Effect of mesoporous silica under Neisseria meningitidis transformation process: environmental effects under meningococci transformation

<p>Abstract</p> <p>Background</p> <p>This study aimed the use of mesoporous silica under the naturally transformable <it>Neisseria meningitidis</it>, an important pathogen implicated in the genetic horizontal transfer of DNA causing a escape of the principal vaccination measures worldwide by the capsular switching process. This study verified the effects of mesoporous silica under <it>N. meningitidis </it>transformation specifically under the capsular replacement.</p> <p>Methods</p> <p>we used three different mesoporous silica particles to verify their action in <it>N. meningitis </it>transformation frequency.</p> <p>Results</p> <p>we verified the increase in the capsular gene replacement of this bacterium with the three mesoporous silica nanoparticles.</p> <p>Conclusion</p> <p>the mesouporous silica particles were capable of increasing the capsule replacement frequency in <it>N. meningitidis</it>.</p

Renal oncocytoma: Is URO-CT useful in histological diagnosis?

Introdução: Ao longo dos últimos anos, a crescente utilização de exames imagiológicos, nomeadamente ecografia e tomografia computorizada (TC), traduziu-se num aumento do diagnóstico incidental de tumores renais, sobretudo pequenas massas renais (<4 cm). O conhecimento de que até 30% destas massas podem ser benignas, entre elas os oncocitomas, levou á procura de métodos de diagnóstico mais eficazes, de forma a evitar situações de sobretratamento e de forma a tornaram-se decisões terapêuticas mais fundamentadas. Objectivos: Analisar retrospectivamente uma série de tumores renais histologicamente comprovados, nomeadamente oncocitomas e carcinomas de células renais (CCR), e verificar se existem diferenças morfológicas e/ou nos padrões de captação de contraste através da URO-TC. Material e métodos: Identificámos todos os tumores renais entre 2004-2015 com o diagnóstico histológico de oncocitoma e de CCR. Estes resultados foram obtidos por biopsia do tumor renal, tumorectomia/nefrectomia parcial ou nefrectomia radical. Registámos e comparámos as características morfológicas e os padrões de captação de contraste na fase nefrográfica com medição de unidades de Hounsfield (HU) dos oncocitomas e dos CCR (células claras), selecionados de acordo com a dimensão (aprox. idêntica á dos oncocitomas) e obtidos na sequência de tumorectomia renal ou nefrectomia radical. Resultados: Identificaram-se 16 CCR e 31 oncocitomas, dos quais 15 foram excluídos por não termos acesso ás imagens de TC no sistema informático. A dimensão média dos oncocitomas foi 3,7 cm (1,8 – 14) e a dos CCR 3,5 cm (1,9 – 8,4). A atenuação de contraste média dos oncocitomas e dos CCR na fase sem contraste foi de 33 HU e 32 HU, respectivamente. Na fase nefrográfica, a captação média de contraste para os oncocitomas foi de 47,5 HU e 47,4 HU para os CCR. Na fase nefrográfica, a diferença de atenuação entre os oncocitomas e o parênquima renal normal foi 43,5 HU e a diferença de atenuação entre os CCR e o parênquima renal normal foi 59,7 HU. Estes resultados foram estatisticamente significativos (p<0,05). Não se identificaram outras alterações na fase excretora da TC, nem diferenças relevantes de carácter morfológico, nomeadamente nos contornos das lesões, presença de calcificações, ou de cicatriz central. Conclusões: Na avaliação imagiológica por URO-TC, nomeadamente na fase nefrográfica, parece existir uma tendência para maior isodensidade dos oncocitomas em relação ao parênquima renal normal. Este achado poderá contribuir para uma melhor decisão terapêutica, na medida em que nos pode direccionar para uma biópsia de confirmação em detrimento da excisão cirúrgica.info:eu-repo/semantics/publishedVersio

Development and validation of exhaled breath condensate microRNAs to identify and endotype asthma in children

