Role of adipocyte-derived lipoprotein lipase in adipocyte hypertrophy

<p>Abstract</p> <p>Background</p> <p>A major portion of available fatty acids for adipocyte uptake is derived from lipoprotein lipase (LPL)-mediated hydrolysis of circulating lipoprotein particles. In vivo studies aimed at identifying the precise role of adipocyte-derived LPL in fat storage function of adipose tissue have been unable to provide conclusive evidence due to compensatory mechanisms that activate endogenous fatty acid synthesis. To address this gap in knowledge, we have measured the effect of reducing adipocyte LPL expression on intracellular lipid accumulation using a well-established cultured model of adipocyte differentiation.</p> <p>Methods</p> <p>siRNA specific for mouse LPL was transfected into 3T3-L1 adipocytes. Expression of LPL was measured by quantitative real-time PCR and cell surface-associated LPL enzymatic activity was measured by colorimetric detection following substrate (p-nitrophenyl butyrate) hydrolysis. Apolipoprotein CII and CIII expression ratios were also measured by qRT-PCR. Intracellular lipid accumulation was quantified by Nile Red staining.</p> <p>Results</p> <p>During differentiation of 3T3-L1 pre-adipocytes, LPL mRNA expression increases 6-fold resulting in a 2-fold increase in cell surface-associated LPL enzymatic activity. Parallel to this increase in LPL expression, we found that intracellular lipids increased ~10-fold demonstrating a direct correlation between adipocyte-derived LPL expression and lipid storage. We next reduced LPL expression in adipocytes using siRNA transfections to directly quantify the contributions of adipocyte-derived LPL to lipid storage, This treatment reduced LPL mRNA expression and cell surface-associated LPL enzymatic activity to ~50% of non-treated controls while intracellular lipid levels were reduced by 80%. Exogenous addition of purified LPL (to restore extracellular lipolytic activity) or palmitate (as a source of free fatty acids) to siRNA-treated cells restored intracellular lipid levels to those measured for non-treated controls. We also found that adipocytes express apolipoprotein CII and CIII and, in addition, the apoCII/apoCIII ratio remains largely unchanged in cells with reduced LPL expression.</p> <p>Conclusion</p> <p>We provide evidence that adipocyte-derived LPL is required for efficient fatty acid uptake and storage, and that adipocytes express their own source of apoCII and apoCIII for regulating extracellular LPL activity. These findings demonstrate that adipocytes are capable of producing the necessary enzymatic components and co-factors for efficient lipid storage independent of vascular sources.</p

Rhodium complexes bearing tetradentate diamine-bis(phenolate) ligands

Using tetradentate, dianionic ligands, several new rhodium complexes have been prepared. Some of these diamine-bis(phenolate) compounds, are active for C–H activation of benzene. These complexes are air and thermally stable. All four complexes were characterized by X-ray diffraction

Adjuvants : an essential component of neisseria vaccines

Adjuvants may be classified into delivery systems and immune potentiator or modulator molecules based on their mechanism of action. Neisseria vaccines containing traditional adjuvants such as aluminium salts have existed for long time, but meningitis caused by Neisseria meningitidis serogroups, particularly serogroup B, continues to be a global health problem. Novel strategies have applied in silico and recombinant technologies to develop "universal" antigens (e.g. proteins, peptides and plasmid DNA) for vaccines, but these antigens have been shown to be poorly immunogenic even when alum adjuvanted, implying a need for better vaccine design. In this work we review the use of natural, detoxified, or synthetic molecules in combination with antigens to activate the innate immune system and to modulate the adaptive immune responses. In the main, antigenic and imune potentiator signals are delivered using nano-, micro-particles, alum, or emulsions. The importance of interaction between adjuvants and antigens to activate and target dendritic cells, the bridge between the innate and adaptive immune systems, will be discussed. In addition, nasal vaccine strategies based on the development of mucosal adjuvants and Neisseria derivatives to eliminate the pathogen at the site of infection provide promising adjuvants effective not only against respiratory pathogens, but also against pathogens responsible for enteric and sexually transmitted diseases

