Global pharmacogenomics: Impact of population diversity on the distribution of polymorphisms in the CYP2C cluster among Brazilians

The impact of biogeographical ancestry, self-reported 'race/color' and geographical origin on the frequency distribution of 10 CYP2C functional polymorphisms (CYP2C8*2, *3, *4, CYP2C9*2, *3, *5, *11, CYP2C19*2, *3 and *17) and their haplotypes was assessed in a representative cohort of the Brazilian population (n = 1034). TaqMan assays were used for allele discrimination at each CYP2C locus investigated. Individual proportions of European, African and Amerindian biogeographical ancestry were estimated using a panel of insertion-deletion polymorphisms. Multinomial log-linear models were applied to infer the statistical association between the CYP2C alleles and haplotypes (response variables), and biogeographical ancestry, self-reported Color and geographical origin (explanatory variables). The results showed that CYP2C19*3, CYP2C9*5 and CYP2C9*11 were rare alleles (<1%), the frequency of other variants ranged from 3.4% (CYP2C8*4) to 17.3% (CYP2C19*17). Two distinct haplotype blocks were identified: block 1 consists of three single nucleotide polymorphisms (SNPs) (CYP2C19*17, CYP2C19*2 and CYP2C9*2) and block 2 of six SNPs (CYP2C9*11, CYP2C9*3, CYP2C9*5, CYP2C8*2, CYP2C8*4 and CYP2C8*3). Diplotype analysis generated 41 haplotypes, of which eight had frequencies greater than 1% and together accounted for 96.4% of the overall genetic diversity. The distribution of CYP2C8 and CYP2C9 (but not CYP2C19) alleles, and of CYP2C haplotypes was significantly associated with self-reported Color and with the individual proportions of European and African genetic ancestry, irrespective of Color self-identification. The individual odds of having alleles CYP2C8*2, CYP2C8*3, CYP2C9*2 and CYP2C9*3, and haplotypes including these alleles, varied continuously as the proportion of European ancestry increased. Collectively, these data strongly suggest that the intrinsic heterogeneity of the Brazilian population must be acknowledged in the design and interpretation of pharmacogenomic studies of the CYP2C cluster in order to avoid spurious conclusions based on improper matching of study cohorts. This conclusion extends to other polymorphic pharmacogenes among Brazilians, and most likely to other admixed populations of the Americas. The Pharmacogenomics Journal (2012) 12, 267-276; doi: 10.1038/tpj.2010.89; published online 21 December 2010

The globular cluster kinematics and galaxy dark matter content of NGC 3923

This paper presents further results from our spectroscopic study of the globular cluster (GC) system of the group elliptical NGC 3923. From observations made with the GMOS instrument on the Gemini South Telescope, an additional 50 GC and ultra-compact dwarf (UCD) candidates have been spectroscopically confirmed as members of the NGC 3923 system. When the recessional velocities of these GCs are combined with the 29 GC velocities reported previously, a total sample of 79 GC/UCD velocities is produced. This sample extends to over 6 arcmin (>6 R-e similar to 30 kpc) from the centre of NGC 3923 and is used to study the dynamics of the GC system and the dark matter content of NGC 3923. It is found that the GC system of NGC 3923 displays no appreciable rotation, and that the projected velocity dispersion is constant with radius within the uncertainties. The velocity dispersion profiles of the integrated light and GC system of NGC 3923 are indistinguishable over the region in which they overlap. We find some evidence that the diffuse light and GCs of NGC 3923 have radially biased orbits within similar to 130 arcsec. The application of axisymmetric orbit-based models to the GC and integrated light velocity dispersion profiles demonstrates that a significant increase in the mass-to-light ratio (from M/L-V = 8 to 26) at large galactocentric radii is required to explain this observation. We therefore confirm the presence of a dark matter halo in NGC 3923. We find that dark matter comprises 17.5(-4.5)(+7.3) per cent of the mass within 1 R-e, 41.2(-10.6)(+18.2) per cent within 2 R-e and 75.6(-16.8)(+15.4) per cent within the radius of our last kinematic tracer at 6.9 R-e. The total dynamical mass within this radius is found to be 1.5(-0.25)(+0.4) x 10(12) M-circle dot. In common with other studies of large ellipticals, we find that our derived dynamical mass profile is consistently higher than that derived by X-ray observations, by a factor of around 2.

