Medium Chain Fatty Acids Are Selective Peroxisome Proliferator Activated Receptor (PPAR) gamma Activators and Pan-PPAR Partial Agonists

Thiazolidinediones (TZDs) act through peroxisome proliferator activated receptor (PPAR) gamma to increase insulin sensitivity in type 2 diabetes (T2DM), but deleterious effects of these ligands mean that selective modulators with improved clinical profiles are needed. We obtained a crystal structure of PPAR gamma ligand binding domain (LBD) and found that the ligand binding pocket (LBP) is occupied by bacterial medium chain fatty acids (MCFAs). We verified that MCFAs (C8-C10) bind the PPAR gamma LBD in vitro and showed that they are low-potency partial agonists that display assay-specific actions relative to TZDs; they act as very weak partial agonists in transfections with PPAR gamma LBD, stronger partial agonists with full length PPAR gamma and exhibit full blockade of PPAR gamma phosphorylation by cyclin-dependent kinase 5 (cdk5), linked to reversal of adipose tissue insulin resistance. MCFAs that bind PPAR gamma also antagonize TZD-dependent adipogenesis in vitro. X-ray structure B-factor analysis and molecular dynamics (MD) simulations suggest that MCFAs weakly stabilize C-terminal activation helix (H) 12 relative to TZDs and this effect is highly dependent on chain length. By contrast, MCFAs preferentially stabilize the H2-H3/beta-sheet region and the helix (H) 11-H12 loop relative to TZDs and we propose that MCFA assay-specific actions are linked to their unique binding mode and suggest that it may be possible to identify selective PPAR gamma modulators with useful clinical profiles among natural products.

Soil sulfur fractions dynamics and distribution in a tropical grass pasture amended with nitrogen and sulfur fertilizers

Soil sulfur (S) partitioning among the various pools and changes in tropical pasture ecosystems remain poorly understood. Our study aimed to investigate the dynamics and distribution of soil S fractions in an 8-year-old signal grass (Brachiaria decumbens Stapf.) pasture fertilized with nitrogen (N) and S. A factorial combination of two N rates (0 and 600?kg N ha1 y1, as NH4NO3) and two S rates (0 and 60?kg S ha1 y1, as gypsum) were applied to signal grass pastures during 2 y. Cattle grazing was controlled during the experimental period. Organic S was the major S pool found in the tropical pasture soil, and represented 97% to 99% of total S content. Among the organic S fractions, residual S was the most abundant (42% to 67% of total S), followed by ester-bonded S (19% to 42%), and C-bonded S (11% to 19%). Plant-available inorganic SO4-S concentrations were very low, even for the treatments receiving S fertilizers. Low inorganic SO4-S stocks suggest that S losses may play a major role in S dynamics of sandy tropical soils. Nitrogen and S additions affected forage yield, S plant uptake, and organic S fractions in the soil. Among the various soil fractions, residual S showed the greatest changes in response to N and S fertilization. Soil organic S increased in plots fertilized with S following the residual S fraction increment (16.6% to 34.8%). Soils cultivated without N and S fertilization showed a decrease in all soil organic S fractions.

Semi-supervised dimensionality reduction based on partial least squares for visual analysis of high dimensional data

Dimensionality reduction is employed for visual data analysis as a way to obtaining reduced spaces for high dimensional data or to mapping data directly into 2D or 3D spaces. Although techniques have evolved to improve data segregation on reduced or visual spaces, they have limited capabilities for adjusting the results according to user's knowledge. In this paper, we propose a novel approach to handling both dimensionality reduction and visualization of high dimensional data, taking into account user's input. It employs Partial Least Squares (PLS), a statistical tool to perform retrieval of latent spaces focusing on the discriminability of the data. The method employs a training set for building a highly precise model that can then be applied to a much larger data set very effectively. The reduced data set can be exhibited using various existing visualization techniques. The training data is important to code user's knowledge into the loop. However, this work also devises a strategy for calculating PLS reduced spaces when no training data is available. The approach produces increasingly precise visual mappings as the user feeds back his or her knowledge and is capable of working with small and unbalanced training sets.

