Novel Primate-Specific Genes, RMEL 1, 2 and 3, with Highly Restricted Expression in Melanoma, Assessed by New Data Mining Tool

Melanoma is a highly aggressive and therapy resistant tumor for which the identification of specific markers and therapeutic targets is highly desirable. We describe here the development and use of a bioinformatic pipeline tool, made publicly available under the name of EST2TSE, for the in silico detection of candidate genes with tissue-specific expression. Using this tool we mined the human EST (Expressed Sequence Tag) database for sequences derived exclusively from melanoma. We found 29 UniGene clusters of multiple ESTs with the potential to predict novel genes with melanoma-specific expression. Using a diverse panel of human tissues and cell lines, we validated the expression of a subset of three previously uncharacterized genes (clusters Hs.295012, Hs.518391, and Hs.559350) to be highly restricted to melanoma/melanocytes and named them RMEL1, 2 and 3, respectively. Expression analysis in nevi, primary melanomas, and metastatic melanomas revealed RMEL1 as a novel melanocytic lineage-specific gene up-regulated during melanoma development. RMEL2 expression was restricted to melanoma tissues and glioblastoma. RMEL3 showed strong up-regulation in nevi and was lost in metastatic tumors. Interestingly, we found correlations of RMEL2 and RMEL3 expression with improved patient outcome, suggesting tumor and/or metastasis suppressor functions for these genes. The three genes are composed of multiple exons and map to 2q12.2, 1q25.3, and 5q11.2, respectively. They are well conserved throughout primates, but not other genomes, and were predicted as having no coding potential, although primate-conserved and human-specific short ORFs could be found. Hairpin RNA secondary structures were also predicted. Concluding, this work offers new melanoma-specific genes for future validation as prognostic markers or as targets for the development of therapeutic strategies to treat melanoma.

Data Mining Applied to Harmonic Current Sources Identification in Residential Consumers

This work proposes a method based on both preprocessing and data mining with the objective of identify harmonic current sources in residential consumers. In addition, this methodology can also be applied to identify linear and nonlinear loads. It should be emphasized that the entire database was obtained through laboratory essays, i.e., real data were acquired from residential loads. Thus, the residential system created in laboratory was fed by a configurable power source and in its output were placed the loads and the power quality analyzers (all measurements were stored in a microcomputer). So, the data were submitted to pre-processing, which was based on attribute selection techniques in order to minimize the complexity in identifying the loads. A newer database was generated maintaining only the attributes selected, thus, Artificial Neural Networks were trained to realized the identification of loads. In order to validate the methodology proposed, the loads were fed both under ideal conditions (without harmonics), but also by harmonic voltages within limits pre-established. These limits are in accordance with IEEE Std. 519-1992 and PRODIST (procedures to delivery energy employed by Brazilian`s utilities). The results obtained seek to validate the methodology proposed and furnish a method that can serve as alternative to conventional methods.

Environmental management system and human resource practices: is there a link between them in four Brazilian companies?

The aim of this article is to analyze the theoretical model proposed by [Jabbour CJC, Santos FCA. Relationships between human resource dimensions and environmental management in companies: proposal of a model. Journal of Cleaner Production 2008;16(1):5 1-8.] based on the data collected in four Brazilian companies. This model investigates how the phases of the environmental management system can be linked to human resource practices in order to attain continuous improvement of a company`s environmental performance. Our aim is to contribute to a field, which has little empirical evidence. Although the interaction between the phases of the environmental management system and human resource practices is recommended by the specialized literature [Daily BE Huang S. Achieving sustainability through attention to human resource factors in environmental management. International Journal of Operations and Production Management 2001:21(12):1539-52.], the results indicate that most of the theoretical assumptions could not be confirmed in these Brazilian companies. (C) 2008 Elsevier Ltd. All rights reserved.

Assessing the evolution of sustainability reporting in the mining sector

Since the 1990s several large companies have been publishing nonfinancial performance reports. Focusing initially on the physical environment, these reports evolved to consider social relations, as well as data on the firm`s economic performance. A few mining companies pioneered this trend, and in the last years some of them incorporated the three dimensions of sustainable development, publishing so-called sustainability reports. This article reviews 31 reports published between 2001 and 2006 by four major mining companies. A set of 62 assessment items organized in six categories (namely context and commitment, management, environmental, social and economic performance, and accessibility and assurance) were selected to guide the review. The items were derived from international literature and recommended best practices, including the Global Reporting Initiative G3 framework. A content analysis was performed using the report as a sampling unit, and using phrases, graphics, or tables containing certain information as data collection units. A basic rating scale (0 or 1) was used for noting the presence or absence of information and a final percentage score was obtained for each report. Results show that there is a clear evolution in report`s comprehensiveness and depth. Categories ""accessibility and assurance"" and ""economic performance"" featured the lowest scores and do not present a clear evolution trend in the period, whereas categories ""context and commitment"" and ""social performance"" presented the best results and regular improvement; the category ""environmental performance,"" despite it not reaching the biggest scores, also featured constant evolution. Description of data measurement techniques, besides more comprehensive third-party verification are the items most in need of improvement.