12 item Allodynia Symptom Checklist/Brasil: cross-cultural adaptation, internal consistency and reproducibility

Since there was no Portuguese questionnaire to evaluate cutaneous allodynia, which has been pointed out as a risk factor of migraine, we aimed to perform the cross-cultural adaptation of the 12 item Allodynia Symptom Checklist for the Brazilian population and to test its measurement properties. It consisted in six stages: translation, synthesis, back translation, revision by a specialist committee, pretest and submission the documents to the committee. In the pretest stage, the questionnaire was applied to 30 migraineurs of both sexes, who had some difficulty in understanding it. Thus, a second version was applied to 30 additional subjects, with no difficulties being reported. The mean filling out time was 3'36", and the internal consistency was 0.76. To test reproducibility, 15 other subjects filled out the questionnaire at two different times, it was classified as moderate (weighted kappa=0.58). We made available to Brazilian population an easy, quick and reliable questionnaire.

Copper ore type definition from Sossego Mine using X-ray diffraction and cluster analysis technique

This paper presents the classification of 110 copper ore samples from Sossego Mine, based on X-ray diffraction and cluster analysis. The comparison based on the position and the intensity of the diffracted peaks allowed the distinction of seven ore types, whose differences refer to the proportion of major minerals: quartz, feldspar, actinolite, iron oxides, mica and chlorite. There was a strong correlation between the grouping and the location of the samples in Sequeirinho and Sossego orebodies. This relationship is due to different types and intensities of hydrothermal alteration prevailing in each body, which reflect the mineralogical composition and thus the X-ray diffractograms of samples.

The young stellar cluster [DBS2003] 157 associated with the H ii region GAL 331.31-00.34

We report a study of the stellar content of the near-infrared (NIR) cluster [DBS2003] 157 embedded in the extended H ii region GAL 331.31-00.34, which is associated with the IRAS source 16085-5138. JHK photometry was carried out in order to identify potential ionizing candidates, and the follow-up NIR spectroscopy allowed the spectral classification of some sources, including two O-type stars. A combination of NIR photometry and spectroscopy data was used to obtain the distance of these two stars, with the method of spectroscopic parallax: IRS 298 (O6 V, 3.35 +/- 0.61 kpc) and IRS 339 (O9 V, 3.24 +/- 0.56 kpc). Adopting the average distance of 3.29 +/- 0.58 kpc and comparing the Lyman continuum luminosity of these stars with that required to account for the radio continuum flux of the H ii region, we conclude that these two stars are the ionizing sources of GAL 331.31-00.34. Young stellar objects (YSOs) were searched by using our NIR photometry and mid-infrared (MIR) data from the Galactic Legacy Infrared Mid-Plane Survey Extraordinaire (GLIMPSE) survey. The analysis of NIR and MIR colourcolour diagrams resulted in 47 YSO candidates. The GLIMPSE counterpart of IRAS 16085-5138, which presents IRAS colour indices compatible with an ultracompact H ii region, has been identified. The analysis of its spectral energy distribution between 2 and m revealed that this source shows a spectral index a= 3.6 between 2 and m, which is typical of a YSO immersed in a protostellar envelope. Lower limits to the bolometric luminosity and the mass of the embedded protostar have been estimated as L= 7.7 x 10(3) L? and M= 10 M?, respectively, which correspond to a B0B1 V zero-age main sequence star.

