Exercise training provides cardioprotection via a reduction in reactive oxygen species in rats submitted to myocardial infarction induced by isoproterenol

Exercise training has demonstrated cardioprotection effects. However, the exact mechanism behind this effect is not is clear. The present study evaluated the effects of 12 weeks of previous treadmill training on the levels of oxidative damage, antioxidant enzyme activity and injury in the myocardium of rats submitted to infarction induced by isoproterenol (ISO). Isoproterenol treatment (80 mg/kg given over 2 days in two equal doses) caused arrhythmias and 60% mortality within 24 h of the last injection in the control group (C + ISO) group when compared with the saline control group (saline). Creatine Kinase ? MB levels were markedly increased in hearts from ISO-treated animals in the C + ISO group. Twelve weeks of treadmill training reduced superoxide production, lipid peroxidation levels and protein carbonylation in these animals, as well as increasing the activities and expressions of SOD and CAT. Previous training also reduced CK-MB levels and numbers of deaths by 40%, preventing the deleterious effects of ISO. Based on the data obtained in this study, it is suggested that 12-week treadmill training increases antioxidant enzymes, decreases oxidative damage and reduces the degree of infarction induced by ISO in the hearts of male rats.     

Charged surfactants induce a non‐fibrillar aggregation pathway of amyloid‐beta peptide

The amyloid β‐peptide with a sequence of 42 amino acids is the major constituent of extracellular amyloid deposits in Alzheimer's disease plaques. The control of the peptide self‐assembly is difficult to achieve because the process is fast and is affected by many variables. In this paper, we describe the effect of different charged and non‐charged surfactants on Aβ_(1‐42) fibrillation to define common alternate aggregation pathways. The characterization of the peptide‐surfactant interactions by ultra‐structural analysis, thioflavin T assay and secondary structure analysis, suggested that charged surfactants interact with Aβ_(1‐42) through electrostatic interactions. Charged micelles slow down the aggregation process and stabilize the peptide in the oligomeric state, whereas non‐charged surfactants promote the Aβ_(1‐42) fibril formation. Copyright © 2013 European Peptide Society and John Wiley & Sons, Ltd.     

Sequencing of the Dutch Elm Disease Fungus Genome Using the Roche/454 GS-FLX Titanium System in a Comparison of Multiple Genomics Core Facilities

As part of the DNA Sequencing Research Group of the Association of Biomolecular Resource Facilities, we have tested the reproducibility of the Roche/454 GS-FLX Titanium System at five core facilities. Experience with the Roche/454 system ranged from <10 to >340 sequencing runs performed. All participating sites were supplied with an aliquot of a common DNA preparation and were requested to conduct sequencing at a common loading condition. The evaluation of sequencing yield and accuracy metrics was assessed at a single site. The study was conducted using a laboratory strain of the Dutch elm disease fungus Ophiostoma novo-ulmi strain H327, an ascomycete, vegetatively haploid fungus with an estimated genome size of 30–50 Mb. We show that the Titanium System is reproducible, with some variation detected in loading conditions, sequencing yield, and homopolymer length accuracy. We demonstrate that reads shorter than the theoretical minimum length are of lower overall quality and not simply truncated reads. The O. novo-ulmi H327 genome assembly is 31.8 Mb and is comprised of eight chromosome-length linear scaffolds, a circular mitochondrial conti of 66.4 kb, and a putative 4.2-kb linear plasmid. We estimate that the nuclear genome encodes 8613 protein coding genes, and the mitochondrion encodes 15 genes and 26 tRNAs.     

Reproductive strategy of the invasive Oxalis pes-caprae: distribution patterns of floral morphs, ploidy levels and sexual reproduction

Oxalis pes-caprae, a tristylous flowering plant native to South Africa, is described in the western Mediterranean basin as an asexual—only 5x short-styled morph (5x S-morph) invasive weed losing all mating partners after introduction. The objective of this study was to reassess the patterns of floral morph and cytotype distribution and the sexual reproduction ability in this invaded range. For that, floral morph and cytotype composition were evaluated in 39 populations of O. pes-caprae in a methodical sampling. The reproductive success of natural populations was assessed as fruit and seed production and seed germination for all floral morphs and cytotypes detected. Self- and morph-incompatibility were also studied with controlled hand pollinations. A remarkable diversity in floral morph and cytotype composition was observed. Furthermore, we observed successful sexual reproduction in several localities across the surveyed area. The S-morph is still dominant in this invaded area, and although it was mostly 5x, an additional cytotype (4x) was also recorded. Records of both a mid-styled morph (M-morph) and an area with trimorphic populations of this species are reported here for the first time in the invasive range of the Mediterranean basin. The long-styled morph appears to occur randomly across the surveyed area, while the M-morph is concentrated mainly in Estremadura province (Portugal), where a breakdown in the incompatibility system was observed. These distribution patterns may result from events of sexual reproduction after incompatibility breakdown and/or from multiple introduction events from the native area. The ability to reproduce sexually, undetected so far, may have important impacts in the population dynamics and major consequences for the adaptation and selection potential of O. pes-caprae in this invaded area.     

