Endothelial dysfunction in aged humans is related with oxidative stress and vascular inflammation

Vascular endothelial dysfunction occurs during the human aging process, and it is considered as a crucial event in the development of many vasculopathies. We investigated the underlying mechanisms of this process, particularly those related with oxidative stress and inflammation, in the vasculature of subjects aged 18–91 years without cardiovascular disease or risk factors. In isolated mesenteric microvessels from these subjects, an age‐dependent impairment of the endothelium‐dependent relaxations to bradykinin was observed. Similar results were observed by plethysmography in the forearm blood flow in response to acetylcholine. In microvessels from subjects aged less than 60 years, most of the bradykinin‐induced relaxation was due to nitric oxide release while the rest was sensitive to cyclooxygenase (COX) blockade. In microvessels from subjects older than 60 years, this COX‐derived vasodilatation was lost but a COX‐derived vasoconstriction occurred. Evidence for age‐related vascular oxidant and inflammatory environment was observed, which could be related to the development of endothelial dysfunction. Indeed, aged microvessels showed superoxide anions (O₂^?) and peroxynitrite (ONOO^?) formation, enhancement of NADPH oxidase and inducible NO synthase expression. Pharmacological interference of COX, thromboxane A₂/prostaglandin H₂ receptor, O₂^?, ONOO^?, inducible NO synthase, and NADPH oxidase improved the age‐related endothelial dysfunction. In situ vascular nuclear factor‐κB activation was enhanced with age, which correlated with endothelial dysfunction. We conclude that the age‐dependent endothelial dysfunction in human vessels is due to the combined effect of oxidative stress and vascular wall inflammation.     

Graphene-Based Plasmonic Waveguides: a Mini Review

Plasmonics - Graphene plasmonics is one of the most explored fields since the successful experimental discovery of the graphene due to its unprecedented properties. The dynamical modulation and...     

Role of protein kinases in mediating diabetes-induced augmented vasoconstriction to endothelin-1 in the renal arteries of STZ-diabetic rats

Diabetes is associated with increased reactivity of the renal vascular bed to endothelin-1 (ET-1). It has been observed that diabetes is associated with over-expression of ET(A)- and ET(B)-receptors in the rat renal cortex. However it is not known if these receptors are over-expressed in the renal artery. The objectives of this study were to determine changes in ET-1 receptors and signalling pathways in diabetic renal arteries, to determine the relative roles of protein kinase C and tyrosine kinase activation in mediating these responses and to investigate the role of Rho-kinase activity in mediating the vasoconstrictor responses to ET-1. This study was performed on isolated renal artery segments obtained from STZ-diabetic rats. Results from this study showed that the vasoconstrictor response to ET-1 was potentiated in the diabetic renal artery segments compared to the control animals. Using selective ET-1 receptor antagonists, BQ123 and BQ788, the enhanced ET-1-induced vasoconstriction was shown in this study not to be related to changes in receptor affiinity or receptor subtype distribution. However, the augmented vasoconstrictor response to ET-1 in the diabetic renal artery preparations may be related to increased influx of Ca(2+) through L-type channels and also to increased tyrosine kinase activity.     

β2-Adrenergic receptor polymorphisms: pharmacogenetic response to bronchodilator among African American asthmatics

Beta2-adrenergic receptor (beta2AR) gene polymorphisms have been reported to be associated with various asthma-related traits in different racial/ethnic populations. However, it is unknown whether beta2AR genetic variants are associated with asthma in African Americans. In this study, we have examined whether there is association between beta2AR genetic variants and asthma in African Americans. We have recruited 264 African American asthmatic subjects and 176 matched healthy controls participating in the Study of African Americans, Asthma, Genes and Environments (SAGE). We genotyped seven known and recently identified beta2AR SNP variants, then tested genotype and haplotype association of asthma-related traits with the beta2AR SNPs in our African American cohort with adjustment of confounding effect due to admixture background and environmental risk factors. We found a significant association of the SNP -47 (Arg-19Cys) polymorphism with DeltaFEF(25-75), a measure of bronchodilator drug responsiveness, in African American asthmatics after correction for multiple testing (P = 0.001). We did not observe association of the SNP +46 (Arg16Gly) variant with asthma disease diagnosis and asthma-related phenotypes. In contrast to previous results between the Arg16Gly variant and traits related to bronchodilator responsiveness, our results indicate that the Arg-19Cys polymorphism in beta upstream peptide may play an important role in bronchodilator drug responsiveness in African American subjects. Our findings highlight the importance of investigating genetic risk factors for asthma in different populations.     

