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.

Expression of eight genes of nuclear factor-kappa B pathway in multiple myeloma using bone marrow aspirates obtained at diagnosis

Purpose: To evaluate the expression of NF-kappa B pathway genes in total bone marrow samples obtained from MM at diagnosis using real-time quantitative PCR and to evaluate its possible correlation with disease clinical features and survival. Material and methods: Expression of eight genes related to NF-kappa B pathway (NFKB1, IKB, RANK, RANKL, OPG, IL6, VCAM1 and ICAM1) were studied in 53 bone marrow samples from newly diagnosed MM patients and in seven normal controls, using the Taqman system. Genes were considered overexpressed when tumor expression level was at least four times higher than that observed in normal samples. Results: The percentages of overexpression of the eight genes were: NFKB1 0%, IKB 22.6%, RANK 15.1%, RANKL 31.3%, OPG 7.5%, IL6 39.6%, VCAM1 10% and ICAM1 26%. We found association between IL6 expression level and International Staging System (ISS) (p = 0.01), meaning that MM patients with high ISS scores have more chance of overexpression of IL6. The mean value of ICAM1 relative expression was also associated with the ISS score (p = 0.02). Regarding OS, cases with IL6 overexpression present worse evolution than cases with IL6 normal expression (p = 0.04). Conclusion: We demonstrated that total bone marrow aspirates can be used as a source of material for gene expression studies in MM. In this context, we confirmed that IL6 overexpression was significantly associated with worse survival and we described that it is associated with high ISS scores. Also, ICAM1 was overexpressed in 26% of cases and its level was associated with ISS scores.

Report of a chimeric origin of transposable elements in a bovine-coding gene

Despite the wide distribution of transposable elements (TEs) in mammalian genomes, part of their evolutionary significance remains to be discovered. Today there is a substantial amount of evidence showing that TEs are involved in the generation of new exons in different species. In the present study, we searched 22,805 genes and reported the occurrence of TE-cassettes in coding sequences of 542 cow genes using the RepeatMasker program. Despite the significant number (542) of genes with TE insertions in exons only 14 (2.6%) of them were translated into protein, which we characterized as chimeric genes. From these chimeric genes, only the FAST kinase domains 3 (FASTKD3) gene, present on chromosome BTA 20, is a functional gene and showed evidence of the exaptation event. The genome sequence analysis showed that the last exon coding sequence of bovine FASTKD3 is similar to 85% similar to the ART2A retrotransposon sequence. In addition, comparison among FASTKD3 proteins shows that the last exon is very divergent from those of Homo sapiens, Pan troglodytes and Canis familiares. We suggest that the gene structure of bovine FASTKD3 gene could have originated by several ectopic recombinations between TE copies. Additionally, the absence of TE sequences in all other species analyzed suggests that the TE insertion is clade-specific, mainly in the ruminant lineage.

Primary Hyperparathyroidism as the First Clinical Manifestation of Multiple Endocrine Neoplasia Type 2A in a 5-Year-Old Child

Background: Primary hyperparathyroidism occurs in only 10%-30% of patients with multiple endocrine neoplasia type 2A (MEN2A), rarely as the sole clinical manifestation, and is usually diagnosed after the third decade of life. Summary: A5-year-old girl was referred for prophylactic thyroidectomy as she carried the p.C634R RET mutation. She was clinically asymptomatic, with a normally palpable thyroid and with the cervical region free of lymphadenopathy or other nodules. Preoperative tests revealed hypercalcemia associated with elevation of parathyroid hormone (PTH) (calcium = 11.2mg/dL, calcium ion = 1.48mmol/L, phosphorus = 4.0 mg/dL, alkaline phosphatase = 625U/L, parathyroid hormone (PTH) PTH = 998 pg/mL). A thyroid ultrasound was normal and parathyroid scintigraphy with (99m)Tc-Sestamibi revealed an area of radioconcentration in the upper half of the left thyroid lobe suggesting hyperfunctioning parathyroid tissue. She underwent total thyroidectomy and parathyroidectomy and developed hypocalcemia. The anatomopathological examination showed no histopathological changes in the thyroid tissue and an adenoma of the parathyroid gland, confirming the diagnosis of hyperparathyroidism. Conclusions: Primary hyperparathyroidism can be a precocious manifestation of MEN2A. This case report highlights that asymptomatic hypercalcemia should be scrutinized in children related to patients with MEN2A who carry a mutation in the RET proto-oncogene, especially mutations in the codon 634, before the currently recommended age of 8 years.

