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

Análisis de crecimiento del ajonjolí (Sesamun indicum L.) bajo diferentes condiciones de suministro de agua.

Ajonjolí-Sésamo - Sesamum indicu

The Imaging Magnetograph eXperiment (IMaX) for the Sunrise balloon-borne solar observatory

The Imaging Magnetograph eXperiment (IMaX) is a spectropolarimeter built by four institutions in Spain that flew on board the Sunrise balloon-borne telesocope in June 2009 for almost six days over the Arctic Circle. As a polarimeter IMaX uses fast polarization modulation (based on the use of two liquid crystal retarders), real-time image accumulation, and dual beam polarimetry to reach polarization sensitivities of 0.1%. As a spectrograph, the instrument uses a LiNbO3 etalon in double pass and a narrow band pre-filter to achieve a spectral resolution of 85 mAA. IMaX uses the high Zeeman sensitive line of Fe I at 5250.2 AA and observes all four Stokes parameters at various points inside the spectral line. This allows vector magnetograms, Dopplergrams, and intensity frames to be produced that, after reconstruction, reach spatial resolutions in the 0.15-0.18 arcsec range over a 50x50 arcsec FOV. Time cadences vary between ten and 33 seconds, although the shortest one only includes longitudinal polarimetry. The spectral line is sampled in various ways depending on the applied observing mode, from just two points inside the line to 11 of them. All observing modes include one extra wavelength point in the nearby continuum. Gauss equivalent sensitivities are four Gauss for longitudinal fields and 80 Gauss for transverse fields per wavelength sample. The LOS velocities are estimated with statistical errors of the order of 5-40 m/s. The design, calibration and integration phases of the instrument, together with the implemented data reduction scheme are described in some detail.Comment: 17 figure

A comparative analysis of SLA-DRB1 genetic diversity in Colombian (creoles and commercial line) and worldwide swine populations

Analysing pig class II mayor histocompatibility complex (MHC) molecules is mainly related to antigen presentation. Identifying frequently-occurring alleles in pig populations is an important aspect to be considered when developing peptide-based vaccines. Colombian creole pig populations have had to adapt to local conditions since entering Colombia; a recent census has shown low amounts of pigs which is why they are considered protected by the Colombian government. Commercial hybrids are more attractive regarding production. This research has been aimed at describing the allele distribution of Colombian pigs from diverse genetic backgrounds and comparing Colombian SLA-DRB1 locus diversity to that of internationally reported populations. Twenty SLA-DRB1 alleles were identified in the six populations analysed here using sequence-based typing. The amount of alleles ranged from six (Manta and Casco Mula) to nine (San Pedreño). Only one allele (01:02) having > 5% frequency was shared by all three commercial line populations. Allele 02:01:01 was shared by five populations (around > 5% frequency). Global FST indicated that pig populations were clearly structured, as 20.6% of total allele frequency variation was explained by differences between populations (FST = 0.206). This study’s results confirmed that the greatest diversity occurred in wild boars, thereby contrasting with low diversity in domestic pig populations.This work was supported by the Universidad de Ciencias Aplicadas y Ambientales (U.D.C.A)

The Effect of Epstein-Barr Virus Latent Membrane Protein 2 Expression on the Kinetics of Early B Cell Infection

