National longitudinal tobacco product discontinuation rates among US youth from the PATH Study: 2013-2019 (waves 1-5).

OBJECTIVE: Determine longitudinal tobacco product discontinuation rates among youth (ages 12-17 years) in the USA between 2013 and 2019. METHODS: The Population Assessment of Tobacco and Health Study, a nationally representative, longitudinal cohort study, was used to determine annual/biennial rates of tobacco product discontinuation behaviours among youth across 2013-2019: (1) discontinuing product use (transition from past 30-day use to no past 30-day use), (2) attempting to quit product use and (3) discontinuing product use among those who attempted to quit. Discontinuing use was evaluated separately for cigarettes, electronic nicotine delivery systems (ENDS), cigars, hookah, smokeless tobacco and any tobacco. Attempting to quit and discontinuing use among those who attempted were each evaluated for cigarettes and ENDS. Generalised estimating equations were used to evaluate linear and non-linear trends in rates across the study period. RESULTS: Between 2013 and 2019, biennial rates of discontinuing tobacco product use among youth increased for cigarettes from 29% to 40%, increased for smokeless tobacco from 39% to 60%, and decreased for ENDS from 53% to 27%. By 2018/2019, rates of discontinuing use among attempters were 30% for those who used ENDS and 30% for those who smoked cigarettes. CONCLUSIONS: Findings show decreasing rates of discontinuing ENDS use among youth in the USA alongside the changing ENDS marketplace and increasing rates of discontinuing cigarette smoking and smokeless tobacco use. Findings will serve as benchmarks against which future tobacco product discontinuation rates can be compared with evaluating impacts of subsequent tobacco regulatory policies, ENDS product development and public education campaigns.

National longitudinal tobacco product cessation rates among US adults from the PATH Study: 2013-2019 (waves 1-5).

OBJECTIVE: To report on longitudinal tobacco product cessation rates, by product type, among adults (ages 18+ years) in the USA between 2013 and 2019. METHODS: The Population Assessment of Tobacco and Health Study, a nationally representative, longitudinal cohort study was used to report on annual and biennial rates of the following three cessation behaviours across 2013-2019: (1) discontinuing tobacco product use (ie, transition from past 30-day use to no past 30-day use), (2) attempting to quit tobacco product use and (3) quitting tobacco product use among those who attempted to quit. Each cessation behaviour was evaluated separately for cigarettes, electronic nicotine delivery systems (ENDS), cigars, hookah and smokeless tobacco. Generalised estimating equations were used to evaluate linear and nonlinear trends in cessation rates across the study period. RESULTS: Between 2013 and 2019, rates of discontinuing cigarette smoking among adults in the USA statistically increased from 16% to 18%, though these were consistently lower than rates of discontinuing use of other tobacco products. Similarly, quit attempt rates and rates of quitting among attempters increased for cigarette smokers. However, rates of discontinuing ENDS use sharply declined across the study period, from 62% to 44%. CONCLUSIONS: Findings show that tobacco product cessation rates have been changing in recent years in the USA alongside the changing tobacco product marketplace and regulatory environment, though rates of discontinuing cigarette smoking remain relatively low. Findings can serve as a benchmark against which future cessation rates can be compared with evaluate the impacts of future tobacco regulatory policies.

Smokeless Tobacco Use and Prevalence of Cardiovascular Disease Among Males in the Population Assessment of Tobacco and Health (PATH) Study, Waves 1-4.

