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Made available in DSpace on 2022-05-01T06:31:27Z (GMT). No. of bitstreams: 0 Previous issue date: 2021-01-01 Cohabitation with a partner undergoing chronic pain induces pain hypersensitivity. Among a lot of other neurochemical pathways, the serotonin (5-HT) role, specifically the 5-HT3 receptor (5-HT3R), in the amygdala has never been evaluated in this model. Here we studied the effects of the amygdala’s chemical inhibition, its neuronal activation pattern, and 5-HT, 5-HIAA, and 5-HT turnover within the amygdala. Furthermore, the systemic and intra-amygdala 5-HT3R activation and blockade in mice that cohabited with a conspecific subjected to chronic constriction injury were investigated. Male Swiss mice were housed in partners for 28 days. The dyads were divided into two groups on the 14th day: cagemate nerve constriction (CNC) and cagemate sham (CS). On the 24th day, cagemates underwent a stereotaxic surgery (when necessary) and, on the 28th day, they were evaluated on the writhing test. The amygdala inactivation promotes pain-hypersensitivity behaviors in groups and dyads; cohabitation with a partner with chronic pain did not change FosB-labeled cells in the amygdala’s nucleus and increases 5-HT turnover in cagemates. Systemic and intra-amygdala 5-HT3R activation attenuated and enhanced the number of writhes, respectively. In contrast, 5-HT3R blockade reduced hypersensitivity pain response. Results suggest the involvement of amygdala serotonergic signaling via 5-HT3R in empathy-like behavior. Psychobiology Group Department of Psychology/CECH Universidade Federal de São Carlos - UFSCar Joint Graduate Program in Physiological Sciences UFSCar/UNESP Lab. Pharmacology School of Pharmaceutical Sciences Univ. Estadual Paulista - UNESP Neuroscience and Behavior Institute - IneC Program in Psychology UFSCar Joint Graduate Program in Physiological Sciences UFSCar/UNESP Lab. Pharmacology School of Pharmaceutical Sciences Univ. Estadual Paulista - UNESP

Aims B cell functions in the process of atherogenesis have been investigated but several aspects remain to be clarified., Methods and results In this study, we show that follicular regulatory helper T cells (T-FR) control regulatory B cell (B-REG) populations in Apoe(-/)(-) mice models on a high-cholesterol diet (HCD). Feeding mice with HCD resulted in up-regulation of T-FR and B-REG cell populations, causing the suppression of proatherogenic follicular helper T cell (T-FH) response. T-FH cell modulation is correlated with the growth of atherosclerotic plaque size in thoracoabdominal aortas and aortic root plaques, suggesting that T-FR cells are atheroprotective. During adoptive transfer experiments, T-FR cells transferred into HCD mice decreased T-FH cell populations, atherosclerotic plaque size, while B-REG cell population and lymphangiogenesis are significantly increased., Conclusion Our results demonstrate that, through different strategies, both T-FR and T-FH cells modulate anti- and proatherosclerotic immune processes in an Apoe(-/-) mice model since T-FR cells are able to regulate both T-FH and B-REG cell populations as well as lymphangiogenesis and lipoprotein metabolism., [GRAPHICS]

RESUMO Objetivo: Descrever a experiência de implementação de uma unidade satélite de vacinação em sistema drive-through, durante a campanha contra COVID-19. Método: Trata-se de um relato de experiência, realizado em uma unidade satélite de vacinação em sistema drive-through. O desenvolvimento do estudo foi norteado pela tríade estrutura-processo-resultados, proposta por Donabedian. Resultados: A unidade foi estruturada em um estádio de futebol, permitindo o atendimento de grandes públicos de forma segura. O fluxo de atendimento ocorreu por etapas, e os profissionais foram organizados por setores, com destaque para atuação da equipe de enfermagem. Inicialmente, realizou-se a triagem, posteriormente, o usuário dirigia-se ao setor de cadastramento, e, por fim, era encaminhado à estação de aplicação. A unidade contava também com os setores de urgência e emergência, rede de frio, espaço para os profissionais e uma Unidade Básica de Saúde como ponto de apoio. Em 25 dias de atuação, foram administradas 9698 doses, com 1,8% de doses perdidas. Conclusão: A implementação deste sistema exigiu planejamento, estrutura, desenvolvimento de processos e intensa articulação em equipe, com destaque para o papel fundamental e estratégico do enfermeiro em diferentes pontos de atuação e liderança.

