Crosstalk reduction in a piezoelectric phononic plate induced by electrical boundary conditions: Application to multi-element transducers.

This paper proposes a method of passive electrical decoupling which aimed at found application in reducing the crosstalk phenomenon in multi-element ultrasonic transducers. A homogeneous piezoelectric plate, covered on one side by a 1D periodic arrangement of thin metallic electrodes and on the other side by a full electrode, is considered. Finite element analysis and experimental measurements are performed to obtain the dispersion curves and normal displacements at the surface of the structure. It is shown that applying inductive shunts at the electrodes, band gaps can be created in the first Brillouin zone, which can prevent from the establishment of the first thickness mode in the plate. In that way the mechanical inter-element coupling can be lowered. Thus, the acoustic radiation in water from one sector excited at the resonance frequency is found to be closer to that of a piston mode. The transposition of this principle to the situation of a transducer including a rear medium and a front matching layer confirms the possibility of reducing the inter-element coupling. However, the physical effects at the origin of this reduction are different from those inherent to the cutting of a piezocomposite ceramic as it is done in most probes available in the market. As a result, we show that taking advantage of the electrical boundary conditions upon the passive elements in a transducer gives real opportunities for crosstalk reduction that may be implemented in ultrasonic systems for imaging in the medical field and in NDT.

Symmetric Reflector Ultrasonic Transducer Modeling and Characterization: Role of the Matching Layer on Electroacoustic Performance.

Symmetric reflector ultrasonic transducers (SRUTs) are a new type of ultrasonic transducer that take advantage of the ultrasonic wave emitted on the rear face of the active element. In this work, the electroacoustic modeling and characterization of such a structure is reported. Using the well-known Krimholtz, Leedom, et Matthaei (KLM) model, the electroacoustic response of a SRUT based on a piezoelectric ceramic with one matching layer is calculated. Simulations show that the optimal acoustic impedance of the matching layer should be lower than for conventional transducers, leading to a relative bandwidth of approximately 50%. The characterization of such a transducer based on a piezoceramic plate has been carried out. Bandwidth and sensitivity are reported. They are found to be close to the simulation results and demonstrate that these new types of transducers need to be designed according to new rules compared to conventional ones.

Antimicrobial Resistance Pilot Surveillance of Pigs and Chickens in Vietnam, 2017-2019.

Antimicrobial use (AMU) and antimicrobial resistance (AMR) are a growing public health and economic threat in Vietnam. We conducted a pilot surveillance programme in five provinces of Vietnam, two in the south and three in the north, to identify antimicrobial resistance (AMR) in rectal swab samples from pigs and fecal samples from chickens at slaughter points during three different points in time from 2017 to 2019. Escherichia coli (E. coli) and non-typhoidal Salmonella (NTS) isolates were tested for antimicrobial susceptibility using disk diffusion assay for 19 antimicrobial agents belonging to nine antimicrobial classes and Etest for colistin (polymyxin). Almost all E. coli (99%; 1029/1042) and NTS (96%; 208/216) isolates were resistant to at least one antimicrobial agent; 94% (981/1042) of E. coli and 89% (193/216) of NTS isolates were multidrug-resistant (MDR). Higher proportions of E. coli and NTS isolated from chickens were resistant to all antimicrobial classes than those isolates from pigs. There was a significantly higher proportion of MDR NTS isolates from the southern provinces of Ho Chi Minh City and Long An (p = 0.008). Although there were increasing trends of NTS in proportion of resistance to fluoroquinolone over the three surveillance rounds, there was a significant decreasing trend of NTS in proportion of resistance to polymyxin (p = 0.002). It is important to establish an annual AMR surveillance program for livestock in Vietnam to assess the impact of interventions, observe trends and drive decision making that ultimately contributes to reducing AMR public health threat.

Free carrier enhanced depletion in ZnO nanorods decorated with bimetallic AuPt nanoclusters.

