Biochemical Pathways Triggered by Antipsychotics in Human Oligodendrocytes: Potential of Discovering New Treatment Targets

Schizophrenia is a psychiatric disorder that affects more than 21 million people worldwide. It is an incurable disorder and the primary means of managing symptoms is through administration of pharmacological treatments, which consist heavily of antipsychotics. First-generation antipsychotics have the properties of D2 receptor antagonists. Second-generation antipsychotics are antagonists of both D2 and 5HT2 receptors. Recently, there has been increasing interest in the effects of antipsychotics beyond their neuronal targets and oligodendrocytes are one of the main candidates. Thus, our aim was to evaluate the molecular effects of typical and atypical drugs across the proteome of the human oligodendrocyte cell line, MO3.13. For this, we performed a mass spectrometry-based, bottom-up shotgun proteomic analysis to identify differences triggered by typical (chlorpromazine and haloperidol) and atypical (quetiapine and risperidone) antipsychotics. Proteins which showed changes in their expression levels were analyzed in silico using Ingenuity® Pathway Analysis, which implicated dysregulation of canonical pathways for each treatment. Our results shed light on the biochemical pathways involved in the mechanisms of action of these drugs, which may guide the identification of novel biomarkers and the development of new and improved treatments

Ovariectomy modifies lipid metabolism of retroperitoneal white fat in rats: a proteomic approach

Menopause is often accompanied by visceral obesity. With the aim of exploring the consequences of ovarian failure on visceral fat, we evaluated the effects of ovariectomy and estrogen replacement on the proteome/phosphoproteome and on the fatty acids profile of the retroperitoneal adipose depot (RAT) of rats. Eighteen three months old female Wistar rats were either ovariectomized or sham-operated and fed with standard chow for three months. A sub-group of ovariectomized rats received estradiol replacement. RAT samples were analyzed using data-independent acquisitions LC-MS/MS and pathway analysis was performed with the differentially expressed/phosphorylated proteins. RAT lipid profile was analyzed by gas chromatography. Ovariectomy induced high adiposity and insulin resistance and promoted alterations in protein expression and phosphorylation. Pathway analysis showed that 5 pathways were significantly affected by ovariectomy, namely metabolism of lipids (included fatty acid metabolism and mitochondrial fatty acid β-oxidation), fatty acyl-CoA biosynthesis, innate immune system (included neutrophil degranulation), metabolism of vitamins and cofactors, and integration of energy metabolism (included ChREBP activates metabolic gene expression). Lipid profile analysis showed increased palmitic and palmitoleic acids content. The analysis of the data indicated that ovariectomy favored lipogenesis while it impaired fatty acids oxidation, and induced a pro-inflammatory state in the visceral adipose tissue. These effects are consistent with the findings of high adiposity, hyperleptinemia, and impaired insulin sensitivity. The observed alterations were partially attenuated by estradiol replacement. The data point to a role of disrupted lipid metabolism in adipose tissue in the genesis of obesity after menopause

Trajetórias da Educomunicação nas Políticas Públicas e a Formação de seus Profissionais

Esta obra é composta com os trabalhos apresentados no primeiro subtema, TRAJETÓRIA – Educação para a Comunicação como Política pública, nas perspectivas da Educomunicação e da Mídia-Educação, do II Congresso Internacional de Comunicação e Educação. Os artigos pretendem propiciar trocas de informações e produzir reflexões com os leitores sobre os caminhos percorridos, e ainda a percorrer, tendo como meta a expansão e a legitimação das práticas educomunicativas e/ou mídia-educativas como política pública para o atendimento à formação de crianças, adolescentes, jovens e adultos, no Brasil e no mundo

Ion mobility-enhanced data-independent acquisitions enable a deep proteomic landscape of oligodendrocytes

