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StructRNAfinder: an automated pipeline and web server for RNA families prediction
No full textAbstract\ud
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Background\ud
The function of many noncoding RNAs (ncRNAs) depend upon their secondary structures. Over the last decades, several methodologies have been developed to predict such structures or to use them to functionally annotate RNAs into RNA families. However, to fully perform this analysis, researchers should utilize multiple tools, which require the constant parsing and processing of several intermediate files. This makes the large-scale prediction and annotation of RNAs a daunting task even to researchers with good computational or bioinformatics skills.\ud
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Results\ud
We present an automated pipeline named StructRNAfinder that predicts and annotates RNA families in transcript or genome sequences. This single tool not only displays the sequence/structural consensus alignments for each RNA family, according to Rfam database but also provides a taxonomic overview for each assigned functional RNA. Moreover, we implemented a user-friendly web service that allows researchers to upload their own nucleotide sequences in order to perform the whole analysis. Finally, we provided a stand-alone version of StructRNAfinder to be used in large-scale projects. The tool was developed under GNU General Public License (GPLv3) and is freely available at \ud
http://structrnafinder.integrativebioinformatics.me\ud
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Conclusions\ud
The main advantage of StructRNAfinder relies on the large-scale processing and integrating the data obtained by each tool and database employed along the workflow, of which several files are generated and displayed in user-friendly reports, useful for downstream analyses and data exploration.This work was supported by the Programa Becas Iberoamérica, Jóvenes Profesores e Investigadores, Santander Universidades, Chile; Fondecyt Iniciación, Comisión Nacional de Investigación Científica y Tecnológica (CONICYT), Chile, grant 11161020; Programa Nacional de Inserción de Capital Humano Avanzado en la Academia, PAI-CONICYT, Chile, grant PAI79170021; Fondo de Financiamiento de Centro de Investigación en Áreas Prioritárias (FONDAP), CONICYT, grant 15130011; Programa de Bienes Públicos Estratégicos para la Competitividad, Corporación de Fomento de la Producción (CORFO), Chile, grant 16BPE-62321; Subsidio Semilla de Asignación Flexible (SSAF), CORFO, grant 14-SSAF-27061-9; and Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP), Brazil, grant 12/19278–6. RAC received a PhD fellowship from Vicerrectoría de Investigación, Universidad Mayor, Chile.
Association between plasma fatty acids and inflammatory markers in patients with and without insulin resistance and in secondary prevention of cardiovascular disease, a cross-sectional study
No full textAbstract\ud
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Background\ud
Proinflammatory biomarkers levels are increased among patients with cardiovascular disease, and it is known that both the presence of insulin resistance and diet may influence those levels. However, these associations are not well studied among patients with established cardiovascular disease. Our objective is to compare inflammatory biomarker levels among cardiovascular disease secondary prevention patients with and without insulin resistance, and to evaluate if there is any association between plasma fatty acid levels and inflammatory biomarker levels among them.\ud
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Methods\ud
In this cross-sectional sub-study from the BALANCE Program Trial, we collected data from 359 patients with established cardiovascular disease. Plasma fatty acids and inflammatory biomarkers (interleukin (IL)-1β, IL-6, IL-8, IL-10, IL-12, high sensitive C-reactive protein (hs-CRP), adiponectin, and tumor necrosis factor (TNF)-alpha) were measured. Biomarkers and plasma fatty acid levels of subjects across insulin resistant and not insulin resistant groups were compared, and general linear models were used to examine the association between plasma fatty acids and inflammatory biomarkers.\ud
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Results\ud
Subjects with insulin resistance had a higher concentration of hs-CRP (p = 0.002) and IL-6 (p = 0.002) than subjects without insulin resistance. Among subjects without insulin resistance there was a positive association between stearic fatty acid and IL-6 (p = 0.032), and a negative association between alpha-linolenic fatty acid and pro-inflammatory biomarkers (p < 0.05). Among those with insulin resistance there was a positive association between monounsaturated fatty acids and arachidonic fatty acid and adiponectin (p < 0.05), and a negative association between monounsaturated and polyunsaturated fatty acids and pro-inflammatory biomarkers (p < 0.05), as well as a negative association between polyunsaturated fatty acids and adiponectin (p < 0.05). Our study has not found any association between hs-CRP and plasma fatty acids.\ud
