Defensive Sesquiterpenes from Senecio candidans and S. magellanicus,and Their Structure?Activity Relationships

Eleven eremophilanolides, 1 – 3 and 6 – 13 , and two eremophilanes, 24 and 25 , were isolated from Senecio candidans and S. magellanicus from the Magallanes Region (Chile). Compounds 2, 3, 9 , and 10 have not been previously reported as natural products. Their structures were established by NMR spectroscopic analysis and chemical transformations. The X‐ray analysis of compounds 11, 13 , and 17 were also performed. Different semisynthetic analogs from eremophilanolide 11 were generated to carry out a structure? activity relationship study. Their possible plant defensive role was tested against herbivorous insects (Spodoptera littoralis, Rhopalosiphum padi, and Myzus persicae) and plants (Lactuca sativa). Additionally, their effects on insect (Sf9) and mammalian (CHO) cell lines were tested.     

Defensive sesquiterpenes from Senecio candidans and S. magellanicus, and their structure-activity relationships

Eleven eremophilanolides, 1-3 and 6-13, and two eremophilanes, 24 and 25, were isolated from Senecio candidans and S. magellanicus from the Magallanes Region (Chile). Compounds 2, 3, 9, and 10 have not been previously reported as natural products. Their structures were established by NMR spectroscopic analysis and chemical transformations. The X-ray analysis of compounds 11, 13, and 17 were also performed. Different semisynthetic analogs from eremophilanolide 11 were generated to carry out a structure-activity relationship study. Their possible plant defensive role was tested against herbivorous insects (Spodoptera littoralis, Rhopalosiphum padi, and Myzus persicae) and plants (Lactuca sativa). Additionally, their effects on insect (Sf9) and mammalian (CHO) cell lines were tested.     

A remodelling metric for angular fibre distributions and its application to diseased carotid bifurcations

Many soft biological tissues contain collagen fibres, which act as major load bearing constituents. The orientation and the dispersion of these fibres influence the macroscopic mechanical properties of the tissue and are therefore of importance in several areas of research including constitutive model development, tissue engineering and mechanobiology. Qualitative comparisons between these fibre architectures can be made using vector plots of mean orientations and contour plots of fibre dispersion but quantitative comparison cannot be achieved using these methods. We propose a 'remodelling metric' between two angular fibre distributions, which represents the mean rotational effort required to transform one into the other. It is an adaptation of the earth mover's distance, a similarity measure between two histograms/signatures used in image analysis, which represents the minimal cost of transforming one distribution into the other by moving distribution mass around. In this paper, its utility is demonstrated by considering the change in fibre architecture during a period of plaque growth in finite element models of the carotid bifurcation. The fibre architecture is predicted using a strain-based remodelling algorithm. We investigate the remodelling metric's potential as a clinical indicator of plaque vulnerability by comparing results between symptomatic and asymptomatic carotid bifurcations. Fibre remodelling was found to occur at regions of plaque burden. As plaque thickness increased, so did the remodelling metric. A measure of the total predicted fibre remodelling during plaque growth, TRM, was found to be higher in the symptomatic group than in the asymptomatic group. Furthermore, a measure of the total fibre remodelling per plaque size, TRM/TPB, was found to be significantly higher in the symptomatic vessels. The remodelling metric may prove to be a useful tool in other soft tissues and engineered scaffolds where fibre adaptation is also present.     

Prevalence of molecular subtypes and prognosis of invasive breast cancer in north-east of Morocco: retrospective study

ABSTRACT: BACKGROUND: Breast carcinoma is known as a heterogeneous disease because gene expression analyses identify several subtypes and the molecular profiles are prognostic and predictive for patients. Our aim, in this study, is to estimate the prevalence of breast cancer subtypes and to determine the relationship between clinico-pathological characteristics, overall survival (OS) and disease free survival (DFS) for patients coming from north-east of Morocco. METHODS: We reviewed 366 cases of breast cancer diagnosed between January 2007 to June 2010 at the Department of pathology. Age, size tumor, metastatic profile, node involvement profile, OS and DFS were analyzed on 181 patients. These last parameters were estimated by Kaplan-Meier analysis and log-rank test to estimate outcome differences among subgroups. RESULTS: The average age was 45 years, our patients were diagnosed late (57% stage III, 17.5% stage IV) with a high average tumor size. Luminal A subtype was more prevalent (53.6%) associated with favorable clinic-pathological characteristics, followed by luminal B (16.4%), Her2-overexpressing (12.6%), basal-like (12.6%) and unclassified subtype (4.9%).Survival analysis showed a significant difference between subtypes. The triple negative tumors were associated with poor prognosis (49% OS, 39% DFS), whereas the luminal A were associated with a better prognosis (88% OS, 59% DFS). The luminal B and the Her2-overexpressing subtypes were associated with an intermediate prognosis (77% and 75% OS, and 41% and 38% DFS respectively). CONCLUSION: This study showed that molecular classification by immunohistochemistry was necessary for therapeutic decision and prognosis of breast carcinoma. The luminal A subtype was associated with favorable biological characteristics and a better prognosis than triple negative tumors that were associated with a poor prognosis and unfavorable clinic-pathological characteristics.     

