The role of the CNR1 gene in schizophrenia: a systematic review including unpublished data

Objective: Schizophrenia is a multifactorial disorder. It is known that a combination of extensive multiple common alleles may be involved in its etiology, each contributing with a small to moderate effect, and, possibly, some rare alleles with a much larger effect size. We aimed to perform a systematic review of association studies between schizophrenia (and its subphenotypes) and polymorphisms in the CNR1 gene, which encodes cannabinoid receptors classically implicated in schizophrenia pathophysiology, as well as to present unpublished results of an association study in a Brazilian population. Methods: Two reviewers independently searched for eligible studies and extracted outcome data using a structured form. Papers were retrieved from PubMed and ISI Web of Knowledge using the search term schizophrenia in combination with CNR1 or CB1 or cannabinoid receptor. Twenty-four articles met our inclusion criteria. We additionally present data from a study of our own comparing 182 patients with schizophrenia and 244 healthy controls. Results: No consistent evidence is demonstrated. Conclusion: Some seemingly positive association studies stress the need for further investigations of the possible role of endocannabinoid genetics in schizophrenia.Fundacao de Amparo e Pesquisa do Estado de Sao Paulo (FAPESP) [2010/08968-6, 2011/50740-5, 2011/00030-1]Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPq)FAPESPCNPqCoordenacao de Aperfeicoamento de Pessoal de Nivel Superior (CAPES)Fundacao SafraFundacao ABADSUniv Fed Sao Paulo UNIFESP, Dept Psiquiatria, Sao Paulo, SP, BrazilUniv Fed Sao Paulo, Lab Interdisciplinar Neurociencias Clin LiNC, Sao Paulo, SP, BrazilIrmandade Santa Casa Misericordia Sao Paulo, Dept Psiquiatria, Sao Paulo, SP, BrazilUniv Fed Sao Paulo, Dept Morfol & Genet, Sao Paulo, SP, BrazilUniv Fed Sao Paulo UNIFESP, Dept Psiquiatria, Sao Paulo, SP, BrazilUniv Fed Sao Paulo, Lab Interdisciplinar Neurociencias Clin LiNC, Sao Paulo, SP, BraziWeb of Scienc

Untargeted Metabolomics Reveals Antidepressant Effects in a Marine Photosynthetic Organism: The Diatom Phaeodactylum tricornutum as a Case Study

The increased use of antidepressants, along with their increased occurrence in aquatic environments, is of concern for marine organisms. Although these pharmaceutical compounds have been shown to negatively affect marine diatoms, their mode of action in these non-target, single-cell phototrophic organisms is yet unknown. Using a Fourier-transform ion cyclotron-resonance mass spectrometer (FT-ICR-MS) we evaluated the effects of fluoxetine in the metabolomics of the model diatom Phaeodactylum tricornutum, as well as the potential use of the identified metabolites as exposure biomarkers. Diatom growth was severely impaired after fluoxetine exposure, particularly in the highest dose tested, along with a down-regulation of photosynthetic and carbohydrate metabolisms. Notably, several mechanisms that are normally down-regulated by fluoxetine in mammal organisms were also down-regulated in diatoms (e.g., glycerolipid metabolism, phosphatidylinositol signalling pathway, vitamin metabolism, terpenoid backbone biosynthesis and serotonin remobilization metabolism). Additionally, the present work also identified a set of potential biomarkers of fluoxetine exposure that were up-regulated with increasing fluoxetine exposure concentration and are of high metabolic significance following the disclosed mode of action, reinforcing the use of metabolomics approaches in ecotoxicology.info:eu-repo/semantics/publishedVersio