Objective: To describe the experience of implementing a satellite vaccination unit in a drive-through system during a campaign against COVID-19. Method: This is an experience report carried out in a drive-through vaccination satellite unit. The study development was guided by the triad structure-process-results, proposed by Donabedian. Results: The unit was structured in a soccer stadium, allowing it to serve large audiences safely. Care flow occurred in stages and professionals were organized by sectors, with emphasis on the nursing team’ work. Initially, screening was performed; later, users went to the registration sector, and, finally, they were forwarded to the application station. The unit also had emergency sectors, a cold chain, space for professionals and a Basic Health Unit as a point of support. In 25 days of operation, 9698 doses were administered, with 1.8% of doses lost. Conclusion: The implementation of this system required planning, structure, process development and intense team articulation, with emphasis on the fundamental and strategic role of nurses in different points of action and leadership.

Background Although produced by several types of tumours, the role of serotonin on cancer biology is yet to be understood. Methods The effects of serotonin (5-HT) on human breast cancer cells proliferation, signalling pathways and metabolic profile were evaluated by cytometry, western blotting, qPCR, enzymology and confocal microscopy. Results Our results revealed that incubation of MCF-7 cells with 10 µM 5-HT increased cell growth rate by 28%, an effect that was prevented by the 5-HTR2A/C antagonist, ketanserin. Conversely, increasing concentrations of 5-HT promoted glucose consumption and lactate production by MCF-7 cells. We also showed that increased glucose metabolism is provoked by the upregulation of pyruvate kinase M2 (PKM2) isoform through 5-HTR2A/C-triggered activation of Jak1/STAT3 and ERK1/2 subcellular pathways. However, we noticed a decrease in the rate of produced lactate per consumed glucose as a function of the hormone concentration, suggesting a disruption of the Warburg effect. The latter effect is due to 5-HTR2A/C-dependent mitochondrial biogenesis and metabolism, which is triggered by adenylyl cyclase/PKA, enhancing the oxidation of lactate within these cells. Conclusions We showed that serotonin, through 5-HTR2A/C, interferes with breast cancer cells proliferation and metabolism by triggering two distinct signalling pathways: Jak1/STAT3 that boosts glycolysis through upregulation of PKM2, and adenylyl cyclase/PKA that enhances mitochondrial biogenesis.

The affective component of pain may be shared among conspecifics through emotional contagion, a form of empathic expression. In this sense, reverberation of negative emotions could generate distress behavioral responses, such as pathological anxiety. Evidences reported that amygdala and its benzodiazepine receptors are involved in perception of pain in others. However, relatively little is known about the neural processes underlying emotional contagion induced by pain observation. In the present study, we investigated the effects of midazolam, an allosteric GABAergic receptor agonist, in anxiety-like behaviors induced by cohabitation with cagemate submitted to sciatic nerve constriction. For this purpose, we administrated systemic (0.5, 1.0 and 2.0 mg/kg) and intra-amygdala midazolam injections (3.0 and 30.0 nmol) in observer cagemates before elevated plus-maze (EPM) evaluation. We found that mice subjected to nerve constriction and their observer cagemates increased anxiety-like behavior in the EPM. Further, systemically (1.0 and 2.0 mg/kg) and intra-amygdala administration of midazolam (3.0 and 30 nmol) reverse this anxiogenic effect. Collectively, these results suggest that social interaction with a cagemate under chronic pain produces anxiety-like responses that could be blocked through midazolam application.

Cohabitation with a partner undergoing chronic pain induces pain hypersensitivity. Among a lot of other neurochemical pathways, the serotonin (5-HT) role, specifically the 5-HT

The monoamine neurotransmitter serotonin (5-HT) modulates anxiety by its activity on 5-HT

