The heart of a hibernator: EGFR and MAPK signaling in cardiac muscle during the hibernation of thirteen-lined ground squirrels, Ictidomys tridecemlineatus

Background: Thirteen-lined ground squirrels (Ictidomys tridecemlineatus) experience dramatic changes in physiological and molecular parameters during winter hibernation. Notably, these animals experience reduced blood circulation during torpor, which can put numerous stresses on their hearts. The present study evaluates the role played by the epidermal growth factor receptor (EGFR) in signal transduction during hibernation at low body temperature to evaluate signaling mechanisms. By investigating the regulation of intracellular mitogen activated protein kinase (MAPK) pathway responses, anti-apoptosis signals, downstream transcription factors, and heat shock proteins in cardiac muscle we aim to determine the correlation between upstream tyrosine phosphorylation events and downstream outcomes. Methods: Protein abundance of phosphorylated EGFR, MAPKs and downstream effector proteins were quantified using immunoblotting and Luminex_ multiplex assays. Results: Monitoring five time points over the torpor/arousal cycle, EGFR phosphorylation on T654, Y1068, Y1086 was found to increase signifi

ULTRA-LOCAL TEMPERATURE MAPPING WITH AN INTRINSIC THERMOCOUPLE

Submitted on behalf of EDA Publishing Association (http://irevues.inist.fr/handle/2042/5920)International audienceWe report on a set-up derived from an Electrostatic Force Microscope (EFM) allowing us to probe temperature with a high spatial resolution. The system uses the well-known Seebeck effect through an intrinsic thermocouple made from an EFM conducting tip put in contact with a conducting sample. The contact radius between tip and sample is currently estimated to be in the 50 to 100 nm range depending on the elastic or the plastic deformation. The contact area can be assimilated to the electrical and thermal contact areas. In those conditions, the issue of heat conduction in air is solved. The thermal measurement is related to the Seebeck junction effect : it will therefore not be sensitive to buried materials or impurities

Un colloque sur la pluridisciplinariaté dans les problèmes d'environnement : quelques enseignements et orientations pour l'avenir

International audienceAn experiment has been carried out in Rennes (Brittany, West of France) in June 2000 to estimate atrazine and alachlor volatilisation fluxes after application over a maize crop. Fluxes were calculated using the classical aerodynamic micrometeorological method from vertical gradients of pesticide concentrations, temperature and wind speed. Volatilisation fluxes showed a diurnal pattern of the order of few ng/m2/s for atrazine and the order of a few 10 ng/m2/s for alachlor, leading to cumulated losses of approximately 0.1% of the theoretical application dose for atrazine and several-fold of that in the case of alachlor

Entanglement of Dirac fields in non-inertial frames

We analyze the entanglement between two modes of a free Dirac field as seen by two relatively accelerated parties. The entanglement is degraded by the Unruh effect and asymptotically reaches a non-vanishing minimum value in the infinite acceleration limit. This means that the state always remains entangled to a degree and can be used in quantum information tasks, such as teleportation, between parties in relative uniform acceleration. We analyze our results from the point of view afforded by the phenomenon of entanglement sharing and in terms of recent results in the area of multi-qubit complementarity.Comment: 15 pages, with 8 figures (Mar 2006); accepted to Physical Review A, July 2006 - slightly revise

Temperature Measurement of Microsystems by Scanning Thermal Microscopy

Submitted on behalf of EDA Publishing Association (http://irevues.inist.fr/handle/2042/5920)International audienceSurface temperature measurements were performed with a Scanning Thermal Microscope. We aim at proving an eventual sub-micrometric resolution of this metrology when using a wollaston wire probe of micrometric size. A dedicated CMOS device was designed with arrays of lines 0.35mm in size with 0.8 mm and 10mm periods. Integrated Circuits with or without a passivition layer were tested. To enhance sensitivity, the IC heat source was excited with an AC current. We show that the passivation layer spreads heat so that the lines are not distinguishable. Removing this layer allows us to distinguish the lines in the case of the 10mm period

Modulation of Gene Expression in Key Survival Pathways During Daily Torpor in the Gray Mouse Lemur, Microcebus murinus

AbstractA variety of mammals employ torpor as an energy-saving strategy in environments of marginal or severe stress either on a daily basis during their inactive period or on a seasonal basis during prolonged multi-day hibernation. Recently, a few Madagascar lemur species have been identified as the only primates that exhibit torpor; one of these is the gray mouse lemur (Microcebus murinus). To explore the regulatory mechanisms that underlie daily torpor in a primate, we analyzed the expression of 28 selected genes that represent crucial survival pathways known to be involved in squirrel and bat hibernation. Array-based real-time PCR was used to compare gene expression in control (aroused) versus torpid lemurs in five tissues including the liver, kidney, skeletal muscle, heart, and brown adipose tissue. Significant differences in gene expression during torpor were revealed among genes involved in glycolysis, fatty acid metabolism, antioxidant defense, apoptosis, hypoxia signaling, and protein protection. The results showed upregulation of select genes primarily in liver and brown adipose tissue. For instance, both tissues showed elevated gene expression of peroxisome proliferator activated receptor gamma (ppargc), ferritin (fth1), and protein chaperones during torpor. Overall, the data show that the expression of only a few genes changed during lemur daily torpor, as compared with the broader expression changes reported for hibernation in ground squirrels. These results provide an indication that the alterations in gene expression required for torpor in lemurs are not as extensive as those needed for winter hibernation in squirrel models. However, identification of crucial genes with altered expression that support lemur torpor provides key targets to be explored and manipulated toward a goal of translational applications of inducible torpor as a treatment option in human biomedicine

