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Find video protocols related to scientific articles indexed in Pubmed.
Genome of the avirulent human-infective trypanosome--Trypanosoma rangeli.
PLoS Negl Trop Dis
PUBLISHED: 09-01-2014
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Trypanosoma rangeli is a hemoflagellate protozoan parasite infecting humans and other wild and domestic mammals across Central and South America. It does not cause human disease, but it can be mistaken for the etiologic agent of Chagas disease, Trypanosoma cruzi. We have sequenced the T. rangeli genome to provide new tools for elucidating the distinct and intriguing biology of this species and the key pathways related to interaction with its arthropod and mammalian hosts.
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The role of prestroke glycemic control on severity and outcome of acute ischemic stroke.
Stroke Res Treat
PUBLISHED: 05-18-2014
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Background/Aim. Relatively few studies have investigated the association of prestroke glycemic control and clinical outcome in acute ischemic stroke (IS) patients, regardless of presence of diabetes mellitus (DM). The aim of this study was to investigate the importance of prestroke glycemic control on survival, stroke severity, and functional outcome of patients with acute IS. Methods. We performed a retrospective survival analysis of 501 patients with IS admitted to Sahlgrenska University Hospital from February 15, 2005, through May 31, 2009. The outcomes of interest were acute and long-term survival; the stroke severity (NIHSS) and the functional outcome, mRS, at 12 months. Results. HbA1c was a good predictor of acute (HR 1.45; CI, 1.09 to 1.93, P = 0.011) and long-term mortality (HR 1.29; CI 1.03 to 1.62; P = 0.029). Furthermore, HbA1c >6% was significantly correlated with acute stroke severity (OR 1.29; CI 1.01 to 1.67; P = 0.042) and predicted worse functional outcome at 12 months (OR 2.68; CI 1.14 to 6.03; P = 0.024). Conclusions. Our study suggests that poor glycemic control (baseline HbA1c) prior to IS is an independent risk factor for poor survival and a marker for increased stroke severity and unfavorable long-term functional outcome.
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Short-term changes in bone formation markers following growth hormone (GH) treatment in short prepubertal children with a broad range of GH secretion.
Clin. Endocrinol. (Oxf)
PUBLISHED: 03-12-2014
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Growth hormone (GH) promotes longitudinal growth and bone modelling/remodelling. This study investigated the relationship between levels of bone formation markers and growth during GH treatment in prepubertal children with widely ranging GH secretion levels.
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Trypanosoma cruzi Clone Dm28c Draft Genome Sequence.
Genome Announc
PUBLISHED: 02-01-2014
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Trypanosoma cruzi affects millions of people worldwide. Clinical variability of Chagas disease can be due to the genetic variability of this parasite, requiring further genome studies. Here we report the genome sequence of the T. cruzi Dm28c clone (TcI), a strain related to the sylvatic cycle of the parasite.
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Role of growth hormone in enchondroplasia and chondral osteogenesis: evaluation by X-ray of the hand.
Pediatr. Res.
PUBLISHED: 01-22-2014
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The process of growth and maturation of long (radius and ulna) and short (metacarpals and phalanges) bones of the hand (enchondroplasia) differs from that of the carpal cuboid bones (chondral osteogenesis). This study aimed to assess the impact of growth hormone (GH) on these two processes of bone maturation.
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Neuronal and glia-related biomarkers in cerebrospinal fluid of patients with acute ischemic stroke.
J Cent Nerv Syst Dis
PUBLISHED: 01-01-2014
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Cerebral ischemia promotes morphological reactions of the neurons, astrocytes, oligodendrocytes, and microglia in experimental studies. Our aim was to examine the profile of CSF (cerebrospinal fluid) biomarkers and their relation to stroke severity and degree of white matter lesions (WML).
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Intraclonal Variations Among Streptococcus pneumoniae Isolates Influence the Likelihood of Invasive Disease in Children.
