ROTEIROS TURÍSTICOS DA REGIÃO CENTRAL DO RIO GRANDE DO SUL – Estudo sobre as Principais Características e Atrativos aos Turistas

Um roteiro turístico caracteriza-se pela convergência de ações e de atrativos aos turistas numa determinada localidade ou região. Considerado importante para dinamizar o setor de turismo, os roteiros turísticos necessitam ser planejados, organizados e promovidos de forma adequada para atrair os turistas. Nesta perspectiva, este estudo objetiva mapear os roteiros turísticos da Região Central do estado do Rio Grande do Sul (RS) e, mais especificamente, verificar a localização/região em que estão organizados e as características principais destes roteiros. Como procedimento metodológico utilizou-se a abordagem exploratória, com uma pesquisa qualitativa. Observou-se que na região estudada ainda existem poucos roteiros turísticos organizados, com predominância de utilização dos recursos naturais como principal atrativo turístico.

Obstructive sleep apnea and objective short sleep duration are independently associated with the risk of serum vitamin D deficiency

BACKGROUND:Studies demonstrate an association between vitamin D (25(OH)D) deficiency and sleep disturbances, such as obstructive sleep apnea (OSA) and short sleep duration. However, to date, no studies have concurrently and objectively evaluated the effect of these factors on 25(OH)D. OBJECTIVES:To evaluate whether OSA and objective short sleep duration are independently associated with reduced 25(OH)D in an adult population sample. METHODS:A cross-sectional study included 657 individuals from the city of Sao Paulo, Brazil, as part of the ERA project. Participants fulfilled questionnaires and underwent clinical evaluation, polysomnography and blood sample collection for 25(OH)D quantification. OSA was classified into three categories (mild, moderate and severe). The risk of 25(OH)D deficiency was considered as levels<30 ng/mL. Short sleep duration was defined as total sleep time<6 hours. RESULTS:The risk of 25(OH)D deficiency was observed in 59.5% of the sample, affecting more individuals of the female gender, obese, with African American ethnicity, and those that were smokers, sedentary and presented hypertension and diabetes. In the final logistic model adjusted for age, gender, ethnicity, obesity, smoking, hypertension, diabetes, sedentary lifestyle, seasonality and creatinine serum levels, both OSA and short sleep duration showed significant independent associations with the risk of 25(OH)D deficiency (moderate OSA: OR for 25(OH)D<30 = 2.21, 95% CI: 1.35-3.64, p<0.01; severe OSA: OR for 25(OH)D<30 = 1.78, 95% CI: 1.06-3.00, p = 0.03; short sleep duration: OR for 25(OH)D<30 = 1.61, 95% CI: 1.15-2.26, p = 0.01). After a subgroup analysis, similar results were observed only in participants ≥50 years. CONCLUSION:OSA and short sleep duration are independently associated with the risk of 25(OH)D deficiency in an adult population. Age-related changes in vitamin D metabolism and the frequency of sleep disorders may be involved in these associations. Future studies exploring whether 25(OH)D levels may modulate OSA and sleep curtailment-related outcomes are needed

Marketing Digital e Turismo: Uso de Websites para Atração de Turistas nos Municípios do Rio Grande Do Sul/ Brasil

Com a utilização cada vez mais frequente da internet na busca de informações para a escolha dentre as opções de turismo disponíveis, a otimização dos websites turísticos por parte dos municípios pode ser uma ferramenta importante para o desenvolvimento do turismo. Informações  claras sobre os atrativos turísticos facilitam aos turistas escolher o destino, assim como informações sobre a disponibilidade de hotéis e, também, a gastronomia que o local oferece. Com o objetivo de analisar qualitativamente os websites de municípios do Rio Grande do Sul, este estudo, através de uma pesquisa exploratória, pretende disponibilizar aos gestores um diagnóstico comparativo, no intuito de auxiliar na visibilidade do atrativo turístico e sensibilização dos turistas potenciais, para incremento do setor e da economia local

Pathogenic Carboxyl Ester Lipase (CEL) Variants Interact with the Normal CEL Protein in Pancreatic Cells