Infection of human B cells with wild-type Epstein-Barr virus (EBV) in vitro leads to activation and proliferation that result in efficient production of lymphoblastoid cell lines (LCLs). Latent Membrane Protein 2 (LMP2) is expressed early after infection and previous research has suggested a possible role in this process. Therefore, we generated recombinant EBV with knockouts of either or both protein isoforms, LMP2A and LMP2B (Δ2A, Δ2B, Δ2A/Δ2B) to study the effect of LMP2 in early B cell infection. Infection of B cells with Δ2A and Δ2A/Δ2B viruses led to a marked decrease in activation and proliferation relative to wild-type (wt) viruses, and resulted in higher percentages of apoptotic B cells. Δ2B virus infection showed activation levels comparable to wt, but fewer numbers of proliferating B cells. Early B cell infection with wt, Δ2A and Δ2B viruses did not result in changes in latent gene expression, with the exception of elevated LMP2B transcript in Δ2A virus infection. Infection with Δ2A and Δ2B viruses did not affect viral latency, determined by changes in LMP1/Zebra expression following BCR stimulation. However, BCR stimulation of Δ2A/Δ2B cells resulted in decreased LMP1 expression, which suggests loss of stability in viral latency. Long-term outgrowth assays revealed that LMP2A, but not LMP2B, is critical for efficient long-term growth of B cells in vitro. The lowest levels of activation, proliferation, and LCL formation were observed when both isoforms were deleted. These results suggest that LMP2A appears to be critical for efficient activation, proliferation and survival of EBV-infected B cells at early times after infection, which impacts the efficient long-term growth of B cells in culture. In contrast, LMP2B did not appear to play a significant role in these processes, and long-term growth of infected B cells was not affected by the absence of this protein. © 2013 Wasil et al

Alternativas práticas ao modelo de saúde ocidental, utilizadas pelos cuidadores de pacientes com neoplasia hematológicas

Introducción: Las neoplasias hematológicas tienen la carga cultural de la palabra cáncer lo cual lleva a los cuidadores a buscar diversas alternativas. Objetivo: Describir las prácticas consideradas alternativas al modelo de salud occidental utilizadas para el cuidado de la salud, desde la experiencia de los cuidadores de pacientes adultos con neoplasias hematológicas en un Servicio de Hematología. Metodología: Estudio cualitativo descriptivo. Participaron 17 cuidadores de pacientes adultos con neoplasias hematológicas, seleccionados por conveniencia del registro del servicio de Hematología. Como técnica de recolección se realizaron dos grupos de discusión. Las sesiones fueron grabadas y transcritas en su totalidad. El análisis se hizo de acuerdo con la propuesta de Janice M. Morse y se efectuó triangulación por parte de investigadores. Resultados: Emergieron tres tipos de prácticas. 1. Prácticas espirituales: la voluntad de Dios como influyente en la recuperación.; 2. Las prácticas afectivas: los lazos familiares hacen más llevadera la enfermedad y el tratamiento, y 3. Prácticas Corporales: productos de origen, vegetal, animal, semisintético y farmacológicos no convencionales. Conclusión: Los cuidadores de la población con Cáncer utilizan prácticas alternativas al tratamiento convencional, por tanto, el equipo de salud no puede ignorarlas y necesita fortalecer la orientación al paciente y sus cuidadores.Introduction: Hematological neoplasms have the cultural burden of the word cancer which leads caregivers to look for different alternatives. Objective: To analyse the anthropological link between care and tenderness to potentiate care as an essential “way to be” of the human being, who ontological way was born of care and needs care. Methodology: Descriptive qualitative study. The participants were 17 caregivers, who were selected by convenience. Two discussion groups’ sessions were performed. The sessions were recorded and transcribed in full. The analysis followed the Janice M. Morse framework. Results: The findings that emerged permitted an approach toward understanding the practices used to care for patients affected by malignant hematological disease. The practices were organized in three types: 1. Spiritual practices: God´s Will as determinant in the recovery process; 2. Emotional Practices: the familiar ties make more bearable the illness and the treatment, and, 3. Corporal practices: origin products, vegetal, animal, semi-synthetic and no conventional pharmacological products. Conclusion: The utilization of alternative practices is very common by caregivers. Healthcare practitioners cannot ignore this reality and need tools to adequately guide and inform patients and caregivers.Introdução: As neoplasias hematológicas têm carga cultural da palavra câncer, levando aos cuidadores das pessoas que o sofrem a procurar diversas alternativas. Objetivo: Descrever as práticas consideradas alternativas ao modelo de saúde Ocidental usado para cuidados de saúde, a partir da experiência de cuidadores de pacientes adultos com doenças hematológicas malignas no servicio de Hematologia Hospital San José de Bogotá. Metodologia: Estudo qualitativo descritiva. Participaram 17 cuidadores de pacientes adultos com neoplasias hematológicas, seleccionados por conveniência dos registos do servicio Hematologia. Como uma técnica de coleta de informações dois grupos de discussão foram realizadas. As sessões foram gravadas e transcritas em sua totalidade. A análise foi feita de acordo com a proposta Janice M Morse e se efectou uma triangulação foi realizado por pesquisadores. Resultados: Surgiram três tipos de práticas utilizadas para cuidar de pessoas afectadas pela doença hematológica maligna; 1. As práticas espirituais: a vontade de Deus tão influente na recuperação;. 2. práticas Affective: laços familiares tornar mais suportável a doença e o tratamento, e 3. práticas corporais: produtos de origem vegetal, animal, semi-sintético e farmacológico não convencional. Conclusão: Os cuidadores de pessoas com câncer muitas vezes usam alternativa às práticas convencionais de tratamento, assim, a equipe de saúde não pode ignorar esta realidade e precisa de reforçar a orientação aos pacientes e seus cuidadores

