Adiponectin Gene Polymorphism Is Selectively Associated with the Concomitant Presence of Metabolic Syndrome and Essential Hypertension

OBJECTIVE: Cardiovascular risk increases with the presence of both metabolic syndrome (MetS) and hypertension (HTN). Although the adiponectin (ADIPOQ) gene has been reported to be involved in MetS, its association with HTN remained undetermined. This study aimed to investigate the association of ADIPOQ gene with the phenotypes of HTN and MetS. METHODS: A total of 962 participants from 302 families from the Taiwan young-onset hypertension genetic study were enrolled. Plasma adiponectin were measured, and association analysis was conducted by using GEE regression-based method. Another study, of 1448 unrelated participants, was conducted to replicate the association between ADIPOQ gene and variable phenotypes of MetS with or without HTN. RESULTS: Among 962 subjects from family samples, the lowest plasma adiponectin value was observed in MetS with HTN component (9.3±0.47 µg/ml) compared with hypertensives (13.4±0.74 µg /ml) or MetS without HTN (11.9±0.60 µg/ml, P<0.05). The SNP rs1501299 (G276T) in ADIPOQ gene was found associated with the presence of HTN in MetS (odds ratio for GG+GT vs. TT = 2.46; 95% CI: 1.14-5.3, p = 0.02), but not rs2241766 (T45G). No association of ADIPOQ gene with HTN alone or MetS without HTN was observed. The significant association of the SNP rs1501299 (G276T) with the phenotype of presence of HTN in MetS was confirmed (odds ratio for GG+GT vs. TT = 2.15; 95% CI: 1.1-4.3) in the replication study. CONCLUSIONS: ADIPOQ genetic variants were selectively and specifically associated with the concomitant presence of MetS and HTN, suggesting potential genetic linkage between MetS and HTN

Functional domains of SP110 that modulate its transcriptional regulatory function and cellular translocation

Abstract Background SP110, an interferon-induced nuclear protein, belongs to the SP100/SP140 protein family. Very recently, we showed that SP110b, an SP110 isoform, controls host innate immunity to Mycobacterium tuberculosis infection by regulating nuclear factor-κB (NF-κB) activity. However, it remains unclear how the structure of SP110 relates to its cellular functions. In this study, we provide experimental data illustrating the protein domains that are responsible for its functions. Methods We examined the effects of SP110 isoforms and a series of deletion mutants of SP110 on transcriptional regulation by luciferase reporter assays. We also employed confocal microscopy to determine the cellular distributions of enhanced green fluorescent protein-tagged SP110 isoforms and SP110 mutants. In addition, we performed immunoprecipitation and Western blotting analyses to identify the regions of SP110 that are responsible for protein interactions. Results Using reporter assays, we first demonstrated that SP110 isoforms have different regulatory effects on NF-κB-mediated transcription, supporting the notion that SP110 isoforms may have distinct cellular functions. Analysis of deletion mutants of SP110 showed that the interaction of the N-terminal fragment (amino acids 1–276) of SP110 with p50, a subunit of NF-κB, in the cytoplasm plays a crucial role in the down-regulation of the p50-driven tumor necrosis factor-α (TNFα) promoter activity in the nucleus, while the middle and C-terminal regions of SP110 localize it to various cellular compartments. Surprisingly, a nucleolar localization signal (NoLS) that contains one monopartite nuclear localization signal (NLS) and one bipartite NLS was identified in the middle region of SP110. The identification of a cryptic NoLS in the SP110 suggests that although this protein forms nuclear speckles in the nucleoplasm, it may be directed into the nucleolus to carry out distinct functions under certain cellular conditions. Conclusions The findings from this study elucidating the multidomain structure of the SP110 not only identify functional domains of SP110 that are required for transcriptional regulation, cellular translocation, and protein interactions but also implicate that SP110 has additional functions through its unexpected activity in the nucleolus

Photodissociation of HNO 3 at 193 nm: Near-infrared emission of NO detected by time-resolved Fourier transform spectroscopy

Rotationally resolved emission of NO, produced from photolysis of HNO 3 at 193 nm, in the near infrared region ͑8900-9300 cm Ϫ1 ͒ was recorded with a step-scan Fourier-transform interferometer at a resolution of 0.1 cm Ϫ1 . The emission is assigned as NO NO (vЉϭ1) in the ground electronic state. The measured distribution of intensity implies that NO is produced highly rotationally excited; the most likely mechanism for formation of NO is from the unstable NO 2 fragment undergoing secondary dissociation

