A Preliminary Study Of Workgroup Dynamics: A Critique And Reconceptualization Of Oetzel\u27s Effective Intercultural Workgroup Communication Theory

The primary focus of this research was to critique and reconceptualize Oetzel’s (2005) Effective Intercultural Workgroup Communication Theory (EIWCT). The research explored the foundational research concepts in Oetzel’s theory: situational features (history of unresolved conflicts, equal/unequal status, and ingroup/outgroup), self-construals, face-concerns, interaction climate, and task and relational group effectiveness and satisfaction. The central critique of Oetzel’s theory was the operationalization of group diversity through self-construals, face concerns and ethnic identification. The current study proposed that relational models and horizontal/vertical individualism/collectivism may more completely and accurately capture diversity dimensions because they are considered deep-level diversity features (Fiske, 2004; Triandis & Gelfand, 1998). Even though not all hypotheses were supported, several variables were significantly correlated with the tested outcomes, i.e. interaction climate, group satisfaction and group effectiveness. Specifically, the relational model of market pricing, and the cultural dimensions of vertical collectivism and vertical individualism were significantly related to some outcomes variables

Possible common central pathway for resistin and insulin in regulating food intake.

Aim: Adipose tissue has been the object of intense research in the field of obesity and diabetes diseases in the last decade. Examination of adipocyte-secreted peptides led to the identification of a unique polypeptide, resistin (RSTN), which has been suggested as a link between obesity and diabetes. RSTN plays a clearly documented role in blocking insulin (INS)-induced hypoglycaemia. As brain injection of INS affects feeding behaviour, we studied the possible interaction between INS and RSTN in food-deprived rats, measuring effects on food intake. In addition, we examined how RSTN might affect neuropeptide Y (NPY)-induced feeding, as studies have shown that rat RSTN can interfere with the NPY system. Methods: Overnight food-deprived rats were injected into the third brain ventricle (3V) with either INS (10 or 20 mUI), RSTN (0.1–0.4 nmol/rat), or saline before access to food. Another group of rats was injected into the 3V with RSTN alone, NPY alone or RSTN plus NPY. Their food intake and body weight were measured. Results: Our results confirm the hypophagic effect of RSTN on food deprivation-induced food intake, and more importantly, show that RSTN neither potentiates nor blocks the effects of INS on food intake, but does reduce the hyperphagic effect of NPY. Conclusion:  The observation that RSTN does not modify feeding INS-induced hypophagia, but does influence NPY-induced feeding, points to the possibility that RSTN may be involved in control of food intake through an NPY-ergic mechanism as INS

Apolipoprotein O is mitochondrial and promotes lipotoxicity in heart

Diabetic cardiomyopathy is a secondary complication of diabetes with an unclear etiology. Based on a functional genomic evaluation of obesity-associated cardiac gene expression, we previously identified and cloned the gene encoding apolipoprotein O (APOO), which is overexpressed in hearts from diabetic patients. Here, we generated APOO-Tg mice, transgenic mouse lines that expresses physiological levels of human APOO in heart tissue. APOO-Tg mice fed a high-fat diet exhibited depressed ventricular function with reduced fractional shortening and ejection fraction, and myocardial sections from APOO-Tg mice revealed mitochondrial degenerative changes. In vivo fluorescent labeling and subcellular fractionation revealed that APOO localizes with mitochondria. Furthermore, APOO enhanced mitochondrial uncoupling and respiration, both of which were reduced by deletion of the N-terminus and by targeted knockdown of APOO. Consequently, fatty acid metabolism and ROS production were enhanced, leading to increased AMPK phosphorylation and Ppara and Pgc1a expression. Finally, we demonstrated that the APOO-induced cascade of events generates a mitochondrial metabolic sink whereby accumulation of lipotoxic byproducts leads to lipoapoptosis, loss of cardiac cells, and cardiomyopathy, mimicking the diabetic heart-associated metabolic phenotypes. Our data suggest that APOO represents a link between impaired mitochondrial function and cardiomyopathy onset, and targeting APOO-dependent metabolic remodeling has potential as a strategy to adjust heart metabolism and protect the myocardium from impaired contractility

