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Deep Brain Stimulation of the Subthalamic Nucleus (STN-DBS) is an effective treatment for Parkinson's disease (PD), but only few studies investigated its long-term efficacy. Furthermore, little is known about the role of PD-subtype on STN-DBS long-term outcome.

It is known that food intake is regulated by interactions between neuronal and hormonal signals arising throughout the body and specific areas of the brain, mainly in the hypothalamus. Among the peripheral mediators, ghrelin could have a primary role in the regulation of feeding. Ghrelin is an endogenous 28 amino acid peptide produced and secreted mainly by the stomach, and it is characterized by endocrine and extra-endocrine effects including the ability to stimulate GH secretion and feeding behaviour. In the last several years new synthetic peptidic and non peptidic compounds, named growth hormone secretagogues, have been shown to share with ghrelin many activities. The purpose of this study was the characterization of new peptide-mimetic analogues of ghrelin, synthesized at the Institut des Biomolecules Max Mousseron, University of Montpellier, that might be considered for developing novel therapeutic agents useful in the treatment of cachexia or, at the opposite, of diet-induced obesity. Cachexia is a condition characterized by loss of lean and fat body mass, anorexia, asthenia and increased energy expenditure. On the other hand obesity results in a chronic imbalance between energy intake and energy expenditure. We set up a chinese hamster ovary (CHO) cell line stably expressing the human GHS-R1a. The activity of the novel compounds was studied using an intracellular mobilization calcium assay. Cells stimulated with ghrelin or hexarelin showed a significant and specific increase in intracellular free calcium. Hexarelin, a synthetic hexapeptide, known to be a full agonist of the GHS-R1a, was used as positive control in all the following experiment. This in vitro model allowed to characterize four agonists and four antagonists of the GHS-R1a. Next, the agonists have been tested in vivo in a rat model of cachexia. Rats were treated daily with 1 mg/kg cisplatin from day 1 through day 3, whereas the test compounds were administered twice a day from day 1 through day

The orexigenic and anabolic effects induced by ghrelin and the synthetic GH secretagogues (GHSs) are thought to positively contribute to therapeutic approaches and the adjunct treatment of a number of diseases associated with muscle wasting such as cachexia and sarcopenia. However, many questions about the potential utility and safety of GHSs in both therapy and skeletal muscle function remain unanswered. By using fura-2 cytofluorimetric technique, we determined the acute effects of ghrelin, as well as of peptidyl and nonpeptidyl synthetic GHSs on calcium homeostasis, a critical biomarker of muscle function, in isolated tendon-to-tendon male rat skeletal muscle fibers. The synthetic nonpeptidyl GHSs, but not peptidyl ghrelin and hexarelin, were able to significantly increase resting cytosolic calcium [Ca(2+)]i. The nonpeptidyl GHS-induced [Ca(2+)]i increase was independent of GHS-receptor 1a but was antagonized by both thapsigargin/caffeine and cyclosporine A, indicating the involvement of the sarcoplasmic reticulum and mitochondria. Evaluation of the effects of a pseudopeptidyl GHS and a nonpeptidyl antagonist of the GHS-receptor 1a together with a drug-modeling study suggest the conclusion that the lipophilic nonpeptidyl structure of the tested compounds is the key chemical feature crucial for the GHS-induced calcium alterations in the skeletal muscle. Thus, synthetic GHSs can have different effects on skeletal muscle fibers depending on their molecular structures. The calcium homeostasis dysregulation specifically induced by the nonpeptidyl GHSs used in this study could potentially counteract the beneficial effects associated with these drugs in the treatment of muscle wasting of cachexia- or other age-related disorders

The synthesis and the in vitro antibacterial activity of novel linezolid-like oxadiazoles is reported. Replacement of the linezolid morpholine C-ring with 1,2,4-oxadiazole results in an antibacterial activity against Staphylococcus aureus both methicillin-susceptible and methicillin-resistant comparable or even superior to that of linezolid. While acetamidomethyl or thioacetoamidomethyl moieties in the C(5) side-chain are required, fluorination of the phenyl B ring exhibits a slight effect on an antibacterial activity but its presence seems to reduce the compounds cytotoxicity. Molecular modeling performed using two different approaches - FLAP and Amber software - shows that in the binding pose of the newly synthesized compounds as compared with the crystallographic pose of linezolid, the 1,2,4-oxadiazole moiety seems to perfectly mimic the function of the morpholinic ring, since the H-bond interaction with U2585 is retained

