Decreased AIRE Expression and Global Thymic Hypofunction in Down Syndrome

The Down syndrome (DS) immune phenotype is characterized by thymus hypotrophy, higher propensity to organ-specific autoimmune disorders, and higher susceptibility to infections, among other features. Considering that AIRE (autoimmune regulator) is located on 21q22.3, we analyzed protein and gene expression in surgically removed thymuses from 14 DS patients with congenital heart defects, who were compared with 42 age-matched controls with heart anomaly as an isolated malformation. Immunohistochemistry revealed 70.48 +/- 49.59 AIRE-positive cells/mm(2) in DS versus 154.70 +/- 61.16 AIRE-positive cells/mm(2) in controls (p < 0.0001), and quantitative PCR as well as DNA microarray data confirmed those results. The number of FOXP3-positive cells/mm(2) was equivalent in both groups. Thymus transcriptome analysis showed 407 genes significantly hypoexpressed in DS, most of which were related, according to network transcriptional analysis (FunNet), to cell division and to immunity. Immune response-related genes included those involved in 1) Ag processing and presentation (HLA-DQB1, HLA-DRB3, CD1A, CD1B, CD1C, ERAP) and 2) thymic T cell differentiation (IL2RG, RAG2, CD3D, CD3E, PRDX2, CDK6) and selection (SH2D1A, CD74). It is noteworthy that relevant AIRE-partner genes, such as TOP2A, LAMNB1, and NUP93, were found hypoexpressed in DNA microarrays and quantitative real-time PCR analyses. These findings on global thymic hypofunction in DS revealed molecular mechanisms underlying DS immune phenotype and strongly suggest that DS immune abnormalities are present since early development, rather than being a consequence of precocious aging, as widely hypothesized. Thus, DS should be considered as a non-monogenic primary immunodeficiency. The Journal of Immunology, 2011, 187: 3422-3430.

Prospects for biodiversity conservation in the Atlantic Forest: Lessons from aging human-modified landscapes

Recent global assessments have shown the limited coverage of protected areas across tropical biotas, fuelling a growing interest in the potential conservation services provided by anthropogenic landscapes. Here we examine the geographic distribution of biological diversity in the Atlantic Forest of South America, synthesize the most conspicuous forest biodiversity responses to human disturbances, propose further conservation initiatives for this biota, and offer a range of general insights into the prospects of forest species persistence in human-modified tropical forest landscapes worldwide. At the biome scale, the most extensive pre-Columbian habitats across the Atlantic Forest ranged across elevations below 800 masl, which still concentrate most areas within the major centers of species endemism. Unfortunately, up to 88% of the original forest habitat has been lost, mainly across these low to intermediate elevations, whereas protected areas are clearly skewed towards high elevations above 1200 masl. At the landscape scale, most remaining Atlantic Forest cover is embedded within dynamic agro-mosaics including elements such as small forest fragments, early-to-late secondary forest patches and exotic tree mono-cultures. In this sort of aging or long-term modified landscapes, habitat fragmentation appears to effectively drive edge-dominated portions of forest fragments towards an early-successional system, greatly limiting the long-term persistence of forest-obligate and forest-dependent species. However, the extent to which forest habitats approach early-successional systems, thereby threatening the bulk of the Atlantic Forest biodiversity, depends on both past and present landscape configuration. Many elements of human-modified landscapes (e.g. patches of early-secondary forests and tree mono-cultures) may offer excellent conservation opportunities, but they cannot replace the conservation value of protected areas and hitherto unprotected large patches of old-growth forests. Finally, the biodiversity conservation services provided by anthropogenic landscapes across Atlantic Forest and other tropical forest regions can be significantly augmented by coupling biodiversity corridor initiatives with biota-scale attempts to plug existing gaps in the representativeness of protected areas. (C) 2010 Elsevier Ltd. All rights reserved.

Previsões climáticas sazonais sobre o Brasil: avaliação do RegCM3 aninhado no modelo global CPTEC/COLA

