mTORC2 sustains thermogenesis via Akt-induced glucose uptake and glycolysis in brown adipose tissue

Activation of non-shivering thermogenesis (NST) in brown adipose tissue (BAT) has been proposed as an anti-obesity treatment. Moreover, cold-induced glucose uptake could normalize blood glucose levels in insulin-resistant patients. It is therefore important to identify novel regulators of NST and cold-induced glucose uptake. Mammalian target of rapamycin complex 2 (mTORC2) mediates insulin-stimulated glucose uptake in metabolic tissues, but its role in NST is unknown. We show that mTORC2 is activated in brown adipocytes upon β-adrenergic stimulation. Furthermore, mice lacking mTORC2 specifically in adipose tissue (AdRiKO mice) are hypothermic, display increased sensitivity to cold, and show impaired cold-induced glucose uptake and glycolysis. Restoration of glucose uptake in BAT by overexpression of hexokinase II or activated Akt2 was sufficient to increase body temperature and improve cold tolerance in AdRiKO mice. Thus, mTORC2 in BAT mediates temperature homeostasis via regulation of cold-induced glucose uptake. Our findings demonstrate the importance of glucose metabolism in temperature regulation

Simplified modelling of nonlinear electromethanogenesis stack for power-to-gas applications

Bioelectrochemical systems performing electromethanogenesis (EMG-BES) represent an emerging technology for Power-to-gas as well as wastewater treatment. Moreover, EMG-BES can be used as a high-capacity energy storage system to absorb surplus energy in the electrical grid. This paper presents a modelling approach, which is based on building an equivalent electric circuit of the EMG-BES, which can be used to emulate static and dynamic non-linear behaviour of EMG-BES for different input voltages, which is advantageous if compared to other existing models. This model is a suitable choice for future studies in the development of the electric converters for EMG-BES plants connected to the electrical grid. The proposed model consists of practical and commercial elements, including capacitors, resistors, voltage sources, and a diode. The modelling of non-linear behaviour is achieved by adding a diode to the model. Four simple tests were performed to determine the equivalent circuit parameters in a medium-scale EMG-BES prototype. This prototype was built by stacking 45 cells together and connecting them in parallel, and it was long-term operated and tested under different electric inputs to determine the model parameters. A comparative study was finally conducted as reported in this paper in order to validate the proposed model against experimental results and values collected with other models.The research leading to these results has received funding from the European Union's Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie grant agreement No 712949 (TECNIOspring PLUS) and from the Agency for Business Competitiveness of the Government of Catalonia. Also, this work has been supported by the Spanish Ministry of Economy and Competitiveness under the projects RTI2018-100921-BC21. Any opinions, findings and conclusions or recommendations expressed in this material are those of the authors and do not necessarily reflect those of the host institutions or funders. The authors wish to acknowledge the Leitat collaborators who took part in Power2Biomethane project, which was financially supported by the Spanish Ministry of Economy and Competitiveness (RTC-2016- 5024-3, 2016).Peer ReviewedPostprint (author's final draft

Contribution of Intronic miR-338-3p and Its Hosting Gene AATK to Compensatory β-Cell Mass Expansion.

The elucidation of the mechanisms directing β-cell mass regeneration and maintenance is of interest, because the deficit of β-cell mass contributes to diabetes onset and progression. We previously found that the level of the microRNA (miRNA) miR-338-3p is decreased in pancreatic islets from rodent models displaying insulin resistance and compensatory β-cell mass expansion, including pregnant rats, diet-induced obese mice, and db/db mice. Transfection of rat islet cells with oligonucleotides that specifically block miR-338-3p activity increased the fraction of proliferating β-cells in vitro and promoted survival under proapoptotic conditions without affecting the capacity of β-cells to release insulin in response to glucose. Here, we evaluated the role of miR-338-3p in vivo by injecting mice with an adeno-associated viral vector permitting specific sequestration of this miRNA in β-cells. We found that the adeno-associated viral construct increased the fraction of proliferating β-cells confirming the data obtained in vitro. miR-338-3p is generated from an intron of the gene coding for apoptosis-associated tyrosine kinase (AATK). Similarly to miR-338-3p, we found that AATK is down-regulated in rat and human islets and INS832/13 β-cells in the presence of the cAMP-raising agents exendin-4, estradiol, and a G-protein-coupled Receptor 30 agonist. Moreover, AATK expression is reduced in islets of insulin resistant animal models and selective silencing of AATK in INS832/13 cells by RNA interference promoted β-cell proliferation. The results point to a coordinated reduction of miR-338-3p and AATK under insulin resistance conditions and provide evidence for a cooperative action of the miRNA and its hosting gene in compensatory β-cell mass expansion

