ATIVIDADE OCUPACIONAL E CATARATA SENIL – OPINIÃO DE PACIENTES DE HOSPITAL UNIVERSITÁRIO

Purpose: To identify perceptions about relationship between the occupational activity and origin of the disease in persons with senile cataract. Methods: A descriptive observational transversal study was developed by a structured questionnaire which was applied during interviews elaborated from an exploratory study . The sample was accessible with patients with cataract in an ophthalmogical clinic of an university hospital. Results: One hundred and ten persons of boths genders (34,5% males and 65,5% females aged between 43 and 89 years old were submitted to the study. The great proportion of persons was not developing payed activities (87,3%). Among the most frequent opinions about the causes of cataract were advanced age (69,1%), excessive use of the vision (57,3%) and influence of hot temperatures against the eyes (40,9%). Regarding the opinions about the relation between professional activities and development of cataract, 56,4% did not believe that the activity shown had influence in the origin of disease, while 43,6% believed in a relation between the occupational activity and the development of the disease. Visual strain (37,5%), excessive hot temperatures (12,5%) and use of chemical substances (10,3%) were the attributable causes of cataract related to professional activities. Conclusions: We observed a great predominance of aged with low schooling and not developing payed activities persons and retired from the work market suggesting low socio-economic levels and low acquisitive power. Situations indicated by the examined persons as excessive use of the vision and hot temperatures suffered by the eyes during occupational activities suggest an erroneous knowledge about disease. Objetivo: Identificar a situação ocupacional e percepções de portadores de catarata senil sobre a relação entre a atividade ocupacional exercida e o surgimento da doença. Métodos: Desenvolveu-se estudo observacional transversal descritivo, por meio de questionário estruturado, aplicado por entrevista, elaborado a partir de estudo exploratório. A amostra, prontamente acessível, foi formada por pacientes atendidos pelo setor de catarata da clínica oftalmológica de um hospital universitário. Resultados: A amostra foi constituída por 110 sujeitos de ambos os sexos (34,5% homens; 65,5% mulheres), com idade entre 43 e 89 anos, ± 10,3 anos. A maior proporção dos entrevistados não exercia atividade remunerada (87,3%). Dentre as opiniões acerca das causas da catarata, destacaram-se a velhice (69,1%), o uso excessivo dos olhos (57,3%) e a exposição ao calor nos olhos (40,9%). Quanto à opinião sobre relação entre atividades profissionais exercidas e catarata, 56,4% não acreditavam que o trabalho tivesse influído, enquanto 43,6% atribuíram às atividades ocupacionais a essa afecção ocular. Foram atribuídos às atividades profissionais: o cansaço visual (37,5%), contato com calor excessivo (12,5%) e uso de produto químico (10,3%). Conclusões: Evidenciou-se predominância acentuada de idosos de baixa escolaridade, não mais exercendo atividade ocupacional e inativos no mercado de trabalho. Entre os que exerciam, prevaleceram as ocupações manuais especializadas, o que sugere reduzido nível socioeconômico e baixo poder aquisitivo. Atribuíram como causas do comprometimento visual situações decorrentes de atividades ocupacionais, como o uso excessivo dos olhos e a exposição ao calor, evidenciando-se conhecimentos errôneos.

Insertion of Horizontally Transferred Genes within Conserved Syntenic Regions of Yeast Genomes

