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    Small RNAs in metastatic and non-metastatic oral squamous cell carcinoma

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    Abstract\ud \ud Background\ud Small non-coding regulatory RNAs control cellular functions at the transcriptional and post-transcriptional levels. Oral squamous cell carcinoma is among the leading cancers in the world and the presence of cervical lymph node metastases is currently its strongest prognostic factor. In this work we aimed at finding small RNAs expressed in oral squamous cell carcinoma that could be associated with the presence of lymph node metastasis.\ud \ud \ud Methods\ud Small RNA libraries from metastatic and non-metastatic oral squamous cell carcinomas were sequenced for the identification and quantification of known small RNAs. Selected markers were validated in plasma samples. Additionally, we used in silico analysis to investigate possible new molecules, not previously described, involved in the metastatic process.\ud \ud \ud Results\ud Global expression patterns were not associated with cervical metastases. MiR-21, miR-203 and miR-205 were highly expressed throughout samples, in agreement with their role in epithelial cell biology, but disagreeing with studies correlating these molecules with cancer invasion. Eighteen microRNAs, but no other small RNA class, varied consistently between metastatic and non-metastatic samples. Nine of these microRNAs had been previously detected in human plasma, eight of which presented consistent results between tissue and plasma samples. MiR-31 and miR-130b, known to inhibit several steps in the metastatic process, were over-expressed in non-metastatic samples and the expression of miR-130b was confirmed in plasma of patients showing no metastasis. MiR-181 and miR-296 were detected in metastatic tumors and the expression of miR-296 was confirmed in plasma of patients presenting metastasis. A novel microRNA-like molecule was also associated with non-metastatic samples, potentially targeting cell-signaling mechanisms.\ud \ud \ud Conclusions\ud We corroborate literature data on the role of small RNAs in cancer metastasis and suggest the detection of microRNAs as a tool that may assist in the evaluation of oral squamous cell carcinoma metastatic potential.The authors acknowledge the contribution of GENCAPO (Brazilian Head and\ud Neck Genome Project) for clinical samples and for clinical and pathological\ud Severino et al. BMC Medical Genomics (2015) 8:31 Page 13 of 15\ud data collection and analysis (complete list of members and affiliations\ud presented at http://www.gencapo.famerp.br) and the technical expertise and\ud accessibility of Dr. Susan Ienne da Silva Vançan and of Dr. Tiago Antonio de\ud Souza at CEFAP-USP during small RNA sequencing. This work was supported\ud by FAPESP (grant 10/51168-0) and by Hospital Israelita Albert Einstein

    Low fatness, reduced fat intake and adequate plasmatic concentrations of LDL-cholesterol are associated with high bone mineral density in women: a cross-sectional study with control group

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    Abstract Background Several parameters are associated with high bone mineral density (BMD), such as overweight, black background, intense physical activity (PA), greater calcium intake and some medications. The objectives are to evaluate the prevalence and the main aspects associated with high BMD in healthy women. Methods After reviewing the database of approximately 21,500 BMD scans performed in the metropolitan area of São Paulo, Brazil, from June 2005 to October 2010, high BMD (over 1400 g/cm2 at lumbar spine and/or above 1200 g/cm2 at femoral neck) was found in 421 exams. Exclusion criteria were age below 30 or above 60 years, black ethnicity, pregnant or obese women, disease and/or medications known to interfere with bone metabolism. A total of 40 women with high BMD were included and matched with 40 healthy women with normal BMD, paired to weight, age, skin color and menopausal status. Medical history, food intake and PA were assessed through validated questionnaires. Body composition was evaluated through a GE-Lunar DPX MD + bone densitometer. Radiography of the thoracic and lumbar spine was carried out to exclude degenerative alterations or fractures. Biochemical parameters included both lipid and hormonal profiles, along with mineral and bone metabolism. Statistical analysis included parametric and nonparametric tests and linear regression models. P < 0.05 was considered significant. Results The mean age was 50.9 (8.3) years. There was no significant difference between groups in relation to PA, smoking, intake of calcium and vitamin D, as well as laboratory tests, except serum C-telopeptide of type I collagen (s-CTX), which was lower in the high BMD group (p = 0.04). In the final model of multivariate regression, a lower fat intake and body fatness as well a better profile of LDL-cholesterol predicted almost 35% of high BMD in women. (adjusted R2 = 0.347; p < 0.001). In addition, greater amounts of lean mass and higher IGF-1 serum concentrations played a protective role, regardless age and weight. Conclusion Our results demonstrate the potential deleterious effect of lipid metabolism-related components, including fat intake and body fatness and worse lipid profile, on bone mass and metabolism in healthy women