The purpose of this period prevalence study is to compare the prevalence of cardiovascular disease (CVD) in current/former established smokeless tobacco (SLT) users (ever SLT users who have used the product fairly regularly) to those who were: 1) never established cigarette smokers and SLT users, and 2) current/former established exclusive cigarette smokers (have smoked at least a 100 or more cigarettes in lifetime) only, adjusting for known risk factors for CVD. Analyses included 4,703 men ≥ 40 years of age who participated in the Population Assessment of Tobacco and Health (PATH) Study, Waves: 1-4, conducted between 2013 and 2017. Current users were those using SLT products daily or on some days, whereas former users had not used SLT and/or cigarettes in the past 12 months. CVD prevalence was defined as a self-reported diagnosis of congestive heart failure, stroke, or myocardial infarction. Among current/former established SLT users, years of use defined exposure history, while pack-years defined exposure history for smokers. Adjusted odds ratios (AOR) and 95% confidence intervals (CI) were reported with trend tests to examine dose-response associations. Current/former established exclusive SLT users were not significantly more likely to have had any CVD compared to never established cigarette and SLT users (OR = 1.7 [0.8-3.7]), or current/former established exclusive cigarette smokers (OR = 0.9 [0.5-1.8]). Current/former established exclusive cigarette smokers were more likely to have had any CVD compared to those who were never established cigarette and SLT users (OR = 1.6 [1.1-2.3]).

Biomarkers of Potential Harm among Adult Cigarette and Smokeless Tobacco Users in the PATH Study Wave 1 (2013-2014): A Cross-sectional Analysis.

BACKGROUND: While smokeless tobacco (ST) causes oral cancer and is associated with cardiovascular diseases, less is known about how its effects differ from other tobacco use. Biomarkers of potential harm (BOPH) can measure short-term health effects such as inflammation and oxidative stress. METHODS: We compared BOPH concentrations [IL6, high-sensitivity C-reactive protein, fibrinogen, soluble intercellular adhesion molecule-1 (sICAM-1), and F2-isoprostane] across 3,460 adults in wave 1 of the Population Assessment of Tobacco and Health study (2013-2014) by tobacco use groups: primary ST users (current exclusive ST use among never smokers), secondary ST users (current exclusive ST use among former smokers), exclusive cigarette smokers, dual users of ST and cigarettes, former smokers, and never tobacco users. We estimated geometric mean ratios using never tobacco users, cigarette smokers, and former smokers as referents, adjusting for demographic and health conditions, creatinine (for F2-isoprostane), and pack-years in smoker referent models. RESULTS: BOPH levels among primary ST users were similar to both never tobacco users and former smokers. Most BOPH levels were lower among ST users compared with current smokers. Compared with never tobacco users, dual users had significantly higher sICAM-1, IL6, and F2-isoprostane. However, compared with smokers, dual users had similar biomarker levels. Former smokers and secondary ST users had similar levels of all five biomarkers. CONCLUSIONS: ST users have lower levels of inflammatory and oxidative stress biomarkers than smokers. IMPACT: ST use alone and in combination with smoking may result in different levels of inflammatory and oxidative stress levels.

Imaging the electrical activity of organelles in living cells.

Eukaryotic cells are complex systems compartmentalized in membrane-bound organelles. Visualization of organellar electrical activity in living cells requires both a suitable reporter and non-invasive imaging at high spatiotemporal resolution. Here we present hVoSorg, an optical method to monitor changes in the membrane potential of subcellular membranes. This method takes advantage of a FRET pair consisting of a membrane-bound voltage-insensitive fluorescent donor and a non-fluorescent voltage-dependent acceptor that rapidly moves across the membrane in response to changes in polarity. Compared to the currently available techniques, hVoSorg has advantages including simple and precise subcellular targeting, the ability to record from individual organelles, and the potential for optical multiplexing of organellar activity.

Determinantes económicos en la incidencia de tuberculosis en México / Economic determinants in the incidence of tuberculosis in Mexico

Resumen Introducción La tuberculosis es la causa principal de muerte por un solo agente infeccioso en el mundo. Anualmente, ocurren 10 millones de casos nuevos y más del 95% en países en vías de desarrollo; este problema de salud se vincula a las condiciones sociales y económicas de la población. Objetivo Analizar la relación entre el gasto en salud y la pobreza con la incidencia de tuberculosis en México. Material y métodos Investigación no experimental en el que se analizan reportes económicos y epidemiológicos de tuberculosis de México, periodo 2009-2015. Resultados El producto interno bruto (PIB) de México creció 45% en 2014 con relación al año 2009. El porcentaje del PIB invertido en salud disminuyó desde 2009, pasando de 6.2 a 5.9% en 2015. La población en pobreza aumentó de 2010 a 2014, de 46.1 a 46.2%; la pobreza extrema disminuyó de 11.3 a 9.5%. En 2015, se diagnosticaron 20,561 casos nuevos de tuberculosis, con una incidencia de 17 casos por cada 100,000 habitantes, incrementando dos décimas con relación al año previo. Conclusión El incremento de la incidencia de tuberculosis en México se relaciona con las condiciones socioeconómicas de la población. Las políticas públicas deberán atender los determinantes sociales.

