Association of single nucleotide polymorphisms in the microRNA miR‐1596 locus with residual feed intake in chickens

MicroRNAs are an abundant class of small non‐coding RNAs that regulate gene expression. Genetic variations in microRNA sequences may be associated with phenotype differences by influencing the expression of microRNAs and/or their targets. This study identified two single nucleotide polymorphisms (SNPs) in the genomic region of the microRNA miR‐1596 locus of chicken. Of the two SNPs, one was 95 bp upstream of miR‐1596 (g.5678784A>T) and the other was in the middle of the sequence producing the mature microRNA gga‐miR‐1596‐3p (g.5678944A>G). Genotypic distribution of the two SNPs had large differences among 12 chicken breeds (lines), especially between the fast‐growing commercial lines and the slow‐growing Chinese indigenous breeds for the g.5678784A>T SNP. Only the g.5678784A>T SNP was significantly associated with residual feed intake (RFI) in the F₂ population derived from a fast‐growing and a slow‐growing broiler as well as in the pure Huiyang bearded chicken. The birds with the AA genotype of the g.5678784A>T SNP had lower RFI and higher expression of the mature gga‐miR‐1596‐3p microRNA of miR‐1596 than did those with the other genotypes of the same SNP. We also found that the expression of the mature gga‐miR‐1596‐3p microRNA of miR‐1596 was significantly associated with RFI. These findings suggest that miR‐1596 can become a candidate gene related to RFI, and its genetic variation may contribute to changes in RFI by altering expression levels of the mature gga‐miR‐1596‐3p microRNA in chicken.     

Drought stress-induced autophagy gene expression is correlated with carbohydrate concentrations in Caragana korshinskii

Protoplasma - Autophagy has been reported to be an adapt function of plant cells under various stresses. In this report, autophagy-related gene expressions and carbohydrate...     

miR‐124a inhibits the proliferation and inflammation in rheumatoid arthritis fibroblast‐like synoviocytes via targeting PIK3/NF‐κB pathway

Abnormal hyperplasia of fibroblast‐like synoviocytes (FLS) leads to the progression of rheumatoid arthritis (RA). This study aimed to investigate the role of miR‐124a in the pathogenesis of RA. The viability and cell cycle of FLS in rheumatoid arthritis (RAFLS) were evaluated by Cell Counting Kit 8 and flow cytometry assay. The expression of PIK3CA, Akt, and NF‐κB in RAFLS was examined by real‐time PCR and Western blot analysis. The production of tumour necrosis factor (TNF)‐α and interleukin (IL)‐6 was detected by ELISA. The joint swelling and inflammation in collagen‐induced arthritis (CIA) mice were examined by histological and immunohistochemical analysis. We found that miR‐124a suppressed the viability and proliferation of RAFLS and increased the percentage of cells in the G1 phase. miR‐124a suppressed PIK3CA 3'UTR luciferase reporter activity and decreased the expression of PIK3CA at mRNA and protein levels. Furthermore, miR‐124a inhibited the expression of the key components of the PIK3/Akt/NF‐κB signal pathway and inhibited the expression of pro‐inflammatory factors TNF‐α and IL‐6. Local overexpression of miR‐124a in the joints of CIA mice inhibited inflammation and promoted apoptosis in FLS by decreasing PIK3CA expression. In conclusion, miR‐124a inhibits the proliferation and inflammation in RAFLS via targeting PIK3/NF‐κB pathway. miR‐124a is a promising therapeutic target for RA.     

The severe phenotype of females with tiny ring X chromosomes is associated with inability of these chromosomes to undergo X inactivation.

