Autotaxin-LPA Signaling Contributes to Obesity-Induced Insulin Resistance in Muscle and Impairs Mitochondrial Metabolism

Autotaxin (ATX) is an adipokine that generates the bioactive lipid, lysophosphatidic acid (LPA). ATX-LPA signaling has been implicated in diet-induced obesity and systemic insulin resistance. However, it remains unclear whether the ATX-LPA pathway influences insulin function and energy metabolism in target tissues, particularly skeletal muscle, the major site of insulin-stimulated glucose disposal. The objective of this study was to test whether the ATX-LPA pathway impacts tissue insulin signaling and mitochondrial metabolism in skeletal muscle during obesity. Male mice with heterozygous ATX deficiency (ATX+/−) were protected from obesity, systemic insulin resistance, and cardiomyocyte dysfunction following high-fat high-sucrose (HFHS) feeding. HFHS-fed ATX+/− mice also had improved insulin-stimulated AKT phosphorylation in white adipose tissue, liver, heart, and skeletal muscle. Preserved insulin-stimulated glucose transport in muscle from HFHS-fed ATX+/− mice was associated with improved mitochondrial pyruvate oxidation in the absence of changes in fat oxidation and ectopic lipid accumulation. Similarly, incubation with LPA decreased insulin-stimulated AKT phosphorylation and mitochondrial energy metabolism in C2C12 myotubes at baseline and following palmitate-induced insulin resistance. Taken together, our results suggest that the ATX-LPA pathway contributes to obesity-induced insulin resistance in metabolically relevant tissues. Our data also suggest that LPA directly impairs skeletal muscle insulin signaling and mitochondrial function

Integrating transposable elements in the 3D genome

Chromosome organisation is increasingly recognised as an essential component of genome regulation, cell fate and cell health. Within the realm of transposable elements (TEs) however, the spatial information of how genomes are folded is still only rarely integrated in experimental studies or accounted for in modelling. Whilst polymer physics is recognised as an important tool to understand the mechanisms of genome folding, in this commentary we discuss its potential applicability to aspects of TE biology. Based on recent works on the relationship between genome organisation and TE integration, we argue that existing polymer models may be extended to create a predictive framework for the study of TE integration patterns. We suggest that these models may offer orthogonal and generic insights into the integration profiles (or "topography") of TEs across organisms. In addition, we provide simple polymer physics arguments and preliminary molecular dynamics simulations of TEs inserting into heterogeneously flexible polymers. By considering this simple model, we show how polymer folding and local flexibility may generically affect TE integration patterns. The preliminary discussion reported in this commentary is aimed to lay the foundations for a large-scale analysis of TE integration dynamics and topography as a function of the three-dimensional host genome

Soluble TNF Mediates the Transition from Pulmonary Inflammation to Fibrosis

BACKGROUND: Fibrosis, the replacement of functional tissue with excessive fibrous tissue, can occur in all the main tissues and organ systems, resulting in various pathological disorders. Idiopathic Pulmonary Fibrosis is a prototype fibrotic disease involving abnormal wound healing in response to multiple sites of ongoing alveolar epithelial injury. METHODOLOGY/PRINCIPAL FINDINGS: To decipher the role of TNF and TNF-mediated inflammation in the development of fibrosis, we have utilized the bleomycin-induced animal model of Pulmonary Fibrosis and a series of genetically modified mice lacking components of TNF signaling. Transmembrane TNF expression is shown to be sufficient to elicit an inflammatory response, but inadequate for the transition to the fibrotic phase of the disease. Soluble TNF expression is shown to be crucial for lymphocyte recruitment, a prerequisite for TGF-b1 expression and the development of fibrotic lesions. Moreover, through a series of bone marrow transfers, the necessary TNF expression is shown to originate from the non-hematopoietic compartment further localized in apoptosing epithelial cells. CONCLUSIONS: These results suggest a primary detrimental role of soluble TNF in the pathologic cascade, separating it from the beneficial role of transmembrane TNF, and indicate the importance of assessing the efficacy of soluble TNF antagonists in the treatment of Idiopathic Pulmonary Fibrosis

Genomics and proteomics approaches to the study of cancer-stroma interactions

<p>Abstract</p> <p>Background</p> <p>The development and progression of cancer depend on its genetic characteristics as well as on the interactions with its microenvironment. Understanding these interactions may contribute to diagnostic and prognostic evaluations and to the development of new cancer therapies. Aiming to investigate potential mechanisms by which the tumor microenvironment might contribute to a cancer phenotype, we evaluated soluble paracrine factors produced by stromal and neoplastic cells which may influence proliferation and gene and protein expression.</p> <p>Methods</p> <p>The study was carried out on the epithelial cancer cell line (Hep-2) and fibroblasts isolated from a primary oral cancer. We combined a conditioned-medium technique with subtraction hybridization approach, quantitative PCR and proteomics, in order to evaluate gene and protein expression influenced by soluble paracrine factors produced by stromal and neoplastic cells.</p> <p>Results</p> <p>We observed that conditioned medium from fibroblast cultures (FCM) inhibited proliferation and induced apoptosis in Hep-2 cells. In neoplastic cells, 41 genes and 5 proteins exhibited changes in expression levels in response to FCM and, in fibroblasts, 17 genes and 2 proteins showed down-regulation in response to conditioned medium from Hep-2 cells (HCM). Nine genes were selected and the expression results of 6 down-regulated genes (<it>ARID4A</it>, <it>CALR</it>, <it>GNB2L1</it>, <it>RNF10</it>, <it>SQSTM1</it>, <it>USP9X</it>) were validated by real time PCR.</p> <p>Conclusions</p> <p>A significant and common denominator in the results was the potential induction of signaling changes associated with immune or inflammatory response in the absence of a specific protein.</p

