Immunolocalization of KATP channel subunits in mouse and rat cardiac myocytes and the coronary vasculature.

BACKGROUND: Electrophysiological data suggest that cardiac KATP channels consist of Kir6.2 and SUR2A subunits, but the distribution of these (and other KATP channel subunits) is poorly defined. We examined the localization of each of the KATP channel subunits in the mouse and rat heart. RESULTS: Immunohistochemistry of cardiac cryosections demonstrate Kir6.1 protein to be expressed in ventricular myocytes, as well as in the smooth muscle and endothelial cells of coronary resistance vessels. Endothelial capillaries also stained positive for Kir6.1 protein. Kir6.2 protein expression was found predominantly in ventricular myocytes and also in endothelial cells, but not in smooth muscle cells. SUR1 subunits are strongly expressed at the sarcolemmal surface of ventricular myocytes (but not in the coronary vasculature), whereas SUR2 protein was found to be localized predominantly in cardiac myocytes and coronary vessels (mostly in smaller vessels). Immunocytochemistry of isolated ventricular myocytes shows co-localization of Kir6.2 and SUR2 proteins in a striated sarcomeric pattern, suggesting t-tubular expression of these proteins. Both Kir6.1 and SUR1 subunits were found to express strongly at the sarcolemma. The role(s) of these subunits in cardiomyocytes remain to be defined and may require a reassessment of the molecular nature of ventricular KATP channels. CONCLUSIONS: Collectively, our data demonstrate unique cellular and subcellular KATP channel subunit expression patterns in the heart. These results suggest distinct roles for KATP channel subunits in diverse cardiac structures

Glycosidase activity in the excretory-secretory products of the liver fluke, Fasciola hepatica

Fasciola hepatica secretes proteolytic enzymes and other molecules that are essential for host penetration and migration. This mixture may include enzymes required for the degradation of supramucosal gels, which defend epithelial surfaces against pathogen entry. These contain hydrated mucins that are heavily glycosylated. Excretory-secretory products (ES) from F. hepatica were examined for a range of glycosidase activities, using synthetic 4-methylumbelliferyl glycosides as substrates. The ES product contained at least 8 different glycosidase activities, the most abundant of which were β-N- acetylhexosaminidase, β-galactosidase and β-glucosidase. Alpha-fucosidase, β-glucuronidase, α-galactosidase, α-mannosidase and neuraminidase were also present. β-N- acetylhexosaminidase and β-galactosidase were present in multiple isoforms (at least 4), whereas β-glucosidase appeared to exist as one isoenzyme with a pI <3.8. All three enzymes had acidic pH optima (4.5-5.0). Ovine small intestinal mucin was degraded by ES at pH 4.5 or 7.0, with or without active cathepsin L, the major protease found in F. hepatica ES. The ability of F. hepatica ES to degrade mucin in the presence or absence of active cathepsin L suggests that cathepsin L is not essential for mucin degradation. The abundance of β-galactosidase and β-hexosaminidase in ES supports a role for these enzymes in mucin degradation

Melaena with Peutz-Jeghers syndrome: a case report

Introduction: Peutz-Jeghers syndrome (PJS) is a rare familial disorder characterised by mucocutaneous pigmentation, gastrointestinal and extragastrointestinal hamartomatous polyps and an increased risk of malignancy. Peutz-Jeghers polyps in the bowel may result in intussusception. This complication usually manifests with abdominal pain and signs of intestinal obstruction. Case Presentation: We report the case of a 24-year-old Caucasian male who presented with melaena. Pigmentation of the buccal mucosa was noted but he was pain-free and examination of the abdomen was unremarkable. Upper gastrointestinal endoscopy revealed multiple polyps. An urgent abdominal computed tomography (CT) scan revealed multiple small bowel intussusceptions. Laparotomy was undertaken on our patient, reducing the intussusceptions and removing the polyps by enterotomies. Bowel resection was not needed. Conclusion: Melaena in PJS needs to be urgently investigated through a CT scan even in the absence of abdominal pain and when clinical examination of the abdomen shows normal findings. Although rare, the underlying cause could be intussusception, which if missed could result in grave consequences

18S rRNA processing requires base pairings of snR30 H/ACA snoRNA to eukaryote-specific 18S sequences

The H/ACA RNAs represent an abundant, evolutionarily conserved and functionally diverse class of non-coding RNAs. Many H/ACA RNAs direct pseudouridylation of rRNAs and snRNAs, while members of the rapidly growing group of ‘orphan' H/ACA RNAs participate in pre-rRNA processing, telomere synthesis and probably, in other nuclear processes. The yeast snR30 ‘orphan' H/ACA snoRNA has long been known to function in the nucleolytic processing of 18S rRNA, but its molecular role remained unknown. Here, we provide biochemical and genetic evidence demonstrating that during pre-rRNA processing, two evolutionarily conserved sequence elements in the 3′-hairpin of snR30 base-pair with short pre-rRNA sequences located in the eukaryote-specific internal region of 18S rRNA. The newly discovered snR30-18S base-pairing interactions are essential for 18S rRNA production and they constitute a complex snoRNA target RNA transient structure that is novel to H/ACA RNAs. We also demonstrate that besides the 18S recognition motifs, the distal part of the 3′-hairpin of snR30 contains an additional snoRNA element that is essential for 18S rRNA processing and that functions most likely as a snoRNP protein-binding site

Changes in Treatment Content of Services During Trauma-informed Integrated Services for Women with Co-occurring Disorders

