Genetic characterization of interleukins (IL-1α, IL-1β, IL-2, IL-4, IL-8, IL-10, IL-12A, IL-12B, IL-15 and IL-18) with relevant biological roles in lagomorphs

Disponível em: www.ncbi.nlm.nih.gov/pmc/articles/pmid/26395994/ILs, as essential innate immune modulators, are involved in an array of biological processes. In the European rabbit (Oryctolagus cuniculus) IL-1α, IL-1β, IL-2, IL-4, IL-8, IL-10, IL-12A, IL-12B, IL-15 and IL-18 have been implicated in inflammatory processes and in the immune response against rabbit hemorrhagic disease virus and myxoma virus infections. In this study we characterized these ILs in six Lagomorpha species (European rabbit, pygmy rabbit, two cottontail rabbit species, European brown hare and American pika). Overall, these ILs are conserved between lagomorphs, including in their exon/intron structure. Most differences were observed between leporids and American pika. Indeed, when comparing both, some relevant differences were observed in American pika, such as the location of the stop codon in IL-1α and IL-2, the existence of a different transcript in IL8 and the number of cysteine residues in IL-1β. Changes at N-glycosylation motifs were also detected in IL-1, IL-10, IL-12B and IL-15. IL-1α is the protein that presents the highest evolutionary distances, which is in contrast to IL-12A where the distances between lagomorphs are the lowest. For all these ILs, sequences of human and European rabbit are more closely related than between human and mouse or European rabbit and mouse.Research Subject Categories::NATURAL SCIENCES::Biology::Cell and molecular biology::ImmunologyResearch Subject Categories::NATURAL SCIENCES::Biology::Cell and molecular biology::GeneticsFCT and North Portugal Regional Operational Programme 2007/2013 (ON.2) grants supported this work

Activity-regulated cytoskeleton-associated protein controls AMPAR endocytosis through a direct interaction with clathrin-adaptor protein 2

The activity-regulated cytoskeleton-associated (Arc) protein controls synaptic strength by facilitating AMPA receptor (AMPAR) endocytosis. Here we demonstrate that Arc targets AMPAR to be internalized through a direct interaction with the clathrin-adaptor protein 2 (AP-2). We show that Arc overexpression in dissociated hippocampal neurons obtained from C57BL/6 mouse reduces the density of AMPAR GluA1 subunits at the cell surface and reduces the amplitude and rectification of AMPAR-mediated miniature-EPSCs (mEPSCs). Mutations of Arc, that prevent the AP-2 interaction reduce Arc-mediated endocytosis of GluA1 and abolish the reduction in AMPAR-mediated mEPSC amplitude and rectification. Depletion of the AP-2 subunit µ2 blocks the Arc-mediated reduction in mEPSC amplitude, an effect that is restored by reintroducing µ2. The Arc-AP-2 interaction plays an important role in homeostatic synaptic scaling as the Arc-dependent decrease in mEPSC amplitude, induced by a chronic increase in neuronal activity, is inhibited by AP-2 depletion. These data provide a mechanism to explain how activity-dependent expression of Arc decisively controls the fate of AMPAR at the cell surface and modulates synaptic strength, via the direct interaction with the endocytic clathrin adaptor AP-2

Cissus Sicyoides: Pharmacological Mechanisms Involved In The Anti-inflammatory And Antidiarrheal Activities

The objective of this study was to evaluate the pharmacological mechanisms involved in anti-inflammatory and antidiarrheal actions of hydroalcoholic extract obtained from the leaves of Cissus sicyoides (HECS). The anti-inflammatory effect was evaluated by oral administration of HECS against acute model of edema induced by xylene, and the mechanisms of action were analysed by involvement of arachidonic acid (AA) and prostaglandin E2 (PGE2). The antidiarrheal effect of HECS was observed and we analyzed the motility and accumulation of intestinal fluid. We also analyzed the antidiarrheal mechanisms of action of HECS by evaluating the role of the opioid receptor, α2 adrenergic receptor, muscarinic receptor, nitric oxide (NO) and PGE2. The oral administration of HECS inhibited the edema induced by xylene and AA and was also able to significantly decrease the levels of PGE2. The extract also exhibited significant anti-diarrheal activity by reducing motility and intestinal fluid accumulation. This extract significantly reduced intestinal transit stimulated by muscarinic agonist and intestinal secretion induced by PGE2. Our data demonstrate that the mechanism of action involved in the anti-inflammatory effect of HECS is related to PGE2. The antidiarrheal effect of this extract may be mediated by inhibition of contraction by acting on the intestinal smoothmuscle and/or intestinal transit. © 2016 by the authors; licensee MDPI, Basel, Switzerland.17