Embrittlement of case hardened steel chain link

Various steel chain links presented cracking during their manufacturing process, which includes induction case hardening and electrogalvanizing steps. Fractographic examination of the exposed crack surfaces revealed intergranular cracking with some areas featuring a thin layer of iron oxide, indicating that the cracking took place after the electrogalvanizing step. The location of the cracks coincided with the position of the deepest case hardened layer, suggesting the occurrence of localized overheating during the induction case hardening step. Inductive heating finite element analysis (COSMOS Designstar Software) confirmed that during the case hardening the austenitising temperature reached in the crack region values of approximately 1050 degrees C. The results indicated that intergranular cracking was caused by hydrogen embrittlement. (C) 2009 Elsevier Ltd. All rights reserved.

Perspectives on sexual and reproductive health among women in an ancient mining area in Brazil

The purpose of this study was to describe the reproductive profile and frequency of genital infections among women living in the Serra Pelada, a former mining village in the Para state, Brazil. A descriptive study of women living in the mining area of Serra Pelada was performed in 2004 through interviews that gathered demographics and clinical data, and assessed risk behaviors of 209 randomly-selected women. Blood samples were collected for rapid assay for HIV; specimens were taken for Pap smears and Gram stains. Standard descriptive statistical analyses were performed and prevalence was calculated to reflect the relative frequency of each disease. Of the 209 participants, the median age was 38 years, with almost 70% having less than four years of education and 77% having no income or under 1.9 times the minimum wage of Brazil. About 30% did not have access to health care services during the preceding year. Risk behaviors included: alcohol abuse, 24.4%; illicit drug abuse, 4.3%; being a sex worker, 15.8%; and domestic violence, 17.7%. Abnormal Pap smear was found in 8.6%. Prevalence rates of infection were: HIV, 1.9%; trichomoniasis, 2.9%; bacterial vaginosis, 18.7%; candidiasis, 5.7%; Chlamydial-related cytological changes, 3.3%; and HPV-related cytological changes, 3.8%. Women living in this mining area in Brazil are economically and socially vulnerable to health problems. It is important to point out the importance of concomitant broader strategies that include reducing poverty and empowering women to make improvements regarding their health.

Reduced frequency of CD4(+)CD25(HIGH)FOXP3(+) cells and diminished FOXP3 expression in patients with Common Variable Immunodeficiency: A link to autoimmunity?

Common Variable Immunodeficiency (CVID) is a primary immunodeficiency disease characterized by defective immunoglobulin production and often associated with autoimmunity. We used flow cytometry to analyze CD4(+)CD25(HIGH)FOXP3(+) T regulatory (Treg) cells and ask whether perturbations in their frequency in peripheral blood could underlie the high incidence of autoimmune disorders in CVID patients. In this study, we report for the first time that CVID patients with autoimmune disease have a significantly reduced frequency of CD4(+)CD25(HIGH)FOXP3(+) cells in their peripheral blood accompanied by a decreased intensity of FOXP3 expression. Notably, although CVID patients in whom autoimmunity was not diagnosed had a reduced frequency of CD4(+)CD25(HIGH)FOXP3(+) cells, FOXP3 expression levels did not differ from those in healthy controls. In conclusion, these data suggest compromised homeostasis of CD4(+)CD25(HIGH)FOXP3(+) cells in a subset of CVID patients with autoimmunity, and may implicate Treg cells in pathological mechanisms of CVID. (C) 2009 Elsevier Inc. All rights reserved.

Distinguishing links up to link-homotopy by algebraic methods

In this paper we provide a complete algebraic invariant of link-homotopy, that is, an algebraic invariant that distinguishes two links if and only if they are link-homotopic. The paper establishes a connection between the ""peripheral structures"" approach to link-homotopy taken by Milnor, Levine and others, and the string link action approach taken by Habegger and Lin. (C) 2009 Elsevier B.V. All rights reserved.

