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.     

From genetics to epigenetics: new insights into keloid scarring

Keloid scarring is a dermal fibroproliferative response characterized by excessive and progressive deposition of collagen; aetiology and molecular pathology underlying keloid formation and progression remain unclear. Genetic predisposition is important in the pathogenic processes of keloid formation, however, environmental factors and epigenetic mechanisms may also play pivotal roles. Epigenetic modification is a recent area of investigation in understanding the molecular pathogenesis of keloid scarring and there is increasing evidence that epigenetic changes may play a role in induction and persistent activation of fibroblasts in keloid scars. Here we have reviewed three epigenetic mechanisms: DNA methylation, histone modification and the role of non‐coding RNAs. We also review the evidence that these mechanisms may play a role in keloid formation ‐ in future, it may be possible that epigenetic markers may be used instead of prognostic or diagnostic markers here. However, there is a significant amount of work required to increase our current understanding of the role of epigenetic modification in keloid disease.     

Acylation-stimulating protein/C5L2-neutralizing antibodies alter triglyceride metabolism in vitro and in vivo

Acylation-stimulating protein (ASP), a lipogenic hormone, stimulates triglyceride (TG) synthesis and glucose transport upon activation of C5L2, a G protein-coupled receptor. ASP-deficient mice have reduced adipose tissue mass due to increased energy expenditure despite increased food intake. The objective of this study was to evaluate the blocking of ASP-C5L2 interaction via neutralizing antibodies (anti-ASP and anti-C5L2-L1 against C5L2 extracellular loop 1). In vitro, anti-ASP and anti-C5L2-L1 blocked ASP binding to C5L2 and efficiently inhibited ASP stimulation of TG synthesis and glucose transport. In vivo, neither anti-ASP nor anti-C5L2-L1 altered body weight, adipose tissue mass, food intake, or hormone levels (insulin, leptin, and adiponectin), but they did induce a significant delay in TG clearance [P < 0.0001, 2-way repeated-measures (RM) ANOVA] and NEFA clearance (P < 0.0001, 2-way RM ANOVA) after a fat load. After treatment with either anti-ASP or anti-C5L2-L1 antibody there was no change in adipose tissue AMPK activity, but neutralizing antibodies decreased perirenal TG mass (-38.4% anti-ASP, -18.8% anti-C5L2, P < 0.01-0.001) and perirenal LPL activity (-75.6% anti-ASP, -72.5% anti-C5L2, P < 0.05). In liver, anti-C5L2-L1 decreased TG mass (-42.8%, P < 0.05), whereas anti-ASP increased AMPK activity (+34.6%, P < 0.001). In the muscle, anti-C5L2-L1 significantly increased TG mass (+128.0%, P < 0.05), LPL activity (+226.1%, P < 0.001), and AMPK activity (+71.1%, P < 0.01). In addition, anti-ASP increased LPL activity (+164.4, P < 0.05) and AMPK activity (+53.9%, P < 0.05) in muscle. ASP/C5L2-neutralizing antibodies effectively block ASP-C5L2 interaction, altering lipid distribution and energy utilization.     

First record of Cricetops rodent in the Oligocene of southwestern China

The muroid Cricetops Matthew and Granger, 1923 commonly occurred in the Oligocene terrestrial deposits in central and northern Asia. Here we report the first record of Cricetops in the southern part of Asia. Isolated rodent molars named as a new species, Cricetops auster sp. nov., were discovered from the early Oligocene sediments at the Lijiawa locality in Yunnan Province in southwestern China. Compared to previously known Cricetops, C. auster is smaller than Cricetops dormitor Matthew and Granger, 1923 and Cricetops aeneus Shevyreva, 1965, but larger than Cricetops minor Wang, 1987. The cusps of C. auster are less conical. The ridges and crests are longer, higher and thicker. Relatively long and high crests, ridges and arms extending from the main cusps in the new species make those cusps more crescent in appearance than in C. dormitor, C. aeneus and C. minor. C. auster is a rare species in the Lijiawa mammalian fauna. Well-developed shearing tooth crests and ridges of C. auster probably suggest a different diet from the Cricetops from the northern part of Asia.     

Role of IKK/NF-κB signaling in extinction of conditioned place aversion memory in rats

The inhibitor κB protein kinase/nuclear factor κB (IKK/NF-κB) signaling pathway is critical for synaptic plasticity. However, the role of IKK/NF-κB in drug withdrawal-associated conditioned place aversion (CPA) memory is unknown. Here, we showed that inhibition of IKK/NF-κB by sulphasalazine (SSZ; 10 mM, i.c.v.) selectively blocked the extinction but not acquisition or expression of morphine-induced CPA in rats. The blockade of CPA extinction induced by SSZ was abolished by sodium butyrate, an inhibitor of histone deacetylase. Thus, the IKK/NF-κB signaling pathway might play a critical role in the extinction of morphine-induced CPA in rats and might be a potential pharmacotherapy target for opiate addiction.     