Additional file 2: of Functional domains of SP110 that modulate its transcriptional regulatory function and cellular translocation

Figure S1. Subcellular localization of FLAG-tagged wild-type SP110 or SP110 mutant proteins. (a) Schematic representation of FLAG-tagged proteins containing SP110 deletion mutants. SP100: SP100 domain; SAND: SAND domain; PHD: PHD finger; Bromo: Bromodomain. (b-c) HEK293T cells were transfected with the indicated constructs, and the cellular distribution of FLAG-tagged SP110 proteins (wild-type (b) and mutated forms (c)) was visualized using confocal microscopy at 2 days post-transfection (upper panels). The cells were also subjected to Hoechst staining to identify nuclei (lower panels). Scale bars: 10 μm. The data represent 3 independent experiments. (PDF 738 kb

Additional file 1: of Functional domains of SP110 that modulate its transcriptional regulatory function and cellular translocation

Table S1. A list of primers used for plasmid construction. Table S2. A list of primers used for generating deletion mutants of SP110. Table S3. A list of primers used for site-directed mutagenesis of SP110. Table S4. A list of antibodies used in this study. (PDF 45 kb

Effects of Micro-Shot Peening on the Fatigue Strength of Anodized 7075-T6 Alloy

Micro-shot peening under two Almen intensities was performed to increase the fatigue endurance limit of anodized AA 7075 alloy in T6 condition. Compressive residual stress (CRS) and a nano-grained structure were present in the outermost as-peened layer. Microcracks in the anodized layer obviously abbreviated the fatigue strength/life of the substrate. The endurance limit of the anodized AA 7075 was lowered to less than 200 MPa. By contrast, micro-shot peening increased the endurance limit of the anodized AA 7075 to above that of the substrate (about 300 MPa). Without anodization, the fatigue strength of the high peened (HP) specimen fluctuated; this was the result of high surface roughness of the specimen, as compared to that of the low peened (LP) one. Pickling before anodizing was found to erode the outermost peened layer, which caused a decrease in the positive effect of peening. After anodization, the HP sample had a greater fatigue strength/endurance limit than that of the LP one. The fracture appearance of an anodized fatigued sample showed an observable ring of brittle fracture. Fatigue cracks present in the brittle coating propagated directly into the substrate, significantly damaging the fatigue performance of the anodized sample. The CRS and the nano-grained structure beneath the anodized layer accounted for a noticeable increase in resistance to fatigue failure of the anodized micro-shot peened specimen

Associations between MetS trait and ADIPOQ genetic variants.

<p>Data are mean ± SEM or β(P). HDL-C indicates high-density lipoprotein cholesterol; WC, waist circumference; BP, blood pressure.</p><p>All estimates were analyzed using liner regression model, and adjustments were made for age, sex, body mass index, glucose, blood pressure, waist circumference, triglycerides, and HDL-choleserol.</p>a<p>Model 1: additive model; ^bModel 2: dominant model; ^cModel 3: recessive model.</p

Baseline characteristics of case-control designed replication study.

<p>Data are mean ± SEM or number (%); HTN indicates hypertension; MetS, metabolic syndrome; BMI, indicates body mass index; HDL-C, high density lipoprotein cholesterol; LDL-C, low density lipoprotein cholesterol.</p><p>*<i>P</i>< 0.001 vs. MetS(−) HTN(−);</p><p>†<i>P</i>< 0.001 vs. MetS(+) HTN(−);</p><p>‡<i>P</i>< 0.001 vs. MetS(−) HTN(+);</p><p>§<i>P</i>< 0.001 vs. MetS(+) HTN(+).</p

Baseline characteristics of all family subjects.

<p>Data are mean ± SEM or number (%); HTN indicates hypertension; MetS, metabolic syndrome; BMI, indicates body mass index; HDL-C, high-density lipoprotein cholesterol; LDL-C, low-density lipoprotein cholesterol.</p><p>*P< 0.001 vs.MetS(-)HTN(−);</p><p>†P< 0.001 vs. MetS(+)HTN(−);</p><p>‡P< 0.001 vs. MetS(−)HTN(+);</p><p>§P< 0.001 vs. MetS(+)HTN(+).</p