F-box protein-32 down-regulates small-conductance calcium-activated potassium channel 2 in diabetic mouse atria

Diabetes mellitus (DM) is an independent risk factor for atrial fibrillation, but the underlying ionic mechanism for this association remains unclear. We recently reported that expression of the small-conductance calcium-activated potassium channel 2 (SK2, encoded by KCCN2) in atria from diabetic mice is significantly down-regulated, resulting in reduced SK currents in atrial myocytes from these mice. We also reported that the level of SK2 mRNA expression is not reduced in DM atria but that the ubiquitin-proteasome system (UPS), a major mechanism of intracellular protein degradation, is activated in vascular smooth muscle cells in DM. This suggests a possible role of the UPS in reduced SK currents. To test this possibility, we examined the role of the UPS in atrial SK2 down-regulation in DM. We found that a muscle-specific E3 ligase, F-box protein 32 (FBXO-32, also called atrogin-1), was significantly up-regulated in diabetic mouse atria. Enhanced FBXO-32 expression in atrial cells significantly reduced SK2 protein expression, and siRNA-mediated FBXO-32 knockdown increased SK2 protein expression. Furthermore, co-transfection of SK2 with FBXO-32 complementary DNA in HEK293 cells significantly reduced SK2 expression, whereas co-transfection with atrogin-1ΔF complementary DNA (a nonfunctional FBXO-32 variant in which the F-box domain is deleted) did not have any effects on SK2. These results indicate that FBXO-32 contributes to SK2 down-regulation and that the F-box domain is essential for FBXO-32 function. In conclusion, DM-induced SK2 channel down-regulation appears to be due to an FBXO-32-dependent increase in UPS-mediated SK2 protein degradation

Effect of NiO nanoparticle addition on the structural, microstructural, magnetic, electrical, and magneto-transport properties of La0.67Ca0.33MnO3 nanocomposites

Incorporation of the secondary oxide phase into the manganite composite capable of enhancing low-field magnetoresistance (LFMR) for viability in high-performance spintronic applications. Polycrystalline La0.67Ca0.33MnO3 (LCMO) was prepared via the sol–gel route in this study. The structural, microstructural, magnetic, electrical, and magneto-transport properties of (1−x) LCMO: x NiO, x = 0.00, 0.05, 0.10, 0.15 and 0.20 were investigated in detail. The X-ray diffraction (XRD) patterns showed the coexistence of LCMO and NiO in the composites. The microstructural analysis indicated the amount of NiO nanoparticles segregated at the grain boundaries or on the surface of LCMO grains increased with the increasing secondary phase content. LCMO and NiO still retained their individual magnetic phase as observed from AC susceptibility (ACS) measurement. This further confirmed that there is no interfacial diffusion reaction between these two compounds. The NiO nanoparticle acted as a barrier to charge transport and caused an increase in resistivity for composite samples. The residual resistivity due to the grain/domain boundary is responsible for the scattering mechanism in the metallic region as suggested by the theoretical model fitting, ρ(T)=ρ0+ρ2T2+ρ4.5T4.5. The magnetoresistance values of LCMO and its composites were found to increase monotonically with the decrease in temperature. Hence, the LFMR was observed. Nonetheless, the slight reduction of LFMR in composites was attributed to the thick boundary layer created by NiO and impaired the spin polarised tunnelling process

A reference-grade wild soybean genome

Wild relatives of crop plants are invaluable germplasm for genetic improvement. Here, Xie et al. report a reference-grade wild soybean genome and show that it can be used to identify structural variation and refine quantitative trait loci

A reference-grade wild soybean genome

Efficient crop improvement depends on the application of accurate genetic information contained in diverse germplasm resources. Here we report a reference-grade genome of wild soybean accession W05, with a final assembled genome size of 1013.2 Mb and a contig N50 of 3.3 Mb. The analytical power of the W05 genome is demonstrated by several examples. First, we identify an inversion at the locus determining seed coat color during domestication. Second, a translocation event between chromosomes 11 and 13 of some genotypes is shown to interfere with the assignment of QTLs. Third, we find a region containing copy number variations of the Kunitz trypsin inhibitor (KTI) genes. Such findings illustrate the power of this assembly in the analysis of large structural variations in soybean germplasm collections. The wild soybean genome assembly has wide applications in comparative genomic and evolutionary studies, as well as in crop breeding and improvement programs

Coronary Arterial BK Channel Dysfunction Exacerbates Ischemia Reperfusion-Induced Myocardial Injury in Diabetic Mice

The large conductance Ca2+-activated K+ (BK) channels, abundantly expressed in coronary artery smooth muscle cells (SMCs), play a pivotal role in regulating coronary circulation. A large body of evidence indicates that coronary arterial BK channel function is diminished in both type 1 and type 2 diabetes. However, the consequence of coronary BK channel dysfunction in diabetes is not clear. We hypothesized that impaired coronary BK channel function exacerbates myocardial ischemia/reperfusion (I/R) injury in streptozotocin-induced diabetic mice. Combining patch-clamp techniques and cellular biological approaches, we found that diabetes facilitated the colocalization of angiotensin II (Ang II) type 1 receptors and BK channel α-subunits (BK-α), but not BK channel β1-subunits (BK-β1), in the caveolae of coronary SMCs. This caveolar compartmentation in vascular SMCs not only enhanced Ang II-mediated inhibition of BK-α but also produced a physical disassociation between BK-α and BK-β1, leading to increased infarct size in diabetic hearts. Most importantly, genetic ablation of caveolae integrity or pharmacological activation of coronary BK channels protected the cardiac function of diabetic mice from experimental I/R injury in both in vivo and ex vivo preparations. Our results demonstrate a vascular ionic mechanism underlying the poor outcome of myocardial injury in diabetes. Hence, activation of coronary BK channels may serve as a therapeutic target for cardiovascular complications of diabetes.The accepted manuscript in pdf format is listed with the files at the bottom of this page. The presentation of the authors' names and (or) special characters in the title of the manuscript may differ slightly between what is listed on this page and what is listed in the pdf file of the accepted manuscript; that in the pdf file of the accepted manuscript is what was submitted by the author

Three-Dimensional Graphene: A Biocompatible and Biodegradable Scaffold with Enhanced Oxygenation

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Left Atrial Remodeling and Atrioventricular Coupling in a Canine Model of Early Heart Failure With Preserved Ejection Fraction

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Structural, electrical, and magneto-transport properties of Pr0.7Sr0.3MnO3: Al2O3 composites

Incorporation of insulating secondary phase into manganite composites can enhance the low-field magnetoresistance (LFMR). This work reports the structural and electrical transport properties of (1-x) Pr0.7Sr0.3MnO3 (PSMO): x Al2O3 composites synthesised by solid-state reaction method. X-ray diffraction (XRD) patterns indicated that Mn-O-Mn bond distance and angle were disturbed due to the substitution of Al3+ at Mn-site of PSMO system. This subsequently increased the resistivity of composite samples and shifted the metal-insulator transition temperature (TMI) to lower temperatures as increasing content of Al2O3. LFMR effect was observed as the magnetoresistance values increase monotonically with the decreasing temperature