Detrusor overactivity is associated with downregulation of large-conductance calcium- and voltage-activated potassium channel protein

Chang S, Gomes CM, Hypolite JA, Marx J, Alanzi J, Zderic SA, Malkowicz B, Wein AJ, Chacko S. Detrusor overactivity is associated with downregulation of large-conductance calcium-and voltage-activated potassium channel protein. Am J Physiol Renal Physiol 298: F1416-F1423, 2010. First published April 14, 2010; doi: 10.1152/ajprenal.00595.2009.-Large-conductance voltage-and calcium-activated potassium (BK) channels have been shown to play a role in detrusor overactivity (DO). The goal of this study was to determine whether bladder outlet obstructioninduced DO is associated with downregulation of BK channels and whether BK channels affect myosin light chain 20 (MLC(20)) phosphorylation in detrusor smooth muscle (DSM). Partial bladder outlet obstruction (PBOO) was surgically induced in male New Zealand White rabbits. The rabbit PBOO model shows decreased voided volumes and increased voiding frequency. DSM from PBOO rabbits also show enhanced spontaneous contractions compared with control. Both BK channel alpha- and beta-subunits were significantly decreased in DSM from PBOO rabbits. Immunostaining shows BK beta mainly expressed in DSM, and its expression is much less in PBOO DSM compared with control DSM. Furthermore, a translational study was performed to see whether the finding discovered in the animal model can be translated to human patients. The urodynamic study demonstrates several overactive DSM contractions during the urine-filling stage in benign prostatic hyperplasia (BPH) patients with DO, while DSM is very quiet in BPH patients without DO. DSM biopsies revealed significantly less BK channel expression at both mRNA and protein levels. The degree of downregulation of the BK beta-subunit was greater than that of the BK alpha-subunit, and the downregulation of BK was only associated with DO, not BPH. Finally, the small interference (si) RNA-mediated downregulation of the BK beta-subunit was employed to study the effect of BK depletion on MLC(20) phosphorylation. siRNA-mediated BK channel reduction was associated with an increased MLC(20) phosphorylation level in cultured DSM cells. In summary, PBOO-induced DO is associated with downregulation of BK channel expression in the rabbit model, and this finding can be translated to human BPH patients with DO. Furthermore, downregulation of the BK channel may contribute to DO by increasing the basal level of MLC(20) phosphorylation.

Accent accommodation in the job interview - Impact of interviewer accent and gender

Using the framework of Communication Accommodation Theory, this study investigated the extent to which job applicants objectively and subjectively altered their accents to converge to or diverge from the speech style of the interviewer Forty-eight male and 48 female job applicants participated in two interviews for a casual research assistant position. In one interview, the interviewer had a broad Australian English accent, and in the other one, the interviewer had a cultivated accent. Applicants showed broader accents with broad-accented interviewers than with cultivated-accented interviewers. Applicants did not converge to the cultivated-accented interviewers, however and male job applicants were more likely than mere females to diverge from the cultivated-accented interviewers. There were also discrepancies between objectively rated changes to applicants' accents and their subjective judgments about the extent of accent accommodation.

Inhibition of natural killer cells by a cytomegalovirus MHC class I homologue in vivo

Herpesviruses, such as murine and human cytomegalovirus (MCMV and HCMV), can establish a persistent infection within the host and have diverse mechanisms as protection from host immune defences'. Several herpesvirus genes that are homologous to host immune modulators have been identified, and are implicated in viral evasion of the host immune response(2,3). The discovery of a viral major histocompatibility complex (MHC) class I homologue, encoded by HCMV(4), led to speculation that it might function as an immune modulator and disrupt presentation of peptides by MHC class I to cytotoxic T cells(5). However, there is no evidence concerning the biological significance of this gene during viral infection. Recent analysis of the MCMV genome has also demonstrated the presence of a MHC class I homologue(6). Here we show that a recombinant MCMV,in which. the gene encoding the class I homologue has been disrupted, has severely restricted replication during the acute stage of infection compared with wild-type MCMV, We demonstrate by in vivo depletion studies that natural killer (NK) cells are responsible for the attenuated phenotype of the mutant. Thus the viral MHC dass I homologue contributes to immune evasion through interference with NK cell-mediated clearance.

