A PPARγ-FGF1 axis is required for adaptive adipose remodelling and metabolic homeostasis

Although feast and famine cycles illustrate that remodelling of adipose tissue in response to fluctuations in nutrient availability is essential for maintaining metabolic homeostasis, the underlying mechanisms remain poorly understood. Here we identify fibroblast growth factor 1 (FGF1) as a critical transducer in this process in mice, and link its regulation to the nuclear receptor PPARγ (peroxisome proliferator activated receptor γ), which is the adipocyte master regulator and the target of the thiazolidinedione class of insulin sensitizing drugs. FGF1 is the prototype of the 22-member FGF family of proteins and has been implicated in a range of physiological processes, including development, wound healing and cardiovascular changes. Surprisingly, FGF1 knockout mice display no significant phenotype under standard laboratory conditions. We show that FGF1 is highly induced in adipose tissue in response to a high-fat diet and that mice lacking FGF1 develop an aggressive diabetic phenotype coupled to aberrant adipose expansion when challenged with a high-fat diet. Further analysis of adipose depots in FGF1-deficient mice revealed multiple histopathologies in the vasculature network, an accentuated inflammatory response, aberrant adipocyte size distribution and ectopic expression of pancreatic lipases. On withdrawal of the high-fat diet, this inflamed adipose tissue fails to properly resolve, resulting in extensive fat necrosis. In terms of mechanisms, we show that adipose induction of FGF1 in the fed state is regulated by PPARγ acting through an evolutionarily conserved promoter proximal PPAR response element within the FGF1 gene. The discovery of a phenotype for the FGF1 knockout mouse establishes the PPARγ–FGF1 axis as critical for maintaining metabolic homeostasis and insulin sensitization.     

Glycine binding primes NMDA receptor internalization

NMDA (N-methyl-d-aspartate) receptors (NMDARs) are a principal subtype of excitatory ligand-gated ion channel with prominent roles in physiological and disease processes in the central nervous system. Recognition that glycine potentiates NMDAR-mediated currents as well as being a requisite co-agonist of the NMDAR subtype of 'glutamate' receptor profoundly changed our understanding of chemical synaptic communication in the central nervous system. The binding of both glycine and glutamate is necessary to cause opening of the NMDAR conductance pore. Although binding of either agonist alone is insufficient to cause current flow through the channel, we report here that stimulation of the glycine site initiates signalling through the NMDAR complex, priming the receptors for clathrin-dependent endocytosis. Glycine binding alone does not cause the receptor to be endocytosed; this requires both glycine and glutamate site activation of NMDARs. The priming effect of glycine is mimicked by the NMDAR glycine site agonist d-serine, and is blocked by competitive glycine site antagonists. Synaptic as well as extrasynaptic NMDARs are primed for internalization by glycine site stimulation. Our results demonstrate transmembrane signal transduction through activating the glycine site of NMDARs, and elucidate a model for modulating cell-cell communication in the central nervous system.     

Effects of Eriobotrya japonica (Lindl.) flower extracts on mercuric chloride-induced hepatotoxicity in rats

Mercury(II) is an important factor in hepatotoxicity that can enter the body through marine diets and amalgams.In the present study,the protective effect of the Eriobotrya japonica flower extract(EJFE) on HgCl 2-induced hepatotoxicity was investigated.Five mg/kg of mercuric chloride in drinking water was given to rats either with saline or EJFE(100 and 200 mg/kg as intraperitoneal(IP)) for 30 d.The mercury levels in different groups of liver tissues of the rats were measured with flameless atomic absorption spectroscopy(F-AAS).Also,mercury accumulation in the liver of the rats was modeled by using a parallel chemical kinetic model.The results showed that HgCl 2-induced oxidative damage led to a significant decrease in glutathione(GSH) and the total antioxidant capacity(TAC) levels,and to a significant increase in lipid peroxidation level.Accumulated mercury was 14.47% more in the livers of the stress groups than in those of the control groups(P<0.001),whereas the amount of Hg was adjusted to 13.49% and 13.93% in groups treated with 100 and 200 mg/kg of EJFE respectively,as compared with stress groups(P<0.001).HPLC analysis of EJFE revealed that hesperetin and gallic acid are the major antioxidants in EJFE.Results demonstrate that flowers of the Eriobotrya japonica cause a significant protection against HgCl 2 induced hepatotoxicity in all diagnostic parameters by strengthening the antioxidant defense mechanisms and they may have a therapeutic function in free radical mediated diseases.     

