Thioredoxin-interacting protein deficiency alleviates phenotypic alterations of podocytes via inhibition of mTOR activation in diabetic nephropathy

Thioredoxin-interacting protein (TXNIP) is induced by high glucose (HG), whereupon it acts to inhibit thioredoxin, thereby promoting oxidative stress. We have found that TXNIP knockdown in human renal tubular cells helped prevent the epithelial-to-mesenchymal transition (EMT). Here, we studied the potential effect of TXNIP on podocyte phenotypic alterations in diabetic nephropathy (DN) in vivo and in vitro. In conditionally immortalized mouse podocytes under HG conditions, knocking down TXNIP disrupted EMT, reactive oxygen species (ROS) production, and mammalian target of rapamycin (mTOR) pathway activation. Further, Raptor short hairpin RNA (shRNA), Rictor shRNA, and mTOR specific inhibitor KU-0063794 were used to assess if the mTOR signal pathway is involved in HG-induced EMT in podocytes. We found that Raptor shRNA, Rictor shRNA, and KU-0063794 could all restrain HG-induced EMT and ROS production in podocytes. In addition, antioxidant Tempol or N-acetylcysteine presented a prohibitive effect on HG-induced EMT in podocytes. Streptozotocin was utilized to render equally diabetic in wild-type (WT) control and TXNIP ^−/− (TKO) mice. Diabetes did not increase levels of 24-hr urinary protein, serum creatinine, blood urea nitrogen, and triglyceride in TXNIP ^−/− mice. Podocyte phenotypic alterations and podocyte loss were detected in WT but not in TKO diabetic mice. Oxidative stress was also suppressed in diabetic TKO mice relative to WT controls. Also, TXNIP deficiency suppresses the activation of mTOR in glomeruli of streptozotocin-induced diabetic mice. Moreover, TXNIP expression, mTOR activation, Nox1, and Nox4 could be detected in renal biopsy tissues of patients with DN. This suggests that decreased TXNIP could ameliorate phenotypic alterations of podocytes via inhibition of mTOR in DN, highlighting TXNIP as a promising therapeutic target.     

Long term experimental drought alters community plant trait variation,not trait means,across three semiarid grasslands

Plant and Soil - Mechanisms by which soil pH affects rice growth await further elucidation. We have used a Systems Biology approach to elucidate the nature of the damage caused by extreme pH to...     

Comprehensive metabolomic,proteomic and physiological analyses of grain yield reduction in rice under abrupt drought–flood alternation stress

Abrupt drought–flood alternation (T1) is a meteorological disaster that frequently occurs during summer in southern China and the Yangtze river basin, often causing a significant loss of rice production. In this study, the response mechanism of yield decline under abrupt drought–flood alternation stress at the panicle differentiation stage was analyzed by looking at the metabolome, proteome as well as yield and physiological and biochemical indexes. The results showed that drought and flood stress caused a decrease in the yield of rice at the panicle differentiation stage, and abrupt drought–flood alternation stress created a synergistic effect for the reduction of yield. The main reason for the decrease of yield per plant under abrupt drought–flood alternation was the decrease of seed setting rate. Compared with CK0 (no drought and no flood), the net photosynthetic rate and soluble sugar content of T1 decreased significantly and its hydrogen peroxidase, superoxide dismutase, peroxidase activity increased significantly. The identified differential metabolites and differentially expressed proteins indicated that photosynthesis metabolism, energy metabolism pathway and reactive oxygen species response have changed strongly under abrupt drought–flood alteration stress, which are factors that leads to the rice grain yield reduction.     