Este trabalho avalia o desempenho de previsões sazonais do modelo climático regional RegCM3, aninhado ao modelo global CPTEC/COLA. As previsões com o RegCM3 utilizaram 60 km de resolução horizontal num domínio que inclui grande parte da América do Sul. As previsões do RegCM3 e CPTEC/COLA foram avaliadas utilizando as análises de chuva e temperatura do ar do Climate Prediction Center (CPC) e National Centers for Enviromental Prediction (NCEP), respectivamente. Entre maio de 2005 e julho de 2007, 27 previsões sazonais de chuva e temperatura do ar (exceto a temperatura do CPTEC/COLA, que possui 26 previsões) foram avaliadas em três regiões do Brasil: Nordeste (NDE), Sudeste (SDE) e Sul (SUL). As previsões do RegCM3 também foram comparadas com as climatologias das análises. De acordo com os índices estatísticos (bias, coeficiente de correlação, raiz quadrada do erro médio quadrático e coeficiente de eficiência), nas três regiões (NDE, SDE e SUL) a chuva sazonal prevista pelo RegCM3 é mais próxima da observada do que a prevista pelo CPTEC/COLA. Além disto, o RegCM3 também é melhor previsor da chuva sazonal do que da média das observações nas três regiões. Para temperatura, as previsões do RegCM3 são superiores às do CPTEC/COLA nas áreas NDE e SUL, enquanto o CPTEC/COLA é superior no SDE. Finalmente, as previsões de chuva e temperatura do RegCM3 são mais próximas das observações do que a climatologia observada. Estes resultados indicam o potencial de utilização do RegCM3 para previsão sazonal, que futuramente deverá ser explorado através de previsão por conjunto.

Fatores associados à prática de atividade física global e de lazer em idosos: Inquérito de Saúde no Estado de São Paulo (ISA-SP), Brasil

The purpose of this study was to measure the prevalence of global and leisure-time physical activity and associated factors in the elderly. This was a population-based cross-sectional study covering a multiple-stage sample of 1,950 subjects 60 years or older living in areas of São Paulo State, Brazil. Prevalence of global physical activity (assessed through the short version of the International Physical Activity Questionnaire - IPAQ) was 73.9%, and prevalence of leisure-time physical activity was 28.4%. The results highlight the differences between factors associated with global and leisure-time physical activities. The social groups most prone to overall sedentary lifestyle and especially to lack of leisure-time physical activity should be the main targets of health policies aimed at promoting healthier lifestyles.

Analysis of the prevalence of and factors associated with urinary incontinence among elderly people in the Municipality of São Paulo, Brazil: SABE Study (Health, Wellbeing and Aging)

To investigate the prevalence of urinary incontinence among elderly people living in São Paulo, Brazil and their associated risk factors. The Pan-American Health Organization and World Health Organization coordinated a multicenter study named Health, Wellbeing and Aging (SABE Study) in elderly people (over 60 years old) living in seven countries in Latin America and the Caribbean. In Brazil, the study was carried out in São Paulo in the year 2000. The total Brazilian sample included 2,143 people. The prevalence of self reported urinary incontinence was 11.8% among men and 26.2% for women. It was verified that among those reporting urinary incontinence, 37% also reported stroke and 34% depression. It was found that the greater the dependence that the elderly people presented, the greater the prevalence of urinary incontinence. The associated factors found were depression (odds ratio = 2.49), female (2.42), advanced age (2.35), important functional limitation (2.01). Urinary incontinence is a highly prevalent symptom among the elderly population of the municipality of São Paulo, especially among women. The adoption of preventive measures can reduce the negative effects of urinary incontinence.

Fatores associados à obesidade global e à obesidade abdominal em mulheres na pós-menopausa

OBJETIVOS: avaliar a prevalência de obesidade global e obesidade abdominal, em mulheres pós-menopausa, segundo o grau de instrução, nível de atividade física, uso de terapia hormonal na menopausa (THM) e paridade. MÉTODOS: foram entrevistadas 157 mulheres na pós-menopausa, atendidas em dois ambulatórios públicos da cidade de São Paulo, São Paulo, Brasil. A obesidade foi determinada segundo o índice de massa corporal (IMC > 30,0) e segundo o percentual de gordura corporal (%GC > 37%). A obesidade abdominal foi determinada pela relação cintura-quadril (RCQ > 0,85). RESULTADOS: a prevalência de obesidade global foi 34,4% (segundo o IMC) e de 40,1% (segundo o %GC). A prevalência de obesidade abdominal foi de 73,8%. Grande parte das entrevistadas referiu até sete anos de instrução formal (47,8%), foi considerada sedentária ou insuficientemente ativa (52,3%) e nunca tinha utilizado THM oral ou tinha utilizado por menos de 12 meses (72,0%). Foi constatada maior prevalência de obesidade global no grupo de mulheres sedentárias ou insuficientemente ativas e no grupo de não usuárias de THM (p<0,05). Quanto à obesidade abdominal, fator de risco para doenças cardiovasculares (DCV), apenas o grau de instrução mostrou-se associado à RCQ (p<0,05). CONCLUSÕES: mulheres após a menopausa, fisicamente ativas e usuárias de THM exibiram menor prevalência de obesidade global, porém a prevalência de obesidade abdominal foi alta e ainda maior nas mulheres com menor grau de instrução