Retinol binding protein 4 and retinol in steatotic and nonsteatotic rat livers in the setting of partial hepatectomy under ischemia/reperfusion

Steatotic livers show increased hepatic damage and impaired regeneration after partial hepatectomy (PH) under ischemia/reperfusion (I/R), which is commonly applied in clinical practice to reduce bleeding. The known function of retinol-binding protein 4 (RBP4) is to transport retinol in the circulation. We examined whether modulating RBP4 and/or retinol could protect steatotic and nonsteatotic livers in the setting of PH under I/R. Steatotic and nonsteatotic livers from Zucker rats were subjected to PH (70%) with 60 minutes of ischemia. RBP4 and retinol levels were measured and altered pharmacologically, and their effects on hepatic damage and regeneration were studied after reperfusion. Decreased RBP4 levels were observed in both liver types, whereas retinol levels were reduced only in steatotic livers. RBP4 administration exacerbated the negative consequences of liver surgery with respect to damage and liver regeneration in both liver types. RBP4 affected the mobilization of retinol from steatotic livers, and this revealed actions of RBP4 independent of simple retinol transport. The injurious effects of RBP4 were not due to changes in retinol levels. Treatment with retinol was effective only for steatotic livers. Indeed, retinol increased hepatic injury and impaired liver regeneration in nonsteatotic livers. In steatotic livers, retinol reduced damage and improved regeneration after surgery. These benefits of retinol were associated with a reduced accumulation of hepatocellular fat. Thus, strategies based on modulating RBP4 could be ineffective and possibly even harmful in both liver types in the setting of PH under I/R. In terms of clinical applications, a retinol pretreatment might open new avenues for liver surgery that specifically benefit the steatotic liver. Liver Transpl 18:1198-1208, 2012. (c) 2012 AASLD.

Leishmanicidal activity in vitro of Musa paradisiaca L. and Spondias mombin L. fractions

Visceral leishmaniasis (VL) is a zoonotic disease characterized by infection of mononuclear phagocytes by Leishmania chagasi. The primary vector is Lutzomyia longipalpis and the dog is the main domestic reservoir. The control and current treatment of dogs using synthetic drugs have not shown effectiveness in reducing the incidence of disease in man. In attempt to find new compounds with leishmanicidal action, plant secondary metabolites have been studied in search of treatments of VL. This study aimed to evaluate the leishmanicidal activity of Musa paradisiaca (banana tree) and Spondias mombin (cajazeira) chemical constituents on promastigotes and amastigotes of L. chagasi. Phytochemical analysis by column chromatography was performed on ethanol extracts of two plants and fractions were isolated. Thin layer chromatography was used to compare the fractions and for isolation the substances to be used in vitro tests. The in vitro tests on promastigotes of L chagasi used the MTT colorimetric method and the method of ELISA in situ was used against amastigotes besides the cytotoxicity in RAW 264.7 cells. Of the eight fractions tested, Sm1 and Sm2 from S. mombin had no action against promastigotes, but had good activity against amastigotes. The fractions Mp1 e Mp4 of M. paradisiaca were very cytotoxic to RAW 264.7 cells. The best result was obtained with the fraction Sm3 from S. mombin with IC50 of 11.26 mu g/ml against promastigotes and amastigotes of 0.27 mu g/ml. The fraction Sm3 characterized as tannic acid showed the best results against both forms of Leishmania being a good candidate for evaluation in in vivo tests. (C) 2012 Published by Elsevier B.V.

Study of La2-xCaxCuO4 perovskites for the low temperature water gas shift reaction

The effects of small fractions of calcium (x = 0, 0.05, 0.1, 0.15, and 0.20) on the structure and the catalytic properties of La2-xCaxCuO4 peroviskites have been investigated. The samples have been synthesized using the co-precipitation method. Perovskite-type oxides were characterized by XRD, TPR, XPS, XANES, SEM, and TEM. Catalytic tests for the water gas shift reaction (WGSR) were carried out in a tubular reactor at 290 degrees C. All samples showed a well-defined perovskite structure with surface areas between 6 and 18 m(2) g(-1). The partial substitution of La by Ca enhanced the stability of the perovskites and increased their reduction temperature. All catalysts were actives for WGSR, and the best catalytic performance was obtained for the La1.85Ca0.15CuO4 catalyst, but the samples with 5 and 10% of Ca had the best TOF values for reaction. These results can be associated to promoter effect of calcium, the high surface area, and the reducible species Cu-0 and Cu1+. (C) 2011 Elsevier B.V. All rights reserved.

Partial projective representations and partial actions II

This paper is a continuation of Dokuchaev and Novikov (2010) [8]. The interaction between partial projective representations and twisted partial actions of groups considered in Dokuchaev and Novikov (2010) [8] is treated now in a categorical language. In the case of a finite group G, a structural result on the domains of factor sets of partial projective representations of G is obtained in terms of elementary partial actions. For arbitrary G we study the component pM'(G) of totally-defined factor sets in the partial Schur multiplier pM(G) using the structure of Exel's semigroup. A complete characterization of the elements of pM'(G) is obtained for algebraically closed fields. (C) 2011 Elsevier B.V. All rights reserved.

