Effets de la réserpine sur le développement d'Oedipoda coerulescens L. (Acridien,Orthoptère)

Summary Inhibitory effects of reserpine on ecdysis and chromatic adaptation inOedipoda appear to be linked with changes observed in both neural and neuro-endocrine regulating systems.     

Activation of stress signalling pathways enhances tolerance of fungi to chemical fungicides and antifungal proteins

Fungal disease is an increasing problem in both agriculture and human health. Treatment of human fungal disease involves the use of chemical fungicides, which generally target the integrity of the fungal plasma membrane or cell wall. Chemical fungicides used for the treatment of plant disease, have more diverse mechanisms of action including inhibition of sterol biosynthesis, microtubule assembly and the mitochondrial respiratory chain. However, these treatments have limitations, including toxicity and the emergence of resistance. This has led to increased interest in the use of antimicrobial peptides for the treatment of fungal disease in both plants and humans. Antimicrobial peptides are a diverse group of molecules with differing mechanisms of action, many of which remain poorly understood. Furthermore, it is becoming increasingly apparent that stress response pathways are involved in the tolerance of fungi to both chemical fungicides and antimicrobial peptides. These signalling pathways such as the cell wall integrity and high-osmolarity glycerol pathway are triggered by stimuli, such as cell wall instability, changes in osmolarity and production of reactive oxygen species. Here we review stress signalling induced by treatment of fungi with chemical fungicides and antifungal peptides. Study of these pathways gives insight into how these molecules exert their antifungal effect and also into the mechanisms used by fungi to tolerate sub-lethal treatment by these molecules. Inactivation of stress response pathways represents a potential method of increasing the efficacy of antifungal molecules.     

Human metabolic individuality in biomedical and pharmaceutical research

Genome-wide association studies (GWAS) have identified many risk loci for complex diseases, but effect sizes are typically small and information on the underlying biological processes is often lacking. Associations with metabolic traits as functional intermediates can overcome these problems and potentially inform individualized therapy. Here we report a comprehensive analysis of genotype-dependent metabolic phenotypes using a GWAS with non-targeted metabolomics. We identified 37 genetic loci associated with blood metabolite concentrations, of which 25 show effect sizes that are unusually high for GWAS and account for 10-60% differences in metabolite levels per allele copy. Our associations provide new functional insights for many disease-related associations that have been reported in previous studies, including those for cardiovascular and kidney disorders, type 2 diabetes, cancer, gout, venous thromboembolism and Crohn's disease. The study advances our knowledge of the genetic basis of metabolic individuality in humans and generates many new hypotheses for biomedical and pharmaceutical research.     

Common variants near TARDBP and EGR2 are associated with susceptibility to Ewing sarcoma

Ewing sarcoma, a pediatric tumor characterized by EWSR1-ETS fusions, is predominantly observed in populations of European ancestry. We performed a genome-wide association study (GWAS) of 401 French individuals with Ewing sarcoma, 684 unaffected French individuals and 3,668 unaffected individuals of European descent and living in the United States. We identified candidate risk loci at 1p36.22, 10q21 and 15q15. We replicated these loci in two independent sets of cases and controls. Joint analysis identified associations with rs9430161 (P = 1.4 × 10(-20); odds ratio (OR) = 2.2) located 25 kb upstream of TARDBP, rs224278 (P = 4.0 × 10(-17); OR = 1.7) located 5 kb upstream of EGR2 and, to a lesser extent, rs4924410 at 15q15 (P = 6.6 × 10(-9); OR = 1.5). The major risk haplotypes were less prevalent in Africans, suggesting that these loci could contribute to geographical differences in Ewing sarcoma incidence. TARDBP shares structural similarities with EWSR1 and FUS, which encode RNA binding proteins, and EGR2 is a target gene of EWSR1-ETS. Variants at these loci were associated with expression levels of TARDBP, ADO (encoding cysteamine dioxygenase) and EGR2.     

