Simple sequence repeat genetic linkage maps of A-genome diploid cotton (Gossypium arboreum)

This study introduces the construction of the first intraspacific genetic linkage map of the A-genome diploid cotton with newly developed simple sequence repeat (SSR) markers using 189 F2 plants derived from the cross of two Asiatic parents were detected using 6 092 pairs of SSR primers. Two-hundred and sixty-eight pairs of SSR pdmers with better polymorphisms were picked out to analyze the F2 population. In total, 320 polymorphic bands were generated and used to construct a linkage map with JoinMap3.0. Two-hundred and sixty-seven loci, Including three phenotypic traits were mapped at a logarithms of odds ratio (LOD) ≥ 3.0 on 13 linkage groups. The total length of the map was 2 508.71 cM, and the average distance between adjacent markers was 9.40 cM. Chromosome assignments were according to the association of linkages with our backbone tetraploid specific map using the 89 similar SSR loci. Comparisons among the 13 suites of orthologous linkage groups revealed that the A-genome chromosomes are largely collinear with the At and Dt sub-genome chromosomes. Chromosomes associated with inversions suggested that allopolyploidization was accompanied by homologous chromosomal rearrangement. The inter-chromosomal duplicated loci supply molecular evidence that the A-genome diploid Asiatic cotton is paleopolyploid.     

Premortem autophagy determines the immunogenicity of chemotherapy-induced cancer cell death

One particular strategy to render anticancer therapies efficient consists of converting the patient's own tumor cells into therapeutic vaccines, via the induction of immunogenic cell death (ICD). One of the hallmarks of ICD dwells in the active release of ATP by cells committed to undergo, but not yet having succumbed to, apoptosis. We observed that the knockdown of essential autophagy-related genes (ATG3, ATG5, ATG7 and BECN1) abolishes the pre-apoptotic secretion of ATP by several human and murine cancer cell lines undergoing ICD. Accordingly, autophagy-competent, but not autophagy-deficient, tumor cells treated with ICD inducers in vitro could induce a tumor-specific immune response in vivo. Cancer cell lines stably depleted of ATG5 or ATG7 normally generate tumors in vivo, and such autophagy-deficient neoplasms, upon systemic treatment with ICD inducers, exhibit the same levels of apoptosis (as monitored by nuclear shrinkage and caspase-3 activation) and necrosis (as determined by following the kinetics of HMGB1 release) as their autophagy-proficient counterparts. However, autophagy-incompetent cancers fail to release ATP, to recruit immune effectors into the tumor bed and to respond to chemotherapy in conditions in which autophagy-competent tumors do so. The intratumoral administration of ecto-ATPase inhibitors increases extracellular ATP concentrations, re-establishes the therapy-induced recruitment of dendritic cells and T cells into the tumor bed, and restores the chemotherapeutic response of autophagy-deficient cancers. Altogether, these results suggest that autophagy-incompetent tumor cells escape from chemotherapy-induced (and perhaps natural?) immunosurveillance because they are unable to release ATP.     

A novel thermostable phytase from the fungus Aspergillus aculeatus RCEF 4894: gene cloning and expression in Pichia pastoris

A novel gene of thermostable phytase, phyA, was isolated by polymerase chain reaction (PCR) techniques from Aspergillus aculeatus RCEF 4894. The full-length phyA gene comprises 1,404 bp and encodes 467 amino-acid residues, including a 19-residue putative N-terminal signal peptide. The phytase of A. aculeatus was a novel addition to the histidine-acid phosphatase family, as evidenced by both the conserved motifs RHGXRXP and HD in the amino-acid sequence, and 3D structure models. The recombinant phytase was overexpressed in Pichia pastoris, and its specific activity reached 3,000 U mL⁻¹ at the optimum pH of 5.5. This recombinant, thermostable phytase was able to withstand temperatures of up to 90 °C for 10 min, with a loss of only 13.9% of initial enzymatic activity, and showed high activity with phytic-acid sodium salt at a pH range of 2.5–6.5. The broad pH optima and high thermostability of the phytase makes it a promising candidate for feed-pelleting applications.     

Disease-driven detection of differential inherited SNP modules from SNP network

Detection of the synergetic effects between variants, such as single-nucleotide polymorphisms (SNPs), is crucial for understanding the genetic characters of complex diseases. Here, we proposed a two-step approach to detect differentially inherited SNP modules (synergetic SNP units) from a SNP network. First, SNP-SNP interactions are identified based on prior biological knowledge, such as their adjacency on the chromosome or degree of relatedness between the functional relationships of their genes. These interactions form SNP networks. Second, disease-risk SNP modules (or sub-networks) are prioritised by their differentially inherited properties in IBD (Identity by Descent) profiles of affected and unaffected sibpairs. The search process is driven by the disease information and follows the structure of a SNP network. Simulation studies have indicated that this approach achieves high accuracy and a low false-positive rate in the identification of known disease-susceptible SNPs. Applying this method to an alcoholism dataset, we found that flexible patterns of susceptible SNP combinations do play a role in complex diseases, and some known genes were detected through these risk SNP modules. One example is GRM7, a known alcoholism gene successfully detected by a SNP module comprised of two SNPs, but neither of the two SNPs was significantly associated with the disease in single-locus analysis. These identified genes are also enriched in some pathways associated with alcoholism, including the calcium signalling pathway, axon guidance and neuroactive ligand-receptor interaction. The integration of network biology and genetic analysis provides putative functional bridges between genetic variants and candidate genes or pathways, thereby providing new insight into the aetiology of complex diseases.     

