Adiposity Is Associated with Gender-Specific Reductions in Left Ventricular Myocardial Perfusion during Dobutamine Stress

Background

Obesity and visceral adiposity are increasingly recognized risk factors for cardiovascular disease. Visceral fat may reduce myocardial perfusion by impairing vascular endothelial function. Women experience more anginal symptoms compared to men despite less severe coronary artery stenosis, as assessed by angiography. Women and men have different fat storage patterns which may account for the observed differences in cardiovascular disease. Therefore, our objective was to evaluate the relationship between visceral adipose tissue distributions and myocardial perfusion in men and women.

Methods

Visceral and subcutaneous fat distributions and myocardial perfusion were measured in 69 men and women without coronary artery disease using magnetic resonance imaging techniques. Myocardial perfusion index was quantified after first-pass perfusion with gadolinium contrast at peak dose dobutamine stress.

Results

We observed inverse relationships between female gender (r = -0.35, p = 0.003), pericardial fat (r = -0.36, p = 0.03), intraperitoneal fat (r = -0.37, p = 0.001), and retroperitoneal fat (r = -0.36, p = 0.002) and myocardial perfusion index. Visceral fat depots were not associated with reduced myocardial perfusion at peak dose dobutamine in men. However, in women, BMI (r = -0.33, p = 0.04), pericardial fat (r = -0.53, p = 0.02), subcutaneous fat (r = -0.39, p = 0.01) and intraperitoneal fat (r = -0.30, p = 0.05) were associated with reduced myocardial perfusion during dobutamine stress.

Conclusions

Higher visceral fat volumes are associated with reduced left ventricular myocardial perfusion at peak dose dobutamine stress in women but not in men. These findings suggest that visceral fat may contribute to abnormal microcirculatory coronary artery perfusion syndromes, explaining why some women exhibit more anginal symptoms despite typically lower grade epicardial coronary artery stenoses than men.     

p110γ/δ Double-Deficiency Induces Eosinophilia and IgE Production but Protects from OVA-Induced Airway Inflammation

The catalytical isoforms p110γ and p110δ of phosphatidylinositide 3-kinase γ (PI3Kγ) and PI3Kδ play an important role in the pathogenesis of asthma. Two key elements in allergic asthma are increased levels of eosinophils and IgE. Dual pharmacological inhibition of p110γ and p110δ reduces asthma-associated eosinophilic lung infiltration and ameliorates disease symptoms, whereas the absence of enzymatic activity in p110γ^KOδ^D910A mice increases IgE and basal eosinophil counts. This suggests that long-term inhibition of p110γ and p110δ might exacerbate asthma. Here, we analysed mice genetically deficient for both catalytical subunits (p110γ/δ^-/-) and determined basal IgE and eosinophil levels and the immune response to ovalbumin-induced asthma. Serum concentrations of IgE, IL-5 and eosinophil numbers were significantly increased in p110γ/δ^-/- mice compared to single knock-out and wildtype mice. However, p110γ/δ^-/- mice were protected against OVA-induced infiltration of eosinophils, neutrophils, T and B cells into lung tissue and bronchoalveolar space. Moreover, p110γ/δ^-/- mice, but not single knock-out mice, showed a reduced bronchial hyperresponsiveness. We conclude that increased levels of eosinophils and IgE in p110γ/δ^-/- mice do not abolish the protective effect of p110γ/δ-deficiency against OVA-induced allergic airway inflammation.     

A betaine aldehyde dehydrogenase gene in quinoa (<Emphasis Type="Italic">Chenopodium quinoa</Emphasis>): structure,phylogeny, and expression pattern