Genome-wide association study identifies a new melanoma susceptibility locus at 1q21.3

We performed a genome-wide association study of melanoma in a discovery cohort of 2,168 Australian individuals with melanoma and 4,387 control individuals. In this discovery phase, we confirm several previously characterized melanoma-associated loci at MC1R, ASIP and MTAP-CDKN2A. We selected variants at nine loci for replication in three independent case-control studies (Europe: 2,804 subjects with melanoma, 7,618 control subjects; United States 1: 1,804 subjects with melanoma, 1,026 control subjects; United States 2: 585 subjects with melanoma, 6,500 control subjects). The combined meta-analysis of all case-control studies identified a new susceptibility locus at 1q21.3 (rs7412746, P = 9.0 × 10(-11), OR in combined replication cohorts of 0.89 (95% CI 0.85-0.95)). We also show evidence suggesting that melanoma associates with 1q42.12 (rs3219090, P = 9.3 × 10(-8)). The associated variants at the 1q21.3 locus span a region with ten genes, and plausible candidate genes for melanoma susceptibility include ARNT and SETDB1. Variants at the 1q21.3 locus do not seem to be associated with human pigmentation or measures of nevus density.     

Mass march of termites into the deadly trap.

Carnivorous pitcher plants of the genus Nepenthes are not usually very selective about their prey, catching anything that is careless enough to walk on their slippery peristome, but Nepenthes albomarginata is an exception. We show here that this plant uses a fringe of edible white hairs to lure and then trap its prey, which consists exclusively of termites in enormous numbers. This singular feature accounts for the specialization of N. albomarginata for one prey taxon, unique so far among carnivorous plants.     

Identification of SLC39A4, a gene involved in acrodermatitis enteropathica

We have characterized the human gene SLC39A4, which encodes a protein with features characteristic of a ZIP zinc transporter. The chromosomal location and expression of SLC39A4, together with mutational analysis of eight families affected with acrodermatitis enteropathica, suggest that SLC39A4 is centrally involved in the pathogenesis of this condition.     

Minimum Sum of Squares Clustering in a Low Dimensional Space

Clustering with a criterion which minimizes the sum of squared distances to cluster centroids is usually done in a heuristic way. An exact polynomial algorithm, with a complexity in O(N ^p+1 logN), is proposed for minimum sum of squares hierarchical divisive clustering of points in a p-dimensional space with small p. Empirical complexity is one order of magnitude lower. Data sets with N = 20000 for p = 2, N = 1000 for p = 3, and N = 200 for p = 4 are clustered in a reasonable computing time.     

异常黑胆质成熟剂中各单味药对HL-60细胞增殖的抑制作用

异常黑胆质成熟剂是维吾尔医复方制剂,由甘草、红枣、破布木、牛舌草、铁线蕨、地锦草、小茴香、薰衣草、蜜蜂花和刺糖10味药组成,用于治疗由异常黑胆质所导致的肿瘤、糖尿病和心血管疾病等。研究了异常黑胆质成熟剂中各单味药(除刺糖外)对HL-60细胞增殖的抑制作用。HL-60细胞暴露于各单味药两种不同提取物(二氯甲烷和甲醇),于37℃、CO2体积分数为5%的恒温孵箱中培养后24、48、72h,用台盼蓝染色法检测细胞存活率。结果表明,各单味药的二氯甲烷提取物除小茴香外均显著降低HL-60癌细胞的存活率(P<0.05)。在甲醇提取物中,只有甘草和地锦草两味药的甲醇提取物可显著降低HL-60癌细胞的存活率(P<0.05)。与各单味药甲醇提取物相比,其二氯甲烷提取物均显著降低HL-60癌细胞的存活率(P<0.05)。结果显示,破布木、地锦草、铁线蕨、甘草、红枣、薰衣草、牛舌草和蜜蜂花8味药的二氯甲烷提取物和甘草、地锦草两味药的甲醇提取物均能抑制HL-60癌细胞的体外增殖。各单味药二氯甲烷提取物对HL-60细胞增殖的抑制作用均明显强于其相应的甲醇提取物。     

Insulin secretion and (pro)insulin biosynthesis of cultured mice islets after glibenclamide loading in vitro

Summary Isolated islets from C57B1/6J mice exposed to 10 mmoles/1 glucose supplemented with 5 g/ml glibenclamide for 48 h released significantly less insulin in the subsequent short-time incubation thanuntreated controls (without glibenclamide), whereas insulin biosynthesis was not suppressed by glibenclamide treatment.Investigations were carried out as a part of the ForschungsprojektDiabetes mellitus und Fettstoffwechselstörungen, supported by the Ministry of Health of the GDR.