Epigenetic repression of microRNA-129-2 leads to overexpression of SOX4 in gastric cancer

High levels of SOX4 expression have been found in a variety of human cancers, such as lung, brain and breast cancers. However, the expression of SOX4 in gastric tissues remains unknown. The SOX4 expression was detected using immunohistochemical staining and semi-quantitative RT-PCR, and our results showed that SOX4 was up-regulated in gastric cancer compared to benign gastric tissues. To further elucidate the molecular mechanisms underlying up-regulation of SOX4 in gastric cancers, we analyzed the expression of microRNA-129-2 (miR-129-2) gene, the epigenetic repression of which leads to overexpression of SOX4 in endometrial cancer. We found that up-regulation of SOX4 was inversely associated with the epigenetic silencing of miR-129-2 in gastric cancer, and restoration of miR-129-2 down-regulated SOX4 expression. We also found that inactivation of SOX4 by siRNA and restoration of miR-129-2 induced apoptosis in gastric cancer cells.     

铅锌尾矿中耐重金属镉的丝状真菌的分离鉴定

【目的】旨在从重金属污染地分离出耐重金属镉真菌, 获得耐受重金属镉污染的高效菌株, 为重金属污染微生物修复提供菌种资源。【方法】利用稀释平板涂布法, 采用4种培养基对粤东北梅州市梅县铅锌尾矿废弃地9个样品进行分离, 并结合形态学和ITS rDNA基因序列分析, 鉴定分离到的耐镉真菌, 最后对分离到的耐镉真菌进行最小抑制浓度 (MIC) 检测。【结果】从粤东北梅州市梅县铅锌尾矿废弃地分离出72株丝状真菌, 经形态学和分子技术鉴定, 它们主要属于曲霉属(Aspergillus)、青霉属(Penicillium)、枝孢属(Cladosporium)、油瓶霉属(Lecythophora)、拟青霉属(Paecilomyces)、镰刀孢属(Fusarium)等。MIC检测发现有4株丝状真菌耐镉浓度较高, Paecilomyces lilacinus (Thom) Samson (6?20 p), Penicillium pinophilum Hedgcock (6?16 p), Penicillium rolfsii Thom (6?16 m) 和Fusarium oxysporum Schlecht. (8?11 p) 分别为200、40、25和15 mmol/L。【结论】从粤东北梅州市梅县铅锌尾矿废弃地分离到的72株丝状真菌, 不同程度耐受重金属镉, 在重金属污染的治理中有可能发挥作用。本研究为镉污染环境的微生物修复提供了重要菌株。     

Regulation of cystic fibrosis transmembrane regulator trafficking and protein expression by a Rho family small GTPase TC10

The cystic fibrosis transmembrane conductance regulator (CFTR)-interacting protein, CFTR-associated ligand (CAL) down-regulates total and cell surface CFTR by targeting CFTR for degradation in the lysosome. Here, we report that a Rho family small GTPase TC10 interacts with CAL. This interaction specifically up-regulates CFTR protein expression. Co-expression of the constitutively active form, TC10Q75L, increases total and cell surface CFTR in a dose-dependent fashion. Moreover, co-expression of the dominant-negative mutant TC10T31N causes a dose-dependent reduction in mature CFTR. The effect of TC10 is independent of the level of CFTR expression, because a similar effect was observed in a stable cell line that expresses one-tenth of CFTR. Co-expression of TC10Q75L did not have a similar effect on the expression of plasma membrane proteins such as Frizzled-3 and Pr-cadherin or cytosolic proteins such as tubulin and green fluorescent protein. TC10Q75L also did not have a similar effect on the vesicular stomatitis virus glycoprotein. Co-expression of constitutively active and dominant-negative forms of Cdc42 or RhoA did not affect CFTR expression in a manner similar to TC10, indicating that the effect of TC10 is unique within the Rho family. Metabolic pulse-chase experiments show that TC10 did not affect CFTR maturation, suggesting that it exerts its effects on the mature CFTR. Importantly, TC10Q75L reverses CAL-mediated CFTR degradation, suggesting that TC10Q75L inhibits CAL-mediated degradation of CFTR. TC10Q75L does not operate by reducing CAL protein expression or its ability to form dimers or interact with CFTR. Interestingly, the expression of TC10Q75L causes a dramatic redistribution of CAL from the juxtanuclear region to the plasma membrane where the two molecules overlap. These data suggest that TC10 regulates both total and plasma membrane CFTR expression by interacting with CAL. The GTP-bound form of TC10 directs the trafficking of CFTR from the juxtanuclear region to the secretory pathway toward the plasma membrane, away from CAL-mediated degradation of CFTR in the lysosome.     