KRAS gene mutations in Noonan syndrome familial cases cluster in the vicinity of the switch II region of the G-domain: Report of another family with metopic craniosynostosis

Noonan syndrome (NS) and Noonan-related disorders [cardio-facio-cutaneous (CFC), Costello, Noonan syndrome with multiple lentigines (NS-ML), and neurofibromatosis-Noonan syndromes (NFNS)] are a group of developmental disorders caused by mutations in genes of the RAS/MAPK pathway. Mutations in the KRAS gene account for only a small proportion of affected Noonan and CFC syndrome patients that present an intermediate phenotype between these two syndromes, with more frequent and severe intellectual disability in NS and less ectodermal involvement in CFC syndrome, as well as atypical clinical findings such as craniosynostosis. Recently, the first familial case with a novel KRAS mutation was described. We report on a second vertical transmission (a mother and two siblings) with a novel mutation (p.M72L), in which the proband has trigonocephaly and the affected mother and sister, prominent ectodermal involvement. Metopic suture involvement has not been described before, expanding the main different cranial sutures which can be affected in NS and KRAS gene mutations. The gene alteration found in the studied family is in close proximity to the one reported in the other familial case (close to the switch II region of the G-domain), suggesting that this specific region of the gene could have less severe effects on intellectual ability than the other KRAS gene mutations found in NS patients and be less likely to hamper reproductive fitness. (c) 2012 Wiley Periodicals, Inc.

Diversity of the KIR gene cluster in an urban Brazilian population

The activity of natural killer cells depends on the balance between activating and inhibitory signals coming from their receptors. Among these are the killer cell immunoglobulin-like receptors (KIR) that recognize specific HLA class I allotypes. Here we characterized KIR genetic diversity and their HLA ligands in the population of Curitiba, Parana State (n = 164), and compared it with other worldwide populations. The distribution of 2DL4 alleles was also analyzed. The Curitiba population did not differ significantly from European and Euro-descendant populations, but as an admixed population showed higher genetic diversity. We found 27 KIR profiles, many of them uncommon in European populations, in agreement with the elevated historically recent gene flow in the study population. The frequencies of KIR genes and their respective HLA ligands were distributed independently and none of the analyzed individuals lacked functional KIR-HLA ligand combinations. KIR gene frequencies of 33 worldwide populations were consistent with geographic and ethnic distribution, in agreement with demography being the major factor shaping the observed gene content diversity of the KIR locus.

KRONBERGER 49: A NEW LOW-MASS GLOBULAR CLUSTER OR AN UNPRECEDENTED BULGE WINDOW?

We employ optical and near-infrared photometry to study the stars in the direction of the star cluster candidate Kronberger 49. The optical color-magnitude diagrams (V, I, and Gunn z photometry obtained with the Galileo Telescope) are tight and present evidence of a main-sequence turnoff. We may be dealing with a low-mass, metal-rich globular cluster located in the bulge at a distance from the Sun of d(circle dot) = 8 +/- 1 kpc. Alternatively, it may be a dust hole through which we are sampling the bulge stellar population affected by a very low amount of differential reddening.

CNO and F abundances in the globular cluster M22 (NGC 6656)

Context. Recent studies have confirmed the long standing suspicion that M 22 shares a metallicity spread and complex chemical enrichment history similar to that observed in omega Cen. M 22 is among the most massive Galactic globular clusters and its color-magnitude diagram and chemical abundances reveal the existence of sub-populations. Aims. To further constrain the chemical diversity of M 22, necessary to interpret its nucleosynthetic history, we seek to measure relative abundance ratios of key elements (carbon, nitrogen, oxygen, and fluorine) best studied, or only available, using high-resolution spectra at infrared wavelengths. Methods. High-resolution (R = 50 000) and high S/N infrared spectra were acquired of nine red giant stars with Phoenix at the Gemini-South telescope. Chemical abundances were calculated through a standard 1D local thermodynamic equilibrium analysis using Kurucz model atmospheres. Results. We derive [Fe/H] = -1.87 to -1.44, confirming at infrared wavelengths that M 22 does present a [Fe/H] spread. We also find large C and N abundance spreads, which confirm previous results in the literature but based on a smaller sample. Our results show a spread in A(C+N+O) of similar to 0.7 dex. Similar to mono-metallic globular clusters, M 22 presents a strong [Na/Fe]-[O/Fe] anticorrelation as derived from Na and CO lines in the K band. For the first time we recover F abundances in M 22 and find that it exhibits a 0.6 dex variation. We find tentative evidence for a flatter A(F)-A(O) relation compared to higher metallicity globular clusters. Conclusions. Our study confirms and expands upon the chemical diversity seen in this complex stellar system. All elements studied to date show large abundance spreads which require contributions from both massive and low mass stars.

