Perilipin regulates the thermogenic actions of norepinephrine in brown adipose tissue

In response to cold, norepinephrine (NE)-induced triacylglycerol hydrolysis (lipolysis) in adipocytes of brown adipose tissue (BAT) provides fatty acid substrates to mitochondria for heat generation (adaptive thermogenesis). NE-induced lipolysis is mediated by protein kinase A (PKA)-dependent phosphorylation of perilipin, a lipid droplet-associated protein that is the major regulator of lipolysis. We investigated the role of perilipin PKA phosphorylation in BAT NE-stimulated thermogenesis using a novel mouse model in which a mutant form of perilipin, lacking all six PKA phosphorylation sites, is expressed in adipocytes of perilipin knockout (Peri KO) mice. Here, we show that despite a normal mitochondrial respiratory capacity, NE-induced lipolysis is abrogated in the interscapular brown adipose tissue (IBAT) of these mice. This lipolytic constraint is accompanied by a dramatic blunting (∼70%) of the in vivo thermal response to NE. Thus, in the presence of perilipin, PKA-mediated perilipin phosphorylation is essential for NE-dependent lipolysis and full adaptive thermogenesis in BAT. In IBAT of Peri KO mice, increased basal lipolysis attributable to the absence of perilipin is sufficient to support a rapid NE-stimulated temperature increase (∼3.0°C) comparable to that in wild-type mice. This observation suggests that one or more NE-dependent mechanism downstream of perilipin phosphorylation is required to initiate and/or sustain the IBAT thermal response

Interventions for physical activity promotion applied to the primary healthcare settings for people living in regions of low socioeconomic level: study protocol for a non-randomized controlled trial.

BACKGROUND: Regular physical activity practice has been widely recommended for promoting health, but the physical activity levels remain low in the population. Therefore, the study of interventions to promote physical activity is essential. OBJECTIVE: To present the methodology of two physical activity interventions from the "Ambiente Ativo" ("Active Environment") project. METHODS: 12-month non-randomized controlled intervention trial. 157 healthy and physically inactive individuals were selected: health education (n = 54) supervised exercise (n = 54) and control (n = 49). Intervention based on health education: a multidisciplinary team of health professionals organized the intervention in group discussions, phone calls, SMS and educational material. Intervention based on supervised exercise program: consisted of offering an exercise program in groups supervised by physical education professionals involving strength, endurance and flexibility exercises. The physical activity level was assessed by the International Physical Activity Questionnaire (long version), physical activities recalls, pedometers and accelerometers over a seven-day period. RESULT: This study described two different proposals for promoting physical activity that were applied to adults attended through the public healthcare settings. The participants were living in a region of low socioeconomic level, while respecting the characteristics and organization of the system and its professionals, and also adapting the interventions to the realities of the individuals attended. CONCLUSION: Both interventions are applicable in regions of low socioeconomic level, while respecting the social and economic characteristics of each region. TRIAL REGISTRATION: ClinicalTrials.gov NCT01852981

Exploring the Elastic Properties and Fracture Patterns of Me-Graphene Monolayers and Nanotubes through Reactive Molecular Dynamics Simulations

Me-graphene (MeG) is a novel two-dimensional (2D) carbon allotrope. Due to its attractive electronic and structural properties, it is important to study the mechanical behavior of MeG in its monolayer and nanotube topologies. In this work, we conducted fully atomistic reactive molecular dynamics simulations using the Tersoff force field to investigate their mechanical properties and fracture patterns. Our results indicate that Young's modulus of MeG monolayers is about 414 GPa and in the range of 421-483 GPa for the nanotubes investigated here. MeG monolayers and MeGNTs directly undergo from elastic to complete fracture under critical strain without a plastic regime.Comment: 10 pages, 01 table, and 05 figure