FGF negatively regulates muscle membrane extension in Caenorhabditis elegans

Striated muscles from Drosophila and several vertebrates extend plasma membrane to facilitate the formation of the neuromuscular junction (NMJ) during development. However, the regulation of these membrane extensions is poorly understood. In C. elegans, the body wall muscles (BWMs) also have plasma membrane extensions called muscle arms that are guided to the motor axons where they form the postsynaptic element of the NMJ. To investigate the regulation of muscle membrane extension, we screened 871 genes by RNAi for ectopic muscle membrane extensions (EMEs) in C. elegans. We discovered that an FGF pathway, including let-756(FGF), egl-15(FGF receptor), sem-5(GRB2) and other genes negatively regulates plasma membrane extension from muscles. Although compromised FGF pathway activity results in EMEs, hyperactivity of the pathway disrupts larval muscle arm extension, a phenotype we call muscle arm extension defective or MAD. We show that expression of egl-15 and sem-5 in the BWMs are each necessary and sufficient to prevent EMEs. Furthermore, we demonstrate that let-756 expression from any one of several tissues can rescue the EMEs of let-756 mutants, suggesting that LET-756 does not guide muscle membrane extensions. Our screen also revealed that loss-of-function in laminin and integrin components results in both MADs and EMEs, the latter of which are suppressed by hyperactive FGF signaling. Our data are consistent with a model in which integrins and laminins are needed for directed muscle arm extension to the nerve cords, while FGF signaling provides a general mechanism to regulate muscle membrane extension.     

Experimental reconsideration of the utility of serum starvation as a method for synchronizing mammalian cells

Accurate cell-size determinations support the prediction that serum starvation and related whole-culture methods cannot synchronize cells. Theoretical considerations predict that whole-culture methods of synchronization cannot synchronize cells. Upon serum starvation, the fraction of cells with a G1-phase amount of DNA increased, but the cell-size distribution is not narrowed. In true synchronization, the cell-size distribution should be narrower than the cell-size distribution of the original culture. In contrast, cells produced by a selective (i.e. non-whole-culture) method have a specific DNA content, a narrow size distribution, and divide synchronously. The general theory leading to the conclusion that whole-culture methods for synchronization do not work implies that one can generalize these serum-starvation results to other cell lines and other whole-culture methods, to conclude that these methods do not synchronize cells.     

In vitro regeneration and morphogenesis studies in common bean

An efficient protocol for high frequency in vitro regeneration of multiple shoots and somatic embryos from the embryonic axis of common bean (Phaseolus vulgaris) was developed. Ten common bean cultivars representing a wide range of diversity among current commercial market classes were used for in vitro regeneration evaluation in our study. These cultivars were tested on 63 different media formulations consisting of combinations of cytokinins, namely benzyladenine (BA) and thidiazuron (TDZ) at concentration levels of 0.0, 1.0, 2.5, 5.0 and 10.0 mg l⁻¹ and auxin, namely naphthalene acetic acid (NAA) and indole-3-acetic acid (IAA) at concentration levels of 0.0, 0.05, 0.1 and 1.0 mg l⁻¹. P. vulgaris cv. Olathe pinto bean performed the best producing over 20 multiple shoots per explant while cv. Condor black bean was the poorest with nine multiple shoots per explant. The optimum media for regeneration of multiple shoots was 4.4 mg l⁻¹ Murashige and Skoog (MS) containing 2.5 mg l⁻¹ BA and 0.1 mg l⁻¹ IAA supplemented with 30 mg l⁻¹ silver nitrate. Adventitious shoots and somatic embryos were regenerated on 4.4 mg l⁻¹ MS medium containing 1 mg l⁻¹ TDZ and 0.05 mg l⁻¹ NAA supplemented with 30 mg l⁻¹ silver nitrate or activated charcoal. Efficient and effective rooting of plantlets was achieved by dipping the cut end base of in vitro regenerated shoots in 1.0 mg l⁻¹ indole-3-butyric acid (IBA) solution and culturing on media containing 4.4 mg l⁻¹ MS supplemented by 0.1 mg l⁻¹ IAA, NAA or IBA.