    Hidden impacts of the Samarco mining waste dam collapse to Brazilian marine fauna – an example from the staurozoans (Cnidaria)

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    The collapse of the Fundão tailings dam at Mariana (State of Minas Gerais, Brazil) started a huge human tragedy and likely the most serious environmental disaster in recent Brazilian history. The dam had contained waste from processing iron ore from mines owned by Samarco, a joint venture company of the Brazilian Vale S.A. and the Anglo-Australian BHP Billiton Ltd. Following ineffective attempts to contain the disaster, after 16 days the mud flood reached the sea, where its impact is expected to affect thousands of marine fauna and flora species. Here, we provide an example of one of these species, the cnidarian Kishinouyea corbini Larson 1980 (Staurozoa), emblematic because it is extremely rare, poorly studied, and its known distribution overlaps the threatened area on the Brazilian coast. Based on this case, we discuss the need for efforts to monitor and minimize the possible impacts of this socio-environmental crime, as well as to identify and punish all responsible players in this tragedy, including negligent licensing and supervisory state agencies, in order to prevent future similar tragedies.FAPESP (2011/50242-5, 2013/50484-4)CNPq (305805/2013-4, 445444/2014-2)CAPES PNP

    Nanocrystalline yttria-doped zirconia sintered by fast firing

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    Sintering of powders commonly leads to simultaneous densification and grain growth, particularly for nanocrystalline materials. Currently, methods such as spark plasma sintering (SPS), hot pressing (HP), two-step sintering (TSS) and fast firing (FF) are employed to hinder grain growth while maintaining a high densification. In this work, FF consisting in thermal treatments with high heating rates (>500° C/min) and shorter holding times (10 min or less) and conventional sintering (CS) approaches were experimentally compared in the sintering of commercial yttria doped zirconia (3YSZ and 8YSZ) compacts. CS-samples presented larger grain sizes by a factor of ~2 and ~4 in comparison to the initial 3YSZ and 8YSZ powders. Conversely, FF method significantly suppressed grain growth with a growth factor of ~1. Those results and comparison with previous work indicated that high heat inputs could indeed minimize grain growthCNP

    The nutritional state of children and adolescents with cerebral palsy is associated with oral motor dysfunction and social conditions: a cross sectional study

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    Abstract\ud \ud Background\ud Cerebral palsy (CP) is the main cause of severe physical impairment during childhood and has commonly shown oral motor association. It has been considered as the main cause of the high prevalence of problems in children’s nutrition. Respiration, chewing, swallowing, speaking and facial expressionare part of the orofacial motor functions and when affected they can interfere in children’s well-being. The aim of this study was to correlate two methods of orofacial motor evaluation, analyze the influence of orofacial motor functional impairment on the nutritional status of children and adolescents with CP, and the association between socioeconomic factors.\ud \ud \ud Methods\ud Seventy children and adolescents with CP were selected, age range 6–16 years and following the exclusion criteria previously determined; 129 normoreactive children (control group), sex and age-matched to patients with CP. For the orofacial motor analysis two evaluation instruments were applied, the “Oral Motor Assessment Scale” (OMAS) and “Nordic Orofacial Test-Screening” (NOT-S). The anthropometric evaluation was based on the World Health Organization (WHO) and followed the criteria recommended by the Brazilian Ministry of Health.\ud \ud \ud Results\ud There was statistically significant correlation between the oral motor methods of evaluation (r = -0.439, p < 0.0001). Concerning the nutritional status evaluation, being overweight was associated with dystonic and mixed CP forms variables (p = 0.034), mother with no partnership (p = 0.045) and mild oral motor impairment (p = 0.028).\ud \ud \ud Conclusion\ud It could be concluded that, the weight’s gain by children and adolescents might be favored by a better functional oral motor performance and social factors

    Liver transcriptomic networks reveal main biological processes associated with feed efficiency in beef cattle

