Intrinsic Lipid Curvature and Bilayer Elasticity as Regulators of Channel Function: A Comparative Single-Molecule Study.

Perturbations in bilayer material properties (thickness, lipid intrinsic curvature and elastic moduli) modulate the free energy difference between different membrane protein conformations, thereby leading to changes in the conformational preferences of bilayer-spanning proteins. To further explore the relative importance of curvature and elasticity in determining the changes in bilayer properties that underlie the modulation of channel function, we investigated how the micelle-forming amphiphiles Triton X-100, reduced Triton X-100 and the HII lipid phase promoter capsaicin modulate the function of alamethicin and gramicidin channels. Whether the amphiphile-induced changes in intrinsic curvature were negative or positive, amphiphile addition increased gramicidin channel appearance rates and lifetimes and stabilized the higher conductance states in alamethicin channels. When the intrinsic curvature was modulated by altering phospholipid head group interactions, however, maneuvers that promote a negative-going curvature stabilized the higher conductance states in alamethicin channels but destabilized gramicidin channels. Using gramicidin channels of different lengths to probe for changes in bilayer elasticity, we found that amphiphile adsorption increases bilayer elasticity, whereas altering head group interactions does not. We draw the following conclusions: first, confirming previous studies, both alamethicin and gramicidin channels are modulated by changes in lipid bilayer material properties, the changes occurring in parallel yet differing dependent on the property that is being changed; second, isolated, negative-going changes in curvature stabilize the higher current levels in alamethicin channels and destabilize gramicidin channels; third, increases in bilayer elasticity stabilize the higher current levels in alamethicin channels and stabilize gramicidin channels; and fourth, the energetic consequences of changes in elasticity tend to dominate over changes in curvature.

How and when community-oriented-corporate social responsibility affects employee societal behavior: A moderated-mediated model.

The psychology of micro-corporate social responsibility (micro-CSR) and employee outcome has emerged in the contemporary literature of interdisciplinary management science. Previous studies have ignored the testing of mediating effects and boundary conditions in the association between micro-CSR and employee outcomes. Drawing on social identity theory (SIT) and social information processing theory (SIPT), this research aims to investigate how, why, and when the perceived CSR community (PCSRc; a micro-CSR activity) affects employee societal behavior (ESB; a voluntary behavior) accounting the mediating role of perceived external prestige (PEP) and moderating role of organizational identification (OI). Our research recruited 452 employees in Bangladesh via questionnaire and tested the proposed measurement model and structural relationships in AMOS. The results report a significant and positive relationship between PCSRc and ESB. It also reveals that PEP mediates PCSRc and ESB link, and OI regulates the straight association of PCSRc and PEP and ancillary links of PCSRc and ESB (via PEP). Finally, we recorded the research implications and future research directions.

Knowledge and awareness of infection control practices among nursing professionals: A cross-sectional survey from South Asia and the Middle East.

BACKGROUND: The proficiency of nursing professionals in the infection prevention and control (IPC) practices is a core component of the strategy to mitigate the challenge of healthcare associated infections. AIM: To test knowledge of nurses working in intensive care units (ICU) in South Asia and Middle East countries on IPC practices. METHODS: An online self-assessment questionnaire based on various aspects of IPC practices was conducted among nurses over three weeks. RESULTS: A total of 1333 nurses from 13 countries completed the survey. The average score was 72.8% and 36% of nurses were proficient (mean score > 80%). 43% and 68.3% of respondents were from government and teaching hospitals, respectively. 79.2% of respondents worked in < 25 bedded ICUs and 46.5% in closed ICUs. Statistically, a significant association was found between the knowledge and expertise of nurses, the country's per-capita income, type of hospitals, accreditation and teaching status of hospitals and type of ICUs. Working in high- and upper-middle-income countries (ß = 4.89, 95%CI: 3.55 to 6.22) was positively associated, and the teaching status of the hospital (ß = -4.58, 95%CI: -6.81 to -2.36) was negatively associated with the knowledge score among respondents. CONCLUSION: There is considerable variation in knowledge among nurses working in ICU. Factors like income status of countries, public vs private and teaching status of hospitals and experience are independently associated with nurses' knowledge of IPC practices.