Genome-wide association study in two cohorts from a multi-generational mouse advanced intercross line highlights the difficulty of replication due to study-specific heterogeneity

There has been extensive discussion of the Replication Crisis in many fields, including genome-wide association studies

Discursos sobre juventude e práticas psicológicas: a produção dos modos de ser jovem. Brasil

O jovem tem sido foco de atenção de instituições sociais, sejam públicas ou privadas. Nos discursos da sociedade sobre essa população, o jovem aparece associado, mais recentemente, à idéia de inserção nos processos sociais. No campo acadêmico, vê-se uma grande produção de pesquisas e de conhecimento em torno da juventude. Nas produções de conhecimento sobre a juventude, circula um discurso de preocupação com relação aos jovens no tocante à sua integração na ordem social, envolvendo a produção econômica e a constituição familiar. Assim, neste artigo, nos remetemos às concepções de juventude que foram sendo veiculadas em diferentes momentos sociais e a como foi se visibilizando um determinado discurso sobre a categoria juventude, articulado à noção de problema. Buscamos discutir a implicação do modo como as práticas psicológicas foram prescrevendo e legitimando esse discurso e como os jovens estão sendo afetados por determinadas práticas sociais presentes no contemporâneo, gerando diferentes formas de subjetivação que, por sua vez, serão pensadas, investidas e implicadas em relações de poder e verdade, sustentadas por saberes, como, por exemplo, o psicológico. Ainda, procuramos evidenciar como esses sujeitos, neste contemporâneo, estão sendo foco de investimento do mercado capitalista como consumidores potenciais.-I. Introdução. -II. Algumas concepções de juventude. -III. O Campo Psi: prescrições nas concepções de juventude. -IV. A inscrição do jovem no contemporâneo: de sujeito problema a sujeito consumidor. -V. À guisa de conclusão: uma categoria de juventude a ser pensada... -Bibliografia

RESEARCH CAPABILITIES OF PUBLIC ELEMENTARY SCHOOL TEACHERS AND MANAGEMENT SUPPORT OF THE SCHOOLS DIVISION OF NUEVA VIZCAYA, PHILIPPINES

Purpose of the study: This study determined the research capabilities of public elementary teachers in the Schools Division of Nueva Vizcaya and also to determine the management support extended to them in terms of research support and research environment condition. Methodology: This study employed the descriptive-correlational method. The descriptive method described the characteristics of the respondents, the level of research capabilities and dissemination, and management research support factors. Two hundred eighteen respondents were drawn from the population. A Stratified random sampling method was used to determine samples per stratum. The researchers observed research ethics and protocols during the gathering process. Descriptive-Inferential statistics were used to interpret the data. Main Findings: The study found out that respondents who attained higher educational attainment and attended national training have improved research skills and are more knowledgeable in the research process and dissemination. The respondents are moderately capable in their research capabilities and research dissemination. The level of research capabilities was significantly correlated with educational attainment and training. Research support was inadequate; a favourable research environment was provided. Applications of this study: The findings of the study provide data to the Department of Education to know the factors affecting the research capabilities of public school teachers. The DepEd school heads can come up with a workable plan to enhance research capabilities and manage their resources, policies, time, space, and personnel for maximum effect. Novelty/Originality of this study: The fast trend in instructional technology and innovative approaches and teaching pedagogies, knowledge, and skills in the research of all academic professionals is essential. Conducting research becomes now mandatory in the educational institutions in the Philippines; thus, needs continuous assessment to produce a community of teacher-researchers

A subarcsecond near-infrared view of massive galaxies at z > 1 with Gemini Multiconjugate Adaptive Optics