Highlights • Intra-BLA ZIP, a cell-permeable inhibitor of aPKC, attenuated hyperalgesic priming induced by plantar incision in both sexes. • Priming upregulated aPKC in the BLA only in male mice. • Deficits in hyperalgesic priming were only seen in male Prkcz−/− mice. • Pep2m, a peptide that interferes GluA2 AMPA receptors, reduced priming in both male and female mice. • GluA2 expression was upregulated in the BLA of male and female primed mice. • GluA2 in the BLA is crucial for the initiation of both reflexive and affective pain-related behaviors in both sexes., Though sex differences in chronic pain have been consistently described in the literature, their underlying neural mechanisms are poorly understood. Previous work in humans has demonstrated that men and women differentially invoke distinct brain regions and circuits in coping with subjective pain unpleasantness. The goal of the present work was to elucidate the molecular mechanisms in the basolateral nucleus of the amygdala (BLA) that modulate hyperalgesic priming, a pain plasticity model, in males and females. We used plantar incision as the first, priming stimulus and prostaglandin E2 (PGE2) as the second stimulus. We sought to assess whether hyperalgesic priming can be prevented or reversed by pharmacologically manipulating molecular targets in the BLA of male or female mice. We found that administering ZIP, a cell-permeable inhibitor of aPKC, into the BLA attenuated aspects of hyperalgesic priming induced by plantar incision in males and females. However, incision only upregulated PKCζ/PKMζ immunoreactivity in the BLA of male mice, and deficits in hyperalgesic priming were seen only when we restricted our analysis to male Prkcz−/− mice. On the other hand, intra-BLA microinjections of pep2m, a peptide that interferes with the trafficking and function of GluA2-containing AMPA receptors, a downstream target of aPKC, reduced mechanical hypersensitivity after plantar incision and disrupted the development of hyperalgesic priming in both male and female mice. In addition, pep2m treatment reduced facial grimacing and restored aberrant behavioral responses in the sucrose splash test in male and female primed mice. Immunofluorescence results demonstrated upregulation of GluA2 expression in the BLA of male and female primed mice, consistent with pep2m findings. We conclude that, in a model of incision-induced hyperalgesic priming, PKCζ/PKMζ in the BLA is critical for the development of hyperalgesic priming in males, while GluA2 in the BLA is crucial for the expression of both reflexive and affective pain-related behaviors in both male and female mice in this model. Our findings add to a growing body of evidence of sex differences in molecular pain mechanisms in the brain.

Made available in DSpace on 2021-06-25T11:16:07Z (GMT). No. of bitstreams: 0 Previous issue date: 2021-07-01 Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) Mice cohabiting with a conspecific in chronic pain display anxiogenesis in the elevated plus-maze (EPM). Given that the anterior cingulate (ACC) and insular (InC) cortices play a role in the modulation of anxiety, pain, and emotional contagion, we investigated (a) the FosB activation in both brain areas and (b) the effects of intra-ACC or -InC injection of cobalt chloride (CoCl2, a synaptic blocker), on the anxiety of mice cohabiting with a cagemate suffering pain. Twenty-one days after birth, male Swiss mice were housed in pairs for 14 days to establish familiarity. On the 14th day, mice were divided into two groups: cagemate sciatic nerve constriction (CNC; i.e., one animal of each pair was subjected to sciatic nerve constriction), and cagemate sham (CS; i.e., a similar procedure but without suffering nerve constriction). After that, both groups were housed again with the same pairs for the other 14 days. On the 28th day, mice had their brains removed for the immunoassays analyses (Exp. 1). For experiments 2 and 3, on the 23rd day, the cagemates received guide cannula implantation bilaterally in the ACC or InC and, on the 28th day, they received local injections of saline or CoCl2, and then were exposed to the EPM. Results showed that cohabitation with a conspecific with chronic pain decreases and increases neuronal activation (FosB) within the ACC and InC, respectively. Intra-ACC or InC injection of CoCl2 reversed the anxiogenic effect in those animals that cohabited with a conspecific in chronic pain. ACC and InC seem to modulate anxiety induced by emotional contagion in animals cohabitating with a conspecific suffering pain. Psychobiology Group/Department of Psychology/CECH - Universidade Federal de São Carlos - UFSCar, São Carlos, SP Graduate Program in Psychology/CECH - UFSCar, Rod. Washington Luís, km 235, São Carlos, SP Lab. Pharmacology School of Pharmaceutical Sciences Univ. Estadual Paulista – UNESP, SP Joint Graduate Program in Physiological Sciences UFSCar/UNESP, Rod. Washington Luís, km 235, São Carlos, SP Institute of Neuroscience and Behavior, Av. do Café, 2.450Ribeirão Preto, SP Lab. Pharmacology School of Pharmaceutical Sciences Univ. Estadual Paulista – UNESP, SP Joint Graduate Program in Physiological Sciences UFSCar/UNESP, Rod. Washington Luís, km 235, São Carlos, SP