Effect of invader removal: pollinators stay but some native plants miss their new friend

Removal of invasive species often benefits biological diversity allowing ecosystems’ recovery. However, it is important to assess the functional roles that invaders may have established in their new areas to avoid unexpected results from species elimination. Invasive animal-pollinated plants may affect the plant–pollination interactions by changing pollinator availability and/or behaviour in the community. Thus, removal of an invasive plant may have important effects on pollinator community that may then be reflected positive or negatively on the reproductive success of native plants. The objective of this study was to assess the effect of removing Oxalis pes-caprae, an invasive weed widely spread in the Mediterranean basin, on plant–pollinator interactions and on the reproductive success of co-flowering native plants. For this, a disturbed area in central Portugal, where this species is highly abundant, was selected. Visitation rates, natural pollen loads, pollen tube growth and natural fruit set of native plants were compared in the presence of O. pes-caprae and after manual removal of their flowers. Our results showed a highly resilient pollination network but also revealed some facilitative effects of O. pes-caprae on the reproductive success of co-flowering native plants. Reproductive success of the native plants seems to depend not only on the number and diversity of floral visitors, but also on their efficiency as pollinators. The information provided on the effects of invasive species on the sexual reproductive success of natives is essential for adequate management of invaded areas.     

Nucleolar organizer regions in Sittasomus griseicapillus and Lepidocolaptes angustirostris (Aves,Dendrocolaptidae): Evidence of a chromosome inversion

Cytogenetic studies in birds are still scarce compared to other vertebrates. Woodcreepers (Dendrocolaptidae) are part of a highly specialized group within the Suboscines of the New World. They are forest birds exclusive to the Neotropical region and similar to woodpeckers, at a comparable evolutionary stage. This paper describes for the first time the karyotypes of the Olivaceous and the Narrow-billed Woodcreeper using conventional staining with Giemsa and silver nitrate staining of the nucleolar organizer regions (Ag-NORs). Metaphases were obtained by fibular bone marrow culture. The chromosome number of the Olivaceous Woodcreeper was 2n = 82 and of the Narrow-billed Woodcreeper, 2n = 82. Ag-NORs in the largest macrochromosome pair and evidence of a chromosome inversion are described herein for the first time for this group.     

Insulin/IGF-I Signaling Pathways Enhances Tumor Cell Invasion through Bisecting GlcNAc N-glycans Modulation. An Interplay with E-Cadherin

Changes in glycosylation are considered a hallmark of cancer, and one of the key targets of glycosylation modifications is E-cadherin. We and others have previously demonstrated that E-cadherin has a role in the regulation of bisecting GlcNAc N-glycans expression, remaining to be determined the E-cadherin-dependent signaling pathway involved in this N-glycans expression regulation. In this study, we analysed the impact of E-cadherin expression in the activation profile of receptor tyrosine kinases such as insulin receptor (IR) and IGF-I receptor (IGF-IR). We demonstrated that exogenous E-cadherin expression inhibits IR, IGF-IR and ERK 1/2 phosphorylation. Stimulation with insulin and IGF-I in MDA-MD-435 cancer cells overexpressing E-cadherin induces a decrease of bisecting GlcNAc N-glycans that was accompanied with alterations on E-cadherin cellular localization. Concomitantly, IR/IGF-IR signaling activation induced a mesenchymal-like phenotype of cancer cells together with an increased tumor cell invasion capability. Altogether, these results demonstrate an interplay between E-cadherin and IR/IGF-IR signaling as major networking players in the regulation of bisecting N-glycans expression, with important effects in the modulation of epithelial characteristics and tumor cell invasion. Here we provide new insights into the role that Insulin/IGF-I signaling play during cancer progression through glycosylation modifications.     

