Movement and Crevices Around a Sodium Channel S3 Segment

Voltage sensing is due mainly to the movement of positively charged S4 segments through the membrane electric field during changes of membrane potential. The roles of other transmembrane segments are under study. The S3 segment of domain 4 (D4/S3) in the sodium channel Nav1.4 carries two negatively charged residues and has been implicated in voltage-dependent gating. We substituted cysteines into nine putative “high impact” sites along the complete length of D4/S3 and evaluated their accessibilities to extracellular sulfhydryl reagents. Only the four outermost substituted cysteines (L1433C, L1431C, G1430C, and S1427C) are accessible to extracellular sulfhydryl reagents. We measured the voltage-dependent modification rates of the two cysteines situated at the extreme ends of this accessible region, L1433C and S1427C. Independent of the charge on the sulfhydryl reagents, depolarization increases the reactivity of both of these residues. Thus, the direction of the voltage dependence is opposite to that expected for a negatively charged voltage sensor, namely an inward translational movement in response to depolarization. Intrinsic electrostatic potentials were probed by charged sulfhydryl reagents and were either negative or positive, respectively, near L1433C and S1427C. The magnitude of the electrostatic potential near S1427C decreases with depolarization, suggesting that the extracellular crevice next to it widens during depolarization. S1427C experiences 44% of the electric field, as probed by charged cysteine reagents. To further explore movements around D4/S3, we labeled cysteines with the photoactivatable cross-linking reagent benzophenone-4-carboxamidocysteine methanethiosulfonate and examined the effects of UV irradiation on channel gating. After labeling with this reagent, all accessible cysteine mutants show altered gating upon brief UV irradiation. In each case, the apparent insertion efficiency of the photoactivated benzophenone increases with depolarization, indicating voltage-dependent movement near the extracellular end of D4/S3

Remarkable charge-transfer mobility from [6] to [10]phenacene as a high performance p-type organic semiconductor

The relationship between structure and charge transport properties of phenacene organic semiconductors has been studied with focus on [6] -> [10] phenacene. Upon inserting phenyl rings, the p-extended structure results in strong electronic coupling interactions and reduction of reorganization energy. Using the classical Marcus charge transport theory, we predict that hole mobility in the phenacene series increases gradually up to 8.0 cm(2) V-1 s(-1) at [10] phenacene. This is remarkably high among other discovered OSCs, surpassing that of pentacene. Moreover, we notice that the experimental hole mobility of [6] phenacene is unusually low, inconsistent with other members in the same series. Thus, we performed full structural relaxation on phenacene and revealed similarities between theoretical and experimental crystal structures for all the members except [6] phenacene. We propose a new structure of [6] phenacene under the consideration of van der Waals force with smaller lattice parameters a* and b* compared to the experimental structure. Our new structural calculation fits well with the existing trend of hole mobility, energy gaps, effective masses, bandwidth and lattice parameters. Single-shot G(0)W(0) calculations are performed to verify our structures. The results give a hint that the improvement in [6] phenacene efficiency lies on the intermolecular distance along the stacking direction of the crystal. Phenacene compounds generally have small effective masses, high charge transfer integrals and moderate reorganization energies necessary for hole transport. Our results suggest that the phenacene series, in particular [6] -> [10]phenacene, have high charge mobility and air stability essential for achieving high efficiency electronic devices.11Ysciescopu

An Improved 96-well Turbidity Assay for T4 Lysozyme Activity

T4 lysozyme (T4L) is an important model system for investigating the relationship between protein structure and function. Despite being extensively studied, a reliable, quantitative activity assay for T4L has not been developed. Here, we present an improved T4L turbidity assay as well as an affinity-based T4L expression and purification protocol. This assay is designed for 96-well format and utilizes conditions amenable for both T4L and other lysozymes. This protocol enables easy, efficient, and quantitative characterization of T4L variants and allows comparison between different lysozymes. Our method: •Is applicable for all lysozymes, with enhanced sensitivity for T4 lysozyme compared to other 96-well plate turbidity assays;•Utilizes standardized conditions for comparing T4 lysozyme variants and other lysozymes; and•Incorporates a simplified expression and purification protocol for T4 lysozyme

