Canine mesenteric artery and vein convey no difference in the content of major contractile proteins

BACKGROUND: Mesenteric arteries and veins are composed of tonic smooth muscles and serve distinct functions in the peripheral circulation. However, the basis for the functional disparity of the resistive and capacitative parts of the mesenteric circulation is poorly understood. We studied potential differences in the expression levels of six contractile proteins in secondary and tertiary branches of the inferior mesenteric artery and vein along with differences in the vessel wall morphology. RESULTS: Bright field and electron microscopy showed that both vessel walls had the same major structural elements. The arterial walls, however, had greater number, and more tightly assembled, smooth muscle cell layers compared to vein walls. The content of actin, myosin heavy chain, myosin light chain, and calponin was similar in the two blood vessels. The artery expressed higher amount of the actin-binding protein caldesmon than the vein (41.86 ± 2.33 and 30.13 ± 3.37 μg/mg respectively, n = 12). Although the total tropomyosin content was almost identical in both blood vessels, the alpha isoform dominated in the artery, while the beta isoform prevailed in the vein. CONCLUSIONS: Canine mesenteric artery and vein differ in vessel wall morphology but do not convey differences in the expression levels of actin, myosin light chain, myosin heavy chain and calponin. The two vascular networks express distinct amounts of caldesmon and tropomyosin, which might contribute to the fine tuning of the contractile machinery in a manner consistent with the physiological functions of the two vascular networks

Proposal for a low cost close air support aircraft for the year 2000: The Raptor

The Raptor is a proposed low cost Close Air Support (CAS) aircraft for the U.S. Military. The Raptor incorporates a 'cranked arrow' wing planform, and uses canards instead of a traditional horizontal tail. The Raptor is designed to be capable of responsive delivery of effective ordnance in close proximity to friendly ground forces during the day, night, and 'under the weather' conditions. Details are presented of the Raptor's mission, configuration, performance, stability and control, ground support, manufacturing, and overall cost to permit engineering evaluation of the proposed design. A description of the design process and analysis methods used is also provided

Differential gene expression in the murine gastric fundus lacking interstitial cells of Cajal.

BACKGROUND: The muscle layers of murine gastric fundus have no interstitial cells of Cajal at the level of the myenteric plexus and only possess intramuscular interstitial cells and this tissue does not generate electric slow waves. The absence of intramuscular interstitial cells in W/WV mutants provides a unique opportunity to study the molecular changes that are associated with the loss of these intercalating cells. METHOD: The gene expression profile of the gastric fundus of wild type and W/WV mice was assayed by murine microarray analysis displaying a total of 8734 elements. Queried genes from the microarray analysis were confirmed by semi-quantitative reverse transcription-polymerase chain reaction. RESULTS: Twenty-one genes were differentially expressed in wild type and W/WV mice. Eleven transcripts had 2.0-2.5 fold higher mRNA expression in W/WV gastric fundus when compared to wild type tissues. Ten transcripts had 2.1-3.9 fold lower expression in W/WV mutants in comparison with wild type animals. None of these genes have ever been implicated in any bowel motility function. CONCLUSIONS: These data provides evidence that several important genes have significantly changed in the murine fundus of W/WV mutants that lack intramuscular interstitial cells of Cajal and have reduced enteric motor neurotransmission

Differential gene expression profile in the small intestines of mice lacking pacemaker interstitial cells of Cajal.

BACKGROUND: We previously identified eight known and novel genes differentially expressed in the small intestines of wild type and W/WV mice, which have greatly reduced populations of the interstitial cells of Cajal, that are responsible for the generation of electrical slow waves, by using a differential gene display method. METHODS: By using the same method we isolated additional candidate genes that were specifically down- or up-regulated in W/WV mice. Novel transcripts were designated as DDWMEST. RESULTS: We isolated seven candidates that were specifically down- or up-regulated in W/WV mice. Two novel transcripts, DDWMEST 1 and -91 were increased in both fed and fasted W/WV mice. Expression of another five genes was suppressed in W/WV mice: ARG2 (Arginase II), ONZIN (encoding leukemia inhibitory factor regulated protein), and three novel transcripts: DDWMEST62, -84, and -100. Together with the previous report, we identified fifteen differentially expressed genes in total in the small intestines of W/WV mice. Eight of these genes were reduced in the jejunums of W/WV mice compared to age matched wild type mice, whereas the other seven genes showed an increase in expression. Differential expression was the same in fasted and fed animals, suggesting that the differences were independent of the dietetic state of the animal. CONCLUSIONS: Several known and novel genes are differentially expressed in the small intestines of W/WV mice. Differential gene comparison might contribute to our understanding of motility disorders associated with the loss of the interstitial cells of Cajal.RIGHTS : This article is licensed under the BioMed Central licence at http://www.biomedcentral.com/about/license which is similar to the 'Creative Commons Attribution Licence'. In brief you may : copy, distribute, and display the work; make derivative works; or make commercial use of the work - under the following conditions: the original author must be given credit; for any reuse or distribution, it must be made clear to others what the license terms of this work are

