Antioxidants preserve macrophage phagocytosis of Pseudomonas aeruginosa during hyperoxia

Pseudomonas. aeruginosa (PA) is a leading cause of nosocomial pneumonia in patients receiving mechanical ventilation with hyperoxia. Exposure to supraphysiological concentrations of reactive oxygen species during hyperoxia may result in macrophage damage that reduces their ability to phagocytose PA. We tested this hypothesis in cultured macrophage-like RAW 264.7 cells and alveolar macrophages from mice exposed to hyperoxia. Exposure to hyperoxia induced a similarly impaired phagocytosis of both the mucoid and the nonmucoid forms of PA in alveolar macrophages and RAW cells. Compromised PA phagocytosis was associated with cytoskeleton disorganization and actin oxidation in hyperoxic macrophages. To test whether moderate concentrations of O(2) limit the loss of phagocytic function induced by > or =95% O(2), mice and RAW cells were exposed to 65% O(2). Interestingly, although the resulting lung injury/cell proliferation was not significant, exposure to 65% O(2) resulted in a marked reduction in PA phagocytosis that was comparable to that of > or =95% O(2). Treatment with antioxidants, even post hyperoxic exposure, preserved actin cytoskeleton organization and phagocytosis of PA. These data suggest that hyperoxia reduces macrophage phagocytosis through effects on actin functions which can be preserved by antioxidant treatment. In addition, administration of moderate rather than higher concentrations of O2 does not improve macrophage phagocytosis of PA.     

A defect in the ionotropic glutamate receptor 6 gene (GRIK2) is associated with autosomal recessive mental retardation

Nonsyndromic mental retardation is one of the most important unresolved problems in genetic health care. Autosomal forms are far more common than X-linked forms, but, in contrast to the latter, they are still largely unexplored. Here, we report a complex mutation in the ionotropic glutamate receptor 6 gene (GRIK2, also called “GLUR6”) that cosegregates with moderate-to-severe nonsyndromic autosomal recessive mental retardation in a large, consanguineous Iranian family. The predicted gene product lacks the first ligand-binding domain, the adjacent transmembrane domain, and the putative pore loop, suggesting a complete loss of function of the GLU_K6 protein, which is supported by electrophysiological data. This finding provides the first proof that GLU_K6 is indispensable for higher brain functions in humans, and future studies of this and other ionotropic kainate receptors will shed more light on the pathophysiology of mental retardation.     

Sympatric morphotypes of the restricted-range Tashan Cave Garra: distinct species or a case of phenotypic plasticity?

Environmental Biology of Fishes - Among Tashan cave barb Garra tashanensis inhabiting a small cave in southwest Iran, two mental disc (sucking mouth disc) forms were observed. To assess their...     

Young Plasma Induces Antidepressant-Like Effects in Aged Rats Subjected to Chronic Mild Stress by Suppressing Indoleamine 2,3-Dioxygenase Enzyme and Kynurenine Pathway in the Prefrontal Cortex

Pathophysiology of depression in elderlies is linked to aging-associated increase in indoleamine 2,3-dioxygenase (IDO) levels and activity and kynurenine (Kyn) metabolites. Moreover, these aging-induced changes may alter the brain’s responses to stress. Growing evidence suggested that young plasma can positively affect brain dysfunctions in old age. The present study aimed to investigate whether the antidepressant effects of young plasma administration in aged rats subjected to chronic unpredictable mild stress (CUMS) and underlying mechanisms, focusing on the prefrontal cortex (PFC). Young (3 months old) and aged (22 months old) male rats were divided into five groups; young control, aged control, aged rats subjected to CUMS (A?+?CUMS), aged rats subjected to CUMS and treated with young plasma (A?+?CUMS?+?YP), and aged rats subjected to CUMS and treated with old plasma (A?+?CUMS?+?OP). Plasma was injected (1 ml, intravenously) three times per week for four weeks. Young plasma significantly improved CUMS-induced depressive-like behaviors, evidenced by the increased sucrose consumption ratio in the sucrose preference test and the reduced immobility time in the forced swimming test. Furthermore, young plasma markedly reduced the levels of interferon-gamma (IFN-γ), IDO, Kyn, and Kyn to tryptophan (Kyn/Trp) ratio in PFC tissue. Expression levels of the serotonin transporter and growth-associated protein (GAP)-43 were also significantly increased after chronic administration of young plasma. These findings provide evidence for the antidepressant effect of young plasma in old age; however, whether it improves depressive behaviors or faster recovery from stress-induced deficits is required to be elucidated.

