ent-Kauranoid derivatives from Sideritis moorei

Seven new ent-kauranoid derivatives ent-7alpha,18-dihydroxykaur-16-en-3-one, ent-18-acetoxy-3beta,7alpha-dihydroxykaur-15-en-17-al, ent-3beta-acetoxy-7alpha,18-dihydroxykaur-15-en-17-al, ent-18-acetoxy-3beta,7alpha,17-trihydroxykaur-15-ene, ent-3beta-acetoxy-7alpha,17,18-trihydroxykaur-15-ene, ent-18-acetoxy-3beta,7alpha,17-trihydroxy-15beta,16beta-epoxykaurane and ent-3beta-acetoxy-7alpha,17,18-trihydroxy-15beta,16beta-epoxykaurane have been isolated from Sideritis moorei. The structures of these compounds have been established by spectroscopic means and chemical correlations.     

Mechanistic aspects of biosynthesis of silver nanoparticles by several <Emphasis Type="Italic">Fusarium oxysporum</Emphasis> strains

Extracellular production of metal nanoparticles by several strains of the fungus Fusarium oxysporum was carried out. It was found that aqueous silver ions when exposed to several Fusarium oxysporum strains are reduced in solution, thereby leading to the formation of silver hydrosol. The silver nanoparticles were in the range of 20–50 nm in dimensions. The reduction of the metal ions occurs by a nitrate-dependent reductase and a shuttle quinone extracellular process. The potentialities of this nanotechnological design based in fugal biosynthesis of nanoparticles for several technical applications are important, including their high potential as antibacterial material.     

Dm3 is one member of a large constitutively expressed family of nucleotide binding site-leucine-rich repeat encoding genes

The major cluster of resistance genes in lettuce cv. Diana contains approximately 32 nucleotide binding site-leucine-rich repeat encoding genes. Previous molecular dissection of this complex region had identified a large gene, RGC2B, as a candidate for encoding the downy mildew resistance gene, Dm3. This article describes genetic and transgenic complementation data that demonstrated RGC2B is necessary and sufficient to confer resistance with Dm3 specificity. Ethylmethanesulphonate was used to induce mutations to downy mildew susceptibility in cv. Diana (Dm1, Dm3, Dm7, and Dm8). Nineteen families were identified with a complete loss of resistance in one of the four resistance specificities. Sequencing revealed a variety of point mutations in RGC2B in the six dm3 mutants. Losses of resistance were due to single changes in amino acid sequence or a change in an intron splice site. These mutations did not cluster in any particular region of RGC2B. A full-length genomic copy of RGC2B was isolated from a lambdaphage library and introduced into two genotypes of lettuce. Transgenics expressing RGC2B exhibited resistance to all isolates expressing Avr3 from a wide range of geographical origins. In a wildtype Dm3-expressing genotype, many of the RGC2 family members are expressed at low levels throughout the plant.     

Experimental transmission of Enteromyxum scophthalmi (Myxozoa), an enteric parasite of turbot Scophthalmus maximus

Several experiments were designed to elucidate the modes of transmission of the myxozoan parasite Enteromyxum scophthalmi to turbot Scophthalmus maximus. Direct transmission of the infections was achieved by cohabitation of infected and test fish, through waterborne contamination from the effluent of a tank containing infected fish, and via the oral route using parasite-infected intestines. The transmission of the turbot enteromyxosis was successful in all the fish exposed to the parasite by the 3 routes; accumulated mortality reached 100% at the end of most experiments. The progress of the infections was monitored by study of the histopathology. Influence of the mode of exposure was observed, with the oral route the fastest to initiate the parasite infections. The temperature also affected the course of the infections, which were established earlier at higher water temperature. Direct fish-to-fish transmission of the disease explains the rapid spreading of the turbot enteromyxosis in farms.     

Epigrass: a tool to study disease spread in complex networks

Background  

The construction of complex spatial simulation models such as those used in network epidemiology, is a daunting task due to the large amount of data involved in their parameterization. Such data, which frequently resides on large geo-referenced databases, has to be processed and assigned to the various components of the model. All this just to construct the model, then it still has to be simulated and analyzed under different epidemiological scenarios. This workflow can only be achieved efficiently by computational tools that can automate most, if not all, these time-consuming tasks. In this paper, we present a simulation software, Epigrass, aimed to help designing and simulating network-epidemic models with any kind of node behavior.     

