Reversion of Steatosis by SREBP-1c Antisense Oligonucleotide did not Improve Hepatic Insulin Action in Diet-induced Obesity Mice

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)The literature has associated hepatic insulin action with NAFLD. In this sense, treatments to revert steatosis and improve hepatic insulin action become important. Our group has demonstrated that inhibition of Sterol Regulatory Element Binding Proteins-1c (SREBP-1c) reverses hepatic steatosis. However, insulin signals after NAFLD reversion require better investigation. Thus, in this study, we investigated if the reversal of NAFLD by SREBP-1c inhibitor results in improvement in the hepatic insulin signal in obesity mice. After installation/achievement of diet-induced obesity and insulin resistance, Swiss mice were divided into 3 groups: i) Lean, ii) D-IHS, diet-induced hepatic steatosis [no treatment with antisense oligonucleotide (ASO)], and iii) RD-IHS, reversion of diet-induced hepatic steatosis (treated with ASO). The mice were treated with ASO SREBP-1c as previously described by our group. After ASO treatment, one set of animals was anesthetized and used for in vivo test, and another mice set was anesthetized and used for histology and Western blot analysis. Reversion of diet-induced hepatic steatosis did not change blood glucose, glucose decay constant (k(ITT)), body weight, or serum insulin levels. In addition, results showed that the protocol did not improve insulin pathway signaling, as confirmed by the absence of changes in IR, IRS1, Akt and Foxo1 phosphorylation in hepatic tissue. In parallel, no alterations were observed in proinflammatory molecules. Thus, our results suggest that the inhibition of SREBP-1c reverts steatosis, but without improving insulin hepatic resistance.4412885890Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Fundacao de Amparo a Pesquisa do Estado de Santa Catarina (FAPESC)Universidade do Extremo Sul Catarinense (UNESC)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq

Global longitudinal strain at rest predicts significant coronary artery stenosis in patients with peripheral arterial disease

Abstract Funding Acknowledgements Type of funding sources: None. Background Critical peripheral artery disease (PAD) is expression of systemic chronic atherosclerosis, it being often associated with cardiovascular events. The assessment of global longitudinal strain (GLS) at rest by speckle tracking echocardiography could be useful to unmask significant coronary artery disease (CAD) in asymptomatic PAD patients. Purpose To determine whether resting GLS is able to predict significant coronary artery stenosis in PAD patients selected for peripheral or carotid angiography. Methods One-hundred three clinically relevant PAD patients (M/F = 76/27, age = 66.8 ± 10,2 years, 72 with significant lower limb artery stenosis and 31 with carotid artery stenosis ≥50%), asymptomatic for CAD, underwent standard echo-Doppler exam at rest, comprehensive of GLS analysis, prior peripheral and coronary angiography. Information on cardiovascular (CV) risk factors and comorbidities were collected. Patients with know CAD and previous myocardial infarction, left ventricular (LV) ejection fraction < 50% and inadequate echocardiographic imaging were excluded. According to the results of coronary angiography, patients were divided in two groups: with significant coronary artery stenosis (>50% of obstruction. n = 73) and without significant coronary artery lesions (n = 30). Results No intergroup difference in the prevalence of CV risk factors and comorbidities was found. Age, body mass index and blood pressure were comparable between the two groups. LV ejection fraction (59.9 ± 4.2% in patients with significant coronary stenosis vs. 60.2 ± 4.7% in those without coronary stenosis, p = 0.75) and wall motion score index (1.02 ± 0.09 vs 1.03 ± 0.09 respectively, p = 0.67) did not differ significantly. Conversely, GLS was lower in patients with significant coronary artery stenosis than in those without (21.6 ± 2.7% vs. 22.8 ± 2%, p < 0.02) (Figure 1). This difference remained significant comparing the carotid subgroup with coronary stenosis vs. those without (p < 0.05) whereas it did not achieve the statistical significance in patients with lower limb artery lesions (p = 0.42). Conclusion In PAD patients, GLS at rest shoes the capability in identifying patients at higher probability of significant coronary artery stenosis. This involves in particular patients with carotid artery stenosis. GLS might be helpful to select patients who need to extend the peripheral angiographic evaluation to the coronary tree

REST Controls Self-Renewal and Tumorigenic Competence of Human Glioblastoma Cells

The Repressor Element 1 Silencing Transcription factor (REST/NRSF) is a master repressor of neuronal programs in non-neuronal lineages shown to function as a central regulator of developmental programs and stem cell physiology. Aberrant REST function has been associated with a number of pathological conditions. In cancer biology, REST has been shown to play a tumor suppressor activity in epithelial cancers but an oncogenic role in brain childhood malignancies such as neuroblastoma and medulloblastoma. Here we examined REST expression in human glioblastoma multiforme (GBM) specimens and its role in GBM cells carrying self-renewal and tumorigenic competence. We found REST to be expressed in GBM specimens, its presence being particularly enriched in tumor cells in the perivascular compartment. Significantly, REST is highly expressed in self-renewing tumorigenic-competent GBM cells and its knock down strongly reduces their self-renewal in vitro and tumor-initiating capacity in vivo and affects levels of miR-124 and its downstream targets. These results indicate that REST contributes to GBM maintenance by affecting its self-renewing and tumorigenic cellular component and that, hence, a better understanding of these circuitries in these cells might lead to new exploitable therapeutic targets