Abstract Introduction Tuberculosis, the main cause of death by a single infectious agent in the world. Annually there are 10 million new cases and more than 95% in developing countries; this health problem is linked to the social and economic conditions of the population. Objective To analyze the relationship between health spending and poverty with the incidence of tuberculosis in Mexico. Material and methods Non-experimental research, analyzing economic and epidemiological reports of tuberculosis in Mexico, period 2009-2015. Results Mexico's Gross Domestic Product (GDP) grew 45% in 2014 compared to 2009. The percentage of GDP invested in health decreased since 2009, from 6.2 to 5.9% in 2015. The population in poverty increased from 2010 to 2014, from 46.1 to 46.2%; extreme poverty decreased from 11.3 to 9.5%. In 2015, 20,561 new cases of tuberculosis were diagnosed, with an incidence of 17 cases per 100,000 inhabitants, increasing two tenths in relation to the previous year. Conclusion The increase in the incidence of tuberculosis in Mexico is related to the socioeconomic conditions of the population. Public policies must address social determinants.

Exploring the associations between systemic inflammation, obesity and healthy days: a health related quality of life (HRQOL) analysis of NHANES 2005-2008.

BACKGROUND: Obesity is positively associated with low-level chronic inflammation, and negatively associated with several indices of health-related quality of life (HRQOL). It is however not clear if obesity-associated inflammation is partly responsible for the observed negative associations between obesity and HRQOL, and also whether systemic inflammation independently affects HRQOL. We conducted an exploratory analysis to investigate the relationships between obesity, systemic inflammation and indices of HRQOL, using NHANES survey data. METHODS: Data for the variables of interest were available for 6325 adults (aged 20-75 years, BMI > 18.5 kg/m2). Demographic, body mass index (BMI), C-reactive protein (CRP), inflammatory disease status, medication use, smoking, and HRQOL data were obtained from NHANES (2005-2008) and analyzed using sampling-weighted generalized linear models. Data was subjected to multiple imputation in order to mitigate information loss from survey non-response. Both main effects and interaction effects were analyzed to evaluate possible mediation or moderation effects. Model robustness was ascertained via sensitivity analysis. Averaged results from the imputed datasets were reported in as odds ratios (OR) and confidence intervals (CI). RESULTS: Obesity was positively associated with poor physical healthy days (OR: 1.59, 95% CI: 1.15-2.21) in unadjusted models. 'Elevated' and 'clinically raised' levels of the inflammation marker CRP were also positively associated with poor physical healthy days (OR = 1.61, 95% CI: 1.23-2.12, and OR = 2.45, 95% CI: 1.84-3.26, respectively); additionally, 'clinically raised' CRP was positively associated with mental unhealthy days (OR = 1.66, 95% CI: 1.26-2.19). The association between obesity and physical HRQOL was rendered non-significant in models including CRP. Association between 'elevated' and 'clinically raised' CRP and physical unhealthy days remained significant even after adjustment for obesity or inflammation-modulating covariates (OR = 1.36, 95% CI: 1.02-1.82, and OR = 1.75, 95% CI: 1.21-2.54, respectively). CONCLUSIONS: Systemic inflammation appears to mediate the association between obesity and physical unhealthy days. Clinically raised inflammation is an independent determinant of physical and mental unhealthy days. Importantly, elevated (but sub-clinical) inflammation is also negatively associated with physical healthy days, and may warrant more attention from a population health perspective than currently appreciated.

Use Behaviors, Dependence, and Nicotine Exposure Associated with Ad Libitum Cigar Smoking.

