Well-defined regions of the Plasmodium falciparum reticulocyte binding protein homologue 4 mediate interaction with red blood cell membrane

Two widely studied parasite protein families are considered attractive targets for developing a fully effective antimalarial vaccine: the erythrocyte binding antigen (EBA) family defining a sialic acid-dependent invasion pathway, and reticulocyte-binding homologue (RH) proteins associated with sialic acid-independent red blood cell (RBC) invasion. In this study, the micronemal invasive PfRH4 protein was finely mapped using 20-mer-long synthetic peptides spanning the entire protein length to identify protein regions that establish high affinity interactions with human RBCs. Twenty conserved, mainly ?-helical high-activity binding peptides (HABPs) with nanomolar dissociation constants and recognizing 32, 25, 22, and 20 kDaRBCmembrane molecules in a chymotrypsin and/or trypsin-sensitive manner were identified in this protein. Anti-PfRH4 rabbit sera and PfRH4 HABPs inhibited merozoite invasion in vitro, therefore suggesting the implication of these HABPs in Plasmodium falciparum invasion and supporting their inclusion in further structural and immunological studies to design potential components of a minimal subunit-based, multiantigenic, chemically synthesized antimalarial vaccine. ©2009 American Chemical Society

Functional, immunological and three-dimensional analysis of chemically synthesisedsporozoite peptides as components of a fully-effective antimalarial vaccine

Our ongoing search for a fully-effective vaccine against the Plasmodium falciparum parasite (causing the most lethal form ofhuman malaria) has been focused on identifying and characterising proteins' amino acid sequences (high activity binding peptides orHABPs) involved in parasite invasion of red blood cells (RBC) by the merozoite and hepatocytes by the sporozoite. Many such merozoiteHABPs have been recognised and molecularly and structurally characterised; however, native HABPs are immunologically silentsince they do not induce any immune response or protection against P. falciparum malaria infection and they have to be structurallymodified to allow them to fit perfectly into immune system molecules.A deeply structural analysis of these conserved merozoite HABPs and their modified analogues has led to rules or principles becomingrecognised for constructing a logical and rational methodology for a minimal subunit-based, multi-epitope, multi-stage, chemicallysynthesisedvaccine. The same in-depth analysis of the most relevant sporozoite proteins involved in sporozoite cell-traversal and hepatocyteinvasion as well as the hepatic stage is shown here.Specifically modifying these HABPs has resulted in a new set of potential pre-erythrocyte targets which are able to induce high, longlastingantibody titres in Aotus monkeys, against their corresponding recombinant proteins and the complete parasite native molecules.This review shows how these rules may be applied against the first stage of parasite invasion (i.e. the sporozoite) to mount the first line ofdefence against the malarial parasite, which may indeed be the most effective one. Our results strongly support including some of thesemodified sporozoite HABPs in combination with the previously-described modified merozoite HABPs for obtaining the aforementionedfully-protective, multiepitope, multi-stage, minimal subunit-based, chemically-synthesized, antimalarial vaccine. © 2011 Bentham Science Publishers

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

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

Multiple high-risk HPV genotypes are grouped by type and are associated with viral load and risk factors

Investigating whether high-risk human papillomavirus (HR-HPV) types tend to become grouped in a particular way and whether factors are associated with such grouping is important for measuring the real impact of vaccination. In total, 219 women proving positive for HPV as detected by real-time PCR were included in the study. Each sample was analysed for detecting and quantifying six viral types and the hydroxymethylbilane synthase gene. Multiple correspondence analysis led to determining grouping patterns for six HR-HPV types and simultaneous association with multiple variables and whether viral load was related to the coexistence of other viral types. Two grouping profiles were identified: the first included HPV-16 and HPV-45 and the second profile was represented by HPV-31, HPV-33 and HPV-58. Variables such as origin, contraceptive method, births and pregnancies, educational level, healthcare affiliation regime, atypical squamous cells of undetermined significance and viral load were associated with these grouping profiles. Different socio-demographic characteristics were found when coinfection occurred by phylogenetically related HPV types and when coinfection was due to non-related types. Biological characteristics, the number of viral copies, temporality regarding acquiring infection and competition between viral types could influence the configuration of grouping patterns. Characteristics related to women and HPV, influence such interactions between coexisting HPV types reflecting the importance of their evaluation. Copyright © Cambridge University Press 2017

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

Ajonjolí-Sésamo - Sesamum indicu

Characterising PvRBSA: an exclusive protein from Plasmodium species infecting reticulocytes

Background: Plasmodium vivax uses multiple ligand-receptor interactions for preferential invasion of human reticulocytes. Several of these ligands have been identified by in silico approaches based on the role displayed by their orthologs in other Plasmodium species during initial adhesion or invasion. However, the cell adhesion role of proteins that are exclusive to species that specifically invade reticulocytes (as P. vivax and P. cynomolgi) has not been evaluated to date. This study aimed to characterise an antigen shared between Plasmodium species that preferentially infect reticulocytes with a focus on assessing its binding activity to target cells. Results: An in silico analysis was performed using P. vivax proteome data to identify and characterise one antigen shared between P. vivax and P. cynomolgi. This led to identification of the pvrbsa gene present in the P. vivax VCG-I strain genome. This gene is transcribed in mature schizonts and encodes a protein located on the parasite surface. rPvRBSA was antigenic and capable of binding to a population of reticulocytes with a different Duffy phenotype. Interestingly, the molecule showed a higher percentage of binding to immature human reticulocytes (CD71hi). Conclusions: This study describes for the first time, a molecule involved in host cell binding that is exclusive in reticulocyte-infecting Plasmodium species. This suggest that PvRBSA is an antigenic adhesin that plays a role in parasite binding to target cells. © 2017 The Author(s)

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