Tyrosine Nitration of Voltage-dependent Anion Channels in Cardiac Ischemia-reperfusion: Reduction by Peroxynitrite Scavenging

Excess superoxide (O2−) and nitric oxide (NO) forms peroxynitrite (ONOO−) during cardiac ischemia reperfusion (IR) injury, which in turn induces protein tyrosine nitration (tyr-N). Mitochondria are both a source of and target for ONOO−. Our aim was to identify specific mitochondrial proteins that display enhanced tyr-N after cardiac IR injury, and to explore whether inhibiting O2−/ONOO− during IR decreases mitochondrial protein tyr-N and consequently improves cardiac function. We show here that IR increased tyr-N of 35 and 15 kDa mitochondrial proteins using Western blot analysis with 3-nitrotyrosine antibody. Immunoprecipitation (IP) followed by LC–MS/MS identified 13 protein candidates for tyr-N. IP and Western blot identified and confirmed that the 35 kDa tyr-N protein is the voltage-dependent anion channel (VDAC). Tyr-N of native cardiac VDAC with IR was verified on recombinant (r) VDAC with exogenous ONOO−. We also found that ONOO− directly enhanced rVDAC channel activity, and rVDAC tyr-N induced by ONOO− formed oligomers. Resveratrol (RES), a scavenger of O2−/ONOO−, reduced the tyr-N levels of both native and recombinant VDAC, while L-NAME, which inhibits NO generation, only reduced tyr-N levels of native VDAC. O2− and ONOO− levels were reduced in perfused hearts during IR by RES and L-NAME and this was accompanied by improved cardiac function. These results identify tyr-N of VDAC and show that reducing ONOO− during cardiac IR injury can attenuate tyr-N of VDAC and improve cardiac function

Structure of the full-length TRPV2 channel by cryo-EM.

Transient receptor potential (TRP) proteins form a superfamily Ca(2+)-permeable cation channels regulated by a range of chemical and physical stimuli. Structural analysis of a 'minimal' TRP vanilloid subtype 1 (TRPV1) elucidated a mechanism of channel activation by agonists through changes in its outer pore region. Though homologous to TRPV1, other TRPV channels (TRPV2-6) are insensitive to TRPV1 activators including heat and vanilloids. To further understand the structural basis of TRPV channel function, we determined the structure of full-length TRPV2 at ∼5 Å resolution by cryo-electron microscopy. Like TRPV1, TRPV2 contains two constrictions, one each in the pore-forming upper and lower gates. The agonist-free full-length TRPV2 has wider upper and lower gates compared with closed and agonist-activated TRPV1. We propose these newly revealed TRPV2 structural features contribute to diversity of TRPV channels

Development of a photonic gauging sensor for hazardous liquids

Previous papers have described the use of a Long Period Grating (LPG) as a simple photonic level sensor. We show how a useful performance of 1 mm resolution over 1 m could be obtained in a system that requires only a low-cost interrogator rather than an Optical Spectrum Analyzer

Osteoprotegerin reduces osteoclast resorption activity without affecting osteogenesis on nanoparticulate mineralized collagen scaffolds.

The instructive capabilities of extracellular matrix-inspired materials for osteoprogenitor differentiation have sparked interest in understanding modulation of other cell types within the bone regenerative microenvironment. We previously demonstrated that nanoparticulate mineralized collagen glycosaminoglycan (MC-GAG) scaffolds efficiently induced osteoprogenitor differentiation and bone healing. In this work, we combined adenovirus-mediated delivery of osteoprotegerin (AdOPG), an endogenous anti-osteoclastogenic decoy receptor, in primary human mesenchymal stem cells (hMSCs) with MC-GAG to understand the role of osteoclast inactivation in augmentation of bone regeneration. Simultaneous differentiation of osteoprogenitors on MC-GAG and osteoclast progenitors resulted in bidirectional positive regulation. AdOPG expression did not affect osteogenic differentiation alone. In the presence of both cell types, AdOPG-transduced hMSCs on MC-GAG diminished osteoclast-mediated resorption in direct contact; however, osteoclast-mediated augmentation of osteogenic differentiation was unaffected. Thus, the combination of OPG with MC-GAG may represent a method for uncoupling osteogenic and osteoclastogenic differentiation to augment bone regeneration

Translating the Diabetes Prevention Program into the Community The DEPLOY Pilot Study

Background The Diabetes Prevention Program (DPP) found that an intensive lifestyle intervention can reduce the development of diabetes by more than half in adults with prediabetes, but there is little information about the feasibility of offering such an intervention in community settings. This study evaluated the delivery of a group-based DPP lifestyle intervention in partnership with the YMCA. Methods This pilot cluster-randomized trial was designed to compare group-based DPP lifestyle intervention delivery by the YMCA to brief counseling alone (control) in adults who attended a diabetes risk-screening event at one of two semi-urban YMCA facilities and who had a BMI ≥24 kg/m2, ≥2 diabetes risk factors, and a random capillary blood glucose of 110–199 mg/dL. Multivariate regression was used to compare between-group differences in changes in body weight, blood pressures, HbA1c, total cholesterol, and HDL-cholesterol after 6 and 12 months. Results Among 92 participants, controls were more often women (61% vs 50%) and of nonwhite race (29% vs 7%). After 6 months, body weight decreased by 6.0% (95% CI=4.7, 7.3) in intervention participants and 2.0% (95% CI=0.6, 3.3) in controls (p<0.001; difference between groups). Intervention participants also had greater changes in total cholesterol (–22 mg/dL vs +6 mg/dL controls; p<0.001). These differences were sustained after 12 months, and adjustment for differences in race and gender did not alter these findings. With only two matched YMCA sites, it was not possible to adjust for potential clustering by site. Conclusions The YMCA may be a promising channel for wide-scale dissemination of a low-cost approach to lifestyle diabetes prevention

An Origami-Inspired Design of a Thermal Mixing Element Within a Concentrated Solar Power System

A Concentrated Solar Power on Demand (CSPonD) system heats a tank of molten salt with sunlight, storing the sun's energy thermally and generating electricity when needed using a heat exchanger. To prevent the heated salt from forming thermal gradients (reducing the heat exchanger's efficiency) or overheating (and becoming corrosive), a thermal mixing element mixes the heated salt both axially and radially. Since the mixing element can only move axially within the tank, it contains internal, radial channels to induce radial flow of the salt. These channels are constructed from tabbed wall-components, whose tabs seat into and extend past slots in the top-and bottom-plates of the mixing element. The top-and bottom-plates are constructed from multiple panels with overlapping slots, allowing the panels to form the plates when the tabs are inserted. This interlocking design allows majority of the mixing element to be rapidly manufactured at a low cost from sheet metal and simplifies transportation. In situ, the assembled components fasten together by bending the overextending tabs, minimizing the number of fasteners needed. Topics: Design, Concentrating solar powerMasdar Institute of Science and Technolog

Probing flavor changing interactions in hadron collisions

The subprocess $gg \to t\bar{c}+\bar{t}c$ in the two-Higgs-doublet model with flavor-changing scalar couplings is examined at the one loop level. With perturbative QCD factorization theorem, the corresponding cross sections for hadron-hadron collisions are computed numerically. The results are applicable to the whole mass range of the weakly coupled Higgs bosons. In case we could efficiently exclude the severe backgrounds of the $t\bar{c}(\bar{t}c)$ production signal, probing the flavor-changing top-charm-scalar vertex at hadron colliders would be very promising and accessible experimentally.Comment: LaTex file, 14 pages, 8 EPS figure