The role of spin in the formation and evolution of galaxies

Using the SDSS spectroscopic sample, we estimate the dark matter halo spin parameter lambda for ~53,000 disk galaxies for which MOPED star formation histories are available. We investigate the relationship between spin and total stellar mass, star formation history, and environment. First, we find a clear anti-correlation between stellar mass and spin, with low mass galaxies generally having high dark matter spins. Second, galaxies which have formed more than ~5% of their stars in the last 0.2 Gyr have more broadly distributed and typically higher spins (including a significant fraction with lambda > 0.1) than galaxies which formed a large fraction of their stars more than 10 Gyr ago. Finally, we find little or no correlation between the value of spin of the dark halo and environment as determined both by proximity to a new cluster catalog and a marked correlation study. This agrees well with the predictions from linear hierarchical torquing theory and numerical simulations.Comment: Accepted to MNRAS after moderate revisio

In Vivo Adeno-Associated Viral Vector-Mediated Genetic Engineering of White and Brown Adipose Tissue in Adult Mice

Adipose tissue is pivotal in the regulation of energy homeostasis through the balance of energy storage and expenditure and as an endocrine organ. An inadequate mass and/or alterations in the metabolic and endocrine functions of adipose tissue underlie the development of obesity, insulin resistance, and type 2 diabetes. To fully understand the metabolic and molecular mechanism(s) involved in adipose dysfunction, in vivo genetic modification of adipocytes holds great potential. Here, we demonstrate that adeno-associated viral (AAV) vectors, especially serotypes 8 and 9, mediated efficient transduction of white (WAT) and brown adipose tissue (BAT) in adult lean and obese diabetic mice. The use of short versions of the adipocyte protein 2 or uncoupling protein-1 promoters or micro-RNA target sequences enabled highly specific, long-term AAV-mediated transgene expression in white or brown adipocytes. As proof of concept, delivery of AAV vectors encoding for hexokinase or vascular endothelial growth factor to WAT or BAT resulted in increased glucose uptake or increased vessel density in targeted depots. This method of gene transfer also enabled the secretion of stable high levels of the alkaline phosphatase marker protein into the bloodstream by transduced WAT. Therefore, AAV-mediated genetic engineering of adipose tissue represents a useful tool for the study of adipose pathophysiology and, likely, for the future development of new therapeutic strategies for obesity and diabetes

Biocleaning of nitrate alterations on wall paintings by Pseudomonas stutzeri

Microorganisms have been considered as causative agents of biodeterioration in multiple artworks. In this paper, we argue that microorganisms can be positively used for the cleaning of salt crusts otherwise difficult to remove by traditional restoration methods. We use Pseudomonas stutzeri to efficiently clean wall paintings. The bacteria allow for adequate and homogenous removal of insoluble salt efflorescence without damaging the painted layer. We also make use of a new application support consisting of agar. This new technology has been successfully applied in the biocleaning of eighteen-century murals located in a lunette of the Santos Juanes church in Valencia, Spain.This work has appreciated partial financial support from the Universitat Politecnica de Valencia (PAID-05-09: Biotecnologia microbiana aplicada a la limpieza y restauracion de superficies de obras de arte), coordination by Rosa Maria Montes Estelles, and support from the Spanish Ministerio de Ciencia e Innovacion, with a Ph.D. scholarship for Pilar Bosch Roig (BES-2006-12110). The authors wish to thank to the priest of the Santos Juanes Church of Valencia; the 'Direccion General de Patrimonio'; Professor Pilar Roig Picazo; Gianluigi Colalucci, Donatella Zari and Carlo Giantomassi restorers of the Campo Santo di Pisa; Jose Juan Baldo and Irene Carpio, restorers of the Santos Juanes church of Valencia; to Mathieu Viau-Courville; the Instituto Universitario de Restauracion del Patrimonio; and Restaura BioTech S.L.; and particularly to Giancarlo Ranalli due to his invaluable help for the development of this manuscript.Bosch Roig, MDP.; Regidor Ros, JL.; Montes Estellés, RM. (2013). Biocleaning of nitrate alterations on wall paintings by Pseudomonas stutzeri. International Biodeterioration and Biodegradation. 84:266-274. https://doi.org/10.1016/j.ibiod.2012.09.009S2662748

A Pectin Methylesterase ZmPme3 Is Expressed in Gametophyte factor1-s (Ga1-s) Silks and Maps to that Locus in Maize (Zea mays L.)