Detection and quantification of microRNAs (miRNAs) in exhaled breath condensate (EBC) has been poorly explored. Therefore we aimed to assess miRNAs in EBC as potential biomarkers to diagnose and endotype asthma in school aged children. In a cross sectional, nested case control study, all the asthmatic children (n = 71) and a random sample of controls (n = 115), aged 7 to 12 years, attending 71 classrooms from 20 local schools were selected and arbitrarily allocated to the development or validation set. Participants underwent skin-prick testing, spirometry with bronchodilation, had exhaled level of nitric oxide determined and EBC collected. Based on previous studies eleven miRNAs were chosen and analyzed in EBC by reverse transcription-quantitative real-time PCR. Principal component analysis was applied to identify miRNAs profiles and associations were estimated using regression models. In the development set (n = 89) two clusters of miRNAs were identified. After adjustments, cluster 1 and three of its clustered miRNAs, miR-126-3p, miR-133a-3p and miR-145-5p were positively associated with asthma. Moreover miR-21-5p was negatively associated with symptomatic asthma and positively associated with positive bronchodilation without symptoms. An association was also found between miR-126-3p, cluster 2 and one of its clustered miRNA, miR-146-5p, with higher FEF25-75 reversibility. These findings were confirmed in the validation set (n = 97) where two identical clusters of miRNAs were identified. Additional significant associations were observed between miR-155-5p with symptomatic asthma, negative bronchodilation with symptoms and positive bronchodilation without symptoms. We showed that microRNAs can be measured in EBC of children and may be used as potential biomarkers of asthma, assisting asthma endotype establishment.Authors gratefully acknowledge the funding by Fundação para a Ciência e Tecnologia through the Project NORTE-01-0145-FEDER-000010 - Health, Comfort and Energy in the Built Environment (HEBE), cofinanced by Programa Operacional Regional do Norte (NORTE2020), through Fundo Europeu de Desenvolvimento Regional (FEDER) and EXALAR 21 project financed by FEDER/FNR and by Fundação para a Ciência e Tecnologia (EXALAR 21 02/SAICT/2017 - Project nº 30193). FCM kindly acknowledges the scholarship SFRH/BD/144563/2019 granted by Fundação para a Ciência e Tecnologia, as well as the Fulbright Research Grant 2019/2020 granted by Fulbright Portugal. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript

Crystallization, data collection and phasing of two digestive lysozymes from Musca domestica

Lysozymes are mostly known for their defensive role against bacteria, but in several animals lysozymes have a digestive function. Here, the initial crystallographic characterization of two digestive lysozymes from Musca domestica are presented. The proteins were crystallized using the sitting-drop vapour-diffusion method in the presence of ammonium sulfate or PEG/2-propanol as the precipitant. X-ray diffraction data were collected to a maximum resolution of 1.9 angstrom using synchrotron radiation. The lysozyme 1 and 2 crystals belong to the monoclinic space group P2(1) (unit-cell parameters a = 36.52, b = 79.44, c = 45.20 angstrom, beta = 102.97 degrees) and the orthorhombic space group P2(1)2(1)2 (unit-cell parameters a = 73.90, b = 96.40, c = 33.27 angstrom), respectively. The crystal structures were solved by molecular replacement and structure refinement is in progress.62875075

Close phylogenetic relationship between Angolan and Romanian HIV-1 subtype F1 isolates

<p>Abstract</p> <p>Background</p> <p>Here, we investigated the phylogenetic relationships of the HIV-1 subtype F1 circulating in Angola with subtype F1 strains sampled worldwide and reconstructed the evolutionary history of this subtype in Central Africa.</p> <p>Methods</p> <p>Forty-six HIV-1-positive samples were collected in Angola in 2006 and subtyped at the <it>env</it>-gp41 region. Partial <it>env</it>-gp120 and <it>pol-RT </it>sequences and near full-length genomes from those <it>env</it>-gp41 subtype F1 samples were further generated. Phylogenetic analyses of partial and full-length subtype F1 strains isolated worldwide were carried out. The onset date of the subtype F1 epidemic in Central Africa was estimated using a Bayesian Markov chain Monte Carlo approach.</p> <p>Results</p> <p>Nine Angolan samples were classified as subtype F1 based on the analysis of the <it>env</it>-gp41 region. All nine Angolan sequences were also classified as subtype F1 in both <it>env-gp120 </it>and <it>pol-RT </it>genomic regions, and near full-length genome analysis of four of these samples confirmed their classification as "pure" subtype F1. Phylogenetic analyses of subtype F1 strains isolated worldwide revealed that isolates from the Democratic Republic of Congo (DRC) were the earliest branching lineages within the subtype F1 phylogeny. Most strains from Angola segregated in a monophyletic group together with Romanian sequences; whereas South American F1 sequences emerged as an independent cluster. The origin of the subtype F1 epidemic in Central African was estimated at 1958 (1934–1971).</p> <p>Conclusion</p> <p>"Pure" subtype F1 strains are common in Angola and seem to be the result of a single founder event. Subtype F1 sequences from Angola are closely related to those described in Romania, and only distantly related to the subtype F1 lineage circulating in South America. Original diversification of subtype F1 probably occurred within the DRC around the late 1950s.</p

Brazilian Plasmodium falciparum isolates: investigation of candidate polymorphisms for artemisinin resistance before introduction of artemisinin-based combination therapy