Description of a Prospective 17DD Yellow Fever Vaccine Cohort in Recife, Brazil

From September 2005 to March 2007, 238 individuals being vaccinated for the first time with the yellow fever (YF) -17DD vaccine were enrolled in a cohort established in Recife, Brazil. A prospective study indicated that, after immunization, anti-YF immunoglobulin M (IgM) and anti-YF IgG were present in 70.6% (IgM) and 98.3% (IgG) of the vaccinated subjects. All vaccinees developed protective immunity, which was detected by the plaque reduction neutralization test (PRNT) with a geometric mean titer of 892. Of the 238 individuals, 86.6% had IgG antibodies to dengue virus; however, the presence of anti-dengue IgG did not interfere significantly with the development of anti-YF neutralizing antibodies. In a separate retrospective study of individuals immunized with the 17DD vaccine, the PRNT values at 5 and 10 years post-vaccination remained positive but showed a significant decrease in neutralization titer (25% with PRNT titers < 100 after 5 years and 35% after 10 years)

Contemporary specificities of labour in the health care sector: introductory notes for discussion

BACKGROUND: This paper combines the literature on public health, on economics of health and on economics of technological innovation to discuss the peculiarities of labour in the health care sector. METHOD AND FRAMEWORK: The starting point is the investigation of the economic peculiarities of medical care. RESULTS AND DISCUSSIONS: This investigation leads to the identification of the prevalence of non-market forms of medical care in the countries of the Organisation for Economic Co-operation and Development (OECD). Furthermore, the health care system has a distinctive characteristic from other economic sectors: it is the intersection between social welfare and innovation systems. The relationship between technological innovation and cost in the health care sector is surveyed. Finally, the Brazilian case is discussed as an example of a developing country. CONCLUSION: The peculiarities of labour in the health care sector suggest the need to recognize the worth of sectoral labour and to cease to treat it separately. This process should take into account the rapid development of the health innovation system and one important consequence: the obsolescence of the acquired knowledge. One way to dignify labour is to implement continued education and training of health professions personnel

Parasitoid Increases Survival of Its Pupae by Inducing Hosts to Fight Predators

Many true parasites and parasitoids modify the behaviour of their host, and these changes are thought to be to the benefit of the parasites. However, field tests of this hypothesis are scarce, and it is often unclear whether the host or the parasite profits from the behavioural changes, or even if parasitism is a cause or consequence of the behaviour. We show that braconid parasitoids (Glyptapanteles sp.) induce their caterpillar host (Thyrinteina leucocerae) to behave as a bodyguard of the parasitoid pupae. After parasitoid larvae exit from the host to pupate, the host stops feeding, remains close to the pupae, knocks off predators with violent head-swings, and dies before reaching adulthood. Unparasitized caterpillars do not show these behaviours. In the field, the presence of bodyguard hosts resulted in a two-fold reduction in mortality of parasitoid pupae. Hence, the behaviour appears to be parasitoid-induced and confers benefits exclusively to the parasitoid

Alternative Complement Pathway Deregulation Is Correlated with Dengue Severity

BACKGROUND:The complement system, a key component that links the innate and adaptive immune responses, has three pathways: the classical, lectin, and alternative pathways. In the present study, we have analyzed the levels of various complement components in blood samples from dengue fever (DF) and dengue hemorrhagic fever (DHF) patients and found that the level of complement activation is associated with disease severity. METHODS AND RESULTS:Patients with DHF had lower levels of complement factor 3 (C3; p = 0.002) and increased levels of C3a, C4a and C5a (p<0.0001) when compared to those with the less severe form, DF. There were no significant differences between DF and DHF patients in the levels of C1q, immunocomplexes (CIC-CIq) and CRP. However, small but statistically significant differences were detected in the levels of MBL. In contrast, the levels of two regulatory proteins of the alternative pathway varied widely between DF and DHF patients: DHF patients had higher levels of factor D (p = 0.01), which cleaves factor B to yield the active (C3bBb) C3 convertase, and lower levels of factor H (p = 0.03), which inactivates the (C3bBb) C3 convertase, than did DF patients. When we considered the levels of factors D and H together as an indicator of (C3bBb) C3 convertase regulation, we found that the plasma levels of these regulatory proteins in DHF patients favored the formation of the (C3bBb) C3 convertase, whereas its formation was inhibited in DF patients (p<0.0001). CONCLUSION:The data suggest that an imbalance in the levels of regulatory factors D and H is associated with an abnormal regulation of complement activity in DHF patients

