Involvement of Noradrenergic Neurotransmission in the Stress- but not Cocaine-Induced Reinstatement of Extinguished Cocaine-Induced Conditioned Place Preference in Mice: Role for β-2 Adrenergic Receptors

The responsiveness of central noradrenergic systems to stressors and cocaine poses norepinephrine as a potential common mechanism through which drug re-exposure and stressful stimuli promote relapse. This study investigated the role of noradrenergic systems in the reinstatement of extinguished cocaine-induced conditioned place preference by cocaine and stress in male C57BL/6 mice. Cocaine- (15 mg/kg, i.p.) induced conditioned place preference was extinguished by repeated exposure to the apparatus in the absence of drug and reestablished by a cocaine challenge (15 mg/kg), exposure to a stressor (6-min forced swim (FS); 20–25°C water), or administration of the α-2 adrenergic receptor (AR) antagonists yohimbine (2 mg/kg, i.p.) or BRL44408 (5, 10 mg/kg, i.p.). To investigate the role of ARs, mice were administered the nonselective β-AR antagonist, propranolol (5, 10 mg/kg, i.p.), the α-1 AR antagonist, prazosin (1, 2 mg/kg, i.p.), or the α-2 AR agonist, clonidine (0.03, 0.3 mg/kg, i.p.) before reinstatement testing. Clonidine, prazosin, and propranolol failed to block cocaine-induced reinstatement. The low (0.03 mg/kg) but not high (0.3 mg/kg) clonidine dose fully blocked FS-induced reinstatement but not reinstatement by yohimbine. Propranolol, but not prazosin, blocked reinstatement by both yohimbine and FS, suggesting the involvement of β-ARs. The β-2 AR antagonist ICI-118551 (1 mg/kg, i.p.), but not the β-1 AR antagonist betaxolol (10 mg/kg, i.p.), also blocked FS-induced reinstatement. These findings suggest that stress-induced reinstatement requires noradrenergic signaling through β-2 ARs and that cocaine-induced reinstatement does not require AR activation, even though stimulation of central noradrenergic neurotransmission is sufficient to reinstate

Sugar Versatility—Chemical and Bioprocessing of Many Phytobiomass Polysaccharides Using a Milder Hydrolytic Catalyst: Diluted Thermopressurized Phosphoric Acid

Phytobiomasses, given the qualitative and quantitative dominance of polysaccharides, are a dominant wealth available in nature. Cellulose and hemicelluloses from softwoods, hardwoods and grasses, starch from tubercles and roots, pectins from fruits and gums from some seeds may be explored as such or following acid or alkaline pretreatments as well enzymatic deconstruction, and even simple chemical derivatization toward more added-value products. A general view in the chemistry of these valuable polymers is here broached, following a sharper focus on acid pretreatments for L(h)C—ligno(hemi)cellulosic materials from sugarcane and other feedstocks. Our particular experience using a gentler proton donor but keeping very advantageous aspects for polysaccharide chemo/biotechnological processing—thermopressurized diluted phosphoric acid (oPA)—is presented with a more detailed description as a result of its validity for the hydrolytic deconstruction of hemicelluloses—heteroxylans and heteromannans, cassava starch, dahlia inulin and mixed glucans from microalgae cell walls. The opportunity of NOs—nutraceutical oligosacchrides—generation from these particular glycopolymers is also shortly commented

Stress-Induced Reinstatement of Drug Seeking: 20 Years of Progress

In human addicts, drug relapse and craving are often provoked by stress. Since 1995, this clinical scenario has been studied using a rat model of stress-induced reinstatement of drug seeking. Here, we first discuss the generality of stress-induced reinstatement to different drugs of abuse, different stressors, and different behavioral procedures. We also discuss neuropharmacological mechanisms, and brain areas and circuits controlling stress-induced reinstatement of drug seeking. We conclude by discussing results from translational human laboratory studies and clinical trials that were inspired by results from rat studies on stress-induced reinstatement. Our main conclusions are (1) The phenomenon of stress-induced reinstatement, first shown with an intermittent footshock stressor in rats trained to self-administer heroin, generalizes to other abused drugs, including cocaine, methamphetamine, nicotine, and alcohol, and is also observed in the conditioned place preference model in rats and mice. This phenomenon, however, is stressor specific and not all stressors induce reinstatement of drug seeking. (2) Neuropharmacological studies indicate the involvement of corticotropin-releasing factor (CRF), noradrenaline, dopamine, glutamate, kappa/dynorphin, and several other peptide and neurotransmitter systems in stress-induced reinstatement. Neuropharmacology and circuitry studies indicate the involvement of CRF and noradrenaline transmission in bed nucleus of stria terminalis and central amygdala, and dopamine, CRF, kappa/dynorphin, and glutamate transmission in other components of the mesocorticolimbic dopamine system (ventral tegmental area, medial prefrontal cortex, orbitofrontal cortex, and nucleus accumbens). (3) Translational human laboratory studies and a recent clinical trial study show the efficacy of alpha-2 adrenoceptor agonists in decreasing stress-induced drug craving and stress-induced initial heroin lapse