Contractile activity per se induces transcriptional activation of SLC2A4 gene in soleus muscle: involvement of MEF2D, HIF-1a, and TR alpha transcriptional factors

Lima GA, Anhe GF, Giannocco G, Nunes MT, Correa-Giannella ML, Machado UF. Contractile activity per se induces transcriptional activation of SLC2A4 gene in soleus muscle: involvement of MEF2D, HIF-1a, and TR alpha transcriptional factors. Am J Physiol Endocrinol Metab 296: E132-E138, 2009. First published October 28, 2008; doi: 10.1152/ajpendo.90548.2008.-Skeletal muscle is a target tissue for approaches that can improve insulin sensitivity in insulin-resistant states. In muscles, glucose uptake is performed by the GLUT-4 protein, which is encoded by the SLC2A4 gene. SLC2A4 gene expression increases in response to conditions that improve insulin sensitivity, including chronic exercise. However, since chronic exercise improves insulin sensitivity, the increased SLC2A4 gene expression could not be clearly attributed to the muscle contractile activity per se and/or to the improved insulin sensitivity. The present study was designed to investigate the role of contractile activity per se in the regulation of SLC2A4 gene expression as well as in the participation of the transcriptional factors myocyte enhancer factor 2D (MEF2D), hypoxia inducible factor 1a (HIF-1a), and thyroid hormone receptor-alpha (TR alpha). The performed in vitro protocol excluded the interference of metabolic, hormonal, and neural effects. The results showed that, in response to 10 min of electrically induced contraction of soleus muscle, an early 40% increase in GLUT-4 mRNA (30 min) occurred, with a subsequent 65% increase (120 min) in GLUT-4 protein content. EMSA and supershift assays revealed that the stimulus rapidly increased the binding activity of MEF2D, HIF-1a, and TR alpha into the SLC2A4 gene promoter. Furthermore, chromatin immunoprecipitation assay confirmed, in native nucleosome, that contraction induced an approximate fourfold (P < 0.01) increase in MEF2D and HIF-1a-binding activity. In conclusion, muscle contraction per se enhances SLC2A4 gene expression and that involves MEF2D, HIF-1a, and TR alpha transcription factor activation. This finding reinforces the importance of physical activity to improve glycemic homeostasis independently of other additional insulin sensitizer approaches.

Speech disorder in preschool children exposed to Cantonese and English

Speech disorder in monolingual Cantonese- or English-speaking children has been well described in the literature. There appear to be no reports, however, that describe speech-disordered children who have been exposed to both languages. Here we report on the error patterns of two preschool speech-disordered children who were learning two languages. Both children's first language was Cantonese, but they were also exposed to English through the media and child care. Their disorders were of unknown aetiology. The following questions were asked of the data: (a) Do bilingual children, suspected of having speech problems, make errors in Cantonese and English that reflect delay or disorder when compared with normative data on monolingual speech development in each language? (b) How does the children's speech differ from other bilingual children from the same language learning background? (c) Are the children's speech difficulties apparent in both languages? (d) Is the pattern of errors the same in both languages or do language-specific processes operate? The results bear on theories of acquisition, disorder and bilingualism; they also have clinical implications for speech-language pathologists whose caseloads include bilingual preschool children.

Growth hormone-binding protein in normal and pathologic gestation: Correlations with maternal diabetes and fetal growth