The ga1 locus of maize confers unilateral cross incompatibility, preventing cross pollination between females carrying the incompatible Ga1-s allele and males not carrying a corresponding compatible allele. To characterize this system at the molecular level, we carried out a transcript profiling experiment in which silks from near isogenic lines carrying the Ga1-sand ga1 alleles were compared. While several differentially expressed genes were identified, only one mapped to the known location of ga1. This gene is a pectin methylesterase (PME), which we designated as ZmPme3, and is present and expressed only in Ga1-s genotypes. While a functional ZmPME3 is not present in the ga1 genotypes examined, a pectin methylesterase gene cluster is found in ga1 genotypes. The gene cluster in W22 contains 58 tandem full-length or partial PME pseudo genes. These data combined with a wealth of previously published data on the involvement of PMEs in pollen tube growth suggest a role for cell wall modification enzymes in the pollen exclusion component of Ga1-s gametophytic incompatibility. Consistent with this role, a third allele which lacks the female function of Ga1-s, Ga1-m, has a mutationally inactivated version of ZmPme3

Star formation histories and evolution of 35 brightest E+A galaxies from SDSS DR5

We pick out the 35 brightest galaxies from Goto's E+A galaxies catalogue which are selected from the Sloan Digital Sky Survey Data Release 5. The spectra of E+As are prominently characterized by the strong Balmer absorption lines but little [Oii] or H_alpha emission lines. In this work we study the stellar populations of the sample galaxies by fitting their spectra using ULySS, which is a robust full spectrum fitting method. We fit each of the sample with 1-population (a single stellar population-a SSP) and 3-population (3 SSPs) models, separately. By 1-population fits, we obtain SSP-equivalent ages and metallicities which correspond to the `luminosity-weighted' averages. By 3-population fits, we divide components into three groups in age (old stellar population-OSP, intermediate-age stellar population-ISP, and young stellar population-YSP), and then get the optimal age, metallicity and population fractions in both mass and light for OSP, ISP and YSP. During the fits, both Pegase.HR/Elodie3.1 and Vazdekis/Miles are used as two independent population models. The two models result in generally consistent conclusions as follows: for all the sample galaxies, YSPs (< 1Gyr) make important contributions to the light. However, the dominant contributors to mass are OSPs. We also reconstruct the smoothing star formation histories (SFHs) by giving star formation rate (SFR) versus evolutionary age. In addition, we fit the E+A sample and 34 randomly selected elliptical galaxies with 2-population (2 SSPs) model. We obtain the equivalent age of old components for each of the E+A sample and elliptical galaxies. By comparison, the old components of E+As are statistically much younger than those of ellipticals. From the standpoint of the stellar population age, this probably provides an evidence for the proposed evolutionary link from E+As to early-types (E/S0s).Comment: 16 pages, 9 figures, Accepted for publication on MNRA

BMP7 overexpression in adipose tissue induces white adipogenesis and improves insulin sensitivity in ob/ob mice

Altres ajuts: ICREA Academia AwardBackground/objectives: During obesity, hypertrophic enlargement of white adipose tissue (WAT) promotes ectopic lipid deposition and development of insulin resistance. In contrast, WAT hyperplasia is associated with preservation of insulin sensitivity. The complex network of factors that regulates white adipogenesis is not fully understood. Bone morphogenic protein 7 (BMP7) can induce brown adipogenesis, but its role on white adipogenesis remains to be elucidated. Here, we assessed BMP7-mediated effects on white adipogenesis in ob/ob mice. Methods: BMP7 was overexpressed in either WAT or liver of ob/ob mice using adeno-associated viral (AAV) vectors. Analysis of gene expression, histological and morphometric alterations, and metabolites and hormones concentrations were carried out. Results: Overexpression of BMP7 in adipocytes of subcutaneous and visceral WAT increased fat mass, the proportion of small-size adipocytes and the expression of adipogenic and mature adipocyte genes, suggesting induction of adipogenesis irrespective of fat depot. These changes were associated with reduced hepatic steatosis and improved insulin sensitivity. In contrast, liver-specific overproduction of BMP7 did not promote WAT hyperplasia despite BMP7 circulating levels were similar to those achieved after genetic engineering of WAT. Conclusions: This study unravels a new autocrine/paracrine role of BMP7 on white adipogenesis and highlights that BMP7 may modulate WAT plasticity and increase insulin sensitivity