J. Infect. Dis.
PUBLISHED: 09-05-2013
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Background.?Pneumococcal serotypes are represented by a varying number of clonal lineages with different genetic contents, potentially affecting invasiveness. However, genetic variation within the same genetic lineage may be larger than anticipated.Methods.?A total of 715 invasive and carriage isolates from children in the same region and during the same period were compared using pulsed-field gel electrophoresis (PFGE) and multilocus sequence typing. Bacterial genome sequencing, functional assays, and in vivo virulence mice studies were performed.Results.?Clonal types of the same serotype but also intraclonal variants within clonal complexes (CCs) showed differences in invasive-disease potential. CC138, a common CC, was divided into several PFGE patterns, partly explained by number, location, and type of temperate bacteriophages. Whole-genome sequencing of 4 CC138 isolates representing PFGE clones with different invasive-disease potentials revealed intraclonal sequence variations of the virulence-associated proteins pneumococcal surface protein A (PspA) and pneumococcal choline-binding protein C (PspC). A carrier isolate lacking PcpA exhibited decreased virulence in mice, and there was a differential binding of human factor H, depending on invasiveness.Conclusions.?Pneumococcal clonal types but also intraclonal variants exhibited different invasive-disease potentials in children. Intraclonal variants, reflecting different prophage contents, showed differences in major surface antigens. This suggests ongoing immune selection, such as that due to PspC-mediated complement resistance through varied human factor H binding, that may affect invasiveness in children.
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Genotypic diversity and migration patterns of Phytophthora infestans in the Nordic countries.
Fungal Biol
PUBLISHED: 08-07-2013
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In this study we investigated the genotypic diversity and the migration patterns of Phytophthora infestans in the Nordic countries. Isolates of P. infestans from outbreaks in 43 fields sampled in 2008 were collected using stratified sampling with country, field, and disease foci as the different strata. Microsatellites were used as markers to determine the genotypic variation in the sampled material. The results show a high genotypic variation of P. infestans in the Nordic countries with most of the genotypes found only once among the collected isolates. The major part of the genotypic variation was observed within the fields, with low differentiation between the fields. The observed low association of alleles among loci is consistent with frequent sexual reproduction of P. infestans in the Nordic countries. Coalescence analyses did not support a single common population for the four countries, thus indicating some degree of geographic differentiation. The analyses of migration patterns showed differing levels of gene flow among the Nordic countries. No correlation between migration rates and geographical distance could be seen. This could be explained by different degrees of genetic similarity between the pathogen populations in the different countries.
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Electrocardiographic abnormalities and elevated cTNT at admission for intracerebral hemorrhage: predictors for survival?
Ann Noninvasive Electrocardiol
PUBLISHED: 05-03-2013
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Cerebrovascular lesions are often associated with electrocardiographic (ECG) abnormalities. The main purpose of this work was to investigate the prognostic value of ECG abnormalities and/or elevated cardiac troponin (cTNT) on admission in patients with nontraumatic intracerebral hemorrhage (ICH).
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Protein markers predict body composition during growth hormone treatment in short prepubertal children.
Clin. Endocrinol. (Oxf)
PUBLISHED: 03-04-2013
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A high-throughput pharmaco-proteomic approach has previously been successfully used to identify lipoprotein biomarkers related to changes in longitudinal growth and bone mass in response to growth hormone (GH) treatment. The aim of this study was to identify protein markers involved in the diverse anabolic and lipolytic remodelling of body composition during GH treatment.
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The Norway spruce genome sequence and conifer genome evolution.
Nature
PUBLISHED: 02-10-2013
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Conifers have dominated forests for more than 200?million years and are of huge ecological and economic importance. Here we present the draft assembly of the 20-gigabase genome of Norway spruce (Picea abies), the first available for any gymnosperm. The number of well-supported genes (28,354) is similar to the >100 times smaller genome of Arabidopsis thaliana, and there is no evidence of a recent whole-genome duplication in the gymnosperm lineage. Instead, the large genome size seems to result from the slow and steady accumulation of a diverse set of long-terminal repeat transposable elements, possibly owing to the lack of an efficient elimination mechanism. Comparative sequencing of Pinus sylvestris, Abies sibirica, Juniperus communis, Taxus baccata and Gnetum gnemon reveals that the transposable element diversity is shared among extant conifers. Expression of 24-nucleotide small RNAs, previously implicated in transposable element silencing, is tissue-specific and much lower than in other plants. We further identify numerous long (>10,000?base pairs) introns, gene-like fragments, uncharacterized long non-coding RNAs and short RNAs. This opens up new genomic avenues for conifer forestry and breeding.