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Conclusions\ud
Subjects in secondary prevention for cardiovascular disease with insulin resistance have a higher concentration of hs-CRP and IL-6 than individuals without insulin resistance, and these inflammatory biomarkers are positively associated with saturated fatty acids and negatively associated with unsaturated fatty acids.Part of this work was supported by Hospital do Coração (HCor) as part of the “Hospitais de Excelência a Serviço do SUS (PROADI-SUS)” Program, in partnership with the Brazilian Ministry of Health
The practice of intensive care in Latin America: a survey of academic intensivists
No full textAbstract
Background
Intensive care medicine is a relatively young discipline that has rapidly grown into a full-fledged medical subspecialty. Intensivists are responsible for managing an ever-increasing number of patients with complex, life-threatening diseases. Several factors may influence their performance, including age, training, experience, workload, and socioeconomic context. The aim of this study was to examine individual- and work-related aspects of the Latin American intensivist workforce, mainly with academic appointments, which might influence the quality of care provided. In consequence, we conducted a cross-sectional study of intensivists at public and private academic and nonacademic Latin American intensive care units (ICUs) through a web-based electronic survey submitted by email. Questions about personal aspects, work-related topics, and general clinical workflow were incorporated.
Results
Our study comprised 735 survey respondents (53% return rate) with the following country-specific breakdown: Brazil (29%); Argentina (19%); Chile (17%); Uruguay (12%); Ecuador (9%); Mexico (7%); Colombia (5%); and Bolivia, Peru, Guatemala, and Paraguay combined (2%). Latin American intensivists were predominantly male (68%) young adults (median age, 40 [IQR, 35–48] years) with a median clinical ICU experience of 10 (IQR, 5–20) years. The median weekly workload was 60 (IQR, 47–70) h. ICU formal training was between 2 and 4 years. Only 63% of academic ICUs performed multidisciplinary rounds. Most intensivists (85%) reported adequate conditions to manage patients with septic shock in their units. Unsatisfactory conditions were attributed to insufficient technology (11%), laboratory support (5%), imaging resources (5%), and drug shortages (5%). Seventy percent of intensivists participated in research, and 54% read scientific studies regularly, whereas 32% read no more than one scientific study per month. Research grants and pharmaceutical sponsorship are unusual funding sources in Latin America. Although Latin American intensivists are mostly unsatisfied with their income (81%), only a minority (27%) considered changing to another specialty before retirement.
Conclusions
Latin American intensivists constitute a predominantly young adult workforce, mostly formally trained, have a high workload, and most are interested in research. They are under important limitations owing to resource constraints and overt dissatisfaction. Latin America may be representative of other world areas with similar challenges for intensivists. Specific initiatives aimed at addressing these situations need to be devised to improve the quality of critical care delivery in Latin America
In vitro gentamicin exposure alters caveolae protein profile in cochlear spiral ligament pericytes
No full textAbstract
Background
The aminoglycoside antibiotic gentamicin is an ototoxic drug and has been used experimentally to investigate cochlear damage induced by noise.
We have investigated the changes in the protein profile associated with caveolae in gentamicin treated and untreated spiral ligament (SL) pericytes, specialized cells in the blood labyrinth barrier of the inner ear microvasculature. Pericytes from various microvascular beds express caveolae, protein and cholesterol rich microdomains, which can undergo endocytosis and transcytosis to transport small molecules in and out the cells. A different protein profile in transport-specialized caveolae may induce pathological changes affecting the integrity of the blood labyrinth barrier and ultimately contributing to hearing loss.
Method
Caveolae isolation from treated and untreated cells is achieved through ultracentrifugation of the lysates in discontinuous gradients. Mass spectrometry (LC-MS/MS) analysis identifies the proteins in the two groups. Proteins segregating with caveolae isolated from untreated SL pericytes are then compared to caveolae isolated from SL pericytes treated with the gentamicin for 24 h. Data are analyzed using bioinformatic tools.
