Molecular modeling and in silico characterization of Mycobacterium tuberculosis TlyA: Possible misannotation of this tubercle bacilli-hemolysin

<p>Abstract</p> <p>Background</p> <p>The TlyA protein has a controversial function as a virulence factor in <it>Mycobacterium tuberculosis </it>(<it>M. tuberculosis</it>). At present, its dual activity as hemolysin and RNA methyltransferase in <it>M. tuberculosis </it>has been indirectly proposed based on <it>in vitro </it>results. There is no evidence however for TlyA relevance in the survival of tubercle bacilli inside host cells or whether both activities are functionally linked. A thorough analysis of structure prediction for this mycobacterial protein in this study shows the need for reevaluating TlyA's function in virulence.</p> <p>Results</p> <p>Bioinformatics analysis of TlyA identified a ribosomal protein binding domain (S4 domain), located between residues 5 and 68 as well as an FtsJ-like methyltranferase domain encompassing residues 62 and 247, all of which have been previously described in translation machinery-associated proteins. Subcellular localization prediction showed that TlyA lacks a signal peptide and its hydrophobicity profile showed no evidence of transmembrane helices. These findings suggested that it may not be attached to the membrane, which is consistent with a cytoplasmic localization. Three-dimensional modeling of TlyA showed a consensus structure, having a common core formed by a six-stranded β-sheet between two α-helix layers, which is consistent with an RNA methyltransferase structure. Phylogenetic analyses showed high conservation of the <it>tlyA </it>gene among <it>Mycobacterium </it>species. Additionally, the nucleotide substitution rates suggested purifying selection during <it>tlyA </it>gene evolution and the absence of a common ancestor between TlyA proteins and bacterial pore-forming proteins.</p> <p>Conclusion</p> <p>Altogether, our manual <it>in silico </it>curation suggested that TlyA is involved in ribosomal biogenesis and that there is a functional annotation error regarding this protein family in several microbial and plant genomes, including the <it>M. tuberculosis </it>genome.</p

Molecular modeling and in silico characterization of Mycobacterium tuberculosis TlyA : Possible misannotation of this tubercle bacilli-hemolysin

Background: The TlyA protein has a controversial function as a virulence factor in Mycobacterium tuberculosis (M. tuberculosis). At present, its dual activity as hemolysin and RNA methyltransferase in M. tuberculosis has been indirectly proposed based on in vitro results. There is no evidence however for TlyA relevance in the survival of tubercle bacilli inside host cells or whether both activities are functionally linked. A thorough analysis of structure prediction for this mycobacterial protein in this study shows the need for reevaluating TlyA's function in virulence. Results: Bioinformatics analysis of TlyA identified a ribosomal protein binding domain (S4 domain), located between residues 5 and 68 as well as an FtsJ-like methyltranferase domain encompassing residues 62 and 247, all of which have been previously described in translation machinery-associated proteins. Subcellular localization prediction showed that TlyA lacks a signal peptide and its hydrophobicity profile showed no evidence of transmembrane helices. These findings suggested that it may not be attached to the membrane, which is consistent with a cytoplasmic localization. Three-dimensional modeling of TlyA showed a consensus structure, having a common core formed by a six-stranded β-sheet between two α-helix layers, which is consistent with an RNA methyltransferase structure. Phylogenetic analyses showed high conservation of the tlyA gene among Mycobacterium species. Additionally, the nucleotide substitution rates suggested purifying selection during tlyA gene evolution and the absence of a common ancestor between TlyA proteins and bacterial pore-forming proteins. Conclusion: Altogether, our manual in silico curation suggested that TlyA is involved in ribosomal biogenesis and that there is a functional annotation error regarding this protein family in several microbial and plant genomes, including the M. tuberculosis genome. © 2011 Arenas et al; licensee BioMed Central Ltd

Micronutrient Adequacy in Preschool Children Attending Family Child Care Homes

Limited data is available on the micronutrient intake and adequacy in preschool children enrolled in family child care homes (FCCH). The goal of this paper is to describe the micronutrient adequacy relative to age-specific recommendations of preschool-aged children (aged 2–5 years) attending FCCH in Rhode Island (RI). Dietary data among younger preschoolers (aged 2–3 years), n = 245) and older preschoolers (aged 4–5 years), n = 121) in 118 RI FCCH (N = 366 children) were analyzed. Nutrient adequacy was assessed as the amount of nutrient per 1000 kcal of the diet that would meet the Institute of Medicine nutrient requirements (critical nutrient density), and it was compared to the observed nutrient densities of the children. The sodium:potassium ratio was also calculated. For most micronutrients, the observed density met or exceeded the recommendation, meaning the children’s intake was adequate. However, a high proportion of children had nutrient densities under the recommendation for vitamins D, E, K, and potassium (86.1%, 89.1%, 70.8%, and 99.2% of children, respectively). The mean vitamin B12, potassium, and zinc densities were statistically higher in younger vs. older preschoolers (p \u3c 0.05 for all). Low densities in calcium and vitamins K and B5 were more frequent in older children vs. younger children (p \u3c 0.05). In addition, older preschoolers had a higher sodium:potassium ratio than younger children (p \u3c 0.05). The micronutrient intake density was adequate for most nutrients. However, intake of some nutrients was of concern. Further attention to training and compliance in FCCH may improve the diet quality of those cared for in these settings

