Calcium sensing receptor regulates cardiomyocyte function through nuclear calcium

Nuclear Ca2+ plays a pivotal role in the regulation of gene expression. IP3 (inositol-1,4,5-trisphosphate) is an important regulator of nuclear Ca2+. We hypothesized that the CaR (calcium sensing receptor) stimulates nuclear Ca2+ release through IICR (IP3-induced calcium release) from perinuclear stores. Spontaneous Ca2+ oscillations and the spark frequency of nuclear Ca2+ were measured simultaneously in NRVMs (neonatal rat ventricular myocytes) using confocal imaging. CaR-induced nuclear Ca2+ release through IICR was abolished by inhibition of CaR and IP3Rs (IP3 receptors). However, no effect on the inhibition of RyRs (ryanodine receptors) was detected. The results suggest that CaR specifically modulates nuclear Ca2+ signalling through the IP3R pathway. Interestingly, nuclear Ca2+ was released from perinuclear stores by CaR activator-induced cardiomyocyte hypertrophy through the Ca2+-dependent phosphatase CaN (calcineurin)/NFAT (nuclear factor of activated T-cells) pathway. We have also demonstrated that the activation of the CaR increased the NRVM protein content, enlarged cell size and stimulated CaN expression and NFAT nuclear translocation in NRVMs. Thus, CaR enhances the nuclear Ca2+ transient in NRVMs by increasing fractional Ca2+ release from perinuclear stores, which is involved in cardiac hypertrophy through the CaN/NFAT pathway.     

Aphids as models for ecological and evolutionary studies

Aphids （Hemiptera： Aphididae） are a group of phloemfeeding insects numbering more than 5 000 extant species（Favret, 2014a）. Most species have complex life cycles that include both asexual （viviparous parthenogenesis）and sexual reproduction. They display a high degree of intraspecific polyphenism with multiple phenotypes froman identical genotype, and they have specialized associations with their host plants （Blackman ＆ Eastop, 2000）.Some aphid species are gall-makers and even have evolved sociality with division of labor （Aoki, 1977; Stern ＆Foster, 1996）. Many aphid species are agricultural and forestry pests. They incur damage to plants and carryvector plant viruses （Blackman ＆ Eastop, 2000）. Due to their fascinating biological character and economic importance, aphids have long been popular animals for research in basic and applied biology, and are becominguseful research models for studying important questions in ecology and evolution, especially in the genomic era（Brisson ＆ Stem, 2006; Huang ＆ Qiao, 2006; Srinivasan ＆ Brisson, 2012）.     

Decreased miR-30b-5p expression by DNMT1 methylation regulation involved in gastric cancer metastasis

miRNAs have emerged as crucial regulators in the regulation of development as well as human diseases, especially tumorigenesis. The aims of this study are to evaluate miR-30b-5p expression pattern and mechanism in gastric carcinogenesis due to which remains to be determined. Expression of miR-30b-5p was analyzed in 51 gastric cancer cases and 4 cell lines by qRT-PCR. The effect of DNA methylation on miR-30b-5p expression was assessed by MSP and BGS. In order to know whether DNMT1 increased miR-30b-5p promoter methylation, DNMT1 was depleted in cell lines AGS and BGC-823. The role of miR-30b-5p on cell migration was evaluated by wound healing assays. Decreased expression of miR-30b-5p was found in gastric cancer samples. In tumor, the expression level of miR-30b-5p was profound correlated with lymph node metastasis (P = 0.019). The level of miR-30b-5p may be restored by DNA demethylation and DNMT1 induced miR-30b-5p promoter methylation. In vitro functional assays implied that enforced miR-30b-5p expression affected cell migration, consistent with tissues analysis. Our findings uncovered that miR-30b-5p is significantly diminished in gastric cancer tissues, providing the first insight into the epigenetic mechanism of miR-30b-5p down-regulation, induced by DNMT1, and the role of miR-30b-5p in gastric cancer carcinogenesis. Overexpression of miR-30b-5p inhibited cell migration. Thus, miR-30b-5p may represent a potential therapeutic target for gastric cancer therapy.     

Negligible Immunogenicity of Induced Pluripotent Stem Cells Derived from Human Skin Fibroblasts

Human induced pluripotent stem cells (hiPSCs) have potential applications in cell replacement therapy and regenerative medicine. However, limited information is available regarding the immunologic features of iPSCs. In this study, expression of MHC and T cell co-stimulatory molecules in hiPSCs, and the effects on activation, proliferation and cytokine production in allogeneic human peripheral blood mononuclear cells were examined. We found that no-integrate hiPSCs had no MHC-II and T cell co-stimulatory molecules expressions but had moderate level of MHC-I and HLA-G expressions. In contrast to human skin fibroblasts (HSFs) which significantly induced allogeneic T cell activation and proliferation, hiPSCs failed to induce allogeneic CD45⁺ lymphocyte and CD8⁺ T cell activation and proliferation but could induce a low level of allogeneic CD4⁺ T cell proliferation. Unlike HSFs which induced allogeneic lymphocytes to produce high levels of IFN-γ, TNF-α and IL-17, hiPSCs only induced allogeneic lymphocytes to produce IL-2 and IL-10, and promote IL-10-secreting regulatory T cell (Treg) generation. Our study suggests that the integration-free hiPSCs had low or negligible immunogenicity, which may result from their induction of IL-10-secreting Treg.     