Mutations in the gene encoding the digestive enzyme carboxyl ester lipase (CEL) are linked to pancreatic disease. The CEL variant denoted CEL-HYB predisposes to chronic pancreatitis, whereas the CEL-MODY variant causes MODY8, an inherited disorder of endocrine and exocrine pancreatic dysfunction. Both pathogenic variants exhibit altered biochemical and cellular properties compared with the normal CEL protein (CEL-WT, wild type). We here aimed to investigate effects of CEL variants on pancreatic acinar and ductal cell lines. Following extracellular exposure, CEL-HYB, CEL-MODY, and CEL-WT were endocytosed. The two pathogenic CEL proteins significantly reduced cell viability compared with CEL-WT. We also found evidence of CEL uptake in primary human pancreatic acinar cells and in native ductal tissue. Moreover, coexpression of CEL-HYB or CEL-MODY with CEL-WT affected secretion of the latter, as CEL-WT was observed to accumulate intracellularly to a higher degree in the presence of either pathogenic variant. Notably, in coendocytosis experiments, both pathogenic variants displayed a modest effect on cell viability when CEL-WT was present, indicating that the normal protein might diminish toxic effects conferred by CEL-HYB and CEL-MODY. Taken together, our findings provide valuable insight into how the pathogenic CEL variants predispose to pancreatic disease and why these disorders develop slowly over time.publishedVersio

Pathogenic Carboxyl Ester Lipase (CEL) Variants Interact with the Normal CEL Protein in Pancreatic Cells

Mutations in the gene encoding the digestive enzyme carboxyl ester lipase (CEL) are linked to pancreatic disease. The CEL variant denoted CEL-HYB predisposes to chronic pancreatitis, whereas the CEL-MODY variant causes MODY8, an inherited disorder of endocrine and exocrine pancreatic dysfunction. Both pathogenic variants exhibit altered biochemical and cellular properties compared with the normal CEL protein (CEL-WT, wild type). We here aimed to investigate effects of CEL variants on pancreatic acinar and ductal cell lines. Following extracellular exposure, CEL-HYB, CEL-MODY, and CEL-WT were endocytosed. The two pathogenic CEL proteins significantly reduced cell viability compared with CEL-WT. We also found evidence of CEL uptake in primary human pancreatic acinar cells and in native ductal tissue. Moreover, coexpression of CEL-HYB or CEL-MODY with CEL-WT affected secretion of the latter, as CEL-WT was observed to accumulate intracellularly to a higher degree in the presence of either pathogenic variant. Notably, in coendocytosis experiments, both pathogenic variants displayed a modest effect on cell viability when CEL-WT was present, indicating that the normal protein might diminish toxic effects conferred by CEL-HYB and CEL-MODY. Taken together, our findings provide valuable insight into how the pathogenic CEL variants predispose to pancreatic disease and why these disorders develop slowly over time

Genetic and cellular studies of carboxyl-ester lipase (CEL), a protein involved in exocrine and endocrine pancreatic disease