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Transcriptome profiling of Giardia intestinalis using strand-specific RNA-seq.
PLoS Comput. Biol.
PUBLISHED: 02-02-2013
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Giardia intestinalis is a common cause of diarrheal disease and it consists of eight genetically distinct genotypes or assemblages (A-H). Only assemblages A and B infect humans and are suggested to represent two different Giardia species. Correlations exist between assemblage type and host-specificity and to some extent symptoms. Phenotypical differences have been documented between assemblages and genome sequences are available for A, B and E. We have characterized and compared the polyadenylated transcriptomes of assemblages A, B and E. Four genetically different isolates were studied (WB (AI), AS175 (AII), P15 (E) and GS (B)) using paired-end, strand-specific RNA-seq. Most of the genome was transcribed in trophozoites grown in vitro, but at vastly different levels. RNA-seq confirmed many of the present annotations and refined the current genome annotation. Gene expression divergence was found to recapitulate the known phylogeny, and uncovered lineage-specific differences in expression. Polyadenylation sites were mapped for over 70% of the genes and revealed many examples of conserved and unexpectedly long 3 UTRs. 28 open reading frames were found in a non-transcribed gene cluster on chromosome 5 of the WB isolate. Analysis of allele-specific expression revealed a correlation between allele-dosage and allele expression in the GS isolate. Previously reported cis-splicing events were confirmed and global mapping of cis-splicing identified only one novel intron. These observations can possibly explain differences in host-preference and symptoms, and it will be the basis for further studies of Giardia pathogenesis and biology.
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Heart dysfunction in patients with acute ischemic stroke or TIA does not predict all-cause mortality at long-term follow-up.
BMC Neurol
PUBLISHED: 01-23-2013
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Despite heart failure being a substantial risk factor for stroke, few studies have evaluated the predictive value of heart dysfunction for all-cause mortality in patients with acute ischemic stroke, in particular in the elderly. The aim of this study was to investigate whether impaired heart function in elderly patients can predict all-cause mortality after acute ischemic stroke or transient ischemic attack (TIA).
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PCR-induced transitions are the major source of error in cleaned ultra-deep pyrosequencing data.
PLoS ONE
PUBLISHED: 01-01-2013
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Ultra-deep pyrosequencing (UDPS) is used to identify rare sequence variants. The sequence depth is influenced by several factors including the error frequency of PCR and UDPS. This study investigated the characteristics and source of errors in raw and cleaned UDPS data.
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Can weed hosts increase aggressiveness of Phytophthora infestans on potato?
Phytopathology
PUBLISHED: 12-30-2011
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Potato late blight, caused by Phytophthora infestans, is a major disease in potato production throughout the world. In Southern Sweden, hairy nightshade (Solanum physalifolium), an alternative non-crop host to the pathogen has become a frequent weed. Single lesion leaves infected by P. infestans were collected from potato and hairy nightshade to determine phenotypic and genotypic population differentiation of P. infestans between the two hosts. Genotypic variation was estimated using microsatellites as markers. The results showed no genotypic differentiation in the samples between the two hosts. Cross-inoculations were performed to compare the respective aggressiveness of isolates sampled on potato or hairy nightshade. The proportion of infected leaves, latency period, lesion growth rate, and sporulation capacity were measured. The odds of successful infection were higher for isolates from hairy nightshade on both hosts combined. When tested on potato leaves, isolates from hairy nightshade showed a significantly shorter latency period and higher sporulation capacity compared to isolates from potato. These results indicate that an alternative host can filter populations of P.infestans towards higher aggressiveness, leading to increased difficulty in managing potato late blight.
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An efficient simulator of 454 data using configurable statistical models.
BMC Res Notes
PUBLISHED: 07-13-2011
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Roche 454 is one of the major 2nd generation sequencing platforms. The particular characteristics of 454 sequence data pose new challenges for bioinformatic analyses, e.g. assembly and alignment search algorithms. Simulation of these data is therefore useful, in order to further assess how bioinformatic applications and algorithms handle 454 data.
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The short non-coding transcriptome of the protozoan parasite Trypanosoma cruzi.
