Modulatory effects of Duguetia furfuracea (A. St. Hil) Benth. and Hook. f. in Drosophila melanogaster somatic and germinative cells

Mutagenic and antimutagenic activities of the medicinal plant Duguetia furfuracea were assessed using SMART/wing and ring-X-loss tests. For the ring-X-loss test, 2- to 3-day-old Drosophila melanogaster ring-X-lineage males and virgin ywsn3 females received D. furfuracea infusion at doses of 0.085, 0.042, or 0.014 g/mL for 24 h. We found that D. furfuracea did not produce any mutagenic effects in D. melanogaster germinative cells. The somatic cells of D. melanogaster were analyzed using the SMART/wing test involving three lineages - mwh, flr3, and ORR - and the same doses of D. furfuracea infusion employed in the ring-X-loss test, as well as 20 mM urethane. The results of both standard (ST) and high bioactivation (HB) crosses showed absence of mutagenic activity of D. furfuracea. In contrast, in both ST and HB crosses, we observed a modulatory effect of D. furfuracea against the genotoxic activity of urethane.     

Convergence of miRNA expression profiling, α-synuclein interacton and GWAS in Parkinson's disease

miRNAs were recently implicated in the pathogenesis of numerous diseases, including neurological disorders such as Parkinson''s disease (PD). miRNAs are abundant in the nervous system, essential for efficient brain function and play important roles in neuronal patterning and cell specification. To further investigate their involvement in the etiology of PD, we conducted miRNA expression profiling in peripheral blood mononuclear cells (PBMCs) of 19 patients and 13 controls using microarrays. We found 18 miRNAs differentially expressed, and pathway analysis of 662 predicted target genes of 11 of these miRNAs revealed an over-representation in pathways previously linked to PD as well as novel pathways. To narrow down the genes for further investigations, we undertook a parallel approach using chromatin immunoprecipitation-sequencing (ChIP-seq) analysis to uncover genome-wide interactions of α-synuclein, a molecule with a central role in both monogenic and idiopathic PD. Convergence of ChIP-seq and miRNomics data highlighted the glycosphingolipid biosynthesis and the ubiquitin proteasome system as key players in PD. We then tested the association of target genes belonging to these pathways with PD risk, and identified nine SNPs in USP37 consistently associated with PD susceptibility in three genome-wide association studies (GWAS) datasets (0.46≤OR≤0.63) and highly significant in the meta-dataset (3.36×10⁻⁴−3). A SNP in ST8SIA4 was also highly associated with PD (p = 6.15×10⁻³) in the meta-dataset. These findings suggest that several miRNAs may act as regulators of both known and novel biological processes leading to idiopathic PD.     

Subclinical regional left ventricular dysfunction in obese patients with and without hypertension or hypertrophy

We investigated the impact of obesity on the abnormalities of systolic and diastolic regional left ventricular (LV) function in patients with or without hypertension or hypertrophy, and without heart failure. We studied 120 individuals divided into 6 groups of 20 patients (42 ± 6 years, 60 females) using standard and pulsed-wave tissue Doppler imaging (TDI) echocardiography, and heterogeneity index (HI): nonobese (I: no hypertension, no hypertrophy, control group; II: hypertension, no hypertrophy; III: hypertension and hypertrophy) and obese (IV: no hypertension, no hypertrophy; V: hypertension, no hypertrophy; VI: hypertension and hypertrophy). The criterion for obesity was BMI ≥30 kg/m2, for hypertension was blood pressure ≥ 140/90 mm Hg, for hypertrophy in nonobese was LV mass/body surface area (BSA) >134 g/m(2) (men) and >110 mg/m2 (women), and in obese was LV mass/height(2.7) >50 (men) and >40 (women). Obese groups had normal LV ejection fraction compared with nonobese groups, but decreased longitudinal and radial systolic myocardial peak velocities (S'), and early diastolic myocardial peak velocity (E'). Also, a great variability of E' and late diastolic myocardial peak velocity (A') from the longitudinal basal region was observed in obese groups (E'basal nonobese: 11 ± 7 vs. obese 19 ± 11, P < 0.001, A'basal nonobese: 7 ± 4 vs. obese 11 ± 7, P < 0.001). Our findings were more evident when comparing groups IV with V and VI, with the latter having concentric hypertrophy and obvious segmental systolic and diastolic dysfunctions. Subclinical myocardial alterations and increased variability of the velocities were observed in obese groups, especially with hypertension and hypertrophy, reflecting impaired regional LV relaxation, segmental atrial, and systolic dysfunctions.     