Magnetic Study of Phases in FeVO₄-Co₃V₂O₈ System

Magnetic properties of four nFeVO₄/(1-n)Co₃V₂O₈ samples obtained in reactions between FeVO₄ and Co₃V₂O₈ (n = 0.96, 0.86, 0.84 and 0.83, samples designated S1, S3, S4, S5, respectively) have been investigated by DC magnetisation in field cooling and zero-field-cooling modes and EPR. DC magnetic susceptibility showed paramagnetic behavior of all samples in high-temperature range (T > 20 K) and transition to antiferromagnetic state at 16-18 K (depending on sample iron content). Additional magnetic freezing at 8 K was registered for S3-S5 samples containing larger amount of cobalt. The Curie-Weiss law in 100-300 K temperature range indicates that Co²⁺ is in the high-spin state (S = 3/2). From the parameters of the hysteresis loop observed for the samples it was calculated that 0.58% of all magnetic (Fe³⁺, Co²⁺) ions were involved in the ferromagnetic states. EPR spectra of the samples were recorded in high temperature range (T > 90 K). The temperature dependence of the spectral parameters (resonance field, linewidth, integrated intensity) suggested the Fe³⁺ high-spin ions coupled by antiferromagnetic interaction and clusters of ions play major role in EPR spectra

High temperature EPR study of the M3Fe4V6O24 (M = Cu, Zn, Mg and Mn)

Electron paramagnetic resonance (EPR) spectra of M3Fe4V6O24 (M = Cu, Zn, Mg and Mn) compounds in high temperature range (293 K to 493 K) have been investigated. The role of magnetic (Cu, Mn) and non-magnetic (Zn, Mg) ions in M3Fe4V6O24 structure in formation of magnetic resonance spectra was studied. Temperature dependence of EPR parameters: resonance field, linewidth and integrated intensity were examined. Similarities and differences in temperature behavior of these parameters has been discussed in terms of different relaxation mechanisms and magnetic interactions in the spin systems. An important role of additional magnetic ions (M = Mn or Cu) in the M3Fe4V6O24 structure has been identified and its consequences considered. © 2016 Wroclaw University of Technology

Si1-xGex structures fabricated by focused ion beam implantation

In this work we present a study of the spreading resistance for Si1-xGex structures fabricated by F.I.B - L.M.I.S. technique. Maskless ion implantation using a Focused Ion Beam has the advantages of high resolution, the possibility to vary dose, energy and pattern design within a chip or within a structure

Medical and safety monitoring system over an in-cabin optical wireless network

An integrated health and safety monitoring system for aircraft environments using commercially available medical sensor modules and custom made safety sensors in conjunction with an appropriate database supervised through a human-machine interface is implemented. The application described aims at preventing critical health- or safety-related situations during the flight. The health monitoring part of the system is capable of collecting all relevant data, essential in analysing a passenger&apos;s health profile. These data, comprising of body temperature, blood pressure, pulse oximetry and electrocardiogram, are throughput and transmitted over a wireless optical intra-cabin link to a server. Furthermore, and in order to reduce the cabin crew workload, along with the health data from a specific passenger group, seat-embedded safety sensors provide information for all passengers&apos; flight safety parameters (such as table upright, seat-belt closed, etc.). The data gathered by the system in a central server can, in its entirety, be stored, processed or acted upon in real time. © 2011 Taylor &amp; Francis

Soluble TNF mediates the transition from pulmonary inflammation to fibrosis

Background. Fibrosis, the replacement of functional tissue with excessive fibrous tissue, can occur in all the main tissues and organ systems, resulting in various pathological disorders. Idiopathic Pulmonary Fibrosis is a prototype fibrotic disease involving abnormal wound healing in response to multiple sites of ongoing alveolar epithelial injury. Methodology/Principal Findings. To decipher the role of TNF and TNF-mediated inflammation in the development of fibrosis, we have utilized the bleomycin-induced animal model of Pulmonary Fibrosis and a series of genetically modified mice lacking components of TNF signaling. Transmembrane TNF expression is shown to be sufficient to elicit an inflammatory response, but inadequate for the transition to the fibrotic phase of the disease. Soluble TNF expression is shown to be crucial for lymphocyte recruitment, a prerequisite for TGF-b1 expression and the development of fibrotic lesions. Moreover, through a series of bone marrow transfers, the necessary TNF expression is shown to originate from the non-hematopoietic compartment further localized in apoptosing epithelial cells. Conclusions. These results suggest a primary detrimental role of soluble TNF in the pathologic cascade, separating it from the beneficial role of transmembrane TNF, and indicate the importance of assessing the efficacy of soluble TNF antagonists in the treatment of Idiopathic Pulmonary Fibrosis. © 2006 Oikonomou et al