Electrochemically activated coordenative assembly of a triruthenium cluster metallopolymer

A general strategy for electrochemically induced assembly of coordination metallopolymers is demonstrated using the tritopic bridging [Ru-3(mu(3)-O)(CH3COO)(6)(pytpy)(3)](+) cluster complex, where pytpy is the 4'-(4-pyridyl)-2,2':6',2 ''-terpyridine ligand, and iron(III) ions. The concept of such an electrochemically induced coordinative assembly was proven exploring the large difference in the [Fe(pytpy)2 complex formation constants depending on the iron ion oxidation state. Much more stable bridging complexes are formed in the presence of Fe(II) in contrast to Fe(III) ions. The build-up of electrochemically active films on FTO electrodes was confirmed by the growth of the corresponding voltammetric peaks concomitantly with the rise of typical triruthenium cluster and [Fe(pytpy)(2)](2+) complex absorption bands. The metallopolymer was constituted by agglomerates of more or less fused tape like structures, exhibiting large voids and pinholes, as revealed by SEM and AFM images. The adhesion/deposition on FTO was improved by functionalizing the surface with TES-tpy and HOOC-tpy, which increased the surface coverage up to 80%, as estimated by impedance spectroscopy. (C) 2012 Elsevier Ltd. All rights reserved.

Obsessive-compulsive symptom dimensions correlate to specific gray matter volumes in treatment-naive patients

Background: Clinical and sociodemographic findings have supported that OCD is heterogeneous and composed of multiple potentially overlapping and stable symptom dimensions. Previous neuroimaging investigations have correlated different patterns of OCD dimension scores and gray matter (GM) volumes. Despite their relevant contribution, some methodological limitations, such as patient's previous medication intake, may have contributed to inconsistent findings. Method: Voxel-based morphometry was used to investigate correlations between regional GM volumes and symptom dimensions severity scores in a sample of 38 treatment-naive OCD patients. Several standardized instruments were applied, including an interview exclusively developed for assessing symptom dimensions severity (DY-BOCS). Results: Scores on the "aggression" dimension were positively correlated with GM volumes in lateral parietal cortex in both hemispheres and negatively correlated with bilateral insula, left putamen and left inferior OFC. Scores on the "sexual/religious" dimension were positively correlated with GM volumes within the right middle lateral OFC and right DLPFC and negatively correlated with bilateral ACC. Scores on the "hoarding" dimension were positively correlated with GM volumes in the left superior lateral OFC and negatively correlated in the right parahippocampal gyrus. No significant correlations between GM volumes and the "contamination" or "symmetry" dimensions were found. Conclusions: Building upon preexisting findings, our data with treatment-naive OCD patients have demonstrated distinct GM substrates implicated in both cognitive and emotion processing across different OCS dimensions. (C) 2012 Elsevier Ltd. All rights reserved.

