High Levels of Asymmetric Dimethylarginine Are Strongly Associated with Low HDL in Patients with Acute Myocardial Infarction

Objectives

Low levels of high-density lipoprotein (HDL) cholesterol are associated with an increased risk of acute myocardial infarction possibly through impaired endothelial atheroprotection and decreased nitric oxide (NO) bioavailability. Asymmetric dimethylarginine (ADMA) mediates endothelial function by inhibiting nitric oxide synthase activity. In patients with acute myocardial infarction, we investigated the relationship between serum levels of HDL and ADMA.

Approach and Results

Blood samples from 612 consecutive patients hospitalized for acute MI <24 hours after symptom onset were taken on admission. Serum levels of ADMA, its stereoisomer, symmetric dimethylarginine (SDMA) and L-arginine were determined using high-performance liquid chromatography. Patients with low HDL (<40 mg/dL for men and <50 mg/dL for women) were compared with patients with higher HDL. Most patients (59%) had low HDL levels. Median ADMA levels were markedly higher in the low HDL group (0.69 vs. 0.50 µmole/L, p<0.001). In contrast, SDMA and L-arginine levels were similar for the two groups (p = 0.120 and p = 0.064). Notably, ADMA, but not SDMA or L-arginine, was inversely correlated with HDL (r = −0.311, p<0.001). In stratified analysis, this relationship was only found for low HDL levels (r = −0.265, p<0.001), but not when HDL levels were higher (r = −0.077, p = 0.225). By multivariate logistic regression analysis, ADMA level was strongly associated with low HDL levels (OR(95%CI):6.06(3.48–10.53), p<0.001), beyond traditional confounding factors.

Conclusions

Our large population-based study showed for the first time a strong inverse relationship between HDL and ADMA in myocardial infarction patients, suggesting a functional interaction between HDL and endothelium, beyond metabolic conditions associated with low HDL levels.     

The Bacterial Protein Azurin Impairs Invasion and FAK/Src Signaling in P-Cadherin-Overexpressing Breast Cancer Cell Models

P-cadherin overexpression occurs in about 30% of all breast carcinomas, being a poor prognostic factor for breast cancer patients. In a cellular background of wild-type E-cadherin, we have previously shown that its expression promotes invasion, motility and migration of breast cancer cells due to the induced secretion of metalloproteases (MMPs) to the extracellular medium and to the concomitant shedding of a pro-invasive soluble form of this protein (sP-cad). Azurin is secreted by Pseudomonas aeruginosa and induces in vitro and in vivo cytotoxicity after its preferential penetration in human cancer cells relative to normal cells. Three different breast cancer cell lines, MCF-7/AZ.Mock, MCF-7/AZ.Pcad and SUM149 were treated with sub-killing doses of azurin. Invasion of these cells was measured using Matrigel Invasion Assays and MTT assays were performed to determine cell viability upon treatment and the effects on cadherins expression was determined by Western blot and Immunofluorescence. Gelatin Zymography was used to determine activity of MMP2 in the conditioned media of azurin treated and untreated cells and the phosphorylation levels of intracellular signaling proteins were determined by Western blot. The invasive phenotype of these breast cancer cells was significantly reduced by azurin. Azurin (50–100 µM) also caused a specific decrease on P-cadherin protein levels from 30–50% in MCF-7/AZ.Pcad and SUM149 breast cancer cell lines, but the levels of E-cadherin remain unaltered. More, the levels of sP-cad and the activity of MMP2 were reduced in the extracellular media of azurin treated cells and we also observed a decrease in the phosphorylation levels of both FAK and Src proteins. Our data show that azurin specifically targets P-cadherin, not E-cadherin, abrogating P-cadherin-mediated invasive effects and signaling. Therefore, azurin could possibly be considered a therapeutic tool to treat poor-prognosis breast carcinomas overexpressing P-cadherin in a wild type E-cadherin context.     

