Enhanced Electron Correlation and Significantly Suppressed Thermal Conductivity in Dirac Nodal-Line Metal Nanowires by Chemical Doping.

Enhancing electron correlation in a weakly interacting topological system has great potential to promote correlated topological states of matter with extraordinary quantum properties. Here, the enhancement of electron correlation in a prototypical topological metal, namely iridium dioxide (IrO2 ), via doping with 3d transition metal vanadium is demonstrated. Single-crystalline vanadium-doped IrO2 nanowires are synthesized through chemical vapor deposition where the nanowire yield and morphology are improved by creating rough surfaces on substrates. Vanadium doping leads to a dramatic decrease in Raman intensity without notable peak broadening, signifying the enhancement of electron correlation. The enhanced electron correlation is further evidenced by transport studies where the electrical resistivity is greatly increased and follows an unusual T $\sqrt T $ dependence on the temperature (T). The lattice thermal conductivity is suppressed by an order of magnitude via doping even at room temperature where phonon-impurity scattering becomes less important. Density functional theory calculations suggest that the remarkable reduction of thermal conductivity arises from the complex phonon dispersion and reduced energy gap between phonon branches, which greatly enhances phase space for phonon-phonon Umklapp scattering. This work demonstrates a unique system combining 3d and 5d transition metals in isostructural materials to enrich the system with various types of interactions.

Identification of genetic variants related to metabolic syndrome by next-generation sequencing.

BACKGROUND: Metabolic syndrome (MetS) is a cluster of conditions associated with glucose intolerance, hypertension, abdominal obesity, dyslipidemia, and insulin resistance that increase the risk of cardiovascular diseases (CVD) and type 2 diabetes (T2D). Since MetS is known as a complex symptom with a high incidence of genetic factors, it is important to identify genetic variants for each clinical characteristic of MetS. METHODS: We performed targeted next-generation sequencing (NGS) to identify genetic variants related to obesity, blood glucose, triacylglycerol (TG), and high-density lipoprotein (HDL)-cholesterol level, and hypertension in 48 subjects with MetS and in 48 healthy subjects. RESULTS: NGS analysis revealed that 26 of 48 subjects (54.2%) with MetS had putative non-synonymous variants related to the clinical features of MetS. Of the subjects with MetS, 8 (16.7%) had variants in 4 genes (COL6A2, FTO, SPARC, and MTHFR) related to central obesity, 17 (35.4%) had variants in 6 genes (APOB, SLC2A2, LPA, ABCG5, ABCG8, and GCKR) related to hyperglycemia, 3 (6.3%) had variants in 4 genes (APOA1, APOC2, APOA4, and LMF1) related to hypertriglyceridemia, 8 (16.7%) had variants in 4 genes (ABCA1, CETP, SCARB1, and LDLR) related to low HDL-cholesterolemia, and 5 (10.4%) had variants in ADD1 related to hypertension. CONCLUSIONS: Our findings may contribute to broadening the genetic spectrum of risk variants related to the development of MetS.

Genetic Variants Associated with Elevated Plasma Ceramides in Individuals with Metabolic Syndrome.

Metabolic syndrome (MetS) is a complex condition of metabolic disorders and shows a steady onset globally. Ceramides are known as intracellular signaling molecules that influence key metabolism through various pathways such as MetS and insulin resistance. Therefore, it is important to identify novel genetic factors related to increased plasma ceramides in subjects with MetS. Here we first measured plasma ceramides levels in 37 subjects with MetS and in 38 healthy subjects by ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). Specifically, levels of C16 ceramide (Cer-16), C18 ceramide (Cer-18), C20 ceramide (Cer-20), C18 dihydroceramide (DhCer-18), C24 dihydroceramide (DhCer-24), and C24:1 dihydroceramide (DhCer-24:1) were significantly increased in MetS group (p < 5.0 × 10−2). We then performed single nucleotide polymorphism (SNP) genotyping to identify variants associated with elevated plasma ceramides in MetS group using Axiom® Korea Biobank Array v1.1 chip. We also performed linear regression analysis on genetic variants involved in ceramide synthesis and significantly elevated plasma ceramides and dihydroceramides. Ten variants (rs75397325, rs4246316, rs80165332, rs62106618, rs12358192, rs11006229, rs10826014, rs149162405, rs6109681, and rs3906631) across six genes (ACER1, CERS3, CERS6, SGMS1, SPTLC2, and SPTLC3) functionally involved in ceramide biosynthesis showed significant associations with the elevated levels of at least one of the ceramide species in MetS group at a statistically significant threshold of false discovery rate (FDR)-adjusted p < 5.0 × 10−2. Our findings suggest that the variants may be genetic determinants associated with increased plasma ceramides in individuals with MetS.