OBJECTIVES: To examine factors important to cigar smoking and subsequent nicotine exposure, we evaluated the impact of cigar type, cigarette smoking history, and inhalation behaviors on nicotine dependence, smoking topography, and biomarkers of exposure in current exclusive cigar smokers. METHODS: Adult, exclusive cigar smokers (N = 77) were recruited based on cigar type, cigarette smoking history, and self-reported inhalation behaviors. Participants smoked their own brand product ad libitum for up to one hour; dependence symptoms, smoking topography, and biomarkers of exposure were assessed. RESULTS: Cigar smokers showed low levels of dependence. Cigar smoking alleviated withdrawal and craving symptoms, increased plasma nicotine concentration, and increased exhaled CO. Multiple regression analyses indicate that inhalation behaviors were associated with increased dependence and greater reductions in withdrawal symptoms upon cigar smoking. Large cigar smokers smoked longer and smoked more tobacco than small cigar and cigarillo smokers. Furthermore, large cigar smokers and self-reported inhalers were exposed to more nicotine than small cigar smokers and non-inhalers. CONCLUSIONS: Our study suggests that cigar type and smoking behaviors affect dependence and nicotine exposure upon cigar smoking. These findings provide additional insight into the substantial risks associated with cigar smoking.

Endoplasmic reticulum proteostasis impairment in aging.

Perturbed neuronal proteostasis is a salient feature shared by both aging and protein misfolding disorders. The proteostasis network controls the health of the proteome by integrating pathways involved in protein synthesis, folding, trafficking, secretion, and their degradation. A reduction in the buffering capacity of the proteostasis network during aging may increase the risk to undergo neurodegeneration by enhancing the accumulation of misfolded proteins. As almost one-third of the proteome is synthetized at the endoplasmic reticulum (ER), maintenance of its proper function is fundamental to sustain neuronal function. In fact, ER stress is a common feature of most neurodegenerative diseases. The unfolded protein response (UPR) operates as central player to maintain ER homeostasis or the induction of cell death of chronically damaged cells. Here, we discuss recent evidence placing ER stress as a driver of brain aging, and the emerging impact of neuronal UPR in controlling global proteostasis at the whole organismal level. Finally, we discuss possible therapeutic interventions to improve proteostasis and prevent pathological brain aging.

A TRP conductance modulates repolarization after sensory-dependent depolarization in Chlamydomonas reinhardtii.

Sensory integration is vital for motile organisms constantly exposed to changing surroundings. Chlamydomonas reinhardtii is a single-celled green alga found swimming in freshwater. In this type of alga, sensory input is first detected by membrane receptors located in the cell body, and then transduced to the beating cilia by membrane depolarization. Many components of the machinery associated with sensory integration in C. reinhardtii, such as chemoreceptors and repolarization-associated channels, are yet uncharacterized. TRP channels are known mediators for cellular sensing in animal cells and it has been suggested that the C. reinhardtii genome encodes for a set of TRP proteins. Here, by combining behavioral studies with electrophysiological experiments conducted on both population and single alga, we test whether TRP channel blockers affect algal swimming behavior. Our results suggest that a TRP conductance is associated to the repolarization that follows a depolarizing receptor potential, highlighting a primitive function of TRP proteins.

Systems Genetics Analysis of Genome-Wide Association Study Reveals Novel Associations Between Key Biological Processes and Coronary Artery Disease.