The decoration of semiconductor nanostructures with small metallic clusters usually leads to an improvement of their properties in sensing or catalysis. Bimetallic cluster decoration typically is claimed to be even more effective. Here, we report a detailed investigation of the effects of Au, Pt or AuPt nanocluster decoration of ZnO nanorods on charge transport, photoluminescence and UV sensitivity. ZnO nanorods were synthesized by chemical bath deposition while decoration with small nanoclusters (2-3 nm in size) was achieved by a laser-ablation based cluster beam deposition technology. The structural properties were investigated by scanning electron microscopy, high resolution transmission electron microscopy, X-ray photoelectron spectroscopy and Rutherford backscattering spectrometry, and the optoelectronic properties by current-voltage and photoluminescence measurements. The extent of band bending at the cluster-ZnO interface was quantitatively modeled through numerical simulations. The decoration of ZnO nanorods with monometallic Au or Pt nanoclusters causes a significant depletion of free electrons below the surface, leading to a reduction of UV photoluminescence, an increase of ZnO nanorod dark resistance (up to 200 times) and, as a consequence, an improved sensitivity (up to 6 times) to UV light. These effects are strongly enhanced (up to 450 and 10 times, respectively) when ZnO nanorods are decorated with bimetallic AuPt nanoclusters that substantially augment the depletion of free carriers likely due to a more efficient absorption of the gas molecules on the surface of the bimetallic AuPt nanoclusters than on that of their monometallic counterparts. The depletion of free carriers in cluster decorated ZnO nanorods is quantitatively investigated and modelled, allowing the application of these composite materials in UV sensing and light induced catalysis.

Structural transition and magnetic properties of Mn doped Bi0.88Sm0.12FeO3 ceramics.

We investigated the effects of Mn doping on the crystal structure, phonon vibration, and magnetic properties of Bi0.88Sm0.12FeO3 ceramics. Mn doping effectively modified the rhombohedral symmetry and induced a structural transition from an R3c rhombohedral to Pnam orthorhombic structure. Magnetic measurements revealed a weak ferromagnetic behavior, which was related to the canted antiferromagnetic order of the Pnam structure. The cycloidal spin structure of the R3c phase could not be suppressed by substitution of Mn at the Fe site. Studies on the self-phase transition and electric field-induced structural transition revealed many changes in coercivity and remanent magnetization, which are believed to originate from the R3c/Pnam phase switching along with spin frustration. Observations of the field step-dependent hysteresis loop and the ferromagnetic-like hysteresis loop after poling in an electric field provided direct evidence of phase boundary (PB) ferromagnetism and magnetic coupling at the PB.

Exact formula for the horizontal-to-vertical displacement ratio of Rayleigh waves in layered orthotropic half-spaces.

This paper is concerned with the propagation of Rayleigh waves in a compressible orthotropic half-space coated by a compressible orthotropic layer. The main purpose of the paper is to establish an explicit exact formula for the H/V ratio (the horizontal-to-vertical displacement ratio) of the Rayleigh wave. This formula is derived by using the transfer matrix for an orthotropic elastic layer and by the effective boundary condition technique. The formula recovers the H/V formula by Malischewsky and Scherbaum [(2004). Wave Motion 40, 57-67] for the compressible isotropic case and the H/V formula by Love [(1911). Some Problems of Geodynamics (Cambridge University Press, Cambridge)] for the incompressible isotropic case. The effect of anisotropy on the H/V ratio's properties is examined and it is numerically shown that the anisotropy strongly affects the peak and zero frequency of the H/V ratio and its prograde domain as well. As the H/V ratio is a dimensionless quantity and it is easily experimentally measured, the obtained formula will be a useful tool for the nondestructive evaluation of mechanical properties of thin films deposited onto half-spaces. Two numerical examples are performed to show how the obtained formula can be used to extract the material properties of deposited layers from measured values of the H/V ratio.