Immunochip Meta-Analysis of Inflammatory Bowel Disease Identifies Three Novel Loci and Four Novel Associations in Previously Reported Loci.

BACKGROUND AND AIMS: Recent meta-analysis of genome-wide association studies have identified over 241 inflammatory bowel disease susceptibility loci. However, the known variants only account for a fraction of inflammatory bowel disease heritability. To identify additional susceptibility loci, we performed a trans-ethnic meta-analysis as well as an Asian-specific meta-analysis, using all published Immunochip association results of inflammatory bowel disease. METHODS: An inverse-variance fixed-effects meta-analysis was carried out across Korean and East Asian Immunochip datasets of 4156 cases and 4904 controls [Asian ancestry]. A trans-ethnic meta-analysis of inflammatory bowel disease was performed together with the European datasets of 38 155 cases and 48 485 controls genotyped on the immunochip using a Bayesian approach, Meta-Analysis of Trans-ethnic Association studies [MANTRA]. RESULTS: We identified seven novel associations, including three novel susceptibility loci at MYO10-BASP1, PPP2R3C/KIAA0391/PSMA6/NFKB1A and LRRK1 as well as four novel secondary associations within previously known loci at NCF4, TSPAN32, CIITA and VANGL2. The new loci further implicate alterations in B cell biology in Crohn's disease pathogenesis. The effects of five loci were universal across European and Asian ancestries, whereas the NCF4 and CIITA loci showed significant heterogeneity between European and East Asian populations. In addition, 103 previously known IBD loci showed supporting evidence of association with nominal significance [p < 0.05] in Asians. CONCLUSIONS: Our findings of new loci not previously associated with IBD support the importance of studying inflammatory bowel disease genetics in diverse populations.

Association of CDKN2A/CDKN2B with inflammatory bowel disease in Koreans.

BACKGROUND AND AIM: CDKN2A/CDKN2B locus on 9p21 is reported to be associated with various diseases, including cancer and cardiovascular and inflammatory diseases. Significant downregulation of CDKN2B-AS1 in inflamed colon tissue of inflammatory bowel disease (IBD) cases was reported in Europeans. This study aimed to confirm the suggestive association of CDKN2A/CDKN2B with IBD identified in our recent genome-wide association study (GWAS). METHODS: We examined the association of CDKN2A/CDKN2B locus with IBD in an additional sample of 574 IBD cases and 542 controls, totaling 4068 cases and 8074 controls. In silico study was performed at various levels for functional annotation of the causal variant. Co-localization of the GWAS association signals and the corresponding expression quantitative trait loci in IBD-related tissues was evaluated using eCAVIAR. RESULTS: An expanded GWAS showed genome-wide significant association of rs3731257 at 9p21 with IBD (odds ratio = 1.17, 95% confidence interval = 1.12-1.22, Pcombined  = 5.68 × 10-9 ) and Crohn's disease (odds ratio = 1.22, 95% confidence interval = 1.15-1.28, Pcombined  = 8.85 × 10-9 ) in the Korean population. Co-localization study suggested that both CDKN2B-AS1 and CDKN2A might be functionally associated with the locus in the small intestine. CONCLUSIONS: rs3731257 in CDKN2A/CDKN2B is an IBD-susceptible locus in Koreans, with a suggestive role for small intestine-specific gene regulation. Our findings suggested that alterations of the CDKN2A/CDKN2B locus could affect the pathophysiology of IBD.

Erratum: Analysis of Dosage Mutation in PARK2 among Korean Patients with Early-Onset or Familial Parkinson's Disease.

[This corrects the article on p. 244 in vol. 10, PMID: 25045378.].