Active peer-mentored learning can improve student understanding of physiological concepts in an undergraduate journal club

One of the most ubiquitous active learning modalities in the biological sciences at third level is the journal club. Journal club can promote several beneficial learning outcomes for students such as gaining critical reading skills to evaluate the scientific literature, improving scientific literacy, serving as an introduction to new concepts and techniques and improving communication skills. However, it can be difficult for instructors who facilitate journal club to gauge student audiences' understanding of topics being related by presenters. At the University of Nevada, Reno School of Medicine, international life sciences undergraduate students enrolled in our research program undergo a 12-month placement in selected research laboratories within the medical school in order to develop an understanding of basic medical scientific research and physiological concepts. As such, an integral component of this program is participation in regular journal club sessions which we had assumed helped students to develop such an understanding. However as we had never empirically assessed if this was the case or not, the aim of the current study was to determine if student understanding could be improved by complementing the standard journal club with peer-mentored workshop presentations. Data from this case study suggest that by allowing students to undergo peer-mentored learning in conjunction with journal club, student understanding of physiological concepts, as well as student confidence in presenting and communication, increases

Genomic Reconstruction of an Uncultured Hydrothermal Vent Gammaproteobacterial Methanotroph (Family Methylothermaceae) Indicates Multiple Adaptations to Oxygen Limitation

Hydrothermal vents are an important contributor to marine biogeochemistry, producing large volumes of reduced fluids, gasses, and metals and housing unique, productive microbial and animal communities fueled by chemosynthesis. Methane is a common constituent of hydrothermal vent fluid and is frequently consumed at vent sites by methanotrophic bacteria that serve to control escape of this greenhouse gas into the atmosphere. Despite their ecological and geochemical importance, little is known about the ecophysiology of uncultured hydrothermal vent-associated methanotrophic bacteria. Using metagenomic binning techniques, we recovered and analyzed a near-complete genome from a novel gammaproteobacterial methanotroph (B42) associated with a white smoker chimney in the Southern Lau basin. B42 was the dominant methanotroph in the community, at ∼80x coverage, with only four others detected in the metagenome, all on low coverage contigs (7x–12x). Phylogenetic placement of B42 showed it is a member of the Methylothermaceae, a family currently represented by only one sequenced genome. Metabolic inferences based on the presence of known pathways in the genome showed that B42 possesses a branched respiratory chain with A- and B-family heme copper oxidases, cytochrome bd oxidase and a partial denitrification pathway. These genes could allow B42 to respire over a wide range of oxygen concentrations within the highly dynamic vent environment. Phylogenies of the denitrification genes revealed they are the result of separate horizontal gene transfer from other Proteobacteria and suggest that denitrification is a selective advantage in conditions where extremely low oxygen concentrations require all oxygen to be used for methane activation

Mining Public Domain Data to Develop Selective DYRK1A Inhibitors

Kinases represent one of the most intensively pursued groups of targets in modern-day drug discovery. Often it is desirable to achieve selective inhibition of the kinase of interest over the remaining ∼500 kinases in the human kinome. This is especially true when inhibitors are intended to be used to study the biology of the target of interest. We present a pipeline of open-source software that analyzes public domain data to repurpose compounds that have been used in previous kinase inhibitor development projects. We define the dual-specificity tyrosine-regulated kinase 1A (DYRK1A) as the kinase of interest, and by addition of a single methyl group to the chosen starting point we remove glycogen synthase kinase β (GSK3β) and cyclin-dependent kinase (CDK) inhibition. Thus, in an efficient manner we repurpose a GSK3β/CDK chemotype to deliver 8b, a highly selective DYRK1A inhibitor