Reduced serum levels of adiponectin in elderly patients with major depression

Recent studies have implicated adiponectin and other adipocytokines in brain function, particularly in processes related to memory and cognition. Blood levels of adiponectin are reduced in patients with primary cognitive disorders, such as Alzheimer's disease and mild cognitive impairment, and in adult patients with major depression. The aim of the present study is to determine serum levels of adiponectin in a sample of elderly patients with major depressive disorder (MOD) as compared to healthy older adults, and to examine the correlations between adiponectin levels and parameters indicative of mood and cognitive state. We recruited fifty-one unmedicated outpatients with late-life depression (LLD) and 47 age-matched controls in this study. The diagnosis of MDD was made according to the DSM-IV criteria, and the severity of depressive episode was determined with the 21-item Hamilton Depression Scale (HORS). Cognitive state was ascertained with the Cambridge Cognitive Test (CAMCOG) and the Mini-Mental State Examination (MMSE). Serum concentrations of adiponectin were determined using a sandwich ELISA method. Serum levels of adiponectin were significantly reduced in individuals with LLD (F = p < 0.001). Adiponectin level remained significantly reduced in after controlling for BMI index, scores on the CAMCOG, MMSE and HDRS and educational level (p < 0.001). Adiponectin levels showed a negative correlation with HORS scores (r = -0.59, p < 0.001) and BMI index (r = -0.42, p < 0.001); and showed a positive correlation with CAMCOG (r = 0.34, p < 0.01) and MMSE scores (r = 0.20, p = 0.05). The availability of circulating adiponectin is reduced in older adults with major depression, with likely implications on cognitive and mood state. Additional studies are required to determine whether this abnormality pertains to the pathophysiology of geriatric depression per se, or is a consequence of the morbid state. (C) 2012 Elsevier Ltd. All rights reserved.

Effect of hydrogen bond formation on the elastic molecular scattering: a case study with methanol

Rayleigh optical activities of small hydrogen-bonded methanol clusters containing two to five molecules are reported. For the methanol trimer, tetramer, and pentamer both cyclic and linear structures are considered. After the geometry optimizations, the dipole moments and the dipole polarizabilities (mean, interaction, and anisotropic components) are calculated using HF, MP2 and DFT (B3LYP, B3P86 and BH&HLYP) with aug-cc-pVDZ extended basis set. The polarizabilities are used to analyse the depolarization ratios and the Rayleigh scattering activities. The variations in the activity and in the depolarization for Rayleigh scattered radiation with the increase in the cluster size for both cyclic and linear structures are analysed.

A comparative transcriptome analysis reveals expression profiles conserved across three Eimeria spp. of domestic fowl and associated with multiple developmental stages

Coccidiosis of the domestic fowl is a worldwide disease caused by seven species of protozoan parasites of the genus Eimeria. The genome of the model species, Eimeria tenella, presents a complexity of 55-60 MB distributed in 14 chromosomes. Relatively few studies have been undertaken to unravel the complexity of the transcriptome of Eimeria parasites. We report here the generation of more than 45,000 open reading frame expressed sequence tag (ORESTES) cDNA reads of E. tenella, Eimeria maxima and Eimeria acervulina, covering several developmental stages: unsporulated oocysts, sporoblastic oocysts, sporulated oocysts, sporozoites and second generation merozoites. All reads were assembled to constitute gene indices and submitted to a comprehensive functional annotation pipeline. In the case of E. tenella, we also incorporated publicly available ESTs to generate an integrated body of information. Orthology analyses have identified genes conserved across different apicomplexan parasites, as well as genes restricted to the genus Eimeria. Digital expression profiles obtained from ORESTES/EST countings, submitted to clustering analyses, revealed a high conservation pattern across the three Eimeria spp. Distance trees showed that unsporulated and sporoblastic oocysts constitute a distinct clade in all species, with sporulated oocysts forming a more external branch. This latter stage also shows a close relationship with sporozoites, whereas first and second generation merozoites are more closely related to each other than to sporozoites. The profiles were unambiguously associated with the distinct developmental stages and strongly correlated with the order of the stages in the parasite life cycle. Finally, we present The Eimeria Transcript Database (http://www.coccidia.icb.usp.br/eimeriatdb), a website that provides open access to all sequencing data, annotation and comparative analysis. We expect this repository to represent a useful resource to the Eimeria scientific community, helping to define potential candidates for the development of new strategies to control coccidiosis of the domestic fowl. (C) 2011 Australian Society for Parasitology Inc. Published by Elsevier Ltd. All rights reserved.