Oligodendrocytes are a type of neuroglia that provide trophic support and insulation to axons in the central nervous system. The genesis and maturation of oligodendrocytes are essential processes for myelination and the course of CNS development. Using ion mobility-enhanced, data-independent acquisitions and 2D-nanoUPLC fractionation operating at nanoscale flow rates, we established a comprehensive data set of proteins expressed by the human oligodendroglia cell line MO3.13. The final dataset incorporating all fractions comprised 223 531 identified peptides assigned to 10 390 protein hits, an improvement of 4.5 times on identified proteins described previously by our group using the same cell line. Identified proteins play pivotal roles in many biological processes such as cell growth and development and energy metabolism, providing a rich resource for future studies on oligodendrocyte development, myelination, axonal support, and the regulation of such process. Our results can help further studies that use MO3.13 cells as a tool of investigation, not only in relation to oligodendrocyte maturation, but also to diseases that have oligodendrocytes as key players. All MS data have been deposited in the ProteomeXchange with identifier PXD0046961721CONSELHO NACIONAL DE DESENVOLVIMENTO CIENTÍFICO E TECNOLÓGICO - CNPQFUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULO - FAPESP460289/2014-42014/14881-1; 2015/23049-0; 2013/08711-3; 2014/10068-

The Penicillium brasilianum Histone Deacetylase Clr3 Regulates Secondary Metabolite Production and Tolerance to Oxidative Stress

Most of the biosynthetic gene clusters (BGCs) found in microbes are silent under standard laboratory cultivation conditions due to the lack of expression triggering stimuli, representing a considerable drawback in drug discovery. To access the full biosynthetic potential, studies towards the activation of cryptic BGCs are essential. Histone acetylation status is an important regulator of chromatin structure, which impacts cell physiology and the expression of BGCs. In this study, clr3, a gene encoding a histone deacetylase in Penicillium brasilianum LaBioMMi 136, is deleted and associated phenotypic and metabolic changes are evaluated. The results indicate reduced growth under oxidative stress conditions in the ∆clr3 strain, higher intracellular reactive oxygen species (ROS) levels, and a different transcriptional profile of 13 ROS-related genes of both strains under basal and ROS-induced conditions. Moreover, the production of 14 secondary metabolites, including austin-related meroterpenoids, brasiliamides, verruculogen, penicillic acid, and cyclodepsipeptides was evaluated in the ∆clr3 strain, most of them being reduced. Accordingly, the addition of epigenetic modulators responsible for HDAC inhibition into P. brasilianum’s growth media also culminated in the reduction in secondary metabolite production. The results suggest that Clr3 plays an essential role in secondary metabolite biosynthesis in P. brasilianum, thus offering new strategies for the regulation of natural product synthesis by assessing chromatin modification

Protein Succinylation and Malonylation as Potential Biomarkers in Schizophrenia

Two protein post-translational modifications, lysine succinylation and malonylation, are implicated in protein regulation, glycolysis, and energy metabolism. The precursors of these modifications, succinyl-CoA and malonyl-CoA, are key players in central metabolic processes. Both modification profiles have been proven to be responsive to metabolic stimuli, such as hypoxia. As mitochondrial dysfunction and metabolic dysregulation are implicated in schizophrenia and other psychiatric illnesses, these modification profiles have the potential to reveal yet another layer of protein regulation and can furthermore represent targets for biomarkers that are indicative of disease as well as its progression and treatment. In this work, data from shotgun mass spectrometry-based quantitative proteomics were compiled and analyzed to probe the succinylome and malonylome of postmortem brain tissue from patients with schizophrenia against controls and the human oligodendrocyte precursor cell line MO3.13 with the dizocilpine chemical model for schizophrenia, three antipsychotics, and co-treatments. Several changes in the succinylome and malonylome were seen in these comparisons, revealing these modifications to be a largely under-studied yet important form of protein regulation with broad potential applications

Effect of flexible family visitation on delirium among patients in the Intensive Care Unit: the ICU visits randomized clinical trial