     

Relationship between serum high sensitivity C-reactive protein with angiographic severity of coronary artery disease and traditional cardiovascular risk factors

Serum high-sensitivity C-reactive protein (hs-CRP) is predictive of coronary artery disease (CAD). The aim of this study was to examine the possible association of hs-CRP with presence and severity of CAD and traditional CAD risk factors. This case-control study was carried out on 2,346 individuals from September 2011 to May 2013. Of these 1,187 had evidence of coronary disease, and were subject to coronary angiography, and the remainder were healthy controls (n = 1,159). Characteristics were determined using standard laboratory techniques and serum Hs-CRP levels were estimated using enzyme-linked immunosorbent assay (ELISA) kits, and severity of CAD was assessed according to the score of obstruction in coronary artery. Serum hs-CRP levels were higher in those with severe coronary disease, who had stenosis ≥ 50% stenosis of at least one coronary artery (all p < 0.001 vs. individuals in healthy control), and correlated significantly with the score for coronary artery disease (all p < 0.01). After adjustment for conventional risk factors, regression analysis revealed that smoking habits, fasting blood glucose, total cholesterol, high-density lipoprotein, hs-CRP, blood pressure, anxiety, dietary intake of vitamin E, and cholesterol remained as independent determinants for angiographic severity of CAD. The area under the receiving operating characteristic (ROC) curve for serum hs-CRP was 0.869 (CI 95% 0.721–0.872, p < 0.001). The optimal values for the cut-off point was a serum hs-CRP of 2.78 mg/l (sensitivity 80.20%, specificity 85%) to predict severity of CAD. Increased serum hs-CRP levels are significantly associated with angiographic severity of CAD, suggesting its value as a biomarkers for predicting CAD.     

Health Risk Assessment for Human Exposure to Trace Metals and Arsenic via Consumption of Hen Egg Collected from Largest Poultry Industry in Iran

Biological Trace Element Research - The relative contribution of foodstuffs to intake of heavy metal is still equivocal, and thus, available data are rare. Here, the concentration of ten heavy...     

Designing of a Functional Chimeric Protein for Production of Nanobodies Against Human CD20: Molecular Dynamics Simulation and In Vitro Verification

International Journal of Peptide Research and Therapeutics - One major issue in cancer immunotherapy is the large size of mAbs (150&nbsp;kDa) which usually causes limitation in tumor...     

Production of Novel Camelid Anti-CXCL10 Specific Polyclonal Antibodies and Evaluation of Their Bioreactivity

International Journal of Peptide Research and Therapeutics - CXCL10 chemokine is a member of CXC chemokine family. It is secreted from a variety of cells in response to IFN-γ and stimulates a...     

Chilling and forcing temperatures interact to predict the onset of wood formation in Northern Hemisphere conifers

The phenology of wood formation is a critical process to consider for predicting how trees from the temperate and boreal zones may react to climate change. Compared to leaf phenology, however, the determinism of wood phenology is still poorly known. Here, we compared for the first time three alternative ecophysiological model classes (threshold models, heat‐sum models and chilling‐influenced heat‐sum models) and an empirical model in their ability to predict the starting date of xylem cell enlargement in spring, for four major Northern Hemisphere conifers (Larix decidua, Pinus sylvestris, Picea abies and Picea mariana). We fitted models with Bayesian inference to wood phenological data collected for 220 site‐years over Europe and Canada. The chilling‐influenced heat‐sum model received most support for all the four studied species, predicting validation data with a 7.7‐day error, which is within one day of the observed data resolution. We conclude that both chilling and forcing temperatures determine the onset of wood formation in Northern Hemisphere conifers. Importantly, the chilling‐influenced heat‐sum model showed virtually no spatial bias whichever the species, despite the large environmental gradients considered. This suggests that the spring onset of wood formation is far less affected by local adaptation than by environmentally driven plasticity. In a context of climate change, we therefore expect rising winter–spring temperature to exert ambivalent effects on the spring onset of wood formation, tending to hasten it through the accumulation of forcing temperature, but imposing a higher forcing temperature requirement through the lower accumulation of chilling.