Identification of Continuous Human B-Cell Epitopes in the Envelope Glycoprotein of Dengue Virus Type 3 (DENV-3)

BACKGROUND:Dengue virus infection is a growing global public health concern in tropical and subtropical regions of the world. Dengue vaccine development has been hampered by concerns that cross-reactive immunological memory elicited by a candidate vaccine could increase the risk of development of more severe clinical forms. One possible strategy to reduce risks associated with a dengue vaccine is the development of a vaccine composed of selected critical epitopes of each of the serotypes. METHODOLOGY/PRINCIPAL FINDINGS:Synthetic peptides were used to identify B-cell epitopes in the envelope (E) glycoprotein of dengue virus type 3 (DENV-3). Eleven linear, immunodominant epitopes distributed in five regions at amino acid (aa) positions: 51-65, 71-90, 131-170, 196-210 and 246-260 were identified by employing an enzyme- linked immunosorbent assay (ELISA), using a pool of human sera from dengue type 3 infected individuals. Peptides 11 (aa51-65), 27 and 28 (aa131-150) also reacted with dengue 1 (DENV-1) and dengue 2 (DENV-2) patient sera as analyzed through the ROC curves generated for each peptide by ELISA and might have serotype specific diagnostic potential. Mice immunized against each one of the five immunogenic regions showed epitopes 51-65, 131-170, 196-210 and 246-260 elicited the highest antibody response and epitopes131-170, 196-210 and 246-260, elicited IFN-gamma production and T CD4+ cell response, as evaluated by ELISA and ELISPOT assays respectively. CONCLUSIONS/SIGNIFICANCE:Our study identified several useful immunodominant IgG-specific epitopes on the envelope of DENV-3. They are important tools for understanding the mechanisms involved in antibody dependent enhancement and immunity. If proven protective and safe, in conjunction with others well-documented epitopes, they might be included into a candidate epitope-based vaccine