Genotoxicity assessment of water soluble fractions of biodiesel and its diesel blends using the Salmonella assay and the in vitro MicroFlow (R) kit (Litron) assay

The designation of biodiesel as an environmental-friendly alternative to diesel oil has improved its commercialization and use. However, most biodiesel environmental safety studies refer to air pollution and so far there have been very few literature data about its impacts upon other biotic systems, e.g. water, and exposed organisms. Spill simulations in water were carried out with neat diesel and biodiesel and their blends aiming at assessing their genotoxic potentials should there be contaminations of water systems. The water soluble fractions (WSF) from the spill simulations were submitted to solid phase extraction with C-18 cartridge and the extracts obtained were evaluated carrying out genotoxic and mutagenic bioassays [the Salmonella assay and the in vitro MicroFlow (R) kit (Litron) assay]. Mutagenic and genotoxic effects were observed, respectively, in the Salmonella/microsome preincubation assay and the in vitro MN test carried out with the biodiesel WSF. This interesting result may be related to the presence of pollutants in biodiesel derived from the raw material source used in its production chain. The data showed that care while using biodiesel should be taken to avoid harmful effects on living organisms in cases of water pollution. (C) 2011 Elsevier Ltd. All rights reserved.

Comparative performance evaluation of hepatitis C virus genotyping based on the 5' untranslated region versus partial sequencing of the NS5B region of brazilian patients with chronic hepatitis C

Background Genotyping of hepatitis C virus (HCV) has become an essential tool for prognosis and prediction of treatment duration. The aim of this study was to compare two HCV genotyping methods: reverse hybridization line probe assay (LiPA v.1) and partial sequencing of the NS5B region. Methods Plasma of 171 patients with chronic hepatitis C were screened using both a commercial method (LiPA HCV Versant, Siemens, Tarrytown, NY, USA) and different primers targeting the NS5B region for PCR amplification and sequencing analysis. Results Comparison of the HCV genotyping methods showed no difference in the classification at the genotype level. However, a total of 82/171 samples (47.9%) including misclassification, non-subtypable, discrepant and inconclusive results were not classified by LiPA at the subtype level but could be discriminated by NS5B sequencing. Of these samples, 34 samples of genotype 1a and 6 samples of genotype 1b were classified at the subtype level using sequencing of NS5B. Conclusions Sequence analysis of NS5B for genotyping HCV provides precise genotype and subtype identification and an accurate epidemiological representation of circulating viral strains.

Leishmanicidal activity of fractions rich in aporphine alkaloids from Amazonian Unonopsis species

In vitro evaluation of alkaloidal fractions of twigs, barks and leaves from two Unonopsis species, Unonopsis guatterioides R.E. Fr. and Unonopsis duckei R.E. Fr., Annonaceae, against promastigote forms of Leishmania amazonensis revealed these species as sources of substances with promising leishmanicidal potential. All alkaloidal fractions from twigs, barks and leaves of U. guatterioides were classified as highly active, with IC50 1.07, 1.90, and 2.79 mg/mL, respectively. Only the alkaloidal fraction from the twigs of U. duckei was classified as inactive.

Quantitative chemical profile and multivariate statistical analysis of alembic distilled sugarcane spirit fractions

As concentrações de 39 compostos orgânicos foram determinadas em três frações (cabeça, coração e cauda) obtidas da destilação em alambique do caldo de cana fermentado. Os resultados foram avaliados utilizando-se análise de variância (ANOVA), teste de Tukey, análise de componentes principais (PCA), agrupamento hierárquico (HCA) e análise discriminante linear (LDA). De acordo com PCA e HCA, os dados experimentais conduzem à formação de três agrupamentos. As frações de cabeça deram origem a um grupo mais definido. As frações coração e cauda apresentaram alguma sobreposição coerente com sua composição em ácidos. As habilidades preditivas de calibração e validação dos modelos gerados pela LDA para a classificação das três frações foram de 90,5 e 100%, respectivamente. Este modelo reconheceu como coração doze de treze cachaças comerciais (92,3%) com boas características sensoriais, apresentando potencial para a orientação do processo de cortes.

