Stress and immune response in the mussel Mytilus galloprovincialis

The present study investigates the effects on immune-related parameters of various stress factors (air exposure, mechanical stress, high temperature and extreme salinity conditions) faced by the bivalve mollusc Mytilus galloprovincialis during marketing procedures. We observed that some stress typologies increase phagocytosis and the number of circulating immunocytes, while others can modify immunocyte response towards a further perturbation, i.e. the marine algal toxin yessotoxin. Our results suggest that non-lethal stress can be counteracted for sometime by increasing the level of some defence parameters. Moreover, our data indicate that fishing and transport procedures could interfere with mussel immunosurveillance.     

Identification of the best ovitrap installation sites for gravid Aedes (Stegomyia) aegypti in residences in Mirassol, state of São Paulo, Brazil

This study aimed at identifying the best ovitrap installation sites for gravid Aedes aegypti in Mirassol, state of S?o Paulo, Brazil. Ovitraps were installed in ten houses per block over ten blocks. Four ovitraps were placed per residence, one in the bedroom, one in the living room, and two outdoors with one in a sheltered area and one in an outside site. Each week for eleven weeks, visits were made to examine the ovitraps and to change the paddles used for egg-laying. Eggs were analyzed according to the trap location. The results showed that the outdoor sites received significantly more oviposition than indoor sites. Additionally, in respect to the outdoor sites, the outside site received significantly more oviposition than the sheltered site. A strong correlation was observed between positive traps and egg numbers. The results are discussed with respect to the best installation site of the traps and their implications in surveillance and control of dengue vectors.     

The effect of Enalapril on PGI(2) and NO levels in hypertensive patients

The effects of the angiotensin-converting enzyme inhibitors (ACEIs), may be partially mediated by the kinins' paracrine influence. Their actions may be exerted through nitric oxide and prostacyclin (PGI(2)) synthesis stimulation. The aim of our study was to determine whether the antihypertensive effect of Enalapril correlated with the increment in the plasmatic levels of NO and PGI(2) in essential moderate hypertensive patients. Normalization of blood pressure was observed in 20 patients, four on the 28th day, 15 on the 42th day and one on the 56th day. Enalapril-respondent subjects showed increased nitrate/nitrite levels on the 14th day (30% increment), on the 28th day (64%), on the 42th day (93.5%) and on the 56th day (96.2%) compared with basal levels, but they did not modify the circulating 6-keto PGF(1 alpha) levels. Four non-respondent patients showed a diminution in nitrate/nitrite and 6-keto PGF(1 alpha) circulating levels along the treatment. We conclude that the administration of 5-30 mg of Enalapril increases circulating NO metabolites in respondent-essential hypertensive subjects. The lack of responsiveness to the treatment may be related to the presence of risk factors such as those linked to an increase of oxidative stress. Finally, we consider that the evaluation of circulating NO may represent a predictive of the response to Enalapril in essential hypertensive patients.     

Effects of the marine toxins okadaic acid and palytoxin on mussel phagocytosis

The present study analyzes the effects of the marine toxins okadaic acid (OA) and palytoxin (PTX) on the phagocytic activity of immunocytes from the mussel Mytilus galloprovincialis. In particular, we describe how the effects of the two biotoxins are influenced by the temperature and experimental stress applied before hemolymph withdrawal. The collected data indicate that OA increases phagocytic activity only when hemolymph incubation is performed at 25 degrees C, but not at 20 degrees C, suggesting a certain degree of dependence of OA effects from the status of mussel immunocytes. Conversely, PTX plays an active role in immunocyte signalling transduction pathways, increases the phagocytic activity and markedly promotes the involvement of p38 mitogen-activated protein (MAP) kinase in phagocytosis. Overall, we conclude that both OA and PTX influence mussel phagocytic activity, and the toxic effects may depend on both the mollusc conditions and the activation of specific signalling pathways.     

Prioritizing CD4 Count Monitoring in Response to ART in Resource-Constrained Settings: A Retrospective Application of Prediction-Based Classification

Background

Global programs of anti-HIV treatment depend on sustained laboratory capacity to assess treatment initiation thresholds and treatment response over time. Currently, there is no valid alternative to CD4 count testing for monitoring immunologic responses to treatment, but laboratory cost and capacity limit access to CD4 testing in resource-constrained settings. Thus, methods to prioritize patients for CD4 count testing could improve treatment monitoring by optimizing resource allocation.

