Double-strand break DNA repair genotype predictive of later mortality and cancer incidence in a cohort of non-smokers

We followed-up for mortality and cancer incidence 1088 healthy non-smokers from a population-based study, who were characterized for 22 variants in 16 genes involved in DNA repair pathways. Follow-up was 100% complete. The association between polymorphism and mortality or cancer incidence was analyzed using Cox Proportional Hazard regression models. Ninety-five subjects had died in a median follow-up time of 78 months (inter-quartile range 59-93 months). None of the genotypes was clearly associated with total mortality, except variants for two Double-Strand Break DNA repair genes, XRCC3 18067 C>T (rs#861539) and XRCC2 31479 G>A (rs#3218536). Adjusted hazard ratios were 2.25 (1.32-3.83) for the XRCC3 C/T genotype and 2.04 (1.00-4.13) for the T/T genotype (reference C/C), and 2.12 (1.14-3.97) for the XRCC2 G/A genotype (reference G/G). For total cancer mortality, the adjusted hazard ratios were 3.29 (1.23-7.82) for XRCC3 C/T, 2.84 (0.81-9.90) for XRCC3 T/T and 3.17 (1.21-8.30) for XRCC2 G/A. With combinations of three or more adverse alleles, the adjusted hazard ratio for all cause mortality was 17.29 (95% C.I. 8.13-36.74), and for all incident cancers the HR was 5.28 (95% C.I. 2.17-12.85). Observations from this prospective study suggest that polymorphisms of genes involved in the repair of DNA double-strand breaks significantly influence the risk of cancer and non-cancer disease, and can influence mortality.     

Helminth communities of loggerhead turtles (Caretta caretta) from Central and Western Mediterranean Sea: The importance of host's ontogeny

We investigated the factors providing structure to the helminth communities of 182 loggerhead sea turtles, Caretta caretta, collected in 6 localities from Central and Western Mediterranean. Fifteen helminth taxa (10 digeneans, 4 nematodes and 1 acanthocephalan) were identified, of which 12 were specialist to marine turtles; very low numbers of immature individuals of 3 species typical from fish or cetaceans were also found. These observations confirm the hypothesis that phylogenetic factors restrict community composition to helminth species specific to marine turtles. There were significant community dissimilarities between turtles from different localities, the overall pattern being compatible with the hypothesis that parasite communities reflect the ontogenetic shift that juvenile loggerheads undergo from oceanic to neritic habitats. The smallest turtles at the putative oceanic, pelagic-feeding stage harboured only the 2 digenean species that were regionally the most frequent, i.e. Enodiotrema megachondrus and Calycodes anthos; the largest turtles at the putative neritic, bottom-feeding stage harboured 11 helminth taxa, including 3 nematode species that were rare or absent in turtles that fed partially on pelagic prey. Mean species richness per host was low (range: 1.60–1.89) and did not differ between localities. Variance ratio tests indicated independent colonization of each helminth species. Both features are expected in ectothermic and vagrant hosts living in the marine environment.     

Multi-scale relationships between numbers and size in the evolution of arthropod body features

Size-related changes of form in animals with periodically patterned body axes and post-embryonic growth discontinuously obtained throughout a series of moulting episodes cannot be accounted for by allometry alone. We address here the relationships between body size and number and size of appropriately selected structural units (e.g., segments), which may more or less closely approximate independent developmental units, or unitary targets of selection, or both. Distinguishing between units fundamentally involving one cell only or a small and fixed number of cells (e.g., the ommatidia in a compound eye), and units made of an indeterminate number of cells (e.g., trunk segments), we analyze and discuss a selection of body features of either kind, both in ontogeny and in phylogeny, through a review of current literature and meta-analyses of published and unpublished data. While size/number relationships are too diverse to allow easy generalizations, they provide conspicuous examples of the complex interplay of selective forces and developmental constraints that characterizes the evolution of arthropod body patterning.     