A novel transflectance near infrared spectroscopy technique for monitoring hot melt extrusion

yesA transflectance near infra red (NIR) spectroscopy approach has been used to simultaneously measure drug and plasticiser content of polymer melts with varying opacity during hot melt extrusion. A high temperature reflectance NIR probe was mounted in the extruder die directly opposed to a highly reflective surface. Carbamazepine (CBZ) was used as a model drug, with polyvinyl pyrollidone-vinyl acetate co-polymer (PVP-VA) as a matrix and polyethylene glycol (PEG) as a plasticiser. The opacity of the molten extrudate varied from transparent at low CBZ loading to opaque at high CBZ loading. Particulate amorphous API and voids formed around these particles were found to cause the opacity. The extrusion process was monitored in real time using transflectance NIR; calibration and validation runs were performed using a wide range of drug and plasticiser loadings. Once calibrated, the technique was used to simultaneously track drug and plasticiser content during applied step changes in feedstock material. Rheological and thermal characterisations were used to help understand the morphology of extruded material. The study has shown that it is possible to use a single NIR spectroscopy technique to monitor opaque and transparent melts during HME, and to simultaneously monitor two distinct components within a formulation

Balanço do nitrogênio e fósforo em solo com cultivo orgânico de hortaliças após a incorporação de biomassa de guandu.

Os objetivos deste trabalho foram avaliar os efeitos de faixas de guandu (Cajanus cajan) e da incorporação da biomassa proveniente de sua poda na fertilidade do solo e na produtividade de três hortaliças sob cultivo orgânico. O delineamento usado foi de blocos casualizados completos em esquema de parcelas subsubdivididas com três repetições. As produtividades de beterraba, cenoura e feijão-de-vagem não foram afetadas pelos tratamentos. Nas parcelas onde não houve incorporação da biomassa de guandu, o balanço de nitrogênio no sistema foi negativo, ao passo que com a incorporação, esse balanço foi positivo. Embora tenha ocorrido balanço positivo para o fósforo nas parcelas sem a incorporação de biomassa de guandu, houve um aumento significativo na absorção desse elemento pelas hortaliças quando o material foi incorporado. O sistema de cultivo em aléias de guandu pode representar uma prática vantajosa para os produtores orgânicos, por contribuir na manutenção da fertilidade do solo

Polymorphism In Lep And Lepr May Modify Leptin Levels And Represent Risk Factors For Thyroid Cancer

