Lipid sensing and lipid sensors: Cytoplasmic fatty acid binding protein sensing fatty acids for peroxisome proliferator activated receptor activation

Abstract.: Translation of nutrient stimuli through intracellular signaling is important for adaption and regulation of metabolic processes, while deregulation by either genetic or environmental factors predisposes towards the development of metabolic disorders. Besides providing energy, fatty acids act as prominent signaling molecules by altering cell membrane structures, affecting the lipid modification status of proteins, and by modulating ligand-activated nuclear receptor activity. Given their highly hydrophobic nature, fatty acids in the aqueous intracellular compartment are bound to small intracellular lipid binding proteins which function as intracellular carriers of these hydrophobic components. This review describes recent advances in identifying intracellular pathways for cytosolic fatty acid signaling through ligand activated receptors by means of small intracellular lipid binding proteins. The mechanism behind intracellular fatty acid transport and subsequent nuclear receptor activation is an emerging concept, and advances in understanding this process provide new potential therapeutic targets towards the treatment of metabolic disorder

Tissue inhibitor of matrix metalloproteinase 1 (TIMP1) controls adipogenesis in obesity in mice and in humans

Aims/hypothesis: Extracellular matrix reorganisation is a crucial step of adipocyte differentiation and is controlled by the matrix metalloproteinase-tissue inhibitor of matrix metalloproteinase (TIMP) enzyme system. We therefore sought to define the role of TIMP1 in adipogenesis and to elucidate whether upregulation of TIMP1 in obesity has direct effects on adipocyte formation. Methods: TIMP1 protein levels and mRNA were measured in lean and obese mice with a focus on levels in adipose tissue. We also analysed the effect of recombinant murine TIMP1 on adipogenesis, adipocyte size and metabolic control in vitro and in vivo. Results: TIMP1 levels were increased in the serum and adipose tissue of obese mouse models. Recombinant murine TIMP1 inhibited adipocyte differentiation in 3T3-L1 as well as in subcutaneous primary pre-adipocytes. Conversely, neutralising TIMP1 with a specific antibody enhanced adipocyte differentiation. In vivo, injection of recombinant TIMP1 in mice challenged with a high-fat diet led to enlarged adipocytes. TIMP1-treated mice developed an impaired metabolic profile with increased circulating NEFA levels, hepatic triacylglycerol accumulation and accelerated insulin resistance. Altered glucose clearance in TIMP1-injected mice was due to changes in adipose tissue glucose uptake, whereas muscle glucose clearance remained unaffected. Conclusions/interpretation: TIMP1 is a negative regulator of adipogenesis. In vivo, TIMP1 leads to enlarged adipocytes in the state of overnutrition. This might contribute to the detrimental metabolic consequences seen in TIMP1-injected mice, such as systemic fatty acid overload, hepatic lipid accumulation and insulin resistanc

Исследование влияния механоактивации порошковой композиции на структуру спеченных изделий

Laser-based imaging of fuel vapor distribution, ignition, and soot formation in diesel sprays was carried out in a high-pressure, high-temperature spray chamber under conditions that correspond to temperature and pressure in a diesel engine. Rayleigh scattering and laser-induced incandescence are used to image fuel density and soot volume fraction. The experimental results provide data for comparison with numerical simulations. An interactive cross-sectionally averaged spray model based on Eulerian transport equations was used for the simulation of the spray, and the turbulence-chemistry interaction was modeled with the representative interactive flamelet (RIF) concept. The flamelet calculation is coupled to the Kiva3V computational fluid dynamics (CFD) code using the scalar dissipation rate and pressure as an input to the RIF-code. The flamelet code computes the instationary flamelet profiles for every time step. These profiles were integrated over mixture fraction space using a prescribed β-PDF to obtain mean values, which are passed back to the CFD-code. Thereby, the temperature and the relevant species in each CFD-cell were obtained. The fuel distribution, the average ignition delay as well as the location of ignition are well predicted by the simulation. Furthermore, simulations show that the experimentally observed injection-to-injection variations in ignition delay are due to temperature inhomogeneities. Experimental and simulated spatial soot and fuel vapor density distributions are compared during and after second stage ignition. 2004 The Combustion Institute. Published by Elsevier Inc. All rights reserved