Carboxyl-ester lipase (CEL) is a digestive enzyme mainly expressed in pancreatic acinar cells, from which it is secreted into the duodenum as a component of pancreatic juice. Mutations in the human CEL gene have been linked to pancreatic disease. All pathogenic CEL variants identified so far affect the C-terminal region of the protein, which is very polymorphic due to repeated segments of 11 amino acids. A single-base deletion in the CEL repeat region causes a dominantly inherited syndrome of exocrine and endocrine pancreatic dysfunction denoted MODY8, whereas a copy number variant of the CEL locus, designated CEL-HYB, predisposes for chronic pancreatitis. To explore the role of CEL variants in pancreatic disease, we examined if CEL CNVs and VNTR length polymorphisms could affect the risk for developing pancreatic cancer. No studies have so far linked this disease to CEL, despite the fact that chronic pancreatitis is a known risk factor for pancreatic cancer. Our results from CNV screening and DNA fragment analyses in two pancreatic cancer cohorts of Caucasian origin did, however, not show an association between pancreatic cancer and the investigated CEL variants. Still, the CEL gene is highly polymorphic and a role of CEL variants in influencing pancreatic cancer risk cannot be excluded. To gain knowledge of how the pathogenic CEL protein variants, CEL-MODY and CEL-HYB, may cause or predispose for pancreatic disease, we started studies in cellular model systems. We found that both normal CEL and CEL-MODY most likely followed a classical secretory pathway. Their subcellular distributions did, however, differ as only CEL-MODY was observed as an aggregate at the cell surface and inside large cytoplasmic vacuoles, identified as components of the endosomal system. We further aimed to investigate the uptake of CEL protein variants in pancreatic acinar, beta and ductal cell lines and to study their effect on cell viability, as endocytosis may play a central role in disease pathogeneses. We found all CEL variants to be internalized, and compared to normal CEL, endocytosed CEL-MODY protein significantly reduced viability of all pancreatic cell line models, manifesting as a decrease in cellular metabolism and increased caspase3/7 activity. We found that also endocytosed CEL-HYB significantly reduced the viability of pancreatic acinar and ductal cell lines, as compared to normal CEL. Moreover, we developed a co- expression model as patients are heterozygous carriers of either CEL-MODY or CEL- HYB along with one copy of the normal CEL gene. Interestingly, we found both CEL- MODY and CEL-HYB to affect the intracellular fate of normal CEL, whilst the cellular toxicity of the two pathogenic variants after co-endocytosis became reduced in the presence of normal CEL. In conclusion, these studies highlight the exceedingly polymorphic nature of the human CEL gene and may be important for our understanding of how the pathogenic CEL variants predispose for pancreatic disease

FOOD RECREATED BY THE PORTUGUESE LITERATURE: INTERVIEW WITH CARLOS REIS

Dalva Calvão and Monica Figueiredo interview Carlos Reis.</p

The Human N-Alpha-Acetyltransferase 40 (hNaa40p/ hNatD) Is Conserved from Yeast and N-Terminally Acetylates Histones H2A and H4

Protein Na-terminal acetylation (Nt-acetylation) is considered one of the most common protein modification in eukaryotes, and 80-90% of all soluble human proteins are modified in this way, with functional implications ranging from altered protein function and stability to translocation potency amongst others. Nt-acetylation is catalyzed by N-terminal acetyltransferases (NATs), and in yeast five NAT types are identified and denoted NatA-NatE. Higher eukaryotes additionally express NatF. Except for NatD, human orthologues for all yeast NATs are identified. yNatD is defined as the catalytic unit Naa40p (Nat4) which co-translationally Nt-acetylates histones H2A and H4. In this study we identified and characterized hNaa40p/hNatD, the human orthologue of the yeast Naa40p. An in vitro proteome-derived peptide library Nt-acetylation assay indicated that recombinant hNaa40p acetylates N-termini starting with the consensus sequence Ser-Gly-Gly-Gly-Lys-, strongly resembling the N-termini of the human histones H2A and H4. This was confirmed as recombinant hNaa40p Nt-acetylated the oligopeptides derived from the N-termini of both histones. In contrast, a synthetically Nt-acetylated H4 N-terminal peptide with all lysines being non-acetylated, was not significantly acetylated by hNaa40p, indicating that hNaa40p catalyzed H4 Na- acetylation and not H4 lysine Ne-acetylation. Also, immunoprecipitated hNaa40p specifically Nt-acetylated H4 in vitro. Heterologous expression of hNaa40p in a yeast naa40-D strain restored Nt-acetylation of yeast histone H4, but not H2A in vivo, probably reflecting the fact that the N-terminal sequences of human H2A and H4 are highly similar to each other and to yeast H4 while the N-terminal sequence of yeast H2A differs. Thus, Naa40p seems to have co-evolved with the human H2A sequence. Finally, a partial co-sedimentation with ribosomes indicates that hNaa40p co-translationally acetylates H2A and H4. Combined, our results strongly suggest that human Naa40p/NatD is conserved from yeast. Thus, the NATs of all classes of N-terminally acetylated proteins in humans now appear to be accounted for