A Bayesian framework for parameter estimation in dynamical models

Mathematical models in biology are powerful tools for the study and exploration of complex dynamics. Nevertheless, bringing theoretical results to an agreement with experimental observations involves acknowledging a great deal of uncertainty intrinsic to our theoretical representation of a real system. Proper handling of such uncertainties is key to the successful usage of models to predict experimental or field observations. This problem has been addressed over the years by many tools for model calibration and parameter estimation. In this article we present a general framework for uncertainty analysis and parameter estimation that is designed to handle uncertainties associated with the modeling of dynamic biological systems while remaining agnostic as to the type of model used. We apply the framework to fit an SIR-like influenza transmission model to 7 years of incidence data in three European countries: Belgium, the Netherlands and Portugal.     

Microsatellite variation and evolution of human lactase persistence

The levels of haplotype diversity within the lineages defined by two single-nucleotide polymorphisms (SNPs) (–13910 C/T and –22018 G/A) associated with human lactase persistence were assessed with four fast-evolving microsatellite loci in 794 chromosomes from Portugal, Italy, Fulbe from Cameroon, São Tomé and Mozambique. Age estimates based on the intraallelic microsatellite variation indicate that the –13910*T allele, which is more tightly associated with lactase persistence, originated in Eurasia before the Neolithic and after the emergence of modern humans outside Africa. We detected significant departures from neutrality for the –13910*T variant in geographically and evolutionary distant populations from southern Europe (Portuguese and Italians) and Africa (Fulbe) by using a neutrality test based on the congruence between the frequency of the allele and the levels of intraallelic variability measured by the number of mutations in adjacent microsatellites. This result supports the role of selection in the evolution of lactase persistence, ruling out possible confounding effects from recombination suppression and population history. Reevaluation of the available evidence on variation of the –13910 and –22018 loci indicates that lactase persistence probably originated from different mutations in Europe and most of Africa, even if 13910*T is not the causal allele, suggesting that selective pressure could have promoted the convergent evolution of the trait. Our study shows that a limited number of microsatellite loci may provide sufficient resolution to reconstruct key aspects of the evolutionary history of lactase persistence, providing an alternative to approaches based on large numbers of SNPs.Electronic supplementary material Supplementary material is available for this article at     

Effect of Different Carbon Sources on Endochitinase Production by Colletotrichum gloeosporioides

The present work analyzes the production of endochitinase by Colletotrichum gloeosporioides, a phytopathogenic fungus, using six different carbon sources and two pH values. For quantitative assay of endochitinase activity in solution, the synthetic substrate 4-methylumbelliferyl-β-D-N,N’,N”-triacetylchitotrioside was used. The major productions were obtained at pH 7.0 and 9.0, when colloidal chitin and glucose were used, whereas xylose and lactose were not good carbon sources. When testing different concentrations of colloidal chitin, glucose and glucosamine, colloidal chitin 0.5% was the best substrate, giving values of 2.4 U at the fifth day. When using glucose, best production occurred at 0.3% concentration, after 5 days growth, with values of 1.31 U. Endochitinase production was markedly decreased in high levels of glucose and in all glucosamine concentrations tested. SDS-PAGE co-polymerized with glycol-chitin analysis showed three major activity bands of 200, 100, and 95 kDa, when incubated at 50°C.