Evaluation of light-emitting diodes as attractant for sandflies (Diptera: Psychodidae: Phlebotominae) in northeastern Brazil

Hoover Pugedo light traps were modified for use with green and blue-light-emitting diodes to trap phlebotomine sandflies in northeastern Brazil. A total of 2,267 specimens belonging to eight genera and 15 species were sampled. The predominant species were Nyssomyia whitmani(34.41%) and Micropygomyia echinatopharynx(17.25%).The green LED trap prevailed over the blue and control lights; however, no statistically significant difference could be detected among the three light sources. Even without statistical significance, we suggest using LEDs as an attractant for the capture of sandflies because of several advantages over the conventional method with incandescent lamps.     

Vegetarianism,female gender and increasing age,but not <Emphasis Type="Italic">CNDP1</Emphasis> genotype,are associated with reduced muscle carnosine levels in humans

Carnosine is found in high concentrations in skeletal muscles, where it is involved in several physiological functions. The muscle carnosine content measured within a population can vary by a factor 4. The aim of this study was to further characterize suggested determinants of the muscle carnosine content (diet, gender and age) and to identify new determinants (plasma carnosinase activity and testosterone). We investigated a group of 149 healthy subjects, which consisted of 94 men (12 vegetarians) and 55 women. Muscle carnosine was quantified in M. soleus, gastrocnemius and tibialis anterior using magnetic resonance proton spectroscopy and blood samples were collected to determine CNDP1 genotype, plasma carnosinase activity and testosterone concentrations. Compared to women, men have 36, 28 and 82% higher carnosine concentrations in M. soleus, gastrocnemius and tibialis anterior muscle, respectively, whereas circulating testosterone concentrations were unrelated to muscle carnosine levels in healthy men. The carnosine content of the M. soleus is negatively related to the subjects’ age. Vegetarians have a lower carnosine content of 26% in gastrocnemius compared to omnivores. In contrast, there is no difference in muscle carnosine content between omnivores with a high or low ingestion of β-alanine. Muscle carnosine levels are not related to the polymorphism of the CNDP1 gene or to the enzymatic activity of the plasma carnosinase. In conclusion, neither CNDP1 genotype nor the normal variation in circulating testosterone levels affects the muscular carnosine content, whereas vegetarianism, female gender and increasing age are the factors associated with reduced muscle carnosine stores.     

Synthesis and evaluation of strand and turn modified ring-extended gramicidin S derivatives

In this paper, we describe the crystal structure of previously reported ring-extended gramicidin S (GS) derivative 2 (GS14K4), containing a d-amino acid residue in one of the β-strand regions. This structure is in agreement with a previously reported modeling study of the same molecule. The polar side chain of the additional d-amino acid residue is positioned at the same face of the molecule as the hydrophobic side chains, and we believe that because of this compound 2 is considerably less hydrophobic than extended GS derivatives in which the strand regions are exclusively composed of l-amino acids. Using this backbone structure as our benchmark we prepared a small series of ring-extended GS analogues featuring sugar amino acid dipeptide isosteres of varied hydrophobicity at the turn region. We show that via this approach hydrophobicity of extended GS analogues can be tuned without affecting the secondary structure (as observed from NMR and CD spectra). Biological evaluation reveals that hydrophobicity correlates to cell toxicity, but still bacteriolysis is induced with GS analogues that are too hydrophilic to efficiently lyse human red blood cells.     

An alpha/beta-fold C--C bond hydrolase is involved in a central step of nicotine catabolism by Arthrobacter nicotinovorans

The enzyme catalyzing the hydrolytic cleavage of 2,6-dihydroxypseudooxynicotine to 2,6-dihydroxypyridine and gamma-N-methylaminobutyrate was found to be encoded on pAO1 of Arthrobacter nicotinovorans. The new enzyme answers an old question about nicotine catabolism and may be the first C--C bond hydrolase that is involved in the biodegradation of a heterocyclic compound.     

Tumor suppression by the von Hippel-Lindau protein requires phosphorylation of the acidic domain

The tumor suppressor function of the von Hippel-Lindau protein (pVHL) has previously been linked to its role in regulating hypoxia-inducible factor levels. However, VHL gene mutations suggest a hypoxia-inducible factor-independent function for the N-terminal acidic domain in tumor suppression. Here, we report that phosphorylation of the N-terminal acidic domain of pVHL by casein kinase-2 is essential for its tumor suppressor function. This post-translational modification did not affect the levels of hypoxia-inducible factor; however, it did change the binding of pVHL to another known binding partner, fibronectin. Cells expressing phospho-defective mutants caused improper fibronectin matrix deposition and demonstrated retarded tumor formation in mice. We propose that phosphorylation of the acidic domain plays a role in the regulation of proper fibronectin matrix deposition and that this may be relevant for the development of VHL-associated malignancies.     

