Aluminium and the human breast

The human population is exposed to aluminium (Al) from diet, antacids and vaccine adjuvants, but frequent application of Al-based salts to the underarm as antiperspirant adds a high additional exposure directly to the local area of the human breast. Coincidentally the upper outer quadrant of the breast is where there is also a disproportionately high incidence of breast cysts and breast cancer. Al has been measured in human breast tissues/fluids at higher levels than in blood, and experimental evidence suggests that at physiologically relevant concentrations, Al can adversely impact on human breast epithelial cell biology. Gross cystic breast disease is the most common benign disorder of the breast and evidence is presented that Al may be a causative factor in formation of breast cysts. Evidence is also reviewed that Al can enable the development of multiple hallmarks associated with cancer in breast cells, in particular that it can cause genomic instability and inappropriate proliferation in human breast epithelial cells, and can increase migration and invasion of human breast cancer cells. In addition, Al is a metalloestrogen and oestrogen is a risk factor for breast cancer known to influence multiple hallmarks. The microenvironment is established as another determinant of breast cancer development and Al has been shown to cause adverse alterations to the breast microenvironment. If current useage patterns of Al-based antiperspirant salts contribute to causation of breast cysts and breast cancer, then reduction in exposure would offer a strategy for prevention, and regulatory review is now justified.

A novel locus for split-hand/foot malformation associated with tibial hemimelia (SHFLD syndrome) maps to chromosome region 17p13.1-17p13.3

Split-hand/foot malformation (SHFM) associated with aplasia of long bones, SHFLD syndrome or Tibial hemimelia-ectrodactyly syndrome is a rare condition with autosomal dominant inheritance, reduced penetrance and an incidence estimated to be about 1 in 1,000,000 liveborns. To date, three chromosomal regions have been reported as strong candidates for harboring SHFLD syndrome genes: 1q42.2-q43, 6q14.1 and 2q14.2. We characterized the phenotype of nine affected individuals from a large family with the aim of mapping the causative gene. Among the nine affected patients, four had only SHFM of the hands and no tibial defects, three had both defects and two had only unilateral tibial hemimelia. In keeping with previous publications of this and other families, there was clear evidence of both variable expression and incomplete penetrance, the latter bearing hallmarks of anticipation. Segregation analysis and multipoint Lod scores calculations (maximum Lod score of 5.03 using the LINKMAP software) using all potentially informative family members, both affected and unaffected, identified the chromosomal region 17p13.1-17p13.3 as the best and only candidate for harboring a novel mutated gene responsible for the syndrome in this family. The candidate gene CRK located within this region was sequenced but no pathogenic mutation was detected.

História, memória e patrimônio da Escola Militar do Realengo

Esta dissertação analisa a influência das instituições militares, particularmente a Escola Militar, no período de 1912 a 1944, na configuração urbana de Realengo, bairro localizado no subúrbio do município do Rio de Janeiro. Tendo como principal corpus documental os relatórios do Ministério da Guerra e a legislação pertinente, são estabelecidos marcos históricos para análise do processo de transformação da antiga zona rural do município em uma área militar, enfatizando os impactos que incidiram sobre a região em decorrência da transferência da sede da Escola Militar do Brazil, da Praia Vermelha para o Realengo. Preliminarmente, são identificadas as primeiras unidades militares que ocuparam a região, estabelecendo conexões entre o funcionamento dessas organizações, a constituição do seu patrimônio e o desenvolvimento urbano de Realengo. Para contextualização, também são apresentadas as sedes ocupadas pela Escola Militar ao longo do século XIX e as circunstâncias que motivaram sua saída da Praia Vermelha no início do século XX. O recorte temporal se inicia no período compreendido entre o início do século XIX, quando as chamadas terras realengas foram doadas à Câmara da cidade do Rio de Janeiro por D. João VI; atravessa o século XX, quando se consolidaram o patrimônio da Escola Militar em Realengo e a urbanização do bairro; e chega aos dias atuais, quando, após a extinção da escola, a decadência e o abandono são as marcas das antigas edificações militares do bairro. Também são assinalados o funcionamento da Fábrica de Cartuchos e a criação de duas grandes áreas militares, a Vila Militar de Deodoro e o Campo dos Afonsos. Por fim, são levantadas as perspectivas e ações do Exército Brasileiro e de outros órgãos da sociedade na preservação do patrimônio e da memória da antiga escola.