To date, measurements of GH-binding protein (GHBP) during human pregnancy have been carried out using;assays susceptible to interference by the elevated levels of human placental GH typical of late gestation. We recruited a large cohort of pregnant women (n = 140) for serial measurements of GHBP and used the ligand immunofunctional assay for GHBP. For normal gravidas, GHBP levels fell throughout gestation. Mean levels were 1.07 nmol/L (SE = 0.18) in the first trimester, 0.90 nmol/L (SE = 0.08) at 18-20 weeks, 0.73 nmol/L (SE = 0.05) at 28-30 weeks, and 0.62 nmol/L (SE = 0.06) at 36-38 weeks. GHBP levels in the first trimester correlated significantly with maternal body mass index (r = 0.58; P < 0.01). GHBP levels in pregnancies complicated by noninsulin-dependent diabetes mellitus (NIDDM) were substantially elevated at all gestational ages. The mean value in the first quarter (2.29 nmol/L) was more than double the normal mean (P < 0.01). In contrast, patients with insulin-dependent diabetes mellitus (IDDM) showed reduced GHBP concentrations at 36-38 weeks. The correlation between body mass index and GHBP is consistent with a metabolic role for GHBP during pregnancy, as is the dramatic elevation in GHBP observed in cases of NIDDM. At 36 weeks gestation, GHBP was significantly elevated (P < 0.01) in those women whose neonates had low birth weight (

Magnetic characterization by SQUID and FMR of a biocompatible ferrofluid based on Fe(3)O(4)

Biocompatible superparamagnetic iron oxide nanoparticles of magnetite coated with dextran were magnetically characterized using the techniques of SQUID (superconducting quantum interference device) magnetometry and ferromagnetic resonance (FMR). The SQUID magnetometry characterization was performed by isothermal measurements under applied magnetic field using the methods of zero-field-cooling (ZFC) and field-cooling (FC). The magnetic behavior of the nanoparticles indicated their superparamagnetic nature and it was assumed that they consisted exclusively of monodomains. The transition to a blocked state was observed at the temperature T(B) = (43 +/- 1) K for frozen ferrofluid and at (52 +/- 1) K for the lyophilized ferrofluid samples. The FMR analysis showed that the derivative peak-to-peak linewidth (Delta H(PP)), gyromagnetic factor (g), number of spins (N(S)), and spin-spin relaxation time (T(2)) were strongly dependent on both temperature and super-exchange interaction. This information is important for possible nanotechnological applications, mainly those which are strongly dependent on the magnetic parameters.

Stuttering treatment control using P300 event-related potentials

Positron emission tomography studies during speech have indicated a failure to show the normal activation of auditory cortical areas in stuttering individuals. In the present study, P300 event-related potentials were used to investigate possible effects of behavioral treatment on the pattern of signal amplitude and latency between waves. In order to compare variations in P300 measurements, a control group paired by age and gender to the group of stutterers, was included in the study. Findings suggest that the group of stutterers presented a significant decrease in stuttering severity after the fluency treatment program. Regarding P300 measurements, stutterers and their controls presented results within normal limits in all testing situations and no significant statistical variations between pre and post treatment testing. When comparing individual results between the testing situations, stutterers presented a higher average decrease in wave latency for the right ear following treatment. The results are discussed in light of previous P300 event-related potentials and functional imaging studies with stuttering adults. Educational objectives: The reader will learn about and be able to describe the: (1) use of P300 event-related potentials in the study of stuttering; (2) differences between stuttering and non-stuttering adults; and (3) effects of behavioral fluency treatment on cerebral activity in stuttering speakers. (C) 2011 Elsevier Inc. All rights reserved.

Assessing deaf and hearing children`s communication in Brazil

In Brazil there are no specific tests for either signed or spoken language for deaf children. A protocol evaluating communicative abilities independent of modality of communication (sign language or spoken language), and comprising assessments of (a) pragmatic profile; (b) modality of communication and linguistic level; (c) complexity of communication; and (d) style and efficacy of communication between parent and child was administered to 127 deaf and hearing children. The children, aged 3-6 years old, were distributed in three groups: 20 with severe hearing loss, 40 with profound hearing loss and 67 normally hearing. Deaf children were found to be delayed, independent of their linguistic level and preferred modality of communication. The protocol in this study proved to be an useful instrument for gathering relevant information about the three groups of preschool children`s communicative abilities, and particularly suitable for use in countries where standardized assessments are not available. Learning outcomes: The reader will be introduced to the use of an assessment protocol comprising its development, application and data analysis. The reader will be informed about assessment of deaf children`s preferred modality of communication, by the participation of a bilingual (sign language user) professional. Communication abilities can be assessed independently of the linguistic modality. In developing countries in general, where simple and easy to administer assessments tools are scarce, such a protocol is of specific value. (c) 2010 Elsevier Inc. All rights reserved.