Anti-apolipoprotein A-1 (anti-apoA-1 IgG) and anti-double stranded DNA (anti-dsDNA IgG) autoantibodies have been described as mediators of atherogenesis in mice and humans. In the present study, we aim to investigate the association between atherosclerotic parameters, autoantibodies and plaque vulnerability in the context of systemic lupus erythematosus (SLE). We therefore bred a lupus prone-mouse model (Nba2.Yaa mice) with Apoe−/− mice resulting in Apoe−/−Nba2.Yaa mice spontaneously producing anti-apoA-1 IgG antibodies. Although Apoe−/−Nba2.Yaa and Apoe−/− mice subject to a high cholesterol diet displayed similar atherosclerosis lesions size in aortic roots and abdominal aorta, the levels of macrophage and neutrophil infiltration, collagen, MMP-8 and MMP-9 and pro-MMP-9 expression in Apoe−/−Nba2.Yaa mice indicated features of atherosclerotic plaque vulnerability. Even though Apoe−/−Nba2.Yaa mice and Apoe−/− mice had similar lipid levels, Apoe−/−Nba2.Yaa mice showed higher anti-apoA-1 and anti-dsDNA IgG levels. Apoe−/−Nba2.Yaa mice displayed a reduction of the size of the kidney, splenomegaly and lymph nodes (LN) hypertrophy. In addition, anti-apoA-1 and anti-dsDNA IgG increased also in relation with mRNA levels of GATA3, IL-4, Bcl-6 and CD20 in the spleen and aortic arch of Apoe−/−Nba2.Yaa mice. Our data show that although atherosclerosis-lupus-prone Apoe−/−Nba2.Yaa mice did not exhibit exacerbated atherosclerotic lesion size, they did show features of atherosclerotic plaque destabilization in correlation with the increase of pro-atherogenic autoantibodies.

Background: Neutrophils accumulate in atherosclerotic plaques. Neutrophil extracellular traps (NET) were recently identified in experimental atherosclerosis and in complex human lesions. However, not much is known about the NET marker citrullinated histone-3 (H3Cit) expression and functionality in human carotid plaques. Moreover, the association between the proatherosclerotic autoantibody anti-apolipoprotein A-1 (anti-ApoA-1 IgG) and NET has never been investigated. Methods: Atherosclerotic plaques have been obtained from 36 patients with severe carotid stenosis that underwent carotid endarterectomy for severe carotid stenosis. Samples were sectioned into upstream and downstream regions from the same artery segment. Plaque composition and expression of NET markers neutrophil elastase (NE) and H3Cit were quantified by immunohistochemistry. H3Cit expression and function was evaluated by immunofluorescence and confocal analysis in a subset of patients. Results: Pathological features of vulnerable phenotypes were exacerbated in plaques developed at downstream regions, including higher accumulation of neutrophils and enhanced expression of NE and H3Cit, as compared to plaques from upstream regions. The H3Cit signal was also more intense in downstream regions, with significant extracellular distribution in spaces outside of neutrophils. The percentage of H3Cit colocalization with CD66b (neutrophils) was markedly lower in downstream portions of carotid plaques, confirming the extrusion of NET in this region. In agreement, the maximum distance of the H3Cit signal from neutrophils, extrapolated from vortex distance calculation in all possible directions, was also higher in downstream plaques. The serum anti-ApoA-1index positively correlated with the expression of H3Cit in downstream segments of plaques. Expression of the H3Cit signal outside of neutrophils and H3Cit maximal distance from CD66b-positive cells increased in plaques from serum positive anti-ApoA-1 patients compared with serum negative patients. Conclusion: NET elements are differentially expressed in upstream versus downstream regions of human carotid plaques and may be influenced by circulating levels of anti-ApoA-1 IgG. These findings could warrant the investigation of NET elements as potential markers of vulnerability.