Productive uses of domestic water: a household-level study from Vietnam

The use of domestic water in South-East Asia and its scale, values and importance to livelihoods and poverty reduction has been identified as a key policy issue in the region. In particular, the potential for including productive uses of domestic water in the design and economic assessment of water supply programmes has the potential to increase sustainability and transform the economic rationale of these investments. The research described below explored this issue, conducting fieldwork on the ways in which rural and peri-urban households in Vietnam are using domestic water. The study found that domestic water is being used for a broad range of productive activities, including widespread use in household gardens, animal husbandry and many type of micro enterprises. It also found that it was most often poor households engaging in these activities. The paper concludes by considering the implications of these findings for policy makers

Prevalence and Determinants of Medication Adherence among Patients with HIV/AIDS in Southern Vietnam

This study was conducted to determine the prevalence and determinants of medication adherence among patients with HIV/AIDS in southern Vietnam. METHODS: A cross-sectional study was conducted in a hospital in southern Vietnam from June to December 2019 on patients who began antiretroviral therapy (ART) for at least 6 months. Using a designed questionnaire, patients were considered adherent if they took correct medicines with right doses, on time and properly with food and beverage and had follow-up visits as scheduled. Multivariable logistic regression was used to identify determinants of adherence. KEY FINDINGS: A total of 350 patients (from 861 medical records) were eligible for the study. The majority of patients were male (62.9%), and the dominant age group (≥35 years old) accounted for 53.7% of patients. Sexual intercourse was the primary route of transmission of HIV (95.1%). The proportions of participants who took the correct medicine and at a proper dose were 98.3% and 86.3%, respectively. In total, 94.9% of participants took medicine appropriately in combination with food and beverage, and 75.7% of participants were strictly adherent to ART. The factors marital status (odds ratio (OR) = 2.54; 95%CI = 1.51-4.28), being away from home (OR = 1.7; 95%CI = 1.03-2.78), substance abuse (OR = 2.7; 95%CI = 1.44-5.05), general knowledge about ART (OR = 2.75; 95%CI = 1.67-4.53), stopping medication after improvement (OR = 4.16; 95%CI = 2.29-7.56) and self-assessment of therapy adherence (OR = 9.83; 95%CI = 5.44-17.77) were significantly associated with patients' adherence. CONCLUSIONS: Three-quarters of patients were adherent to ART. Researchers should consider these determinants of adherence in developing interventions in further studies

Inactivation and Secondary Structure in the D4/S4-5 Region of the SkM1 Sodium Channel

The D4/S4-5 interhelical region plays a role in sodium channel fast inactivation. Examination of S4-5 primary structure in all domains suggests a possible amphipathic helical conformation in which a conserved group of small hydrophobic residues occupies one contiguous surface with a more variable complement of nonpolar and polar residues on the opposite face. We evaluated this potential structure by replacing each residue in D4/S4-5 of the rat SkM1 skeletal muscle sodium channel with substitutions having different side chain properties. Of the 63 mutations analyzed, 44 produced functional channels. P1473 was intolerant of substitutions. Nonpolar substitutions in the conserved hydrophobic region were functionally similar to wild type, while charged mutations in this region before P1473 were nonfunctional. Charged mutations at F1466, M1469, M1470, and A1474, located on the opposite surface of the predicted helix, produced functional channels with pronounced slowing of inactivation, shifted voltage dependence of steady-state inactivation, and increased rate of recovery from inactivation. The substituted-cysteine-accessibility method was used to probe accessibility at each position. Residues L1465, F1466, A1467, M1469, M1470, L1472, A1474, and F1476C were easily accessible for modification by sulfhydryl reagents; L1464, L1468, S1471, and L1475 were not accessible within the time frame of our measurements. Molecular dynamics simulations of residues A1458 to N1477 were then used to explore energetically favorable local structures. Based on mutagenesis, substituted-cysteine-accessibility method, and modeling results, we suggest a secondary structure for the D4/S4-5 region in which the peptide chain is α-helical proximal to P1473, bends at this residue, and may continue beyond this point as a random coil. In this configuration, the entire resultant loop is amphipathic; four residues on one surface could form part of the binding site for the inactivation particle

Knowledge of Antiretroviral Treatment and Associated Factors in HIV-Infected Patients