Molecular typing of HLA class II loci has been performed on a sample of 196 patients with Hodgkin lymphoma. Division of patients into two histological categories--nodular sclerosing Hodgkin disease versus all other types--shows significant overall association of the nodular sclerosing group with the HLA class II region. Haplotypes and alleles defined for the four loci typed--DRB1, DQA1, DQB1, and DPB1--were present in both excess and deficit in the nodular sclerosing sample. Some of the effects are attributable to particular DRB1 and DQB1 alleles, while other effects are best explained by haplotypes marking the entire class II region. The latter effects might be due to variation in additional, as-yet-unexamined loci in the class II region or to particular combinations of alleles from two or more loci. These data also explain why earlier studies showed HLA linkage but not association, and they substantiate the specific involvement of the immune system in certain neoplastic diseases.     

Multimeric BLM is dissociated upon ATP hydrolysis and functions as monomers in resolving DNA structures

Bloom (BLM) syndrome is an autosomal recessive disorder characterized by an increased risk for many types of cancers. Previous studies have shown that BLM protein forms a hexameric ring structure, but its oligomeric form in DNA unwinding is still not well clarified. In this work, we have used dynamic light scattering and various stopped-flow assays to study the active form and kinetic mechanism of BLM in DNA unwinding. It was found that BLM multimers were dissociated upon ATP hydrolysis. Steady-state and single-turnover kinetic studies revealed that BLM helicase always unwound duplex DNA in the monomeric form under conditions of varying enzyme and ATP concentrations as well as 3′-ssDNA tail lengths, with no sign of oligomerization being discerned. Measurements of ATPase activity further indicated that BLM helicase might still function as monomers in resolving highly structured DNAs such as Holliday junctions and D-loops. These results shed new light on the underlying mechanism of BLM-mediated DNA unwinding and on the molecular and functional basis for the phenotype of heterozygous carriers of BLM syndrome.     

Analysis and characterization of the functional TGFβ receptors required for BMP6-induced osteogenic differentiation of mesenchymal progenitor cells

Although BMP6 is highly capable of inducing osteogenic differentiation of mesenchymal progenitor cells (MPCs), the molecular mechanism involved remains to be fully elucidated. Using dominant negative (dn) mutant form of type I and type II TGFβ receptors, we demonstrated that three dn-type I receptors (dnALK2, dnALK3, dnALK6), and three dn-type II receptors (dnBMPRII, dnActRII, dnActRIIB), effectively diminished BMP6-induced osteogenic differentiation of MPCs. These findings suggested that ALK2, ALK3, ALK6, BMPRII, ActRII and ActRIIB are essential for BMP6-induced osteogenic differentiation of MPCs. However, MPCs in this study do not express ActRIIB. Moreover, RNA interference of ALK2, ALK3, ALK6, BMPRII and ActRII inhibited BMP6-induced osteogenic differentiation in MPCs. Our results strongly suggested that BMP6-induced osteogenic differentiation of MPCs is mediated by its functional TGFβ receptors including ALK2, ALK3, ALK6, BMPRII, and ActRII. [BMB Reports 2013; 46(2): 107-112]     

靶向突变p53聚集体的肿瘤治疗研究进展

突变p53 (mutant p53, Mut-53)聚集体的形成是p53突变后使原本包裹在其疏水核心内部的黏附序列暴露,黏附序列迅速成核组装,形成无定形的原纤维. Mut-p53聚集体不仅可以以显性负效应(dominant-negative effect,DN)的方式使野生型p53 (wild type p53,Wt-p53)失活,还表现出功能获得(gain-of-function,GOF)特性,促进肿瘤的发生和发展.在卵巢癌、结肠癌、前列腺癌等多种肿瘤细胞中均发现了Mut-p53的异常聚集,其与肿瘤的转移、耐药和预后不良具有显著的相关性.因此,p53聚集是逆转化疗耐药及肿瘤治疗的潜在靶点.设计和发现靶向Mut-p53聚集体的小分子化合物,抑制p53疏水核心内部黏附序列的暴露,恢复p53的功能从而发挥抗肿瘤作用成为了当今研究热点.本文就p53聚集体对肿瘤发生发展的影响及目前靶向Mut-p53聚集体的研究策略进行了综述.