Prognostic significance of human pituitary tumor-transforming gene immunohistochemical expression in differentiated thyroid cancer

Context: Human securin pituitary tumor-transforming gene (hPTTG) is overexpressed in a variety of primary neoplasias, including differentiated thyroid cancer (DTC). Objective: The objective of this study was to examine the immunohistochemical expression of hPTTG in DTC and its association with known prognostic factors. Design: hPTTG expression was analyzed by immunostaining on paraffin-embedded tissues. Clinical data were used to determine any associations between the expression of hPTTG and prognostic variables of DTC. A median follow-up of 43 months allowed us to analyze the persistence of disease and the response to radioiodine therapy. Setting: The study was conducted at a tertiary university hospital. Patients: Ninety-five patients undergoing surgical resection for DTC (n = 60) or benign nodular thyroid disease (n = 35) were studied. Main Outcome Measure: The main outcome measure was the association between hPTTG expression and prognostic factors in DTC. Results: Among DTC cases, 21 (35%) had low and 39 (65%) had high hPTTG immunostaining. Adjacent nonneoplastic thyroid tissue was largely unstained. Among benign nodular thyroid disease cases, immunostaining was detected focally in eight (22.8%). A significant association was found between hPTTG expression and the presence of nodal (P < 0.01) or distant metastases (P < 0.05). A significant association with TNM was also found, because 83.3% of advanced TNM stages showed elevated hPTTG (P < 0.05). The association between hPTTG overexpression and decreased radioiodine uptake during follow-up was also significant (P < 0.05). The expression levels of hPTTG were confirmed as an independent prognostic factor for persistent disease (relative risk, 3.0; 95% confidence interval, 1.1-8.7; P < 0.05). Conclusions: Immunohistochemical analysis of hPTTG is of potential value in the determination of tumor aggressiveness in DTC.Peer Reviewe

An outflow in the Seyfert ESO 362-G18 revealed by Gemini-GMOS/IFU Observations

We present two-dimensional stellar and gaseous kinematics of the inner 0.7 $\times$ 1.2 kpc$^{2}$ of the Seyfert galaxy ESO 362-G18, derived from optical spectra obtained with the GMOS/IFU on the Gemini South telescope at a spatial resolution of $\approx$170 pc and spectral resolution of 36 km s$^{-1}$. ESO 362-G18 is a strongly perturbed galaxy of morphological type Sa or S0/a, with a minor merger approaching along the NE direction. Previous studies have shown that the [OIII] emission shows a fan-shaped extension of $\approx$ 10\arcsec\ to the SE. We detect the [OIII] doublet, [NII] and H${\alpha}$ emission lines throughout our field of view. The stellar kinematics is dominated by circular motions in the galaxy plane, with a kinematic position angle of $\approx$137$^{\circ}$. The gas kinematics is also dominated by rotation, with kinematic position angles ranging from 122$^{\circ}$ to 139$^{\circ}$. A double-Gaussian fit to the [OIII]$\lambda$5007 and H${\alpha}$ lines, which have the highest signal to noise ratios of the emission lines, reveal two kinematic components: (1) a component at lower radial velocities which we interpret as gas rotating in the galactic disk; and (2) a component with line of sight velocities 100-250 km s$^{-1}$ higher than the systemic velocity, interpreted as originating in the outflowing gas within the AGN ionization cone. We estimate a mass outflow rate of 7.4 $\times$ 10$^{-2}$ M$_{\odot}$ yr$^{-1}$ in the SE ionization cone (this rate doubles if we assume a biconical configuration), and a mass accretion rate on the supermassive black hole (SMBH) of 2.2 $\times$ 10$^{-2}$ M$_{\odot}$ yr$^{-1}$. The total ionized gas mass within $\sim$84 pc of the nucleus is 3.3 $\times$ 10$^{5}$ M$_{\odot}$; infall velocities of $\sim$34 km s$^{-1}$ in this gas would be required to feed both the outflow and SMBH accretion.Comment: 18 pages, 14 figure

Galaxy clustering in the VVV Near-IR Galaxy Catalogue

Mapping galaxies at low Galactic latitudes and determining their clustering status are fundamental steps in defining the large-scale structure in the nearby Universe. The VVV Near-IR Galaxy Catalogue (VVV NIRGC) allows us to explore this region in great detail. Our goal is to identify galaxy overdensities and characterize galaxy clustering in the Zone of Avoidance. We use different clustering algorithms to identify galaxy overdensities: the Voronoi tessellations, the Minimum Spanning Tree and the Ordering Points To Identify the Clustering Structure. We studied the membership, isolation, compactness, and flux limits to identify compact groups of galaxies. Each method identified a variety of galaxy systems across the Galactic Plane that are publicly available.We also explore the probability that these systems are formed by concordant galaxies using mock catalogues. Nineteen galaxy systems were identified in all of the four methods. They have the highest probability to be real overdensities. We stress the need for spectroscopic follow-up observations to confirm and characterize these new structures.Comment: 16 pages, 10 figures, 9 tables. Accepted for publication in Monthly Notices of the Royal Astronomical Society (MNRAS

