Aldosterone signaling through transient receptor potential melastatin 7 cation channel (TRPM7) and its α-kinase domain

We demonstrated a role for the Mg2 + transporter TRPM7, a bifunctional protein with channel and α-kinase domains, in aldosterone signaling. Molecular mechanisms underlying this are elusive. Here we investigated the function of TRPM7 and its α-kinase domain on Mg2 + and pro-inflammatory signaling by aldosterone. Kidney cells (HEK-293) expressing wild-type human TRPM7 (WThTRPM7) or constructs in which the α-kinase domain was deleted (ΔKinase) or rendered inactive with a point mutation in the ATP binding site of the α-kinase domain (K1648R) were studied. Aldosterone rapidly increased [Mg2 +]i and stimulated NADPH oxidase-derived generation of reactive oxygen species (ROS) in WT hTRPM7 and TRPM7 kinase dead mutant cells. Translocation of annexin-1 and calpain-II and spectrin cleavage (calpain target) were increased by aldosterone in WT hTRPM7 cells but not in α-kinase-deficient cells. Aldosterone stimulated phosphorylation of MAP kinases and increased expression of pro-inflammatory mediators ICAM-1, Cox-2 and PAI-1 in Δkinase and K1648R cells, effects that were inhibited by eplerenone (mineralocorticoid receptor (MR) blocker). 2-APB, a TRPM7 channel inhibitor, abrogated aldosterone-induced Mg2 + responses in WT hTRPM7 and mutant cells. In 2-APB-treated ΔKinase and K1648R cells, aldosterone-stimulated inflammatory responses were unchanged. These data indicate that aldosterone stimulates Mg2 + influx and ROS production in a TRPM7-sensitive, kinase-insensitive manner, whereas activation of annexin-1 requires the TRPM7 kinase domain. Moreover TRPM7 α-kinase modulates inflammatory signaling by aldosterone in a TRPM7 channel/Mg2 +-independent manner. Our findings identify novel mechanisms for non-genomic actions of aldosterone involving differential signaling through MR-activated TRPM7 channel and α-kinase

Transition in incompressible boundary layers with two-dimensional excrescences

An experimental investigation of the transition process in boundary layers subjected to forward- or aft-facing two-dimensional step excrescences is described. The objective of the work was to characterize the variation of transition Reynolds numbers with measurable roughness and boundary layer parameters, with the specific goal of specifying new tolerance criteria for laminar flow airfoils, alongside a fundamental investigation of linear boundary layer stability mechanisms. Results from an ongoing program of increasing complexity on effects of pressure gradient on excrescence-induced transition are presented. Preliminary N-factor calculations are used to determine the effects of boundary layer stability and attempt to isolate the effect of the disturbance due to the excrescence

Effect of Personalized Incentives on Dietary Quality of Groceries Purchased A Randomized Crossover Trial

