Evolution of elliptical SAXS patterns in aligned systems.

Small-angle X-ray and neutron scattering (SAXS and SANS) patterns from certain semicrystalline polymers and liquid crystals contain discrete reflections from ordered assemblies and central diffuse scattering (CDS) from uncorrelated structures. Systems with imperfectly ordered lamellar structures aligned by stretching or by a magnetic field produce four distinct SAXS patterns: two-point 'banana', four-point pattern, four-point 'eyebrow' and four-point 'butterfly'. The peak intensities of the reflections lie not on a layer line, or the arc of a circle, but on an elliptical trajectory.

Subparalyzing Doses of Rocuronium Reduce Muscular Endurance without Detectable Effect on Single Twitch Height in Awake Subjects.

Purpose: To test the hypothesis that a low-dose rocuronium acts mainly by means of reducing muscular endurance rather than by reducing momentary force.

Methods: In a randomized placebo-controlled double-blinded study, eight healthy volunteers were studied in two sets of experiments. In the first set, the subjects made a sustained maximum effort with the dominant hand for 80 seconds while squeezing an electronic handgrip dynamometer at three minutes after intravenous administration of placebo, 0.

Chronic Contractile Dysfunction without Hypertrophy Does Not Provoke a Compensatory Transcriptional Response in Mouse Hearts.

Diseased myocardium from humans and experimental animal models shows heightened expression and activity of a specific subtype of phospholipase C (PLC), the splice variant PLCβ1b. Previous studies from our group showed that increasing PLCβ1b expression in adult mouse hearts by viral transduction was sufficient to cause sustained contractile dysfunction of rapid onset, which was maintained indefinitely in the absence of other pathological changes in the myocardium. We hypothesized that impaired contractility alone would be sufficient to induce a compensatory transcriptional response.

Expressing an inhibitor of PLCβ1b sustains contractile function following pressure overload.

The activity of phospholipase Cβ1b (PLCβ1b) is selectively elevated in failing myocardium and cardiac expression of PLCβ1b causes contractile dysfunction. PLCβ1b can be selectively inhibited by expressing a peptide inhibitor that prevents sarcolemmal localization. The inhibitory peptide, PLCβ1b-CT was expressed in heart from a mini-gene using adeno-associated virus (rAAV6-PLCβ1b-CT).

The atypical 'b' splice variant of phospholipase Cβ1 promotes cardiac contractile dysfunction.

The activity of the early signaling enzyme, phospholipase Cβ1b (PLCβ1b), is selectively elevated in diseased myocardium and activity increases with disease progression. We aimed to establish the contribution of heightened PLCβ1b activity to cardiac pathology. PLCβ1b, the alternative splice variant, PLCβ1a, and a blank virus were expressed in mouse hearts using adeno-associated viral vectors (rAAV6-FLAG-PLCβ1b, rAAV6-FLAG-PLCβ1a, or rAAV6-blank) delivered intravenously (IV).

Phospholipase Cβ1b directly binds the SH3 domain of Shank3 for targeting and activation in cardiomyocytes.

Phospholipase Cβ1b (PLCβ1b) is an atypical splice variant of PLCβ1 that has a C-terminal proline-rich sequence instead of the PDZ-interacting motif common to other PLCβ subtypes. PLCβ1b targets to the cardiomyocyte sarcolemma through an undefined association with the scaffolding protein Shank3. The C-terminal splice variant specific sequence of PLCβ1b bound to deletion mutants of Shank3 that included the SH3 domain, but not to constructs lacking this domain.

Detection of mouth alcohol during breath alcohol analysis.

The presence of mouth alcohol (MA) during alcohol breath test for law enforcement is the most common cause of falsely high breath alcohol concentrations (BrAC). A fast and reliable test for detection of MA roadside at the scene of the act would facilitate the police efforts for proper prosecution. A tentative technique to use orally exhaled water vapour as a reference gas to position the origin of alcohol was validated.

The phosphatidylinositol(4,5)bisphosphate-binding sequence of transient receptor potential channel canonical 4α is critical for its contribution to cardiomyocyte hypertrophy.

Cardiomyocyte hypertrophy requires a source of Ca(2+) distinct from the Ca(2+) that regulates contraction. The canonical transient receptor potential channel (TrpC) family, a family of cation channels regulated by activation of phospholipase C (PLC), has been implicated in this response. Cardiomyocyte hypertrophy downstream of Gq-coupled receptors is mediated specifically by PLCβ1b that is scaffolded onto a SH3 and ankyrin repeat protein 3 (Shank3) complex at the sarcolemma.

Regulation of autophagy in cardiomyocytes by Ins(1,4,5)P(3) and IP(3)-receptors.

Autophagy is a process that removes damaged proteins and organelles and is of particular importance in terminally differentiated cells such as cardiomyocytes, where it has primarily a protective role. We investigated the involvement of inositol(1,4,5)trisphosphate (Ins(1,4,5)P(3)) and its receptors in autophagic responses in neonatal rat ventricular myocytes (NRVM). Treatment with the IP(3)-receptor (IP(3)-R) antagonist 2-aminoethoxydiphenyl borate (2-APB) at 5 or 20 μmol/L resulted in an increase in autophagosome content, defined as puncta labeled by antibody to microtubule associated light chain 3 (LC3).