The experience of trauma is highly prevalent in the lives of women with mental health and substance abuse problems. We examined how an intervention targeted to provide trauma-informed integrated services in the treatment of co-occurring disorders has changed the content of services reported by clients. We found that the intervention led to an increased provision of integrated services as well as services addressing each content area: trauma, mental health and substance abuse. There was no increase in service quantity from the intervention. Incorporation of trauma-specific element in the treatment of mental health and substance abuse may have been successfully implemented at the service level thereby better serve women with complex behavioral health histories

Integrity of H1 helix in prion protein revealed by molecular dynamic simulations to be especially vulnerable to changes in the relative orientation of H1 and its S1 flank

In the template-assistance model, normal prion protein (PrPC), the pathogenic cause of prion diseases such as Creutzfeldt-Jakob (CJD) in human, Bovine Spongiform Encephalopathy (BSE) in cow, and scrapie in sheep, converts to infectious prion (PrPSc) through an autocatalytic process triggered by a transient interaction between PrPC and PrPSc. Conventional studies suggest the S1-H1-S2 region in PrPC to be the template of S1-S2 $\beta$-sheet in PrPSc, and the conformational conversion of PrPC into PrPSc may involve an unfolding of H1 in PrPC and its refolding into the $\beta$-sheet in PrPSc. Here we conduct a series of simulation experiments to test the idea of transient interaction of the template-assistance model. We find that the integrity of H1 in PrPC is vulnerable to a transient interaction that alters the native dihedral angles at residue Asn$^{143}$, which connects the S1 flank to H1, but not to interactions that alter the internal structure of the S1 flank, nor to those that alter the relative orientation between H1 and the S2 flank.Comment: A major revision on statistical analysis method has been made. The paper now has 23 pages, 11 figures. This work was presented at 2006 APS March meeting session K29.0004 at Baltimore, MD, USA 3/13-17, 2006. This paper has been accepted for pubcliation in European Biophysical Journal on Feb 2, 200

Dark Force Detection in Low Energy e-p Collisions

We study the prospects for detecting a light boson X with mass m_X < 100 MeV at a low energy electron-proton collider. We focus on the case where X dominantly decays to e+ e- as motivated by recent "dark force" models. In order to evade direct and indirect constraints, X must have small couplings to the standard model (alpha_X 10 MeV). By comparing the signal and background cross sections for the e- p e+ e- final state, we conclude that dark force detection requires an integrated luminosity of around 1 inverse attobarn, achievable with a forthcoming JLab proposal.Comment: 38 pages, 19 figures; v2, references adde

Influence of Different Plant Species on Methane Emissions from Soil in a Restored Swiss Wetland

Plants are a major factor influencing methane emissions from wetlands, along with environmental parameters such as water table, temperature, pH, nutrients and soil carbon substrate. We conducted a field experiment to study how different plant species influence methane emissions from a wetland in Switzerland. The top 0.5 m of soil at this site had been removed five years earlier, leaving a substrate with very low methanogenic activity. We found a sixfold difference among plant species in their effect on methane emission rates: Molinia caerulea and Lysimachia vulgaris caused low emission rates, whereas Senecio paludosus, Carex flava, Juncus effusus and Typha latifolia caused relatively high rates. Centaurea jacea, Iris sibirica, and Carex davalliana caused intermediate rates. However, we found no effect of either plant biomass or plant functional groups – based on life form or productivity of the habitat – upon methane emission. Emissions were much lower than those usually reported in temperate wetlands, which we attribute to reduced concentrations of labile carbon following topsoil removal. Thus, unlike most wetland sites, methane production in this site was probably fuelled chiefly by root exudation from living plants and from root decay. We conclude that in most wetlands, where concentrations of labile carbon are much higher, these sources account for only a small proportion of the methane emitted. Our study confirms that plant species composition does influence methane emission from wetlands, and should be considered when developing measures to mitigate the greenhouse gas emissions

Effect of cross exercise on quadriceps acceleration reaction time and subjective scores (Lysholm questionnaire) following anterior cruciate ligament reconstruction

Abstract Background Anterior cruciate ligament (ACL) injury or reconstruction can cause knee impairments and disability. Knee impairments are related to quadriceps performance – accelerated reaction time (ART) – and disability to performance of daily living activities which is assessed by questionnaires such as the Lysholm knee score. The purposes of this study were to investigate the effect of cross exercise, as supplementary rehabilitation to the early phase of ACL reconstruction: a) on quadriceps ART at the angles 45°, 60° and 90° of knee flexion and, b) on the subjective scores of disability in ACL reconstructed patients. Methods 42 patients who underwent ACL reconstruction were randomly divided into 3 groups, two experimental and one control. All groups followed the same rehabilitation program. The experimental groups followed 8 weeks of cross eccentric exercise (CEE) on the uninjured knee; 3 d/w, and 5 d/w respectively. Quadriceps ART was measured at 45°, 60° and 90° of knee flexion pre and nine weeks post-operatively using an isokinetic dynamometer. Patients also completed pre and post operatively the Lysholm questionnaire whereby subjective scores were recorded. Results Two factor ANOVA showed significant differences in ART at 90° among the groups (F = 4.29, p = 0.02, p Significant differences were also found in the Lysholm score among the groups (F = 4.75, p = 0.01, p Conclusion CEE showed improvements on quadriceps ART at 90° at a sequence of 3 d/w and in the Lysholm score at a sequence of 3 d/w and 5 d/w respectively on ACL reconstructed patients.</p