Catch bonds: physical models, structural bases, biological function and rheological relevance

Force can shorten the lifetimes of macromolecular complexes (e.g., receptor-ligand bonds) by accelerating their dissociation. Perhaps paradoxical at first glance, bond lifetimes can also be prolonged by force. This counterintuitive behavior was named catch bonds, which is in contrast to the ordinary slip bonds that describe the intuitive behavior of lifetimes being shortened by force. Fifteen years after their theoretical proposal, catch bonds have finally been observed. In this article we review recently published data that have demonstrated catch bonds in the selectin system and suggested catch bonds in other systems, the theoretical models for their explanations, possible structural bases, their relation to flow-enhanced adhesion, and the potential biorheological relevance.     

Multi‐Length‐Scale Morphologies in PCPDTBT/PCBM Bulk‐Heterojunction Solar Cells

Additives are known to improve the performance of organic photovoltaic devices based on mixtures of a low bandgap polymer, poly[2,6‐(4,4‐bis(2‐ethylhexyl)‐4H‐cyclopenta[2,1‐b;3,4‐b′]‐dithiophene)‐alt‐4,7‐(2,1,3‐benzothiadiazole)] (PCPDTBT) and [6,6]‐phenyl C61‐butyric acid methyl ester (PCBM). The evolution of the morphology during the evaporation of the mixed solvent, which comprises additive and chlorobenzene (CB), is investigated by in‐situ grazing incidence X‐ray scattering, providing insight into the key role the additive plays in developing a multi‐length‐scale morphology. Provided the additive has a higher vapor pressure and a selective solubility for PCBM, as the host solvent (CB) evaporates, the mixture of the primary solvent and additive becomes less favorable for the PCPDTBT, while completely solubilizing the PCBM. During this process, the PCPDTBT first crystallizes into fibrils and then the PCBM, along with the remaining PCPDTBT, is deposited, forming a phase‐separated morphology comprising domains of pure, crystalline PCPDTBT fibrils and another domain that is a PCBM‐rich mixture with amorphous PCPDTBT. X‐ray/neutron scattering and diffraction methods, in combination with UV–vis absorption spectroscopy and transmission electron microscopy, are used to determine the crystallinity and phase separation of the resultant PCPDTBT/PCBM thin films processed with or without additives. Additional thermal annealing is carried out and found to change the packing of the PCPDTBT. The two factors, degree of crystallinity and degree of phase separation, control the multi‐length‐scale morphology of the thin films and significantly influence device performance.     

Membrane proteins organize a symmetrical virus

Alphaviruses are enveloped icosahedral viruses that mature by budding at the plasma membrane. According to a prevailing model maturation is driven by binding of membrane protein spikes to a preformed nucleocapsid (NC). The T = 4 geometry of the membrane is thought to be imposed by the NC through one-to-one interactions between spike protomers and capsid proteins (CPs). This model is challenged here by a Semliki Forest virus capsid gene mutant. Its CPs cannot assemble into NCs, or its intermediate structures, due to defective CP-CP interactions. Nevertheless, it can use its horizontal spike-spike interactions on membrane surface and vertical spike-CP interactions to make a particle with correct geometry and protein stoichiometry. Thus, our results highlight the direct role of membrane proteins in organizing the icosahedral conformation of alphaviruses.     

Profiling of Volatile Compounds and Associated Gene Expression and Enzyme Activity during Fruit Development in Two Cucumber Cultivars

Changes in volatile content, as well as associated gene expression and enzyme activity in developing cucumber fruits were investigated in two Cucumis sativus L. lines (No. 26 and No. 14) that differ significantly in fruit flavor. Total volatile, six-carbon (C6) aldehyde, linolenic and linoleic acid content were higher during the early stages, whereas the nine-carbon (C9) aldehyde content was higher during the latter stages in both lines. Expression of C. sativus hydroperoxide lyase (CsHPL) mirrored 13-hydroperoxide lyase (13-HPL) enzyme activity in variety No. 26, whereas CsHPL expression was correlated with 9-hydroperoxide lyase (9-HPL) enzyme activity in cultivar No. 14. 13-HPL activity decreased significantly, while LOX (lipoxygenase) and 9-HPL activity increased along with fruit ripening in both lines, which accounted for the higher C6 and C9 aldehyde content at 0-6 day post anthesis (dpa) and 9-12 dpa, respectively. Volatile compounds from fruits at five developmental stages were analyzed by principal component analysis (PCA), and heatmaps of volatile content, gene expression and enzyme activity were constructed.