<p>Abstract</p> <p>Background</p> <p>This study was performed to better understand the genetic diversity of known polymorphisms in <it>pfatpase6 </it>and <it>pfmdr1 </it>genes before the introduction of ACT in Brazil, in order to get a genotypic snapshot of <it>Plasmodium falciparum </it>parasites that may be used as baseline reference for future studies.</p> <p>Methods</p> <p>Parasites from <it>P. falciparum </it>samples collected in 2002, 2004 and 2006-2007 were genotyped using PCR and DNA sequencing at codons 86, 130, 184, 1034, 1042, 1109 and 1246 for <it>pfmdr1 </it>gene, and 243, 263, 402, 431, 623, 630, 639, 683, 716, 776, 769 and 771 for <it>pfatpase6 </it>gene.</p> <p>Results</p> <p>A <it>pfmdr1 </it>haplotype NEF/CDVY was found in 97% of the samples. In the case of <it>pfatpase6</it>, four haplotypes, wild-type (37%), 630 S (35%), 402 V (5%) and double-mutant 630 S + 402 V (23%), were detected.</p> <p>Conclusion</p> <p>Although some polymorphism in <it>pfmdr1 </it>and <it>pfatpase6 </it>were verified, no reported haplotypes in both genes that may mediate altered response to ACT was detected before the introduction of this therapy in Brazil. Thus, the haplotypes herein described can be very useful as a baseline reference of <it>P. falciparum </it>populations without ACT drug pressure.</p

MHD models of Pulsar Wind Nebulae

Pulsar Wind Nebulae (PWNe) are bubbles or relativistic plasma that form when the pulsar wind is confined by the SNR or the ISM. Recent observations have shown a richness of emission features that has driven a renewed interest in the theoretical modeling of these objects. In recent years a MHD paradigm has been developed, capable of reproducing almost all of the observed properties of PWNe, shedding new light on many old issues. Given that PWNe are perhaps the nearest systems where processes related to relativistic dynamics can be investigated with high accuracy, a reliable model of their behavior is paramount for a correct understanding of high energy astrophysics in general. I will review the present status of MHD models: what are the key ingredients, their successes, and open questions that still need further investigation.Comment: 18 pages, 5 figures, Invited Review, Proceedings of the "ICREA Workshop on The High-Energy Emission from Pulsars and their Systems", Sant Cugat, Spain, April 12-16, 201

Gene expression and splicing alterations analyzed by high throughput RNA sequencing of chronic lymphocytic leukemia specimens.

BackgroundTo determine differentially expressed and spliced RNA transcripts in chronic lymphocytic leukemia specimens a high throughput RNA-sequencing (HTS RNA-seq) analysis was performed.MethodsTen CLL specimens and five normal peripheral blood CD19+ B cells were analyzed by HTS RNA-seq. The library preparation was performed with Illumina TrueSeq RNA kit and analyzed by Illumina HiSeq 2000 sequencing system.ResultsAn average of 48.5 million reads for B cells, and 50.6 million reads for CLL specimens were obtained with 10396 and 10448 assembled transcripts for normal B cells and primary CLL specimens respectively. With the Cuffdiff analysis, 2091 differentially expressed genes (DEG) between B cells and CLL specimens based on FPKM (fragments per kilobase of transcript per million reads and false discovery rate, FDR q &lt; 0.05, fold change &gt;2) were identified. Expression of selected DEGs (n = 32) with up regulated and down regulated expression in CLL from RNA-seq data were also analyzed by qRT-PCR in a test cohort of CLL specimens. Even though there was a variation in fold expression of DEG genes between RNA-seq and qRT-PCR; more than 90 % of analyzed genes were validated by qRT-PCR analysis. Analysis of RNA-seq data for splicing alterations in CLL and B cells was performed by Multivariate Analysis of Transcript Splicing (MATS analysis). Skipped exon was the most frequent splicing alteration in CLL specimens with 128 significant events (P-value &lt;0.05, minimum inclusion level difference &gt;0.1).ConclusionThe RNA-seq analysis of CLL specimens identifies novel DEG and alternatively spliced genes that are potential prognostic markers and therapeutic targets. High level of validation by qRT-PCR for a number of DEG genes supports the accuracy of this analysis. Global comparison of transcriptomes of B cells, IGVH non-mutated CLL (U-CLL) and mutated CLL specimens (M-CLL) with multidimensional scaling analysis was able to segregate CLL and B cell transcriptomes but the M-CLL and U-CLL transcriptomes were indistinguishable. The analysis of HTS RNA-seq data to identify alternative splicing events and other genetic abnormalities specific to CLL is an added advantage of RNA-seq that is not feasible with other genome wide analysis