Levels of Angiotensin-Converting Enzyme and Apolipoproteins Are Associated with Alzheimer’s Disease and Cardiovascular Diseases

Angiotensin-converting enzyme-1 (ACE1) and apolipoproteins (APOs) may play important roles in the development of Alzheimer’s disease (AD) and cardiovascular diseases (CVDs). This study aimed to examine the associations of AD, CVD, and endocrine-metabolic diseases (EMDs) with the levels of ACE1 and 9 APO proteins (ApoAI, ApoAII, ApoAIV, ApoB, ApoCI, ApoCIII, ApoD, ApoE, and ApoH). Non-Hispanic white individuals including 109 patients with AD, 356 mild cognitive impairment (MCI), 373 CVD, 198 EMD and controls were selected from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) dataset. Multivariable general linear model (GLM) was used to examine the associations. ApoE ε4 allele was associated with AD, as well as ApoAIV, ApoB and ApoE proteins, but not associated with CVD and EMD. Both AD and CVD were associated with levels of ACE1, ApoB, and ApoH proteins. AD, MCI and EMD were associated with levels of ACE1, ApoAII, and ApoE proteins. This is the first study to report associations of ACE1 and several APO proteins with AD, MCI, CVD and EMD, respectively, including upregulated and downregulated protein levels. In conclusion, as specific or shared biomarkers, the levels of ACE1 and APO proteins are implicated for AD, CVD, EMD and ApoE ε4 allele. Further studies are required for validation to establish reliable biomarkers for these health condition

Ultrahigh Piezoelectric Performance through Synergistic Compositional and Microstructural Engineering

Piezoelectric materials enable the conversion of mechanical energy into electrical energy and vice-versa. Ultrahigh piezoelectricity has been only observed in single crystals. Realization of piezoelectric ceramics with longitudinal piezoelectric constant (d33) close to 2000 pC N–1, which combines single crystal-like high properties and ceramic-like cost effectiveness, large-scale manufacturing, and machinability will be a milestone in advancement of piezoelectric ceramic materials. Here, guided by phenomenological models and phase-field simulations that provide conditions for flattening the energy landscape of polarization, a synergistic design strategy is demonstrated that exploits compositionally driven local structural heterogeneity and microstructural grain orientation/texturing to provide record piezoelectricity in ceramics. This strategy is demonstrated on [001]PC-textured and Eu3+-doped Pb(Mg1/3Nb2/3)O3-PbTiO3 (PMN-PT) ceramics that exhibit the highest piezoelectric coefficient (small-signal d33 of up to 1950 pC N–1 and large-signal d33* of ≈2100 pm V–1) among all the reported piezoelectric ceramics. Extensive characterization conducted using high-resolution microscopy and diffraction techniques in conjunction with the computational models reveals the underlying mechanisms governing the piezoelectric performance. Further, the impact of losses on the electromechanical coupling is identified, which plays major role in suppressing the percentage of piezoelectricity enhancement, and the fundamental understanding of loss in this study sheds light on further enhancement of piezoelectricity. These results on cost-effective and record performance piezoelectric ceramics will launch a new generation of piezoelectric applications

Pyrosequencing analysis of IRS1 methylation levels in schizophrenia with tardive dyskinesia

Tardive dyskinesia (TD) is a serious side effect of certain antipsychotic medications that are used to treat schizophrenia (SCZ) and other mental illnesses. The methylation status of the insulin receptor substrate 1 (IRS1) gene is reportedly associated with SCZ; however, no study, to the best of the authors\u27 knowledge, has focused on the quantitative DNA methylation levels of the IRS1 gene using pyrosequencing in SCZ with or without TD. The present study aimed to quantify DNA methylation levels of 4 CpG sites in the IRS1 gene using a Chinese sample including SCZ patients with TD and without TD (NTD) and healthy controls (HCs). The general linear model (GLM) was used to detect DNA methylation levels among the 3 proposed groups (TD vs. NTD vs. HC). Mean DNA methylation levels of 4 CpG sites demonstrated normal distribution. Pearson\u27s correlation analysis did not reveal any significant correlations between the DNA methylation levels of the 4 CpG sites and the severity of SCZ. GLM revealed significant differences between the 3 groups for CpG site 1 and the average of the 4 CpG sites (P=0.0001 and P=0.0126, respectively). Furthermore, the TD, NTD and TD + NTD groups demonstrated lower methylation levels in CpG site 1 (P=0.0003,

Polymorphisms Within RYR3 Gene Are Associated With Risk and Age at Onset of Hypertension, Diabetes, and Alzheimer’s Disease

BACKGROUND Hypertension affects 33% of Americans while type 2 diabetes and Alzheimer’s disease (AD) affect 10% of Americans, respectively. Ryanodine receptor 3 gene (RYR3) codes for the RYR which functions to release stored endoplasmic reticulum calcium ions (Ca2+) to increase intracellular Ca2+ concentration. Increasing studies demonstrate that altered levels of intracellular Ca2+ affect cardiac contraction, insulin secretion, and neurodegeneration. In this study, we investigated associations of the RYR3 genetic variants with hypertension, AD, and diabetes. METHODS Family data sets were used to explore association of RYR3 polymorphisms with risk and age at onset (AAO) of hypertension, diabetes, and AD. RESULTS Family-based association tests using generalized estimating equations (FBAT–GEE) showed several unique or shared disease-1 associated variants in the RYR3 gene. Three single nuclear polymorphisms (SNPs; rs2033610, rs2596164, and rs2278317) are significantly associated with risk for hypertension, diabetes, and AD. Two SNPs (rs4780174 and rs7498093) are significantly associated with AAO of the 3 diseases. CONCLUSIONS RYR3 variants are associated with hypertension, diabetes, and AD. Replication of these results of this gene in these 3 complex traits may help to better understand the genetic basis of calcium-signaling gene, RYR3 in association with risk and AAO of these diseases

Polymorphisms Within RYR3 Gene Are Associated With Risk and Age at Onset of Hypertension, Diabetes, and Alzheimer\u27s Disease

Background: Hypertension affects 33% of Americans while type 2 diabetes and Alzheimer\u27s disease (AD) affect 10% of Americans, respectively. Ryanodine receptor 3 gene (RYR3) codes for the RYR which functions to release stored endoplasmic reticulum calcium ions (Ca2+) to increase intracellular Ca2+ concentration. Increasing studies demonstrate that altered levels of intracellular Ca2+ affect cardiac contraction, insulin secretion, and neurodegeneration. In this study, we investigated associations of the RYR3 genetic variants with hypertension, AD, and diabetes. Methods: Family data sets were used to explore association of RYR3 polymorphisms with risk and age at onset (AAO) of hypertension, diabetes, and AD. Results: Family-based association tests using generalized estimating equations (FBAT-GEE) showed several unique or shared disease-1 associated variants in the RYR3 gene. Three single nuclear polymorphisms (SNPs; rs2033610, rs2596164, and rs2278317) are significantly associated with risk for hypertension, diabetes, and AD. Two SNPs (rs4780174 and rs7498093) are significantly associated with AAO of the 3 diseases. Conclusions: RYR3 variants are associated with hypertension, diabetes, and AD. Replication of these results of this gene in these 3 complex traits may help to better understand the genetic basis of calcium-signaling gene, RYR3 in association with risk and AAO of these diseases