Recently, we demonstrated that TLQP-21 triggers lipolysis and induces resistance to obesity by reducing fat accumulation [1]. TLQP-21 is a 21 amino acid peptide cleavage product of the neuroprotein VGF and was first identified in rat brain. Although TLQP-21 biological activity and its molecular signaling is under active investigation, a receptor for TLQP-21 has not yet been characterized. We now demonstrate that TLQP-21 stimulates intracellular calcium mobilization in CHO cells. Furthermore, using Atomic Force Microscopy (AFM), we also provide evidence of TLQP-21 binding-site characteristics in CHO cells. AFM was used in force mapping mode equipped with a cantilever suitably functionalized with TLQP-21. Attraction of this functionalized probe to the cell surface was specific and consistent with the biological activity of TLQP-21; by contrast, there was no attraction of a probe functionalized with biologically inactive analogues. We detected interaction of the peptide with the binding-site by scanning the cell surface with the cantilever tip. The attractive force between TLQP-21 and its binding site was measured, statistically analyzed and quantified at approximately 40 pN on average, indicating a single class of binding sites. Furthermore we observed that the distribution of these binding sites on the surface was relatively uniform. © 2012 Elsevier B.V. All rights reserved.

Amphiphilic bile acids linked through an oligoethylene glycol to a biotin moiety were synthesized and shown to create micellar structures in aqueous environment, interact with avidin and be efficiently incorporated into hepatocyte cells, suggesting their potential as a drug delivery system against liver diseases. © 2011 The Royal Society of Chemistry.

We consider a 4D model for photon production induced by a refractive index perturbation in a dielectric medium. We show that, in this model, we can infer the presence of a Hawking type effect. This prediction shows up both in the analogue Hawking framework, which is implemented in the pulse frame and relies on the peculiar properties of the effective geometry in which quantum fields propagate, as well as in the laboratory frame, through standard quantum field theory calculations. Effects of optical dispersion are also taken into account, and are shown to provide a limited energy bandwidth for the emission of Hawking radiation. © 2011 The American Physical Society.

Amphiphilic bile acids linked through an oligoethylene glycol to a biotin moiety were synthesized and shown to create micellar structures in aqueous environment, interact with avidin and be efficiently incorporated into hepatocyte cells, suggesting their potential as a drug delivery system against liver diseases. © 2011 The Royal Society of Chemistry.

In the framework of transformation optics, we show that the propagation of a locally superluminal refractive index perturbation (RIP) in a Kerr medium can be described, in the eikonal approximation, by means of a stationary metric, which we prove to be of Gordon type. Under suitable hypotheses on the RIP, we obtain a stationary but not static metric, which is characterized by an ergosphere and by a peculiar behaviour of the geodesics, which are studied numerically, also accounting for material dispersion. Finally, the equation to be satisfied by an event horizon is also displayed and briefly discussed. © IOP Publishing Ltd and Deutsche Physikalische Gesellschaft.

Event horizons of astrophysical black holes and gravitational analogues have been predicted to excite the quantum vacuum and give rise to the emission of quanta, known as Hawking radiation. We experimentally create such a gravitational analogue using ultrashort laser pulse filaments and our measurements demonstrate a spontaneous emission of photons that confirms theoretical predictions. © 2010 The American Physical Society.

We present near- and mid-infrared (IR) photometric data of the Type Ibn supernova (SN) 2006jc obtained with the United Kingdom Infrared Telescope (UKIRT), the Gemini North Telescope, and the Spitzer Space Telescope between days 86 and 493 post-explosion. We find that the IR behaviour of SN 2006jc can be explained as a combination of IR echoes from two manifestations of circumstellar material. The bulk of the near-IR emission arises from an IR echo from newly-condensed dust in a cool dense shell (CDS) produced by the interaction of the ejecta outward shock with a dense shell of circumstellar material ejected by the progenitor in a luminous blue variable (LBV) like outburst about two years prior to the SN explosion. The CDS dust mass reaches a modest 3.0 x 10^(-4) M(solar) by day 230. While dust condensation within a CDS formed behind the ejecta inward shock has been proposed before for one event (SN 1998S), SN 2006jc is the first one showing evidence for dust condensation in a CDS formed behind the ejecta outward shock in the circumstellar material. At later epochs, a substantial and growing contribution to the IR fluxes arises from an IR echo from pre-existing dust in the progenitor wind. The mass of the pre-existing CSM dust is at least ~8 x 10^(-3) M(solar). This work therefore adds to the evidence that mass-loss from the progenitors of core-collapse supernovae could be a major source of dust in the universe. However, yet again, we see no direct evidence that the explosion of a supernova produces anything other than a very modest amount of dust., Comment: 18 pages, 10 figures, accepted to MNRAS

