses on exploring the influence of different operating conditions (operating voltage, feed solution concentration, temperature, acidity and alkalinity, current density, etc.) on the desalination performance of electrodialysis and the acid-base performance of bipolar membrane electrodialysis. Then, based on the experimental data and an economic evaluation model, the economic feasibility is explored, aiming to explore the membrane integration technology suitable for the treatment of high-salinity mine water in the western mining areas, and provide some new research ideas for the development of green resource utilization processes for high-salinity mine water. Through the exploration of the electrodialysis-bipolar membrane electrodialysis experimental process, it is found that the feed solution concentration of the bipolar membrane system should not exceed 80 g/L, the appropriate operating voltage is 18 V, the suitable feed solution temperature is 25 ℃, the feed solution pH should be kept neutral, and constant voltage operation is more suitable. In addition, it is confirmed that the membrane integration system centered on bipolar membrane electrodialysis can achieve the green resource utilization of high-salinity mine water. Taking the total salt content of the electrodialysis system feed solution as an example (20 g/L), the overall net profit is ¥18604299 per year, and it has a significant carbon dioxide emission reduction effect when coupled with a photovoltaic power supply system, with a carbon dioxide emission reduction of over 3162 tons per year, demonstrating good economic and social benefits
Gut microbiome is associated with metabolic syndrome accompanied by elevated gamma-glutamyl transpeptidase in men
It is predicted that by 2035, metabolic syndrome (MS) will be found in nearly more than half of our adult population, seriously affecting the health of our body. MS is usually accompanied by the occurrence of abnormal liver enzymes, such as elevated gamma-glutamyl transpeptidase (GGT). More and more studies have shown that the gut microbiota is involved in MS; however, the correlation between gut microbiota and MS with elevated GGT has not been studied comprehensively. Especially, there are few reports about its role in the physical examination of the population of men with MS and elevated GGT. By using the whole-genome shotgun sequencing technology, we conducted a genome-wide association study of the gut microbiome in 66 participants diagnosed as having MS accompanied by high levels of GGT (case group) and 66 participants with only MS and normal GGT level (control group). We found that the number of gut microbial species was reduced in participants in the case group compared to that of the control group. The overall microbial composition between the two groups is of significant difference. The gut microbiota in the case group is characterized by increased levels of “harmful bacteria” such as Megamonas hypermegale, Megamonas funiformis, Megamonas unclassified, Klebsiella pneumoniae, and Fusobacterium mortiferum and decreased levels of “beneficial bacteria” such as Faecalibacterium prausnitzii, Eubacterium eligens, Bifidobacterium longum, Bifidobacterium pseudocatenulatum, Bacteroides dorei, and Alistipes putredinis. Moreover, the pathways of POLYAMSYN-PWY, ARG+POLYAMINE-SYN, PWY-6305, and GOLPDLCAT-PWY were also increased in the case group, which may play a role in the elevation of GGT by producing amine, polyamine, putrescine, and endogenous alcohol. Taken together, there are apparent changes in the composition of the gut microbiome in men with MS and abnormal GGT levels, and it is high time to discover specific gut microbiome as a potential therapeutic target in that population. More in-depth studies of relevant mechanism could offer some new methods for the treatment of MS with elevated GGT
Activation of Cdc6 by MyoD is associated with the expansion of quiescent myogenic satellite cells
Cdc6, which alters chromatin ultrastructure to allow DNA replication in muscle stem cells transitioning out of quiescence, is identified as a target of the MyoD transcription factor
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