Direct and indirect activation of eukaryotic elongation factor 2 kinase by AMP-activated protein kinase.

BACKGROUND: Eukaryotic elongation factor 2 (eEF2) kinase (eEF2K) is a key regulator of protein synthesis in mammalian cells. It phosphorylates and inhibits eEF2, the translation factor necessary for peptide translocation during the elongation phase of protein synthesis. When cellular energy demand outweighs energy supply, AMP-activated protein kinase (AMPK) and eEF2K become activated, leading to eEF2 phosphorylation, which reduces the rate of protein synthesis, a process that consumes a large proportion of cellular energy under optimal conditions. AIM: The goal of the present study was to elucidate the mechanisms by which AMPK activation leads to increased eEF2 phosphorylation to decrease protein synthesis. METHODS: Using genetically modified mouse embryo fibroblasts (MEFs), effects of treatments with commonly used AMPK activators to increase eEF2 phosphorylation were compared with that of the novel compound 991. Bacterially expressed recombinant eEF2K was phosphorylated in vitro by recombinant activated AMPK for phosphorylation site-identification by mass spectrometry followed by site-directed mutagenesis of the identified sites to alanine residues to study effects on the kinetic properties of eEF2K. Wild-type eEF2K and a Ser491/Ser492 mutant were retrovirally re-introduced in eEF2K-deficient MEFs and effects of 991 treatment on eEF2 phosphorylation and protein synthesis rates were studied in these cells. RESULTS & CONCLUSIONS: AMPK activation leads to increased eEF2 phosphorylation in MEFs mainly by direct activation of eEF2K and partly by inhibition of mammalian target of rapamycin complex 1 (mTORC1) signaling. Treatment of MEFs with AMPK activators can also lead to eEF2K activation independently of AMPK probably via a rise in intracellular Ca2+. AMPK activates eEF2K by multi-site phosphorylation and the newly identified Ser491/Ser492 is important for activation, leading to mTOR-independent inhibition of protein synthesis. Our study provides new insights into the control of eEF2K by AMPK, with implications for linking metabolic stress to decreased protein synthesis to conserve energy reserves, a pathway that is of major importance in cancer cell survival.

Thromboembolic Disease in Patients with Metastatic Femoral Lesions: A Comparison Between Prophylactic Fixation and Fracture Fixation.

BACKGROUND: We are not aware of any previous studies that have compared the rate of venous thromboembolic events in patients who underwent prophylactic intramedullary nailing because of an impending fracture with the rate in patients who underwent intramedullary nailing after a pathological fracture. The objective of the present study was to determine if the rate of venous thromboembolic events varies between patients who are managed with prophylactic fixation and those who are managed with fixation after a pathological fracture. METHODS: We performed a retrospective comparative study in which the Nationwide Inpatient Sample database was used to identify all patients who had undergone femoral stabilization, either for a pathological femoral fracture or for prophylactic fixation of femoral metastatic lesion, over a period of 10 consecutive years (between 2002 and 2011) in the United States. Demographic data, comorbidities, venous thromboembolic event rates, and other common postoperative complications were compared between the 2 groups. RESULTS: Patients who were managed with prophylactic fixation had significantly higher rates of pulmonary embolism (p < 0.001; adjusted odds ratio, 2.1) and deep-vein thrombosis (p = 0.03; adjusted odds ratio, 1.5). Patients who were managed with fixation after a pathological fracture had a significantly greater need for blood transfusion, higher rates of postoperative urinary tract infection, and a decreased likelihood of being discharged to home (p < 0.001 for all). CONCLUSIONS: Patients with metastatic disease who undergo prophylactic intramedullary nailing have higher observed rates of venous thromboembolic events than those who undergo nailing for the treatment of a pathological fracture and should be actively and vigilantly managed in the postoperative period. LEVEL OF EVIDENCE: Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.