Results
The caveolae proteome in gentamicin treated cells shows that 40% of total proteins are uniquely associated with caveolae during the treatment, and 15% of the proteins normally associated with caveolae in untreated cell are suppressed. Bioinformatic analysis of the data shows a decreased expression of proteins involved in genetic information processing, and an increase in proteins involved in metabolism, vesicular transport and signal transduction in gentamicin treated cells. Several Rab GTPases proteins, ubiquitous transporters, uniquely segregate with caveolae and are significantly enriched in gentamicin treated cells.
Conclusion
We report that gentamicin exposure modifies protein profile of caveolae from SL pericytes. We identified a pool of proteins which are uniquely segregating with caveolae during the treatment, mainly participating in metabolic and biosynthetic pathways, in transport pathways and in genetic information processing. Finally, we show for the first time proteins associated with caveolae SL pericytes linked to nonsyndromic hearing loss
Regional differences in the prevalence of diabetic retinopathy: a multi center study in Brazil
No full textAbstract\ud
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Background\ud
Diabetic retinopathy has a significant impact in every healthcare system. Despite that fact, there are few accurate estimates in the prevalence of DR in Brazil’s different geographic regions, particularly proliferative DR and diabetic macular edema. This study aims to determine the prevalence of diabetic retinopathy in Brazil’s five continental regions and its determinant factors.\ud
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Methods\ud
This multi center, cross-sectional, observational study, conducted between August 2011 and December 2014, included patients with type 1 diabetes from the 5 Brazilian geographic regions (South, Southeast, North, Northeast and Midwest). During a clinical visit, a structured questionnaire was applied, blood sampling was collected and each patient underwent mydriatic binocular indirect ophthalmoscopy evaluation.\ud
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Results\ud
Data was obtained from 1644 patients, aged 30.2 ± 12 years (56.1% female, 54.4% Caucasian), with a diabetes duration of 15.5 ± 9.3 years. The prevalence of diabetic retinopathy was 242 (36.1%) in the Southeast, 102 (42.9%) in the South, 183 (29.9%) in the North and Northeast and 54 (41.7%) in the Midwest. Multinomial regression showed no difference in the prevalence of non-proliferative diabetic retinopathy in each geographic region, although, prevalence of proliferative diabetic retinopathy (p = 0.022), and diabetic macular edema (p = 0.003) was higher in the Midwest. Stepwise analyses reviled duration of diabetes, level of HbA1c and hypertension as independent variables.\ud
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Conclusions\ud
The prevalence of non proliferative diabetic retinopathy in patients with type 1 diabetes was no different between each geographic region of Brazil. The Midwest presented higher prevalence of proliferative diabetic retinopathy and diabetic macular edema. Duration of DM and glycemic control is of central importance to all. Hypertension is another fundamental factor to every region, at special in the South and Southeast. Glycemic control and patients in social and economic vulnerability deserves special attention in the North and Northeast of Brazil.This work was partially supported by Conselho Nacional de Desenvolvimento Científico e Tecnológico—CNPq and Fundação de Amparo à Pesquisa do Estado do Rio de Janeiro—Faperj
Patient-specific neurosurgical phantom: assessment of visual quality, accuracy, and scaling effects
No full textAbstract\ud
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Background\ud
Training in medical education depends on the availability of standardized materials that can reliably mimic the human anatomy and physiology. One alternative to using cadavers or animal bodies is to employ phantoms or mimicking devices. Styrene-ethylene/butylene-styrene (SEBS) gels are biologically inert and present tunable properties, including mechanical properties that resemble the soft tissue. Therefore, SEBS is an alternative to develop a patient-specific phantom, that provides real visual and morphological experience during simulation-based neurosurgical training.\ud
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Results\ud