The oligodeoxynucleotide sequences corresponding to never-expressed peptide motifs are mainly located in the non-coding strand

Background  

We study the usage of specific peptide platforms in protein composition. Using the pentapeptide as a unit of length, we find that in the universal proteome many pentapeptides are heavily repeated (even thousands of times), whereas some are quite rare, and a small number do not appear at all. To understand the physico-chemical-biological basis underlying peptide usage at the proteomic level, in this study we analyse the energetic costs for the synthesis of rare and never-expressed versus frequent pentapeptides. In addition, we explore residue bulkiness, hydrophobicity, and codon number as factors able to modulate specific peptide frequencies. Then, the possible influence of amino acid composition is investigated in zero- and high-frequency pentapeptide sets by analysing the frequencies of the corresponding inverse-sequence pentapeptides. As a final step, we analyse the pentadecamer oligodeoxynucleotide sequences corresponding to the never-expressed pentapeptides.     

Effects of water garlic extracts on cell cycle and viability of HepG2 hepatoma cells

Garlic extracts, either aqueous or oily, are commonly employed to prepare garlic derivative supplements used as nutraceuticals for the treatment of different pathologies. In this study, we investigated the effects of water garlic extracts from two different areas of Italy well known for garlic production, Latina (GEL) and Sulmona (GES), on cell cycle and death of HepG2 hepatoma cells. The effects of the treatments with GEL and GES were also compared with the oil-soluble sulfur compound of garlic, diallyl disulfide (DADS). GEL and GES induced a p53/p21-dependent cell cycle arrest in G2/M phase and apoptosis, although to a different extent, whereas DADS, under the experimental conditions used, was not detrimental to HepG2 cells. GEL and GES committed HepG2 cells to apoptosis by the activation of c-Jun-NH(2) terminal kinase (JNK)/c-Jun phosphorylative cascade without a detectable increase in the flux of reactive oxygen species. Moreover, differentiation of HepG2 cells induced by retinoic acid determined resistance to GEL and GES treatments without the activation of JNK signaling pathway. Overall, the results obtained indicate that water-soluble garlic extracts are more inhibitory of the growth of transformed hepatoma cells than the oil-soluble isolated compound DADS, and that their antiproliferative properties are different depending on the area of origin of the starting material.     

Enzyme inhibition-based biosensors for food safety and environmental monitoring

Analytical technology based on sensors is an extremely broad field which impacts on many major industrial sectors such as the pharmaceutical, healthcare, food, and agriculture industries as well as environmental monitoring. This review will highlight the research carried out during the last 5 years on biosensors that are based on enzyme inhibition for determination of pollutants and toxic compounds in a wide range of samples. Here the different enzymes implicated in the inhibition, different transducers forming the sensing devices, and the different contaminants analyzed are considered. The general application of the various biosensors developed, with emphasis on food and environmental applications, is reviewed as well as the general approaches that have been used for enzyme immobilization, the enzyme catalysis, and the inhibition mechanism.     

3-Arylpiperazinylethyl-1H-pyrrolo[2,3-d]pyrimidine-2,4(3H,7H)-dione derivatives as novel, high-affinity and selective alpha(1)-adrenoceptor ligands

The discovery of a new series of selective and high-affinity alpha(1)-adrenoceptor (alpha(1)-AR) ligands, characterized by a 1H-pyrrolo[2,3-d]-pyrimidine-2,4(3H,7H)-dione system, is described in this paper. Some synthesized compounds, including 20, 22, and 30, displayed affinity in the nanomolar range for alpha(1)-ARs and substantial selectivity with respect to 5-HT(1A) and dopaminergic D(1) and D(2) receptors. Functional assays, performed on selected derivatives, showed antagonistic properties.     

Exploring alternative Zn-binding groups in the design of HDAC inhibitors: squaric acid, N-hydroxyurea, and oxazoline analogues of SAHA

Analogues of suberoylanilide hydroxamic acid (SAHA) were prepared by replacing the Zn-binding group with squaric acid, N-hydroxyurea, and 4-hydroxymethyl oxazoline units, also varying the length of the aliphatic chain. No inhibitory activity on HDAC was observed below 1.0 microM and no cytotoxic activity on different tumor cell lines was seen below 20.0 microM.