AMPK antagonizes hepatic glucagon-stimulated cyclic AMP signalling via phosphorylation-induced activation of cyclic nucleotide phosphodiesterase 4B.

Biguanides such as metformin have previously been shown to antagonize hepatic glucagon-stimulated cyclic AMP (cAMP) signalling independently of AMP-activated protein kinase (AMPK) via direct inhibition of adenylate cyclase by AMP. Here we show that incubation of hepatocytes with the small-molecule AMPK activator 991 decreases glucagon-stimulated cAMP accumulation, cAMP-dependent protein kinase (PKA) activity and downstream PKA target phosphorylation. Moreover, incubation of hepatocytes with 991 increases the Vmax of cyclic nucleotide phosphodiesterase 4B (PDE4B) without affecting intracellular adenine nucleotide concentrations. The effects of 991 to decrease glucagon-stimulated cAMP concentrations and activate PDE4B are lost in hepatocytes deleted for both catalytic subunits of AMPK. PDE4B is phosphorylated by AMPK at three sites, and by site-directed mutagenesis, Ser304 phosphorylation is important for activation. In conclusion, we provide a new mechanism by which AMPK antagonizes hepatic glucagon signalling via phosphorylation-induced PDE4B activation.

Real-time mobile teledermoscopy for skin cancer screening targeting an agricultural population: an experiment on 289 patients in France.

BACKGROUND: The incidence of skin cancer has reached epidemic proportions in the white population and is significantly elevated in agricultural populations, who are exposed to ultraviolet radiation during their professional activities. In 2014, the Agricultural Social Insurance Mutual Benefit Fund (MSA) offered its customers who work in agriculture and live in rural areas with reduced access to dermatologists the ability to participate in a 1-day teledermoscopic (TDS) screening event. OBJECTIVE: This study's aim was to assess the feasibility of real-time mobile TDS triage of a large number of agricultural workers by trained medical officers and occupational physicians. METHODS: Fifteen TDS screening centres were located in different areas of France. Individuals older than 18 years who worked in agriculture and lived in rural area near a TDS screening centre were invited to participate in a 1-day screening event and were examined by an MSA physician. In cases of suspicious skin lesions, clinical and dermoscopic images were obtained and transferred immediately to four dermatologists who were simultaneously present at the tele-platform for diagnosis and decision-making. Low-quality images were retaken. RESULTS: Two-hundred eighty-nine patients underwent skin cancer screening. Among 199 patients (69%), 390 suspicious lesions were identified and generated 412 pictures. All lesions were analysed by dermatologists. For 105 patients (53%), no follow-up was required. Seventeen patients were referred to local dermatologists for rapid examination, including 12 cases of suspected malignant melanocytic lesions. Among the 12 patients with suspected melanoma, face-to-face visits were conducted within 10 days for 11 of them, and 1 case of melanoma was confirmed by histopathology. CONCLUSIONS: Our study suggests that teledermoscopy performed in the context of occupational medicine and targeted to agricultural populations is feasible and could be useful for improving skin cancer screening in at-risk populations while avoiding face-to-face examinations by a dermatologist in 53% of cases.

A comparison of 1D analytical model and 3D finite element analysis with experiments for a rosen-type piezoelectric transformer.

