Application of solid-state NMR restraint potentials in membrane protein modeling

We have developed a set of orientational restraint potentials for solid-state NMR observables including (15)N chemical shift and (15)N-(1)H dipolar coupling. Torsion angle molecular dynamics simulations with available experimental (15)N chemical shift and (15)N-(1)H dipolar coupling as target values have been performed to determine orientational information of four membrane proteins and to model the structures of some of these systems in oligomer states. The results suggest that incorporation of the orientational restraint potentials into molecular dynamics provides an efficient means to the determination of structures that optimally satisfy the experimental observables without an extensive geometrical search.     

Latrophilin-2 is a novel receptor of LRG1 that rescues vascular and neurological abnormalities and restores diabetic erectile function

Diabetes mellitus (DM) is a chronic metabolic disorder characterized by inappropriate hyperglycemia, which causes endothelial dysfunction and peripheral neuropathy, ultimately leading to multiple complications. One prevalent complication is diabetic erectile dysfunction (ED), which is more severe and more resistant to treatment than nondiabetic ED. The serum glycoprotein leucine-rich ɑ-2-glycoprotein 1 (LRG1) is a modulator of TGF-β-mediated angiogenesis and has been proposed as a biomarker for a variety of diseases, including DM. Here, we found that the adhesion GPCR latrophilin-2 (LPHN2) is a TGF-β-independent receptor of LRG1. By interacting with LPHN2, LRG1 promotes both angiogenic and neurotrophic processes in mouse tissue explants under hyperglycemic conditions. Preclinical studies in a diabetic ED mouse model showed that LRG1 administration into the penile tissue, which exhibits significantly increased LPHN2 expression, fully restores erectile function by rescuing vascular and neurological abnormalities. Further investigations revealed that PI3K, AKT, and NF-κB p65 constitute the key intracellular signaling pathway of the LRG1/LPHN2 axis, providing important mechanistic insights into LRG1-mediated angiogenesis and nerve regeneration in DM. Our findings suggest that LRG1 can be a potential new therapeutic option for treating aberrant peripheral blood vessels and neuropathy associated with diabetic complications, such as diabetic ED.Subject terms: Biological therapy, Cytokines, Recombinant protein therapy, Extracellular signalling molecules     

Harmonious Heterointerfaces Formed on 2D-Pt Nanodendrites by Facet-Respective Stepwise Metal Deposition for Enhanced Hydrogen Evolution Reaction

The performance of nanocrystal (NC) catalysts could be maximized by introducing rationally designed heterointerfaces formed by the facet- and spatio-specific modification with other materials of desired size and thickness. However, such heterointerfaces are limited in scope and synthetically challenging. Herein, we applied a wet chemistry method to tunably deposit Pd and Ni on the available surfaces of porous 2D−Pt nanodendrites (NDs). Using 2D silica nanoreactors to house the 2D-PtND, an 0.5-nm-thick epitaxial Pd or Ni layer ( e - Pd or e -Ni ) was exclusively formed on the flat {110} surface of 2D−Pt, while a non-epitaxial Pd or Ni layer ( n - Pd or n -Ni ) was typically deposited at the {111/100} edge in absence of nanoreactor. Notably, these differently located Pd/Pt and Ni/Pt heterointerfaces experienced distinct electronic effect to influence unequally in electrocatalytic synergy for hydrogen evolution reaction (HER). For instance, an enhanced H₂ generation on the Pt{110} facet with 2D-2D interfaced e -Pd deposition and faster water dissociation on the edge-located n -Ni overpowered their facet-located counterparts in respective HER catalysis. Therefore, a feasible assembling of the valuable heterointerfaces in the optimal 2D n -Ni/e-Pd/Pt catalyst overcame the sluggish alkaline HER kinetics, with a catalytic activity 7.9 times higher than that of commercial Pt/C.     

Characterization of the surface structural,mechanical, and thermal properties of benzocyclobutene dielectric polymers using scanned probe microscopy

Scanning probe microscopy (SPM) techniques are used to characterize surfaces related to the processing of benzocyclobutene (BCB) dielectric thin films. Thermally cured resins and photodefineable resins are sold under the trade name CYLCOTENE^TM1) for electronic applications. TappingMode AFM (TMAFM) imaging is used to follow changes in adhesion promoter morphology upon baking to help explain adhesion performance. Power spectral density (PSD) analysis of TMAFM images of plasma treated BCB surfaces are unique and can be used to ‘fingerprint’ processes. Selective oxidation of the BCB surface can be used to fabricate a phase imaging standard for TMAFM. Near surface modulus of the BCB materials is 3.6 ± 0.2 GPa and the hardness is 0.38 ± 0.2 GPa measured by depth‐sensing nanoindentation. Creep recovery of indents can be used to qualitatively distinguish between thermal and photocureable materials. A heated tip in a scanning thermal microscope can induce the thermal curing of BCB over micron sized areas. Local thermal analysis with the same probe allows the measurement of the changes in the glass transition, T_g, at the surface with cure temperature.     

Rank gain of Jacobians over number field extensions with prescribed Galois groups

We investigate the rank gain of elliptic curves, and more generally, Jacobian varieties, over non-Galois extensions whose Galois closure has a Galois group permutation-isomorphic to a prescribed group G (in short, “G-extensions”). In particular, for alternating groups and (an infinite family of) projective linear groups G, we show that most elliptic curves over (for example) $\mathbb{Q}$ gain rank over infinitely many G-extensions, conditional only on the parity conjecture. More generally, we provide a theoretical criterion, which allows to deduce that “many” elliptic curves gain rank over infinitely many G-extensions, conditional on the parity conjecture and on the existence of geometric Galois realizations with group G and certain local properties.