This study aimed to assess the knowledge of antiretroviral (ARV) treatment and the associated factors in HIV-infected patients in Vietnam. We conducted a cross-sectional descriptive study of 350 human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome (AIDS) patients being treated with ARV at outpatient clinics at Soc Trang, Vietnam, from June 2019 to December 2019. Using an interview questionnaire, patients who answered at least eight out of nine questions correctly, including some required questions, were considered to have a general knowledge of ARV treatment. Using multivariate logistic regression to identify factors associated with knowledge of ARV treatment, we found that 62% of HIV-infected patients had a general knowledge of ARV treatment, with a mean score of 8.2 (SD 1.4) out of 9 correct. A higher education level (p < 0.001); working away from home (p = 0.013); getting HIV transmitted by injecting drugs or from mother-to-child contact (p = 0.023); the presence of tension, anxiety, or stress (p = 0.005); self-reminding to take medication (p = 0.024); and a high self-evaluated adherence (p < 0.001) were found to be significantly associated with an adequate knowledge of ARV treatment. In conclusion, education programs for patients, as well as the quality of medical services and support, should be strengthened

Mechanisms for Increased Arrhythmia Risk in Aged Hearts

La prueba de Comprensión Lectora ha sido construida según lo que señalan el Diseño Curricular Nacional (DCN), el Mapa de Progreso de Lectura y las Rutas del Aprendizaje. En la ECE 2013, la prueba presenta los siguientes tipos de texto: anécdota, nota, carta, afiche, artículo enciclopédico, texto de recomendaciones, texto de opinión, cuento y descripción. En la ECE, los resultados de los estudiantes en la prueba de Comprensión Lectora se presentan por medio de niveles de logro. A partir de sus respuestas en la prueba, los estudiantes se ubicaron en alguno de estos niveles: Nivel Satisfactorio, Nivel En Proceso o Nivel En Inicio

Petrographic Characteristics and Depositional Environment Evolution of Middle Miocene Sediments in the Thien Ung - Mang Cau Structure of Nam Con Son Basin

This paper introduces the petrographic characteristics and depositional environment of Middle Miocene rocks of the Thien Ung - Mang Cau structure in the central area of Nam Con Son Basin based on the results of analyzing thin sections and structural characteristics of core samples. Middle Miocene sedimentary rocks in the studied area can be divided into three groups: (1) Group of terrigenous rocks comprising greywacke sandstone, arkosic sandstone, lithic-quartz sandstone, greywacke-lithic sandstone, oligomictic siltstone, and bitumenous claystone; (2) Group of carbonate rocks comprising dolomitic limestone and bituminous limestone; (3) Mixed group comprising calcareous sandstone, calcarinate sandstone, arenaceous limestone, calcareous claystone, calcareous silty claystone, dolomitic limestone containing silt, and bitumen. The depositional environment is expressed through petrographic characteristics and structure of the sedimentary rocks in core samples. The greywacke and arkosic sandstones are of medium grain size, poor sorting and roundness, and siliceous cement characterizing the alluvial and estuarine fan environment expressed by massive structure of core samples. The mixed calcareous limestone, arenaceous dolomitic limestone, and calcareous and bituminous clayey siltstone in the core samples are of turbulent flow structure characterizing shallow bay environment with the action of bottom currents. The dolomitic limestones are of relatively homogeneous, of microgranular and fine-granular texture, precipitated in a weakly reducing, semi-closed, and relatively calm bay environment

An Investigation of Barriers to Adopt Green Innovation Among Manufacturing Organizations in Vietnam

This research aims to identify the main barriers to green innovation in Vietnam manufacturing organizations. This study began by reviewing the relevant literature and providing a solid theoretical framework to understand the determinants of green innovation for manufacturing firms in the global context. It also helps internal and external stakeholders figure out what influence and how to implement green innovation more efficiently by removing all impediments. Additionally, this article is considered a valuable and rational evidence for prioritizing and directing innovation policies in the manufacturing industry. Based on numerical data from 143 employees at middleand upper-level managers among manufacturing companies around Vietnam, the study found that deficiency of financial resources primarily significantly impacts green innovation adoption, followed by the uncertainty of market demand and lack of government support. However, with limited observations, the investigation did not observe the dynamic effect of green innovation over periods and only focused on the manufacturing sector instead of different industries for generalizing the research results. Moreover, the circumstances of green innovation would be diverse in other nations. Keywords: green innovation, manufacturing organizations, government supports, financial barriers, market barrier