Alternativas práticas ao modelo de saúde ocidental, utilizadas pelos cuidadores de pacientes com neoplasia hematológicas

Introducción: Las neoplasias hematológicas tienen la carga cultural de la palabra cáncer lo cual lleva a los cuidadores a buscar diversas alternativas. Objetivo: Describir las prácticas consideradas alternativas al modelo de salud occidental utilizadas para el cuidado de la salud, desde la experiencia de los cuidadores de pacientes adultos con neoplasias hematológicas en un Servicio de Hematología. Metodología: Estudio cualitativo descriptivo. Participaron 17 cuidadores de pacientes adultos con neoplasias hematológicas, seleccionados por conveniencia del registro del servicio de Hematología. Como técnica de recolección se realizaron dos grupos de discusión. Las sesiones fueron grabadas y transcritas en su totalidad. El análisis se hizo de acuerdo con la propuesta de Janice M. Morse y se efectuó triangulación por parte de investigadores. Resultados: Emergieron tres tipos de prácticas. 1. Prácticas espirituales: la voluntad de Dios como influyente en la recuperación.; 2. Las prácticas afectivas: los lazos familiares hacen más llevadera la enfermedad y el tratamiento, y 3. Prácticas Corporales: productos de origen, vegetal, animal, semisintético y farmacológicos no convencionales. Conclusión: Los cuidadores de la población con Cáncer utilizan prácticas alternativas al tratamiento convencional, por tanto, el equipo de salud no puede ignorarlas y necesita fortalecerla orientación al paciente y sus cuidadores.Introduction: Hematological neoplasms have the cultural burden of the word cancer which leads caregivers to look for different alternatives. Objective: To analyse the anthropological link between care and tenderness to potentiate care as an essential “way to be” of the human being, who ontological way was born of care and needs care. Methodology: Descriptive qualitative study. The participants were 17 caregivers, who were selected by convenience. Two discussion groups’ sessions were performed. The sessions were recorded and transcribed in full. The analysis followed the Janice M. Morse framework. Results: The findings that emerged permitted an approach toward understanding the practices used to care for patients affected by malignant hematological disease. The practices were organized in three types: 1. Spiritual practices: God´s Will as determinant in the recovery process; 2. Emotional Practices: the familiar ties make more bearable the illness and the treatment, and, 3. Corporal practices: origin products, vegetal, animal, semi-synthetic and no conventional pharmacological products. Conclusion: The utilization of alternative practices is very common by caregivers. Healthcare practitioners cannot ignore this reality and need tools to adequately guide and inform patients and caregivers. Keywords: Complementary therapies, culture, hematology, neoplasms, qualitative research, caregivers

Identification of Plasmodium vivax Proteins with Potential Role in Invasion Using Sequence Redundancy Reduction and Profile Hidden Markov Models

