Pattern of seismicity in the Lucanian Apennines and foredeep (Southern Italy) from recording by SAPTEX temporary array

The deployment of a temporary seismic network in Southern Italy during 2001-2004 (the SAPTEX array, Southern APennine Tomography EXperiment) allowed us to relocate the hypocenters of Southern Apennines earthquakes with low uncertainty among the location parameters. The best array distribution of the SAPTEX network for the analysis of seismicity in the Lucanian Apennines and foredeep was reached in the first two years of recording. The SAPTEX data were merged with those of the Italian National Seismic Network (RSNC) operated by the Istituto Nazionale di Geofisica e Vulcanologia (INGV). For the hypocenters computation of events in the upper Agri Valley we also included P- and S- waves arrivals from the local Eni-Agip network. The seismicity for the Lucanian Apennines and foredeep in the analyzed period has magnitudes ranging from 2.0 to 4.1. A major finding is the identification of two different crustal domains: the westernmost characterizing the chain, mostly with shallow earthquakes (within about 20 km of depth), and the easternmost one belonging to the outer margin of the chain and to the foredeep, with deeper seismicity (mostly between 20-40 km of depth). Thirty fault-plane solutions were computed and used for stress inversion; most of them are related to earthquakes within the chain sector and indicate a generalized NE-SW extension. Moreover, the dense network allowed us to improve the location of events relative to two low magnitude sequences which occurred in the study period

Low temperature exposure induces browning of bone marrow stem cell derived adipocytes in vitro

Brown and beige adipocytes are characterised as expressing the unique mitochondrial uncoupling protein (UCP)1 for which the primary stimulus in vivo is cold exposure. The extent to which cold-induced UCP1 activation can also be achieved in vitro, and therefore perform a comparable cellular function, is unknown. We report an in vitro model to induce adipocyte browning using bone marrow (BM) derived mesenchymal stem cells (MSC), which relies on differentiation at 32°C instead of 37°C. The low temperature promoted browning in adipogenic cultures, with increased adipocyte differentiation and upregulation of adipogenic and thermogenic factors, especially UCP1. Cells exhibited enhanced uncoupled respiration and metabolic adaptation. Cold-exposed differentiated cells showed a marked translocation of leptin to adipocyte nuclei, suggesting a previously unknown role for leptin in the browning process. These results indicate that BM-MSC can be driven to forming beige-like adipocytes in vitro by exposure to a reduced temperature. This in vitro model will provide a powerful tool to elucidate the precise role of leptin and related hormones in hitherto functions in the browning process

The NuGO proof of principle study package: a collaborative research effort of the European Nutrigenomics Organisation

Acknowledgments This project is funded by the Nutrigenomics Organisation, EC funded Network of Excellence, grant nr.FOOD- 2004-506360.Peer reviewedPublisher PD

UCP1 Induction during Recruitment of Brown Adipocytes in White Adipose Tissue Is Dependent on Cyclooxygenase Activity

Background The uncoupling protein 1 (UCP1) is a hallmark of brown adipocytes and pivotal for cold- and diet-induced thermogenesis. Methodology/Principal Findings Here we report that cyclooxygenase (COX) activity and prostaglandin E2 (PGE2) are crucially involved in induction of UCP1 expression in inguinal white adipocytes, but not in classic interscapular brown adipocytes. Cold-induced expression of UCP1 in inguinal white adipocytes was repressed in COX2 knockout (KO) mice and by administration of the COX inhibitor indomethacin in wild-type mice. Indomethacin repressed β-adrenergic induction of UCP1 expression in primary inguinal adipocytes. The use of PGE2 receptor antagonists implicated EP4 as a main PGE2 receptor, and injection of the stable PGE2 analog (EP3/4 agonist) 16,16 dm PGE2 induced UCP1 expression in inguinal white adipose tissue. Inhibition of COX activity attenuated diet-induced UCP1 expression and increased energy efficiency and adipose tissue mass in obesity-resistant mice kept at thermoneutrality. Conclusions/Significance Our findings provide evidence that induction of UCP1 expression in white adipose tissue, but not in classic interscapular brown adipose tissue is dependent on cyclooxygenase activity. Our results indicate that cyclooxygenase-dependent induction of UCP1 expression in white adipose tissues is important for diet-induced thermogenesis providing support for a surprising role of COX activity in the control of energy balance and obesity development

The obesity and inflammatory marker haptoglobin attracts monocytes via interaction with chemokine (C-C motif) receptor 2 (CCR2)

<p>Abstract</p> <p>Background</p> <p>Obesity is a chronic low inflammatory state. In the obesity condition the white adipose tissue (WAT) is massively infiltrated with monocytes/macrophages, and the nature of the signals recruiting these inflammatory cells has yet to be fully elucidated. Haptoglobin (Hp) is an inflammatory marker and its expression is induced in the WAT of obese subjects. In an effort to elucidate the biological significance of Hp presence in the WAT and of its upregulation in obesity we formulated the hypothesis that Hp may serve as a macrophage chemoattractant.</p> <p>Results</p> <p>We demonstrated by chemotaxis assay that Hp is able to attract chemokine (C-C motif) receptor 2 (CCR2)-transfected pre-B lymphocytes and monocytes in a dose-dependent manner. Moreover, Hp-mediated migration of monocytes is impaired by CCR2-specific inhibition or previous cell exposure to monocyte chemoattractant protein 1 (MCP1) (also known as CCR2 ligand or chemokine (C-C motif) ligand 2 (CCL2)). Downstream effects of Hp/CCR2 interaction were also investigated: flow cytometry proved that monocytes treated with Hp show reduced CCR2 expression on their surface; Hp interaction induces calcium release that is reduced upon pretreatment with CCR2 antagonist; extracellular signal-regulated kinase (ERK)1/2, a signal transducer activated by CCR2, is phosphorylated following Hp treatment and this phosphorylation is reduced when cells are pretreated with a specific CCR2 inhibitor. Consistently, blocking the ERK1/2 pathway with U0126, the selective inhibitor of the ERK upstream mitogen-activated protein (MAP)-ERK kinase (MEK), results in a dramatic reduction (by almost 100%) of the capability of Hp to induce monocyte migration.</p> <p>Conclusions</p> <p>Our data show that Hp is a novel monocyte chemoattractant and that its chemotactic potential is mediated, at least in part. by its interaction with CCR2.</p