Leadership in Orchestra Emerges from the Causal Relationships of Movement Kinematics

Non-verbal communication enables efficient transfer of information among people. In this context, classic orchestras are a remarkable instance of interaction and communication aimed at a common aesthetic goal: musicians train for years in order to acquire and share a non-linguistic framework for sensorimotor communication. To this end, we recorded violinists' and conductors' movement kinematics during execution of Mozart pieces, searching for causal relationships among musicians by using the Granger Causality method (GC). We show that the increase of conductor-to-musicians influence, together with the reduction of musician-to-musician coordination (an index of successful leadership) goes in parallel with quality of execution, as assessed by musical experts' judgments. Rigorous quantification of sensorimotor communication efficacy has always been complicated and affected by rather vague qualitative methodologies. Here we propose that the analysis of motor behavior provides a potentially interesting tool to approach the rather intangible concept of aesthetic quality of music and visual communication efficacy

Measurement of the Bottom-Strange Meson Mixing Phase in the Full CDF Data Set

We report a measurement of the bottom-strange meson mixing phase \beta_s using the time evolution of B0_s -> J/\psi (->\mu+\mu-) \phi (-> K+ K-) decays in which the quark-flavor content of the bottom-strange meson is identified at production. This measurement uses the full data set of proton-antiproton collisions at sqrt(s)= 1.96 TeV collected by the Collider Detector experiment at the Fermilab Tevatron, corresponding to 9.6 fb-1 of integrated luminosity. We report confidence regions in the two-dimensional space of \beta_s and the B0_s decay-width difference \Delta\Gamma_s, and measure \beta_s in [-\pi/2, -1.51] U [-0.06, 0.30] U [1.26, \pi/2] at the 68% confidence level, in agreement with the standard model expectation. Assuming the standard model value of \beta_s, we also determine \Delta\Gamma_s = 0.068 +- 0.026 (stat) +- 0.009 (syst) ps-1 and the mean B0_s lifetime, \tau_s = 1.528 +- 0.019 (stat) +- 0.009 (syst) ps, which are consistent and competitive with determinations by other experiments.Comment: 8 pages, 2 figures, Phys. Rev. Lett 109, 171802 (2012

Ablation of the Pro-Apoptotic Protein Bax Protects Mice from Glucocorticoid-Induced Bone Growth Impairment

Dexamethasone (Dexa) is a widely used glucocorticoid to treat inflammatory diseases; however, a multitude of undesired effects have been reported to arise from this treatment including osteoporosis, obesity, and in children decreased longitudinal bone growth. We and others have previously shown that glucocorticoids induce apoptosis in growth plate chondrocytes. Here, we hypothesized that Bax, a pro-apoptotic member of the Bcl-2 family, plays a key role in Dexa-induced chondrocyte apoptosis and bone growth impairment. Indeed, experiments in the human HCS-2/8 chondrocytic cell line demonstrated that silencing of Bax expression using small-interfering (si) RNA efficiently blocked Dexa-induced apoptosis. Furthermore, ablation of Bax in female mice protected against Dexa-induced bone growth impairment. Finally, Bax activation by Dexa was confirmed in human growth plate cartilage specimens cultured ex vivo. Our findings could therefore open the door for new therapeutic approaches to prevent glucocorticoid-induced bone growth impairment through specific targeting of Bax

Factors associated with Toxoplasma gondii infection in confined farrow-to-finish pig herds in western France: an exploratory study in 60 herds

Background: Infection by Toxoplasma gondii postnatally can occur after ingestion of contaminated meat or water (tissue cysts/oocysts). In Europe, percentage of meat borne infections is estimated between 30 and 63 %, out of which pork makes the most important source. The aim of this study was to (i) investigate the seroprevalence of T. gondii in intensive pig farms from western France; and (ii) identify the risk factors associated with seropositivity. Methods: Data were collected between November 2006 and February 2008 in 60 intensive farrow-to-finish farms, where sera were taken from 3595 fattening pigs, weaned and suckling piglets. Information about three classes of potential seropositivity risk factors were obtained through a questionnaire concerning: (i) breeding characteristics; (ii) farm management; and (iii) husbandry and hygiene. The modified agglutination test (MAT) was used for detection of specific anti T. gondii antibodies in pig sera, starting from 1/6 dilution. Results: The overall proportion of seropositive animals was 6.9 %, but the proportion of herds with at least one positive pig was 100 %. Multivariate logistic mixed model showed an increased seropositivity risk in weaned compared to suckling piglets, and a decreasing risk for mid-sized and large farms. The presence of a Danish entry facility, that clearly separates clean and dirty areas, had a protective effect on T. gondii seropositivity as well. Conclusions: The observed proportion of herds with at least one T. gondii seropositive animal provides further evidence that even in confined conditions of pig breeding, infection occurs, and is common. The highest risk for acquiring T. gondii is at the end of weaning period. Smaller confined pig farms demonstrate higher T. gondii seropositivity levels. This study also showed that Danish entry on farm buildings provides effective protection against T. gondii