蝙蝠在维护生态系统中的作用

蝙蝠是世界上分布最广、种群数量最多、进化最成功的哺乳动物类群之一,它们在维护生态系统中具有重要的作用：蝙蝠在生态系统中占据了独特的生存空间;蝙蝠是许多农、林及卫生害虫的天敌;蝙蝠是种子的传播者和花粉的传授者;在一定生态系统中蝙蝠可能起到关键种的作用;食虫蝙蝠粪便和酮体均是我国传统中药中的主要药材之一。研究和保护蝙蝠在维护生态环境中具有十分重要的意义。     

Optimization and elucidation of interactions between ammonium, nitrate and phosphate inCentella asiatica cell culture using response surface methodology

The effects of macronutrients (NO₃ ⁻, NH₄ ⁺ and PO₄ ³⁻) on cell growth and triterpenoids production inCentella asiatica cell suspension cultures were analyzed using the Box-Behnken response surface model experimental design. In screening and optimization experiments, PO₄ ³⁻ as a single factor significantly influenced cell growth where increasing the phosphate level from 0.1 to 2.4 or 2.6 mM, elevated cell growth from 3.9 to 14–16 g/L. The optimum values predicted from the response surface model are 5.05 mM NH₄ ⁺, 15.0 mM NO₃ ⁻ and 2.6 mM PO₄ ³⁻, yielding 16.0 g/L cell dry weight with 99% fitness to the experimental data. While the NH₄ ⁺-NO₃ ⁻ interaction influenced cell growth positively in the optimization experiment, NH₄ ⁺ and NO₃ ⁻ as single factors; and interactions of NO₃ ⁻-PO₄ ³⁻, NH₄ ⁺-PO₄ ³⁻ and NH₄ ⁺-NO₃ ⁻ were all negative in the screening experiment. Cell growth and the final pH level were positively affected by PO₄ ³⁻, but negatively affected by NH₄ ⁺ and NH₄ ⁺-PO₄ ³⁻ interactions. The different effects of factors and their interactions on cell growth and final pH are influenced by a broad or narrow range of macronutrient concentrations. The productions of triterpenoids however were lower than 4 mg/g cell dry weight.     

Probing the structural states of human immunodeficiency virus type 1 pr55gag by using monoclonal antibodies

Gag-FP (fluorescent protein) fusion constructs are commonly used to study human immunodeficiency virus type 1 assembly, yielding diffuse signals throughout the cytoplasm along with punctate signals routinely described as virus-like particles (VLPs) representing assembled but unprocessed Gag. However, these particles cannot be accurately described as VLPs, since fluorescence microscopy cannot provide structural resolution. We demonstrate here that the inability of a monoclonal p24 antibody to bind its cognate epitope when unprocessed Gag is assembled distinguishes VLPs from unassembled, monomeric Gag. Furthermore, we show that assembled and unassembled Gag punctate signals travel along microtubules. These monoclonal antibody studies provide a new tool for examining retroviral assembly.     

Uncoupling the roles of HLA-DRB1 and HLA-DRB5 genes in multiple sclerosis

Genetic susceptibility to multiple sclerosis (MS) is associated with the MHC located on chromosome 6p21. This signal maps primarily to a 1-Mb region encompassing the HLA class II loci, and it segregates often with the HLA-DQB1*0602, -DQA1*0102, -DRB1*1501, -DRB5*0101 haplotype. However, the identification of the true predisposing gene or genes within the susceptibility haplotype has been handicapped by the strong linkage disequilibrium across the locus. African Americans have greater MHC haplotypic diversity and distinct patterns of linkage disequilibrium, which make this population particularly informative for fine mapping efforts. The purpose of this study was to establish the telomeric boundary of the HLA class II region affecting susceptibility to MS by assessing genetic association with the neighboring HLA-DRB5 gene as well as seven telomeric single nucleotide polymorphisms in a large, well-characterized African American dataset. Rare DRB5*null individuals were previously described in African populations. Although significant associations with both HLA-DRB1 and HLA-DRB5 loci were present, HLA-DRB1*1503 was associated with MS in the absence of HLA-DRB5, providing evidence for HLA-DRB1 as the primary susceptibility gene. Interestingly, the HLA-DRB5*null subjects appear to be at increased risk for developing secondary progressive MS. Thus, HLA-DRB5 attenuates MS severity, a finding consistent with HLA-DRB5's proposed role as a modifier in experimental autoimmune encephalomyelitis. Additionally, conditional haplotype analysis revealed a susceptibility signal at the class III AGER locus independent of DRB1. The data underscore the power of the African American MS dataset to identify disease genes by association in a region of high linkage disequilibrium.