Deep neural network-estimated electrocardiographic age as a mortality predictor

The electrocardiogram (ECG) is the most commonly used exam for the evaluation of cardiovascular diseases. Here we propose that the age predicted by artificial intelligence (AI) from the raw ECG (ECG-age) can be a measure of cardiovascular health. A deep neural network is trained to predict a patient’s age from the 12-lead ECG in the CODE study cohort (n = 1,558,415 patients). On a 15% hold-out split, patients with ECG-age more than 8 years greater than the chronological age have a higher mortality rate (hazard ratio (HR) 1.79, p < 0.001), whereas those with ECG-age more than 8 years smaller, have a lower mortality rate (HR 0.78, p < 0.001). Similar results are obtained in the external cohorts ELSA-Brasil (n = 14,236) and SaMi-Trop (n = 1,631). Moreover, even for apparent normal ECGs, the predicted ECG-age gap from the chronological age remains a statistically significant risk predictor. These results show that the AI-enabled analysis of the ECG can add prognostic information

Analysis of binding properties and specificity through identification of the interface forming residues (IFR) for serine proteases in silico docked to different inhibitors

<p>Abstract</p> <p>Background</p> <p>Enzymes belonging to the same super family of proteins in general operate on variety of substrates and are inhibited by wide selection of inhibitors. In this work our main objective was to expand the scope of studies that consider only the catalytic and binding pocket amino acids while analyzing enzyme specificity and instead, include a wider category which we have named the Interface Forming Residues (IFR). We were motivated to identify those amino acids with decreased accessibility to solvent after docking of different types of inhibitors to sub classes of serine proteases and then create a table (matrix) of all amino acid positions at the interface as well as their respective occupancies. Our goal is to establish a platform for analysis of the relationship between IFR characteristics and binding properties/specificity for bi-molecular complexes.</p> <p>Results</p> <p>We propose a novel method for describing binding properties and delineating serine proteases specificity by compiling an exhaustive table of interface forming residues (IFR) for serine proteases and their inhibitors. Currently, the Protein Data Bank (PDB) does not contain all the data that our analysis would require. Therefore, an <it>in silico </it>approach was designed for building corresponding complexes</p> <p>The IFRs are obtained by "rigid body docking" among 70 structurally aligned, sequence wise non-redundant, serine protease structures with 3 inhibitors: bovine pancreatic trypsin inhibitor (BPTI), ecotine and ovomucoid third domain inhibitor. The table (matrix) of all amino acid positions at the interface and their respective occupancy is created. We also developed a new computational protocol for predicting IFRs for those complexes which were not deciphered experimentally so far, achieving accuracy of at least 0.97.</p> <p>Conclusions</p> <p>The serine proteases interfaces prefer polar (including glycine) residues (with some exceptions). Charged residues were found to be uniquely prevalent at the interfaces between the "miscellaneous-virus" subfamily and the three inhibitors. This prompts speculation about how important this difference in IFR characteristics is for maintaining virulence of those organisms.</p> <p>Our work here provides a unique tool for both structure/function relationship analysis as well as a compilation of indicators detailing how the specificity of various serine proteases may have been achieved and/or could be altered. It also indicates that the interface forming residues which also determine specificity of serine protease subfamily can not be presented in a canonical way but rather as a matrix of alternative populations of amino acids occupying variety of IFR positions.</p

Protective Response Mechanisms to Heat Stress in Interaction with High [CO2] Conditions in Coffea spp.