Does Lithium Prevent Alzheimer's Disease?

Lithium salts have a well-established role in the treatment of major affective disorders. More recently, experimental and clinical studies have provided evidence that lithium may also exert neuroprotective effects. In animal and cell culture models, lithium has been shown to increase neuronal viability through a combination of mechanisms that includes the inhibition of apoptosis, regulation of autophagy, increased mitochondrial function, and synthesis of neurotrophic factors. In humans, lithium treatment has been associated with humoral and structural evidence of neuroprotection, such as increased expression of anti-apoptotic genes, inhibition of cellular oxidative stress, synthesis of brain-derived neurotrophic factor (BDNF), cortical thickening, increased grey matter density, and hippocampal enlargement. Recent studies addressing the inhibition of glycogen synthase kinase-3 beta (GSK3B) by lithium have further suggested the modification of biological cascades that pertain to the pathophysiology of Alzheimer's disease (AD). A recent placebo-controlled clinical trial in patients with amnestic mild cognitive impairment (MCI) showed that long-term lithium treatment may actually slow the progression of cognitive and functional deficits, and also attenuate Tau hyperphosphorylation in the MCI-AD continuum. Therefore, lithium treatment may yield disease-modifying effects in AD, both by the specific modification of its pathophysiology via inhibition of overactive GSK3B, and by the unspecific provision of neurotrophic and neuroprotective support. Although the clinical evidence available so far is promising, further experimentation and replication of the evidence in large scale clinical trials is still required to assess the benefit of lithium in the treatment or prevention of cognitive decline in the elderly.

Reduced platelet amyloid precursor protein ratio (APP ratio) predicts conversion from mild cognitive impairment to Alzheimer's disease

Studies have shown that platelet APP ratio (representing the percentage of 120-130 kDa to 110 kDa isoforms of the amyloid precursor protein) is reduced in patients with mild cognitive impairment (MCI) and Alzheimer's disease (AD). In the present study, we sought to determine if baseline APP ratio predicts the conversion from MCI to AD dementia after 4 years of longitudinal assessment. Fifty-five older adults with varying degrees of cognitive impairment (34 with MCI and 21 with AD) were assessed at baseline and after 4 years. MCI patients were re-classified according to the conversion status upon follow-up: 25 individuals retained the diagnostic status of MCI and were considered as stable cases (MCI-MCI); conversely, in nine cases the diagnosis of dementia due to AD was ascertained. The APP ratio (APPr) was determined by the Western blot method in samples of platelets collected at baseline. We found a significant reduction of APPr in MCI patients who converted to dementia upon follow-up. These individuals had baseline APPr values similar to those of demented AD patients. The overall accuracy of APPr to identify subjects with MCI who will progress to AD was 0.74 +/- A 0.10, p = 0.05. The cut-off of 1.12 yielded a sensitivity of 75 % and a specificity of 75 %. Platelet APPr may be a surrogate marker of the disease process in AD, with potential implications for the assessment of abnormalities in the APP metabolism in patients with and at risk for dementia. However, diagnostic accuracy was relatively low. Therefore, studies in larger samples are needed to determine whether APPr may warrant its use as a biomarker to support the early diagnosis of AD.

Circulating Glial-derived neurotrophic factor is reduced in late-life depression

Background: The Glial Cell-line derived neurotrophic factor (GDNF) is part of the TGF-beta superfamily and is abundantly expressed in the central nervous system. Changes in GDNF homeostasis have been reported in affective disorders. Aim: To assess serum GDNF concentration in elderly subjects with late-life depression, before antidepressant treatment, as compared to healthy elderly controls. Methods: Thirty-four elderly subjects with major depression and 37 age and gender-matched healthy elderly controls were included in this study. Diagnosis of major depression was ascertained by the SCID interview for DSM-IV and the severity of depressive symptoms was assessed by the Hamilton Depression Rating Scale (HDRS-21). Serum GDNF concentration were determined by sandwich ELISA. Results: Patients with major depression showed a significant reduction in GDNF levels as compared to healthy elderly controls (p < 0.001). Also, GDNF level was negatively correlated with HDRS-21 scores (r = -0.343, p = 0.003). Discussion: Our data provide evidence that GDNF may be a state marker of depressive episode in older adults. Changes in the homeostatic control of GDNF production may be a target to development of new antidepressant strategies. (C) 2011 Elsevier Ltd. All rights reserved.