This article is dedicated to the study of Piezoelectric Transformers (PTs), which offer promising solutions to the increasing need for integrated power electronics modules within autonomous systems. The advantages offered by such transformers include: immunity to electromagnetic disturbances; ease of miniaturisation for example, using conventional micro fabrication processes; and enhanced performance in terms of voltage gain and power efficiency. Central to the adequate description of such transformers is the need for complex analytical modeling tools, especially if one is attempting to include combined contributions due to (i) mechanical phenomena owing to the different propagation modes which differ at the primary and secondary sides of the PT; and (ii) electrical phenomena such as the voltage gain and power efficiency, which depend on the electrical load. The present work demonstrates an original one-dimensional (1D) analytical model, dedicated to a Rosen-type PT and simulation results are successively compared against that of a three-dimensional (3D) Finite Element Analysis (COMSOL Multiphysics software) and experimental results. The Rosen-type PT studied here is based on a single layer soft PZT (P191) with corresponding dimensions 18 mm × 3 mm × 1.5 mm, which operated at the second harmonic of 176 kHz. Detailed simulational and experimental results show that the presented 1D model predicts experimental measurements to within less than 10% error of the voltage gain at the second and third resonance frequency modes. Adjustment of the analytical model parameters is found to decrease errors relative to experimental voltage gain to within 1%, whilst a 2.5% error on the output admittance magnitude at the second resonance mode were obtained. Relying on the unique assumption of one-dimensionality, the present analytical model appears as a useful tool for Rosen-type PT design and behavior understanding.

Bone Morphogenetic Protein (BMP) signaling in development and human diseases.

Bone Morphogenetic Proteins (BMPs) are a group of signaling molecules that belongs to the Transforming Growth Factor-ß (TGF-ß) superfamily of proteins. Initially discovered for their ability to induce bone formation, BMPs are now known to play crucial roles in all organ systems. BMPs are important in embryogenesis and development, and also in maintenance of adult tissue homeostasis. Mouse knockout models of various components of the BMP signaling pathway result in embryonic lethality or marked defects, highlighting the essential functions of BMPs. In this review, we first outline the basic aspects of BMP signaling and then focus on genetically manipulated mouse knockout models that have helped elucidate the role of BMPs in development. A significant portion of this review is devoted to the prominent human pathologies associated with dysregulated BMP signaling.

Metformin activates AMP-activated protein kinase in primary human hepatocytes by decreasing cellular energy status.

AIM/HYPOTHESIS: The glucose-lowering drug metformin has been shown to activate hepatic AMP-activated protein kinase (AMPK), a master kinase regulating cellular energy homeostasis. However, the underlying mechanisms remain controversial and have never been investigated in primary human hepatocytes. METHODS: Hepatocytes isolated from rat, mouse and human livers were treated with various concentrations of metformin. Isoform-specific AMPKα abundance and activity, as well as intracellular adenine nucleotide levels and mitochondrial oxygen consumption rates were determined at different time points. RESULTS: Metformin dose- and time-dependently increased AMPK activity in rat and human hepatocytes, an effect associated with a significant rise in cellular AMP:ATP ratio. Surprisingly, we found that AMPKα2 activity was undetectable in human compared with rat hepatocytes, while AMPKα1 activities were comparable. Accordingly, metformin only increased AMPKα1 activity in human hepatocytes, although both AMPKα isoforms were activated in rat hepatocytes. Analysis of mRNA expression and protein levels confirmed that only AMPKα1 is present in human hepatocytes; it also showed that the distribution of ß and γ regulatory subunits differed between species. Finally, we demonstrated that the increase in AMP:ATP ratio in hepatocytes from liver-specific Ampkα1/2 (also known as Prkaa1/2) knockout mice and humans is due to a similar and specific inhibition of the mitochondrial respiratory-chain complex 1 by metformin. CONCLUSIONS/INTERPRETATION: Activation of hepatic AMPK by metformin results from a decrease in cellular energy status owing to metformin's AMPK-independent inhibition of the mitochondrial respiratory-chain complex 1. The unique profile of AMPK subunits found in human hepatocytes should be considered when developing new pharmacological agents to target the kinase.

Exact second order formalism for the study of electro-acoustic properties in piezoelectric structures under an initial mechanical stress.