Made available in DSpace on 2022-05-01T10:18:59Z (GMT). No. of bitstreams: 0 Previous issue date: 2022-02-01 Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) Neurobiology of social contagion/empathy aims to collaborate with the development of treatments for human disorders characterized by the absence of this response – autism spectrum disorder, schizophrenia, and antisocial personality disorder. Previous studies using sustained aversive stimuli (e.g., neuropathic pain or stress) to induce social contagion behaviors in rodents have demonstrated that these conditions may increase hypernociception, anxiogenic-like effects, and defensive behaviors in cagemates. To amplify the knowledge about behavioral, hormonal, and neural alterations induced by cohabitation with a pair in neuropathic pain, we investigated the effects of this protocol on (i) pain (writhing, formalin, hot plate tests) and depression (sucrose splash test) responses, (ii) the serum levels of corticosterone, testosterone, and oxytocin, (iii) noradrenalin, dopamine and its metabolite (DOPAC and HVA) levels in the amygdaloid complex and insular cortex, (iv) neuronal activation pattern (FosB labeling) in the ventral tegmental area (VTA), paraventricular nucleus of the hypothalamus (PVN) and supraoptic nucleus (SO). One day after weaning, male Swiss mice were housed in pairs for 14 days. Then, they were divided into two groups: sciatic nerve constricted cagemate [CNC; i.e., one animal of each pair was subjected to sciatic nerve constriction (NC)], and cagemate sham (CS; a similar procedure but with no nerve constriction), and housed for further 14 days. After 28 days of cohabiting, four independent groups were subjected to (a) behavioral analyses (Exp. 1) and (b) blood samples collected for Elisa assays of corticosterone, testosterone, and oxytocin (Exp. 2), remotion of brains for the (c) HPLC in the noradrenaline dopamine and metabolites quantification (Exp. 3) or (d) immunoassays analyses for FosB labeling (Exp. 4). Results showed that cohabitation with a conspecific in chronic pain induces hypernociception and antinociception in the writhing and formalin tests, respectively, and anhedonic-like effects in the sucrose splash test. Hormonal results indicated a decrease in plasma corticosterone only in nerve constricted mice, in testosterone (CNC and NC animals), and an increase in oxytocin serum levels. The neurochemical analyses demonstrated that the social contagion for pain protocol increases in dopamine turnover in the amygdala and insula. This assay also revealed an increase in noradrenaline levels and dopamine turnover within the insula of NC mice. In the FosB labeling measure, we observed a rise in the VTA, PVN and SO in the CNC group whereas for the NC group an increase of this activation pattern occurred only in the VTA. Present results suggest the role of hormones (testosterone and oxytocin) and neurotransmitters (dopamine) in the modulation of behavioral changes induced by social contagion in animals cohabitating with a conspecific in pain. Psychobiology Group/Department of Psychology/CECH - UFSCar Graduate Program in Psychology UFSCar, Rod. Washington Luís, km 235 Lab. Pharmacology School of Pharmaceutical Sciences Univ. Estadual Paulista – UNESP Joint Graduate Program in Physiological Sciences UFSCar/UNESP, Rod. Washington Luís, km 235 Institute of Neuroscience and Behavior, Av. do Café, 2.450 Lab. Pharmacology School of Pharmaceutical Sciences Univ. Estadual Paulista – UNESP Joint Graduate Program in Physiological Sciences UFSCar/UNESP, Rod. Washington Luís, km 235 CNPq: 153163/2016–0 FAPESP: 2017/25409–0 CNPq: 306556/2015–4 CNPq: 309201/2015–2 CNPq: 482356/2013–8

Made available in DSpace on 2022-04-28T19:44:52Z (GMT). No. of bitstreams: 0 Previous issue date: 2022-01-24 Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) The monoamine neurotransmitter serotonin (5-HT) modulates anxiety by its activity on 5-HT2C receptors (5-HT2CR) expressed in the dorsal periaqueductal gray (dPAG). Here, we investigated the presence of 5-HT3A receptors (5-HT3AR) in the dPAG, and the interplay between 5-HT2CR and 5-HT3AR in the dPAG in mediating anxiety-like behavior in mice. We found that 5-HT3AR is expressed in the dPAG and the blockade of these receptors using intra-dPAG infusion of ondansetron (5-HT3AR antagonist; 3.0 nmol) induced an anxiogenic-like effect. The activation of 5-HT3ABR by the infusion of mCPBG [1-(m-Chlorophenyl)-biguanide; 5-HT3R agonist] did not alter anxiety-like behaviors. In addition, blockade of 5-HT3AR (1.0 nmol) prevented the anxiolytic-like effect induced by the infusion of the 5-HT2CR agonist mCPP (1-(3-chlorophenyl) piperazine; 0.03 nmol). None of the treatment effects on anxiety-like behaviors altered the locomotor activity levels. The present results suggest that the anxiolytic-like effect exerted by serotonin activity on 5-HT2CR in the dPAG is modulated by 5-HT3AR expressed in same region. Psychobiology Group/Department of Psychology/CECH–UFSCar Joint Graduate Program in Physiological Sciences UFSCar/UNESP, Rod. Washington Luís, Km 235 Graduate Program in Psychology UFSCar, Rod. Washington Luís, Km 235 Laboratory of Pharmacology School of Pharmaceutical Sciences Univ. Estadual Paulista UNESP Neuroscience and Behavioral Institute, Av. do Café, 2.450 Department of Physiology and Pharmacology Hotchkiss Brain Institute The University of Calgary The University of Texas at Dallas School of Behavior and Brain Sciences, 800 West Campbell Road The University of Texas at Dallas Texas Biomedical Device Center, 800 West Campbell Road Joint Graduate Program in Physiological Sciences UFSCar/UNESP, Rod. Washington Luís, Km 235 Laboratory of Pharmacology School of Pharmaceutical Sciences Univ. Estadual Paulista UNESP FAPESP: 2016/08665-0 CNPq: 88887.194785/2018-00

