The intrinsic mechanisms underlying the maturation of programming sequential spikes at cerebellar Purkinje cells

Cerebellum is involved in the motion coordination and working memory, to which the programming of sequential spikes at Purkinje cells is essential. It is not clear about the intrinsic mechanisms underlying spike capacity and timing precision as well as their postnatal maturation. We investigated the programming and intrinsic property of sequential spikes at Purkinje neurons during postnatal development by whole-cell recording in cerebellar slices. Cerebellar Purkinje neurons demonstrate the increasing of spike capacity and timing precision, as well as the lowering of refractory periods and threshold potentials during the postnatal maturation. In addition, the correlation between spike parameters and intrinsic properties converts to be more linear. This postnatal plasticity of neuronal intrinsic properties improves the timing precision and capacity of spike programming at cerebellar Purkinje neurons.     

MYH9: structure,functions and role of non-muscle myosin ⅡA in human disease

MYH9-related diseases (MYH9-RD) are a group of autosomal dominant diseases caused by mutations in the MYH9 gene, which are featured by thrombocytopenia, giant platelets and granulocyte cytoplasmic inclusion bodies. MYH9-RD patients generally suffer from bleeding syndromes, progressive kidney disease, deafness, or cataracts. Here, we reported on a case of MYH9-RD. A novel heterozygous mutation of MYH9 (c.2344-2345delGTinsTA, p.T782Y) was discovered by targeted sequencing technology. Immunofluorescence analysis of neutrophils confirmed abnormal aggregation of MYH9 protein. The results of this study should expand the MYH9 gene mutation spectrum and provide reference for subsequent researchers and genetic counseling.     

转基因红花中角质细胞生长因子KGF-1的表达

通过构建重组表达质粒载体p139035S-KGF1和根癌农杆菌介导在红花(Carthamus tinctorius)中表达角质细胞生长因子(KGF-1)。从侵染到诱导生根共需要14周, 转化率达0.1%。红花子叶在潮霉素筛选培养基上培养4–5周后便可获得丛生芽, 再生芽移入含潮霉素的伸长生根培养基, 培养4–8周可诱导生根。通过PCR、Southern blot、RT-PCR及Western blot检测证明目的基因KGF-1已经整合到红花细胞的染色体中, 实现了KGF-1外源蛋白在红花中的成功表达, 为开发KGF-1蛋白新的生产途径奠定了基础。     

Growth rates and biomass production of micropropagated apple plants of M26 and Gravenstein on their own roots and in different micrografted combinations under non-limiting and limiting nutrient conditions

Micropropagated apple plants of semi-dwarf rootstock M26 (M26) and vigorous cultivar Gravenstein (GR) on their own roots and different micrograft combinations were used in the experiment. The combinations included GR scion on GR root (GR/GR), M26 on M26 (M26/M26), GR on M26 (GR/M26), and M26 on GR (M26/GR). The plants were grown under non-limiting and limiting relative addition rates of nutrients. Under non-limiting nutrient conditions, M26 and GR showed a similar relative growth rate (RGR). Grafting reduced RGR significantly in the combination of M26/M26 compared to M26. The relative growth rate for the combination of GR/M26 was similar to the GR/GR plants, but it increased greatly compared to the M26/M26 plants. For the reverse combination of M26/GR, the RGR value decreased significantly compared to either the M26/M26 or the GR/GR plants. The RGR value and specific root length were lower for M26/GR than for GR/M26. No clear relationship between carbohydrate allocation and growth parameters of different plants was found under non-limiting nutrient conditions. Nutrient limitation resulted in increased dry weights and soluble sugars in the roots for all plants except for M26/GR. A reduced leaf area ratio and a lower RGR than the set relative addition rate of nitrogen were found for M26 and GR/M26 under limiting conditions. These results suggest that the dwarfing effect is not directly related to RGR of rootstocks or scions, but rather associated with root morphology of grafted plants and the ability of roots to absorb nutrients.     