New reports of Antricola guglielmonei and Antricola delacruzi in Brazil, and a description of a new argasid species (Acari)

Adults of 3 tick species (Acari: Argasidae) identified as Antricola guglielmonei, Antricola delacruzi, and Carios rondoniensis n. sp. were collected oil bill guano in a cave in the state of Rondonia, western Amazon. Brazil. Adults of C. rondoniensis Possess a unique combination of characters that distinguish them front all described adults in the Argasidae. i.e.. a large spiracular plate densely filled with small goblets, a well-developed flap covering the female genital opening, and palpi containing several tufts of long setae oil articles 2 and 3. Unlike Ornithodoros or other Carios species. adults of C rondoniensis have a scooplike hypostome devoid of denticles, as in Antricola spp. Conversely, the presence of a pair of long posthypostomal setae, and a slitlike transverse fissure at the Capsule opening of the Haller's organ, are characters of C. rondonensis that are also found ill species of Carios and Ornithodoros, but not in Antricola species. Molecular analyses inferred from a portion of the 16S rRNA mitochondrial gene indicate that C. rondoniensis is phylogenetically closest to species of Carios. followed by species of Antricola. and then Ornithodoros. Because the highest bootstrap value linking C. rondoniensis to Carios spp. was 62%, further phylogenetic studies are needed to better evaluate the taxonomic Status of the former species.

DESCRIPTION OF ADULTS AND NYMPH, AND REDESCRIPTION OF THE LARVA, OF ORNITHODOROS MARINKELLEI (ACARI: ARGASIDAE), WITH DATA ON ITS PHYLOGENETIC POSITION

The argasid tick Ornithodoros marinkellei Kohls, Clifford, and Jones, 1969 was described 4 decades ago based on larval specimens collected from bats (Pteronotus spp.) in Colombia and Panama. Thereafter, larval O. marinkellei parasitizing bats were reported from Venezuela, Guyana, and Brazil. Herein, we describe the adults and nymph, and redescribe the larva of O. marinkellei based on specimens recently collected in the western Brazilian Amazon region. In contrast to all other known adult argasids, the idiosoma of both males and females of O. marinkellei is covered with sclerotized plaques. The idiosoma of the nymph of O. marinkellei is entirely micromamillated, and differs from the adults by the absence of plaques. The larva of O. marinkellei is morphologically similar to the larvae of the 2 other species belonging to the subgenus Subparmatus, i.e., Ornithodoros viguerasi Cooley and Kohls, 1941 and Ornithodoros mormoops Kohls, Clifford, and Jones, 1969. Because of the long and narrow dorsal plate, the larva of O. marinkellei is readily distinguished from O. viguerasi and O. mormoops. Comparison of our larvae from Brazil with O. marinkellei paratype specimens from Colombia confirmed their taxonomic identification. However, a few morphological differences, particularly in the size of the gnathosoma, were observed. Further studies are necessary to clarify whether O. marinkellei is a complex of different species, or a single species represented by morphologically polymorphic, and geographically distinct populations. Partial mitochondrial 16S rDNA gene sequences were generated for O. marinkellei specimens from Brazil, and compared with available homologous sequences in GenBank. Phylogenetic analyses revealed O. marinkellei to be distinct from the remaining argasid species available in GenBank, including other bat-associated tick species that are found in sympatry with O. marinkellei in the Neotropical region.

Elevated Risk for HIV-1 Infection in Adolescents and Young Adults in Sao Paulo, Brazil

Background. Recent studies have sought to describe HIV infection and transmission characteristics around the world. Identification of early HIV-1 infection is essential to proper surveillance and description of regional transmission trends. In this study we compare people recently infected (RI) with HIV-1, as defined by Serologic Testing Algorithm for Recent HIV Seroconversion (STARHS), to those with chronic infection. Methodology/Principal Findings. Subjects were identified from 2002-2004 at four testing sites in Sao Paulo. Of 485 HIV-1-positive subjects, 57 (12%) were defined as RI. Of the participants, 165 (34.0%) were aware of their serostatus at the time of HIV-1 testing. This proportion was statistically larger (p<0.001) among the individuals without recent infection (n = 158, 95.8%) compared to 7 individuals (4.2%) with recently acquired HIV-1 infection. In the univariate analysis, RI was more frequent in,25 and >59 years-old age strata (p < 0.001). The majority of study participants were male (78.4%), 25 to 45 years-old (65.8%), white (63.2%), single (61.7%), with family income of four or more times the minimum wage (41.0%), but with an equally distributed educational level. Of those individuals infected with HIV-1, the predominant route of infection was sexual contact (89.4%), with both hetero (47.5%) and homosexual (34.5%) exposure. Regarding sexual activity in these individuals, 43.9% reported possible HIV-1 exposure through a seropositive partner, and 49.4% reported multiple partners, with 47% having 2 to 10 partners and 37.4% 11 or more; 53.4% of infected individuals reported condom use sometimes; 34.2% reported non-injecting, recreational drug use and 23.6% were reactive for syphilis by VDRL. Subjects younger than 25 years of age were most vulnerable according to the multivariate analysis. Conclusions/Significance. In this study, we evaluated RI individuals and discovered that HIV-1 has been spreading among younger individuals in Sao Paulo and preventive approaches should, therefore, target this age stratum.

