Distinctive response of CNS glial cells in oro-facial pain associated with injury, infection and inflammation

Oro-facial pain following injury and infection is frequently observed in dental clinics. While neuropathic pain evoked by injury associated with nerve lesion has an involvement of glia/immune cells, inflammatory hyperalgesia has an exaggerated sensitization mediated by local and circulating immune mediators. To better understand the contribution of central nervous system (CNS) glial cells in these different pathological conditions, in this study we sought to characterize functional phenotypes of glial cells in response to trigeminal nerve injury (loose ligation of the mental branch), infection (subcutaneous injection of lipopolysaccharide-LPS) and to sterile inflammation (subcutaneous injection of complete Freund's adjuvant-CFA) on the lower lip. Each of the three insults triggered a specific pattern of mechanical allodynia. In parallel with changes in sensory response, CNS glial cells reacted distinctively to the challenges. Following ligation of the mental nerve, both microglia and astrocytes in the trigeminal nuclear complex were highly activated, more prominent in the principal sensory nucleus (Pr5) and subnucleus caudalis (Sp5C) area. Microglial response was initiated early (days 3-14), followed by delayed astrocytes activation (days 7-28). Although the temporal profile of microglial and astrocyte reaction corresponded respectively to the initiation and chronic stage of neuropathic pain, these activated glial cells exhibited a low profile of cytokine expression. Local injection of LPS in the lower lip skin also triggered a microglial reaction in the brain, which started in the circumventricular organs (CVOs) at 5 hours post-injection and diffused progressively into the brain parenchyma at 48 hours. This LPS-induced microglial reaction was accompanied by a robust induction of IκB-α mRNA and pro-inflammatory cytokines within the CVOs. However, LPS induced microglial activation did not specifically occur along the pain signaling pathway. In contrast, CFA injection led to minor microglial morphological changes and an induction of IκB-α mRNA in the CVO regions; a significant increase in IL-1β and IL-6 mRNA started only at 48 hours post-injection, when the induced pain-related behavior started to resolve. Our detailed analysis of CNS glial response clearly revealed that both nerve injury and oro-facial infection/inflammation induced CNS glial activation, but in a completely different pattern, which suggests a remarkable plasticity of glial cells in response to dynamic changes in their microenvironment and different potential involvement of this non-neuronal cell population in pathological pain development

Phase transitions in MgSiO3 post-perovskite in super-Earth mantles

The highest pressure form of the major Earth-forming mantle silicate is MgSiO3 post-perovskite (PPv). Understanding the fate of PPv at TPa pressures is the first step for understanding the mineralogy of super-Earths-type exoplanets, arguably the most interesting for their similarities with Earth. Modeling their internal structure requires knowledge of stable mineral phases, their properties under compression, and major element abundances. Several studies of PPv under extreme pressures support the notion that a sequence of pressure induced dissociation transitions produce the elementary oxides SiO2 and MgO as the ultimate aggregation form at ~3 TPa. However, none of these studies have addressed the problem of mantle composition, particularly major element abundances usually expressed in terms of three main variables, the Mg/Si and Fe/Si ratios and the Mg#, as in the Earth. Here we show that the critical compositional parameter, the Mg/Si ratio, whose value in the Earth's mantle is still debated, is a vital ingredient for modeling phase transitions and internal structure of super-Earth mantles. Specifically, we have identified new sequences of phase transformations, including new recombination reactions that depend decisively on this ratio. This is a new level of complexity that has not been previously addressed, but proves essential for modeling the nature and number of internal layers in these rocky mantles.Comment: Submitted to Earth Planet. Sci. Lett., 28 pages, 6 figure

Kondo effect in transport through Aharonov-Bohm and Aharonov-Casher interferometers

We derive the extension of the Hubbard model to include Rashba spin-orbit coupling that correctly describes Aharonov-Bohm and Aharonov-Casher phases in a ring under applied magnetic and electric fields. When the ring is connected to conducting leads, we develop a formalism that is able to describe both, Kondo and interference effects. We find that in the Kondo regime, the spin-orbit coupling reduces strongly the conductance from the unitary limit. This effect in combination with the magnetic flux, can be used to produce spin polarized carriers.Comment: 6 pages, 4 figures, presented at SCES2008, Buzios, Brasi

On the Eccentricity Distribution of Short-Period Single-Planet Systems

We apply standard Markov chain Monte Carlo (MCMC) analysis techniques for 50 short- period, single-planet systems discovered with radial velocity technique. We develop a new method for accessing the significance of a non-zero orbital eccentricity, namely {\Gamma} analysis, which combines frequentist bootstrap approach with Bayesian analysis of each simulated data set. We find the eccentricity estimations from {\Gamma} analysis are generally consistent with results from both standard MCMC analysis and previous references. The {\Gamma} method is particular useful for assessing the significance of small eccentricities. Our results suggest that the current sample size is insufficient to draw robust conclusions about the roles of tidal interaction and perturbations in shaping the eccentricity distribution of short-period single-planet systems. We use a Bayesian population analysis to show that a mixture of analytical distributions is a good approximation of the underlying eccentricity distribution. For short-period planets, we find the most probable values of parameters in the analytical functions given the observed eccentricities. These analytical functions can be used in theoretical investigations or as priors for the eccentricity distribution when analyzing short-period planets. As the measurement precision improves and sample size increases, the method can be applied to more complex parametrizations for the underlying distribution of eccentricity for extrasolar planetary systems.Comment: 13 pages, 11 figures, 4 tables, accepted by MNRA

Reversible lysine fatty acylation of an anchoring protein mediates adipocyte adrenergic signaling.