Impact of phosphorus application on drought resistant responses of Eucalyptus grandis seedlings

Eucalyptus grandis is the most widely planted tree species worldwide and can face severe drought during the initial months after planting because the root system is developing. A complete randomized design was used to study the effects of two water regimes (well‐watered and water‐stressed) and phosphorus (P) applications (with and without P) on the morphological and physio‐biochemical responses of E. grandis. Drought had negative effects on the growth and metabolism of E. grandis, as indicated by changes in morphological traits, decreased net photosynthetic rates (P_n), pigment concentrations, leaf relative water contents (LRWCs), nitrogenous compounds, over‐production of reactive oxygen species (ROS) and higher lipid peroxidation. However, E. grandis showed effective drought tolerance strategies, such as reduced leaf area and transpiration rate (E), higher accumulation of soluble sugars and proline and a strong antioxidative enzyme system. P fertilization had positive effects on well‐watered seedlings due to improved growth and photosynthesis, which indicated the high P requirements during the initial E. grandis growth stage. In drought‐stressed seedlings, P application had no effects on the morphological traits, but it significantly improved the LRWC, P_n, quantum efficiency of photosystem II (F_v/F_m), chlorophyll pigments, nitrogenous compounds and reduced lipid peroxidation. P fertilization improved E. grandis seedling growth under well‐watered conditions but also ameliorated some leaf physiological traits under drought conditions. The effects of P fertilization are mainly due to the enhancement of plant N nutrition. Therefore, P can be used as a fertilizer to improve growth and production in the face of future climate change.     

Megabase Length Hypermutation Accompanies Human Structural Variation at 17p11.2

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Biofunctionalized self-assembly of peptide amphiphile induces the differentiation of bone marrow mesenchymal stem cells into neural cells

Molecular and Cellular Biochemistry - Bone marrow mesenchymal stem cells (BMSCs) are multipotential differentiation cells which can differentiate into different cell types such as osteoblasts,...     

Genetic structure in the marbled rockfish (Sebastiscus marmoratus) across most of the distribution in the northwestern Pacific

The marbled rockfish (Sebastiscus marmoratus) is an important species that is widely distributed across the marginal seas of the northwestern Pacific. Several kinds of DNA markers, such as amplified fragment length polymorphisms (AFLP), mitochondrial DNA (mtDNA) and single nucleotide polymorphisms (SNPs), have been used to assess the population genetic characteristics of this species in previous studies. However, there have been no genetic profiling studies to cover the entire distribution. Here, six highly polymorphic microsatellite markers were applied to 18 populations across a spatially large area (from the Sea of Japan in the north to the South China Sea in the south). The results showed that the whole population exhibits high, stable genetic diversity, low relatedness and large effective population size. There was very weak genetic differentiation overall and no isolation by distance occurred among the populations, which may be attributed to significant contemporary gene flow, each generation. The above results may lead us to infer that the recent S. marmoratus population structure could be considered as one large integrated population. The present study will be beneficial to population conservation and fisheries management of S. marmoratus and will lead to better insights into the genetic characteristics of other species that belong to the Sebastidae family.     

Fine‐scale population structure of Collichtys lucidus populations inferred from microsatellite markers

The spinyhead croaker Collichthys lucidus (Richardson) is a small sciaenid species distributed along the inshore waters of northwestern Pacific Ocean, and now has been listed as Key Protected Commercial Sources of Aquatic Animals and Plants in China. To delineate stock boundaries and inform conservation policy for its management, samples were collected from eight locations across the Chinese coastal waters and analyzed at nine microsatellite loci. C. lucidus populations showed low genetic diversity (expected heterozygosity = 0.445–0.542; observed heterozygosity = 0.392–0.539; Polymorphism Information Content = 0.268–0.684). Strong genetic fdifferentiation (F_st = 0.065–0.510, all significant after Bonferroni correction) among all populations and high levels of self‐recruitment (89.2%–91.5%) were observed, which suggested limited genetic exchange for this species. Clustering results of discriminant analysis of principal components and STRUCTURE found strong support for obvious genetic clusters (populations FZ, XM and SZ vs. populations SH, YRE, ZS, WZ and ND). The results of the present study not only supported the phylogeographic pattern of north‐south differentiation, but also suggested that C. lucidus populations may be predominantly sustained by self‐replenishment rather than by recruitment from distant populations.