Cluster Coordination and Photoluminescence Properties of alpha-Ag2WO4 Microcrystals

In this paper, we report our initial research to obtain hexagonal rod-like elongated silver tungstate (alpha-Ag2WO4) microcrystals by different methods [sonochemistry (SC), coprecipitation (CP), and conventional hydrothermal (CH)] and to study their cluster coordination and optical properties. These microcrystals were structurally characterized by X-ray diffraction (XRD), Rietveld refinements, Fourier transform infrared (FT-IR), X-ray absorption near-edge structure (XANES), and extended X-ray absorption fine structure (EXAFS) spectroscopies. The shape and average size of these alpha-Ag2WO4 microcrystals were observed by field-emission scanning electron microscopy (FE-SEM). The optical properties of these microcrystals were investigated by ultraviolet-visible (UV-vis) spectroscopy and photoluminescence (PL) measurements. XRD patterns and Rietveld refinement data confirmed that alpha-Ag2WO4 microcrystals have an orthorhombic structure. FT-IR spectra exhibited four IR-active modes in a range from 250 to 1000 cm(-1). XANES spectra at the W L-3-edge showed distorted octahedral [WO6] clusters in the lattice, while EXAFS analyses confirmed that W atoms are coordinated by six O atoms. FE-SEM images suggest that the alpha-Ag2WO4 microcrystals grow by aggregation and the Ostwald ripening process. PL properties of alpha-Ag2WO4 microcrystals decrease with an increase in the optical band-gap values (3.19-3.23 eV). Finally, we observed that large hexagonal rod-like alpha-Ag2WO4 microcrystals prepared by the SC method exhibited a major PL emission intensity relative to alpha-Ag2WO4 microcrystals prepared by the CP and CH methods.

Space-time cluster analysis of American visceral leishmaniasis in Bauru, Sao Paulo State, Brazil

A space-time analysis of American visceral leishmaniasis (AVL) in humans in the city of Bauru, Sao Paulo State, Brazil was carried out based on 239 cases diagnosed between June 2003 and October 2008. Spatial analysis of the disease showed that cases occurred especially in the city's urban areas. AVL annual incidence rates were calculated, demonstrating that the highest rate occurred in 2006 (19.55/100,000 inhabitants). This finding was confirmed by the time series analysis, which also showed a positive tendency over the period analyzed. The present study allows us to conclude that the disease was clustered in the Southwest side of the city in 2006, suggesting that this area may require special attention with regard to control and prevention measures.

Space-time cluster analysis of American visceral leishmaniasis in Bauru, São Paulo State, Brazil

A space-time analysis of American visceral leishmaniasis (AVL) in humans in the city of Bauru, São Paulo State, Brazil was carried out based on 239 cases diagnosed between June 2003 and October 2008. Spatial analysis of the disease showed that cases occurred especially in the city's urban areas. AVL annual incidence rates were calculated, demonstrating that the highest rate occurred in 2006 (19.55/100,000 inhabitants). This finding was confirmed by the time series analysis, which also showed a positive tendency over the period analyzed. The present study allows us to conclude that the disease was clustered in the Southwest side of the city in 2006, suggesting that this area may require special attention with regard to control and prevention measures.

BDNF gene polymorphism, cognition and symptom severity in a Brazilian population-based sample of first-episode psychosis subjects

OBJECTIVE: To investigate the influence of brain-derived neurotrophic factor (BDNF) gene variations on cognitive performance and clinical symptomatology in first-episode psychosis (FEP). METHODS: We performed BDNF val66met variant genotyping, cognitive testing (verbal fluency and digit spans) and assessments of symptom severity (as assessed with the PANSS) in a population-based sample of FEP patients (77 with schizophreniform psychosis and 53 with affective psychoses) and 191 neighboring healthy controls. RESULTS: There was no difference in the proportion of Met allele carriers between FEP patients and controls, and no significant influence of BDNF genotype on cognitive test scores in either of the psychosis groups. A decreased severity of negative symptoms was found in FEP subjects that carried a Met allele, and this finding reached significance for the subgroup with affective psychoses (p < 0.01, ANOVA). CONCLUSIONS: These results suggest that, in FEP, the BDNF gene Val66Met polymorphism does not exert a pervasive influence on cognitive functioning but may modulate the severity of negative symptoms.