Reduction of Continuous Theta Burst Stimulation-Induced Motor Plasticity in Healthy Elderly With COMT Val158Met Polymorphism.

OBJECTIVE: To delineate whether cortical plasticity induced by continuous theta burst stimulation (cTBS) differed according to catechol-O-methyltransferase (COMT) gene polymorphism in healthy older adults. METHODS: Eighteen healthy older volunteers (mean age 73.78±5.04; 12 females and 6 males) were recruited. Volunteers randomly assigned in either a sham-first or real cTBS first group participated in two separate TMS visits with at least a 2-day wash-out period. Genotyping was carried out at baseline by a separate researcher who was blinded. cTBS was delivered in a hot spot over M1 at an active motor threshold of 80%. Motor evoked potentials (MEPs) were obtained at 120% of the resting motor threshold before and after sham/cTBS. RESULTS: The relative MEP to baseline was significantly decreased 0 and 10 minutes post-stimulation and increased 40 minutes post-stimulation, as compared with the sham condition. Immediately after cTBS, the Val/Val group had a significantly reduced relative MEP value, as compared with the MET carrier group. CONCLUSION: In healthy older persons, cTBS-induced motor plasticity was reduced in the COMT Val/Val group as compared with the (158)Met carrier group.

Analysis of Dosage Mutation in PARK2 among Korean Patients with Early-Onset or Familial Parkinson's Disease.

BACKGROUND AND PURPOSE: There is some controversy regarding heterozygous mutations of the gene encoding parkin (PARK2) as risk factors for Parkinson's disease (PD), and all previous studies have been performed in non-Asian populations. Dosage mutation of PARK2, rather than a point mutation or small insertion/deletion mutation, was reported to be a risk factor for familial PD; dosage mutation of PARK2 is common in Asian populations. METHODS: We performed a gene-dosage analysis of PARK2 using real-time polymerase chain reaction for 189 patients with early-onset PD or familial PD, and 191 control individuals. In the case of PD patients with heterozygous gene-dosage mutation, we performed a sequencing analysis to exclude compound heterozygous mutations. The association between heterozygous mutation of PARK2 and PD was tested. RESULTS: We identified 22 PD patients with PARK2 mutations (11.6%). Five patients (2.6%) had compound heterozygous mutations, and 13 patients (6.9%) had a heterozygous mutation. The phase could not be determined in one patient. Three small sequence variations were found in 30 mutated alleles (10.0%). Gene-dosage mutation accounted for 90% of all of the mutations found. The frequency of a heterozygous PARK2 gene-dosage mutation was higher in PD patients than in the controls. CONCLUSIONS: Heterozygous gene-dosage mutation of PARK2 is a genetic risk factor for patients with early-onset or familial PD in Koreans.

Expansion of the clinicopathological and mutational spectrum of Perry syndrome.

BACKGROUND: Perry syndrome (PS) caused by DCTN1 gene mutation is clinically characterized by autosomal dominant parkinsonism, depression, severe weight loss, and hypoventilation. Previous pathological studies have reported relative sparing of the cerebral cortex in this syndrome. Here, we characterize novel clinical and neuroimaging features in 3 patients with PS. METHODS: (18)F-fluorinated N-3-fluoropropyl-2-ß-carboxymethoxy-3-ß-(4-iodophenyl) nortropane ([(18)F]FP-CIT) PET, [(18)F]fluorodeoxyglucose PET, or volumetric MRI was performed in probands, and imaging data were analyzed and compared with those of control subjects. RESULTS: We identified 2 novel mutations of DCTN1. Oculogyric crisis that presented before levodopa treatment was observed in 1 case. One patient had supranuclear gaze palsy. In 2 cases, [(18)F]FP-CIT showed marked loss of dopamine transporter binding with only mild parkinsonism. Areas of hypometabolism or cortical thickness change were observed in dorsolateral frontal, anterior cingulate, lateral temporal, and inferior parietal cortices. CONCLUSION: Oculomotor manifestations are not uncommon in PS. Neuroimaging studies suggest involvement of the frontotemporoparietal cortex, which may be the clinical correlate of apathy and depression, as well as pathological changes in subcortical structures.