Trends in dermatomyositis- and polymyositis-related mortality in the state of Sao Paulo, Brazil, 1985-2007: multiple cause-of-death analysis

Background: Dermatomyositis (DM) and polymyositis (PM) are rare systemic autoimmune rheumatic diseases with high fatality rates. There have been few population-based mortality studies of dermatomyositis and polymyositis in the world, and none have been conducted in Brazil. The objective of the present study was to employ multiple-cause of-death methodology in the analysis of trends in mortality related to dermatomyositis and polymyositis in the state of Sao Paulo, Brazil, between 1985 and 2007. Methods: We analyzed mortality data from the Sao Paulo State Data Analysis System, selecting all death certificates on which DM or PM was listed as a cause of death. The variables sex, age and underlying, associated or total mentions of causes of death were studied using mortality rates, proportions and historical trends. Statistical analysis were performed by chi-square and H Kruskal-Wallis tests, variance analysis and linear regression. A p value less than 0.05 was regarded as significant. Results: Over a 23-year period, there were 318 DM-related deaths and 316 PM-related deaths. Overall, DM/PM was designated as an underlying cause in 55.2% and as an associated cause in 44.8%; among 634 total deaths females accounted for 71.5%. During the study period, age-and gender-adjusted DM mortality rates did not change significantly, although PM as an underlying cause and total mentions of PM trended lower (p < 0.05). The mean ages at death were 47.76 +/- 20.81 years for DM and 54.24 +/- 17.94 years for PM (p = 0.0003). For DM/PM, respectively, as underlying causes, the principal associated causes of death were as follows: pneumonia (in 43.8%/33.5%); respiratory failure (in 34.4%/32.3%); interstitial pulmonary diseases and other pulmonary conditions (in 28.9%/17.6%); and septicemia (in 22.8%/15.9%). For DM/PM, respectively, as associated causes, the following were the principal underlying causes of death: respiratory disorders (in 28.3%/26.0%); circulatory disorders (in 17.4%/20.5%); neoplasms (in 16.7%/13.7%); infectious and parasitic diseases (in 11.6%/9.6%); and gastrointestinal disorders (in 8.0%/4.8%). Of the 318 DM-related deaths, 36 involved neoplasms, compared with 20 of the 316 PM-related deaths (p = 0.03). Conclusions: Our study using multiple cause of deaths found that DM/PM were identified as the underlying cause of death in only 55.2% of the deaths, indicating that both diseases were underestimated in the primary mortality statistics. We observed a predominance of deaths in women and in older individuals, as well as a trend toward stability in the mortality rates. We have confirmed that the risk of death is greater when either disease is accompanied by neoplasm, albeit to lesser degree in individuals with PM. The investigation of the underlying and associated causes of death related to DM/PM broaden the knowledge of the natural history of both diseases and could help integrate mortality data for use in the evaluation of control measures for DM/PM.

Multiple classical limits in relativistic and nonrelativistic quantum mechanics

The existence of a classical limit describing the interacting particles in a second-quantized theory of identical particles with bosonic symmetry is proved. This limit exists in addition to the previously established classical limit with a classical field behavior, showing that the limit h -> 0 of the theory is not unique. An analogous result is valid for a free massive scalar field: two distinct classical limits are proved to exist, describing a system of particles or a classical field. The introduction of local operators in order to represent kinematical properties of interest is shown to break the permutation symmetry under some localizability conditions, allowing the study of individual particle properties.

The Coupled Aerosol and Tracer Transport model to the Brazilian developments on the Regional Atmospheric Modeling System (CATT-BRAMS) - Part 1: Model description and evaluation