Sequential IL-23 and IL-17 and increased Mmp8 and Mmp14 expression characterize the progression of an experimental model of periodontal disease in type 1 diabetes

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Envelhecimento: um processo multifatorial

O envelhecimento é um processo do desenvolvimento normal, envolvendo alterações neurobiológicas estruturais, funcionais e químicas. Também incidem sobre o organismo fatores ambientais e socioculturais - como qualidade e estilo de vida, dieta, sedentarismo e exercício - intimamente ligados ao envelhecimento sadio ou patológico. Este estudo teórico tem como objetivo ressaltar tópicos relevantes para o envelhecimento sadio e o envelhecimento doentio, fundamentados em resultados recentes da pesquisa em neurociências. Conclui-se que o aumento da idade não significa necessariamente adoecer; com medidas preventivas pode-se manter o idoso em condições saudáveis nos domínios físico e cognitivo, mantendo a autonomia de vida por longo período. Contudo, na presença de disfunções, o diagnóstico e a intervenção precoces podem propiciar uma melhor qualidade de vida ao paciente e sua família.

New treatment strategies for Alzheimer's disease: is there a hope?

Alzheimer's disease (AD) is a progressive and irreversible neurodegenerative disease, and corresponds to the most common cause of dementia worldwide. Although not fully understood, the pathophysiology of AD is largely represented by the neurotoxic events triggered by the beta-amyloid cascade and by cytoskeletal abnormalities subsequent to the hyperphosphorylation of microtubule-associated Tau protein in neurons. These processes lead respectively to the formation of neuritic plaques and neurofibrillary tangles, which are the pathological hallmarks of the disease. Clinical benefits of the available pharmacological treatment for AD with antidementia drugs (namely cholinesterase inhibitors and memantine) are unquestionable, although limited to a temporary, symptomatic support to cognitive and related functions. Over the past decade, substantial funding and research have been dedicated to the search and development of new pharmaceutical compounds with disease-modifying properties. The rationale of such approach is that by tackling key pathological processes in AD it may be possible to attenuate or even change its natural history. In the present review, we summarize the available evidence on the new therapeutic approaches that target amyloid and Tau pathology in AD, focusing on pharmaceutical compounds undergoing phase 2 and phase 3 randomized controlled trials.

Neuropsychiatric symptoms in the prodromal stages of dementia

Purpose of reviewTo critically discuss the neuropsychiatric symptoms in the prodromal stages of dementia in order to improve the early clinical diagnosis of cognitive and functional deterioration.Recent findingsCurrent criteria for cognitive syndrome, including Alzheimer's disease, comprise the neuropsychiatric symptoms in addition to cognitive and functional decline. Although there is growing evidence that neuropsychiatric symptoms may precede the prodromal stages of dementia, these manifestations have received less attention than traditional clinical hallmarks such as cognitive and functional deterioration. Depression, anxiety, apathy, irritability, agitation, sleep disorders, among other symptoms, have been hypothesized to represent a prodromal stage of dementia or, at least, they increase the risk for conversion from minor neurocognitive disorder to major neurocognitive disorder. Longitudinal investigations have provided increased evidence of progression to dementia in individuals with minor neurocognitive disorder when neuropsychiatric symptoms also were present.SummaryAlthough neuropsychiatric symptoms are strongly associated with a higher risk of cognitive and functional deterioration, frequently the clinician does not acknowledge these conditions as increasing the risk of dementia. When the clinician accurately diagnoses neuropsychiatric symptoms in the prodromal stage of dementia, he could early establish appropriate treatment and, may be, delay the beginning of clinical and functional deterioration.