The link between partial melting, granitization and granulite development in central Ribeira Fold Belt, SE Brazil: New evidence from elemental and Sr-Nd isotopic geochemistry

Elemental and Sr-Nd isotopic data on metatexites, diatexites, orthogneisses and charnockites from the central Ribeira Fold Belt indicate that they are LILE-enriched weakly peraluminous granodiorites. Harker and Th-Hf-La correlation trends suggest that these rocks represent a co-genetic sequence, whereas variations on CaO, MnO, Y and HREE for charnockites can be explained by garnet consumption during granulitic metamorphism. Similar REE patterns and isotopic results of epsilon(565)(Nd) = -5.4 to -7.3 and (87)Sr/(86)Sr(565) = 0.706-0.711 for metatexites, diatexites, orthogneisses and charnockites, as well as similar T(DM) ages between 2.0 and 1.5 Ga are consistent with evolution from a relatively homogeneous and enriched common crustal (metasedimentary) protolith. Results suggest a genetic link between metatexites, diatexites, orthogneisses and charnockites and a two-step process for charnockite development: (a) generation of the hydrated igneous protoliths by anatexis of metasedimentary rocks; (b) continuous high-grade metamorphism that transformed the ""S-type granitoids"" (leucosomes and diatexites) into orthogneisses and, as metamorphism and dehydration progressed, into charnockites. (C) 2011 Elsevier Ltd. All rights reserved.

Antioxidant therapy attenuates oxidative stress in the blood of subjects exposed to occupational airborne contamination from coal mining extraction and incineration of hospital residues

Coal mining and incineration of solid residues of health services (SRHS) generate several contaminants that are delivered into the environment, such as heavy metals and dioxins. These xenobiotics can lead to oxidative stress overgeneration in organisms and cause different kinds of pathologies, including cancer. In the present study the concentrations of heavy metals such as lead, copper, iron, manganese and zinc in the urine, as well as several enzymatic and non-enzymatic biomarkers of oxidative stress in the blood (contents of lipoperoxidation = TBARS, protein carbonyls = PC, protein thiols = PT, alpha-tocopherol = AT, reduced glutathione = GSH, and the activities of glutathione S-transferase = GST, glutathione reductase = GR, glutathione peroxidase = GPx, catalase = CAT and superoxide dismutase = SOD), in the blood of six different groups (n = 20 each) of subjects exposed to airborne contamination related to coal mining as well as incineration of solid residues of health services (SRHS) after vitamin E (800 mg/day) and vitamin C (500 mg/day) supplementation during 6 months, which were compared to the situation before the antioxidant intervention (Avila et al., Ecotoxicology 18:1150-1157, 2009; Possamai et al., Ecotoxicology 18:1158-1164, 2009). Except for the decreased manganese contents, heavy metal concentrations were elevated in all groups exposed to both sources of airborne contamination when compared to controls. TBARS and PC concentrations, which were elevated before the antioxidant intervention decreased after the antioxidant supplementation. Similarly, the contents of PC, AT and GSH, which were decreased before the antioxidant intervention, reached values near those found in controls, GPx activity was reestablished in underground miners, and SOD, CAT and GST activities were reestablished in all groups. The results showed that the oxidative stress condition detected previously to the antioxidant supplementation in both directly and indirectly subjects exposed to the airborne contamination from coal dusts and SRHS incineration, was attenuated after the antioxidant intervention.

A ditryptophan cross-link is responsible for the covalent dimerization of human superoxide dismutase 1 during its bicarbonate-dependent peroxidase activity

Unlike intermolecular disulfide bonds, other protein cross-links arising from oxidative modifications cannot be reversed and are presumably more toxic to cells because they may accumulate and induce protein aggregation. However, most of these irreversible protein cross-links remain poorly characterized. For instance, the antioxidant enzyme human superoxide dismutase 1 (hSod1) has been reported to undergo non-disulfide covalent dimerization and further oligomerization during its bicarbonate-dependent peroxidase activity. The dimerization was shown to be dependent on the oxidation of the single, solvent-exposed TrP(32) residue of hSod1, but the covalent dimer was not isolated nor was its structure determined. In this work, the hSod1 covalent dimer was isolated, digested with trypsin in H(2)O and H(2)(18)O, and analyzed by UV-Vis spectroscopy and mass spectrometry (MS). The results demonstrate that the covalent dimer consists of two hSod1 subunits cross-linked by a ditryptophan, which contains a bond between C3 and N1 of the respective Trp(32) residues. We further demonstrate that the cross-link cleaves under usual MS/MS conditions leading to apparently unmodified Trp(32), partially hinders proteolysis, and provides a mechanism to explain the formation of hSod1 covalent trimers and tetramers. This characterization of the covalent hSod1 dimer identifies a novel oxidative modification of protein Trp residues and provides clues for studying its occurrence in vivo. (C) 2010 Elsevier Inc. All rights reserved.