Importance Many factors are associated with food choice. Personalized interventions could help improve dietary intake by using individual purchasing preferences to promote healthier grocery purchases. Objective To test whether a healthy food incentive intervention using an algorithm incorporating customer preferences, purchase history, and baseline diet quality improves grocery purchase dietary quality and spending on healthy foods. Design, Setting, and Participants This was a 9-month randomized clinical crossover trial (AB–BA) with a 2- to 4-week washout period between 3-month intervention periods. Participants included 224 loyalty program members at an independent Rhode Island supermarket who completed baseline questionnaires and were randomized from July to September 2018 to group 1 (AB) or group 2 (BA). Data analysis was performed from September 2019 to May 2020. Intervention Participants received personalized weekly coupons with nutrition education during the intervention period (A) and occasional generic coupons with nutrition education during the control period (B). An automated study algorithm used customer data to allocate personalized healthy food incentives to participant loyalty cards. All participants received a 5% grocery discount. Main Outcomes and Measures Grocery Purchase Quality Index–2016 (GPQI-16) scores (range, 0-75, with higher scores denoting healthier purchases) and percentage spending on targeted foods were calculated from cumulative purchasing data. Participants in the top and bottom 1% of spending were excluded. Paired t tests examined between-group differences. Results The analytical sample included 209 participants (104 in group 1 and 105 in group 2), with a mean (SD) age of 55.4 (14.0) years. They were predominantly non-Hispanic White (193 of 206 participants [94.1%]) and female (187 of 207 participants [90.3%]). Of 161 participants with income data, 81 (50.3%) had annual household incomes greater than or equal to $100 000. Paired t tests showed that the intervention increased GPQI-16 scores (between-group difference, 1.06; 95% CI, 0.27-1.86; P = .01) and percentage spending on targeted foods (between-group difference, 1.38%; 95% CI, 0.08%-2.69%; P = .04). During the initial intervention period, group 1 (AB) and group 2 (BA) had similar mean (SD) GPQI-16 scores (41.2 [6.6] vs 41.0 [7.5]) and mean (SD) percentage spending on targeted healthy foods (32.0% [10.8%] vs 31.0% [10.5%]). During the crossover intervention period, group 2 had a higher mean (SD) GPQI-16 score than group 1 (42.9 [7.7] vs 41.0 [6.8]) and mean (SD) percentage spending on targeted foods (34.0% [12.1%] vs 32.0% [13.1%]). Conclusions and Relevance This pilot trial demonstrated preliminary evidence for the effectiveness of a novel personalized healthy food incentive algorithm to improve grocery purchase dietary quality. Trial Registration ClinicalTrials.gov Identifier: NCT0374805

Amplitude equations near pattern forming instabilities for strongly driven ferromagnets

A transversally driven isotropic ferromagnet being under the influence of a static external and an uniaxial internal anisotropy field is studied. We consider the dissipative Landau-Lifshitz equation as the fundamental equation of motion and treat it in $1+1$~dimensions. The stability of the spatially homogeneous magnetizations against inhomogeneous perturbations is analyzed. Subsequently the dynamics above threshold is described via amplitude equations and the dependence of their coefficients on the physical parameters of the system is determined explicitly. We find soft- and hard-mode instabilities, transitions between sub- and supercritical behaviour, various bifurcations of higher codimension, and present a series of explicit bifurcation diagrams. The analysis of the codimension-2 point where the soft- and hard-mode instabilities coincide leads to a system of two coupled Ginzburg-Landau equations.Comment: LATeX, 25 pages, submitted to Z.Phys.B figures available via [email protected] in /pub/publications/frank/zpb_95 (postscript, plain or gziped

Transitions/relaxations in polyester adhesive/PET system

The correlations between the transitions and the dielectric relaxation processes of the oriented poly(ethylene terephthalate) (PET) pre-impregnated of the polyester thermoplastic adhesive have been investigated by differential scanning calorimetry (DSC) and dynamic dielectric spectroscopy (DDS). The thermoplastic polyester adhesive and the oriented PET films have been studied as reference samples. This study evidences that the adhesive chain segments is responsible for the physical structure evolution in the PET-oriented film. The transitions and dielectric relaxation modes’ evolutions in the glass transition region appear characteristic of the interphase between adhesive and PET film, which is discussed in terms of molecular mobility. The storage at room temperature of the adhesive tape involves the heterogeneity of the physical structure, characterized by glass transition dissociation. Thus, the correlation between the transitions and the dielectric relaxation processes evidences a segregation of the amorphous phases. Therefore, the physical structure and the properties of the material have been linked to the chemical characteristics

Phase Dynamics of Nearly Stationary Patterns in Activator-Inhibitor Systems

The slow dynamics of nearly stationary patterns in a FitzHugh-Nagumo model are studied using a phase dynamics approach. A Cross-Newell phase equation describing slow and weak modulations of periodic stationary solutions is derived. The derivation applies to the bistable, excitable, and the Turing unstable regimes. In the bistable case stability thresholds are obtained for the Eckhaus and the zigzag instabilities and for the transition to traveling waves. Neutral stability curves demonstrate the destabilization of stationary planar patterns at low wavenumbers to zigzag and traveling modes. Numerical solutions of the model system support the theoretical findings