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    Abstract Background The selection of beef cattle for feed efficiency (FE) traits is very important not only for productive and economic efficiency but also for reduced environmental impact of livestock. Considering that FE is multifactorial and expensive to measure, the aim of this study was to identify biological functions and regulatory genes associated with this phenotype. Results Eight genes were differentially expressed between high and low feed efficient animals (HFE and LFE, respectively). Co-expression analyses identified 34 gene modules of which 4 were strongly associated with FE traits. They were mainly enriched for inflammatory response or inflammation-related terms. We also identified 463 differentially co-expressed genes which were functionally enriched for immune response and lipid metabolism. A total of 8 key regulators of gene expression profiles affecting FE were found. The LFE animals had higher feed intake and increased subcutaneous and visceral fat deposition. In addition, LFE animals showed higher levels of serum cholesterol and liver injury biomarker GGT. Histopathology of the liver showed higher percentage of periportal inflammation with mononuclear infiltrate. Conclusion Liver transcriptomic network analysis coupled with other results demonstrated that LFE animals present altered lipid metabolism and increased hepatic periportal lesions associated with an inflammatory response composed mainly by mononuclear cells. We are now focusing to identify the causes of increased liver lesions in LFE animals

    Functional and evolutionary analyses of the miR156 and miR529 families in land plants

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    Abstract Background MicroRNAs (miRNAs) are important regulatory elements of gene expression. Similarly to coding genes, miRNA genes follow a birth and death pattern of evolution likely reflecting functional relevance and divergence. For instance, miRNA529 is evolutionarily related to miRNA156 (a highly conserved miRNA in land plants), but it is lost in Arabidopsis thaliana. Interestingly, both miRNAs target sequences overlap in some members of the SQUAMOSA promoter-binding protein like (SPL) family, raising important questions regarding the diversification of the miR156/miR529-associated regulatory network in land plants. Results In this study, through phylogenic reconstruction of miR156/529 target sequences from several taxonomic groups, we have found that specific eudicot SPLs, despite miRNA529 loss, retained the corresponding target site. Detailed molecular evolutionary analyses of miR156/miR529-target sequence showed that loss of miR529 in core eudicots, such as Arabidopsis, is correlated with a more relaxed selection of the miRNA529 specific target element, while miRNA156-specific target sequence is under stronger selection, indicating that these two target sites might be under distinct evolutionary constraints. Importantly, over-expression in Arabidopsis of MIR529 precursor from a monocot, but not from a basal eudicot, demonstrates specific miR529 regulation of AtSPL9 and AtSPL15 genes, which contain conserved responsive elements for both miR156 and miR529. Conclusions Our results suggest loss of functionality of MIR529 genes in the evolutionary history of eudicots and show that the miR529-responsive element present in some eudicot SPLs is still functional. Our data support the notion that particular miRNA156 family members might have compensated for the loss of miR529 regulation in eudicot species, which concomitantly may have favored diversification of eudicot SPLs

    Predictors of HBeAg status and hepatitis B viraemia in HIV-infected patients with chronic hepatitis B in the HAART era in Brazil

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    Abstract Background HBV-HIV co-infection is associated with an increased liver-related morbidity and mortality. However, little is known about the natural history of chronic hepatitis B in HIV-infected individuals under highly active antiretroviral therapy (HAART) receiving at least one of the two drugs that also affect HBV (TDF and LAM). Information about HBeAg status and HBV viremia in HIV/HBV co-infected patients is scarce. The objective of this study was to search for clinical and virological variables associated with HBeAg status and HBV viremia in patients of an HIV/HBV co-infected cohort. Methods A retrospective cross-sectional study was performed, of HBsAg-positive HIV-infected patients in treatment between 1994 and 2007 in two AIDS outpatient clinics located in the São Paulo metropolitan area, Brazil. The baseline data were age, sex, CD4 T+ cell count, ALT level, HIV and HBV viral load, HBV genotype, and duration of antiretroviral use. The variables associated to HBeAg status and HBV viremia were assessed using logistic regression. Results A total of 86 HBsAg patients were included in the study. Of these, 48 (56%) were using combination therapy that included lamivudine (LAM) and tenofovir (TDF), 31 (36%) were using LAM monotherapy, and 7 patients had no previous use of either one. Duration of use of TDF and LAM varied from 4 to 21 and 7 to 144 months, respectively. A total of 42 (48. 9%) patients were HBeAg positive and 44 (51. 1%) were HBeAg negative. The multivariate analysis revealed that the use of TDF for longer than 12 months was associated with undetectable HBV DNA viral load (serum HBV DNA level < 60 UI/ml) (p = 0. 047). HBeAg positivity was associated with HBV DNA > 60 UI/ml (p = 0. 001) and ALT levels above normality (p = 0. 038). Conclusion Prolonged use of TDF containing HAART is associated with undetectable HBV DNA viral load. HBeAg positivity is associated with HBV viremia and increased ALT levels

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