Increased mean aliphatic lipid chain length in left ventricular hypertrophy secondary to arterial hypertension: A cross-sectional study

About 77.9 million (1 in 4) American adults have high blood pressure. High blood pressure is the primary cause of left ventricular hypertrophy (LVH), which represents a strong predictor of future heart failure and cardiovascular mortality. Previous studies have shown an altered metabolic profile in hypertensive patients with LVH. The goal of this study was to identify blood metabolomic LVH biomarkers by H NMR to provide novel diagnostic tools for rapid LVH detection in populations of hypertensive individuals. This cross-sectional study included 48 hypertensive patients with LVH matched with 48 hypertensive patients with normal LV size, and 24 healthy controls. Two-dimensional targeted M-mode echocardiography was performed to measure left ventricular mass index. Partial least squares discriminant analysis was used for the multivariate analysis of the H NMR spectral data. From the H NMR-based metabolomic profiling, signals coming from methylene (-CH2-) and methyl (-CH3) moieties of aliphatic chains from plasma lipids were identified as discriminant variables. The -CH2-/-CH3 ratio, an indicator of the mean length of the aliphatic lipid chains, was significantly higher (P < 0.001) in the LVH group than in the hypertensive group without LVH and controls. Receiver operating characteristic curve showed that a cutoff of 2.34 provided a 52.08% sensitivity and 85.42% specificity for discriminating LVH (AUC = 0.703, P-value < 0.001). We propose the -CH2-/-CH3 ratio from plasma aliphatic lipid chains as a biomarker for the diagnosis of left ventricular remodeling in hypertension

Body Mass Index is Associated with USF1 Haplotype in Korean Premenopausal Women

The upstream stimulatory factor 1 (USF1) gene has been shown to play an essential role as the cause of familial combined hyperlipidemia, and there are several association studies on the relationship between USF1 and metabolic disorders. In this study, we analyzed two single nucleotide polymorphisms in USF1 rs2073653 (306A>G) and rs2516840 (1748C>T) between the case (dyslipidemia or obesity) group and the control group in premenopausal females, postmenopausal females, and males among 275 Korean subjects. We observed a statistically significant difference in the GC haplotype between body mass index (BMI) ≥25 kg/m2 and BMI <25 kg/m2 groups in premenopausal females (χ2=4.23, p=0.04). It seems that the USF1 GC haplotype is associated with BMI in premenopausal Korean females

Altered Skeletal Muscle Lipase Expression and Activity Contribute to Insulin Resistance in Humans

International audienceOBJECTIVE: Insulin resistance is associated with elevated content of skeletal muscle lipids, including triacylglycerols (TAGs) and diacylglycerols (DAGs). DAGs are by-products of lipolysis consecutive to TAG hydrolysis by adipose triglyceride lipase (ATGL) and are subsequently hydrolyzed by hormone-sensitive lipase (HSL). We hypothesized that an imbalance of ATGL relative to HSL (expression or activity) may contribute to DAG accumulation and insulin resistance. RESEARCH DESIGN AND METHODS: We first measured lipase expression in vastus lateralis biopsies of young lean (n = 9), young obese (n = 9), and obese-matched type 2 diabetic (n = 8) subjects. We next investigated in vitro in human primary myotubes the impact of altered lipase expression/activity on lipid content and insulin signaling. RESULTS: Muscle ATGL protein was negatively associated with whole-body insulin sensitivity in our population (r = -0.55, P = 0.005), whereas muscle HSL protein was reduced in obese subjects. We next showed that adenovirus-mediated ATGL overexpression in human primary myotubes induced DAG and ceramide accumulation. ATGL overexpression reduced insulin-stimulated glycogen synthesis (-30%, P < 0.05) and disrupted insulin signaling at Ser1101 of the insulin receptor substrate-1 and downstream Akt activation at Ser473. These defects were fully rescued by nonselective protein kinase C inhibition or concomitant HSL overexpression to restore a proper lipolytic balance. We show that selective HSL inhibition induces DAG accumulation and insulin resistance. CONCLUSIONS: Altogether, the data indicate that altered ATGL and HSL expression in skeletal muscle could promote DAG accumulation and disrupt insulin signaling and action. Targeting skeletal muscle lipases may constitute an interesting strategy to improve insulin sensitivity in obesity and type 2 diabetes