Exonic Re-Sequencing of the Chromosome 2q24.3 Parkinson’s Disease Locus

Genome-wide association studies (GWAS) in Parkinson’s disease (PD) have identified over 20 genomic regions associated with disease risk. Many of these loci include several candidate genes making it difficult to pinpoint the causal gene. The locus on chromosome 2q24.3 encompasses three genes: B3GALT1, STK39, and CERS6. In order to identify if the causal variants are simple missense changes, we sequenced all 31 exons of these three genes in 187 patients with PD. We identified 13 exonic variants including four non-synonymous and three insertion/deletion variants (indels). These non-synonymous variants and rs2102808, the GWAS tag SNP, were genotyped in three independent series consisting of a total of 1976 patients and 1596 controls. Our results show that the seven identified 2q24.3 coding variants are not independently responsible for the GWAS association signal at the locus; however, there is a haplotype, which contains both rs2102808 and a STK39 exon 1 6bp indel variant, that is significantly associated with PD risk (Odds Ratio [OR] = 1.35, 95% CI: 1.11–1.64, P = 0.003). This haplotype is more associated than each of the two variants independently (OR = 1.23, P = 0.005 and 1.10, P = 0.10, respectively). Our findings suggest that the risk variant is likely located in a non-coding region. Additional sequencing of the locus including promoter and regulatory regions will be needed to pinpoint the association at this locus that leads to an increased risk to PD.     

Sensitivity and Specificity of the World Health Organization Dengue Classification Schemes for Severe Dengue Assessment in Children in Rio de Janeiro

Background

The clinical definition of severe dengue fever remains a challenge for researchers in hyperendemic areas like Brazil. The ability of the traditional (1997) as well as the revised (2009) World Health Organization (WHO) dengue case classification schemes to detect severe dengue cases was evaluated in 267 children admitted to hospital with laboratory-confirmed dengue.

Principal Findings

Using the traditional scheme, 28.5% of patients could not be assigned to any category, while the revised scheme categorized all patients. Intensive therapeutic interventions were used as the reference standard to evaluate the ability of both the traditional and revised schemes to detect severe dengue cases. Analyses of the classified cases (n = 183) demonstrated that the revised scheme had better sensitivity (86.8%, P<0.001), while the traditional scheme had better specificity (93.4%, P<0.001) for the detection of severe forms of dengue.

Conclusions/Significance

This improved sensitivity of the revised scheme allows for better case capture and increased ICU admission, which may aid pediatricians in avoiding deaths due to severe dengue among children, but, in turn, it may also result in the misclassification of the patients'' condition as severe, reflected in the observed lower positive predictive value (61.6%, P<0.001) when compared with the traditional scheme (82.6%, P<0.001). The inclusion of unusual dengue manifestations in the revised scheme has not shifted the emphasis from the most important aspects of dengue disease and the major factors contributing to fatality in this study: shock with consequent organ dysfunction.     

The role of DNA repair in the pluripotency and differentiation of human stem cells

All living cells utilize intricate DNA repair mechanisms to address numerous types of DNA lesions and to preserve genomic integrity, and pluripotent stem cells have specific needs due to their remarkable ability of self-renewal and differentiation into different functional cell types. Not surprisingly, human stem cells possess a highly efficient DNA repair network that becomes less efficient upon differentiation. Moreover, these cells also have an anaerobic metabolism, which reduces the mitochondria number and the likelihood of oxidative stress, which is highly related to genomic instability. If DNA lesions are not repaired, human stem cells easily undergo senescence, cell death or differentiation, as part of their DNA damage response, avoiding the propagation of stem cells carrying mutations and genomic alterations. Interestingly, cancer stem cells and typical stem cells share not only the differentiation potential but also their capacity to respond to DNA damage, with important implications for cancer therapy using genotoxic agents. On the other hand, the preservation of the adult stem cell pool, and the ability of cells to deal with DNA damage, is essential for normal development, reducing processes of neurodegeneration and premature aging, as one can observe on clinical phenotypes of many human genetic diseases with defects in DNA repair processes. Finally, several recent findings suggest that DNA repair also plays a fundamental role in maintaining the pluripotency and differentiation potential of embryonic stem cells, as well as that of induced pluripotent stem (iPS) cells. DNA repair processes also seem to be necessary for the reprogramming of human cells when iPS cells are produced. Thus, the understanding of how cultured pluripotent stem cells ensure the genetic stability are highly relevant for their safe therapeutic application, at the same time that cellular therapy is a hope for DNA repair deficient patients.     

Involvement of 4-hydroxy-2-nonenal in the pathogenesis of pulmonary fibrosis

Molecular and Cellular Biochemistry - Pulmonary fibrosis is a chronic progressive disease with high incidence, prevalence, and mortality rates worldwide. It is characterized by excessive...