Kinome profiling of osteoblasts on hydroxyapatite opens new avenues on biomaterial cell signaling

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Relação entre o ideal e o real: a efetivação do Projeto Ético Político do Serviço Social

Pós-graduação em Serviço Social - FCHS

Modulação da doença periodontal por curcumin modificado quimicamente. Estudo de dose-resposta em roedor

Pós-graduação em Odontologia - FOAR

Structural synaptic elements are differentially regulated in superior temporal cortex of schizophrenia patients

Inaccurate wiring and synaptic pathology appear to be major hallmarks of schizophrenia. A variety of gene products involved in synaptic neurotransmission and receptor signaling are differentially expressed in brains of schizophrenia patients. However, synaptic pathology may also develop by improper expression of intra- and extra-cellular structural elements weakening synaptic stability. Therefore, we have investigated transcription of these elements in the left superior temporal gyrus of 10 schizophrenia patients and 10 healthy controls by genome-wide microarrays (Illumina). Fourteen up-regulated and 22 downregulated genes encoding structural elements were chosen from the lists of differentially regulated genes for further qRT-PCR analysis. Almost all genes confirmed by this method were downregulated. Their gene products belonged to vesicle-associated proteins, that is, synaptotagmin 6 and syntaxin 12, to cytoskeletal proteins, like myosin 6, pleckstrin, or to proteins of the extracellular matrix, such as collagens, or laminin C3. Our results underline the pivotal roles of structural genes that control formation and stabilization of pre- and post-synaptic elements or influence axon guidance in schizophrenia. The glial origin of collagen or laminin highlights the close interrelationship between neurons and glial cells in establishment and maintenance of synaptic strength and plasticity. It is hypothesized that abnormal expression of these and related genes has a major impact on the pathophysiology of schizophrenia.

Cannabidiol protects oligodendrocyte progenitor cells from inflammation-induced apoptosis by attenuating endoplasmic reticulum stress

Cannabidiol (CBD) is the most abundant cannabinoid in Cannabis sativa that has no psychoactive properties. CBD has been approved to treat inflammation, pain and spasticity associated with multiple sclerosis (MS), of which demyelination and oligodendrocyte loss are hallmarks. Thus, we investigated the protective effects of CBD against the damage to oligodendrocyte progenitor cells (OPCs) mediated by the immune system. Doses of 1 mu M CBD protect OPCs from oxidative stress by decreasing the production of reactive oxygen species. CBD also protects OPCs from apoptosis induced by LPS/IFN gamma through the decrease of caspase 3 induction via mechanisms that do not involve CB1, CB2, TRPV1 or PPAR gamma receptors. Tunicamycin-induced OPC death was attenuated by CBD, suggesting a role of endoplasmic reticulum (ER) stress in the mode of action of CBD. This protection against ER stress-induced apoptosis was associated with reduced phosphorylation of eiF2 alpha, one of the initiators of the ER stress pathway. Indeed, CBD diminished the phosphorylation of PKR and eiF2 alpha induced by LPS/IFN gamma. The pro-survival effects of CBD in OPCs were accompanied by decreases in the expression of ER apoptotic effectors (CHOP, Bax and caspase 12), and increased expression of the anti-apoptotic Bcl-2. These findings suggest that attenuation of the ER stress pathway is involved in the 'oligoprotective' effects of CBD during inflammation. Cell Death and Disease (2012) 3, e331; doi:10.1038/cddis.2012.71; published online 28 June 2012

Characterization of Heparin-induced Glyceraldehyde-3-phosphate Dehydrogenase Early Amyloid-like Oligomers and Their Implication in alpha-Synuclein Aggregation

Lewy bodies and Lewy neurites, neuropathological hallmarks of several neurological diseases, are mainly made of filamentous assemblies of alpha-synuclein. However, other macromolecules including Tau, ubiquitin, glyceraldehyde-3-phosphate dehydrogenase, and glycosaminoglycans are routinely found associated with these amyloid deposits. Glyceraldehyde-3-phosphate dehydrogenase is a glycolytic enzyme that can form fibrillar aggregates in the presence of acidic membranes, but its role in Parkinson disease is still unknown. In this work, the ability of heparin to trigger the amyloid aggregation of this protein at physiological conditions of pH and temperature is demonstrated by infrared and fluorescence spectroscopy, dynamic light scattering, small angle x-ray scattering, circular dichroism, and fluorescence microscopy. Aggregation proceeds through the formation of short rod-like oligomers, which elongates in one dimension. Heparan sulfate was also capable of inducing glyceraldehyde-3-phosphate dehydrogenase aggregation, but chondroitin sulfates A, B, and C together with dextran sulfate had a negligible effect. Aided with molecular docking simulations, a putative binding site on the protein is proposed providing a rational explanation for the structural specificity of heparin and heparan sulfate. Finally, it is demonstrated that in vitro the early oligomers present in the glyceraldehyde-3-phosphate dehydrogenase fibrillation pathway promote alpha-synuclein aggregation. Taking into account the toxicity of alpha-synuclein prefibrillar species, the heparin-induced glyceraldehyde-3-phosphate dehydrogenase early oligomers might come in useful as a novel therapeutic strategy in Parkinson disease and other synucleinopathies.