I-mode studies at ASDEX Upgrade: L-I and I-H transitions, pedestal and confinement properties

The I-mode is a plasma regime obtained when the usual L-H power threshold is high, e.g. with unfavourable ion B ∇ direction. It is characterised by the development of a temperature pedestal while the density remains roughly as in the L-mode. This leads to a confinement improvement above the L-mode level which can sometimes reach H-mode values. This regime, already obtained in the ASDEX Upgrade tokamak about two decades ago, has been studied again since 2009 taking advantage of the development of new diagnostics and heating possibilities. The I-mode in ASDEX Upgrade has been achieved with different heating methods such as NBI, ECRH and ICRF. The I-mode properties, power threshold, pedestal characteristics and confinement, are independent of the heating method. The power required at the L-I transition exhibits an offset linear density dependence but, in contrast to the L-H threshold, depends weakly on the magnetic field. The L-I transition seems to be mainly determined by the edge pressure gradient and the comparison between ECRH and NBI induced L-I transitions suggests that the ion channel plays a key role. The I-mode often evolves gradually over a few confinement times until the transition to H-mode which offers a very interesting situation to study the transport reduction and its link with the pedestal formation. Exploratory discharges in which n = 2 magnetic perturbations have been applied indicate that these can lead to an increase of the I-mode power threshold by flattening the edge pressure at fixed heating input power: more heating power is necessary to restore the required edge pressure gradient. Finally, the confinement properties of the I-mode are discussed in detail.European Commission (EUROfusion 633053

Microdissection of human chromosomes by a laser microbeam

A laser microbeam apparatus, based on an excimer laser pumped dye laser is used to microdissect human chromosomes and to isolate a single chromosome slice

A striking correspondence between the dynamics generated by the vector fields and by the scalar parabolic equations

The purpose of this paper is to enhance a correspondence between the dynamics of the differential equations $\dot y(t)=g(y(t))$ on $\mathbb{R}^d$ and those of the parabolic equations $\dot u=\Delta u +f(x,u,\nabla u)$ on a bounded domain $\Omega$. We give details on the similarities of these dynamics in the cases $d=1$, $d=2$ and $d\geq 3$ and in the corresponding cases $\Omega=(0,1)$, $\Omega=\mathbb{T}^1$ and dim($\Omega$)$\geq 2$ respectively. In addition to the beauty of such a correspondence, this could serve as a guideline for future research on the dynamics of parabolic equations

Fast-ion redistribution and loss due to edge perturbations in the ASDEX Upgrade, DIII-D and KSTAR tokamaks

The impact of edge localized modes (ELMs) and externally applied resonant and non-resonant magnetic perturbations (MPs) on fast-ion confinement/transport have been investigated in the ASDEX Upgrade (AUG), DIII-D and KSTAR tokamaks. Two phases with respect to the ELM cycle can be clearly distinguished in ELM-induced fast-ion losses. Inter-ELM losses are characterized by a coherent modulation of the plasma density around the separatrix while intra-ELM losses appear as well-defined bursts. In high collisionality plasmas with mitigated ELMs, externally applied MPs have little effect on kinetic profiles, including fast-ions, while a strong impact on kinetic profiles is observed in low-collisionality, low q 95 plasmas with resonant and non-resonant MPs. In low-collisionality H-mode plasmas, the large fast-ion filaments observed during ELMs are replaced by a loss of fast-ions with a broad-band frequency and an amplitude of up to an order of magnitude higher than the neutral beam injection prompt loss signal without MPs. A clear synergy in the overall fast-ion transport is observed between MPs and neoclassical tearing modes. Measured fast-ion losses are typically on banana orbits that explore the entire pedestal/scrape-off layer. The fast-ion response to externally applied MPs presented here may be of general interest for the community to better understand the MP field penetration and overall plasma response.Ministerio de Economía y Empresa ((RYC-2011-09152 y ENE2012-31087)Marie Curie (Grant PCIG11-GA-2012-321455)US Department of Energy (DE-FC02-04ER54698, SC-G903402, DE-FG02-04ER54761, DE-AC02-09CH11466 and DE-FG02- 08ER54984)NRF Korea contract 2009-0082012MEST under the KSTAR projec

