MODY 2: Mutation identification and molecular ancestry in a Brazilian family

Maturity Onset Diabetes of the Young (MODY) is a heterogeneous group of genetic diseases characterized by a primary defect in insulin secretion and hyperglycemia, non-ketotic disease, monogenic autosomal dominant mode of inheritance, age at onset less than 25 years, and lack of auto-antibodies. It accounts for 2–5% of all cases of non-type 1 diabetes. MODY subtype 2 is caused by mutations in the glucokinase (GCK) gene. In this study, we sequenced the GCK gene of two volunteers with clinical diagnosis for MODY2 and we were able to identify four mutations including one for a premature stop codon (c.76C>T). Based on these results, we have developed a specific PCR-RFLP assay to detect this mutation and tested 122 related volunteers from the same family. This mutation in the GCK gene was detected in 21 additional subjects who also had the clinical features of this genetic disease. In conclusion, we identified new GCK gene mutations in a Brazilian family of Italian descendance, with one due to a premature stop codon located in the second exon of the gene. We also developed a specific assay that is fast, cheap and reliable to detect this mutation. Finally, we built a molecular ancestry model based on our results for the migration of individuals carrying this genetic mutation from Northern Italy to Brazil.     

Genome-wide analysis of the SET DOMAIN GROUP family in grapevine

The SET DOMAIN GROUP (SDG) proteins represent an evolutionarily-conserved family of epigenetic regulators present in eukaryotes and are putative candidates for the catalysis of lysine methylation in histones. Plant genomes analyses of this family have been performed in arabidopsis, maize, and rice and functional studies have shown that SDG genes are involved in the control of plant development. In this work, we describe the identification and structural characterization of SDG genes in the Vitis vinifera genome. This analysis revealed the presence of 33 putative SDG genes that can be grouped into different classes, as it has been previously described for plants. In addition to the SET domain, the proteins identified possessed other domains in the different classes. As part of our study regarding the growth and development of grapevine, we selected eight genes and their expression levels were analyzed in representative vegetative and reproductive organs of this species. The selected genes showed different patterns of expression during inflorescence and fruit development, suggesting that they participate in these processes. Furthermore, we showed that the expression of selected SDGs changes during viral infection, using as a model Grapevine Leafroll Associated Virus 3-infected symptomatic grapevine leaves and fruits. Our results suggest that developmental changes caused by this virus could be the result of alterations in SDG expression.     

In vitro assessment of the toxicity of metal compounds

A review of in vitro mutagenesis assessment of metal compounds in mammalian and nonmammalian test systems has been compiled. Prokaryotic assays are ineffective or inconsistent in their detection of most metals as mutagens, with the notable exception of hexavalent chromium. Mammalian assay systems appear to be similarly inappropriate for the screening of metal compounds based upon the limited number of studies that have employed those compounds having known carcinogenic activity. Although of limited value as screening tests for the detection of potentially carcinogenic metal compounds, the well-characterized in vitro mutagenesis systems may prove to be of significant value as a means to elucidate mechanisms of metal genotoxicity.     

Modelling the effect of forest cover on shallow landslides at the river basin scale

The potential for reducing the occurrence of shallow landslides through targeted reforestation of critical parts of a river basin is explored through mathematical modelling. Through the systematic investigation of land management options, modelling allows the optimum strategies to be selected ahead of any real intervention in the basin. Physically based models, for which the parameters can be evaluated using physical reasoning, offer particular advantages for predicting the effects of possible future changes in land use and climate. Typically a physically based landslide model consists of a coupled hydrological model (for soil moisture) and a geotechnical slope stability model, along with an impact model, such as basin sediment yield. An application of the SHETRAN model to the 65.8-km² Guabalcón basin in central Ecuador demonstrates a technique for identifying the areas of a basin most susceptible to shallow landsliding and for quantifying the effects of different vegetation covers on landslide incidence. Thus, for the modelled scenario, increasing root cohesion from 300 to 1500 Pa causes a two-thirds reduction in the number of landslides. Useful information can be obtained even on the basis of imperfect data availability but model output should be interpreted carefully in the light of parameter uncertainty.     

Different effects of serotonin antagonists on 3H-mianserin and 3H-ketanserin recognition sites

In minces prepared from the frontal cortex of rats treated with ketanserin (10 mg/kg i.p.) or mianserin (5 mg/kg i.p.) twice daily for 21 days, the Vmax of the adenylate cyclase stimulated by NE (100 microM) is attenuated, suggesting that ketanserin and mianserin share with a number of antidepressants the ability to attenuate the adenylate cyclase stimulation by NE. Ketanserin, given with the above mentioned dose schedule for 7 consecutive days, reduced the Bmax of 5HT2 recognition sites but failed to change either the Bmax or the apparent Kd of H-mianserin binding. A significant decrease in the Bmax of 5HT2 binding sites is elicited also by a single injection of mianserin (1). This drug also down-regulates its own binding when given twice daily for 3 weeks. From this and other information (2,3), it is concluded that ketanserin and mianserin bind to distinct recognition sites. The possibility that 5HT2 and mianserin recognition sites are functionally related and that serotonergic synapses are modulated by multiple chemical signals might be considered.     

Euclein: A new binaphthaquinone from Euclea pseudebenus

7-MethyljugIone, 8,8′-dihydroxy-4,4′-dimethoxy-6,6′-dimethyl-2,2′-binaphthyl-1,1′-quinone, 2-methylnaphthazarin, mamegakinone and euclein have been isolated from Euclea pseudebenus. Euclein is the 3,6′-dimer of 7-methyljuglone.     

Survival of Escherichia coli in the environment: fundamental and public health aspects

In this review, our current understanding of the species Escherichia coli and its persistence in the open environment is examined. E. coli consists of six different subgroups, which are separable by genomic analyses. Strains within each subgroup occupy various ecological niches, and can be broadly characterized by either commensalistic or different pathogenic behaviour. In relevant cases, genomic islands can be pinpointed that underpin the behaviour. Thus, genomic islands of, on the one hand, broad environmental significance, and, on the other hand, virulence, are highlighted in the context of E. coli survival in its niches. A focus is further placed on experimental studies on the survival of the different types of E. coli in soil, manure and water. Overall, the data suggest that E. coli can persist, for varying periods of time, in such terrestrial and aquatic habitats. In particular, the considerable persistence of the pathogenic E. coli O157:H7 is of importance, as its acid tolerance may be expected to confer a fitness asset in the more acidic environments. In this context, the extent to which E. coli interacts with its human/animal host and the organism''s survivability in natural environments are compared. In addition, the effect of the diversity and community structure of the indigenous microbiota on the fate of invading E. coli populations in the open environment is discussed. Such a relationship is of importance to our knowledge of both public and environmental health.