This work was supported by national funds from Fundacao para a Ciencia e a Tecnologia through the projects PTDC/AGRPRO/3386/2012, the research units UID/AGR/04129/2013 (LEAF) and UID/GEO/04035/2013 (GeoBioTcc), as well through the grant SFRH/BPD/47563/2008 (AT) co-financed through the POPH program subsidized by the European Social Fund. Brazilian funding from CAPES (grams PDSE: 000427/2014-04, W.P. Rodrigues; 0343/2014-05, MM; 12226/12-2, LM), CNPq and Fapemig (fellowships to FDM, FP, and EC) are also greatly acknowledged.Modeling studies have predicted that coffee crop will be endangered by future global warming, but recent reports highlighted that high [CO2] can mitigate heat impacts on coffee. This work aimed at identifying heat protective mechanisms promoted by CO2 in Coffea arabica (cv. Icatu and IPR108) and Coffea canephora cv. Conilon CL153. Plants were grown at 25/20 degrees C (day/night), under 380 or 700 mu L CO2 L-1, and then gradually submitted to 31/25, 37/30, and 42/34 degrees C. Relevant heat tolerance up to 37/30 degrees C for both [CO2] and all coffee genotypes was observed, likely supported by the maintenance or increase of the pools of several protective molecules (neoxanthin, lutein, carotenes, ohtocopherol, HSP70, raffinose), activities of antioxidant enzymes, such as superoxide dismutase (SOD), ascorbate peroxidase (APX), glutathione reductase (GR), catalase (CAT), and the upregulated expression of some genes (ELIP, Chaperonin 20). However, at 42/34 degrees C a tolerance threshold was reached, mostly in the 380 -plants and Icatu. Adjustments in raffinose, lutein, beta-carotene, alpha-tocopherol and HSP70 pools, and the upregulated expression of genes related to protective (FLIPS, HSP70, Chape 20, and 60) and antioxidant (CAT, CuSOD2, APX Cyt, APX ChI) proteins were largely driven by temperature. However, enhanced [CO2] maintained higher activities of GR (Icatu) and CAT (Icatu and IPR108), kept (or even increased) the Cu,Zn-SOD, APX, and CAT activities, and promoted a greater upregulation of those enzyme genes, as well as those related to HSP70, ELIPs, Chaperonins in CL153, and Icatu. These changes likely favored the maintenance of reactive oxygen species (ROS) at controlled levels and contributed to mitigate of photosystem II photoinhibition at the highest temperature. Overall, our results highlighted the important role of enhanced [CO2] on the coffee crop acclimation and sustainability under predicted future global warming scenarios.publishersversionpublishe

Substrate texture properties induce triatomine probing on bitten warm surfaces

<p>Abstract</p> <p>Background</p> <p>In this work we initially evaluated whether the biting process of <it>Rhodnius prolixus </it>relies on the detection of mechanical properties of the substrate. A linear thermal source was used to simulate the presence of a blood vessel under the skin of a host. This apparatus consisted of an aluminium plate and a nickel-chrome wire, both thermostatized and presented at 33 and 36°C, respectively. To evaluate whether mechanical properties of the substrate affect the biting behaviour of bugs, this apparatus was covered by a latex membrane. Additionally, we evaluated whether the expression of probing depends on the integration of bilateral thermal inputs from the antennae.</p> <p>Results</p> <p>The presence of a latex cover on a thermal source induced a change in the biting pattern shown by bugs. In fact, with latex covered sources it was possible to observe long bites that were never performed in response to warm metal surfaces. The total number of bites was higher in intact versus unilaterally antennectomized insects. These bites were significantly longer in intact than in unilaterally antennectomized insects.</p> <p>Conclusions</p> <p>Our results suggest that substrate recognition by simultaneous input through thermal and mechanical modalities is required for triggering maxillary probing activity.</p

Results of endoscopic biliary drainage in patients with malignant hilar stricture

In Malignant Hilar Biliary Stricture (MHBS) palliative biliary drainage is a frequent strategy, improving the quality of life, reducing pruritus, loss of appetite and relieving cholangitis. The endoscopic approach is an effective, although challenging procedure. This study aimed to evaluate technical and clinical success rates of biliary drainage by ERCP. This is a retrospective study including all patients with MHBS referred to Instituto do Cancer do Hospital de São Paulo (ICESP) submitted to biliary drainage by ERCP, between January 2010 and December 2017. Multivariable logistic regression was performed to evaluate predictors of clinical failure, as total bilirubin levels, Bismuth classification, number of hepatic sectors drained and presence of cholangitis. In total, 82 patients presenting unresectable MHBS were included in this study. 58.5% female and 41.5% male, with a mean age of 60±13 years. Bismuth classification grades II, IIIA, IIIB and IV were noted in 23.2%, 15.9%, 14.6% and 46.3%, respectively. Technical and clinical success was achieved in 92.7% and 53.7% respectively. At multivariable logistic-regression analyses, Bismuth IV strictures were related to higher clinical failure rates when compared to other strictures levels, with an Odds Ratio of 5.8 (95% CI 1.28‒20.88). In conclusion, endoscopic biliary drainage for malignant hilar biliary stricture had a high technical success but suboptimal clinical success rate. Proximal strictures (Bismuth IV) were associated with poor drainage outcomes