Western diet leads to aging-related tumorigenesis via activation of the inflammatory,UPR, and EMT pathways

Among the principal causative factors for the development of complications related to aging is a diet rich in fats and sugars, also known as the Western diet. This diet advocates numerous changes that might increase the susceptibility to initiate cancer and/or to create a tissue microenvironment more conducive to the growth of malignant cells, thus favoring the progression of cancer and metastasis. Hypercaloric diets in general lead to oxidative stress generating reactive oxygen species and induce endoplasmic reticulum stress. Our results demonstrate that mice bearing tumors fed with a Western diet presented bigger tumor mass with increased insulin sensitivity in these tissues. Several markers of insulin signaling, such as AKT phosphorylation and mTOR pathway, are promoted in tumors of Western diet-fed animals. This process is associated with increased macrophage infiltration, activation of unfolded protein response pathway, and initiation of epithelial–mesenchymal transition (EMT) process in these tumor tissues. Summing up, we propose that the Western diet accelerates the aging-related processes favoring tumor development.Subject terms: Melanoma, TOR signalling, Mechanisms of disease, Ageing     

Taenia solium metacestode immunodominant peptides recognized by IgG antibodies in cerebrospinal fluid and serum paired samples from patients with active and inactive neurocysticercosis

The aim of this study was to test if serological distinction between patients with active and inactive neurocysticercosis (NCC), could be accomplished by the recognition of immunodominant peptides in total saline antigenic extract of Taenia solium metacestodes by IgG antibody in cerebrospinal fluid (CSF) and serum paired samples. CSF and serum samples of 10 each, active NCC patients, inactive NCC, and individuals with other neurological disorders, were used to recognize the antigenic peptides by western blot (WB). In the active NCC the 28-32 and 39-42 kDa peptides were more frequently detected in CSF than in sera (p < 0.05). The 47-52, 64-68, and 70 kDa antigens showed high frequencies in both samples from patients with active NCC. All the CSF samples of inactive NCC and other neurological disorder (control) patients tested negative, while serum samples from these last two groups recognized mainly the 80, 86, 95, and 98 kDa bands. This finding eliminates the use of the high molecular weigh bands (>or= 80 kDa) for diagnosis of NCC. The final conclusions were that the difference between active and inactive NCC may be done with the detection of peptides only in the CSF samples and that the 47-52, 64-68, and 70 kDa bands may be included as specific markers for active NCC when detected in CSF samples by WB using total saline extract of T. solium metacestode.     

Biocatalysed synthesis of sn-1,3-diacylglycerol oil from extra virgin olive oil

Enzymatic synthesis of sn-1,3-diacylglycerols (sn-1,3-DAG) in two steps without isolation of the intermediates was investigated. Firstly ethanolysis of extra virgin olive oil (EVO) using immobilized non-regiospecific lipase from Candida antarctica (Novozym 435) was carried out to obtain glycerol (Gly) and fatty acid ethyl esters (FAEE). In the second step the ethanolysis products have been re-esterificated testing different sn-1,3-regiospecific lipases, both immobilized and non-immobilized, in different reaction media, that is in the presence of solvents or in a solvent-free system, for different times, at different temperatures (12, 25 and 40 °C). The lipase from Rhizomucor miehei (Lipozyme IM) has been the most effective among the sn-1,3-specific lipases screened.     

New PCR ribotypes of Clostridium difficile detected in children in Brazil

A total of 35 Brazilian isolates of Clostridium difficile from faecal stools and four isolates from hospital environments were analyzed by PCR ribotyping. A whole cell protein profile (as an alternative for serogrouping), in vitro toxin production and susceptibility to vancomycin, metronidazole and clindamycin were also investigated. All strains were typeable by both phenotypic and genotypic methods, and a total of 13 different PCR ribotypes were identified, of which seven (132, 133, 134, 135, 136, 142 and 143) were considered new types and accounted for 78.5% of all samples evaluated (including hospital environments). A non-toxigenic C. difficile PCR ribotype 133 was detected in all children groups examined (inpatients, outpatients and healthy children), whilst toxigenic PCR ribotypes 015, 131, 134 and 135 were associated mostly with symptomatic children. Serogroups G and D were disseminated both in patients from the community and from the pediatric hospital, with group G prevalent among outpatient children. All strains were susceptible to vancomycin and metronidazole but high levels of resistance to clindamycin were found, especially among serogroups G and D. Co-existence of different ribotypes and serogroups in the same individual was observed. The new seven ribotypes found in this investigation may represent strains characteristic of this region of Brazil.     