In this study we develop the exact second order formalism of piezoelectric structures under an external mechanical stress. Indeed, previous models are approximated since they consist in deriving all the equations in the natural coordinate system (corresponding to the pre-stress free case). Hence, our exact formalism proposes to obtain the whole of equations in the current coordinate system (which is the coordinate system after the pre-deformation). Then, this exact formalism is used to derive the modified Christoffel equations and the modified KLM model. Finally, we quantify the correction with the approximate formalism on several transfer functions and electro-mechanical parameters for a non hysteretic material (lithium niobate). In conclusion, we show that for this material, significant corrections are obtained when studying the plane wave velocities and the electrical input impedance (about 4%), whereas other parameters such as coupling coefficient and impulse response are less influenced by the choice of coordinate systems (corrections less than 0.5%).

Modelling nonlinearity in piezoceramic transducers: From equations to nonlinear equivalent circuits.

Quadratic nonlinear equations of a piezoelectric element under the assumptions of 1D vibration and weak nonlinearity are derived by the perturbation theory. It is shown that the nonlinear response can be represented by controlled sources that are added to the classical hexapole used to model piezoelectric ultrasonic transducers. As a consequence, equivalent electrical circuits can be used to predict the nonlinear response of a transducer taking into account the acoustic loads on the rear and front faces. A generalisation of nonlinear equivalent electrical circuits to cases including passive layers and propagation media is then proposed. Experimental results, in terms of second harmonic generation, on a coupled resonator are compared to theoretical calculations from the proposed model.

Modeling and numerical study of the electroacoustic behavior in integrated piezoelectric structures under external mechanical stress.

The purpose of this study is to model and understand the role of an applied mechanical stress in piezoelectric materials as far as electroacoustic parameters are concerned.In the field of thick or thin film technology, understanding and predicting the behavior of integrated structures when submitted to external or internal mechanical stress is of primary importance. Thus, we propose a modified KLM electroacoustic model of transducer that enables to take into account the effect of a mechanical pre-stress. Then, a numerical study of the electroacoustic parameters for lithium niobate piezoelectric material(coupling coefficient, velocities, associated polarizations,and electrical input impedance) is conducted with regard to the azimuthal and elevation angles, as well as initial pre-stress values. Finally, we study the pulse-echo response of a complete piezoelectric transducer consisting of a piezoelectric film laid down upon a backing material and matching layers, with and without an initial stress, to highlight some benefits of a prestress load.

Comparative Fe and Zn K-edge X-ray absorption spectroscopic study of the ferroxidase centres of human H-chain ferritin and bacterioferritin from Desulfovibrio desulfuricans.

Iron uptake by the ubiquitous iron-storage protein ferritin involves the oxidation of two Fe(II) ions located at the highly conserved dinuclear "ferroxidase centre" in individual subunits. We have measured X-ray absorption spectra of four mutants (K86Q, K86Q/E27D, K86Q/E107D, and K86Q/E27D/E107D, involving variations of Glu to Asp on either or both sides of the dinuclear ferroxidase site) of recombinant human H-chain ferritin (rHuHF) in their complexes with reactive Fe(II) and redox-inactive Zn(II). The results for Fe-rHuHf are compared with those for recombinant Desulfovibrio desulfuricans bacterioferritin (DdBfr) in three states: oxidised, reduced, and oxidised/Chelex-treated. The X-ray absorption near-edge region of the spectrum allows the oxidation state of the iron ions to be assessed. Extended X-ray absorption fine structure simulations have yielded accurate geometric information that represents an important refinement of the crystal structure of DdBfr; most metal-ligand bonds are shortened and there is a decrease in ionic radius going from the Fe(II) to the Fe(III) state. The Chelex-treated sample is found to be partly mineralised, giving an indication of the state of iron in the cycled-oxidised (reduced, then oxidised) form of DdBfr, where the crystal structure shows the dinuclear site to be only half occupied. In the case of rHuHF the complexes with Zn(II) reveal a surprising similarity between the variants, indicating that the rHuHf dinuclear site is rigid. In spite of this, the rHuHf complexes with Fe(II) show a variation in reactivity that is reflected in the iron oxidation states and coordination geometries.