OBJECTIVE: Genome-wide association studies have identified multiple genetic variants affecting the risk of coronary artery disease (CAD). However, individually these explain only a small fraction of the heritability of CAD and for most, the causal biological mechanisms remain unclear. We sought to obtain further insights into potential causal processes of CAD by integrating large-scale GWA data with expertly curated databases of core human pathways and functional networks. APPROACHES AND RESULTS: Using pathways (gene sets) from Reactome, we carried out a 2-stage gene set enrichment analysis strategy. From a meta-analyzed discovery cohort of 7 CAD genome-wide association study data sets (9889 cases/11 089 controls), nominally significant gene sets were tested for replication in a meta-analysis of 9 additional studies (15 502 cases/55 730 controls) from the Coronary ARtery DIsease Genome wide Replication and Meta-analysis (CARDIoGRAM) Consortium. A total of 32 of 639 Reactome pathways tested showed convincing association with CAD (replication P<0.05). These pathways resided in 9 of 21 core biological processes represented in Reactome, and included pathways relevant to extracellular matrix (ECM) integrity, innate immunity, axon guidance, and signaling by PDRF (platelet-derived growth factor), NOTCH, and the transforming growth factor-ß/SMAD receptor complex. Many of these pathways had strengths of association comparable to those observed in lipid transport pathways. Network analysis of unique genes within the replicated pathways further revealed several interconnected functional and topologically interacting modules representing novel associations (eg, semaphoring-regulated axonal guidance pathway) besides confirming known processes (lipid metabolism). The connectivity in the observed networks was statistically significant compared with random networks (P<0.001). Network centrality analysis (degree and betweenness) further identified genes (eg, NCAM1, FYN, FURIN, etc) likely to play critical roles in the maintenance and functioning of several of the replicated pathways. CONCLUSIONS: These findings provide novel insights into how genetic variation, interpreted in the context of biological processes and functional interactions among genes, may help define the genetic architecture of CAD.

Integrative genomics reveals novel molecular pathways and gene networks for coronary artery disease.

The majority of the heritability of coronary artery disease (CAD) remains unexplained, despite recent successes of genome-wide association studies (GWAS) in identifying novel susceptibility loci. Integrating functional genomic data from a variety of sources with a large-scale meta-analysis of CAD GWAS may facilitate the identification of novel biological processes and genes involved in CAD, as well as clarify the causal relationships of established processes. Towards this end, we integrated 14 GWAS from the CARDIoGRAM Consortium and two additional GWAS from the Ottawa Heart Institute (25,491 cases and 66,819 controls) with 1) genetics of gene expression studies of CAD-relevant tissues in humans, 2) metabolic and signaling pathways from public databases, and 3) data-driven, tissue-specific gene networks from a multitude of human and mouse experiments. We not only detected CAD-associated gene networks of lipid metabolism, coagulation, immunity, and additional networks with no clear functional annotation, but also revealed key driver genes for each CAD network based on the topology of the gene regulatory networks. In particular, we found a gene network involved in antigen processing to be strongly associated with CAD. The key driver genes of this network included glyoxalase I (GLO1) and peptidylprolyl isomerase I (PPIL1), which we verified as regulatory by siRNA experiments in human aortic endothelial cells. Our results suggest genetic influences on a diverse set of both known and novel biological processes that contribute to CAD risk. The key driver genes for these networks highlight potential novel targets for further mechanistic studies and therapeutic interventions.

Effects of leucine supplementation and serum withdrawal on branched-chain amino acid pathway gene and protein expression in mouse adipocytes.

The essential branched-chain amino acids (BCAA), leucine, valine and isoleucine, are traditionally associated with skeletal muscle growth and maintenance, energy production, and generation of neurotransmitter and gluconeogenic precursors. Recent evidence from human and animal model studies has established an additional link between BCAA levels and obesity. However, details of the mechanism of regulation of BCAA metabolism during adipogenesis are largely unknown. We interrogated whether the expression of genes and proteins involved in BCAA metabolism are sensitive to the adipocyte differentiation process, and responsive to nutrient stress from starvation or BCAA excess. Murine 3T3-L1 preadipocytes were differentiated to adipocytes under control conditions and under conditions of L-leucine supplementation or serum withdrawal. RNA and proteins were isolated at days 0, 4 and 10 of differentiation to represent pre-differentiation, early differentiation and late differentiation stages. Expression of 16 BCAA metabolism genes was quantified by quantitative real-time PCR. Expression of the protein levels of branched-chain amino acid transaminase 2 (Bcat2) and branched-chain alpha keto acid dehydrogenase (Bckdha) was quantified by immunoblotting. Under control conditions, all genes displayed induction of gene expression during early adipogenesis (Day 4) compared to Day 0. Leucine supplementation resulted in an induction of Bcat2 and Bckdha genes during early and late differentiation. Western blot analysis demonstrated condition-specific concordance between gene and protein expression. Serum withdrawal resulted in undetectable Bcat2 and Bckdha protein levels at all timepoints. These results demonstrate that the expression of genes related to BCAA metabolism are regulated during adipocyte differentiation and influenced by nutrient levels. These results provide additional insights on how BCAA metabolism is associated with adipose tissue function and extends our understanding of the transcriptomic response of this pathway to variations in nutrient availability.