Made available in DSpace on 2018-12-11T17:38:26Z (GMT). No. of bitstreams: 0 Previous issue date: 2018-09-15 Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) The confinement of rodents to the open arm of the elevated-plus maze provokes antinociception (OAA). As a type of defensive reaction, the OAA has been investigated through systemic and intramesencephalic (e.g., dorsal portion of the periaqueductal gray – dPAG) injections of anxiolytic-like drugs [e.g., serotonergic (5-HT) receptor agonists or antagonists]. Here we investigated the effects of (i) intra-dPAG injections of a 5HT2C receptor agonist (MK-212; 0.21 or 0.63 nmol) and antagonist (SB 242084; 0.01, 0.1 or 1.0 nmol); (ii) combined injections of SB 242084 and MK-212 into the dPAG; (iii) combined injections of SB 242084 with 8-OHDPAT (10 nmol) into the dPAG on the OAA in male Swiss mice. Nociception was assessed with the writhing test induced by acetic acid injection. Results showed that (i) intra-dPAG injection of MK-212 (0.63 nmol) increased the OAA; (ii) intra-dPAG SB 242084 (1.0 nmol) prevented the OAA; (iii) SB 242084 (0.1 nmol, a dose devoid of intrinsic effect on nociception) blocked the OAA enhancement provoked by MK-212 and enabled 8-OH-DPAT to prevent the OAA. These results suggest that OAA is mediated by 5-HT2C receptors within the dPAG. Intra-dPAG SB242084 administration provoked similar results on the effects produced by MK-212 and 8-OH-DPAT on OAA. In addition, the dPAG 5-HT1A and 5-HT2C receptors interact each other in the modulation of OAA. Dept. Psychology Federal University of São Carlos-UFSCar Lab. Pharmacology School of Pharmaceutical Sciences Univ. Estadual Paulista – UNESP Joint Graduate Program in Physiological Sciences UFSCar/UNESP Graduate Program in Psychology UFSCar, Rod. Washington Luís, Km 235 Institute of Neuroscience and Behavior, Av. Do Café 2.450 Lab. Pharmacology School of Pharmaceutical Sciences Univ. Estadual Paulista – UNESP Joint Graduate Program in Physiological Sciences UFSCar/UNESP FAPESP: 2009/17938-6 FAPESP: 2010/06654-4 FAPESP: 2011/19472-4 CNPq: 306556/2015-4 CNPq: 309201/2015-2 CNPq: 482356/2013-8