A Genetic Algorithm for Scale-Based Translocon Simulation

Discriminating between secreted and membrane proteins is a challenging task. A recent and important discovery to understand the machinery responsible of the insertion of membrane proteins was the results of Hessa experiments [9]. The authors developed a model system for measuring the ability of insertion of engineered hydrophobic amino acid segments in the membrane. The main results of these experiments are summarized in a new ”biological hydrophobicity scale”. In this scale, each amino acid is represented by a curve that indicates its contribution to the process of protein insertion according to its position inside the membrane. We follow the same hypothesis as Hessa but we propose to determine “in silico” the hydrophobicity scale. This goal is formalized as an optimization problem, where we try to define a set of curves that gives the best discrimination between signal peptide and protein segments which cross the membrane. This paper describes the genetic algorithm that we developed to solve this problem and the experiments that we conducted to assess its performance

The use of leukocytes’ secretome to individually target biological therapy in autoimmune arthritis : a case report

Background: Biological agents have allowed remarkable improvement in controlling autoimmune arthropathies, although none of the numerous biologics readily available represent a universal treatment standard. Moreover, classi‑ cal and genetic predictors are currently unsatisfactory to predict individual response to a biologic, and the best treat‑ ment selection is still based on a trial-and-error approach. Here, we report a clinical case demonstrating the usefulness of examining the leukocytes’ secretome of patients. We set up and standardized a protocol that examines a patient’s immune responses to establish the secretome of the blood mononuclear leukocytes and personalize the biotherapy. Case presentation: A 24-year-old woman was diagnosed with active early rheumatoid arthritis. The initial treat‑ ment regimen (prednisone, methotrexate, hydroxychloroquine, naproxen) was inefcient, as well as the anti-TNF adalimumab. The diagnosis was revised as possible rheumatoid arthritis-like psoriatic arthritis and adalimumab was replaced by abatacept (IgG1 Fc-CTLA-4) to no avail. Five years later, abatacept was replaced by the anti-IL-12/ IL-23 ustekinumab with no objective control over the symptoms. The patient was thus enrolled in a prospective study based on the quantifcation of cytokines secreted by peripheral blood leukocytes stimulated with well-known immune activators of pattern recognition receptors and cytokine signalling. The results of this study revealed that plasma concentrations of cytokines were similar between the patient and healthy donors. In comparison to leuko‑ cytes from healthy donors, the patient’s secretome showed a unique overproduction of IL-6. The anti-IL-6 receptor tocilizumab was, therefore, administered with a rapid improvement of her active psoriatic arthritis that remained dependent on low prednisone dosage. Clinical parameters progressively returned to normal levels and her quality of life was greatly improved, despite the major delay to begin the present personalized treatment. Conclusions: An efcient way to efectively treat patients with complex autoimmune arthropathies, and avoid irreversible disability, is to know their leukocytes’ secretome to identify abnormally secreted cytokines and personalize their biotherapy, as exemplifed by this case report

Proteomic identification of in vivo substrates for matrix metalloproteinases 2 and 9 reveals a mechanism for resolution of inflammation.

Clearance of allergic inflammatory cells from the lung through matrix metalloproteinases (MMPs) is necessary to prevent lethal asphyxiation, but mechanistic insight into this essential homeostatic process is lacking. In this study, we have used a proteomics approach to determine how MMPs promote egression of lung inflammatory cells through the airway. MMP2- and MMP9-dependent cleavage of individual Th2 chemokines modulated their chemotactic activity; however, the net effect of complementing bronchoalveolar lavage fluid of allergen-challenged MMP2(-/-)/MMP9(-/-) mice with active MMP2 and MMP9 was to markedly enhance its overall chemotactic activity. In the bronchoalveolar fluid of MMP2(-/-)/MMP9(-/-) allergic mice, we identified several chemotactic molecules that possessed putative MMP2 and MMP9 cleavage sites and were present as higher molecular mass species. In vitro cleavage assays and mass spectroscopy confirmed that three of the identified proteins, Ym1, S100A8, and S100A9, were substrates of MMP2, MMP9, or both. Function-blocking Abs to S100 proteins significantly altered allergic inflammatory cell migration into the alveolar space. Thus, an important effect of MMPs is to differentially modify chemotactic bioactivity through proteolytic processing of proteins present in the airway. These findings provide a molecular mechanism to explain the enhanced clearance of lung inflammatory cells through the airway and reveal a novel approach to target new therapies for asthma

Nonverbal expression of empathy in healthy human populations : a scoping review protocol

The present scoping review aims to understand the extent and type of evidence related to the nonverbal expression of empathy (and empathic concern) in healthy human (or human-like) empathizers across contexts