Modulation of prion protein oligomerization, aggregation, and beta-sheet conversion by 4,4'-dianilino-1,1'-binaphthyl-5,5'-sulfonate (bis-ANS)

The prion protein (PrP) is the major agent implicated in the diseases known as transmissible spongiform encephalopathies. The onset of transmissible spongiform encephalopathy is related to a change in conformation of the PrP(C), which loses most of its alpha-helical content, becoming a beta-sheet-rich protein, known as PrP(Sc). Here we have used two Syrian hamster prion domains (PrP 109-141 and PrP 109-149) and the murine recombinant PrP (rPrP 23-231) to investigate the effects of anilino-naphtalene compounds on prion oligomerization and aggregation. Aggregation in the presence of bis-ANS (4,4'-dianilino-1,1'-binaphthyl-5,5'-sulfonate), ANS (1-anilinonaphthalene-8-sulfonate), and AmNS (1-amino-5-naphtalenesulfonate) was monitored. Bis-ANS was the most effective inhibitor of prion peptide aggregation. Bis-ANS binds strongly to rPrP 23-231 leading to a substantial increase in beta-sheet content and to limited oligomerization. More strikingly, the binding of bis-ANS to full-length rPrP is diminished by the addition of nanomolar concentrations of oligonucleotides, demonstrating that they compete for the same binding site. Thus, bis-ANS displays properties similar to those of nucleic acids, causing oligomerization and conversion to beta-sheet (Cordeiro, Y., Machado, F., Juliano, L., Juliano, M. A., Brentani, R. R., Foguel, D., and Silva, J. L. (2001) J. Biol. Chem. 276, 49400-49409). This dual effect of bis-ANS on prion protein makes this compound highly important to sequester crucial conformations of the protein, which may be useful to the understanding of the disease and to serve as a lead for the development of new therapeutic strategies.     

三种不同方法固定的石蜡切片中RNA的分析

研究在 10 %中性福尔马林、丙酮、甲醇 氯仿 冰醋酸 3种方法固定的石蜡切片中提取RNA的质量和数量 .取 2 5 0g体重的Wistar大鼠的肾脏 ,分别采用 10 %中性福尔马林、丙酮、甲醇 氯仿 冰醋酸 3种方法固定 ,石蜡包埋 ,H E染色 ;采用RNA裂解液、TRIZOL试剂 2种方法提取切片RNA ,逆转录为cDNA ,采用普通PCR和SYBRGREEN 1定量PCR分析RNA质量和数量 .结果表明 ,3种固定方法都可保持组织良好的结构和形态 ;采用 2种提取方法 ,均可经RT PCR扩增出 180bp大鼠磷酸甘油醛脱氢酶 (G3PDH)、5 6 5bpβ肌动蛋白 (β actin)、10 0bp纤溶酶系活化剂抑制物 1(PAI 1) ;但采用RNA裂解液时 ,比TRIZOL试剂可提取更多的RNA .     

Statin Use and the Risk of Parkinson's Disease: An Updated Meta-Analysis

Introduction

In response to the ongoing debate over the relationship between the use of statins and the risk of Parkinson''s disease (PD), we performed a systematic review and meta-analysis of observational studies to examine their association.

Methods

We conducted a review of the literature using electronic databases supplemented by a manual search to identify potentially relevant case-control or cohort studies. Summary relative risk (RRs) and 95% confidence intervals (CIs) were calculated using a random-effects model. Sensitivity and subgroup analyses were also conducted.

Results

Eleven studies (five case-control and six cohort) with a total of 3,513,209 participants and 21,011 PD cases were included. Statin use was associated with a lower risk of PD, with a summary RR of 0.81 (95% CI 0.71–0.92). Sensitivity analysis demonstrated the robustness of results. Subgroup analyses showed that neither study design nor study region significantly influenced the effect estimates. However, subgroup studies adjusted for age or sex had a greater inverse association than did unadjusted analyses (age-adjusted RR 0.75, 95% CI 0.60–0.95; age-unadjusted RR 0.86, 95% CI 0.75–0.99 and sex-adjusted RR 0.76, 95% CI 0.59–0.98; sex-unadjusted RR 0.85, 95% CI 0.79–0.92).

Conclusions

Results of this systematic review suggest that statin use is associated with a reduced PD risk. However, randomized controlled trials and more observational studies should be performed before strong conclusions are drawn.     

Effect of relative humidity on population growth of <Emphasis Type=Italic>Apolygus lucorum</Emphasis> (Heteroptera: Miridae)

Apolygus lucorum (Meyer-Dür) (Heteroptera: Miridae) is a significant insect pest of cotton, Chinese dates, grapes and many other crops in China, and its populations typically increase after heavy rains. However, the intrinsic mechanism of the rainfall-dependent outbreak is not yet fully understood. In our study, the effect of different relative humidity (RH), 40, 50, 60, 70, and 80% RH, on population growth of A. lucorum was evaluated in the laboratory. High humidity (e.g. 70 and 80% RH) was observed to significantly increase egg and nymph survival, prolong adult life longevity, and improve female fecundity. However, low humidity (e.g. 40 and 50% RH) led to unfavorable effects on survival and fecundity. As a result, the intrinsic capacity for increase (r _m), net production (R _o), and the finite rate of increase (λ) of A. lucorum population greatly increased with increasing relative humidity. Additionally, the relationships between r _m and R _o and relative humidity were good fits to the logistic models y = 36.82/(1 + Exp(10.76 − 0.19x)) (p < 0.001) and y = 0.10/(1 + Exp(9.26 − 0.19x)) (p = 0.003), respectively. This study provides insight into the phenology of A. lucorum, and may contribute to modeling of its population dynamics.