Xylella fastidiosa comparative genomic database is an information resource to explore the annotation, genomic features, and biology of different strains

The Xylella fastidiosa comparative genomic database is a scientific resource with the aim to provide a user-friendly interface for accessing high-quality manually curated genomic annotation and comparative sequence analysis, as well as for identifying and mapping prophage-like elements, a marked feature of Xylella genomes. Here we describe a database and tools for exploring the biology of this important plant pathogen. The hallmarks of this database are the high quality genomic annotation, the functional and comparative genomic analysis and the identification and mapping of prophage-like elements. It is available from web site http://www.xylella.lncc.br.

"Narrativa di frontiera". Fenomenologia di una forma aperta.

«Fiction of frontier». Phenomenology of an open form/voice. Francesco Giustini’s PhD dissertation fits into a genre of research usually neglected by the literary criticism which nevertheless is arousing much interest in recent years: the relationship between Literature and Space. In this context, the specific issue of his work consists in the category of the Frontier including its several implications for the XX century fiction. The preliminary step, at the beginning of the first section of the dissertation, is a semantic analysis: with precision, Giustini describes the meaning of the word “frontier” here declined in a multiplicity of cultural, political and geographical contexts, starting from the American frontier of the pioneers who headed for the West, to the exotic frontiers of the world, with whose the imperialistic colonization has come into contact; from the semi-uninhabited areas like deserts, highlands and virgin forests, to the ethnic frontiers between Indian and white people in South America, since the internal frontiers of the Countries like those ones between the District and the Capital City, the Centre and the Outskirts. In the next step, Giustini wants to focus on a real “ myth of the frontier”, able to nourish cultural and literary imagination. Indeed, the literature has told and chosen the frontier as the scenery for many stories; especially in the 20th Century it made the frontier a problematic space in the light of events and changes that have transformed the perception of space and our relationship with it. Therefore, the dissertation proposes a critical category, it traces the hallmarks of a specific literary phenomenon defined “ Fiction of the frontier” ,present in many literary traditions during the 20th Century. The term “Fiction” (not “Literature” or “Poetics”) does not define a genre but rather a “procedure”, focusing on a constant issue pointed out from the texts examined in this work : the strong call to the act of narration and to its oral traditions. The “Fiction of the Frontier” is perceived as an approach to the world, a way of watching and feeling the objects, an emotion that is lived and told through the story- a story where the narrator ,through his body and his voice, takes the rule of the witness. The following parts, that have an analytic style, are constructed on the basis of this theoretical and methodological reflection. The second section gives a wide range of examples into we can find the figure and the myth of the frontier through the textual analysis which range over several literary traditions. Starting from monographic chapters (Garcia Marquez, Callado, McCarthy), to the comparative reading of couples of texts (Calvino and Verga Llosa, Buzzati and Coetzee, Arguedas and Rulfo). The selection of texts is introduced so as to underline a particular aspect or a form of the frontier at every reading. This section is articulated into thematic voices which recall some actions that can be taken into the ambiguous and liminal space of the frontier (to communicate, to wait, to “trans-culturate”, to imagine, to live in, to not-live in). In this phenomenology, the frontier comes to the light as a physical and concrete element or as a cultural, imaginary, linguistic, ethnic and existential category. In the end, the third section is centered on a more defined and elaborated analysis of two authors, considered as fundamental for the comprehension of the “Fiction of the frontier”: Joseph Conrad and João Guimarães Rosa. Even if they are very different, being part of unlike literary traditions, these two authors show many connections which are pointed by the comparative analysis. Maybe Conrad is the first author that understand the feeling of the frontier , freeing himself from the adventure romance and from the exotic nineteenthcentury tradition. João Guimarães Rosa, in his turn, is the great narrator of Brazilian and South American frontier, he is the man of sertão and of endless spaces of the Centre of Brazil. His production is strongly linked to that one belonged to the author of Heart of Darkness.