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

Prevalence of infection with high-risk human papillomavirus in women in Colombia

AbstractThe prevalence of human papillomavirus (HPV) infections in 2109 females inhabiting five cities of Colombia was determined. Of the 49.2% with an HPV infection, 59.8% were infected with more than one viral type. Species 7 (of the the genus Alphapapillomavirus) was associated with multiple infections. Analysis of the socio-demographic data revealed a statistically significant protective effect associated with the status of civil union (civil recognition of cohabitation without marriage), and indigenous ethnicity proved to be a risk factor for HPV infection. This is the first study comparing HPV infection among women from geographical regions of Colombia with different socio-cultural structures

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

Ajonjolí-Sésamo - Sesamum indicu

Maastrichtian microfossils of the Shallow Marine Umir Formation, Northeastern Colombia

During the Late Cretaceous, northern South America was characterized by broad epicontinental seas, with variable surface productivity and changing bottom-water oxygenation. Global sea-level fluctuations and local tectonic shifts caused their disappearance in the latest Cretaceous. We present an integrated micropaleontological and geochemical study of a section comprising the Umir Formation and its lower stratigraphic contact with the La Luna Formation, in the Middle Magdalena Valley, northeastern Colombia. Foraminiferal assemblages were moderately diverse and mainly dominated by benthic taxa, characterizing the biozones Siphogenerinoides bramlettei and Ammobaculites colombiana (Maastrichtian). Planktonic foraminiferal assemblages were less diversified, being species assigned to Heterohelicidae and scarce keeled forms (Globotruncana spp.) the most recurrent taxa. Ostracod recovery was very scarce, and we could only identify the genus Actinocythereis. In contrast, calcareous nannofossil assemblages were moderately diversified along the section, and composed of typical Late Cretaceous low-latitude taxa such as Micula staurophora, Cribrosphaerella ehrenbergii, Gartnerago segmentatum. The identified microfossils indicate a transition from middle-inner shelf conditions, with moderately oxygenated bottom waters within the La Luna Formation, to a shallower marine setting within the Umir Formation. This interpretation is supported by Sr/Ba and log(Fe/Ca) ratios measured in bulk sediment, which indicate increased continental runoff and terrigenous input in the upper part of the section. Moreover, a significant biotic turnover was identified at the base of the section, suggesting the presence of a xenoconformity at the La Luna-Umir contact, which has been previously described and proposed as a regional stratigraphic feature. El Cretácico Tardío del norte de Sudamérica estuvo dominado por mares epicontinentales extensos, con fluctuaciones de la productividad superficial y oxigenación del agua de fondo. Cambios en los regímenes tectónicos locales y descensos globales en el nivel del mar, llevaron a la desaparición de dichos ambientes hacia fines del Cretácico. Presentamos un estudio micropaleontológico y geoquímico integrado de una sección de la Formación Umir y su contacto basal con la Formación La Luna en el Valle Medio del Magdalena, noreste de Colombia. Las asociaciones de foraminíferos fueron moderadamente diversas y estuvieron dominadas por formas bentónicas que definen las biozonas de asociación locales Siphogenerinoides bramlettei y Ammobaculites colombiana (Maastrichtiano). Las formas planctónicas, menos diversas, incluyeron ejemplares de Heterohelicidae y escasas formas quilladas (Globotruncana spp.). El registro de ostrácodos fue muy escaso, sólo pudimos reconocer al género Actinocythereis. En contraste, las asociaciones de nanofósiles calcáreos fueron moderadamente diversas y comprendieron formas típicas de bajas latitudes del Cretácico Tardío como Micula staurophora, Cribrosphaerella ehrenbergii, Gartnerago segmentatum. Las asociaciones de microfósiles indican una transición de condiciones de plataforma media-interna, moderadamente oxigenada en la Formación La Luna, a un ambiente más somero en la Formación Umir. Esta interpretación es corroborada por las relaciones de Sr/Ba y log(Fe/Ca) del sedimento que indican un aumento en la escorrentía continental y el aporte de terrígenos hacia la parte superior de la sección. De igual forma, la variación significativa en las asociaciones de microfósiles hacia la base sugiere la presencia de una xenoconformidad en el contacto La Luna-Umir, que fue previamente reportada como de carácter regional

Effects of speech rate on anticipatory eye movements in the Visual World Paradigm: Evidence from aging, native, and non-native language processing

Research has shown that suprasegmental cues in conjunction with visual context can lead to anticipatory (or predictive) eye movements. However, the impact of speech rate on anticipatory eye movements has received little empirical attention. The purpose of the current study was twofold. From a methodological perspective, we tested the impact of speech rate on anticipatory eye movements by systemically varying speech rate (3.5, 4.5, 5.5, and 6.0 syllables per second) in the processing of filler-gap dependencies. From a theoretical perspective, we examined two groups thought to show fewer anticipatory eye movements, and thus likely to be more impacted by speech rate. Experiment 1 compared anticipatory eye movements across the lifespan with younger (18-24 years old) and older adults (40-75 years old). Experiment 2 compared L1 speakers of English and L2 speakers of English with an L1 of German. Results showed that all groups made anticipatory eye movements. However, L2 speakers only made anticipatory eye movements at 3.5 syllables per second, older adults at 3.5 and 4.5 syllables per second, and younger adults at speech rates up to 5.5 syllables per second. At the fastest speech rate, all groups showed a marked decrease in anticipatory eye movements. This work highlights (1) the importance of speech rate on anticipatory eye movements, and (2) group-level performance differences in filler-gap prediction

A laminin 511 matrix is regulated by TAZ and functions as the ligand for the alpha6Bbeta1 integrin to sustain breast cancer stem cells

Understanding how the extracellular matrix impacts the function of cancer stem cells (CSCs) is a significant but poorly understood problem. We report that breast CSCs produce a laminin (LM) 511 matrix that promotes self-renewal and tumor initiation by engaging the alpha6Bbeta1 integrin and activating the Hippo transducer TAZ. Although TAZ is important for the function of breast CSCs, the mechanism is unknown. We observed that TAZ regulates the transcription of the alpha5 subunit of LM511 and the formation of a LM511 matrix. These data establish a positive feedback loop involving TAZ and LM511 that contributes to stemness in breast cancer

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