Purpose. To understand the role of polymorphisms in the LEP (rs7799039 and rs2167270) and LEPR (rs1137101 and rs1137100) genes in DTC susceptibility and their effect on leptin levels. Methods. We studied 153 patients with DTC and 234 controls through TaqMan SNP Genotyping and ELISA, comparing these data to the clinicopathological data of patients with DTC. Results. Patients with AA genotype of rs7799039 had higher levels of serum leptin (9.22 ± 0.98 ng/mL) than those with AG genotype (10.07 ± 0.60 ng/mL; P = 0.005). Individuals with AG genotype of rs2167270 also produced higher serum leptin levels (10.05 ± 0.59 ng/mL) than the subjects with GG genotype (9.52 ± 0.79 ng/mL; P A) polymorphism and disease susceptibility and cardiovascular disease in patients with rheumatoid arthritis (2011) Clinical and Experimental Rheumatology, 29 (2), pp. 293-298Jiang, Y., Wilk, J.B., Borecki, I., Common variants in the 5' region of the leptin gene are associated with bodymass index in men fromthe National Heart, Lung, and Blood Institute Family Heart Study (2004) The American Journal of Human Genetics, 75 (2), pp. 220-230He, J., Xi, B., Ruiter, R., Association of LEP G2548A and LEPR Q223R polymorphisms with cancer susceptibility: Evidence froma meta-analysis (2013) PLoS ONE, 8 (10)Furusawa, T., Naka, I., Yamauchi, T., The Q223R polymorphism in LEPR is associated with obesity in Pacific Islanders (2010) Human Genetics, 127 (3), pp. 287-294Saukko, M., Kesäniemi, Y.A., Ukkola, O., Leptin receptor Lys109Arg and Gln223Arg polymorphisms are associated with early atherosclerosis (2010) Metabolic Syndrome and Related Disorders, 8 (5), pp. 425-430Lucas, A., Granada, M.L., Olaizola, I., Leptin and thyrotropin relationship is modulated by smoking status in euthyroid subjects (2013) Thyroid, 23 (8), pp. 964-970Duntas, L.H., Biondi, B., The interconnections between obesity, thyroid function, and autoimmunity: Themultifold role of leptin (2013) Thyroid, 23 (6), pp. 646-653Marzullo, P., Minocci, A., Tagliaferri, M.A., Investigations of thyroid hormones and antibodies in obesity: Leptin levels are associated with thyroid autoimmunity independent of bioanthropometric, hormonal, and weight-related determinants (2010) Journal of Clinical Endocrinology and Metabolism, 95 (8), pp. 3965-3972Guzel, S., Seven, A., Guzel, E.C., Buyuk, B., Celebi, A., Aydemir, B., Visfatin, leptin, and TNF-α: Interrelated adipokines in insulin-resistant clinical and subclinical hypothyroidism (2013) Endocrine Research, 38 (3), pp. 184-194Mammès, O., Betoulle, D., Aubert, R., Herbeth, B., Siest, G., Fumeron, F., Association of the G-2548A polymorphism in the 5' region of the LEP gene with overweight (2000) Annals of Human Genetics, 64 (5), pp. 391-394Portoles, O., Sorli, J.V., Frances, F., Effect of genetic variation in the leptin gene promoter and the leptin receptor gene on obesity risk in a population-based case-control study in Spain (2006) European Journal of Epidemiology, 21 (8), pp. 605-612Liu, C., Liu, L., Polymorphisms in three obesity-related genes (LEP, LEPR, and PON1) and breast cancer risk: A metaanalysis (2011) Tumour Biology, 32 (6), pp. 1233-1240Hoffsted, J., Eriksson, P., Mottagui-Tabar, S., Arner, P., A polymorphism in the leptin promoter region (-2548 G/A) influences gene expression and adipose tissue secretion of leptin (2002) Hormone and Metabolic Research, 34 (7), pp. 355-359Murugesan, D., Arunachalam, T., Ramamurthy, V., Subramanian, S., Association of polymorphisms in leptin receptor gene with obesity and type 2 diabetes in the local population of Coimbatore (2010) Indian Journal of Human Genetics, 16 (2), pp. 72-77Quinton, N.D., Lee, A.J., Ross, R.J.M., Eastell, R., Blakemore, A.I.F., A single nucleotide polymorphism (SNP) in the leptin receptor is associated with BMI, fatmass and leptin levels in postmenopausal Caucasian women (2001) Human Genetics, 108 (3), pp. 233-236Mattevi, V.S., Zembrzuski, V.M., Hutz, M.H., Association analysis of genes involved in the leptin-signaling pathway with obesity in Brazil (2002) International Journal of Obesity, 26 (9), pp. 1179-1185Yiannakouris, N., Yannakoulia, M., Melistas, L., Chan, J.L., Klimis-Zacas, D., Mantzoros, C.S., TheQ223Rpolymorphism of the leptin receptor gene is significantly associated with obesity and predicts a small percentage of bodyweight and body composition variability (2001) Journal of Clinical Endocrinology and Metabolism, 86 (9), pp. 4434-4439Stefan, N., Vozarova, B., Del Parigi, A., The Gln223Arg polymorphism of the leptin receptor in Pima Indians: Influence on energy expenditure, physical activity and lipid metabolism (2002) International Journal of Obesity, 26 (12), pp. 1629-1632Chiu, K.C., Chu, A., Chuang, L.