Overexpression of miR‐483‐5p/3p cooperate to inhibit mouse liver fibrosis by suppressing the TGF‐β stimulated HSCs in transgenic mice

The transition from liver fibrosis to hepatocellular carcinoma (HCC) has been suggested to be a continuous and developmental pathological process. MicroRNAs (miRNAs) are recently discovered molecules that regulate the expression of genes involved in liver disease. Many reports demonstrate that miR‐483‐5p and miR‐483‐3p, which originate from miR‐483, are up‐regulated in HCC, and their oncogenic targets have been identified. However, recent studies have suggested that miR‐483‐5p/3p is partially down‐regulated in HCC samples and is down‐regulated in rat liver fibrosis. Therefore, the aberrant expression and function of miR‐483 in liver fibrosis remains elusive. In this study, we demonstrate that overexpression of miR‐483 in vivo inhibits mouse liver fibrosis induced by CCl₄. We demonstrate that miR‐483‐5p/3p acts together to target two pro‐fibrosis factors, platelet‐derived growth factor‐β and tissue inhibitor of metalloproteinase 2, which suppress the activation of hepatic stellate cells (HSC) LX‐2. Our work identifies the pathway that regulates liver fibrosis by inhibiting the activation of HSCs.     

豆科作物-小麦轮作方式下旱地小麦花后干物质及养分累积、转移与产量的关系

研究旱作条件下豆科绿肥轮作影响旱地小麦产量变化的作物营养生态机制,对优化旱地作物种植施肥制度,促进水分资源高效利用、土壤培肥、作物增产有重要意义。通过两年定位试验,分析了与不同豆科作物轮作引起的后茬小麦产量变化及其与干物质、氮磷钾养分累积、转移的关系。结果表明:与秋豆轮作的第一季,小麦籽粒产量无显著变化,但第二季小麦产量提高23.4%;与绿豆轮作,两季产量分别降低19.2%和4.4%;与大豆轮作,产量无显著变化。与秋豆轮作增加了小麦花后干物质及氮、磷养分累积,和对照相比分别增加了35.1%,128.8%和14.0%,而与大豆和绿豆轮作花后干物质累积分别降低26.7%和17.0%,花后氮累积分别降低44.2%和24.4%,花后磷累积与对照相比无显著差异。与此对应,秋豆-小麦轮作,其后茬小麦花后干物质及养分累积对产量形成的贡献显著增加,茎叶花前累积氮、磷向籽粒的转移对产量的贡献明显小于大豆-小麦和绿豆-小麦轮作处理。与氮、磷不同,小麦茎叶花前累积钾素向籽粒转移的同时,花后植株钾素没有累积,反而明显损失,其中与秋豆轮作的小麦花后植株钾素损失量较小,为3.8 kg/hm2,籽粒钾素占转移钾的81.0%;休闲或与大豆、绿豆轮作的小麦花后植株钾素损失较多,分别为10.9,12.6和5.5kg/hm2,籽粒钾素占转移钾的52.9%,52.9%和66.8%。与秋豆-小麦轮作处理小麦增产的主要原因是花后植株能累积更多干物质和氮、磷养分,减少了花前累积于茎叶的钾素在花后的损失。     

A New GA-Insensitive Semidwarf Mutant of Rice (Oryza sativa L.) with a Missense Mutation in the SDG Gene

A semidwarf line of Indica rice, Xinguiai, was derived from the progeny of a cross between the double dwarf mutant Xinguiaishuangai and the wild-type variety Nanjing 6. The semidwarf phenotype was controlled by the semidwarf gene, sdg. The second sheath and shoot elongation responses of the dwarf mutant to exogenous gibberellin (GA₃) showed that sdg was insensitive to gibberellin (GA), and its endogenous GAs content was higher than that in wild-type cultivars. The SDG gene was cloned by a map-based cloning method and sequencing analysis revealed that the coding region of sdg had a single nucleotide substitution resulting in a single amino acid change from alanine to threonine. A cleaved amplified polymorphic sequence marker was designed according to sequences from mutant and wild-type materials. This sequence marker could be used to distinguish wild types and mutants, and thus, could be used for molecular marker-assisted selection. The dwarf phenotype of the sdg mutant was restored to a normal phenotype by introducing the wild-type SDG gene. Rice transformation experiments and GUS staining demonstrated that the SDG gene was predominantly expressed in vegetative organs.     

Injectable and moldable hydrogels for use in sensitive and wide range strain sensing applications

Recently, the use of hybrid double network (DN) hydrogels has become prominent due to their enhanced mechanical properties, which has opened the door for new applications of these soft materials. Only a few of these gels have demonstrated both injectable and moldable capabilities. In this work, we report the mechanical properties, gauge factor (GF) values and demonstrate both the injectability and moldability of a gelatin/polyacrylamide DN hydrogel. We optimized several parameters, such as, gelatin to polyacrylamide ratio, reactant concentrations and metal ion concentration, to produce a gelatin/polyacrylamide hydrogel with superior mechanical properties. The highest water content gel was capable of withstanding strains of 5000% before failure. These gels were facilely injected into molds where they effectively changed shape and maintained similar properties prior to remolding. When 20 mM calcium was doped into a similar gel, a tensile strength of 1.71 MPa was achieved. Aside from improving the mechanical properties of the gels, both Ca²⁺ and Mg²⁺ also improved their conductivity, so they were tested for use as strain sensors. The sensitivity of the hydrogel strain sensors were measured using the GF. For the 20 mM Ca²⁺ hydrogel, these GF values ranged from 1.63 to 6.85 for strains of 100% to 2100% respectively. Additionally, the sensors showed good stability over continuous cyclic stretching, demonstrating their long term reliability for strain sensing.