Integrative pathway analysis of a genome-wide association study of (V)O(2max) response to exercise training.

We previously reported the findings from a genome-wide association study of the response of maximal oxygen uptake (Vo2max) to an exercise program. Here we follow up on these results to generate hypotheses on genes, pathways, and systems involved in the ability to respond to exercise training. A systems biology approach can help us better establish a comprehensive physiological description of what underlies Vo2maxtrainability. The primary material for this exploration was the individual single-nucleotide polymorphism (SNP), SNP-gene mapping, and statistical significance levels. We aimed to generate novel hypotheses through analyses that go beyond statistical association of single-locus markers. This was accomplished through three complementary approaches: 1) building de novo evidence of gene candidacy through informatics-driven literature mining; 2) aggregating evidence from statistical associations to link variant enrichment in biological pathways to Vo2max trainability; and 3) predicting possible consequences of variants residing in the pathways of interest. We started with candidate gene prioritization followed by pathway analysis focused on overrepresentation analysis and gene set enrichment analysis. Subsequently, leads were followed using in silico analysis of predicted SNP functions. Pathways related to cellular energetics (pantothenate and CoA biosynthesis; PPAR signaling) and immune functions (complement and coagulation cascades) had the highest levels of SNP burden. In particular, long-chain fatty acid transport and fatty acid oxidation genes and sequence variants were found to influence differences in Vo2max trainability. Together, these methods allow for the hypothesis-driven ranking and prioritization of genes and pathways for future experimental testing and validation.

Redundancy control in pathway databases (ReCiPa): an application for improving gene-set enrichment analysis in Omics studies and "Big data" biology.

Abstract Unparalleled technological advances have fueled an explosive growth in the scope and scale of biological data and have propelled life sciences into the realm of "Big Data" that cannot be managed or analyzed by conventional approaches. Big Data in the life sciences are driven primarily via a diverse collection of 'omics'-based technologies, including genomics, proteomics, metabolomics, transcriptomics, metagenomics, and lipidomics. Gene-set enrichment analysis is a powerful approach for interrogating large 'omics' datasets, leading to the identification of biological mechanisms associated with observed outcomes. While several factors influence the results from such analysis, the impact from the contents of pathway databases is often under-appreciated. Pathway databases often contain variously named pathways that overlap with one another to varying degrees. Ignoring such redundancies during pathway analysis can lead to the designation of several pathways as being significant due to high content-similarity, rather than truly independent biological mechanisms. Statistically, such dependencies also result in correlated p values and overdispersion, leading to biased results. We investigated the level of redundancies in multiple pathway databases and observed large discrepancies in the nature and extent of pathway overlap. This prompted us to develop the application, ReCiPa (Redundancy Control in Pathway Databases), to control redundancies in pathway databases based on user-defined thresholds. Analysis of genomic and genetic datasets, using ReCiPa-generated overlap-controlled versions of KEGG and Reactome pathways, led to a reduction in redundancy among the top-scoring gene-sets and allowed for the inclusion of additional gene-sets representing possibly novel biological mechanisms. Using obesity as an example, bioinformatic analysis further demonstrated that gene-sets identified from overlap-controlled pathway databases show stronger evidence of prior association to obesity compared to pathways identified from the original databases.

A cell-free assay to determine the stoichiometry of plasma membrane proteins.

Plasma membrane receptors, transporters, and ion channel molecules are often found as oligomeric structures that participate in signaling cascades essential for cell survival. Different states of protein oligomerization may play a role in functional control and allosteric regulation. Stochastic GFP-photobleaching (SGP) has emerged as an affordable and simple method to determine the stoichiometry of proteins at the plasma membrane. This non-invasive optical approach can be useful for total internal reflection of fluorescence microscopy (TIRFM), where signal-to-noise ratio is very high at the plasma membrane. Here, we report an alternative methodology implemented on a standard laser scanning confocal microscope (LSCM). The simplicity of our method will allow for its implementation in any epifluorescence microscope of choice.