Made available in DSpace on 2018-12-11T16:52:40Z (GMT). No. of bitstreams: 0 Previous issue date: 2018-06-01 Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) It is well-known that the exposure of rodents to threatening environments [e.g., the open arm of the elevated-plus maze (EPM)] elicits pain inhibition. Systemic and/or intracerebral [e.g., periaqueductal gray matter, amygdala) injections of antiaversive drugs [e.g., serotonin (5-HT) ligands, selective serotonin reuptake inhibitors (SSRIs)] have been used to change EPM-open arm confinement induced antinociception (OAA). Here, we investigated (i) the role of the 5-HT1A and 5-HT2C receptors located in the amygdaloid complex on OAA as well as (ii) the effects of systemic pretreatment with fluoxetine (an SSRI) on the effects of intra-amygdala injections of 8-OH-DPAT (a 5-HT1A agonist) or MK-212 (a 5-HT2C agonist) on nociception in mice confined to the open arm or enclosed arm of the EPM. Nociception was assessed by the writhing test. Intra-amygdala injections of 8-OH-DPAT (10 nmol) or MK-212 (0.63 nmol) produced a pronociceptive effect and intensified OAA, respectively. Fluoxetine (2.5 mg/kg, intraperitoneally) did not change 8-OH-DPAT effects on nociception but antagonized the enhancement of the OAA produced by MK-212. Interestingly, prior injection of SB 242084 (a selective 5-HT2C antagonist) into the amygdala also blocked the MK-212 effects on OAA. These results indicate that 5-HT may facilitate nociception and intensify OAA, respectively, at 5-HT1A and 5-HT2C receptors located in the amygdala of mice. The impairment produced by systemic fluoxetine on the OAA enhancement provoked by intra-amygdala MK-212 suggests that this type of fear-induced antinociception may be modulated by SSRIs. Psychobiology Group Department of Psychology/CECH- Federal University of São Carlos-UFSCar Joint Graduate Program in Physiological Sciences UFSCar/UNESP Neuroscience and Behavioral Institute-IneC Program in Psychology UFSCar Joint Graduate Program in Physiological Sciences UFSCar/UNESP CAPES: 482356/2013-8 FAPESP: 2009/17938-6 CNPq: 309201/2015-2

A realização do projeto consiste em estabelecer uma relação entre texto e imagem na obra literária Livro de Mágoas, de Florbela Espanca. Considerada uma das poetisas mais importantes de Portugal, destaca-se pela sua obra carregada de feminismo, simbolismo, sentimento e crítica social relativamente ao papel da Mulher portuguesa do início do século XX. Através da ilustração conceptual, são representados visualmente os seus poemas. Um livro ilustrado e o diagrama cronológico da vida e obra de Florbela Espanca têm o objetivo de reconhecer, valorizar e engrandecer a sua obra. Conclui-se que para a concretização de um projeto ilustrativo existem diversos passos que devem ser implementados, desde a criação de ideias até à representação visual, através de um processo conceptual, da linguagem visual, a técnica e a produção. Além disto, demonstra-se como é possível integrar uma causa social através da poesia ilustrada, proporcionando um enriquecimento visual da obra da poetisa. The achievement of this project consists in establishing a relation between text and image, in the literary work Livro de Mágoas, by Florbela Espanca. Considered one of Portugal's most important poets, she stands out for her work loaded with feminism, symbolism, feelings and social criticism in the role of Women of the early twentieth centur in Portugal. Through conceptual illustration, her poems are visually represented, through an illustrated book and a chronological diagram of the life and work of Florbela Espanca, with the purpose of recognizing, enriching, and enhancing her work. It is concluded that, for the accomplishment of an illustration project, there are several steps that must be implemented, from the creation of ideas to the visual representation through a conceptual process, visual language, technique and production. In addition, it is demonstrated how it is possible to integrate a social cause through illustrated poetry, providing a visual enrichment of the work of the poet.