Methods and Findings

Using a prospective cohort of HIV-infected patients (n = 1,956) monitored upon antiretroviral therapy initiation in seven clinical sites with distinct geographical and socio-economic settings, we retrospectively apply a novel prediction-based classification (PBC) modeling method. The model uses repeatedly measured biomarkers (white blood cell count and lymphocyte percent) to predict CD4⁺ T cell outcome through first-stage modeling and subsequent classification based on clinically relevant thresholds (CD4⁺ T cell count of 200 or 350 cells/µl). The algorithm correctly classified 90% (cross-validation estimate = 91.5%, standard deviation [SD] = 4.5%) of CD4 count measurements <200 cells/µl in the first year of follow-up; if laboratory testing is applied only to patients predicted to be below the 200-cells/µl threshold, we estimate a potential savings of 54.3% (SD = 4.2%) in CD4 testing capacity. A capacity savings of 34% (SD = 3.9%) is predicted using a CD4 threshold of 350 cells/µl. Similar results were obtained over the 3 y of follow-up available (n = 619). Limitations include a need for future economic healthcare outcome analysis, a need for assessment of extensibility beyond the 3-y observation time, and the need to assign a false positive threshold.

Conclusions

Our results support the use of PBC modeling as a triage point at the laboratory, lessening the need for laboratory-based CD4⁺ T cell count testing; implementation of this tool could help optimize the use of laboratory resources, directing CD4 testing towards higher-risk patients. However, further prospective studies and economic analyses are needed to demonstrate that the PBC model can be effectively applied in clinical settings. Please see later in the article for the Editors'' Summary     

Maternal caregiving and DNA methylation in human infants and children: Systematic review

The integration of behavioral epigenetics' principles (eg, DNA methylation) into the study of human infants' development has mainly focused on the effects of early adverse exposures, paying less attention to protective caregiving experiences. The present review focused on DNA methylation linked to variations in maternal behavior in human infants and children. Literature search occurred on three databases (PubMed, Scopus and Web of Science) and 11 records were selected. Key variables were abstracted from each article including: sample size and characteristics, time and type of maternal caregiving behavior exposure, time and locus of methylation biomarker, presence/absence, time and type of adverse exposure. Six out of eleven records documented the predictive effect of maternal caregiving on DNA methylation, whereas the remaining five reported on the role of maternal behavior as an influencing factor of the adversity‐to‐methylation link. Consistent with evidence from the animal model, the quality of maternal caregiving in humans (a) might be associated with variations in DNA methylation status of specific genes involved in socio‐emotional development and (b) might partially buffer the association between early adversities and epigenetic variations in infants and children. Current evidence suggests that the quality of maternal caregiving can contribute to behavioral development trajectories of human infants and children at least partially through epigenetic regulation. Open questions and methodological aspects are discussed to guide future human developmental research in behavioral epigenetics.     

Arthrinium phaeospermum,Phoma cladoniicola and Ulocladium consortiale,New Olive Pathogens in Italy

In recent years, leaf necrosis and twig dieback in the olive crop have been detected in Sicily (Italy). In this article, we identify the predominant fungal species associated with symptomatic leaves and twigs, using morphological features and DNA sequencing of the internal transcribed spacer (ITS) region, as Alternaria alternata, Arthrinium phaeospermum, Phoma cladoniicola and Ulocladium consortiale. The pathogenicity of these four species was tested on olive plants cv. Biancolilla. All species were pathogenic on leaves, but only U. consortiale produced cortical lesions on twigs, thus suggesting its main role in the Olea europaea twig dieback. To our knowledge, this is the first report of A. phaeospermum, P. cladoniicola and U. consortiale as olive pathogens.     

Non Ionising Radiation as a Non Chemical Strategy in Regenerative Medicine: Ca2+-ICR “In Vitro” Effect on Neuronal Differentiation and Tumorigenicity Modulation in NT2 Cells

In regenerative medicine finding a new method for cell differentiation without pharmacological treatment or gene modification and minimal cell manipulation is a challenging goal. In this work we reported a neuronal induced differentiation and consequent reduction of tumorigenicity in NT2 human pluripotent embryonal carcinoma cells exposed to an extremely low frequency electromagnetic field (ELF-EMF), matching the cyclotron frequency corresponding to the charge/mass ratio of calcium ion (Ca²⁺-ICR). These cells, capable of differentiating into post-mitotic neurons following treatment with Retinoic Acid (RA), were placed in a solenoid and exposed for 5 weeks to Ca²⁺-ICR. The solenoid was installed in a μ-metal shielded room to avoid the effect of the geomagnetic field and obtained totally controlled and reproducible conditions. Contrast microscopy analysis reveled, in the NT2 exposed cells, an important change in shape and morphology with the outgrowth of neuritic-like structures together with a lower proliferation rate and metabolic activity alike those found in the RA treated cells. A significant up-regulation of early and late neuronal differentiation markers and a significant down-regulation of the transforming growth factor-α (TGF-α) and the fibroblast growth factor-4 (FGF-4) were also observed in the exposed cells. The decreased protein expression of the transforming gene Cripto-1 and the reduced capability of the exposed NT2 cells to form colonies in soft agar supported these last results. In conclusion, our findings demonstrate that the Ca²⁺-ICR frequency is able to induce differentiation and reduction of tumorigenicity in NT2 exposed cells suggesting a new potential therapeutic use in regenerative medicine.