Early improvement of psychotic symptoms with lithium monotherapy as a predictor of later response in mania

Although lithium has been the first line agent in the treatment of bipolar disorder (BD), few studies have evaluated lithium's efficacy in mania with psychosis and its association with later response. Furthermore, given the widespread concern about antipsychotic side effects, answering a question about whether lithium alone can manage to treat both psychotic and non-psychotic mania seems a very relevant one. The present study addresses the antipsychotic efficacy of lithium monotherapy in acute mania and early improvement of psychotic symptoms as a predictor of later response of manic symptoms. Forty-six patients presenting a manic episode (32 with psychotic features and 14 subjects without psychotic features) were treated for 4 weeks with lithium monotherapy and evaluated weekly using the Young Mania Rating Scale (YMRS). Subjects with rapid cycling, substance abuse/dependence, or mixed episodes were excluded. The overall antimanic efficacy of lithium in psychosis vs. non-psychosis groups was evaluated. In addition, early improvement of psychotic symptoms and its prediction of subsequent response (>50% decrease in total YMRS scores) or remission were evaluated. Lithium showed a similar efficacy in both psychosis and non-psychosis mania. Early improvement of psychotic symptoms was associated with clinical response and remission at endpoint. (C) 2012 Elsevier Ltd. All rights reserved.

A radioenzymatic assay to identify three groups of phospholipase A(2) in platelets

Phospholipases A(2) (PLA(2)) are key enzymes in membrane metabolism. The release of fatty acids and lysophospholipids by PLA(2) activates several intra-cellular second messenger cascades that regulate a wide variety of physiological responses. The aim of the present study is to describe a radioenzymatic assay to determine the activity of three main PLA(2) subtypes in platelets, namely extracellular calcium-dependent PLA(2) (sPLA(2)) and intracellular calcium-dependent (cPLA(2)) and calcium-independent PLA(2) (iPLA(2)). The differentiation of these distinct PLA(2) subtypes was based on the enzyme substrate preference (arachdonic acid or palmitoyl acid) and calcium concentration. Our results indicate that this new assay is feasible, precise and specific to measure the activity of the aforementioned subtypes of PLA(2). Therefore, this protocol can be used to investigate modifications of PLA(2) homeostasis in distinct biological models addressing the pathophysiology of many medical and neuropsychiatric disorders such as schizophrenia and Alzheimer's disease. (C) 2012 Elsevier Ltd. All rights reserved.

Identification of unannotated exons of low abundance transcripts in Drosophila melanogaster and cloning of a new serine protease gene upregulated upon injury

Abstract Background The sequencing of the D.melanogaster genome revealed an unexpected small number of genes (~ 14,000) indicating that mechanisms acting on generation of transcript diversity must have played a major role in the evolution of complex metazoans. Among the most extensively used mechanisms that accounts for this diversity is alternative splicing. It is estimated that over 40% of Drosophila protein-coding genes contain one or more alternative exons. A recent transcription map of the Drosophila embryogenesis indicates that 30% of the transcribed regions are unannotated, and that 1/3 of this is estimated as missed or alternative exons of previously characterized protein-coding genes. Therefore, the identification of the variety of expressed transcripts depends on experimental data for its final validation and is continuously being performed using different approaches. We applied the Open Reading Frame Expressed Sequence Tags (ORESTES) methodology, which is capable of generating cDNA data from the central portion of rare transcripts, in order to investigate the presence of hitherto unnanotated regions of Drosophila transcriptome. Results Bioinformatic analysis of 1,303 Drosophila ORESTES clusters identified 68 sequences derived from unannotated regions in the current Drosophila genome version (4.3). Of these, a set of 38 was analysed by polyA+ northern blot hybridization, validating 17 (50%) new exons of low abundance transcripts. For one of these ESTs, we obtained the cDNA encompassing the complete coding sequence of a new serine protease, named SP212. The SP212 gene is part of a serine protease gene cluster located in the chromosome region 88A12-B1. This cluster includes the predicted genes CG9631, CG9649 and CG31326, which were previously identified as up-regulated after immune challenges in genomic-scale microarray analysis. In agreement with the proposal that this locus is co-regulated in response to microorganisms infection, we show here that SP212 is also up-regulated upon injury. Conclusion Using the ORESTES methodology we identified 17 novel exons from low abundance Drosophila transcripts, and through a PCR approach the complete CDS of one of these transcripts was defined. Our results show that the computational identification and manual inspection are not sufficient to annotate a genome in the absence of experimentally derived data.