A 3D model was reconstructed and printed based on patient-specific magnetic resonance images. The fused deposition of polyactic acid (PLA) filament and selective laser sintering of polyamid were used for 3D printing. Silicone and SEBS materials were employed to mimic soft tissues. A neuronavigation protocol was performed on the 3D-printed models scaled to three different sizes, 100%, 50%, and 25% of the original dimensions. A neurosurgery team (17 individuals) evaluated the phantom realism as “very good” and “perfect” in 49% and 31% of the cases, respectively, and rated phantom utility as “very good” and “perfect” in 61% and 32% of the cases, respectively. Models in original size (100%) and scaled to 50% provided a quantitative and realistic visual analysis of the patient’s cortical anatomy without distortion. However, reduction to one quarter of the original size (25%) hindered visualization of surface details and identification of anatomical landmarks.\ud
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Conclusions\ud
A patient-specific phantom was developed with anatomically and spatially accurate shapes, that can be used as an alternative for surgical planning. Printed models scaled to sizes that avoided quality loss might save time and reduce medical training costs.This study was supported by CAPES, FAEPA, FAPESP (2014/50414–9 and 13/18854–6) and CNPq (448806/2014–2 and 140787/2014–3) and FINEP (2613/09)
Characterization of a novel sugar transporter involved in sugarcane bagasse degradation in Trichoderma reesei
No full textAbstract\ud
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Background\ud
Trichoderma reesei is a saprophytic fungus implicated in the degradation of polysaccharides present in the cell wall of plants. T. reesei has been recognized as the most important industrial fungus that secretes and produces cellulase enzymes that are employed in the production of second generation bioethanol. A few of the molecular mechanisms involved in the process of biomass deconstruction by T. reesei; in particular, the effect of sugar transporters and induction of xylanases and cellulases expression are yet to be known.\ud
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Results\ud
In our study, we characterized a novel sugar transporter, which was previously identified by our group through in silico analysis of RNA-seq data. The novel T. reesei 69957-sugar transport system (Tr69957) is capable of transporting xylose, mannose, and cellobiose using a T. reesei 69957-sugar transport system in Saccharomyces cerevisiae. The deletion of Tr69957 in T. reesei affected the fungal growth and biomass accumulation, and the sugar uptake in the presence of mannose, cellobiose, and xylose. Molecular docking studies revealed that Tr69957 shows reduced protein–ligand binding energy for interactions towards disaccharides in comparison with monosaccharides. Furthermore, the deletion of Tr69957 affected the gene expression of cellobiohydrolases (cel7a and cel6a), β-glucosidases (cel3a and cel1a), and xylanases (xyn1 and xyn2) in the cultures of parental and mutant strains in the presence of cellobiose and sugarcane bagasse (SCB).\ud
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Conclusion\ud
The transporter Tr69957 of T. reesei can transport cellobiose, xylose, and mannose, and can affect the expression of a few genes encoding enzymes, such as cellulases and xylanases, in the presence of SCB. We showed for the first time that a filamentous fungus (T. reesei) contains a potential mannose transporter that may be involved in the degradation of cellulose.This work was supported by the Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) (Processes FAPESP 2015/09553-8)
A genome-wide association study reveals novel genomic regions and positional candidate genes for fat deposition in broiler chickens
No full textAbstract\ud
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Background\ud
Excess fat content in chickens has a negative impact on poultry production. The discovery of QTL associated with fat deposition in the carcass allows the identification of positional candidate genes (PCGs) that might regulate fat deposition and be useful for selection against excess fat content in chicken’s carcass. This study aimed to estimate genomic heritability coefficients and to identify QTLs and PCGs for abdominal fat (ABF) and skin (SKIN) traits in a broiler chicken population, originated from the White Plymouth Rock and White Cornish breeds.\ud
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Results\ud
ABF and SKIN are moderately heritable traits in our broiler population with estimates ranging from 0.23 to 0.33. Using a high density SNP panel (355,027 informative SNPs), we detected nine unique QTLs that were associated with these fat traits. Among these, four QTL were novel, while five have been previously reported in the literature. Thirteen PCGs were identified that might regulate fat deposition in these QTL regions: JDP2, PLCG1, HNF4A, FITM2, ADIPOR1, PTPN11, MVK, APOA1, APOA4, APOA5, ENSGALG00000000477, ENSGALG00000000483, and ENSGALG00000005043. We used sequence information from founder animals to detect 4843 SNPs in the 13 PCGs. Among those, two were classified as potentially deleterious and two as high impact SNPs.\ud
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Conclusions\ud