The role of Tyr605 and Ala607 of thimet oligopeptidase and Tyr606 and Gly608 of neurolysin in substrate hydrolysis and inhibitor binding

The physicochemical properties of TOP (thimet oligopeptidase) and NEL (neurolysin) and their hydrolytic activities towards the FRET (fluorescence resonance energy transfer) peptide series Abz-GFSXFRQ-EDDnp [where Abz is o-aminobenzoyl; X=Ala, Ile, Leu, Phe, Tyr, Trp, Ser, Gln, Glu, His, Arg or Pro; and EDDnp is N-(2,4-dinitrophenyl)-ethylenediamine] were compared with those of site-mutated analogues. Mutations at Tyr605 and Ala607 in TOP and at Tyr606 and Gly608 in NEL did not affect the overall folding of the two peptidases, as indicated by their thermal stability, CD analysis and the pH-dependence of the intrinsic fluorescence of the protein. The kinetic parameters for the hydrolysis of substrates with systematic variations at position P1 showed that Tyr605 and Tyr606 of TOP and NEL respectively, played a role in subsite S1. Ala607 of TOP and Gly608 of NEL contributed to the flexibility of the loops formed by residues 600-612 (GHLAGGYDGQYYG; one-letter amino acid codes used) in NEL and 599-611 (GHLAGGYDAQYYG; one-letter amino acid codes used) in TOP contributing to the distinct substrate specificities, particularly with an isoleucine residue at P1. TOP Y605A was inhibited less efficiently by JA-2 {N-[1-(R,S)-carboxy-3-phenylpropyl]Ala-Aib-Tyr-p-aminobenzoate}, which suggested that the aromatic ring of Tyr605 was an important anchor for its interaction with wild-type TOP. The hydroxy groups of Tyr605 and Tyr606 did not contribute to the pH-activity profiles, since the pKs obtained in the assays of mutants TOP Y605F and NEL Y606F were similar to those of wild-type peptidases. However, the pH-kcat/Km dependence curve of TOP Y605A differed from that of wild-type TOP and from TOP Y606F. These results provide insights into the residues involved in the substrate specificities of TOP and NEL and how they select cytosolic peptides for hydrolysis.     

Concentration of <Emphasis Type="Italic">Cupriavidus necator</Emphasis> cells by flocculation and sedimentation

Separation and cells concentration constitute important stages in most biotechnological processes. Particularly, use of flocculation/sedimentation can improve significantly the extraction of biopolymers accumulated by microorganisms and the biodegradation of xenobiotic compounds by cell sludge. In this work the use of tannin and aluminum sulphate (Al₂(SO₄)₃) as flocculating agents for concentration of cells of Cupriavidus necator DSM 545 is evaluated. Cells were grown in broth nutrient medium in Erlenmeyer flasks, submitted to orbital agitation of 160 rpm at 30 °C for 21 h. The optimal concentrations of flocculating agents, as determined with a standard jar test method, were equal to 2,800 mg/L for tannin and 800 mg/L for Al₂(SO₄)₃, allowing for recovery of 95% of the cells in both cases. Obtained flocs presented density and average diameter of 1.03 g/mL ± 0.01 g/mL and 158 μm ± 19 μm for tannin and of 1.05 g/mL ± 0.01 g/mL and 146 μm ± 14 μm for Al₂(SO₄)₃, respectively. Batch settling tests were performed in order to determine the operational capacity of continuous settlers to be used for separation of the investigated flocculent suspensions. Finally, cultivation of cells using flocs as inoculum indicated that the cells remained viable after flocculation with usage of the optimum flocculating agent concentrations.     

Natural mortality factors of Leucoptera coffeella (Lepidoptera: Lyonetiidae) on Coffea arabica

The natural mortality of the coffee leafminer, Leucoptera coffeella (Guérin-Méneville) was investigated in three strata of coffee plant canopy for three seasons through construction and analysis of ecological life tables. Mortality of the leafminer was similar on all thirds of the canopy. Total mortality of immature stages was 95%, with 38.5, 43.8 and 12.7% occurring during egg, larval, and pupal stages. Rainfall killed 39.3% of eggs and larvae, and together with egg inviability (16.3%) and Vespidae (11.3%), were the highest mortality factors. Six wasp parasitoids caused 8% of larval mortality. Egg and larva were the critical stages. Variation in mortality was primarily associated with egg inviability, rainfall, and parasitism by Horismenus sp. (Hymenoptera: Eulophidae). Physiological disturbances during molting and metamorphosis also contributed for fluctuations in mortality of the leafminer. Tactics of integrated pest management to enhance natural mortality of the leafminer while conserving or augmenting the action of natural enemies are discussed.     

Twenty-four novel mutations in Wilson disease patients of predominantly Italian origin

Herein we report the results of mutation analysis of the ATP7B gene in a group of 134 Wilson disease (WD) families (268 chromosomes) prevalently of Italian origin. Using the SSCP and sequencing methods we identified 71 disease-causing mutations. Twenty-four were novel, while 19 more mutations already described, were identified in new populations in this study. A known mutation G591D showed a regional distribution, since it was only detected in 38.5% of the analyzed chromosomes in WD patients originating from Apulia, a region of South Italy. Detection of new mutations in the ATP7B gene increases our capability of molecular analysis that is essential for early diagnosis and treatment of WD.     

Drosophila melanogaster, a model system for comparative studies on the responses to real and simulated microgravity

A key requirement to enhance our understanding of the response of biological organisms to different levels of gravity is the availability of experimental systems that can simulate microgravity and hypergravity in ground-based laboratories. This paper compares the results obtained from analysing gene expression profiles of Drosophila in space versus those obtained in a random position machine (RPM) and by centrifugation. The correlation found validates the use of the RPM simulation technique to establish the effects of real microgravity on biological systems. This work is being extended to investigate Drosophila development in another gravity modifying instrument, the levitation magnet.