We introduce the Coupled Aerosol and Tracer Transport model to the Brazilian developments on the Regional Atmospheric Modeling System (CATT-BRAMS). CATT-BRAMS is an on-line transport model fully consistent with the simulated atmospheric dynamics. Emission sources from biomass burning and urban-industrial-vehicular activities for trace gases and from biomass burning aerosol particles are obtained from several published datasets and remote sensing information. The tracer and aerosol mass concentration prognostics include the effects of sub-grid scale turbulence in the planetary boundary layer, convective transport by shallow and deep moist convection, wet and dry deposition, and plume rise associated with vegetation fires in addition to the grid scale transport. The radiation parameterization takes into account the interaction between the simulated biomass burning aerosol particles and short and long wave radiation. The atmospheric model BRAMS is based on the Regional Atmospheric Modeling System (RAMS), with several improvements associated with cumulus convection representation, soil moisture initialization and surface scheme tuned for the tropics, among others. In this paper the CATT-BRAMS model is used to simulate carbon monoxide and particulate material (PM(2.5)) surface fluxes and atmospheric transport during the 2002 LBA field campaigns, conducted during the transition from the dry to wet season in the southwest Amazon Basin. Model evaluation is addressed with comparisons between model results and near surface, radiosondes and airborne measurements performed during the field campaign, as well as remote sensing derived products. We show the matching of emissions strengths to observed carbon monoxide in the LBA campaign. A relatively good comparison to the MOPITT data, in spite of the fact that MOPITT a priori assumptions imply several difficulties, is also obtained.

Description and Phylogenetic Relationships of a New Genus and Species of Lizard (Squamata, Gymnophthalmidae) from the Amazonian Rainforest of Northern Brazil

Marinussaurus curupira, a new genus and species of Gymnophthalmidae lizard is described from Iranduba, state of Amazonas, Brazil. The genus is characterized by an elongate body; short and stout pentadactyl limbs; all digits clawed; single frontonasal; two prefrontals; absence of frontoparietals; interparietal and parietals forming a straight posterior margin, with interparietal shorter than parietals; distinctive ear opening and eyelid; few temporals; three pairs of chin shields; nasal divided; a distinct collar; smooth, mainly hexagonal, dorsal scales; smooth quadrangular ventral scales; two precloacal and three femoral pores on each side in males; pores between three or four scales. Parsimony (PAR) and partitioned Bayesian (BA) phylogenetic analyses with morphological and molecular data recovered the new genus as a member of the Ecpleopodini radiation of the Cercosaurinae. A close relationship of the new genus with Arthrosaura is postulated.

Systematic Revision of the granulatus Group of Urophonius Pocock, 1893 (Scorpiones, Bothriuridae), with Description of a New Species from Central Chile

A systematic revision of the granulatus group of the bothriurid scorpion genus Urophonius Pocock, 1893 is presented. Urophonius pizarroi, n. sp., a new species from central Chile, is described. Urophonius granulatus Pocock, 1898, Urophonius somuncura Acosta, 2003, and Urophonius tregualemuensis Cekalovic, 1981, are redescribed using modern standards. The adult males of U. somuncura and U. tregualemuensis are described for the first time. A distribution map and key to the species of the granulatus group are provided, along with a discussion of their phenology.

AN UNIFIED DESCRIPTION OF HERA AND RHIC DATA

Perturbative Quantum Chromodynamics (pQCD) predicts that the small-x gluons in the hadron wavefunction should form a Color Glass Condensate (CGC), which has universal properties, which are the same for nucleon or nuclei. Making use of the results in V.P. Goncalves, M.S. Kugeratski, M.V.T. Machado, F.S. Navarra, Phys. Lett. B643, 273 (2006), we study the behavior of the anomalous dimension in the saturation models as a function of the photon virtuality and of the scaling variable rQ(s), since the main difference among the known parameterizations are characterized by this quantity.

Use of correlated potential harmonic basis functions for the description of the (4)He trimer and small clusters

A correlated many-body basis function is used to describe the (4)He trimer and small helium clusters ((4)HeN) with N = 4-9. A realistic helium dimer potential is adopted. The ground state results of the (4)He dimer and trimer are in close agreement with earlier findings. But no evidence is found for the existence of Efimov state in the trimer for the actual (4)He-(4)He interaction. However, decreasing the potential strength we calculate several excited states of the trimer which exhibit Efimov character. We also solve for excited state energies of these clusters which are in good agreement with Monte Carlo hyperspherical description. (C) 2011 American Institute of Physics. [doi:10.1063/1.3583365]

Deformed Gaussian-orthogonal-ensemble description of small-world networks

The study of spectral behavior of networks has gained enthusiasm over the last few years. In particular, random matrix theory (RMT) concepts have proven to be useful. In discussing transition from regular behavior to fully chaotic behavior it has been found that an extrapolation formula of the Brody type can be used. In the present paper we analyze the regular to chaotic behavior of small world (SW) networks using an extension of the Gaussian orthogonal ensemble. This RMT ensemble, coined the deformed Gaussian orthogonal ensemble (DGOE), supplies a natural foundation of the Brody formula. SW networks follow GOE statistics until a certain range of eigenvalue correlations depending upon the strength of random connections. We show that for these regimes of SW networks where spectral correlations do not follow GOE beyond a certain range, DGOE statistics models the correlations very well. The analysis performed in this paper proves the utility of the DGOE in network physics, as much as it has been useful in other physical systems.