Near-membrane dynamics and capture of TRPM8 channels within transient confinement domains.

BACKGROUND: The cold and menthol receptor, TRPM8, is a non-selective cation channel expressed in a subset of peripheral neurons that is responsible for neuronal detection of environmental cold stimuli. It was previously shown that members of the transient receptor potential (TRP) family of ion channels are translocated toward the plasma membrane (PM) in response to agonist stimulation. Because the spatial and temporal dynamics of cold receptor cell-surface residence may determine neuronal activity, we hypothesized that the movement of TRPM8 to and from the PM might be a regulated process. Single particle tracking (SPT) is a useful tool for probing the organization and dynamics of protein constituents in the plasma membrane. METHODOLOGY/PRINCIPAL FINDINGS: We used SPT to study the receptor dynamics and describe membrane/near-membrane behavior of particles containing TRPM8-EGFP in transfected HEK-293T and F-11 cells. Cells were imaged using total internal reflection fluorescence (TIRF) microscopy and the 2D and 3D trajectories of TRPM8 molecules were calculated by analyzing mean-square particle displacement against time. Four characteristic types of motion were observed: stationary mode, simple Brownian diffusion, directed motion, and confined diffusion. In the absence of cold or menthol to activate the channel, most TRPM8 particles move in network covering the PM, periodically lingering for 2-8 s in confined microdomains of about 800 nm radius. Removing cholesterol with methyl-beta-cyclodextrin (MßCD) stabilizes TRPM8 motion in the PM and is correlated with larger TRPM8 current amplitude that results from an increase in the number of available channels without a change in open probability. CONCLUSIONS/SIGNIFICANCE: These results reveal a novel mechanism for regulating TRPM8 channel activity, and suggest that PM dynamics may play an important role in controlling electrical activity in cold-sensitive neurons.

Correlation between fractal dimension and surface characterization by small angle X-ray scattering in marble.

Among several analysis techniques applied to the study of surface passivation using dicarboxylic acids, small angle X-ray scattering (SAXS) has proved to be relevant in the physicochemical interpretation of the surface association resulting between calcium carbonate and the molecular structure of malonic acid. It is possible to establish chemical affinity principles through bidimensional geometric analysis in terms of the fractal dimension obtained experimentally by SAXS. In this Article, we present results about the adsorption of malonic acid on calcite, using theoretical and mathematical principles of the fractal dimension.

Structural and textural evolution during folding of layers of layered double hydroxides.

Layers of a layered double hydroxide, containing aluminum 4-fold coordinated, were partially folded in order to obtain a fibrous hydrotalcite-like compound. The hydrotalcite layers, in the presence of an anionic surfactant (sodium dodecyl sulfate) after hydrothermal treatment for 2 weeks, acquire a mesoporous-like arrangement. The transformation was monitored by techniques sensitive to structural and textural properties. Results suggest that brucite-like layers can be joined throughout unsaturated coordinated aluminum, that is, tetrahedral aluminum which links through hydrogen bonds to form aluminum octahedrally coordinated. The fractal dimension parameter was very sensitive to evolution from layered to fibrous hydrotalcites.

Comparative study of regioselective synthesis of beta-aminoalcohols under solventless conditions catalyzed by sulfated zirconia and SZ/MCM-41.

Sulfated zirconia and SZ/MCM-41 were used as catalysts for the synthesis of beta-aminoalcohols via epoxide aminolysis. Sulfated zirconia was prepared by sol-gel and SZ/MCM-41 was obtained by impregnation. Solid catalysts were characterized by XRD, SEM-EDS, UV-Vis, FT-IR pyridine desorption and Nitrogen physisorption. Both acid materials were useful as catalysts, even when they were recycled several times. The beta-aminoalcohols were characterized by FT-IR, (1)H- and (13)C-NMR and GC-MS.