PTP1B inhibitor improves both insulin resistance and lipid abnormalities in vivo and in vitro

PTP1B is a negative regulator of insulin signaling pathway. This study investigated the effects of compound CCF06240, a PTP1B inhibitor, on insulin sensitivity and lipid metabolic abnormalities in vivo and in vitro, respectively. The insulin resistant IRM mouse model was induced by HFD. The responses to insulin were determined by OGTT, ITT, and hyperinsulinemic-euglycemic clamp test. The body weight and the levels of serum TC and TG were measured to estimate the lipid metabolism in vivo. Recombinant human GST-PTP1B protein was used to measure the inhibition of CCF06240 on PTP1B activity. The hepatocyte lipid accumulation was induced by high concentrations of FFA and insulin in HepG(2) cells, and evaluated by the Oil Red O method. In IRM mice, the insulin resistance was improved; the body weight and the levels of TC and TG were also reduced by oral CCF06240 administration. In lipid accumulated model cells, CCF06240 was found to reverse the increased PTP1B activity, enhance the insulin-induced tyrosine phosphorylation in insulin signaling pathway, attenuate the FFA-insulin-induced cellular lipid accumulation, and down-regulate the expressions of genes related fatty acid synthesis. These results demonstrated that the PTP1B inhibitor, compound CCF06240, could increase insulin sensitivity through the regulation of insulin signaling pathway, and decrease FFA-insulin-induced hepatocytes lipid accumulation by reducing fatty acid syntheses.     

Characteristics of Arsenic Accumulation by Pteris and non-Pteris Ferns

This research was conducted to understand the mechanisms of arsenic hyperaccumulation in Pteris vittata by comparing the characteristics of arsenic accumulation in Pteris and non-Pteris ferns. Seven Pteris (P.vittata, P. Cretica Rowerii, P. Cretica Parkerii, P. Cretica Albo-lineata, P. Quadriavrita, P. Ensiformis and P. Dentata) and six non-Pteris (Arachnoides simplicor, Didymochlaena truncatula, Dryopteris atrata, Dryopteris erythrosora, Cyrtomium falcatum, and Adiantum hispidulum) ferns were exposed to 0, 1 and 10 mgL⁻¹ arsenic as sodium arsenate for 14-d in hydroponic systems. As a group, the Pteris ferns were more efficient in arsenic accumulation than the non-Pteris ferns, with P. vittata being the most efficient followed by P. cretica. When exposed to 10 mg L⁻¹ As, arsenic concentrations in the fronds and roots of P. vittata were 1748 and 503 mg kg⁻¹. Though not all Pteris ferns were efficient in accumulating arsenic, none of the non-Pteris ferns was an efficient As accumulator (the highest concentration being 452 mg kg⁻¹). The fact that frond arsenic concentrations in the control were highly correlated with those exposed to As (r ² = 0.76–0.87) may suggest that they may be used as a preliminary tool to screen potential arsenic hyperaccumulators. Our research confirms that the ability of P. vittata to translocate arsenic from the roots to the fronds (73–77% As in the fronds), reduce arsenate to arsenite in the fronds (>50% AsIII in the fronds), and maintain high concentrations of phosphate in the roots (48–53% in the roots) all contributed to its arsenic tolerance and hyperaccumulation.     

泛素样蛋白ISG15抗病毒机制研究进展

ISG15(Interferon stimulated gene 15,ISG15)蛋白是由干扰素诱导产生的一种泛素样蛋白分子,分子量大小约为15kD。ISG15同泛素分子相类似可以被共价结合于其他蛋白分子上,这种现象称为ISG化(ISGylation)现象。ISG化系统包括ISG15、UBE1L、UBCH8和HERC5四类蛋白分子,协同完成ISG化过程。ISG15及ISG化系统在抗病毒反应中具有重要作用。近几年对于ISG15的抗病毒作用和机制的研究已经有了很大的突破,ISG15的抗病毒作用也越来越受到人们重视,了解清楚ISG15抗病毒机制对于研制新的抗病毒药物及提出新的抗病毒策略具有重要意义。本文对ISG15在不同种病毒中的抗病毒机制研究进展进行了简要综述。