Context. The ESO-Spitzer Imaging extragalactic Survey (ESIS) is the optical follow up of the Spitzer Wide-area Infra-Red Extragalactic survey (SWIRE) in the ELAIS-S1 region of the sky. Aims. In the era of observational cosmology, the main efforts are focused on the study of galaxy evolution and its environmental dependence. Wide area, multiwavelength, extragalactic surveys are needed in order to probe sufficiently large volumes, minimize cosmic variance and find significant numbers of rare objects. Methods. We present VIMOS I and z band imaging belonging to the ESIS survey. A total of ~4 deg^2 was targeted in I and ~1 deg^2 in z. Accurate data processing includes removal of fringing, and mosaicking of the complex observing pattern. Completeness levels and photometric uncertainties are estimated through simulations. The multi-wavelength data available in the area are exploited to identify high-redshift galaxies, using the IR-peak technique. Results. More than 300 000 galaxies have been detected in the I band and ~50 000 in the z band. Object coordinates are defined within an uncertainty of ~0.2 arcsec rms, with respect to GSC 2.2. We reach a 90% average completeness at 23.1 and 22.5 mag (Vega) in the I and z bands, respectively. On the basis of IRAC colors, we identify galaxies having the 1.6 $\mu$m stellar peak shifted to z = 1-3. The new I, z band data provide reliable constraints to help avoid low-redshift interlopers and reinforce this selection. Roughly 1000 galaxies between z = 2-3 are identified over the ESIS ~4 deg^2, at the SWIRE 5.8 $\mu$m depth (25.8 $\mu$Jy at 3$\sigma$). These are the best galaxy candidates to dominate the massive tail ( M > 1011 $M_\odot$) of the z > 2 mass function.

(abridged) The ESIS survey is the optical follow up of the SWIRE/Spitzer in the ELAIS-S1 region of the sky. In the era of observational cosmology, the main efforts are focused on the study of galaxy evolution and its environmental dependence. Wide area, multiwavelength, extragalactic surveys are needed in order to probe sufficiently large volumes, minimize cosmic variance and find significant numbers of rare objects. We present VIMOS I and z band imaging belonging to the ESIS survey. A total of ~4 deg2 were targeted in I and ~1 deg2 in z. More than 300000 galaxies have been detected in the I band and ~50000 in the z band. Object coordinates are defined within an uncertainty of ~0.2 arcsec r.m.s., with respect to GSC 2.2. We reach a 90% average completeness at 23.1 and 22.5 mag (Vega) in the I and z bands, respectively. On the basis of IRAC colors, we identified galaxies having the 1.6 um stellar peak shifted to z=1-3. The new I, z band data provide reliable constraints to avoid low-redshift interlopers and reinforce this selection. Roughly 1000 galaxies between z=2-3 were identified over the ESIS ~4 deg2, at the SWIRE 5.8 um depth (25.8 uJy at 3sigma). These are the best galaxy candidates to dominate the massive tail (M>1e11 Msun) of the z>2 mass function., Comment: Accepted for publication on A&A. The quality of some figures has been degraded for arXiv purposes. More information about the ESIS survey is available at http://www.astro.unipd.it/esis

We present a study of the evolved stellar populations in the dwarf spheroidal galaxy LeoII, based on JHKs observations obtained with the near-infrared array WFCAM at the UKIRT telescope. Combining the new data with optical data, we derived photometric estimates of the distribution of global metallicity [M/H] of individual red giant stars from their V-Ks colours. We used the new data to derive the properties of a nearly complete sample of asymptotic giant branch (AGB) stars in LeoII. Using a near-infrared two-colour diagram, we were able to obtain a clean separation from Milky Way foreground stars and discriminate between carbon- and oxygen-rich AGB stars. We simulate the JHKs data with the TRILEGAL population synthesis code together with the most updated thermally pulsing AGB models, and using the star formation histories derived from independent work based on deep HST photometry. After scaling the mass of LeoII models to the observed number of upper RGB stars, we find that present models predict too many O-rich TP-AGB stars of higher luminosity due to a likely under-estimation of either their mass-loss rates at low metallicity, and/or their degree of obscuration by circumstellar dust. On the other hand, the TP-AGB models are able to reproduce the observed number and luminosities of carbon stars satisfactorily well, indicating that in this galaxy the least massive stars that became carbon stars should have masses as low as ~1 M_sun., Comment: accepted for publication in MNRAS