The VVV Near-IR Galaxy Catalogue beyond the Galactic disk

Knowledge about the large-scale distribution of galaxies is far from complete in the Zone of Avoidance, which is mostly due to high interstellar extinction and to source confusion at lower Galactic latitudes. Past near-infrared (NIR) surveys, such as the Two Micron All Sky Survey (2MASS), have shown the power of probing large-scale structure at these latitudes. Our aim is to map the galaxy distribution across the Southern Galactic plane using the VISTA Variables in the V\'ia L\'actea Survey (VVV), which reach 2 to 4 magnitudes deeper than 2MASS. We used SExtractor + PSFEx to identify extended objects and to measure their sizes, the light concentration index, magnitudes, and colours. Morphological and colour constraints and visual inspection were used to confirm galaxies. We present the resulting VVV NIR Galaxy Catalogue of 5563 visually confirmed galaxies, of which only 45 were previously known. This is the largest catalogue of galaxies towards the Galactic plane, with 99% of these galaxies being new discoveries. We found that the galaxy density distribution closely resembled the distribution of low interstellar extinction of the existing NIR maps. We also present a description of the 185 2MASS extended sources observed in the region, of which 16% of these objects had no previous description, which we have now classified. We conclude that interstellar extinction and stellar density are the main limitations for the detection of background galaxies in the Zone of Avoidance. The VVV NIR Galaxy Catalogue is a new data set providing information for extragalactic studies in the Galactic plane.Comment: Accepted for publication in Monthly Notices of the Royal Astronomical Society Main Journal 21 page

Randomized, direct comparison study of Saccharomyces boulardii CNCM I-745 versus multi-strained Bacillus clausii probiotics for the treatment of pediatric acute gastroenteritis

Background: The choice of an appropriate probiotic for pediatric acute gastroenteritis (PAGE) can be confusing. Our aim was to compare the efficacy and safety of 2 probiotics (Saccharomyces boulardii CNCM I-745 vs a 4-strain mixture of Bacillus clausii O/C, SIN, N/R, T) for the treatment of PAGE. Methods: A 2-arm parallel, randomized trial recruited children (6 months to 5 years old) with mild-moderate acute diarrhea, from 8 centers in Argentina. A total of 317 children were enrolled and blindly randomized to 5 days of either S boulardii CNCM I-745 (n = 159) or a 4-strain mixture of B clausii (n = 158), then followed for 7 days post-probiotic treatment. A stool sample was collected at inclusion for pathogen identification. The primary outcome was duration of diarrhea defined as the time from enrollment to the last loose stool followed by the first 24-hour period with stool consistency improvement. Secondary outcomes included frequency of loose stools/day, severity of diarrhea, number reporting no diarrhea at Day 6, time-to-first formed stool, recurrence of diarrhea by study end (Day 12) and safety outcomes. Results: Three hundred twelve (98%) children completed the study. S boulardii CNCM I-745 showed a significant reduction (P =.04) in the mean duration of diarrhea (64.6 hours, 95% confidence interval [CI] 56.5-72.8) compared to those given B clausii (78.0 hours, 95% CI 69.9-86.1). Both probiotics showed improvement in secondary outcomes and were well-tolerated. Conclusion: In this study, S boulardii CNCM I-745 demonstrated better efficacy than B clausii mix for reducing the duration of pediatric acute diarrhea.Fil: Altcheh, Jaime Marcelo. Gobierno de la Ciudad de Buenos Aires. Instituto Multidisciplinario de Investigaciones en Patologías Pediátricas. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto Multidisciplinario de Investigaciones en Patologías Pediátricas; ArgentinaFil: Carosella, Mabel V.. No especifíca;Fil: Ceballos, Ana. Instituto Médico Río Cuarto; ArgentinaFil: D'Andrea, Ulises. Instituto Médico Río Cuarto; ArgentinaFil: Jofre, Sandra M.. No especifíca;Fil: Marotta, Carolina. No especifíca;Fil: Mugeri, Domingo. No especifíca;Fil: Sabbaj, Liliana. No especifíca;Fil: Soto, Adriana. No especifíca;Fil: Josse, Constant. No especifíca;Fil: Montestruc, Francois. No especifíca;Fil: McFarland, Lynne V.. No especifíca

Iodinated contrast agents for improving tumor imaging and quantification in rodents

2008 World Molecular Imaging Congress (WMIC 2008), 10-13 september 2008. Nice, Franc

Codificación de telefonía visual: empleando un conjunto de imágenes

En este artículo se presenta un método de codificación de secuencias de imágenes de escenas de telefonía visual que emplea como libro de códigos un conjunto de imágenes naturales. En el diseño del libro de códigos se utilizan métodos de cuantificación vectorial basados en el algoritmo de Lloyd-Max con el criterio de optimización min-max. Se presenta también un método de interpolación de imágenes intermedias empleando búsqueda de Viterbi para obtener secuencias óptimas