Sustained Reduction of the Dengue Vector Population Resulting from an Integrated Control Strategy Applied in Two Brazilian Cities

Aedes aegypti has developed evolution-driven adaptations for surviving in the domestic human habitat. Several trap models have been designed considering these strategies and tested for monitoring this efficient vector of Dengue. Here, we report a real-scale evaluation of a system for monitoring and controlling mosquito populations based on egg sampling coupled with geographic information systems technology. The SMCP-Aedes, a system based on open technology and open data standards, was set up from March/2008 to October/2011 as a pilot trial in two sites of Pernambuco -Brazil: Ipojuca (10,000 residents) and Santa Cruz (83,000), in a joint effort of health authorities and staff, and a network of scientists providing scientific support. A widespread infestation by Aedes was found in both sites in 2008–2009, with 96.8%–100% trap positivity. Egg densities were markedly higher in SCC than in Ipojuca. A 90% decrease in egg density was recorded in SCC after two years of sustained control pressure imposed by suppression of >7,500,000 eggs and >3,200 adults, plus larval control by adding fishes to cisterns. In Ipojuca, 1.1 million mosquito eggs were suppressed and a 77% reduction in egg density was achieved. This study aimed at assessing the applicability of a system using GIS and spatial statistic analysis tools for quantitative assessment of mosquito populations. It also provided useful information on the requirements for reducing well-established mosquito populations. Results from two cities led us to conclude that the success in markedly reducing an Aedes population required the appropriate choice of control measures for sustained mass elimination guided by a user-friendly mosquito surveillance system. The system was able to support interventional decisions and to assess the program’s success. Additionally, it created a stimulating environment for health staff and residents, which had a positive impact on their commitment to the dengue control program.     

The Pneumatron: An automated pneumatic apparatus for estimating xylem vulnerability to embolism at high temporal resolution

Xylem vulnerability to embolism represents an important trait to determine species distribution patterns and drought resistance. However, estimating embolism resistance frequently requires time-consuming and ambiguous hydraulic lab measurements. Based on a recently developed pneumatic method, we present and test the “Pneumatron”, a device that generates high time-resolution and fully automated vulnerability curves. Embolism resistance is estimated by applying a partial vacuum to extract air from an excised xylem sample, while monitoring the pressure change over time. Although the amount of gas extracted is strongly correlated with the percentage loss of xylem conductivity, validation of the Pneumatron was performed by comparison with the optical method for Eucalyptus camaldulensis leaves. The Pneumatron improved the precision of the pneumatic method considerably, facilitating the detection of small differences in the (percentage of air discharged [PAD] < 0.47%). Hence, the Pneumatron can directly measure the 50% PAD without any fitting of vulnerability curves. PAD and embolism frequency based on the optical method were strongly correlated (r² = 0.93) for E. camaldulensis. By providing an open source platform, the Pneumatron represents an easy, low-cost, and powerful tool for field measurements, which can significantly improve our understanding of plant–water relations and the mechanisms behind embolism.     

Letter to the Editor—the Use of Micronucleus Assay on Buccal Mucosa Cells for Risk Assessment: Relevance of Cigarette Smoke and Cytogenotoxicity

Biological Trace Element Research -     

Diphacinone with cholecalciferol for controlling possums and ship rats

ABSTRACT

Potent second-generation anticoagulant rodenticides such as brodifacoum have been used as more effective alternatives to first-generation anticoagulants, such as warfarin. A combination of diphacinone at 0.005% and cholecalciferol at 0.06% produces a slow-acting bait that is effective at killing possums (Trichosurus vulpecula) and rodents. Cage trials with groups of possums and ship rats (Rattus rattus) achieved a mortality of 87% and 86% for possums and ship rats, respectively. Two field trials, each 200 hectares in size, targeting possums, ship rats and mice achieved an average reduction in the abundance of 94% for possums, 94% for ship rats and 80% for mice. The combination of diphacinone and cholecalciferol appears effective and has a favourable risk profile compared with second-generation anticoagulant rodenticides, such as brodifacoum. Approval of this new bait by the New Zealand Environmental Protection Agency was granted in 2018 and final registration obtained from the Ministry of Primary Industries in 2019.     