Control of colorectal metastasis formation by K-Ras

Mutational activation of the K-Ras proto-oncogene is frequently observed during the very early stages of colorectal cancer (CRC) development. The mutant alleles are preserved during the progression from pre-malignant lesions to invasive carcinomas and distant metastases. Activated K-Ras may therefore not only promote tumor initiation, but also tumor progression and metastasis formation. Metastasis formation is a very complex and inefficient process: Tumor cells have to disseminate from the primary tumor, invade the local stroma to gain access to the vasculature (intravasation), survive in the hostile environment of the circulation and the distant microvascular beds, gain access to the distant parenchyma (extravasation) and survive and grow out in this new environment. In this review, we discuss the potential influence of mutant K-Ras on each of these phases. Furthermore, we have evaluated the clinical evidence that suggests a role for K-Ras in the formation of colorectal metastases.     

Estrogen-related receptor alpha (ERRalpha) is a transcriptional regulator of apolipoprotein A-IV and controls lipid handling in the intestine

The estrogen-related receptor alpha (ERRalpha) is an orphan member of the superfamily of nuclear receptors involved in the control of energy metabolism. In particular, ERRalpha induces a high energy expenditure in the presence of the coactivator PGC-1alpha. However, ERRalpha knockout mice have reduced fat mass and are resistant to diet-induced obesity. ERRalpha is expressed in epithelial cells of the small intestine, and because the intestine is the first step in the energy chain, we investigated whether ERRalpha plays a function in dietary energy handling. Gene expression profiling in the intestine identified a subset of genes involved in oxidative phosphorylation that were down-regulated in the absence of ERRalpha. In support of the physiological role of ERRalpha in this pathway, isolated enterocytes from ERRalpha knockout mice display lower capacity for beta-oxidation. Microarray results also show altered expression of genes involved in dietary lipid digestion and absorption, such as pancreatic lipase-related protein 2 (PLRP2), fatty acid-binding protein 1 and 2 (L-FABP and I-FABP), and apolipoprotein A-IV (apoA-IV). In agreement, we found that ERRalpha-/- pups exhibit significant lipid malabsorption. We further show that the apoA-IV promoter is a direct target of ERRalpha and that its presence is required to maintain basal level but not feeding-induced regulation of the apoA-IV gene in mice. ERRalpha, in cooperation with PGC-1alpha, activates the apoA-IV promoter via interaction with the apoC-III enhancer in both human and mouse. Our results demonstrate that apoA-IV is a direct ERRalpha target gene and suggest a function for ERRalpha in intestinal fat transport, a crucial step in energy balance.     

Association between genome-wide association studies reported SNPs and pediatric-onset Crohn’s disease in Canadian children

A recent pediatric-focused genome-wide association study has implicated three novel susceptibility loci for Crohn’ disease (CD).We aimed to investigate whether the three recently reported and other previously reported genes/loci were also associated with CD in Canadian children. A case–control design was implemented at three pediatric gastroenterology clinics in Canada. Children <19 years of age with a confirmed diagnosis of CD were recruited along with controls. Single nucleotide polymorphisms (SNPs) in 19 reported genes/loci were genotyped. Associations between individual SNPs and CD were examined. A total of 563 cases and 553 controls were studied. The mean (±SD) age of the cases was 12.3 (±3.2) years. Most cases were male (56.0%), had ileo-colonic disease (L3 ± L4, 48.8%) and inflammatory behavior (B1 ± p, 87.9%) at diagnosis. Allelic association analysis (two-tailed) showed that 8 of the 19 targeted SNPs were significantly associated with overall susceptibility for CD. Associations with one additional SNP was borderline non-significant. Significantly associated SNPs included SNPs rs1250550 (p = 0.026) and rs8049439 (p = 0.04), recently reported to be specifically associated with pediatric-onset CD.Based on the results, we confirmed associations between two of the three novel pediatric-CD loci and other regions reported for associations with either pediatric and/or adult-onset CD.