Modeling of a high frequency ultrasonic transducer using periodic structures.

Solidly mounted integrated transducers with a Bragg cell inserted between the piezoelectric film and the substrate are investigated for high frequency ultrasonic applications. A numerically stable recursive one dimensional transmission/reflection model was used to analyze the behavior of the periodic structure. This theoretical analysis includes the study of the influence of the acoustic properties of the constitutive layer, the effect of the number of cells and their arrangement. A 35 MHz integrated transducer consisting in a PZT ceramic laid down on a Au/PZT Bragg cell deposited on a porous substrate was fabricated and characterized. Both theoretical and experimental results highlight the interest of using a periodic structure for high frequency ultrasonic applications.

Lack of starvation-induced activation of AMP-activated protein kinase in the hypothalamus of the Lou/C rats resistant to obesity.

OBJECTIVE: The AMP-activated protein kinase (AMPK) is involved in the control of food intake by the hypothalamus. The aim of this work was to investigate if modification of hypothalamic AMPK regulation could be related to the spontaneous food restriction of Lou/C rats, a strain resistant to obesity exhibiting a 40% reduction in caloric intake compared with their lean Wistar counterparts. DESIGN: Three-month-old male Lou/C rats were compared with age-matched male Wistar rats in both fed ad libitum and 24-h food deprivation state. MEASUREMENTS AND RESULTS: We first confirmed that starvation activated both isoforms of AMPK catalytic alpha subunits and enhanced the phosphorylation state of its downstream targets acetyl-CoA carboxylase and elongation factor 2 in the hypothalamus of Wistar rats. These changes were not observed in the hypothalamus of Lou/C rats. Interestingly, the starvation-induced changes in hypothalamic mRNA levels of the main orexigenic and anorexigenic neuropeptides were also blunted in the Lou/C rats. Analysis of the concentrations of circulating substrates and hormones known to regulate hypothalamic AMPK indicated that the starvation-induced changes in ghrelin, adiponectin and leptin were not observed in Lou/C rats. Furthermore, an increased phosphorylation state of signal transducer and activator of transcription 3 (STAT3), which admittedly mediates leptin signaling, was evidenced in the hypothalamus of the starved Lou/C rats, as well as modifications of expression of the leptin-sensitive genes suppressor of cytokine signaling-3 and stearoyl-coenzyme A desaturase 1. In addition, despite reduced leptin level in fed Lou/C rats, the phosphorylation state of hypothalamic STAT3 remained similar to that found in fed Wistar rats, an adaptation that could be explained by the concomitant increase in ObRb leptin receptor mRNA expression. CONCLUSION: Activation of hypothalamic AMPK by starvation, which stimulates food intake through changes in (an)orexigenic neuropeptides in the normal rats, was not observed in the spontaneously hypophagic Lou/C rats.

Antagonistic effects of leucine and glutamine on the mTOR pathway in myogenic C2C12 cells.

This study compared the effects of leucine and glutamine on the mTOR pathway, on protein synthesis and on muscle-specific gene expression in myogenic C(2)C(12) cells. Leucine increased the phosphorylation state of mTOR, on both Ser2448 and Ser2481, and its downstream effectors, p70(S6k), S6 and 4E-BP1. By contrast, glutamine decreased the phosphorylation state of mTOR on Ser2448, p70(S6k) and 4E-BP1, but did not modify the phosphorylation state of mTOR on Ser2481 and S6. Whilst the phosphorylation state of the mTOR pathway is usually related to protein synthesis, the incorporation of labelled methionine/cysteine was only transiently modified by leucine and was unaltered by glutamine. However, these two amino acids affected the mRNA levels of desmin, myogenin and myosin heavy chain in a time-dependant manner. In conclusion, leucine and glutamine have opposite effects on the mTOR pathway. Moreover, they induce modification of muscle-specific gene expression, unrelated to their effects on the mTOR/p70(S6k) pathway.