N-myristoylation on glycine is an irreversible modification that has long been recognized to govern protein localization and function. In contrast, the biological roles of lysine myristoylation remain ill-defined. We demonstrate that the cytoplasmic scaffolding protein, gravin-α/A kinase–anchoring protein 12, is myristoylated on two lysine residues embedded in its carboxyl-terminal protein kinase A (PKA) binding domain. Histone deacetylase 11 (HDAC11) docks to an adjacent region of gravin-α and demyristoylates these sites. In brown and white adipocytes, lysine myristoylation of gravin-α is required for signaling via β(2)- and β(3)-adrenergic receptors (β-ARs), which are G protein–coupled receptors (GPCRs). Lysine myristoylation of gravin-α drives β-ARs to lipid raft membrane microdomains, which results in PKA activation and downstream signaling that culminates in protective thermogenic gene expression. These findings define reversible lysine myristoylation as a mechanism for controlling GPCR signaling and highlight the potential of inhibiting HDAC11 to manipulate adipocyte phenotypes for therapeutic purposes

Mass hierarchy, mass gap and corrections to Newton's law on thick branes with Poincare symmetry

We consider a scalar thick brane configuration arising in a 5D theory of gravity coupled to a self-interacting scalar field in a Riemannian manifold. We start from known classical solutions of the corresponding field equations and elaborate on the physics of the transverse traceless modes of linear fluctuations of the classical background, which obey a Schroedinger-like equation. We further consider two special cases in which this equation can be solved analytically for any massive mode with m^2>0, in contrast with numerical approaches, allowing us to study in closed form the massive spectrum of Kaluza-Klein (KK) excitations and to compute the corrections to Newton's law in the thin brane limit. In the first case we consider a solution with a mass gap in the spectrum of KK fluctuations with two bound states - the massless 4D graviton free of tachyonic instabilities and a massive KK excitation - as well as a tower of continuous massive KK modes which obey a Legendre equation. The mass gap is defined by the inverse of the brane thickness, allowing us to get rid of the potentially dangerous multiplicity of arbitrarily light KK modes. It is shown that due to this lucky circumstance, the solution of the mass hierarchy problem is much simpler and transparent than in the (thin) Randall-Sundrum (RS) two-brane configuration. In the second case we present a smooth version of the RS model with a single massless bound state, which accounts for the 4D graviton, and a sector of continuous fluctuation modes with no mass gap, which obey a confluent Heun equation in the Ince limit. (The latter seems to have physical applications for the first time within braneworld models). For this solution the mass hierarchy problem is solved as in the Lykken-Randall model and the model is completely free of naked singularities.Comment: 25 pages in latex, no figures, content changed, corrections to Newton's law included for smooth version of RS model and an author adde

Macrocalcitonin Is a Novel Pitfall in the Routine of Serum Calcitonin Immunoassay

Context: Calcitonin (CT) is a sensitive marker of medullary thyroid carcinoma (MTC) and is used for primary diagnosis and follow-up after thyroidectomy. However, persistently elevated CT is observed even after complete surgical removal without evidence of a recurrent or persistent tumor. Objective: To investigate the presence of assay interference in the serum CT of MTC patients who are apparently without a structural disease. Patients and Methods: We studied three index MTC cases for CT assay interference and 14 patients with metastatic MTC. The CT level was measured using an immunofluorometric assay. Screening for assay interference was performed by determination of CT levels before and after serum treatment with polyethylene glycol. Additionally, samples were analyzed by chromatography on ultra-performance liquid chromatography and protein A-Sepharose. Results: Patients with biochemical and structural disease showed CT mean recovery of 84.1% after polyethylene glycol treatment, whereas patients suspected of interference showed recovery from 2-7%. The elution profile on UPLC showed that the immunometric CT from these three patients behaved like a high molecular mass aggregate (>300 kDa). Additionally, when these samples were applied to the protein A-Sepharose, CT immunoreactivity was retained on the column and was only released after lowering the pH. Conclusions: For the first time, our results show the presence of a novel pitfall in the CT immunoassay: "macrocalcitonin." Its etiology, frequency, and meaning remain to be defined, but its recognition is of interest and can help clinicians avoid unnecessary diagnostic investigations and treatment during the follow-up of MTC.Sao Paulo State Research Foundation-FAPESPFAPESPFederal Agency of Support and Evaluation of Postgraduate Education (Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior)National Council for Scientific and Technological DevelopmentUniv Fed Sao Paulo, Escola Paulista Med, Div Endocrinol, Dept Med,Thyroid Dis Ctr, BR-04039032 Sao Paulo, SP, BrazilUniv Fed Sao Paulo, Escola Paulista Med, Div Endocrinol, Dept Med,Lab Mol & Translat Endocrinol, BR-04039032 Sao Paulo, SP, BrazilUniv Fed Sao Paulo, Escola Paulista Med, Dept Biochem, Div Mol Biol, BR-04044020 Sao Paulo, SP, BrazilUniv Fed Sao Paulo, Escola Paulista Med, Div Endocrinol, Dept Med,Thyroid Dis Ctr, BR-04039032 Sao Paulo, SP, BrazilUniv Fed Sao Paulo, Escola Paulista Med, Div Endocrinol, Dept Med,Lab Mol & Translat Endocrinol, BR-04039032 Sao Paulo, SP, BrazilUniv Fed Sao Paulo, Escola Paulista Med, Dept Biochem, Div Mol Biol, BR-04044020 Sao Paulo, SP, BrazilFAPESP: 2006/60402-1FAPESP: 2010/51547-1FAPESP: 2010/19478Web of Scienc