Structural and Physiological Analyses of the Alkanesulphonate-Binding Protein (SsuA) of the Citrus Pathogen Xanthomonas citri

Background

The uptake of sulphur-containing compounds plays a pivotal role in the physiology of bacteria that live in aerobic soils where organosulfur compounds such as sulphonates and sulphate esters represent more than 95% of the available sulphur. Until now, no information has been available on the uptake of sulphonates by bacterial plant pathogens, particularly those of the Xanthomonas genus, which encompasses several pathogenic species. In the present study, we characterised the alkanesulphonate uptake system (Ssu) of Xanthomonas axonopodis pv. citri 306 strain (X. citri), the etiological agent of citrus canker.

Methodology/Principal Findings

A single operon-like gene cluster (ssuEDACB) that encodes both the sulphur uptake system and enzymes involved in desulphurisation was detected in the genomes of X. citri and of the closely related species. We characterised X. citri SsuA protein, a periplasmic alkanesulphonate-binding protein that, together with SsuC and SsuB, defines the alkanesulphonate uptake system. The crystal structure of SsuA bound to MOPS, MES and HEPES, which is herein described for the first time, provides evidence for the importance of a conserved dipole in sulphate group coordination, identifies specific amino acids interacting with the sulphate group and shows the presence of a rather large binding pocket that explains the rather wide range of molecules recognised by the protein. Isolation of an isogenic ssuA-knockout derivative of the X. citri 306 strain showed that disruption of alkanesulphonate uptake affects both xanthan gum production and generation of canker lesions in sweet orange leaves.

Conclusions/Significance

The present study unravels unique structural and functional features of the X. citri SsuA protein and provides the first experimental evidence that an ABC uptake system affects the virulence of this phytopathogen.     

Renin-Angiotensin System Blockers Protect Pancreatic Islets against Diet-Induced Obesity and Insulin Resistance in Mice

Background

The associations between obesity, hypertension and diabetes are well established, and the renin-angiotensin system (RAS) may provide a link among them. The effect of RAS inhibition on type 2 diabetes is still unclear; however, RAS seems to play an important role in the regulation of the pancreas and glucose intolerance of mice fed high-fat (HF) diet.

Methods

C57BL/6 mice fed a HF diet (8 weeks) were treated with aliskiren (50 mg/kg/day), enalapril (30 mg/kg/day) or losartan (10 mg/kg/day) for 6 weeks, and the protective effects were extensively compared among groups by morphometry, stereological tools, immunostaining, Western blotting and hormonal analysis.

Results

All RAS inhibitors significantly attenuated the increased blood pressure in mice fed a HF diet. Treatment with enalapril, but not aliskiren or losartan, significantly attenuated body mass (BM) gain, glucose intolerance and insulin resistance, improved the alpha and beta cell mass and prevented the reduction of plasma adiponectin. Furthermore, enalapril treatment improved the protein expression of the pancreatic islet Pdx1, GLUT2, ACE2 and Mas receptors. Losartan treatment showed the greatest AT2R expression.

Conclusion

Our findings indicate that ACE inhibition with enalapril attenuated several of the deleterious effects of the HF diet. In summary, enalapril appears to be responsible for the normalization of islet morphology and function, of alpha and beta cell mass and of Pdx1 and GLUT2 expression. These protective effects of enalapril were attributed, primarily, to the reduction in body mass gain and food intake and the enhancement of the ACE2/Ang (1-7) /Mas receptor axis and adiponectin levels.     

Predictors of Beta-Blocker Intolerance and Mortality in Patients After Acute Coronary Syndrome

Purpose

To investigate the predictors of intolerance to beta-blockers treatment and the 6-month mortality in hospitalized patients with acute coronary syndrome (ACS).

Methods

This was a single-center, prospective, and longitudinal study including 370 consecutive ACS patients in Killip class I or II. BBs were prescribed according to international guidelines and withdrawn if intolerance occurred. The study was approved by the institutional ethics committee of our university. Statistics: the clinical parameters evaluated at admission, and the related intolerance to BBs and death at 6 months were analyzed using logistic regression (p<0.05)in PATIENTS.

Results

BB intolerance was observed in 84 patients and was associated with no prior use of statins (OR: 2.16, 95%CI: 1.26–3.69, p= 0.005) and Killip class II (OR: 2.5, 95%CI: 1.30-4.75, p=0.004) in the model adjusted for age, sex, blood pressure, and renal function. There was no association with ST-segment alteration or left anterior descending coronary artery plaque. Intolerance to BB was associated with the greatest risk of death (OR: 4.5, 95%CI: 2.15–9.40, p<0.001).

Conclusions

After ACS, intolerance to BBs in the first 48 h of admission was associated to non previous use of statin and Killip class II and had a high risk of death within 6 months.