En torno a los mitos y nombres míticos clásicos en Antonio Buero Vallejo

En primer lugar reviso las obras teatrales en sentido diacrónico (vol. I de la Obra completa): La tejedora de sueños (1952), con numerosas huellas de la Odisea, ofrece un tratamiento muy novedoso de las figuras de Penélope y Ulises (la obra es un alegato contra las guerras, las mentiras históricas, las humillaciones sufridas por las mujeres, la pretendida superioridad del varón sobre la mujer); Las Meninas (1960) presenta abundantes referencias a Venus y Marte; El concierto de San Ovidio (1962) alude a Midas, y, asimismo, al pavo real, símbolo de la necedad; y, finalmente, Diálogo secreto (1984) con el tema de Palas y Aracne. En segundo lugar examino el volumen II de su Obra completa (eds. Feijoo-De Paco, Madrid, 1994) donde me adentro en las reflexiones de Buero sobre los mitos clásicos y, asimismo, el problema de la desmitificación y la creación de nuevos mitos. Fuera de eso expongo de modo sumario los principales personajes míticos que hallamos en el orden seguido por buenos manuales de mitología: Venus, Erinis, Júpiter, Juno, Muerte, Parcas, Némesis, Atenea (Palas), Musas, Apolo, Diana, Eurídice, Prometeo, Pandora, Atridas, Dioniso, Edipo y su familia, Medea, Minos, Procrustes, Laocoonte, Orestes, Escila, Caribdis, Mirra.

En torno a los mitos y nombres míticos clásicos en Antonio Buero Vallejo

En primer lugar reviso las obras teatrales en sentido diacrónico (vol. I de la Obra completa): La tejedora de sueños (1952), con numerosas huellas de la Odisea, ofrece un tratamiento muy novedoso de las figuras de Penélope y Ulises (la obra es un alegato contra las guerras, las mentiras históricas, las humillaciones sufridas por las mujeres, la pretendida superioridad del varón sobre la mujer); Las Meninas (1960) presenta abundantes referencias a Venus y Marte; El concierto de San Ovidio (1962) alude a Midas, y, asimismo, al pavo real, símbolo de la necedad; y, finalmente, Diálogo secreto (1984) con el tema de Palas y Aracne. En segundo lugar examino el volumen II de su Obra completa (eds. Feijoo-De Paco, Madrid, 1994) donde me adentro en las reflexiones de Buero sobre los mitos clásicos y, asimismo, el problema de la desmitificación y la creación de nuevos mitos. Fuera de eso expongo de modo sumario los principales personajes míticos que hallamos en el orden seguido por buenos manuales de mitología: Venus, Erinis, Júpiter, Juno, Muerte, Parcas, Némesis, Atenea (Palas), Musas, Apolo, Diana, Eurídice, Prometeo, Pandora, Atridas, Dioniso, Edipo y su familia, Medea, Minos, Procrustes, Laocoonte, Orestes, Escila, Caribdis, Mirra.

En torno a los mitos y nombres míticos clásicos en Antonio Buero Vallejo

En primer lugar reviso las obras teatrales en sentido diacrónico (vol. I de la Obra completa): La tejedora de sueños (1952), con numerosas huellas de la Odisea, ofrece un tratamiento muy novedoso de las figuras de Penélope y Ulises (la obra es un alegato contra las guerras, las mentiras históricas, las humillaciones sufridas por las mujeres, la pretendida superioridad del varón sobre la mujer); Las Meninas (1960) presenta abundantes referencias a Venus y Marte; El concierto de San Ovidio (1962) alude a Midas, y, asimismo, al pavo real, símbolo de la necedad; y, finalmente, Diálogo secreto (1984) con el tema de Palas y Aracne. En segundo lugar examino el volumen II de su Obra completa (eds. Feijoo-De Paco, Madrid, 1994) donde me adentro en las reflexiones de Buero sobre los mitos clásicos y, asimismo, el problema de la desmitificación y la creación de nuevos mitos. Fuera de eso expongo de modo sumario los principales personajes míticos que hallamos en el orden seguido por buenos manuales de mitología: Venus, Erinis, Júpiter, Juno, Muerte, Parcas, Némesis, Atenea (Palas), Musas, Apolo, Diana, Eurídice, Prometeo, Pandora, Atridas, Dioniso, Edipo y su familia, Medea, Minos, Procrustes, Laocoonte, Orestes, Escila, Caribdis, Mirra.