Publisher's version (útgefin grein)., Increased levels of the urinary albumin-to-creatinine ratio (UACR) are associated with higher risk of kidney disease progression and cardiovascular events, but underlying mechanisms are incompletely understood. Here, we conduct trans-ethnic (n = 564,257) and European-ancestry specific meta-analyses of genome-wide association studies of UACR, including ancestry- and diabetes-specific analyses, and identify 68 UACR-associated loci. Genetic correlation analyses and risk score associations in an independent electronic medical records database (n = 192,868) reveal connections with proteinuria, hyperlipidemia, gout, and hypertension. Fine-mapping and trans-Omics analyses with gene expression in 47 tissues and plasma protein levels implicate genes potentially operating through differential expression in kidney (including TGFB1, MUC1, PRKCI, and OAF), and allow coupling of UACR associations to altered plasma OAF concentrations. Knockdown of OAF and PRKCI orthologs in Drosophila nephrocytes reduces albumin endocytosis. Silencing fly PRKCI further impairs slit diaphragm formation. These results generate a priority list of genes and pathways for translational research to reduce albuminuria., Competing interests: Karsten B. Sieber is full-time employee of GlaxoSmithKline. Gardar Sveinbjornsson, Daniel F. Gudbjartsson, Hilma Holm, Unnur Thorsteinsdottir and Kari Stefansson are full-time employees of deCODE genetics, Amgen Inc. John Danesh is member of the Novartis Cardiovascular and Metabolic Advisory Board, received grant support from Novartis. Oscar H. Franco works in ErasmusAGE, a center for aging research across the life course funded by Nestlé Nutrition (Nestec Ltd.), Metagenics Inc., and AXA. Wolfgang Koenig received modest consultation fees for advisory board meetings from Amgen, DalCor, Kowa, Novartis, Pfizer and Sanofi, and modest personal fees for lectures from Amgen, AstraZeneca, Novartis, Pfizer and Sanofi. Anna I. Podgornaia and Dermot F. Reilly are employees of Merck Sharp Dohme Corp., Whitehouse Station, NJ, USA. Kevin Ho disclosed a research and financial relationship with Sanofi-Genzyme. Bruce M. Psaty serves on the DSMB of a clinical trial funded by the manufacturer (Zoll LifeCor) and on the Steering Committee of the Yale Open Data Access Project funded by Johnson & Johnson. Markus Scholz: Consultancy of and grant support from Merck Serono not related to this project. Adam S. Butterworth received grants from MSD, Pfizer, Novartis, Biogen and Bioverativ and personal fees from Novartis. Anna Köttgen received grant support from Gruenenthal not related to this project. The other authors declare no competing interests.

The confinement of rodents to the open arm of the elevated-plus maze provokes antinociception (OAA). As a type of defensive reaction, the OAA has been investigated through systemic and intramesencephalic (e.g., dorsal portion of the periaqueductal gray - dPAG) injections of anxiolytic-like drugs [e.g., serotonergic (5-HT) receptor agonists or antagonists]. Here we investigated the effects of (i) intra-dPAG injections of a 5HT

Atherosclerosis is a chronic inflammatory disease involving the infiltration of immune cells, such as monocytes/macrophages, neutrophils, T cells, and B cells, into the inner layer of vessel walls. T and B cell functions in the process of atherogenesis, as well as their mutual regulation, have been investigated but several aspects remain to be clarified. In the present review, we give a brief overview of the functions of follicular regulatory T cell (Tfr) on follicular T (Tfh) and B cell regulation related to atherosclerosis pathogenesis, including their influence on lymphangiogenesis and lipoprotein metabolism. We will also discuss their potential therapeutics properties in the resolution of established atherosclerotic lesions. Tfr cells are key regulators of atherosclerosis through regulation of Tfh cell population, inducing expansion of atheroprotective Breg cell population and stimulating lymphangiogenesis.

Contains fulltext : 184156.pdf (Publisher’s version ) (Closed access) Magnesium (Mg(2+)) homeostasis is critical for metabolism. However, the genetic determinants of the renal handling of Mg(2+), which is crucial for Mg(2+) homeostasis, and the potential influence on metabolic traits in the general population are unknown. We obtained plasma and urine parameters from 9099 individuals from seven cohorts, and conducted a genome-wide meta-analysis of Mg(2+) homeostasis. We identified two loci associated with urinary magnesium (uMg), rs3824347 (P=4.4x10(-13)) near TRPM6, which encodes an epithelial Mg(2+) channel, and rs35929 (P=2.1x10(-11)), a variant of ARL15, which encodes a GTP-binding protein. Together, these loci account for 2.3% of the variation in 24-hour uMg excretion. In human kidney cells, ARL15 regulated TRPM6-mediated currents. In zebrafish, dietary Mg(2+) regulated the expression of the highly conserved ARL15 ortholog arl15b, and arl15b knockdown resulted in renal Mg(2+) wasting and metabolic disturbances. Finally, ARL15 rs35929 modified the association of uMg with fasting insulin and fat mass in a general population. In conclusion, this combined observational and experimental approach uncovered a gene-environment interaction linking Mg(2+) deficiency to insulin resistance and obesity. 01 januari 2018

It is well-known that the exposure of rodents to threatening environments [e.g., the open arm of the elevated-plus maze (EPM)] elicits pain inhibition. Systemic and/or intracerebral [e.g., periaqueductal gray matter, amygdala) injections of antiaversive drugs [e.g., serotonin (5-HT) ligands, selective serotonin reuptake inhibitors (SSRIs)] have been used to change EPM-open arm confinement induced antinociception (OAA). Here, we investigated (i) the role of the 5-HT