Mucopolysaccharidosis I, II, and VI: brief review and guidelines for treatment

Mucopolysaccharidoses (MPS) are rare genetic diseases caused by the deficiency of one of the lysosomal enzymes involved in the glycosaminoglycan (GAG) breakdown pathway. This metabolic block leads to the accumulation of GAG in various organs and tissues of the affected patients, resulting in a multisystemic clinical picture, sometimes including cognitive impairment. Until the beginning of the XXI century, treatment was mainly supportive. Bone marrow transplantation improved the natural course of the disease in some types of MPS, but the morbidity and mortality restricted its use to selected cases. The identification of the genes involved, the new molecular biology tools and the availability of animal models made it possible to develop specific enzyme replacement therapies (ERT) for these diseases. At present, a great number of Brazilian medical centers from all regions of the country have experience with ERT for MPS I, II, and VI, acquired not only through patient treatment but also in clinical trials. Taking the three types of MPS together, over 200 patients have been treated with ERT in our country. This document summarizes the experience of the professionals involved, along with the data available in the international literature, bringing together and harmonizing the information available on the management of these severe and progressive diseases, thus disclosing new prospects for Brazilian patients affected by these conditions.

O agostinismo político: contribuições e limites para as discussões políticas medievais

Pós-graduação em História - FCLAS

Mudanças climáticas: o discurso da mídia sobre o aquecimento global

This research is aimed at discussing the ways in which social agents influence global warming, analyzing the discourse of social actors involved in the debate on climate change, since there is a wide divergence in the scientific community about how man is able to modify the climate on a global scale. In fact the debate that permeates the issues beyond the limits of science and enter into a political-economic framework that takes extraordinary proportions. This emphasis can be very unscientific in the fundamental design concepts, or even creating a trivialization of the media. The main way to convey these concepts is to disclose them in the media, but the media has enormous power to transform the concepts and often manipulate the news by creating a common sense goes against the interests of the scientific community. Thus was conducted extensive research in major newspapers and magazines that move in the country. We surveyed the first two papers which were: “Folha de S. Paulo” and “O Estado de S. Paulo”, during the period from January 2000 to December 2008, totaling 3285 units for the newspaper Folha and 2555 for the newspaper Estadão. Subsequently a survey was made of data published in two journals that move at the national level, and these are the magazines VEJA and ÉPOCA for the same period. By performing these steps, it was concluded that several factors involving the media and climate change, such as topic relevance, types of approaches, perspectives of analysis, the staff development, supplies, among other factors of utmost importance for building news. As a result we can say that the media in fulfilling its role of mediator scientific, disclosing only a vision that permeates the scientific debate. The newspaper media, especially newspapers, has an informative and instantaneous. Often this preoccupation...(Complete abstract, click electronic access below)

MicroRNAs targeting the immunomodulatory HLA-G gene: a new survey searching for microRNAs with potential to regulate HLA-G

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

Um ofício polivalente: Rodolfo Garcia e a escrita da história (1932-1945)

Pós-graduação em História - FCLAS

Vozes masculinas no cotidiano escolar: desvelando relações de gênero na Educação Infantil sob a perspectiva fenomenológica de Alfred Schutz

Pós-graduação em Educação Sexual - FCLAR

Comunicação pública e acesso à informação: análise da atuação da SABESP em plataformas virtuais

This undergraduate research final paper analyzed the communication process carried out by the São Paulo State Water and Sanitation Company - Sabesp from the perspective of public communication, social capital and right to information theories. By monitoring Sabesp's institutional fanpage and website from 24 to 30 August 2015, it sought to assess the performance of Sabesp in disclosing public information on the context of the water supply crisis in São Paulo, concerning the fulfillment of requirements of the Right to Information Law (12.527/2011) and the need for interaction and dialogue between the institution and its stakeholders, taken as principles of public communication. The results suggest that digital media can enhance information flow and contribute to foster public relations and civic participation, but there are opportunities for Sabesp to improve communication and reach greater transparency

A face neodesenvolvimentista do Estado brasileiro: o falseamento da "questão social"

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Combined pre- and subtemporal transtentorial approach for epidermoid cysts of the cerebellopontine angle

Objective Epidermoid cysts of the cerebellopontine angle (CPA) can be a surgical challenge for the pediatric neurosurgeon. Ideally, total removal must be achieved; however, occasional adhesions of these tumors to vital neurovascular structures and extension far beyond the midline may preclude their total removal. The aims of this article are to present an alternative surgical approach to these lesions and to provide the rationale for this technique. Material and methods A 16-year-old boy was admitted to our pediatric neurosurgery department with a 1-year history of nonspecific headaches. His neurological examination showed right-sided dysmetria and gait ataxia. Magnetic resonance scans showed a space-occupying lesion on the right CPA with low intensity on T-1-weighted images and high intensity on T-2-weighted images. Results Craniotomy for tumor excision via pre- and subtemporal transtentorial approach was performed disclosing a 3.5 x 3 x 2.8-cm(3) well-encapsulated tumor, which was confirmed to be an epidermoid cyst. The postoperative course was uneventful. Conclusions A combined pre- and subtemporal approach utilizes a wide opening of the tentorium and the option of supratentorial retraction of the cerebellum to provide an excellent angle of approach to CPA lesions involving the anterolateral aspect of the brain stem in children.