Current genetic engineering strategies for the production of antihypertensive ACEI peptides

Hypertension is a major and highly prevalent risk factor for various diseases. Among the most frequently prescribed antihypertensive first-line drugs are synthetic angiotensin I-converting enzyme inhibitors (ACEI). However, since  their use in hypertension therapy has been linked to various side effects, interest in the application of food-derived ACEI peptides (ACEIp) as antihypertensive agents is rapidly growing. Although promising, the industrial production of ACEIp through conventional methods such as chemical synthesis or enzymatic hydrolysis of food proteins has been proven troublesome. We here provide an overview of current antihypertensive therapeutics, focusing on ACEI, and illustrate how biotechnology and bioengineering can overcome the limitations of ACEIp large-scale production. Latest advances in ACEIp research and current genetic engineering-based strategies for heterologous production of ACEIp (and precursors) are also presented. Cloning approaches include tandem repeats of single ACEIp, ACEIp fusion to proteins/polypeptides, joining multivariate ACEIp into bioactive polypeptides, and producing ACEIp-containing modified plant storage proteins. Although bacteria have been privileged ACEIp heterologous hosts, particularly when testing for new genetic engineering strategies, plants and microalgae-based platforms are now emerging. Besides being generally safer, cost-effective and scalable, these “pharming” platforms can perform therelevant posttranslational modifications and produce (and eventually deliver) biologically active protein/peptide-based antihypertensive medicines.     

Seed dispersal networks in tropical forest fragments: Area effects,remnant species,and interaction diversity

Seed dispersal interactions involve key ecological processes in tropical forests that help to maintain ecosystem functioning. Yet this functionality may be threatened by increasing habitat loss, defaunation, and fragmentation. However, generalist species, and their interactions, can benefit from the habitat change caused by human disturbance while more specialized interactions mostly disappear. Therefore, changes in the structure of the local, within fragment, networks can be expected. Here we investigated how the structure of seed dispersal networks changes along a gradient of increasing habitat fragmentation. We analyzed 16 bird seed dispersal assemblages from forest fragments of a biodiversity-rich ecosystem. We found significant species–, interaction–, and network–area relationships, yet the later was determined by the number of species remaining in each community. The number of frugivorous bird and plant species, their interactions, and the number of links per species decreases as area is lost in the fragmented landscape. In contrast, network nestedness has a negative relationship with fragment area, suggesting an increasing generalization of the network structure in the gradient of fragmentation. Network specialization was not significantly affected by area, indicating that some network properties may be invariant to disturbance. Still, the local extinction of partner species, paralleled by a loss of interactions and specialist–specialist bird–plant seed dispersal associations, suggests the functional homogenization of the system as area is lost. Our study provides empirical evidence for network–area relationships driven by the presence/absence of remnant species and the interactions they perform.     

High temporal and individual variation in the prevalence and intensity of chytrid infection in the southernmost Leaf Frog of the genus Pithecopus (Anura,Phyllomedusidae)

Hydrobiologia - Pithecopus rusticus is an endemic amphibian restricted to the type locality, in southern Brazil, and possibly endangered to extinction, due to habitat degradation. However, an...     

Trophic ecology and metabolism of two species of nonnative freshwater stingray (Chondrichthyes: Potamotrygonidae)

The stingrays Potamotrygon amandae and Potamotrygon falkneri are nonnative species established in the Upper Paraná basin. Although they are widely distributed, few studies on their diets or respective metabolic responses exist. Therefore, the aim was to evaluate the dietary composition, trophic niche breadth and lipid/protein concentrations in muscle and hepatic tissues of these two species, as well as the interrelationships between them. The individuals were collected in two areas on the Upper Paraná River. The stomachs and samples of muscle and liver tissues were taken for analysis. A broad dietary spectrum was observed for both species, along with differences in dietary composition, with a higher consumption of detritus by P. amandae and Baetidae by P. falkneri. No differences were observed in the trophic niche breadth. Regarding the metabolic variables, differences were only found in the hepatic protein, with a higher content observed in P. falkneri. A significant positive correlation was observed between items of animal origin and detritus with muscle protein for this species. This shows that such feeding habits, which are characteristic of a generalist, influenced the metabolism of the species and possibly contributed to the successful adjustment of the species to new habitats in the Upper Paraná River.