Conotoxins as Sensors of Local pH and Electrostatic Potential in the Outer Vestibule of the Sodium Channel

We examined the block of voltage-dependent rat skeletal muscle sodium channels by derivatives of μ-conotoxin GIIIA (μCTX) having either histidine, glutamate, or alanine residues substituted for arginine-13. Toxin binding and dissociation were observed as current fluctuations from single, batrachotoxin-treated sodium channels in planar lipid bilayers. R13X derivatives of μCTX only partially block the single-channel current, enabling us to directly monitor properties of both μCTX-bound and -unbound states under different conditions. The fractional residual current through the bound channel changes with pH according to a single-site titration curve for toxin derivatives R13E and R13H, reflecting the effect of changing the charge on residue 13, in the bound state. Experiments with R13A provided a control reflecting the effects of titration of all residues on toxin and channel other than toxin residue 13. The apparent pKs for the titration of residual conductance are shifted 2–3 pH units positive from the nominal pK values for histidine and glutamate, respectively, and from the values for these specific residues, determined in the toxin molecule in free solution by NMR measurements. Toxin affinity also changes dramatically as a function of pH, almost entirely due to changes in the association rate constant, kon. Interpreted electrostatically, our results suggest that, even in the presence of the bound cationic toxin, the channel vestibule strongly favors cation entry with an equivalent local electrostatic potential more negative than −100 mV at the level of the “outer charged ring” formed by channel residues E403, E758, D1241, and D1532. Association rates are apparently limited at a transition state where the pK of toxin residue 13 is closer to the solution value than in the bound state. The action of these unique peptides can thus be used to sense the local environment in the ligand-–receptor complex during individual molecular transitions and defined conformational states

Cross-national gender differences in the socioeconomic factors associated with smoking in Australia, the United States of America and South Korea

Objectives: We compared rates of smoking among those aged 45 years and older in Australia, the United States of America and South Korea, and examined cross-national gender differences in key socioeconomic differentials in smoking. Methods: We conducted weighted analyses on cross-sectional data from nationally representative surveys conducted in 2006. Results: Current smoking was more prevalent for males than females in all countries; the gender difference was largest in Korea. Being unpartnered increased the likelihood of smoking in all countries, while greater wealth reduced it. In Korea these effects interacted with gender; both indicators showed larger differentials among women than men. Lower educational attainment increased the likelihood of smoking for all groups except Korean women, among whom high school educated women were less likely to smoke than the tertiary educated. Conclusions: Our findings support a cultural interpretation of gender differences in smoking: in countries with low gender empowerment, gender differences in smoking are greater. With increasing divorce and female tertiary education rates in nations like Korea, we highlight the need for health promotion messages targeted towards older and more educated women

From One to Multiple Accents on a Test of L2 Listening Comprehension

Concerns about the need for assessing multidialectal listening skills for global contexts are becoming increasingly prevalent. However, the inclusion of multiple accents on listening assessments may threaten test fairness because it is not practical to include every accent that may be encountered in the language use domain on these tests. Given this dilemma, this study aimed to determine the extent to which accent strength and familiarity affect comprehension and to provide a defensible direction for assessing multidialectal listening comprehension. A strength of accent scale was developed, and one US, four Australian, and four British English speakers of English were selected based on a judgment of their strength of accent. Next, TOEFL test takers (N = 21,726) were randomly assigned to listen to a common lecture given by one of the nine selected speakers, and respond to six comprehension items and a survey designed to assess their familiarity with various accents. The results suggest that strength of accent and familiarity do affect listening comprehension, and these factors affect comprehension even with quite light accents

Cissus sicyoides C. Linnaeus (Vitaceae), a Potential Exotic Pest in the Lower Rio Grande Valley, Texas

English:Cissus sicyoides C. Linnaeus, a perennial vine native to tropical Mexico, Central America, and the Caribbean, has recently been rediscovered in the Lower Rio Grande Valley,Texas. A dense population of this exotic species has been located in a brushy area along a canal network and in two adjacent citrus groves near Weslaco. This species produces a dense mantle that covers other vegetation, appears to be invasive, and may pose a potential weed problem in citrus in the Lower Rio Grande Valley. Spanish: Cissus sicyoides C. Linnaeus, una enredadera perene nativa de los trópicos de México, América Central y el Caribe, se ha redescubierto recientemente en el Bajo Valle del Río Grande,Texas. Una población densa de esta especie exótica ha sido localizada en una área de matorral a lo largo de una red de canales y en dos huertas adyacentes de cítricos cercanas a Weslaco. Esta especie produce un manto denso que cubre otra vegetación, es invasiva y puede tener el potencial de convertirse en una maleza problemática para el cultivo de cítricos en el Bajo Valle del Río Grande en Texas

Alcohol use and depression from middle age to the oldest old: Gender is more important than age

Background: Alcohol use disorders are associated with other mental health disorders in young adults, but there are few data on alcohol use and mental health outcomes in older adults, particularly the oldest old. This study examines the relationship between alcohol consumption and depressive symptoms. Methods: Data were collected from the Dynamic Analyses to Optimise Ageing (DYNOPTA) project, which has pooled nine Australian longitudinal studies. Alcohol consumption was classified using standard drinks (10 g alcohol)/day as: abstinent, low risk (2–≤4) and short-term risk (>4). Probable depression was classified from harmonized scores on various standard instruments (e.g. Centre for Epidemiological Studies Depression scale). Results: Overall, 39,104 (86%) participants contributed data. Alcohol classification at baseline showed 7,526 abstinent, 28,112 low risk, 2,271 long-term risk, and 1,195 short-term risk participants. Age ranged from 45 to 103 year (median 60). Using generalized estimating equations (GEE), there were significant gender by alcohol and gender by age interactions, so the analysis was split by gender. Among males, the abstinent and short-term risk groups had increased likelihood of depression: in females the abstinent, long- and short-term risk groups had increased odds of depression. Increased odds of depression was also associated with former and current smoking, younger age-group, not being partnered, leaving school before age 15 and increasing levels of health-impaired walking, dressing, or bathing. Conclusion: The impact of alcohol use differs by gender, nevertheless those using higher levels of alcohol or who smoke should be screened for depression and may benefit from interventions

Fibronectin and Cyclic Strain Improve Cardiac Progenitor Cell Regenerative Potential In Vitro.

Cardiac progenitor cells (CPCs) have rapidly advanced to clinical trials, yet little is known regarding their interaction with the microenvironment. Signaling cues present in the microenvironment change with development and disease. This work aims to assess the influence of two distinct signaling moieties on CPCs: cyclic biaxial strain and extracellular matrix. We evaluate four endpoints for improving CPC therapy: paracrine signaling, proliferation, connexin43 expression, and alignment. Vascular endothelial growth factor A (about 900 pg/mL) was secreted by CPCs cultured on fibronectin and collagen I. The application of mechanical strain increased vascular endothelial growth factor A secretion 2-4-fold for CPCs cultured on poly-L-lysine, laminin, or a naturally derived cardiac extracellular matrix. CPC proliferation was at least 25% higher on fibronectin than that on other matrices, especially for lower strain magnitudes. At 5% strain, connexin43 expression was highest on fibronectin. With increasing strain magnitude, connexin43 expression decreased by as much as 60% in CPCs cultured on collagen I and a naturally derived cardiac extracellular matrix. Cyclic mechanical strain induced the strongest CPC alignment when cultured on fibronectin or collagen I. This study demonstrates that culturing CPCs on fibronectin with 5% strain magnitude is optimal for their vascular endothelial growth factor A secretion, proliferation, connexin43 expression, and alignment