The role of HLA-G molecule and HLA-G gene polymorphisms in tumors, viral hepatitis, and parasitic diseases

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Marine-derived fungi: diversity of enzymes and biotechnological applications

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Rhamnolipids: solution against Aedes aegypti?

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Linking genetic and environmental factors in amphibian disease risk

A central question in evolutionary biology is how interactions between organisms and the environment shape genetic differentiation. The pathogen Batrachochytrium dendrobatidis (Bd) has caused variable population declines in the lowland leopard frog (Lithobates yavapaiensis); thus, disease has potentially shaped, or been shaped by, host genetic diversity. Environmental factors can also influence both amphibian immunity and Bd virulence, confounding our ability to assess the genetic effects on disease dynamics. Here, we used genetics, pathogen dynamics, and environmental data to characterize L.yavapaiensis populations, estimate migration, and determine relative contributions of genetic and environmental factors in predicting Bd dynamics. We found that the two uninfected populations belonged to a single genetic deme, whereas each infected population was genetically unique. We detected an outlier locus that deviated from neutral expectations and was significantly correlated with mortality within populations. Across populations, only environmental variables predicted infection intensity, whereas environment and genetics predicted infection prevalence, and genetic diversity alone predicted mortality. At one locality with geothermally elevated water temperatures, migration estimates revealed source-sink dynamics that have likely prevented local adaptation. We conclude that integrating genetic and environmental variation among populations provides a better understanding of Bd spatial epidemiology, generating more effective conservation management strategies for mitigating amphibian declines.

Multi-task control strategy for grid-tied inverters based on conservative power theory

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Antibacterial activity of alkyl gallates is a combination of direct targeting of FtsZ and permeabilization of bacterial membranes

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Continental degassing of He-4 by surficial discharge of deep groundwater

Radiogenic He-4 is produced by the decay of uranium and thorium in the Earths mantle and crust. From here, it is degassed to the atmosphere(1-5) and eventually escapes to space(1,5,6). Assuming that all of the He-4 produced is degassed, about 70% of the total He-4 degassed from Earth comes from the continental crust(2,-5,7). However, the outgoing flux of crustal He-4 has not been directly measured at the Earths surface(2) and the migration pathways are poorly understood(2-4,7,8). Here we present measurements of helium isotopes and the long-lived cosmogenic radio-isotope Kr-81 in the deep, continental-scale Guarani aquifer in Brazil and show that crustal He-4 reaches the atmosphere primarily by the surficial discharge of deep groundwater. We estimate that He-4 in Guarani groundwater discharge accounts for about 20% of the assumed global flux from continental crust, and that other large aquifers may account for about 33%. Old groundwater ages suggest that He-4 in the Guarani aquifer accumulates over half- to one-million-year timescales. We conclude that He-4 degassing from the continents is regulated by groundwater discharge, rather than episodic tectonic events, and suggest that the assumed steady state between crustal production and degassing of He-4, and its resulting atmospheric residence time, should be re-examined.

Protease-inhibiting, molecular modeling and antimicrobial activities of extracts and constituents from Helichrysum foetidum and Helichrysum mechowianum (compositae)

Background Helichrysum species are used extensively for stress-related ailments and as dressings for wounds normally encountered in circumcision rites, bruises, cuts and sores. It has been reported that Helichysum species are used to relief abdominal pain, heart burn, cough, cold, wounds, female sterility, menstrual pain. Results From the extracts of Helichrysum foetidum (L.) Moench, six known compounds were isolated and identified. They were 7, 4′-dihydroxy-5-methoxy-flavanone (1), 6′-methoxy-2′,4, 4′-trihydroxychalcone (2), 6′-methoxy-2′,4-dihydroxychalcone -4′-O-β-D-glucoside (3), apigenin (4), apigenin-7-O-β-D-glucoside (5), kaur-16-en-18-oic acid (6) while two known compounds 3,5,7-trihydroxy-8-methoxyflavone (12), 4,5-dicaffeoyl quinic acid (13) together with a mixture of phytosterol were isolated from the methanol extract of Helichrysum mechowianum Klatt. All the compounds were characterized by spectroscopic and mass spectrometric methods, and by comparison with literature data. Both extracts and all the isolates were screened for the protease inhibition, antibacterial and antifungal activities. In addition, the phytochemical profiles of both species were investigated by ESI-MS experiments. Conclusions These results showed that the protease inhibition assay of H. foetidum could be mainly attributed to the constituents of flavonoids glycosides (3, 5) while the compound (13) from H. mechowianum contributes to the stomach protecting effects. In addition, among the antibacterial and antifungal activities of all the isolates, compound (6) was found to possess a potent inhibitor effect against the tested microorganisms. The heterogeneity of the genus is also reflected in its phytochemical diversity. The differential bioactivities and determined constituents support the traditional use of the species. Molecular modelling was carried out by computing selected descriptors related to drug absorption, distribution, metabolism, excretion and toxicity (ADMET).

