Differential expression of ATP7A, ATP7B and CTR1 in adult rat dorsal root ganglion tissue

Background: ATP7A, ATP7B and CTR1 are metal transporting proteins that control the cellular disposition of copper and platinum drugs, but their expression in dorsal root ganglion (DRG) tissue and their role in platinum-induced neurotoxicity are unknown. To investigate the DRG expression of ATP7A, ATP7B and CTR1, lumbar DRG and reference tissues were collected for real time quantitative PCR, RT-PCR, immunohistochemistry and Western blot analysis from healthy control adult rats or from animals treated with intraperitoneal oxaliplatin (1.85 mg/kg) or drug vehicle twice weekly for 8 weeks.Results: In DRG tissue from healthy control animals, ATP7A mRNA was clearly detectable at levels similar to those found in the brain and spinal cord, and intense ATP7A immunoreactivity was localised to the cytoplasm of cell bodies of smaller DRG neurons without staining of satellite cells, nerve fibres or co-localisation with phosphorylated heavy neurofilament subunit (pNF-H). High levels of CTR1 mRNA were detected in all tissues from healthy control animals, and strong CTR1 immunoreactivity was associated with plasma membranes and vesicular cytoplasmic structures of the cell bodies of larger-sized DRG neurons without co-localization with ATP7A. DRG neurons with strong expression of ATP7A or CTR1 had distinct cell body size profiles with minimal overlap between them. Oxaliplatin treatment did not alter the size profile of strongly ATP7A-immunoreactive neurons but significantly reduced the size profile of strongly CTR1-immunoreactive neurons. ATP7B mRNA was barely detectable, and no specific immunoreactivity for ATP7B was found, in DRG tissue from healthy control animals.Conclusions: In conclusion, adult rat DRG tissue exhibits a specific pattern of expression of copper transporters with distinct subsets of peripheral sensory neurons intensely expressing either ATP7A or CTR1, but not both or ATP7B. The neuron subtype-specific and largely non-overlapping distribution of ATP7A and CTR1 within rat DRG tissue may be required to support the potentially differing cuproenzyme requirements of distinct subsets of sensory neurons, and could influence the transport and neurotoxicity of oxaliplatin.<br /

Production and evolution of Li, Be and B isotopes in the Galaxy

We reassess the problem of the production and evolution of the light elements Li, Be and B and of their isotopes in the Milky Way, in the light of new observational and theoretical developments. The main novelty is the introduction of a new scheme for the origin of Galactic cosmic rays (GCR), which for the first time enables a self-consistent calculation of their composition during galactic evolution. The scheme accounts for key features of the present-day GCR source composition, it is based on the wind yields of the Geneva models of rotating, mass losing stars and it is fully coupled to a detailed galactic chemical evolution code. We find that the adopted GCR source composition accounts naturally for the observations of primary Be and helps understanding why Be follows closer Fe than O. We find that GCR produce ~70% of the solar B11/B10 isotopic ratio; the remaining 30% of B11 presumably result from neutrino-nucleosynthesis in massive star explosions. We find that GCR and primordial nucleosynthesis can make at most 30% of solar Li. At least half of solar Li has to originate in low-mass stellar sources (red giants, asymptotic giant branch stars or novae), but the required average yields of those sources are found to be much larger than obtained in current models of stellar nucleosynthesis. We also present radial profiles of LiBeB elemental and isotopic abundances in the Milky Way disc. We argue that the shape of those profiles - and the late evolution of LiBeB in general - reveals important features of the production of those light elements through primary and secondary processes.Comment: Final version, matches the one to appear in Astronomy and Astrophysics, typos corrected, references adde

Measurement of the Bottom-Strange Meson Mixing Phase in the Full CDF Data Set

We report a measurement of the bottom-strange meson mixing phase \beta_s using the time evolution of B0_s -> J/\psi (->\mu+\mu-) \phi (-> K+ K-) decays in which the quark-flavor content of the bottom-strange meson is identified at production. This measurement uses the full data set of proton-antiproton collisions at sqrt(s)= 1.96 TeV collected by the Collider Detector experiment at the Fermilab Tevatron, corresponding to 9.6 fb-1 of integrated luminosity. We report confidence regions in the two-dimensional space of \beta_s and the B0_s decay-width difference \Delta\Gamma_s, and measure \beta_s in [-\pi/2, -1.51] U [-0.06, 0.30] U [1.26, \pi/2] at the 68% confidence level, in agreement with the standard model expectation. Assuming the standard model value of \beta_s, we also determine \Delta\Gamma_s = 0.068 +- 0.026 (stat) +- 0.009 (syst) ps-1 and the mean B0_s lifetime, \tau_s = 1.528 +- 0.019 (stat) +- 0.009 (syst) ps, which are consistent and competitive with determinations by other experiments.Comment: 8 pages, 2 figures, Phys. Rev. Lett 109, 171802 (2012

Lectin-Dependent Enhancement of Ebola Virus Infection via Soluble and Transmembrane C-type Lectin Receptors