Tissue-specific splicing of an Ndufs6 gene-trap insertion generates a mitochondrial complex I deficiency-specific cardiomyopathy.

Mitochondrial complex I (CI) deficiency is the most common mitochondrial enzyme defect in humans. Treatment of mitochondrial disorders is currently inadequate, emphasizing the need for experimental models. In humans, mutations in the NDUFS6 gene, encoding a CI subunit, cause severe CI deficiency and neonatal death.

Scaffolding protein Homer 1c mediates hypertrophic responses downstream of Gq in cardiomyocytes.

Activation of the heterotrimeric G protein, Gq, causes cardiomyocyte hypertrophy in vivo and in cell models. Responses to activated Gq in cardiomyocytes are mediated exclusively by phospholipase Cβ1b (PLCβ1b), because it localizes at the sarcolemma by binding to Shank3, a high-molecular-weight (MW) scaffolding protein. Shank3 can bind to the Homer family of low-MW scaffolding proteins that fine tune Ca(2+) signaling by facilitating crosstalk between Ca(2+) channels at the cell surface with those on intracellular Ca(2+) stores.

Phospholipase Cbeta1b associates with a Shank3 complex at the cardiac sarcolemma.

Activation of the heterotrimeric G protein Gq causes cardiomyocyte hypertrophy in vivo and in cell models. Our previous studies have shown that responses to activated Gq in cardiomyocytes are mediated exclusively by phospholipase Cβ1b (PLCβ1b), because only this PLCβ subtype localizes at the cardiac sarcolemma. In the current study, we investigated the proteins involved in targeting PLCβ1b to the sarcolemma in neonatal rat cardiomyocytes.

Selective activation of the "b" splice variant of phospholipase Cbeta1 in chronically dilated human and mouse atria.

Atrial fibrillation (AF) is commonly associated with chronic dilatation of the left atrium, both in human disease and animal models. The immediate signaling enzyme phospholipase C (PLC) is activated by mechanical stretch to generate the Ca2+-releasing messenger inositol(1,4,5)trisphosphate (Ins(1,4,5)P3) and sn-1,2-diacylglycerol (DAG), an activator of protein kinase C subtypes. There is also evidence that heightened activity of PLC, caused by the receptor coupling protein Gq, can contribute to atrial remodelling.

Gq-initiated cardiomyocyte hypertrophy is mediated by phospholipase Cbeta1b.

Activation of the heterotrimeric G protein Gq causes cardiomyocyte hypertrophy in vivo and in cell culture models. Hypertrophic responses induced by pressure or volume overload are exacerbated by increased Gq activity and ameliorated by Gq inhibition. Gq activates phospholipase Cbeta (PLCbeta) subtypes, resulting in generation of the intracellular messengers inositol(1,4,5)tris-phosphate [Ins(1,4,5)P(3)] and sn-1,2-diacylglycerol (DAG), which regulate intracellular Ca(2+) and conventional protein kinase C subtypes, respectively.

Ins(1,4,5)P(3) regulates phospholipase Cbeta1 expression in cardiomyocytes.

The functional significance of the Ca2+-releasing second messenger inositol(1,4,5)trisphosphate (Ins(1,4,5)P(3), IP(3)) in the heart has been controversial. Ins(1,4,5)P(3) is generated from the precursor lipid phosphatidylinositol(4,5)bisphosphate (PIP(2)) along with sn-1,2-diacylglycerol, and both of these are important cardiac effectors. Therefore, to evaluate the functional importance of Ins(1,4,5)P(3) in cardiomyocytes (NRVM), we overexpressed IP(3) 5-phosphatase to increase degradation.

The extreme C-terminal region of phospholipase Cbeta1 determines subcellular localization and function; the "b" splice variant mediates alpha1-adrenergic receptor responses in cardiomyocytes.

Phospholipase Cbeta1 (PLCbeta1) exists as two splice variants, PLCbeta1a (150 kDa) and PLCbeta1b (140 kDa), which differ only in their C-terminal sequences of 64 and 31 amino acids, respectively. The 3 C-terminal amino acid residues of PLCbeta1a comprise a PDZ-interacting domain, whereas the PLCbeta1b sequence has no PDZ-interacting domain but contains unique proline-rich domain 5 residues from the C terminus. PLCbeta1a is localized in the cytoplasm, whereas PLCbeta1b targets to the sarcolemma and is enriched in caveolae.

Unexpected rupture of the left ventricular free wall in the echo-lab.

Background: Left ventricular free wall rupture is an uncommon but catastrophic event following myocardial infarction, and considered the second leading cause of death in acute myocardial infarct. Different types of rupture exist from acute to sub acute types, but prognosis is usually poor. Early recognition and aggressive treatment is recommended.

Conformational control of Bax localization and apoptotic activity by Pro168.

In healthy cells, Bax resides inactive in the cytosol because its COOH-terminal transmembrane region (TMB) is tucked into a hydrophobic pocket. During apoptosis, Bax undergoes a conformational change involving NH2-terminal exposure and translocates to mitochondria to release apoptogenic factors. How this process is regulated remains unknown.