Importance of adhesins in virulence of Paracoccidioides spp.

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Sub-MICs of Mentha piperita essential oil and menthol inhibits AHL mediated quorum sensing and biofilm of Gram-negative bacteria

Bacterial quorum sensing (QS) is a density dependent communication system that regulates the expression of certain genes including production of virulence factors in many pathogens. Bioactive plant extract/compounds inhibiting QS regulated gene expression may be a potential candidate as antipathogenic drug. In this study anti-QS activity of peppermint (Menthe piperita) oil was first tested using the Chromobacterium violaceum CVO26 biosensor. Further, the findings of the present investigation revealed that peppermint oil (PMO) at sub-Minimum Inhibitory Concentrations (sub-MICs) strongly interfered with acyl homoserine lactone (AHL) regulated virulence factors and biofilm formation in Pseudomonas aeruginosa and Aeromonas hydrophila. The result of molecular docking analysis attributed the QS inhibitory activity exhibited by PMO to menthol. Assessment of ability of menthol to interfere with QS systems of various Gram-negative pathogens comprising diverse AHL molecules revealed that it reduced the AHL dependent production of violacein, virulence factors, and biofilm formation indicating broad-spectrum anti-QS activity. Using two Escherichia colt biosensors, MG4/pKDT17 and pEAL08-2, we also confirmed that menthol inhibited both the las and pqs QS systems. Further, findings of the in vivo studies with menthol on nematode model Caenorhabditis elegans showed significantly enhanced survival of the nematode. Our data identified menthol as a novel broad spectrum QS inhibitor.

Insights into HLA-G genetics provided by worldwide haplotype diversity

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

The multifaceted roles of metabolic enzymes in the Paracoccidioides species complex

Paracoccidioides species are dimorphic fungi and are the etiologic agents of paracoccidioidomycosis, which is a serious disease that involves multiple organs. The many tissues colonized by this fungus suggest a variety of surface molecules involved in adhesion. A surprising finding is that most enzymes in the glycolytic pathway, tricarboxylic acid (TCA) cycle and glyoxylate cycle in Paracoccidioides spp. have adhesive properties that aid in interacting with the host extracellular matrix and thus act as 'moonlighting'proteins. Moonlighting proteins have multiple functions, which adds a dimension to cellular complexity and benefit cells in several ways. This phenomenon occurs in both eukaryotes and prokaryotes. For example, moonlighting proteins from the glycolytic pathway or TCA cycle can play a role in bacterial pathogenesis by either acting as proteins secreted in a conventional pathway and/or as cell surface components that facilitate adhesion or adherence. This review outlines the multifunctionality exhibited by many Paracoccidioides spp. enzymes, including aconitase, aldolase, glyceraldehyde-3-phosphate dehydrogenase, isocitratelyase, malatesynthase, triose phosphate isomerase, fumarase, and enolase. We discuss the roles that moonlighting activities play in the virulence characteristics of this fungus and several other human pathogens during their interactions with the host.