BACKGROUND: This study describes a bioinformatics approach designed to identify Plasmodium vivax proteins potentially involved in reticulocyte invasion. Specifically, different protein training sets were built and tuned based on different biological parameters, such as experimental evidence of secretion and/or involvement in invasion-related processes. A profile-based sequence method supported by hidden Markov models (HMMs) was then used to build classifiers to search for biologically-related proteins. The transcriptional profile of the P. vivax intra-erythrocyte developmental cycle was then screened using these classifiers. RESULTS: A bioinformatics methodology for identifying potentially secreted P. vivax proteins was designed using sequence redundancy reduction and probabilistic profiles. This methodology led to identifying a set of 45 proteins that are potentially secreted during the P. vivax intra-erythrocyte development cycle and could be involved in cell invasion. Thirteen of the 45 proteins have already been described as vaccine candidates; there is experimental evidence of protein expression for 7 of the 32 remaining ones, while no previous studies of expression, function or immunology have been carried out for the additional 25. CONCLUSIONS: The results support the idea that probabilistic techniques like profile HMMs improve similarity searches. Also, different adjustments such as sequence redundancy reduction using Pisces or Cd-Hit allowed data clustering based on rational reproducible measurements. This kind of approach for selecting proteins with specific functions is highly important for supporting large-scale analyses that could aid in the identification of genes encoding potential new target antigens for vaccine development and drug design. The present study has led to targeting 32 proteins for further testing regarding their ability to induce protective immune responses against P. vivax malaria

Plasmodium vivax lineages: geographical distribution, tandem repeat polymorphism, and phylogenetic relationship

<p>Abstract</p> <p>Background</p> <p>Multi-drug resistance and severe/complicated cases are the emerging phenotypes of vivax malaria, which may deteriorate current anti-malarial control measures. The emergence of these phenotypes could be associated with either of the two <it>Plasmodium vivax </it>lineages. The two lineages had been categorized as Old World and New World, based on geographical sub-division and genetic and phenotypical markers. This study revisited the lineage hypothesis of <it>P. vivax </it>by typing the distribution of lineages among global isolates and evaluated their genetic relatedness using a panel of new mini-satellite markers.</p> <p>Methods</p> <p><it>18S SSU rRNA S-type </it>gene was amplified from 420 <it>Plasmodium vivax </it>field isolates collected from different geographical regions of India, Thailand and Colombia as well as four strains each of <it>P. vivax </it>originating from Nicaragua, Panama, Thailand (Pak Chang), and Vietnam (ONG). A mini-satellite marker panel was then developed to understand the population genetic parameters and tested on a sample subset of both lineages.</p> <p>Results</p> <p><it>18S SSU rRNA S-type </it>gene typing revealed the distribution of both lineages (Old World and New World) in all geographical regions. However, distribution of <it>Plasmodium vivax </it>lineages was highly variable in every geographical region. The lack of geographical sub-division between lineages suggests that both lineages are globally distributed. Ten mini-satellites were scanned from the <it>P. vivax </it>genome sequence; these tandem repeats were located in eight of the chromosomes. Mini-satellites revealed substantial allelic diversity (7-21, <it>AE </it>= 14.6 ± 2.0) and heterozygosity (<it>He </it>= 0.697-0.924, <it>AE </it>= 0.857 ± 0.033) per locus. Mini-satellite comparison between the two lineages revealed high but similar pattern of genetic diversity, allele frequency, and high degree of allele sharing. A Neighbour-Joining phylogenetic tree derived from genetic distance data obtained from ten mini-satellites also placed both lineages together in every cluster.</p> <p>Conclusions</p> <p>The global lineage distribution, lack of genetic distance, similar pattern of genetic diversity, and allele sharing strongly suggested that both lineages are a single species and thus new emerging phenotypes associated with vivax malaria could not be clearly classified as belonging to a particular lineage on basis of their geographical origin.</p