Mechanistic studies using antihydrophobic agents

Abstract: The hydrophobic effect-that decreases the solubilities of organic compounds in water and leads to aggregation of such species in water solution+an be diminished by various additives that we have termed antihydrophobic agents. When relatively small amounts are used, this may be the principal effect of such additives on solubilities and reaction rates. If so, quantitative studies can reveal the amount of hydrophobic surface that becomes isolated from the water solvent in a transition state; this is a direct guide to transition state structure. This paper describes the evidence for this new approach to elucidating transition state structures for some reactions in water, and the relevance of this information to the situation in other solvents. Introduction. Molecules with apolar surfaces tend to aggregate in water solution because of the hydrophobic effect. This-the tendency of non-polar surfaces to avoid contact with water-is often ascribed to the strong self-association of water, but a quantitative study reveals that the major factor is the superior solvation of hydrocarbons by other hydrocarbons, rather than by water (1). Regardless of its cause, the hydrophobic effect can be invoked as a major determinant of the solubility of many organic compounds in water. Thus agents that increase the hydrophobic effect cause a decreased solubility of hydrocarbons in water, while agents that we have termed antihydrophobic cause an increase on hydrocarbon solubility. Such antihydrophobic agents are also denaturants of proteins and nucleic acids, whose three-dimensional structures are in large part the result of hydrophobic interactions between amino acid sidechains or nucleotide bases

Seneca Valley Virus 3Cpro Cleaves PABPC1 to Promote Viral Replication

Seneca Valley Virus (SVV) is an oncolytic virus of the Picornaviridae family, which has emerged in recent years. The impact of SVV on host cell translation remains unknown. Here, we showed, for the first time, that SVV infection cleaved poly(A) binding protein cytoplasmic 1 (PABPC1). In SVV-infected cells, 50 kDa of the N terminal cleaved band and 25 kDa of the C terminal cleaved band of PABPC1 were detected. Further study showed that the viral protease, 3Cpro induced the cleavage of PABPC1 by its protease activity. The SVV strains with inactive point mutants of 3Cpro (H48A, C160A or H48A/C160A) can not be rescued by reverse genetics, suggesting that sites 48 and 160 of 3Cpro were essential for SVV replication. SVV 3Cpro induced the cleavage of PABPC1 at residue 437. A detailed data analysis showed that SVV infection and the overexpression of 3Cpro decreased the protein synthesis rates. The protease activity of 3Cpro was essential for inhibiting the protein synthesis. Our results also indicated that PABPC1 inhibited SVV replication. These data reveal a novel antagonistic mechanism and pathogenesis mediated by SVV and highlight the importance of 3Cpro on SVV replication

Study of Urban Heat Island Based on Remote Sensing in Beijing-Capital Zone

The paper focused on Spatial and temporal distribution of thermal environment by Land Surface Temperature(LST) and brightness temperature retrieved from ASTER and Landsat TM/ETM in Beijing-capital zone, and analyzing scale effect of multi-resolution LST data (LST retrieved by ASTER and MODIS LST product)with the variety of landuse and NDVI. The result showed that the UHI phenomena had increasing tendency. LST waved with difference of the landuse, the highest was in bare-land, and the lowest was in water. Green island was composed Mainly by forest and water, while heavy heat island and serious beat island was mainly composed by built-up and bare-land. The linear equation with a strong negative relationship between means of NDVI and means of LST( ASTER retrieval LST and MODIS LST product) associated with the five cover types has been established. Cross-validation among the LST images retrieved from ASTER and MODIS LST product are reliable. The different spatial resolution of the thermal sensors can be used in urban studies demanding different levels of details. The MODIS thermal sensor can be used for the overview of urban thermal environment. The ASTER, with its TIR 90-m resolution, can be used for more accurate monitoring thermal patterns

Droplet-based single-cell joint profiling of histone modifications and transcriptomes.

We previously reported Paired-Tag, a combinatorial indexing-based method that can simultaneously map histone modifications and gene expression at single-cell resolution at scale. However, the lengthy procedure of Paired-Tag has hindered its general adoption in the community. To address this bottleneck, we developed a droplet-based Paired-Tag protocol that is faster and more accessible than the previous method. Using cultured mammalian cells and primary brain tissues, we demonstrate its superior performance at identifying candidate cis-regulatory elements and associating their dynamic chromatin state to target gene expression in each constituent cell type in a complex tissue

Picornavirus infection enhances aspartate by the SLC38A8 transporter to promote viral replication.

Foot-and-mouth disease, a class of animal diseases, is caused by foot-and-mouth disease virus (FMDV). The metabolic changes during FMDV infection remain unclear. Here, PK-15 cells, serum, and tonsils infected with FMDV were analyzed by metabolomics. A total of 284 metabolites in cells were significantly changed after FMDV infection, and most of them belong to amino acids and nucleotides. Further studies showed that FMDV infection significantly enhanced aspartate in vitro and in vivo. The amino acid transporter solute carrier family 38 member 8 (SLC38A8) was responsible for FMDV-upregulated aspartate. Enterovirus 71 (EV71) and Seneca Valley virus (SVV) infection also enhanced aspartate by SLC38A8. Aspartate aminotransferase activity was also elevated in FMDV-, EV71-, and SVV-infected cells, which may lead to reversible transition between the TCA cycle and amino acids synthesis. Aspartate and SLC38A8 were essential for FMDV, EV71, and SVV replication in cells. In addition, aspartate and SLC38A8 also promoted FMDV and EV71 replication in mice. Detailed analysis indicated that FMDV infection promoted the transfer of mTOR to lysosome to enhance interaction between mTOR and Rheb, and activated PI3K/AKT/TSC2/Rheb/mTOR/p70S6K1 pathway to promote viral replication. The mTORC1 signaling pathway was responsible for FMDV-induced SLC38A8 protein expression. For the first time, our data identified metabolic changes during FMDV infection. These data identified a novel mechanism used by FMDV to upregulate aspartate to promote viral replication and will provide new perspectives for developing new preventive strategies

Anti-proliferative and pro-apoptotic effects of cinobufagin on human breast cancer MCF-7 cells and its molecular mechanism

<p>Cinobufagin (CBF) is an active ingredient isolated from Venenum Bufonis extracted and dried from the secretory glands of <i>Bufo gargarizans Cantor</i>. The purpose of the study was to investigate the effects and underlying mechanisms of CBF on human breast cancer MCF-7 cells <i>in vitro</i>. Our results showed that CBF exhibited obvious cytotoxicity on MCF-7 cells in a dose- and time-dependent manner, as indicated by CCK-8 assays. Also, Hoechst 33258 staining and flow cytometry assays showed that CBF strongly induced MCF-7 cell apoptosis and G1 phase arrest. In addition, further molecular mechanistic investigation demonstrated that cinobufagin significantly increased Bax expression, decreased Bcl-2 expression level and up-regulated the ratio of the pro-apoptosis/anti-apoptosis protein Bax/Bcl-2, which were demonstrated by RT-qPCR and western blot assays. Taken together, our data confirm that CBF inhibits growth and triggers apoptosis of MCF-7 cells by affecting the expression of Bax and Bcl-2 <i>in vitro</i>.</p