Voice Feature Characteristic in Morbid Obese Population

Morbid obesity is highly prevalent in the Western World, and its consequences present a real public health challenge. Voice alterations can represent one of these consequences and represent an opportunity for interference with therapeutic methods. This particularly features of the individual`s voice was the goal of the present study. A group of 45 adult volunteers of both sexes with a BMI greater than 35 Kg/m(2) was selected among patients of the Obesity Ambulatory of the Digestive Surgery Division. The control group consisted of volunteers matched by sex, age (+/- 1 year), and smoking habits, but with a BMI bellow 30 Kg/m(2). All subjects were submitted to laryngoscopic examination, audio perceptive analysis, and voice acoustics determination. Examinations were always performed by the same doctor, and diagnoses were provided by two different physician specialists in laryngology and voice. Obese individuals exhibit the following modifications in voice feature: hoarseness, murmuring, vocal instability, altered jitter and shimmer, and reduced maximum phonation times as well the presence of voice strangulation at the end of emission. The voices of individuals with morbid obesity are different of the voice of nonobese people and demonstrate significant changes in vocal characteristics.

Topological charge and angular momentum of light beams carrying optical vortices

We analyze the properties of light beams carrying phase singularities, or optical vortices. The transformations of topological charge during free-space propagation of a light wave, which is a combination of a Gaussian beam and a multiple charged optical vortex within a Gaussian envelope, are studied both in theory and experiment. We revise the existing knowledge about topological charge conservation, and demonstrate possible scenarios where additional vortices appear or annihilate during free propagation of such a combined beam. Coaxial interference of optical vortices is also analyzed, and the general rule for angular-momentum density distribution in a combined beam is established. We show that, in spite of any variation in the number of vortices in a combined beam, the total angular momentum is constant during the propagation. [S1050-2947(97)09910-1].

SOX2 is an amplified lineage-survival oncogene in lung and esophageal squamous cell carcinomas

Lineage-survival oncogenes are activated by somatic DNA alterations in cancers arising from the cell lineages in which these genes play a role in normal development(1,2). Here we show that a peak of genomic amplification on chromosome 3q26.33 found in squamous cell carcinomas (SCCs) of the lung and esophagus contains the transcription factor gene SOX2, which is mutated in hereditary human esophageal malformations(3), is necessary for normal esophageal squamous development(4), promotes differentiation and proliferation of basal tracheal cells(5) and cooperates in induction of pluripotent stem cells(6-8). SOX2 expression is required for proliferation and anchorage-independent growth of lung and esophageal cell lines, as shown by RNA interference experiments. Furthermore, ectopic expression of SOX2 here cooperated with FOXE1 or FGFR2 to transform immortalized tracheobronchial epithelial cells. SOX2-driven tumors show expression of markers of both squamous differentiation and pluripotency. These characteristics identify SOX2 as a lineage-survival oncogene in lung and esophageal SCC.

Validation of brief pain inventory to Brazilian patients with pain

To validate the Brazilian version of the Brief Pain Inventory (BPI-B) scale and to determine the optimal cutpoints for mild, moderate, and severe pain based on patients` rating of their worst pain. One hundred forty-three outpatients with cancer were recruited in Hospital das Clinicas-University of Sao Paulo, Brazil. Confirmatory factor analysis confirmed two underlying dimensions, pain severity, and pain interference, with Cronbach`s alpha of 0.91 and 0.87, respectively. Convergent validity was shown by the correlation observed between the BPI dimensions with the EORTC-QLQ-C30 pain scale and the McGill Pain Questionnaire. The BPI-B detected significant differences in the two dimensions by disease and performance status, supporting known-group validity. For the worst pain, the optimal cutpoints were 4 and 7 (1-4 = mild pain, 5-7 = moderate, and 8-10 = severe). Our data show that BPI-B is a brief, useful, and valid tool for assessing pain and its impact on patient`s life.