Reestablishment of occlusion through overlay removable partial dentures: a case report

Loss of posterior teeth may cause an imbalance in the stomatognathic system. Overlay removable partial dentures (ORPD) are a reversible and relatively inexpensive treatment for patients with severely worn teeth. This paper presents a treatment with ORPD in a 55-year-old male patient who had severe attrition in the maxillary and mandibular teeth, temporomandibular joint pain and reduced vertical dimension of occlusion (VDO). The treatment consisted in the reestablishment of the VDO using Lucia’s jig, fabricating removable partial denture with reconstruction of the worn teeth without preparation. This therapy can be used as an alternative treatment to provide esthetic, function and stable occlusion in patients with severely worn teeth.

Rice husk derived waste materials as partial cement replacement in lightweight concrete

In this study rice husk ash (RHA) and broiler bed ash from rice husk (BBA), two agricultural waste materials, have been assessed for use as partial cement replacement materials for application in lightweight concrete. Physical and chemical characteristics of RHA and BBA were first analyzed. Three similar types of lightweight concrete were produced, a control type in which the binder was just CEMI cement (CTL) and two other types with 10% cement replacement with, respectively, RHA and BBA. All types of similar lightweight concrete were prepared to present the same workability by adjusting the amount of superplasticizer. Properties of concrete investigated were compressive and flexural strength at different ages, absorption by capillarity, resistivity and resistance to chloride ion penetration (CTH method) and accelerated carbonation. Test results obtained for 10% cement replacement level in lightweight concrete indicate that although the addition of BBA conducted to lower performance in terms of the degradation indicative tests, RHA led to the enhancement of mechanical properties, especially early strength and also fast ageing related results, further contributing to sustainable construction with energy saver lightweight concrete.

Digestion of feed fractions and intake of heifers fed hydrolyzed sugarcane stored for different periods

The objective of this study was to evaluate, in Nellore heifers, intake and digestibility of hydrolyzed sugarcane stored for different periods. The experimental design used was a 4 × 4 Latin square, four diets, four Nellore heifers with ruminal cannulas (initial body weight 285.4±23.08 kg and average initial age 14 months) and four periods of 21 days. The diets were composed by fresh sugarcane (time zero) or hydrolyzed sugarcane with addition of 0.5% of hydrated lime, stored for 24, 48 or 72 hours, as the unique forage. Intake and digestibility of feed fractions, nitrogen balance, microbial synthesis efficiency, total number of ruminal protozoans and ammoniacal nitrogen did not significantly change by storing sugarcane with addition of 0.5% of hydrated lime. Sugarcane pH varied quadratically for storage time, with maximum pH of 7.02 after 24 hours from lime addition. Ruminal liquid pH values were higher for heifers fed fresh sugarcane, in comparison with those fed hydrolyzed sugarcane. Sugarcane treated with 0.5% of hydrated lime stored for up to 72 hours does not change ruminal digestion to alter the amount of feed consumed by pubescent Nellore heifers. Thus, lime is a viable technology, once it allows long-duration storage and bee control on treated forage, which contributes to animal feeding logistics.

Robotic-assisted laparoscopic partial nephrectomy: initial experience in Brazil and a review of the literature

CONTEXT AND PURPOSE: Partial nephrectomy has become the standard of care for renal tumors less than 4 cm in diameter. Controversy still exists, however, regarding the best surgical approach, especially when minimally invasive techniques are taken into account. Robotic-assisted laparoscopic partial nephrectomy (RALPN) has emerged as a promising technique that helps surgeons achieve the standards of open partial nephrectomy care while offering a minimally invasive approach. The objective of the present study was to describe our initial experience with robotic-assisted laparoscopic partial nephrectomy and extensively review the pertinent literature. MATERIALS AND METHODS: Between August 2009 and February 2010, eight consecutive selected patients with contrast enhancing renal masses observed by CT were submitted to RALPN in a private institution. In addition, we collected information on the patients' demographics, preoperative tumor characteristics and detailed operative, postoperative and pathological data. In addition, a PubMed search was performed to provide an extensive review of the robotic-assisted laparoscopic partial nephrectomy literature. RESULTS: Seven patients had RALPN on the left or right sides with no intraoperative complications. One patient was electively converted to a robotic-assisted radical nephrectomy. The operative time ranged from 120 to 300 min, estimated blood loss (EBL) ranged from 75 to 400 mL and, in five cases, the warm ischemia time (WIT) ranged from 18 to 32 min. Two patients did not require any clamping. Overall, no transfusions were necessary, and there were no intraoperative complications or adverse postoperative clinical events. All margins were negative, and all patients were disease-free at the 6-month follow-up. CONCLUSIONS: Robotic-assisted laparoscopic partial nephrectomy is a feasible and safe approach to small renal cortical masses.Further prospective studies are needed to compare open partial nephrectomy with its minimally invasive counterparts.