Horizontal gene transfer has been occasionally mentioned in eukaryotic genomes, but such events appear much less numerous than in prokaryotes, where they play important functional and evolutionary roles. In yeasts, few independent cases have been described, some of which corresponding to major metabolic functions, but no systematic screening of horizontally transferred genes has been attempted so far. Taking advantage of the synteny conservation among five newly sequenced and annotated genomes of Saccharomycetaceae, we carried out a systematic search for HGT candidates amidst genes present in only one species within conserved synteny blocks. Out of 255 species-specific genes, we discovered 11 candidates for HGT, based on their similarity with bacterial proteins and on reconstructed phylogenies. This corresponds to a minimum of six transfer events because some horizontally acquired genes appear to rapidly duplicate in yeast genomes (e.g. YwqG genes in Kluyveromyces thermotolerans and serine recombinase genes of the IS607 family in Saccharomyces kluyveri). We show that the resulting copies are submitted to a strong functional selective pressure. The mechanisms of DNA transfer and integration are discussed, in relation with the generally small size of HGT candidates. Our results on a limited set of species expand by 50% the number of previously published HGT cases in hemiascomycetous yeasts, suggesting that this type of event is more frequent than usually thought. Our restrictive method does not exclude the possibility that additional HGT events exist. Actually, ancestral events common to several yeast species must have been overlooked, and the absence of homologs in present databases leaves open the question of the origin of the 244 remaining species-specific genes inserted within conserved synteny blocks

The Genome of Nectria haematococca: Contribution of Supernumerary Chromosomes to Gene Expansion

The ascomycetous fungus Nectria haematococca, (asexual name Fusarium solani), is a member of a group of >50 species known as the “Fusarium solani species complex”. Members of this complex have diverse biological properties including the ability to cause disease on >100 genera of plants and opportunistic infections in humans. The current research analyzed the most extensively studied member of this complex, N. haematococca mating population VI (MPVI). Several genes controlling the ability of individual isolates of this species to colonize specific habitats are located on supernumerary chromosomes. Optical mapping revealed that the sequenced isolate has 17 chromosomes ranging from 530 kb to 6.52 Mb and that the physical size of the genome, 54.43 Mb, and the number of predicted genes, 15,707, are among the largest reported for ascomycetes. Two classes of genes have contributed to gene expansion: specific genes that are not found in other fungi including its closest sequenced relative, Fusarium graminearum; and genes that commonly occur as single copies in other fungi but are present as multiple copies in N. haematococca MPVI. Some of these additional genes appear to have resulted from gene duplication events, while others may have been acquired through horizontal gene transfer. The supernumerary nature of three chromosomes, 14, 15, and 17, was confirmed by their absence in pulsed field gel electrophoresis experiments of some isolates and by demonstrating that these isolates lacked chromosome-specific sequences found on the ends of these chromosomes. These supernumerary chromosomes contain more repeat sequences, are enriched in unique and duplicated genes, and have a lower G+C content in comparison to the other chromosomes. Although the origin(s) of the extra genes and the supernumerary chromosomes is not known, the gene expansion and its large genome size are consistent with this species' diverse range of habitats. Furthermore, the presence of unique genes on supernumerary chromosomes might account for individual isolates having different environmental niches

Simultaneous Analysis of Proteome, Phospho- and Glycoproteome of Rat Kidney Tissue with Electrostatic Repulsion Hydrophilic Interaction Chromatography

Protein post-translational modifications (PTMs) are regulated separately from protein expression levels. Thus, simultaneous characterization of the proteome and its PTMs is pivotal to an understanding of protein regulation, function and activity. However, concurrent analysis of the proteome and its PTMs by mass spectrometry is a challenging task because the peptides bearing PTMs are present in sub-stoichiometric amounts and their ionization is often suppressed by unmodified peptides of high abundance. We describe here a method for concurrent analysis of phosphopeptides, glycopeptides and unmodified peptides in a tryptic digest of rat kidney tissue with a sequence of ERLIC and RP-LC-MS/MS in a single experimental run, thereby avoiding inter-experimental variation. Optimization of loading solvents and elution gradients permitted ERLIC to be performed with totally volatile solvents. Two SCX and four ERLIC gradients were compared in details, and one ERLIC gradient was found to perform the best, which identified 2929 proteins, 583 phosphorylation sites in 338 phosphoproteins and 722 N-glycosylation sites in 387 glycoproteins from rat kidney tissue. Two hundred low-abundance proteins with important functions were identified only from the glyco- or phospho-subproteomes, reflecting the importance of the enrichment and separation of modified peptides by ERLIC. In addition, this strategy enables identification of unmodified and corresponding modified peptides (partial phosphorylation and N-glycosylation) from the same protein. Interestingly, partially modified proteins tend to occur on proteins involved in transport. Moreover, some membrane or extracellular proteins, such as versican core protein and fibronectin, were found to have both phosphorylation and N-glycosylation, which may permit an assessment of the potential for cross talk between these two vital PTMs and their roles in regulation