Genome-wide association study and ancestral origins of the slick-hair coat in tropically adapted cattle

The slick hair coat (SLICK) is a dominantly inherited trait typically associated with tropically adapted cattle that are from Criollo descent through Spanish colonization of cattle into the New World. The trait is of interest relative to climate change, due to its association with improved thermo-tolerance and subsequent increased productivity. Previous studies localized the SLICK locus to a 4 cM region on chromosome (BTA) 20 and identified signatures of selection in this region derived from Senepol cattle. The current study compares three slick-haired Criollo-derived breeds including Senepol, Carora, and Romosinuano and three additional slick-haired cross-bred lineages to non-slick ancestral breeds. Genome-wide association (GWA), haplotype analysis, signatures of selection, runs of homozygosity (ROH), and identity by state (IBS) calculations were used to identify a 0.8 Mb (37.7-38.5 Mb) consensus region for the SLICK locus on BTA20 in which contains SKP2 and SPEF2 as possible candidate genes. Three specific haplotype patterns are identified in slick individuals, all with zero frequency in non-slick individuals. Admixture analysis identified common genetic patterns between the three slick breeds at the SLICK locus. Principal component analysis (PCA) and admixture results show Senepol and Romosinuano sharing a higher degree of genetic similarity to one another with a much lesser degree of similarity to Carora. Variation in GWA, haplotype analysis, and IBS calculations with accompanying population structure information supports potentially two mutations, one common to Senepol and Romosinuano and another in Carora, effecting genes contained within our refined location for the SLICK locus.

Zirconia-based dental crown to support a removable partial denture: a three-dimensional finite element analysis using contact elements and micro-CT data

Veneer fracture is the most common complication in zirconia-based restorations. The aim of this study was to evaluate the mechanical behavior of a zirconia-based crown in a lower canine tooth supporting removable partial denture (RPD) prosthesis, varying the bond quality of the veneer/coping interface. Microtomography (μCT) data of an extracted left lower canine were used to build the finite element model (M) varying the core material (gold core - MAu; zirconia core - MZi) and the quality of the veneer/core interface (complete bonded - MZi; incomplete bonded - MZi-NL). The incomplete bonding condition was only applied for zirconia coping by using contact elements (Target/Contact) with 0.3 frictional coefficients. Stress fields were obtained using Ansys Workbench 10.0. The loading condition (L = 1 N) was vertically applied at the base of the RPD prosthesis metallic support towards the dental apex. Maximum principal (σmax) and von Mises equivalent (σvM) stresses were obtained. The σmax (MPa) for the bonded condition was similar between gold and zirconia cores (MAu, 0.42; MZi, 0.40). The incomplete bonded condition (MZi-NL) raised σmax in the veneer up to 800% (3.23 MPa) in contrast to the bonded condition. The peak of σvM increased up to 270% in the MZi-NL. The incomplete bond condition increasing the stress in the veneer/zirconia interface.

Prevalence and possible risk factors of peri-implantitis: a concept review

The purpose of this review is to estimate the prevalence of peri-implantitis, as well as to determine possible risk factors associated with its development in patients treated with oral implants. Although implant therapy has been identified as a successful and predictable treatment for partially and fully edentulous patients, complications and failures can occur. Peri-implantitis is considered a biologic complication that results in bone loss around implants and may lead to implant treatment failure. A great variation has been observed in the literature regarding the prevalence of peri-implantitis according to the diagnostic criteria used to define peri-implantitis. The prevalence ranges from 4.7 to 43% at implant level, and from 8.9 to > 56% at patient level. Many risk factors that may lead to the establishment and progression of peri-implantitis have been suggested. There is strong evidence that presence and history of periodontitis are potential risk factors for peri-implantitis. Cigarette smoking has not yet been conclusively established as a risk factor for peri-implantitis, although extra care should be taken with dental implant in smokers. Other risk factors, such as diabetes, genetic traits, implant surface roughness and presence of keratinized mucosa still require further investigation. Peri-implantitis is not an uncommon complication following implant therapy. A higher prevalence of peri-implantitis has been identified for patients with presence or history of periodontal disease and for smokers. Until now, a true risk factor for peri-implantitis has not been established. Supportive maintenance program is essential for the long-term success of treatments with oral implants. The knowledge of the real impact of peri-implantitis on the outcome of treatments with oral implants as well as the identification of risk factors associated to this inflammatory condition are essential for the development of supportive maintenance programs and the establishment of prevention protocols.