-M., Saad, M.F., Association of leptin receptor polymorphism with insulin resistance (2004) European Journal of Endocrinology, 150 (5), pp. 725-729Chu, A., Chuang, L.M., Saad, M., Chiu, K., Association of the Q223R polymorphism of the leptin receptor gene with insulin resistance and metabolic syndrome (2003) Diabetes, 52, p. A510Pimentel Duarte, S.F., Francischetti, E.A., Genelhu-Abreu, V., P. Q223R leptin receptor polymorphism associated with obesity in Brazilianmultiethnic subjects (2006) The American Journal of Human Biology, 18 (4), pp. 448-453Wauters, M., Mertens, I., Chagnon, M., Polymorphisms in the leptin receptor gene, body composition and fat distribution in overweight and obese women (2001) International Journal of Obesity, 25 (5), pp. 714-720Ogawa, T., Hirose, H., Yamamoto, Y., Relationships between serum soluble leptin receptor level and serum leptin and adiponectin levels, insulin resistance index, lipid profile, and leptin receptor gene polymorphisms in the Japanese population (2004) Metabolism: Clinical and Experimental, 53 (7), pp. 879-885Fairbrother, U.L., Tankó, L.B., Walley, A.J., Christiansen, C., Froguel, P., Blakemore, A.I.F., Leptin receptor genotype at Gln223Arg is associated with body composition, BMD, and vertebral fracture in postmenopausal Danish women (2007) Journal of Bone and Mineral Research, 22 (4), pp. 544-550Salopuro, T., Pulkkinen, L., Lindström, J., Genetic variation in leptin receptor gene is associated with type 2 diabetes and body weight: The Finnish Diabetes Prevention Study (2005) International Journal of Obesity, 29 (10), pp. 1245-1251Wauters, M., Mertens, I., Rankinen, T., Chagnon, M., Bouchardt, C., Van Gaal, L., Leptin receptor gene polymorphisms are associated with insulin in obese women with impaired glucose tolerance (2001) Journal of Clinical Endocrinology and Metabolism, 86 (7), pp. 3227-3232Park, K.S., Shin, H.D., Park, B.L., Polymorphisms in the leptin receptor (LEPR)-putative association with obesity and T2DM (2006) Journal of Human Genetics, 51 (2), pp. 85-91Han, C.-Z., Du, L.-L., Jing, J.-X., Associations among lipids, leptin, and leptin receptor geneGin223Arg polymorphisms and breast cancer in China (2008) Biological Trace Element Research, 126 (1-3), pp. 38-48Okobia, M.N., Bunker, C.H., Garte, S.J., Leptin receptor Gln223Arg polymorphism and breast cancer risk in Nigerian women: A case control study (2008) BMC Cancer, 8He, B.-S., Pan, Y.-Q., Zhang, Y., Xu, Y.-Q., Wang, S.-K., Effect of LEPR Gln223Arg polymorphism on breast cancer risk in different ethnic populations: A meta-analysis (2012) Molecular Biology Reports, 39 (3), pp. 3117-3122Lin, D.W., Fitz Gerald, L.M., Fu, R., Genetic variants in the LEPR, CRY1, RNASEL, IL4, and ARVCF genes are prognostic markers of prostate cancer-specific mortality (2011) Cancer Epidemiology, Biomarkers & Prevention, 20 (9), pp. 1928-1936Li, Y.L., Geng, J.L., Wang, Y., The role of leptin receptor gene polymorphisms in determining the susceptibility and prognosis of NSCLC in Chinese patients (2012) Journal of Cancer Research and Clinical Oncology, 138 (2), pp. 311-316Wazir, U., Al Sarakbi, W., Jiang, W.G., Mokbel, K., Evidence of an autocrine role for leptin and leptin receptor in human breast cancer (2012) CancerGenomics and Proteomics, 9 (6), pp. 383-388Li, L., Lee, K.J., Choi, B.C., Baek, K.H., Relationshipbetween leptin receptor and polycystic ovary syndrome (2013) Gene, 527 (1), pp. 71-74Friedlander, Y., Li, G., Fornage, M., Candidate molecular pathway genes related to appetite regulatory neural network, adipocyte homeostasis and obesity: Results from the CARDIA Study (2010) Annals of Human Genetics, 74 (5), pp. 387-39