Fernando Augusto Bozza. Fundação Oswaldo Cruz. Instituto Nacional de Infectologia Evandro Chagas. Documento produzido em parceria ou por autor vinculado à Fiocruz, mas não consta a informação no documento.Intensive Care Unit, Hospital Moinhos de Vento (HMV), Porto Alegre, Rio Grande do Sul, Brazil (Rosa, D. B. da Silva, Eugênio, Haack, Medeiros, Tonietto, Teixeira); Research Projects Office, HMV, Porto Alegre, Rio Grande do Sul, Brazil (Rosa, Falavigna, D. B. da Silva, Sganzerla, Santos, Kochhann, de Moura, Eugênio, Haack, Barbosa, Robinson, Schneider, de Oliveira, Jeffman, Medeiros, Hammes); Brazilian Research in Intensive Care Network (BRICNet), São Paulo, São Paulo (Rosa, Cavalcanti, Machado, Azevedo, Salluh, Nobre, Bozza, Teixeira); HCor Research Institute, São Paulo, São Paulo, Brazil (Cavalcanti); Department of Anesthesiology, Pain and Intensive Care, Universidade Federal de São Paulo (UNIFESP), São Paulo, São Paulo, Brazil (Machado); Intensive Care Unit, Hospital Sírio-Libanês, São Paulo, São Paulo, Brazil (Azevedo); Department of Critical Care, Instituto D’Or de Pesquisa e Ensino, Rio de Janeiro, Rio de Janeiro, Brazil (Salluh, Mesquita, Bozza); Intensive Care Unit, Hospital de Clínicas de Porto Alegre (HCPA), Porto Alegre, Rio Grande do Sul, Brazil (Pellegrini, Moraes); Intensive Care Unit, Hospital Santa Cruz, Santa Cruz do Sul, Rio Grande do Sul, Brazil (Foernges); Intensive Care Unit, Hospital Santa Rita, Porto Alegre, Rio Grande do Sul, Brazil (Torelly); Intensive Care Unit, Hospital Universitário do Oeste do Paraná, Cascavel, Paraná, Brazil (Ayres, Duarte); Intensive Care Unit, Hospital do Câncer de Cascavel, Cascavel, Paraná, Brazil (Duarte); Intensive Care Unit, Hospital das Clínicas, Faculdade de Medicina de Ribeirão Preto, Ribeirão Preto, São Paulo, Brazil (Lovato); Intensive Care Unit, Santa Casa de Misericórdia de Feira de Santana, Feira de Santana, Bahia, Brazil (Sampaio); Intensive Care Unit, Hospital Geral Clériston Andrade, Feira de Santana, Bahia, Brazil (de Oliveira Júnior); Intensive Care Unit, Santa Casa de Misericórdia de São João Del Rei, São João Del Rei, Minas Gerais, Brazil (Paranhos); Intensive Care Unit, Hospital Regional Doutor Deoclécio Marques de Lucena, Parnamirim, Rio Grande do Norte, Brazil (Dantas, de Brito); Intensive Care Unit, Fundação Hospital Adriano Jorge, Manaus, Amazonas, Brazil (Paulo); Intensive Care Unit, Hospital Agamenon Magalhães, Recife, Pernambuco, Brazil (Gallindo); Intensive Care Unit, Hospital da Cidade, Passo Fundo, Rio Grande do Sul, Brazil (Pilau); Intensive Care Unit, Hospital Mãe de Deus, Porto Alegre, Rio Grande do Sul, Brazil (Valentim); Intensive Care Unit, Hospital de Urgências de Goiânia, Goiânia, Goiânia, Brazil (Meira Teles); Intensive Care Unit, Hospital das Clínicas, Universidade Federal de Minas Gerais (UFMG), Belo Horizonte, Minas Gerais, Brazil (Nobre); Intensive Care Unit, Pavilhão Pereira Filho, Porto Alegre, Rio Grande do Sul, Brazil (Birriel); Intensive Care Unit, Hospital Regional do Baixo Amazonas, Santarém, Pará, Brazil (Corrêa e Castro); Intensive Care Unit, Hospital Nossa Senhora da Conceição, Porto Alegre, Rio Grande do Sul, Brazil (Specht); School of Medicine, Universidade Federal de Ciências da Saúde de Porto Alegre (UFCSPA), Porto Alegre, Rio Grande do Sul, Brazil (N. B. da Silva); Department of Public Health Sciences, Medical University of South Carolina, Charleston (Korte); Unit of Pediatric Anesthesia and Intensive Care, Ospedale