Betaine aldehyde dehydrogenase (BADH) is widely considered as a key enzyme in glycine betaine metabolism in higher plants. Several paralogous genes encoding different isozymes of BADH have been identified and characterized in some plants; however, until now, only limited information is available about BADH genes in quinoa (Chenopodium quinoa). Here, we report the molecular cloning, structural organization, phylogenetic evolution, and expression profile of a BADH gene (CqBADH1) from quinoa. The translated putative CqBADH1 protein included five conserved features of the ALDH Family 10. Comparisons between the cDNA and genomic sequences revealed that the CqBADH1 gene contained 15 exons and 14 introns. Comparative screening of introns in homologous genes demonstrated that the number and position of the BADH introns were highly conserved among the BADH genes in Amaranthaceae plants and in other more distantly related plant species. A phylogenetic analysis showed that CqBADH1 had the closest relationship with a protein from Atriplex canescens and belonged to the ALDH10 family. Expression profile analyses indicated that CqBADH1 was expressed only in root, and showed time-dependent expression profiles under NaCl-stress condition. Moreover, in quinoa, NaCl stress led to increased levels of CqBADH1 mRNA accompanied by the accumulation of glycine betaine. This is the first study to describe a BADH gene in quinoa.     

Identification of genetic loci stratified by diabetic status and microRNA related SNPs influencing kidney function in Korean populations

Chronic kidney disease (CKD) is characterized by a progressive loss of kidney function over a period of months or years. It is estimated that about 7.2 % of adults over the age of 30 have CKD worldwide. Although one of the major risk factors of CKD is family history, the heritability of CKD is not fully understood. It is also known that the diabetic condition is highly influential on the onset of CKD. To understand the genetic bases of CKD that remain unidentified, we performed genetic association analyses for kidney function-related traits such as blood urea nitrogen (BUN) and albumin in subjects stratified by diabetic status. In the discovery stage of the study, we used genome-wide scan data and clinical data in about 8800 subjects from the Korean Association Resource (KARE) project. Health2 study data comprising about 1800 subjects were used for the replication stage. Our two stage association analyses demonstrated that the LOC105374266 locus (rs9820070) showed strong evidence of association with BUN (P = 8.47 × 10^?14) in nondiabetic normal subjects (n = ~4300). To extend our knowledge of the genetic determinants influencing kidney function, we also analyzed the association between kidney function-related traits and microRNA related variants. For this analysis, miRNA related SNPs were selected from KARE and Health2 cohort genotype data. Our study suggests the potential relevance of miRNA to the kidney function (miR-518b for BUN; miR-146a and miR-1295a for albumin) in Korean populations.     

Molecular phylogenetic analysis of key <Emphasis Type="Italic">Jatropha</Emphasis> species inferred from nrDNA ITS and chloroplast (<Emphasis Type="Italic">trn</Emphasis>L-F and <Emphasis Type="Italic">rbc</Emphasis>L) sequences

The genus Jatropha (Euphorbiaceae) contains species that are of significant economic and ornamental value. However, Jatropha breeding material is rather limited due to incomplete information regarding phylogenetic relationships among germplasm resources. Phylogenetic analyses were performed based on the internal transcribed spacer of nuclear ribosomal DNA (nrDNA ITS), two chloroplast regions (trnL-F and rbcL), and the combined (ITS+trnL-F+rbcL) dataset among twenty-five specimens representing six key Jatropha species. Phylogenetic relationships of Jatropha were well resolved between subgenus Curcas and subgenus Jatropha, and demonstrated the intermediate position of section Polymorphae among sections of both subgenera. Jatropha curcas and J. integerrima demonstrated a close phylogenetic relationship. The molecular data agreed with the morphological classification that recognized J. multifida and J. podagrica in sec. Peltatae. The distinct intraspecific divergence that occurred in J. curcas could be attributed to restricted gene flow caused by geographical isolation and different ecological conditions. Phylograms produced with trnL-F and rbcL sequence data suggested slow rates of sequence divergence among Jatropha spp., while the ITS gene tree had good resolution suggesting high genetic variation of ITS among Jatropha species.     