This study generated novel results that can contribute to a better understanding of fat deposition in chickens. The use of high density array of SNPs increases genome coverage and improves QTL resolution than would have been achieved with low density. The identified PCGs were involved in many biological processes that regulate lipid storage. The SNPs identified in the PCGs, especially those predicted as potentially deleterious and high impact, may affect fat deposition. Validation should be undertaken before using these SNPs for selection against carcass fat accumulation and to improve feed efficiency in broiler chicken production.This study was supported by the Brazilian Agricultural Research Corporation\ud
– Embrapa (project number 01.11.07.002.04.02) and by the thematic project\ud
(2014/08704–0) from São Paulo Research Foundation (FAPESP). The TT Reference\ud
Population was funded by the National Council of Scientific and Technological\ud
Development (CNPq) grant number 481755/2007–1 from the Brazilian\ud
Government. Boschiero received a fellowship from the program Science\ud
Without Borders - CNPq, grant 370620/2013–5. G.C.M. Moreira received\ud
fellowships from FAPESP, grants 14/21380–9 (in cooperation agreement\ud
with CAPES), and 16/00569–1. T.F. Godoy received fellowship from FAPESP,\ud
grant 15/00616–7 (in cooperation agreement with CAPES). L.L. Coutinho is\ud
recipient of productivity fellowship from CNPq
Identification of putative regulatory regions and transcription factors associated with intramuscular fat content traits
No full textAbstract\ud
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Background\ud
Integration of high throughput DNA genotyping and RNA-sequencing data allows for the identification of genomic regions that control gene expression, known as expression quantitative trait loci (eQTL), on a whole genome scale. Intramuscular fat (IMF) content and carcass composition play important roles in metabolic and physiological processes in mammals because they influence insulin sensitivity and consequently prevalence of metabolic diseases such as obesity and type 2 diabetes. However, limited information is available on the genetic variants and mechanisms associated with IMF deposition in mammals. Thus, our hypothesis was that eQTL analyses could identify putative regulatory regions and transcription factors (TFs) associated with intramuscular fat (IMF) content traits.\ud
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Results\ud
We performed an integrative eQTL study in skeletal muscle to identify putative regulatory regions and factors associated with intramuscular fat content traits. Data obtained from skeletal muscle samples of 192 animals was used for association analysis between 461,466 SNPs and the transcription level of 11,808 genes. This yielded 1268 cis- and 10,334 trans-eQTLs, among which we identified nine hotspot regions that each affected the expression of > 119 genes. These putative regulatory regions overlapped with previously identified QTLs for IMF content. Three of the hotspots respectively harbored the transcription factors USF1, EGR4 and RUNX1T1, which are known to play important roles in lipid metabolism. From co-expression network analysis, we further identified modules significantly correlated with IMF content and associated with relevant processes such as fatty acid metabolism, carbohydrate metabolism and lipid metabolism.\ud
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Conclusion\ud
This study provides novel insights into the link between genotype and IMF content as evident from the expression level. It thereby identifies genomic regions of particular importance and associated regulatory factors. These new findings provide new knowledge about the biological processes associated with genetic variants and mechanisms associated with IMF deposition in mammals.This study was conducted with funding from EMBRAPA (Macroprograma 1,\ud
01/2005) and FAPESP (processes number 2014/11871–5, 2014/22884–0 and\ud
2012/23638–8). LCAR and LLC were granted CNPq fellowships
On the logic of theory change: iteration of expansion
No full textAbstract
Constructing models that allow for iterated changes is one of the most studied problems in the literature on belief change. However, up to now, iteration of expansion was only studied as a special case of consistent revision and, as far we know, there is no work in the literature that deals with expansions into inconsistency in a supraclassical framework.
In this paper, we provide a semantics for iterated expansion, as well as its axiomatic characterization. We extend the model to two well-known families of iterated belief change (natural and lexicographic). Iteration of expansion can be combined with existent models of iteration of revision and contraction. Since we are able to accommodate different inconsistent belief states, iteration of expansion allows us to define new belief change functions that are currently only defined for belief bases: semi-revision, external revision, as well as consolidation