We present images taken using the Gemini South Adaptive Optics Imager (GSAOI) with the Gemini Multiconjugate Adaptive Optics System (GeMS) in three 2 arcmin$^2$ fields in the Spitzer Extragalactic Representative Volume Survey. These GeMS/GSAOI observations are among the first $\approx 0.1^{''}$ resolution data in the near-infrared spanning extragalactic fields exceeding $1.5^{\prime}$ in size. We use these data to estimate galaxy sizes, obtaining results similar to those from studies with the Hubble Space Telescope, though we find a higher fraction of compact star forming galaxies at $z>2$. To disentangle the star-forming galaxies from active galactic nuclei (AGN), we use multiwavelength data from surveys in the optical and infrared, including far-infrared data from Herschel, as well as new radio continuum data from the Australia Telescope Compact Array and Very Large Array. We identify ultraluminous infrared galaxies (ULIRGs) at $z \sim 1-3$, which consist of a combination of pure starburst galaxies and Active Galactic Nuclei (AGN)/starburst composites. The ULIRGs show signs of recent merger activity, such as highly disturbed morphologies and include a rare candidate triple AGN. We find that AGN tend to reside in hosts with smaller scale sizes than purely star-forming galaxies of similar infrared luminosity. Our observations demonstrate the potential for MCAO to complement the deeper galaxy surveys to be made with the James Webb Space Telescope.Comment: 20 pages, AJ, in pres

Syndecan-1 mediates internalization of apoE-VLDL through a low density lipoprotein receptor-related protein (LRP)-independent, non-clathrin-mediated pathway

BACKGROUND: Triacylglyerol-rich very low density lipoprotein (VLDL) particles are the primary carriers of fatty acids in the circulation and as such serve as a rich energy source for peripheral tissues. Receptor-mediated uptake of these particles is dependent upon prior association with apolipoprotein E (apoE-VLDL) and is brought about by cell surface heparan sulfate proteoglycans (HSPG) in some cell types and by the low density lipoprotein receptor-related protein (LRP) in others. Although LRP's role in apoE-VLDL uptake has been well studied, the identity of the HSPG family member that mediates apoE-VLDL uptake has not been established. We investigated if syndecan-1 (Syn-1), a transmembrane cell surface HSPG, is able to mediate the internalization of apoE-VLDL and examined the relationship between Syn-1 and LRP toward apoE-VLDL uptake. For this study, we used a human fibroblast cell line (GM00701) that expresses large amounts of LRP, but possesses no LDL receptor activity to eliminate its contributions toward apoE-VLDL uptake. RESULTS: Although LRP in these cells is fully active as established by substantial α(2)macroglobulin binding and internalization, uptake of apoE-VLDL is absent. Expression of human Syn-1 cDNA restored apoE-VLDL binding and uptake by these cells. Competition for this uptake with an LRP ligand-binding antagonist had little or no effect, whereas co-incubation with heparin abolished apoE-VLDL internalization. Depleting Syn-1 expressing cells of K(+), to block clathrin-mediated endocytosis, showed no inhibition of Syn-1 internalization of apoE-VLDL. By contrast, treatment of cells with nystatin to inhibit lipid raft function, prevented the uptake of apoE-VLDL by Syn-1. CONCLUSION: These data demonstrate that Syn-1 is able to mediate apoE-VLDL uptake in human fibroblasts with little or no contribution from LRP and that the endocytic path taken by Syn-1 is clathrin-independent and relies upon lipid raft function. These data are consistent with previous studies demonstrating Syn-1 association with lipid raft domains

Methane Activation with Rhenium Catalysts. 1. Bidentate Oxygenated Ligands

Trends in methane activation have been explored for rhenium-based catalysts in conjunction with bidentate oxygenated ligands of the form (L_1)(L_2)Re(OH)(OH_2) [L_1, L_2 = acac, catechol, glycol]. When placed in acidic media, the equilibrium for this reference catalyst shifts to the protonated forms (L_1)(L_2)Re(OH_2)(OH_2) in almost all cases. In all cases the activation of the reference complex proceeds through a concerted metathesis type transition state, and only one of the 13 reference complexes proceeds with methane activation through a barrier of less than 35 kcal mol-1. Study of the identity complexes (L_1 = L_2) revealed that protonation of the ligand oxygens is unfavorable for acac and catechol, but favorable for glycol; however in only one case is the barrier for methane activation improved by this route. Electron density on the central rhenium is the best predictor for the magnitude of the methane activation barrier; namely, increased electron density (obtained by considering lower oxidation states) on the metal leads to lower barriers. Lower oxidation states form weaker Re−O bonds, which increase lability of the leaving groups and decrease the barrier to proton transfer from methane