Mannose-binding lectin (MBL) is a key soluble effector of the innate immune system that recognizes pathogen-specific surface glycans. Surprisingly, low-producing MBL genetic variants that may predispose children and immunocompromised individuals to infectious diseases are more common than would be expected in human populations. Since certain immune defense molecules, such as immunoglobulins, can be exploited by invasive pathogens, we hypothesized that MBL might also enhance infections in some circumstances. Consequently, the low and intermediate MBL levels commonly found in human populations might be the result of balancing selection. Using model infection systems with pseudotyped and authentic glycosylated viruses, we demonstrated that MBL indeed enhances infection of Ebola, Hendra, Nipah and West Nile viruses in low complement conditions. Mechanistic studies with Ebola virus (EBOV) glycoprotein pseudotyped lentiviruses confirmed that MBL binds to N-linked glycan epitopes on viral surfaces in a specific manner via the MBL carbohydrate recognition domain, which is necessary for enhanced infection. MBL mediates lipid-raft-dependent macropinocytosis of EBOV via a pathway that appears to require less actin or early endosomal processing compared with the filovirus canonical endocytic pathway. Using a validated RNA interference screen, we identified C1QBP (gC1qR) as a candidate surface receptor that mediates MBL-dependent enhancement of EBOV infection. We also identified dectin-2 (CLEC6A) as a potentially novel candidate attachment factor for EBOV. Our findings support the concept of an innate immune haplotype that represents critical interactions between MBL and complement component C4 genes and that may modify susceptibility or resistance to certain glycosylated pathogens. Therefore, higher levels of native or exogenous MBL could be deleterious in the setting of relative hypocomplementemia which can occur genetically or because of immunodepletion during active infections. Our findings confirm our hypothesis that the pressure of infectious diseases may have contributed in part to evolutionary selection of MBL mutant haplotypes

Successful Weight Loss Surgery Improves Eating Control and Energy Metabolism: A Review of the Evidence

Eating behavior is determined by a balance of memories in terms of reward and punishment to satisfy the urge to consume food. Refilling empty energy stores and hedonistic motivation are rewarding aspects of eating. Overfeeding, associated adverse GI effects, and obesity implicate punishment. In the current review, evidence is given for the hypothesis that bariatric surgery affects control over eating behavior.Moreover, any caloric overload will reduce the feeling of satiety. Durable weight loss after bariatric surgery is probably the result of a new equilibrium between reward and punishment, together with a better signaling of satiation due to beneficial metabolic changes.We propose to introduce three main treatment goals for bariatric surgery: 1) acceptable weight loss, 2) improvement of eating control, and 3) metabolic benefit. To achieve this goal, loss of 50% to 70% of excess weight will be appropriate (i.e. 30% to 40% loss of initial weight), depending on the degree of obesity prior to operation

Instrumentos de avaliação do aleitamento materno e seu uso na prática clínica

RESUMO Objetivos Identificar instrumentos de avaliação da amamentação e sua aplicação na prática clínica, validação e adaptação transcultural. Método Revisão integrativa, realizada em seis bases de dados e em uma biblioteca eletrônica, entre agosto/2014-dezembro/2015, sem limitação temporal. Resultados Foram identificados 19 instrumentos de avaliação do AM. Destes, 12 foram validados e cinco foram adaptados transculturalmente. Quanto à aplicação, destacam-se seu uso para a avaliação do risco de desmame (BAPT) e a percepção/comportamento da mulher em amamentar (BSES-SF e IIFAS). Conclusão A identificação dos instrumentos disponíveis e de suas indicações para a avaliação do AM pode auxiliar profissionais na escolha pelo instrumento a ser utilizado, qualificando a assistência materno-infantil

Caspase involvement in autophagy

Caspases are a family of cysteine proteases widely known as the principal mediators of the apoptotic cell death response, but considerably less so as the contributors to the regulation of pathways outside cellular demise. In regards to autophagy, the modulatory roles of caspases have only recently begun to be adequately described. In contrast to apoptosis, autophagy promotes cell survival by providing energy and nutrients through the lysosomal degradation of cytoplasmic constituents. Under basal conditions autophagy and apoptosis cross-regulate each other through an elaborate network of interconnections which also includes the interplay between autophagyrelated proteins (ATGs) and caspases. In this review we focus on the effects of this crosstalk at the cellular level, as we aim to concentrate the main observations from research conducted so far on the fine-tuning of autophagy by caspases. Several members of this protease-family have been found to directly interact with key ATGs involved in different tiers across the autophagic cascade. Therefore, we firstly outline the core mechanism of macroautophagy in brief. In an effort to emphasize the importance of the intricate cross-regulation of ATGs and caspases, we also present examples drawn from Drosophila and plant models regarding the contribution of autophagy to apoptotic cell death during normal development

Olfactory Interference during Inhibitory Backward Pairing in Honey Bees

Background: Restrained worker honey bees are a valuable model for studying the behavioral and neural bases of olfactory plasticity. The proboscis extension response (PER; the proboscis is the mouthpart of honey bees) is released in response to sucrose stimulation. If sucrose stimulation is preceded one or a few times by an odor (forward pairing), the bee will form a memory for this association, and subsequent presentations of the odor alone are sufficient to elicit the PER. However, backward pairing between the two stimuli (sucrose, then odor) has not been studied to any great extent in bees, although the vertebrate literature indicates that it elicits a form of inhibitory plasticity. Methodology/Principal Findings: If hungry bees are fed with sucrose, they will release a long lasting PER; however, this PER can be interrupted if an odor is presented 15 seconds (but not 7 or 30 seconds) after the sucrose (backward pairing). We refer to this previously unreported process as olfactory interference. Bees receiving this 15 second backward pairing show reduced performance after a subsequent single forward pairing (excitatory conditioning) trial. Analysis of the results supported a relationship between olfactory interference and a form of backward pairing-induced inhibitory learning/ memory. Injecting the drug cimetidine into the deutocerebrum impaired olfactory interference. Conclusions/Significance: Olfactory interference depends on the associative link between odor and PER, rather than between odor and sucrose. Furthermore, pairing an odor with sucrose can lead either to association of this odor to PER or t