Creating highly specific nucleases by fusion of active restriction endonucleases and catalytically inactive homing endonucleases

Zinc-finger nucleases and TALE nucleases are produced by combining a specific DNA-binding module and a non-specific DNA-cleavage module, resulting in nucleases able to cleave DNA at a unique sequence. Here a new approach for creating highly specific nucleases was pursued by fusing a catalytically inactive variant of the homing endonuclease I-SceI, as DNA binding-module, to the type IIP restriction enzyme PvuII, as cleavage module. The fusion enzymes were designed to recognize a composite site comprising the recognition site of PvuII flanked by the recognition site of I-SceI. In order to reduce activity on PvuII sites lacking the flanking I-SceI sites, the enzymes were optimized so that the binding of I-SceI to its sites positions PvuII for cleavage of the composite site. This was achieved by optimization of the linker and by introducing amino acid substitutions in PvuII which decrease its activity or disturb its dimer interface. The most specific variant showed a more than 1000-fold preference for the addressed composite site over an unaddressed PvuII site. These results indicate that using a specific restriction enzyme, such as PvuII, as cleavage module, offers an alternative to the otherwise often used catalytic domain of FokI, which by itself does not contribute to the specificity of the engineered nuclease

Attenuation of Zinc Finger Nuclease Toxicity by Small-Molecule Regulation of Protein Levels

Zinc finger nucleases (ZFNs) have been used successfully to create genome-specific double-strand breaks and thereby stimulate gene targeting by several thousand fold. ZFNs are chimeric proteins composed of a specific DNA-binding domain linked to a non-specific DNA-cleavage domain. By changing key residues in the recognition helix of the specific DNA-binding domain, one can alter the ZFN binding specificity and thereby change the sequence to which a ZFN pair is being targeted. For these and other reasons, ZFNs are being pursued as reagents for genome modification, including use in gene therapy. In order for ZFNs to reach their full potential, it is important to attenuate the cytotoxic effects currently associated with many ZFNs. Here, we evaluate two potential strategies for reducing toxicity by regulating protein levels. Both strategies involve creating ZFNs with shortened half-lives and then regulating protein level with small molecules. First, we destabilize ZFNs by linking a ubiquitin moiety to the N-terminus and regulate ZFN levels using a proteasome inhibitor. Second, we destabilize ZFNs by linking a modified destabilizing FKBP12 domain to the N-terminus and regulate ZFN levels by using a small molecule that blocks the destabilization effect of the N-terminal domain. We show that by regulating protein levels, we can maintain high rates of ZFN-mediated gene targeting while reducing ZFN toxicity

Blood Signature of Pre-Heart Failure: A Microarrays Study

International audienceBACKGROUND: The preclinical stage of systolic heart failure (HF), known as asymptomatic left ventricular dysfunction (ALVD), is diagnosed only by echocardiography, frequent in the general population and leads to a high risk of developing severe HF. Large scale screening for ALVD is a difficult task and represents a major unmet clinical challenge that requires the determination of ALVD biomarkers. METHODOLOGY/PRINCIPAL FINDINGS: 294 individuals were screened by echocardiography. We identified 9 ALVD cases out of 128 subjects with cardiovascular risk factors. White blood cell gene expression profiling was performed using pangenomic microarrays. Data were analyzed using principal component analysis (PCA) and Significant Analysis of Microarrays (SAM). To build an ALVD classifier model, we used the nearest centroid classification method (NCCM) with the ClaNC software package. Classification performance was determined using the leave-one-out cross-validation method. Blood transcriptome analysis provided a specific molecular signature for ALVD which defined a model based on 7 genes capable of discriminating ALVD cases. Analysis of an ALVD patients validation group demonstrated that these genes are accurate diagnostic predictors for ALVD with 87% accuracy and 100% precision. Furthermore, Receiver Operating Characteristic curves of expression levels confirmed that 6 out of 7 genes discriminate for left ventricular dysfunction classification. CONCLUSIONS/SIGNIFICANCE: These targets could serve to enhance the ability to efficiently detect ALVD by general care practitioners to facilitate preemptive initiation of medical treatment preventing the development of HF