Change and Aging Senescence as an Adaptation

Understanding why we age is a long-lived open problem in evolutionary biology. Aging is prejudicial to the individual, and evolutionary forces should prevent it, but many species show signs of senescence as individuals age. Here, I will propose a model for aging based on assumptions that are compatible with evolutionary theory: i) competition is between individuals; ii) there is some degree of locality, so quite often competition will be between parents and their progeny; iii) optimal conditions are not stationary, and mutation helps each species to keep competitive. When conditions change, a senescent species can drive immortal competitors to extinction. This counter-intuitive result arises from the pruning caused by the death of elder individuals. When there is change and mutation, each generation is slightly better adapted to the new conditions, but some older individuals survive by chance. Senescence can eliminate those from the genetic pool. Even though individual selection forces can sometimes win over group selection ones, it is not exactly the individual that is selected but its lineage. While senescence damages the individuals and has an evolutionary cost, it has a benefit of its own. It allows each lineage to adapt faster to changing conditions. We age because the world changes.

Aging and fluctuation-dissipation ratio in a nonequilibrium q-state lattice model

A generalized version of the nonequilibrium linear Glauber model with q states in d dimensions is introduced and analyzed. The model is fully symmetric, its dynamics being invariant under all permutations of the q states. Exact expressions for the two-time autocorrelation and response functions on a d-dimensional lattice are obtained. In the stationary regime, the fluctuation-dissipation theorem holds, while in the transient the aging is observed with the fluctuation-dissipation ratio leading to the value predicted for the linear Glauber model.

GLOBAL SOLUTIONS FOR ABSTRACT FUNCTIONAL DIFFERENTIAL EQUATIONS WITH NONLOCAL CONDITIONS

In this paper we study the existence of global solutions for a class of abstract functional differential equation with nonlocal conditions. An application is considered.

Accelerating aging chemotherapy on aged animals: Protective effect from nutraceutical modulation

The aim of this study was to test a novel phytocompound in an experimental model of antitumor-induced immunosuppression. Five groups of mice were considered: young (Y) and aged (A) that were given intraperitoneally 10 doses of cyclophosphamide (CPX, 25mg/kg/bw) or CPX plus (150 mg/kg/bw) of the nutraceutical DTS (Denshichi-Tochiu-Sen), and control. After sacrifice, macrophage chemotaxis and serum levels of IFN-gamma, IL-2, and GM-CSF were determined. Liver and urinary bladder were examined histologically, as were the liver and kidney for redox enzymes. CPX significantly decreased macrophage chemotaxis and all cytokines (p < 0.05, A >> Y). DTS restored macrophage function and cytokine concentration (p < 0.001) and partly improved the necro-inflammatory score and substance P receptor expression in the bladder and the redox status in liver and kidney (p < 0.05). Such data suggest that DTS effectively prevents CPX-induced immune suppression and oxidative-inflammatory damage, which are particularly enhanced in aged organisms.

Global gene expression under nitrogen starvation in Xylella fastidiosa: contribution of the sigma(54) regulon

Background: Xylella fastidiosa, a Gram-negative fastidious bacterium, grows in the xylem of several plants causing diseases such as citrus variegated chlorosis. As the xylem sap contains low concentrations of amino acids and other compounds, X. fastidiosa needs to cope with nitrogen limitation in its natural habitat. Results: In this work, we performed a whole-genome microarray analysis of the X. fastidiosa nitrogen starvation response. A time course experiment (2, 8 and 12 hours) of cultures grown in defined medium under nitrogen starvation revealed many differentially expressed genes, such as those related to transport, nitrogen assimilation, amino acid biosynthesis, transcriptional regulation, and many genes encoding hypothetical proteins. In addition, a decrease in the expression levels of many genes involved in carbon metabolism and energy generation pathways was also observed. Comparison of gene expression profiles between the wild type strain and the rpoN null mutant allowed the identification of genes directly or indirectly induced by nitrogen starvation in a sigma(54)-dependent manner. A more complete picture of the sigma(54) regulon was achieved by combining the transcriptome data with an in silico search for potential sigma(54)-dependent promoters, using a position weight matrix approach. One of these sigma(54)-predicted binding sites, located upstream of the glnA gene (encoding glutamine synthetase), was validated by primer extension assays, confirming that this gene has a sigma(54)-dependent promoter. Conclusions: Together, these results show that nitrogen starvation causes intense changes in the X. fastidiosa transcriptome and some of these differentially expressed genes belong to the sigma(54) regulon.