Peroxisome Proliferator Activated Receptor Gamma Controls Mature Brown Adipocyte Inducibility through Glycerol Kinase.

Peroxisome proliferator-activated receptors (PPARs) have been suggested as the master regulators of adipose tissue formation. However, their role in regulating brown fat functionality has not been resolved. To address this question, we generated mice with inducible brown fat-specific deletions of PPARα, β/δ, and γ, respectively. We found that both PPARα and β/δδ are dispensable for brown fat function. In contrast, we could show that ablation of PPARγ in vitro and in vivo led to a reduced thermogenic capacity accompanied by a loss of inducibility by β-adrenergic signaling, as well as a shift from oxidative fatty acid metabolism to glucose utilization. We identified glycerol kinase (Gyk) as a partial mediator of PPARγ function and could show that Gyk expression correlates with brown fat thermogenic capacity in human brown fat biopsies. Thus, Gyk might constitute the link between PPARγ-mediated regulation of brown fat function and activation by β-adrenergic signaling

The leber congenital amaurosis protein AIPL1 and EB proteins co-localize at the photoreceptor cilium

Purpose: The aim of this study was to investigate the interaction and co-localization of novel interacting proteins with the Leber congenital amaurosis (LCA) associated protein aryl hydrocarbon receptor interacting protein-like 1 (AIPL1). Methods: The CytoTrapXR yeast two-hybrid system was used to screen a bovine retinal cDNA library. A novel interaction between AIPL1 and members of the family of EB proteins was confirmed by directed yeast two-hybrid analysis and co-immunoprecipitation assays. The localization of AIPL1 and the EB proteins in cultured cells and in retinal cryosections was examined by immunofluorescence microscopy and cryo-immunogold electron microscopy. Results: Yeast two-hybrid (Y2H) analysis identified the interaction between AIPL1 and the EB proteins, EB1 and EB3. EB1 and EB3 were specifically co-immunoprecipitated with AIPL1 from SK-N-SH neuroblastoma cells. In directed 1:1 Y2H analysis, the interaction of EB1 with AIPL1 harbouring the LCA-causing mutations A197P, C239R and W278X was severely compromised. Immunofluorescent confocal microscopy revealed that AIPL1 did not co-localize with endogenous EB1 at the tips of microtubules, endogenous EB1 at the microtu-bule organising centre following disruption of the microtubule network, or with endogenous β-tubulin. Moreover, AIPL1 did not localize to primary cilia in ARPE-19 cells, whereas EB1 co-localized with the centrosomal marker pericentrin at the base of primary cilia. However, both AIPL1 and the EB proteins, EB1 and EB3, co-localized with centrin-3 in the connecting cilium of photoreceptor cells. Cryo-immunogold electron microscopy confirmed the co-localization of AIPL1 and EB1 in the connecting cilia in human retinal photoreceptors. Conclusions: AIPL1 and the EB proteins, EB1 and EB3, localize at the connecting cilia of retinal photore-ceptor cells, but do not co-localize in the cellular microtubule network or in primary cilia in non-retinal cells. These findings suggest that AIPL1 function in these cells is not related to the role of EB proteins in microtubule dynamics or primary ciliogenesis, but that their association may be related to a specific role in the specialized cilia apparatus of retinal photoreceptors