Endothelial Cell Plasma Membrane Biomechanics Mediates Effects of Pro-Inflammatory Factors on Endothelial Mechanosensors: Vicious Circle Formation in Atherogenic Inflammation.

Chronic low-grade vascular inflammation and endothelial dysfunction significantly contribute to the pathogenesis of cardiovascular diseases. In endothelial cells (ECs), anti-inflammatory or pro-inflammatory signaling can be induced by different patterns of the fluid shear stress (SS) exerted by blood flow on ECs. Laminar blood flow with high magnitude is anti-inflammatory, while disturbed flow and laminar flow with low magnitude is pro-inflammatory. Endothelial mechanosensors are the key upstream signaling proteins in SS-induced pro- and anti-inflammatory responses. Being transmembrane proteins, mechanosensors, not only experience fluid SS but also become regulated by the biomechanical properties of the lipid bilayer and the cytoskeleton. We review the apparent effects of pro-inflammatory factors (hypoxia, oxidative stress, hypercholesterolemia, and cytokines) on the biomechanics of the lipid bilayer and the cytoskeleton. An analysis of the available data suggests that the formation of a vicious circle may occur, in which pro-inflammatory cytokines enhance and attenuate SS-induced pro-inflammatory and anti-inflammatory signaling, respectively.

Magnitude and clinical profile of juvenile idiopathic arthritis in a medical college hospital of a socio-economically disadvantaged country.

BACKGROUND: A number of children with Juvenile Idiopathic Arthritis (JIA) got admitted in the pediatrics ward of a medical college hospital. However, burden and clinical pattern of JIA have not been studied in our country. OBJECTIVES: To estimate the burden of JIA admitted in the pediatric department of medical college hospital of Bangladesh and to observe the status of active JIA in respect to magnitude, clinical profile and hematological changes. METHODS: A prospective study was carried out among the patients admitted in pediatric ward of a medical college hospital, Bangladesh from 2008 to 2010. All active JIA patients admitted during this period were included in this study. JIA was diagnosed according to the ILAR criteria. Male/Female ratio, age, Total Leukocyte Count (TLC), Differential count (D/C), Platelet count, Erythrocyte Sedimentation Rate (ESR), C Reactive Protein (CRP), Rheumatoid Factor (RF) of JIA patients were recorded. These were statistically analyzed with the help of SPSS programme using chi-square test. RESULTS: Twenty five cases of active JIA were diagnosed during this period. Magnitude was 3.75 per 1000 admitted cases. Male/Female ratio was 1.08:1. 10 (40%) cases were between the ages of 8 to 11 years. Polyarticular seronegative JIA was found in 10 (40%) cases and oligoarticular JIA in the next order 6 (24%). High ESR, TLC, platelet count was observed in 21 (84%) [p <.001], 19 (76%) [p <.009], 3 (12%) [p <.000] cases respectively. CONCLUSION: Burden of JIA was similar to all the areas of the world. Polyarticular seronegative JIA was commonly observed in our study. High ESR, increased TLC and Platelet count was the reliable predictor of active JIA.

Chemotherapy drugs form ion pores in membranes due to physical interactions with lipids.

We demonstrate the effects on membrane of the tubulin-binding chemotherapy drugs: thiocolchicoside and taxol. Electrophysiology recordings across lipid membranes in aqueous phases containing drugs were used to investigate the drug effects on membrane conductance. Molecular dynamics simulation of the chemotherapy drug-lipid complexes was used to elucidate the mechanism at an atomistic level. Both drugs are observed to induce stable ion-flowing pores across membranes. Discrete pore current-time plots exhibit triangular conductance events in contrast to rectangular ones found for ion channels. Molecular dynamics simulations indicate that drugs and lipids experience electrostatic and van der Waals interactions for short periods of time when found within each other's proximity. The energies from these two interactions are found to be similar to the energies derived theoretically using the screened Coulomb and the van der Waals interactions between peptides and lipids due to mainly their charge properties while forming peptide-induced ion channels in lipid bilayers. Experimental and in silico studies together suggest that the chemotherapy drugs induce ion pores inside lipid membranes due to drug-lipid physical interactions. The findings reveal cytotoxic effects of drugs on the cell membrane, which may aid in novel drug development for treatment of cancer and other diseases.