The southern photometric local universe survey (S-PLUS): Improved SEDs, morphologies, and redshifts with 12 optical filters

The Southern Photometric Local Universe Survey (S-PLUS) is imaging ~9300 deg2 of the celestial sphere in 12 optical bands using a dedicated 0.8mrobotic telescope, the T80-South, at the Cerro Tololo Inter-american Observatory, Chile. The telescope is equipped with a 9.2k × 9.2k e2v detector with 10 μm pixels, resulting in a field of view of 2 deg2 with a plate scale of 0.55 arcsec pixel-1. The survey consists of four main subfields, which include two non-contiguous fields at high Galactic latitudes (|b| > 30° , 8000 deg2) and two areas of the Galactic Disc and Bulge (for an additional 1300 deg2). S-PLUS uses the Javalambre 12-band magnitude system, which includes the 5 ugriz broad-band filters and 7 narrow-band filters centred on prominent stellar spectral features: the Balmer jump/[OII], Ca H + K, Hd, G band, Mg b triplet, Hα, and the Ca triplet. S-PLUS delivers accurate photometric redshifts (δz/(1 + z) = 0.02 or better) for galaxies with r < 19.7 AB mag and z < 0.4, thus producing a 3D map of the local Universe over a volume of more than 1 (Gpc/h)3. The final S-PLUS catalogue will also enable the study of star formation and stellar populations in and around the Milky Way and nearby galaxies, as well as searches for quasars, variable sources, and low-metallicity stars. In this paper we introduce the main characteristics of the survey, illustrated with science verification data highlighting the unique capabilities of S-PLUS. We also present the first public data release of ~336 deg2 of the Stripe 82 area, in 12 bands, to a limiting magnitude of r = 21, available at datalab.noao.edu/splus.Fil: De Oliveira, C. Mendes. Universidade do Sao Paulo. Instituto de Astronomia, Geofísica e Ciências Atmosféricas; BrasilFil: Ribeiro, T.. Universidade Federal de Sergipe; Brasil. National Optical Astronomy Observatory; Estados UnidosFil: Schoenell, W.. Universidade Federal do Rio Grande do Sul; BrasilFil: Kanaan, A.. Universidade Federal de Santa Catarina; BrasilFil: Overzier, R.A.. Universidade do Sao Paulo. Instituto de Astronomia, Geofísica e Ciências Atmosféricas; Brasil. Ministério da Ciência, Tecnologia, Inovação e Comunicações. Observatório Nacional; BrasilFil: Molino, A.. Universidade do Sao Paulo. Instituto de Astronomia, Geofísica e Ciências Atmosféricas; BrasilFil: Sampedro, L.. Universidade do Sao Paulo. Instituto de Astronomia, Geofísica e Ciências Atmosféricas; BrasilFil: Coelho, P.. Universidade do Sao Paulo. Instituto de Astronomia, Geofísica e Ciências Atmosféricas; BrasilFil: Barbosa, C.E.. Universidade do Sao Paulo. Instituto de Astronomia, Geofísica e Ciências Atmosféricas; BrasilFil: Cortesi, A.. Universidade do Sao Paulo. Instituto de Astronomia, Geofísica e Ciências Atmosféricas; BrasilFil: Costa Duarte, M.V.. Universidade do Sao Paulo. Instituto de Astronomia, Geofísica e Ciências Atmosféricas; BrasilFil: Herpich, F.R.. Universidade do Sao Paulo. Instituto de Astronomia, Geofísica e Ciências Atmosféricas; Brasil. Universidade Federal de Santa Catarina; BrasilFil: Hernandez Jimenez, J.A.. Universidade do Sao Paulo. Instituto de Astronomia, Geofísica e Ciências Atmosféricas; BrasilFil: Placco, V.M.. University of Notre Dame; Estados Unidos. JINA Center for the Evolution of the Elements ; Estados UnidosFil: Xavier, H.S.. Universidade do Sao Paulo. Instituto de Astronomia, Geofísica e Ciências Atmosféricas; BrasilFil: Abramo, L.R.. Universidade do Sao Paulo. Instituto de Astronomia, Geofísica e Ciências Atmosféricas; BrasilFil: Saito, R.K.. Universidade Federal de Santa Catarina; BrasilFil: Chies Santos, A.L.. Universidade Federal do Rio Grande do Sul; BrasilFil: Ederoclite, A.. Universidade do Sao Paulo. Instituto de Astronomia, Geofísica e Ciências Atmosféricas; Brasil. Centro de Estudios de Física del Cosmo de Aragon; EspañaFil: De Oliveira, R. Lopes. Universidade Federal de Sergipe; Brasil. Ministério da Ciência, Tecnologia, Inovação e Comunicações. Observatório Nacional; Brasil. University of Maryland; Estados UnidosFil: Goncalves, D.R.. Universidade Federal do Rio de Janeiro; BrasilFil: Akras, S.. Ministério da Ciência, Tecnologia, Inovação e Comunicações. Observatório Nacional; Brasil. Universidade Federal do Rio de Janeiro; BrasilFil: Almeida, L.A.. Universidade do Sao Paulo. Instituto de Astronomia, Geofísica e Ciências Atmosféricas; Brasil. Universidade Federal do Rio Grande do Norte; BrasilFil: Almeida Fernandes, F.. Universidade do Sao Paulo. Instituto de Astronomia, Geofísica e Ciências Atmosféricas; Brasil. Universidade Federal do Rio de Janeiro; BrasilFil: Beers, T.C.. University of Notre Dame; Estados Unidos. JINA Center for the Evolution of the Elements ; Estados UnidosFil: Bonatto, C.. Universidade Federal do Rio Grande do Sul; BrasilFil: Bonoli, S.. Centro de Estudios de Física del Cosmo de Aragon; EspañaFil: Cypriano, E.S.. Universidade do Sao Paulo. Instituto de Astronomia, Geofísica e Ciências Atmosféricas; BrasilFil: Vinicius Lima, E.. Universidade do Sao Paulo. Instituto de Astronomia, Geofísica e Ciências Atmosféricas; BrasilFil: Smith Castelli, Analia Viviana. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Astrofísica La Plata. Universidad Nacional de La Plata. Facultad de Ciencias Astronómicas y Geofísicas. Instituto de Astrofísica La Plata; Argentin