Turing Instability in a Boundary-fed System

The formation of localized structures in the chlorine dioxide-idodine-malonic acid (CDIMA) reaction-diffusion system is investigated numerically using a realistic model of this system. We analyze the one-dimensional patterns formed along the gradients imposed by boundary feeds, and study their linear stability to symmetry-breaking perturbations (Turing instability) in the plane transverse to these gradients. We establish that an often-invoked simple local linear analysis which neglects longitudinal diffusion is inappropriate for predicting the linear stability of these patterns. Using a fully nonuniform analysis, we investigate the structure of the patterns formed along the gradients and their stability to transverse Turing pattern formation as a function of the values of two control parameters: the malonic acid feed concentration and the size of the reactor in the dimension along the gradients. The results from this investigation are compared with existing experiments.Comment: 41 pages, 18 figures, to be published in Physical Review

The Effect of Acoustic Forcing on Instabilities and Breakdown in Swept-Wing Flow over a Backward-Facing Step

Instability interaction and breakdown were experimentally investigated in the flow over a swept backward-facing step. Acoustic forcing was used to excite the Tollmien-Schlichting (TS) instability and to acquire phase-locked results. The phase-averaged results illustrate the complex nature of the interaction between the TS and stationary cross flow instabilities. The weak stationary cross flow disturbance causes a distortion of the TS wavefront. The breakdown process is characterized by large positive and negative spikes in velocity. The positive spikes occur near the same time and location as the positive part of the TS wave. Higher-order spectral analysis was used to further investigate the nonlinear interactions between the TS instability and the traveling cross flow disturbances. The results reveal that a likely cause for the generation of the spikes corresponds to nonlinear interactions between the TS, traveling cross flow, and stationary cross flow disturbances. The spikes begin at low amplitudes of the unsteady and steady disturbances (2-4% U (sub e) (i.e. boundary layer edge velocity)) but can achieve very large amplitudes (20-30 percent U (sub e) (i.e. boundary layer edge velocity)) that initiate an early, though highly intermittent, breakdown to turbulence

Conductive-probe atomic force microscopy characterization of silicon nanowire

The electrical conduction properties of lateral and vertical silicon nanowires (SiNWs) were investigated using a conductive-probe atomic force microscopy (AFM). Horizontal SiNWs, which were synthesized by the in-plane solid-liquid-solid technique, are randomly deployed into an undoped hydrogenated amorphous silicon layer. Local current mapping shows that the wires have internal microstructures. The local current-voltage measurements on these horizontal wires reveal a power law behavior indicating several transport regimes based on space-charge limited conduction which can be assisted by traps in the high-bias regime (> 1 V). Vertical phosphorus-doped SiNWs were grown by chemical vapor deposition using a gold catalyst-driving vapor-liquid-solid process on higly n-type silicon substrates. The effect of phosphorus doping on the local contact resistance between the AFM tip and the SiNW was put in evidence, and the SiNWs resistivity was estimated

Metabolite of SIR2 reaction modulates TRPM2 Ion channel

The transient receptor potential melastatin-related channel 2 (TRPM2) is a nonselective cation channel, whose prolonged activation by oxidative and nitrative agents leads to cell death. Here, we show that the drug puromycin selectively targets TRPM2-expressing cells, leading to cell death. Our data suggest that the silent information regulator 2 (Sir2 or sirtuin) family of enzymes mediates this susceptibility to cell death. Sirtuins are protein deacetylases that regulate gene expression, apoptosis, metabolism, and aging. These NAD+-dependent enzymes catalyze a reaction in which the acetyl group from substrate is transferred to the ADP-ribose portion of NAD+ to form deacetylated product, nicotinamide, and the metabolite OAADPr, whose functions remain elusive. Using cell-based assays and RNA interference, we show that puromycin-induced cell death is greatly diminished by nicotinamide (a potent sirtuin inhibitor), and by decreased expression of sirtuins SIRT2 and SIRT3. Furthermore, we demonstrate using channel current recordings and binding assays that OAADPr directly binds to the cytoplasmic domain of TRPM2 and activates the TRPM2 channel. ADP-ribose binds TRPM2 with similarly affinity, whereas NAD+ displays almost negligible binding. These studies provide the first evidence for the potential role of sirtuin-generated OAADPr in TRPM2 channel gatin