Signaling Events During Cyclic Guanosine Monophosphate-Regulated Pigment Aggregation in Freshwater Shrimp Chromatophores

Crustacean color change results partly from granule aggregation induced by red pigment concentrating hormone (RPCH). In shrimp chromatophores, both the cyclic GMP (3', 5'-guanosine monophosphate) and Ca2+ cascades mediate pigment aggregation. However, the signaling elements upstream and downstream from cGMP synthesis by GC-S (cytosolic guanylyl cyclase) remain obscure. We investigate post-RPCH binding events in perfused red ovarian chromatophores to disclose the steps modulating cGMP concentration, which regulates granule translocation. The inhibition of calcium/calmodulin complex (Ca2+/CaM) by N-(6-aminohexyl)-5-chloro-1-naphthalenesulphonamide (W7) induces spontaneous aggregation but inhibits RPCH-triggered aggregation, suggesting a role in pigment aggregation and dispersion. Nitric oxide synthase inhibition by N omega-nitro-L-arginine methyl ester hydrochloride (L-NAME) strongly diminishes RPCH-induced aggregation; protein kinase G inhibition (by rp-cGMPs-triethylamine) reduces RPCH-triggered aggregation and provokes spontaneous dispersion, disclosing NO/PKG participation in aggregation signaling. Myosin light chain phosphatase inhibition (by cantharidin) accelerates RPCH-triggered aggregation, whereas Rho-associated protein kinase inhibition (by Y-27632, H-11522) reduces RPCH-induced aggregation and accelerates dispersion. MLCP (myosin light chain kinase) and ROCK (Rho-associated protein kinase) may antagonistically regulate myosin light chain (MLC) dephosphorylation/phosphorylation during pigment dispersion/aggregation. We propose the following general hypothesis for the cGMP/Ca2+ cascades that regulate pigment aggregation in crustacean chromatophores: RPCH binding increases Ca2+ (int), activating the Ca2+/CaM complex, releasing NOS-produced nitric oxide, and causing GC-S to synthesize cGMP that activates PKG, which phosphorylates an MLC activation site. Myosin motor activity is initiated by phosphorylation of an MLC regulatory site by ROCK activity and terminated by MLCP-mediated dephosphorylation. Qualitative comparison reveals that this signaling pathway is conserved in vertebrate and invertebrate chromatophores alike.

Polimorphisms in Inflammasome Genes Are Involved in the Predisposition to Systemic Lupus Erythematosus

Recent findings provide evidence of inflammasome critical role in the predisposition to autoimmune disorders. The involvement of inflammasome in the pathogenesis of systemic lupus erythematosus (SLE) has been hypothesized even if no significant association within inflammasome genes mutations or polymorphisms and lupus has been reported yet. We analyzed 14 single nucleotide polymorphisms (SNPs) within 7 inflammasome genes (NLRP1, NLRP3, NLRC4, AIM2, CARD8, CASP1, IL1B) in 144 patients affected by systemic lupus erythematosus and in 158 healthy controls from Southern Brazilian (state of Sao Paulo) with the aim of disclosing the possible role of inflammasome genes in the susceptibility of SLE. Our results demonstrated that NLRP1 rs2670660 SNP and the NLRP1 rs12150220-rs2670660 A-G haplotype were associated with SLE in our study population, and in particular with the development of nephritis, rash and arthritis. These findings are concordant with previously reported association of NLRP1 with vitiligo and type-1 diabetes underlining once more the involvement of NALP1 inflammasome in the pathogenesis of autoimmune disorders.

Brain activity and medical diagnosis: an EEG study

Abstract Background Despite new brain imaging techniques that have improved the study of the underlying processes of human decision-making, to the best of our knowledge, there have been very few studies that have attempted to investigate brain activity during medical diagnostic processing. We investigated brain electroencephalography (EEG) activity associated with diagnostic decision-making in the realm of veterinary medicine using X-rays as a fundamental auxiliary test. EEG signals were analysed using Principal Components (PCA) and Logistic Regression Analysis Results The principal component analysis revealed three patterns that accounted for 85% of the total variance in the EEG activity recorded while veterinary doctors read a clinical history, examined an X-ray image pertinent to a medical case, and selected among alternative diagnostic hypotheses. Two of these patterns are proposed to be associated with visual processing and the executive control of the task. The other two patterns are proposed to be related to the reasoning process that occurs during diagnostic decision-making. Conclusions PCA analysis was successful in disclosing the different patterns of brain activity associated with hypothesis triggering and handling (pattern P1); identification uncertainty and prevalence assessment (pattern P3), and hypothesis plausibility calculation (pattern P2); Logistic regression analysis was successful in disclosing the brain activity associated with clinical reasoning success, and together with regression analysis showed that clinical practice reorganizes the neural circuits supporting clinical reasoning.