Different Transcriptional Control of Metabolism and Extracellular Matrix in Visceral and Subcutaneous Fat of Obese and Rimonabant Treated Mice

BACKGROUND: The visceral (VAT) and subcutaneous (SCAT) adipose tissues play different roles in physiology and obesity. The molecular mechanisms underlying their expansion in obesity and following body weight reduction are poorly defined. METHODOLOGY: C57Bl/6 mice fed a high fat diet (HFD) for 6 months developed low, medium, or high body weight as compared to normal chow fed mice. Mice from each groups were then treated with the cannabinoid receptor 1 antagonist rimonabant or vehicle for 24 days to normalize their body weight. Transcriptomic data for visceral and subcutaneous adipose tissues from each group of mice were obtained and analyzed to identify: i) genes regulated by HFD irrespective of body weight, ii) genes whose expression correlated with body weight, iii) the biological processes activated in each tissue using gene set enrichment analysis (GSEA), iv) the transcriptional programs affected by rimonabant. PRINCIPAL FINDINGS: In VAT, "metabolic" genes encoding enzymes for lipid and steroid biosynthesis and glucose catabolism were down-regulated irrespective of body weight whereas "structure" genes controlling cell architecture and tissue remodeling had expression levels correlated with body weight. In SCAT, the identified "metabolic" and "structure" genes were mostly different from those identified in VAT and were regulated irrespective of body weight. GSEA indicated active adipogenesis in both tissues but a more prominent involvement of tissue stroma in VAT than in SCAT. Rimonabant treatment normalized most gene expression but further reduced oxidative phosphorylation gene expression in SCAT but not in VAT. CONCLUSION: VAT and SCAT show strikingly different gene expression programs in response to high fat diet and rimonabant treatment. Our results may lead to identification of therapeutic targets acting on specific fat depots to control obesity

Stochastic variation of transcript abundance in C57BL/6J mice

<p>Abstract</p> <p>Background</p> <p>Transcripts can exhibit significant variation in tissue samples from inbred laboratory mice. We have designed and carried out a microarray experiment to examine transcript variation across samples from adipose, heart, kidney, and liver tissues of C57BL/6J mice and to partition variation into within-mouse and between-mouse components. Within-mouse variance captures variation due to heterogeneity of gene expression within tissues, RNA-extraction, and array processing. Between-mouse variance reflects differences in transcript abundance between genetically identical mice.</p> <p>Results</p> <p>The nature and extent of transcript variation differs across tissues. Adipose has the largest total variance and the largest within-mouse variance. Liver has the smallest total variance, but it has the most between-mouse variance. Genes with high variability can be classified into groups with correlated patterns of expression that are enriched for specific biological functions. Variation between mice is associated with circadian rhythm, growth hormone signaling, immune response, androgen regulation, lipid metabolism, and the extracellular matrix. Genes showing correlated patterns of within-mouse variation are also associated with biological functions that largely reflect heterogeneity of cell types within tissues.</p> <p>Conclusions</p> <p>Genetically identical mice can experience different individual outcomes for medically important traits. Variation in gene expression observed between genetically identical mice can identify functional classes of genes that are likely to vary in the absence of experimental perturbations, can inform experimental design decisions, and provides a baseline for the interpretation of gene expression data in interventional studies. The extent of transcript variation among genetically identical mice underscores the importance of stochastic and micro-environmental factors and their phenotypic consequences.</p

A re-introduction of environmental mite allergen control strategies for asthma treatment and the debate on their effectiveness

Asthma affects three hundred million people worldwide. The effectiveness of house dust mite allergen control for asthma treatment is debatable. One aspect that has been little discussed in existing meta‐analyses is the possible role of environmental strategies. Here, we re‐introduce the previously defined strategies for mite allergen control and discuss their importance to the debate on clinical effectiveness. The strategy of concurrent bedroom interventions is related to the combined use of a priori defined interventions, while the strategy of exposure‐based control relates to the treatment of relevant textiles after assessing exposure. The air purification strategy aims to purify the human breathing zone of airborne allergens. In Western European patient practice, the use of these strategies differs. A post hoc study of the dominant Cochrane review by Gøtzsche and Johansen (Cochrane Database of Systematic Reviews, 2008, Art. No: CD001187) appears to indicate that a majority of the underlying trials reported on the strategy of concurrent bedroom interventions, which were mainly executed in a minimal manner. Some trials have reported on the air purification strategy and may potentially alter the debate on effectiveness. No trial has reported on the strategy of exposure‐based control. We therefore hypothesize that the absence of evidence for the effectiveness of mite allergen control for asthma treatment applies to the strategy of concurrent bedroom interventions. The evidence‐based effectiveness of the exposure‐based control strategy appears to be undetermined. The results of our post hoc re‐analysis urge that future meta‐analyses of mite allergen control should a priori define the environmental strategy under study. Future trials of mite allergen control are warranted to test the exposure‐based strategy as well as the sparsely tested strategy of air purification