Integrated use of residues from olive mill and winery for lipase production by solid state fermentation with Aspergillus sp

Two phase olive mill waste (TPOMW) is presently the major waste produced by the olive mill industry. This waste has potential to be used as substrate for solid state fermentation (SSF) despite of its high concentration of phenolic compounds and low nitrogen content. In this work, it is demonstrated that mixtures of TPOMW with winery wastes support the production of lipase by Aspergillus spp. By agar plate screening, Aspergillus niger MUM 03.58, Aspergillus ibericus MUM 03.49 and Aspergillus uvarum MUM 08.01 were chosen for lipase production by SSF. Plackett-Burman experimental design was employed to evaluate the effect of substrate composition and time on lipase production. The highest amounts of lipase were produced by A. ibericus on a mixture of TPOMW, urea and exhausted grape mark (EGM). Urea was found to be the most influent factor for the lipase production. Further optimization of lipase production by A. ibericus using a full factorial design (32) conducted to optimal conditions of substrate composition (0.073 g urea/g and 25% of EGM) achieving 18.67 U/g of lipolytic activity.Jose Manuel Salgado is grateful for Postdoctoral fellowship (EX-2010-0402) of Education Ministry of Spanish Government. Luis Abrunhosa was supported by the grant SFRH/BPD/43922/2008 from Fundacao para a Ciencia e Tecnologia-FCT, Portugal. Authors thank Fundacao para a Ciencia e a Tecnologia (FCT) for financial support through the project FCT Pest-OE/EQB/LA0023/2011

A change in the optical polarization associated with a gamma-ray flare in the blazar 3C 279

It is widely accepted that strong and variable radiation detected over all accessible energy bands in a number of active galaxies arises from a relativistic, Doppler-boosted jet pointing close to our line of sight. The size of the emitting zone and the location of this region relative to the central supermassive black hole are, however, poorly known, with estimates ranging from light-hours to a light-year or more. Here we report the coincidence of a gamma-ray flare with a dramatic change of optical polarization angle. This provides evidence for co-spatiality of optical and gamma-ray emission regions and indicates a highly ordered jet magnetic field. The results also require a non-axisymmetric structure of the emission zone, implying a curved trajectory for the emitting material within the jet, with the dissipation region located at a considerable distance from the black hole, at about 10^5 gravitational radii.Comment: Published in Nature issued on 18 February 2010. Corresponding authors: Masaaki Hayashida and Greg Madejsk

Guidance on noncorticosteroid systemic immunomodulatory therapy in noninfectious uveitis: fundamentals of care for uveitis (focus) initiative

Topic: An international, expert-led consensus initiative to develop systematic, evidence-based recommendations for the treatment of noninfectious uveitis in the era of biologics. Clinical Relevance: The availability of biologic agents for the treatment of human eye disease has altered practice patterns for the management of noninfectious uveitis. Current guidelines are insufficient to assure optimal use of noncorticosteroid systemic immunomodulatory agents. Methods: An international expert steering committee comprising 9 uveitis specialists (including both ophthalmologists and rheumatologists) identified clinical questions and, together with 6 bibliographic fellows trained in uveitis, conducted a Preferred Reporting Items for Systematic Reviews and Meta-Analyses protocol systematic reviewof the literature (English language studies from January 1996 through June 2016; Medline [OVID], the Central Cochrane library, EMBASE,CINAHL,SCOPUS,BIOSIS, andWeb of Science). Publications included randomized controlled trials, prospective and retrospective studies with sufficient follow-up, case series with 15 cases or more, peer-reviewed articles, and hand-searched conference abstracts from key conferences. The proposed statements were circulated among 130 international uveitis experts for review.Atotal of 44 globally representativegroupmembersmet in late 2016 to refine these guidelines using a modified Delphi technique and assigned Oxford levels of evidence. Results: In total, 10 questions were addressed resulting in 21 evidence-based guidance statements covering the following topics: when to start noncorticosteroid immunomodulatory therapy, including both biologic and nonbiologic agents; what data to collect before treatment; when to modify or withdraw treatment; how to select agents based on individual efficacy and safety profiles; and evidence in specific uveitic conditions. Shared decision-making, communication among providers and safety monitoring also were addressed as part of the recommendations. Pharmacoeconomic considerations were not addressed. Conclusions: Consensus guidelines were developed based on published literature, expert opinion, and practical experience to bridge the gap between clinical needs and medical evidence to support the treatment of patients with noninfectious uveitis with noncorticosteroid immunomodulatory agents

Fabrication and optical properties of strain-free self-assembled mesoscopic GaAs structures

FUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULO - FAPESPCONSELHO NACIONAL DE DESENVOLVIMENTO CIENTÍFICO E TECNOLÓGICO - CNPQCOORDENAÇÃO DE APERFEIÇOAMENTO DE PESSOAL DE NÍVEL SUPERIOR - CAPESWe use a combined process of Ga-assisted deoxidation and local droplet etching to fabricate unstrained mesoscopic GaAs/AlGaAs structures exhibiting a high shape anisotropy with a length up to 1.2 mu m and a width of 150 nm. We demonstrate good controllability over size and morphology of the mesoscopic structures by tuning the growth parameters. Our growth method yields structures, which are coupled to a surrounding quantum well and present unique optical emission features. Microscopic and optical analysis of single structures allows us to demonstrate that single structure emission originates from two different confinement regions, which are spectrally separated and show sharp excitonic lines. Photoluminescence is detected up to room temperature making the structures the ideal candidates for strain-free light emitting/detecting devices.12114FUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULO - FAPESPCONSELHO NACIONAL DE DESENVOLVIMENTO CIENTÍFICO E TECNOLÓGICO - CNPQCOORDENAÇÃO DE APERFEIÇOAMENTO DE PESSOAL DE NÍVEL SUPERIOR - CAPESFUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULO - FAPESPCONSELHO NACIONAL DE DESENVOLVIMENTO CIENTÍFICO E TECNOLÓGICO - CNPQCOORDENAÇÃO DE APERFEIÇOAMENTO DE PESSOAL DE NÍVEL SUPERIOR - CAPES2012/11382-92014/17141-92015/08344-62016/14001-7475343/2013-1482729/2013-9305769/2015-4Sem informaçãoThe financial support through SisNano (MCTI Brazil), FAPESP (Processo 2012/11382-9, 2014/17141-9, 2015/08344-6 and 2016/14001-7), and CNPq (Processo 482729/2013-9, 305769/2015-4, 475343/2013-1) is acknowledged. SFCS thanks CAPES for the scholarship

Membrane fluidity matters: Hyperthermia from the aspects of lipids and membranes

Hyperthermia is a promising treatment modality for cancer in combination both with radio- and chemotherapy. In spite of its great therapeutic potential, the underlying molecular mechanisms still remain to be clarified. Due to lipid imbalances and 'membrane defects' most of the tumour cells possess elevated membrane fluidity. However, further increasing membrane fluidity to sensitise to chemo-or radiotherapy could have some other effects. In fact, hyperfluidisation of cell membrane induced by membrane fluidiser initiates a stress response as the heat shock protein response, which may modulate positively or negatively apoptotic cell death. Overviewing some recent findings based on a technology allowing direct imaging of lipid rafts in live cells and lipidomics, novel aspects of the intimate relationship between the 'membrane stress' of tumour cells and the cellular heat shock response will be highlighted. Our findings lend support to both the importance of membrane remodelling and the release of lipid signals initiating stress protein response, which can operate in tandem to control the extent of the ultimate cellular thermosensitivity. Overall, we suggest that the fluidity variable of membranes should be used as an independent factor for predicting the efficacy of combinational cancer therapies

Charge control in InP/GaInP single quantum dots embedded in Schottky diodes

We demonstrate control by applied electric field of the charge states in single self-assembled InP quantum dots placed in GaInP Schottky structures grown by metalorganic vapor phase epitaxy. This has been enabled by growth optimization leading to suppression of formation of large dots uncontrollably accumulating charge. Using bias- and polarization-dependent micro-photoluminescence, we identify the exciton multi-particle states and carry out a systematic study of the neutral exciton state dipole moment and polarizability. This analysis allows for the characterization of the exciton wavefunction properties at the single dot level for this type of quantum dots. Photocurrent measurements allow further characterization of exciton properties by electrical means, opening new possibilities for resonant excitation studies for such system.Comment: 7 pages, 4 figure

Genome-wide association analysis identifies six new loci associated with forced vital capacity

Forced vital capacity (FVC), a spirometric measure of pulmonary function, reflects lung volume and is used to diagnose and monitor lung diseases. We performed genome-wide association study meta-analysis of FVC in 52,253 individuals from 26 studies and followed up the top associations in 32,917 additional individuals of European ancestry. We found six new regions associated at genome-wide significance (P < 5 × 10−8) with FVC in or near EFEMP1, BMP6, MIR129-2–HSD17B12, PRDM11, WWOX and KCNJ2. Two loci previously associated with spirometric measures (GSTCD and PTCH1) were related to FVC. Newly implicated regions were followed up in samples from African-American, Korean, Chinese and Hispanic individuals. We detected transcripts for all six newly implicated genes in human lung tissue. The new loci may inform mechanisms involved in lung development and the pathogenesis of restrictive lung disease