dei Bambini—ASST Spedali Civili, Brescia, Italy (Giannini); Oswaldo Cruz Foundation (FIOCRUZ), Rio de Janeiro, Rio de Janeiro, Brazil (Bozza).Submitted by Janaína Nascimento ([email protected]) on 2019-09-11T14:37:38Z No. of bitstreams: 1 ve_Rosa_Regis_etal_INI_2019.pdf: 616825 bytes, checksum: 2aae5be305137324e272a08cc32e9270 (MD5)Approved for entry into archive by Janaína Nascimento ([email protected]) on 2019-09-11T14:52:11Z (GMT) No. of bitstreams: 1 ve_Rosa_Regis_etal_INI_2019.pdf: 616825 bytes, checksum: 2aae5be305137324e272a08cc32e9270 (MD5)Made available in DSpace on 2019-09-11T14:52:11Z (GMT). No. of bitstreams: 1 ve_Rosa_Regis_etal_INI_2019.pdf: 616825 bytes, checksum: 2aae5be305137324e272a08cc32e9270 (MD5) Previous issue date: 2019Múltipla - Ver em Notas.IMPORTANCE: The effects of intensive care unit (ICU) visiting hours remain uncertain. OBJECTIVE: To determine whether a flexible family visitation policy in the ICU reduces the incidence of delirium. DESIGN, SETTING AND PARTICIPANTS: Cluster-crossover randomized clinical trial involving patients, family members, and clinicians from 36 adult ICUs with restricted visiting hours (<4.5 hours per day) in Brazil. Participants were recruited from April 2017 to June 2018, with follow-up until July 2018. INTERVENTIONS: Flexible visitation (up to 12 hours per day) supported by family education (n = 837 patients, 652 family members, and 435 clinicians) or usual restricted visitation (median, 1.5 hours per day; n = 848 patients, 643 family members, and 391 clinicians). Nineteen ICUs started with flexible visitation, and 17 started with restricted visitation. MAIN OUTCOMES AND MEASURES: Primary outcome was incidence of delirium during ICU stay, assessed using the CAM-ICU. Secondary outcomes included ICU-acquired infections for patients; symptoms of anxiety and depression assessed using the HADS (range, 0 [best] to 21 [worst]) for family members; and burnout for ICU staff (Maslach Burnout Inventory). RESULTS: Among 1685 patients, 1295 family members, and 826 clinicians enrolled, 1685 patients (100%) (mean age, 58.5 years; 47.2% women), 1060 family members (81.8%) (mean age, 45.2 years; 70.3% women), and 737 clinicians (89.2%) (mean age, 35.5 years; 72.9% women) completed the trial. The mean daily duration of visits was significantly higher with flexible visitation (4.8 vs 1.4 hours; adjusted difference, 3.4 hours [95% CI, 2.8 to 3.9]; P < .001). The incidence of delirium during ICU stay was not significantly different between flexible and restricted visitation (18.9% vs 20.1%; adjusted difference, −1.7% [95% CI, −6.1% to 2.7%]; P = .44). Among 9 prespecified secondary outcomes, 6 did not differ significantly between flexible and restricted visitation, including ICU-acquired infections (3.7% vs 4.5%; adjusted difference, −0.8% [95% CI, −2.1% to 1.0%]; P = .38) and staff burnout (22.0% vs 24.8%; adjusted difference, −3.8% [95% CI, −4.8% to 12.5%]; P = .36). For family members, median anxiety (6.0 vs 7.0; adjusted difference, −1.6 [95% CI, −2.3 to −0.9]; P < .001) and depression scores (4.0 vs 5.0; adjusted difference, −1.2 [95% CI, −2.0 to −0.4]; P = .003) were significantly better with flexible visitation. CONCLUSIONS AND RELEVANCE: Among patients in the ICU, a flexible family visitation policy, vs standard restricted visiting hours, did not significantly reduce the incidence of delirium

ATLANTIC ANTS: a data set of ants in Atlantic Forests of South America

International audienc