Recent developments in protein–ligand affinity mass spectrometry

This review provides an overview of direct and indirect technologies to screen protein–ligand interactions with mass spectrometry. These technologies have as a key feature the selection or affinity purification of ligands in mixtures prior to detection. Specific fields of interest for these technologies are metabolic profiling of bioactive metabolites, natural extract screening, and the screening of libraries for bioactives, such as parallel synthesis libraries and small combichem libraries. The review addresses the principles of each of the methods discussed, with a focus on developments in recent years, and the applicability of the methods to lead generation and development in drug discovery

Studying protein–protein affinity and immobilized ligand–protein affinity interactions using MS-based methods

This review discusses the most important current methods employing mass spectrometry (MS) analysis for the study of protein affinity interactions. The methods are discussed in depth with particular reference to MS-based approaches for analyzing protein–protein and protein–immobilized ligand interactions, analyzed either directly or indirectly. First, we introduce MS methods for the study of intact protein complexes in the gas phase. Next, pull-down methods for affinity-based analysis of protein–protein and protein–immobilized ligand interactions are discussed. Presently, this field of research is often called interactomics or interaction proteomics. A slightly different approach that will be discussed, chemical proteomics, allows one to analyze selectivity profiles of ligands for multiple drug targets and off-targets. Additionally, of particular interest is the use of surface plasmon resonance technologies coupled with MS for the study of protein interactions. The review addresses the principle of each of the methods with a focus on recent developments and the applicability to lead compound generation in drug discovery as well as the elucidation of protein interactions involved in cellular processes. The review focuses on the analysis of bioaffinity interactions of proteins with other proteins and with ligands, where the proteins are considered as the bioactives analyzed by MS

Pharmacological Properties and Biological Functions of the GPR17 Receptor, a Potential Target for Neuro-Regenerative Medicine

In 2006, cells heterologously expressing the "orphan" receptor GPR17 were shown to acquire responses to both uracil nucleotides and cysteinyl-leukotrienes, two families of signaling molecules accumulating in brain or heart as a result of hypoxic/traumatic injuries. In subsequent years, evidence of GPR17 key role in oligodendrogenesis and myelination has highlighted it as a "model receptor" for new therapies in demyelinating and neurodegenerative diseases. The apparently contrasting evidence in the literature about the role of GPR17 in promoting or inhibiting myelination can be due to its transient expression in the intermediate stages of differentiation, exerting a pro-differentiating function in early oligodendrocyte precursor cells (OPCs), and an inhibitory role in late stage maturing cells. Meanwhile, several papers extended the initial data on GPR17 pharmacology, highlighting a "promiscuous" behavior of this receptor; indeed, GPR17 is able to respond to other emergency signals like oxysterols or the pro-inflammatory cytokine SDF-1, underlying GPR17 ability to adapt its responses to changes of the surrounding extracellular milieu, including damage conditions. Here, we analyze the available literature on GPR17, in an attempt to summarize its emerging biological roles and pharmacological properties

Methotrexate as a possible trigger of macrophage activation syndrome in systemic juvenile idiopathic arthritis.

Macrophage activation syndrome (MAS) is a potentially life threatening complication of chronic rheumatic diseases, particularly systemic juvenile idiopathic arthritis (JIA). A number of triggers have been related to the development of MAS, including viral infections, nonsteroidal antiinflammatory drug therapy, and gold salt injections. We describe a patient with systemic JIA who developed MAS shortly after receiving methotrexate, suggesting that this drug can be regarded as a potential trigger of MAS in children with JIA