Effects of cold rolling on the microstructure and mechanical properties of Fe-Ni-Mn-Mo-Ti-Cr maraging steels

Effects of cold rolling on the microstructure and mechanical properties of Fe-Ni-Mn-Mo-Ti-Cr maraging steels were studied. To investigate the microstructure and mechanical properties, optical microscopy, scanning electron microscopy, X-ray diffraction, tensile test, and hardness test were used. The results show that the solution-annealing treatment in the cold-rolled steel redounds to the formation of submicrocrystalline Fe₂(Mo, Ti) Laves phase particles, which are stable at high temperatures. These secondary Laves phase particles prevent from recrystallization at high temperatures and correspond to semi-brittle fracture in the subsequent aging treatment.     

Towards skin polarization characterization using polarimetric technique

Measurement of optical properties of skin is an expanding and growing field of research. Recent studies have shown that the biological tissue, especially skin, changes the polarization state of the incident light. Using this property will enable the study of abnormalities and diseases that alter not only the light intensity but also its polarization state. In this paper we report an experimental study for measuring changes of polarization state of the light scattered from a phantom similar to a sample model of scattering skin. Using the notation of Stokes vector for the polarized light and Mueller matrix for the sample with its polarization properties, we have shown that some elements of the matrix were particularly sensitive to the changes of the polarization-altering physical properties of the scatterers within the phantom.     

Modeling European industrial production with multivariate singular spectrum analysis: A cross‐industry analysis

In this paper, an optimized multivariate singular spectrum analysis (MSSA) approach is proposed to find leading indicators of cross‐industry relations between 24 monthly, seasonally unadjusted industrial production (IP) series for German, French, and UK economies. Both recurrent and vector forecasting algorithms of horizontal MSSA (HMSSA) are considered. The results from the proposed multivariate approach are compared with those obtained via the optimized univariate singular spectrum analysis (SSA) forecasting algorithm to determine the statistical significance of each outcome. The data are rigorously tested for normality, seasonal unit root hypothesis, and structural breaks. The results are presented such that users can not only identify the most appropriate model based on the aim of the analysis, but also easily identify the leading indicators for each IP variable in each country. Our findings show that, for all three countries, forecasts from the proposed MSSA algorithm outperform the optimized SSA algorithm in over 70% of cases. Accordingly, this new approach succeeds in identifying leading indicators and is a viable option for selecting the SSA choices L and r, which minimizes a loss function.     

Structural and mechanistic insights into the interaction between Rho and mammalian Dia

Formins are involved in a variety of cellular processes that require the remodelling of the cytoskeleton. They contain formin homology domains FH1 and FH2, which initiate actin assembly. The Diaphanous-related formins form a subgroup that is characterized by an amino-terminal Rho GTPase-binding domain (GBD) and an FH3 domain, which bind somehow to the carboxy-terminal Diaphanous autoregulatory domain (DAD) to keep the protein in an inactive conformation. Upon binding of activated Rho proteins, the DAD is released and the ability of the formin to nucleate and elongate unbranched actin filaments is induced. Here we present the crystal structure of RhoC in complex with the regulatory N terminus of mammalian Diaphanous 1 (mDia1) containing the GBD/FH3 region, an all-helical structure with armadillo repeats. Rho uses its 'switch' regions for interacting with two subdomains of GBD/FH3. We show that the FH3 domain of mDia1 forms a stable dimer and we also identify the DAD-binding site. Although binding of Rho and DAD on the N-terminal fragment of mDia1 are mutually exclusive, their binding sites are only partially overlapping. On the basis of our results, we propose a structural model for the regulation of mDia1 by Rho and DAD.     

Singular spectrum analysis: methodology and application to economics data

This paper describes the methodology of singular spectrum analysis (SSA) and demonstrate that it is a powerful method of time series analysis and forecasting, particulary for economic time series. The authors consider the application of SSA to the analysis and forecasting of the Iranian national accounts data as provided by the Central Bank of the Islamic Republic of Iran. This research was in part supported by a grant (No. 88/121230) from Institute for Trade Studies and Research (ITSR), Tehran, Iran.     

Fabrication and densification enhancement of SiC-particulate-reinforced copper matrix composites prepared via the sinter-forging process

The fabrication of copper (Cu) and copper matrix silicon carbide (Cu/SiC_p) particulate composites via the sinter-forging process was investigated. Sintering and sinter-forging processes were performed under an inert Ar atmosphere. The influence of sinter-forging time, temperature, and compressive stress on the relative density and hardness of the prepared samples was systematically investigated and subsequently compared with that of the samples prepared by the conventional sintering process. The relative density and hardness of the composites were enhanced when they were prepared by the sinter-forging process. The relative density values of all Cu/SiC_p composite samples were observed to decrease with the increase in SiC content.