Computational methods for genome screening

Motivation An actual issue of great interest, both under a theoretical and an applicative perspective, is the analysis of biological sequences for disclosing the information that they encode. The development of new technologies for genome sequencing in the last years, opened new fundamental problems since huge amounts of biological data still deserve an interpretation. Indeed, the sequencing is only the first step of the genome annotation process that consists in the assignment of biological information to each sequence. Hence given the large amount of available data, in silico methods became useful and necessary in order to extract relevant information from sequences. The availability of data from Genome Projects gave rise to new strategies for tackling the basic problems of computational biology such as the determination of the tridimensional structures of proteins, their biological function and their reciprocal interactions. Results The aim of this work has been the implementation of predictive methods that allow the extraction of information on the properties of genomes and proteins starting from the nucleotide and aminoacidic sequences, by taking advantage of the information provided by the comparison of the genome sequences from different species. In the first part of the work a comprehensive large scale genome comparison of 599 organisms is described. 2,6 million of sequences coming from 551 prokaryotic and 48 eukaryotic genomes were aligned and clustered on the basis of their sequence identity. This procedure led to the identification of classes of proteins that are peculiar to the different groups of organisms. Moreover the adopted similarity threshold produced clusters that are homogeneous on the structural point of view and that can be used for structural annotation of uncharacterized sequences. The second part of the work focuses on the characterization of thermostable proteins and on the development of tools able to predict the thermostability of a protein starting from its sequence. By means of Principal Component Analysis the codon composition of a non redundant database comprising 116 prokaryotic genomes has been analyzed and it has been showed that a cross genomic approach can allow the extraction of common determinants of thermostability at the genome level, leading to an overall accuracy in discriminating thermophilic coding sequences equal to 95%. This result outperform those obtained in previous studies. Moreover, we investigated the effect of multiple mutations on protein thermostability. This issue is of great importance in the field of protein engineering, since thermostable proteins are generally more suitable than their mesostable counterparts in technological applications. A Support Vector Machine based method has been trained to predict if a set of mutations can enhance the thermostability of a given protein sequence. The developed predictor achieves 88% accuracy.

Multidimensional Measures of Firm Competitiveness: a Model-Based Approach

The concept of competitiveness, for a long time considered as strictly connected to economic and financial performances, evolved, above all in recent years, toward new, wider interpretations disclosing its multidimensional nature. The shift to a multidimensional view of the phenomenon has excited an intense debate involving theoretical reflections on the features characterizing it, as well as methodological considerations on its assessment and measurement. The present research has a twofold objective: going in depth with the study of tangible and intangible aspect characterizing multidimensional competitive phenomena by assuming a micro-level point of view, and measuring competitiveness through a model-based approach. Specifically, we propose a non-parametric approach to Structural Equation Models techniques for the computation of multidimensional composite measures. Structural Equation Models tools will be used for the development of the empirical application on the italian case: a model based micro-level competitiveness indicator for the measurement of the phenomenon on a large sample of Italian small and medium enterprises will be constructed.

Il geografo riluttante. R.K. Narayan e il mondo di Malgudi

Il presente lavoro è dedicato allo studio della geografia immaginaria creata dallo scrittore indiano di lingua inglese R.K. Narayan (1906-2001), allo scopo non solo di indagare la relazione che si stabilisce tra spazio, personaggi e racconto, ma anche di rilevare l’interazione tra il mondo narrativo e le rappresentazioni dominanti dello spazio indiano elaborate nel contesto coloniale e postcoloniale. Dopo un primo capitolo di carattere teorico-metodologico (che interroga le principali riflessioni seguite allo "spatial turn" che ha interessato le scienze umane nel corso del Novecento, i concetti fondamentali formulati nell’ambito della teoria dei "fictional worlds", e i più recenti approcci al rapporto tra spazio e letteratura), la ricerca si articola in due ulteriori sezioni, che si rivolgono ai quattordici romanzi dell’autore attraverso una pratica interpretativa di ispirazione geocritica e “spazializzata”. Nel secondo capitolo, che concerne la dimensione “verticale” che si estende dal cronotopo dei romanzi a quello dell’autore e dei lettori, si procede al rilevamento, all’interno del mondo narrativo, di tre macro-paesaggi, successivamente messi a confronto con le rappresentazioni endogene e esogene dello spazio extratestuale; da questo confronto, la cittadina di Malgudi emerge come proposta autoriale di riorganizzazione sociale e urbana dal carattere innovativo e dallo statuto eterotopico, sia in rapporto alla tradizione letteraria dalla quale origina, sia rispetto alle circostanze ambientali dell’India meridionale in cui essa è finzionalmente collocata. Seguendo una dinamica “orizzontale”, il terzo capitolo esamina infine il rapporto tra lo spazio frazionato di Malgudi, i luoghi praticati dai suoi abitanti e la relazione che questi instaurano con il territorio transfrontaliero e con la figura del forestiero; inoltre, al fine di stabilire la misura in cui la natura dello spazio narrativo influisce sulla forma del racconto, si osservano le coincidenze tra il tema dell’incompiutezza che pervade le vicende dei personaggi e la forma aperta dei finali romanzeschi.