Global gene expression profile in myelodysplastic syndromes using SAGE

The molecular pathogenesis of myelodysplastic syndromes (MDS) is poorly understood. In order to expand our knowledge of genetic defects in MDS, we determined the overall profile of genes expressed in bone marrow from patients with refractory anemia with excess blasts ( RAEB) by serial analysis of gene expression ( SAGE). The present report describes a partial transcriptome of RAEB bone marrow derived from 56,694 sequenced tags that provides information about expressed gene products. This is the first attempt to determine an overall profile of gene expression specifically in RAEB at diagnosis using SAGE, which should be useful in the understanding of the physiopathology of MDS and in identifying the genes involved.

Consequences for the Bovine Embryo of Being Derived from a Spermatozoon Subjected to Post-Ejaculatory Aging and Heat Shock: Development to the Blastocyst Stage and Sex Ratio

The objective was to determine whether aging of sperm caused by incubation at normothermic (38.5 C) or heat shock (40 C) temperatures for 4 h prior to oocyte insemination affects sperm motility, fertilizing ability, competence of the resultant embryo to develop to the blastocyst stage and blastocyst sex ratio. In the first experiment, the percent of sperm that were motile was reduced by aging (P<0.001) and the reduction in motility was greater for sperm at 40 C compared to sperm at 38.5 C (P<0.01). In the second experiment, oocytes were inseminated with aged sperm. A smaller percent of oocytes fertilized with sperm aged at either temperature cleaved by Day 3 after insemination than oocytes fertilized with fresh sperm (P<0.05). There was no effect of sperm aging on the percent of oocytes or cleaved embryos that developed to the blastocyst stage. Aging of sperm before fertilization at 38.5 C reduced the percent of blastocysts that were male (P=0.08). In the third experiment, incubation of sperm at 38.5 C or 40 C for 4 h did not reduce fertilizing ability of sperm as determined by pronuclear formation at 18 h post insemination. In conclusion, aging of sperm reduced cleavage rate and the percent of blastocysts that were males but had no effect on the developmental capacity of the. embryo. The effect of aging on cleavage rate may represent reduced motility and errors occurring after fertilization and pronuclear formation. Aging at a temperature characteristic of maternal hyperthermia had little additional effect except that polyspermy was reduced. Results indicate that embryo competence for development to the blastocyst stage is independent of sperm damage as a result of aging for 4 h at normothermic or hyperthermic temperatures.

Sequential analysis of global gene expression profiles in immature and in vitro matured bovine oocytes: potential molecular markers of oocyte maturation

Background: Without intensive selection, the majority of bovine oocytes submitted to in vitro embryo production (IVP) fail to develop to the blastocyst stage. This is attributed partly to their maturation status and competences. Using the Affymetrix GeneChip Bovine Genome Array, global mRNA expression analysis of immature (GV) and in vitro matured (IVM) bovine oocytes was carried out to characterize the transcriptome of bovine oocytes and then use a variety of approaches to determine whether the observed transcriptional changes during IVM was real or an artifact of the techniques used during analysis. Results: 8489 transcripts were detected across the two oocyte groups, of which similar to 25.0% (2117 transcripts) were differentially expressed (p < 0.001); corresponding to 589 over-expressed and 1528 under-expressed transcripts in the IVM oocytes compared to their immature counterparts. Over expression of transcripts by IVM oocytes is particularly interesting, therefore, a variety of approaches were employed to determine whether the observed transcriptional changes during IVM were real or an artifact of the techniques used during analysis, including the analysis of transcript abundance in oocytes in vitro matured in the presence of a-amanitin. Subsets of the differentially expressed genes were also validated by quantitative real-time PCR (qPCR) and the gene expression data was classified according to gene ontology and pathway enrichment. Numerous cell cycle linked (CDC2, CDK5, CDK8, HSPA2, MAPK14, TXNL4B), molecular transport (STX5, STX17, SEC22A, SEC22B), and differentiation (NACA) related genes were found to be among the several over-expressed transcripts in GV oocytes compared to the matured counterparts, while ANXA1, PLAU, STC1and LUM were among the over-expressed genes after oocyte maturation. Conclusion: Using sequential experiments, we have shown and confirmed transcriptional changes during oocyte maturation. This dataset provides a unique reference resource for studies concerned with the molecular mechanisms controlling oocyte meiotic maturation in cattle, addresses the existing conflicting issue of transcription during meiotic maturation and contributes to the global goal of improving assisted reproductive technology.