Efficient Inhibition of wear debris-induced inflammation by locally delivered siRNA

Aseptic loosening is the most common long-term complication of total joint replacement, which is associated with the generation of wear debris. The purpose of this study was to investigate the inhibitory effect of small interfering RNA (siRNA) targeting tumor necrosis factor-α (TNF-α) on wear debris-induced inflammation. A local delivery of lentivirus-mediated TNF-α siRNA into the modified murine air pouch, which was stimulated by polymethylmethacrylate (PMMA) particles, resulted in significant blockage of TNF-α both in mRNA and protein levels for up to 4 weeks. In addition, significant down-regulation of interleukin-1 (IL-1) and interleukin-6 (IL-6) was observed in TNF-α siRNA-treated pouches. The safety profile of gene therapy was proven by Bioluminescent assay and quantitative fluorescent flux. Histological analysis revealed less inflammatory responses (thinner pouch membrane and decreased cellular infiltration) in TNF-α siRNA-treated pouches. These findings suggest that local delivery of TNF-α siRNA might be an excellent therapeutic candidate to inhibit particle-induced inflammation.     

Elastic priors to dynamically borrow information from historical data in clinical trials

Use of historical data and real-world evidence holds great potential to improve the efficiency of clinical trials. One major challenge is to effectively borrow information from historical data while maintaining a reasonable type I error and minimal bias. We propose the elastic prior approach to address this challenge. Unlike existing approaches, this approach proactively controls the behavior of information borrowing and type I errors by incorporating a well-known concept of clinically significant difference through an elastic function, defined as a monotonic function of a congruence measure between historical data and trial data. The elastic function is constructed to satisfy a set of prespecified criteria such that the resulting prior will strongly borrow information when historical and trial data are congruent, but refrain from information borrowing when historical and trial data are incongruent. The elastic prior approach has a desirable property of being information borrowing consistent, that is, asymptotically controls type I error at the nominal value, no matter that historical data are congruent or not to the trial data. Our simulation study that evaluates the finite sample characteristic confirms that, compared to existing methods, the elastic prior has better type I error control and yields competitive or higher power. The proposed approach is applicable to binary, continuous, and survival endpoints.     

Production of ascorbic acid,total protein,callus and root in vitro of non-heading Chinese cabbage by tissue culture

Molecular Biology Reports - The objective of the present work was the selection of cultivar, suitable medium and explant type for callus, root production, ascorbic acid, total ascorbic acid,...     

The anti-fibrotic effect of betulinic acid is mediated through the inhibition of NF-κB nuclear protein translocation

The purpose of the study was to investigate the anti-fibrotic effect and the potential mechanisms of action of betulinic acid (BA) against hepatic fibrosis in vivo and in vitro. BA is an active compound isolated from the bark of the birch tree Betula spp. (Betulaceae). Liver fibrosis was induced by intraperitoneal injections of thioacetamide (TAA, 200mg/kg) twice weekly for 6weeks in Wistar rats. The administration of BA (20 or 50mg/kg) was started following TAA injections and was continued for 6 or 8weeks to evaluate both the preventive and the protective effects. BA demonstrated great efficacy in preventing and curing hepatic fibrosis via attenuating the TAA-mediated increases in liver tissue hydroxyproline and α-smooth muscle actin (α-SMA). In vitro, BA effectively decreased the HSC-T6 cell viability induced by TNF-α and showed low toxicity in normal human chang liver cells. Moreover, BA significantly attenuated the expression of α-SMA and tissue inhibitor of metalloproteinase-1 (TIMP-1) and increased the levels of matrix metalloprotease (MMP)-13. BA also inhibited the expression of Toll-like receptor 4 (TLR4), myeloid differentiation factor 88 (MyD88) and the activation of nuclear factor-κB (NF-κB) in a time-dependent manner. This study provides evidence that BA exerts a significant anti-fibrosis effect by modulating the TLR4/MyD88/NF-κB signaling pathway.