Genotype–phenotype correlation of Charcot-Marie-Tooth type 1E patients with <Emphasis Type="Italic">PMP22</Emphasis> mutations

Charcot-Marie-Tooth disease type 1E (CMT1E) is a demyelinating motor and sensory neuropathy with peripheral myelin protein 22 (PMP22) point mutations. The objective of this study was to identify genetic causes and determine genotype–phenotype correlation in two Korean demyelinating CMT patients based on whole exome sequencing (WES), histological examination of distal sural nerve, and magnetic resonance imaging (MRI) of leg. WES revealed two de novo PMP22 mutations in the two demyelinating CMT patients, including one novel p.Leu82Pro (c.245T>A) mutation in one patient and one previously reported p.Ser72Leu (c.215C>T) mutation in the other patient. Both mutation sites were located in the well conserved second transmembrane domain. No control had the same mutations. The affected individual with the novel p.Leu82Pro mutation showed early onset, scoliosis, and sensory ataxia with ability to walk without assistance. Histopathological examination showed severe damage of myelin and axons. No compound muscle action potentials (CMAPs) were evoked in the upper or lower limb nerves. Leg MRIs revealed mild fatty infiltration of the bilateral peronei muscles consistent with clinical manifestations. The patient with the p.Ser72Leu mutation showed developmental delay in infancy. No CMAPs were elicited. However, she was also able to walk without assistance. In spite of markedly severe electrophysiological defects, leg MRIs showed almost normal findings except slight muscle atrophies of the lower legs. Both patients presented similar clinical features including no CMAPs in electrophysiological tests and mild fatty replacement in the lower leg MRI. Therefore, there was a good genotype–phenotype correlation in both cases.     

Genomics and expression analysis of DHHC-cysteine-rich domain S-acyl transferase protein family in apple

S-acylation is one of a group of lipid modifications that occurs on eukaryotic proteins, mediated by DHHC-CRD-containing proteins, which plays an important role in regulating the membrane association, trafficking and function of target proteins. Although genome-wide identification of PAT family has been carried out in yeast, mice, humans and Arabidopsis, little is known about apple PAT genes. In this study, a total of 33 putative apple PAT proteins, containing DHHC-CRD by domain analysis, have been identified, and were classified into three groups according to the phylogenetic analysis of PAT proteins in apple and Arabidopsis. More complex TMDs in the most MdPATs revealed the PM location of the gene family. Gene structure, gene chromosomal location and paralogs analysis of MdPAT genes within the apple genome demonstrated that tandem and segmental duplications, as well as whole genome duplications, have likely contributed to the expansion and evolution of the PAT gene family in apple. According to the microarray and expressed sequence tag (ESTs) analysis, the different expression patterns indicate that they may play different roles during fruit development and rootstock-scion interactions process. Moreover, PATs were performed expression profile analyses in different tissues, indicating that the PATs are involved in various aspects of physiological and developmental processes of apple. To our knowledge, this is the first report of a genome-wide analysis of the apple PAT gene family, and this genomic analysis of apple DHHC-CRD PAT genes provides the first step towards a functional study of this gene family in apple.     

Isolation and characterization of proteorhodopsin homologue from Yellow Sea of Korea

Many organisms use proton pump to earn energy for living. Some proton pumps start to work by light and one of the famous proteins are called proteorhodopsin (PR). From recent study it used not only protons but also mono-valent cations, divalent cations, or mono-valent anions during pumping activity. The goal of this study is to find new types of proton pumping proteins in the surface of the ocean. Metagenome samples were collected from the beach in Taean-gun and Incheon (Kkotji beach (36°30′0′′N, 126°19′56′′E), Kkotji mud (36°30′8′′N, 126°19′60′′E), Duegi beach (36°31′6′′N, 126°19′39′′E), Sorae salt pond (37°24′25′′N, 126°44′41′′E), swamp (37°24′59′′N, 126°44′54′′E) and reservoir (37°24′39′′N, 126°45′5′′E) in West Sea of Korea. Genomic DNA of each sample was isolated and used for PCR with specific primers for PR and sodium pumping rhodopsin. As a result, we obtained an unidentified PR in Duegi beach sample. The unidentified PR was expressed with chimeric expression system. It has 528 nm absorption maximum at pH 7. By the light differential spectrum measurement, putative M and O photo-intermediates were detected at around 400 and 600 nm, respectively. Similar to GPR, it has light driven outward proton transfer activity.