CONTEXTUALIZAÇÃO E AS PERSPECTIVAS DA EDUCAÇÃO SALESIANA A PARTIR DO DOCUMENTO DAS LINHAS ORIENTADORAS DA MISSÃO EDUCATIVA DO INSTITUTO DAS FILHAS DE MARIA AUXILIADORA

A presente dissertação teve como objetivos contextualizar e analisar as perspectivas da educação salesiana a partir do documento das Linhas Orientadoras da Missão Educativa do Instituto das Filhas de Maria Auxiliadora, tendo em vista aprofundar o contexto histórico e sociocultural da fundação do Instituto das Filhas de Maria Auxiliadora e do desenvolvimento da missão educativa salesiana, com a finalidade de atuar no campo da educação, indicar os fundamentos interdisciplinares que compreendem os fundamentos teóricos para a prática educativa em relação aos aspectos sociológicos, antropológicos, teológicos e pedagógicos, além de algumas experiências práticas da educação salesiana. A pesquisa considera a contextualização da sua prática educativa a partir de diversas contribuições teóricas realizadas em torno da história do Instituto e dos conhecimentos interdisciplinares que integram seus propósitos e seus projetos educativos. Com a perspectiva de analisar as orientações e conteúdos do documento é utilizada a técnica da análise documental que permite interpretar o seu significado, analisar e indicar algumas perspectivas de educação salesiana presentes no documento e que envolvem os seus princípios, propósitos e as suas ações em relação à educação. Por meio da observação participante alguns aspectos práticos das perspectivas da educação salesiana foram demonstrados. Portanto, a investigação permite o mapeamento das perspectivas fundamentais da educação salesiana a partir das Linhas Orientadoras e a possibilidade de aprofundar a significatividade das perspectivas de referência para a prática educativa conforme são indicadas no documento: as dimensões cultural, evangelizadora, social e comunicativa da educação, que são os elementos e princípios fundamentais do Sistema Educativo Salesiano. A concepção de educação salesiana que se constrói a partir de uma visão interdisciplinar, complexa e dimensional, com uma perspectiva de uma estratégia projetual. Os seus princípios integram alguns valores que são considerados como fundamentais para a realização de uma educação integral: a comunidade educativa, o trabalho educativo realizado em equipe, a espiritualidade juvenil, a preventividade e a pedagogia do ambiente. Sobretudo, os núcleos centrais indicados pelo documento orientam as comunidades para a realização de um pensamento projetual, considerando as diversas dimensões da educação, com uma especial abertura para uma contínua projeção das suas intenções e da sua prática educativa. Enfim, encontramos algumas contribuições para a educação a partir do pensamento pedagógico e prático da educação salesiana, especialmente em relação à proposta de pensar a educação de forma complexa e multidimensional.

Endogenous Msx1 antisense transcript: In vivo and in vitro evidences, structure, and potential involvement in skeleton development in mammals

Msx1 is a key factor for the development of tooth and craniofacial skeleton and has been proposed to play a pivotal role in terminal cell differentiation. In this paper, we demonstrated the presence of an endogenous Msx1 antisense RNA (Msx1-AS RNA) in mice, rats, and humans. In situ analysis revealed that this RNA is expressed only in differentiated dental and bone cells with an inverse correlation with Msx1 protein. These in vivo data and overexpression of Msx1 sense and AS RNA in an odontoblastic cell line (MO6-G3) showed that the balance between the levels of the two Msx1 RNAs is related to the expression of Msx1 protein. To analyze the impact of this balance in the Msx-Dlx homeoprotein pathway, we analyzed the effect of Msx1, Msx2, and Dlx5 overexpression on proteins involved in skeletal differentiation. We showed that the Msx1-AS RNA is involved in crosstalk between the Msx-Dlx pathways because its expression was abolished by Dlx5. Msx1 was shown to down-regulate a master gene of skeletal cells differentiation, Cbfa1. All these data strongly suggest that the ratio between Msx1 sense and antisense RNAs is a very important factor in the control of skeletal terminal differentiation. Finally, the initiation site for Msx1-AS RNA transcription was located by primer extension in both mouse and human in an identical region, including a consensus TATA box, suggesting an evolutionary conservation of the AS RNA-mediated regulation of Msx1 gene expression.