Pulmonary Macrophages Attenuate Hypoxic Pulmonary Vasoconstriction via beta(3)AR/iNOS Pathway in Rats Exposed to Chronic Intermittent Hypoxia

Chronic intermittent hypoxia (IH) induces activation of the sympathoadrenal system, which plays a pivotal role in attenuating hypoxic pulmonary vasoconstriction (HPV) via central beta(1)-adrenergic receptors (AR) (brain) and peripheral beta(2)AR (pulmonary arteries). Prolonged hypercatecholemia has been shown to upregulate beta(3)AR. However, the relationship between IH and beta(3)AR in the modification of HPV is unknown. It has been observed that chronic stimulation of beta(3)AR upregulates inducible nitric oxide synthase (iNOS) in cardiomyocytes and that IH exposure causes expression of iNOS in RAW264.7 macrophages. iNOS has been shown to have the ability to dilate pulmonary vessels. Hence, we hypothesized that chronic IH activates beta(3)AR/iNOS signaling in pulmonary macrophages, leading to the promotion of NO secretion and attenuated HPV. Sprague-Dawley rats were exposed to IH (3-min periods of 4-21% O-2) for 8 h/d for 6 weeks. The urinary catecholamine concentrations of IH rats were high compared with those of controls, indicating activation of the sympathoadrenal system following chronic IH. Interestingly, chronic IH induced the migration of circulating monocytes into the lungs and the predominant increase in the number of proinflammatory pulmonary macrophages. In these macrophages, both beta(3)AR and iNOS were upregulated and stimulation of the beta(3)AR/iNOS pathway in vitro caused them to promote NO secretion. Furthermore, in vivo synchrotron radiation microangiography showed that HPV was significantly attenuated in IH rats and the attenuated HPV was fully restored by blockade of beta(3)AR/iNOS pathway or depletion of pulmonary macrophages. These results suggest that circulating monocyte-derived pulmonary macrophages attenuate HPV via activation of beta(3)AR/iNOS signaling in chronic IH

Vapor-based polymer coatings for potential biomedical applications

Over the last decade, biology and biotechnology have witnessed an extraordinary development spanning genomics, proteomics, and metabolics. This progress was so rapid and definite that it not only changed the face of modern biology, but indeed altered the way day-to-day business is done in biology and related fields. This scientific advancement came with a need for concurrent technological advances. In this context, the ability to interface sophisticated devices with relevant biological microenvironments has emerged as a critical challenge. Already, novel biomaterials are on the horizon that promise to fulfill the rigid criteria of being both biocompatible under the conditions of a versatile range of biological applications and compatible with the increasing demands for miniaturization, integration, and throughput of future device architectures. As currently employed solvent-based polymer coatings are increasingly reaching their limits, a range of unconventional materials, such as vapor-based polymer coatings, are discussed as attractive alternatives. One of the main features of vapor-based polyreactions is their versatility in synthesizing both simple and complex polymers with relative ease and at generally low temperatures. The advantages of the chemical vapor deposition (CVD) technique also include control of the composition and architecture of the resulting materials, high accuracy, solvent-free environments, excellent adhesion, and the ability to accommodate custom-tailored surface modifications. For further illustration, selected examples of polymer-based surface engineering approaches using vapor-based polyreactions are discussed in this review. For instance, reactive coating technology uses CVD polymerization to deposit a wide range of chemically functionalized polymer coatings on various substrate materials. Its simplicity in providing chemically reactive groups and its applicability to three-dimensional geometries (e.g. for microfluidics) enables exact tailoring of surface properties and the preparation of biologically relevant microenvironments. CVD-based reactive coatings are compatible with soft lithographic processes allowing for patterning of proteins, DNA, cytokines, and mammalian cells. Copyright © 2006 Society of Chemical IndustryPeer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/55843/1/2098_ftp.pd

Subtype-specific gout susceptibility loci and enrichment of selection pressure on ABCG2 and ALDH2 identified by subtype genome-wide meta-analyses of clinically defined gout patients

Objectives Genome-wide meta-analyses of clinically defined gout were performed to identify subtype-specific susceptibility loci. Evaluation using selection pressure analysis with these loci was also conducted to investigate genetic risks characteristic of the Japanese population over the last 2000–3000 years. Methods Two genome-wide association studies (GWASs) of 3053 clinically defined gout cases and 4554 controls from Japanese males were performed using the Japonica Array and Illumina Array platforms. About 7.2 million single-nucleotide polymorphisms were meta-analysed after imputation. Patients were then divided into four clinical subtypes (the renal underexcretion type, renal overload type, combined type and normal type), and meta-analyses were conducted in the same manner. Selection pressure analyses using singleton density score were also performed on each subtype. Results In addition to the eight loci we reported previously, two novel loci, PIBF1 and ACSM2B, were identified at a genome-wide significance level (p<5.0×10–8) from a GWAS meta-analysis of all gout patients, and other two novel intergenic loci, CD2-PTGFRN and SLC28A3-NTRK2, from normal type gout patients. Subtype-dependent patterns of Manhattan plots were observed with subtype GWASs of gout patients, indicating that these subtype-specific loci suggest differences in pathophysiology along patients’ gout subtypes. Selection pressure analysis revealed significant enrichment of selection pressure on ABCG2 in addition to ALDH2 loci for all subtypes except for normal type gout. Conclusions Our findings on subtype GWAS meta-analyses and selection pressure analysis of gout will assist elucidation of the subtype-dependent molecular targets and evolutionary involvement among genotype, phenotype and subtype-specific tailor-made medicine/prevention of gout and hyperuricaemia

Role of Splice Variants of Gtf2i, a Transcription Factor Localizing at Postsynaptic Sites, and Its Relation to Neuropsychiatric Diseases

We previously reported that various mRNAs were associated with postsynaptic density (PSD) purified from rat forebrain. Among the thousands of PSD-associated mRNAs, we highlight the biology of the general transcription factor II-I (Gtf2i) mRNA, focusing on the significance of its versatile splicing for targeting its own mRNA into dendrites, regulation of translation, and the effects of Gtf2i expression level as well as its relationship with neuropsychiatric disorders

Bioelectrocatalytic endpoint assays based on steady-state diffusion current at microelectrode array

Highly reproducible bioelectrocatalytic endpoint assays are described. The method is based on a complete redox conversion of a substrate to a redox mediator with a corresponding redox enzyme and an amperometric detection of the reduced mediator on a diffusionally independent microelectrode array. The current reaches a steady state within a few seconds and is proportional to the number of the integrated microelectrodes. The method has successfully been applied to histamine detection at micro-molar level and glucose detection at milli-molar level