Global priority areas for ecosystem restoration

Extensive ecosystem restoration is increasingly seen as being central to conserving biodiversity1 and stabilizing the climate of the Earth2. Although ambitious national and global targets have been set, global priority areas that account for spatial variation in benefits and costs have yet to be identified. Here we develop and apply a multicriteria optimization approach that identifies priority areas for restoration across all terrestrial biomes, and estimates their benefits and costs. We find that restoring 15% of converted lands in priority areas could avoid 60% of expected extinctions while sequestering 299 gigatonnes of CO2—30% of the total CO2 increase in the atmosphere since the Industrial Revolution. The inclusion of several biomes is key to achieving multiple benefits. Cost effectiveness can increase up to 13-fold when spatial allocation is optimized using our multicriteria approach, which highlights the importance of spatial planning. Our results confirm the vast potential contributions of restoration to addressing global challenges, while underscoring the necessity of pursuing these goals synergistically.Fil: Strassburg, Bernardo B. N.. Pontifícia Universidade Católica do Rio de Janeiro; Brasil. Universidade Federal do Rio de Janeiro; BrasilFil: Iribarrem, Alvaro. Pontifícia Universidade Católica do Rio de Janeiro; BrasilFil: Beyer, Hawthorne L.. The University of Queensland; Australia. University of Queensland; AustraliaFil: Cordeiro, Carlos Leandro. Pontifícia Universidade Católica do Rio de Janeiro; BrasilFil: Crouzeilles, Renato. Universidade Federal do Rio de Janeiro; Brasil. Pontifícia Universidade Católica do Rio de Janeiro; BrasilFil: Jakovac, Catarina C.. Pontifícia Universidade Católica do Rio de Janeiro; BrasilFil: Braga Junqueira, André. Pontifícia Universidade Católica do Rio de Janeiro; BrasilFil: Lacerda, Eduardo. Pontifícia Universidade Católica do Rio de Janeiro; Brasil. Universidade Federal Fluminense; BrasilFil: Latawiec, Agnieszka E.. University of East Anglia; Reino Unido. Pontifícia Universidade Católica do Rio de Janeiro; BrasilFil: Balmford, Andrew. University of Cambridge; Estados UnidosFil: Brooks, Thomas M.. University Of The Philippines Los Banos; Filipinas. Institute For Marine And Antarctic Studies; Australia. International Union For Conservation Of Nature And Natural Resources; SuizaFil: Butchart, Stuart H. M.. University of Cambridge; Estados UnidosFil: Chazdon, Robin L.. University Of The Sunshine Coast; Australia. University of Connecticut; Estados UnidosFil: Erb, Karl-Heinz. Universitat Fur Bodenkultur Wien; AustriaFil: Brancalion, Pedro. Universidade de Sao Paulo; BrasilFil: Buchanan, Graeme. Royal Society For The Protection Of Birds; Reino UnidoFil: Cooper, David. Secretariat Of The Convention On Biological Diversity; CanadáFil: Díaz, Sandra Myrna. Universidad Nacional de Córdoba; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto Multidisciplinario de Biología Vegetal. Universidad Nacional de Córdoba. Facultad de Ciencias Exactas Físicas y Naturales. Instituto Multidisciplinario de Biología Vegetal; ArgentinaFil: Donald, Paul F.. University of Cambridge; Estados UnidosFil: Kapos, Valerie. United Nations Environment Programme World Conservation Monitoring Centre; Reino UnidoFil: Leclère, David. International Institute For Applied Systems Analysis, Laxenburg; AustriaFil: Miles, Lera. United Nations Environment Programme World Conservation Monitoring Centre; Reino UnidoFil: Obersteiner, Michael. Oxford Social Sciences Division; Reino Unido. International Institute For Applied Systems Analysis, Laxenburg; AustriaFil: Plutzar, Christoph. Universitat Fur Bodenkultur Wien; Austria. Universidad de Viena; AustriaFil: de M. Scaramuzza, Carlos Alberto. International Institute For Sustainability; BrasilFil: Scarano, Fabio R.. Universidade Federal do Rio de Janeiro; BrasilFil: Visconti, Piero. International Institute For Applied Systems Analysis, Laxenburg; Austri

Gene Expression Profiling during Early Acute Febrile Stage of Dengue Infection Can Predict the Disease Outcome

Background: We report the detailed development of biomarkers to predict the clinical outcome under dengue infection. Transcriptional signatures from purified peripheral blood mononuclear cells were derived from whole-genome gene-expression microarray data, validated by quantitative PCR and tested in independent samples. Methodology/Principal Findings: The study was performed on patients of a well-characterized dengue cohort from Recife, Brazil. The samples analyzed were collected prospectively from acute febrile dengue patients who evolved with different degrees of disease severity: classic dengue fever or dengue hemorrhagic fever (DHF) samples were compared with similar samples from other non-dengue febrile illnesses. The DHF samples were collected 2-3 days before the presentation of the plasma leakage symptoms. Differentially-expressed genes were selected by univariate statistical tests as well as multivariate classification techniques. The results showed that at early stages of dengue infection, the genes involved in effector mechanisms of innate immune response presented a weaker activation on patients who later developed hemorrhagic fever, whereas the genes involved in apoptosis were expressed in higher levels. Conclusions/Significance: Some of the gene expression signatures displayed estimated accuracy rates of more than 95%, indicating that expression profiling with these signatures may provide a useful means of DHF prognosis at early stages of infection. © 2009 Nascimento et al