PLoS Negl Trop Dis
PUBLISHED: 05-10-2011
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The pathway for RNA interference is widespread in metazoans and participates in numerous cellular tasks, from gene silencing to chromatin remodeling and protection against retrotransposition. The unicellular eukaryote Trypanosoma cruzi is missing the canonical RNAi pathway and is unable to induce RNAi-related processes. To further understand alternative RNA pathways operating in this organism, we have performed deep sequencing and genome-wide analyses of a size-fractioned cDNA library (16-61 nt) from the epimastigote life stage. Deep sequencing generated 582,243 short sequences of which 91% could be aligned with the genome sequence. About 95-98% of the aligned data (depending on the haplotype) corresponded to small RNAs derived from tRNAs, rRNAs, snRNAs and snoRNAs. The largest class consisted of tRNA-derived small RNAs which primarily originated from the 3 end of tRNAs, followed by small RNAs derived from rRNA. The remaining sequences revealed the presence of 92 novel transcribed loci, of which 79 did not show homology to known RNA classes.
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The Trypanosoma cruzi genome; conserved core genes and extremely variable surface molecule families.
Res. Microbiol.
PUBLISHED: 02-27-2011
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The protozoan parasite Trypanosoma cruzi is an important but neglected pathogen that causes chagas disease, which affects millions of people, mainly in latin America. The population structure and epidemiology of the parasite are complex, with much variability among strains. The genome sequence of a reference strain, CL Brener, was published in 2005, and the availability of this sequence has both revealed the complexity of the parasite genome and greatly facilitated research into parasite biology and pathogenesis, by making the sequences of more than 8000 core genes available. The T. cruzi genome is highly repetitive, which has resulted in inaccuracies in the genome sequence, and attempts have been made to provide a deeper analysis of repeated genes as a complement to the genome sequence. The genome was found to be organized in stable core regions containing housekeeping and other genes, surrounded by highly repetitive, often sub-telomeric highly variable regions containing multiple members of large families of surface molecule genes. Comparative sequencing of T. cruzi strains has been initiated and the results show that the core gene content of the parasite is highly conserved, but that much sequence variability, 3-4% difference at the DNA level on average between strains in coding regions, is present. The additional genomes will improve the understanding of parasite biology and epidemiology.
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FAAST: Flow-space Assisted Alignment Search Tool.
BMC Bioinformatics
PUBLISHED: 02-24-2011
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High throughput pyrosequencing (454 sequencing) is the major sequencing platform for producing long read high throughput data. While most other sequencing techniques produce reading errors mainly comparable with substitutions, pyrosequencing produce errors mainly comparable with gaps. These errors are less efficiently detected by most conventional alignment programs and may produce inaccurate alignments.
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Shotgun sequencing analysis of Trypanosoma cruzi I Sylvio X10/1 and comparison with T. cruzi VI CL Brener.
PLoS Negl Trop Dis
PUBLISHED: 02-09-2011
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Trypanosoma cruzi is the causative agent of Chagas disease, which affects more than 9 million people in Latin America. We have generated a draft genome sequence of the TcI strain Sylvio X10/1 and compared it to the TcVI reference strain CL Brener to identify lineage-specific features. We found virtually no differences in the core gene content of CL Brener and Sylvio X10/1 by presence/absence analysis, but 6 open reading frames from CL Brener were missing in Sylvio X10/1. Several multicopy gene families, including DGF, mucin, MASP and GP63 were found to contain substantially fewer genes in Sylvio X10/1, based on sequence read estimations. 1,861 small insertion-deletion events and 77,349 nucleotide differences, 23% of which were non-synonymous and associated with radical amino acid changes, further distinguish these two genomes. There were 336 genes indicated as under positive selection, 145 unique to T. cruzi in comparison to T. brucei and Leishmania. This study provides a framework for further comparative analyses of two major T. cruzi lineages and also highlights the need for sequencing more strains to understand fully the genomic composition of this parasite.
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Genetic analysis of Phytophthora infestans populations in the Nordic European countries reveals high genetic variability.
Fungal Biol
PUBLISHED: 01-04-2011
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Late blight, caused by the oomycete Phytophthora infestans, is the most important disease of potato (Solanum tuberosum). The pathogen is highly adaptable and to get an overview of the genetic variation in the Nordic countries, Denmark, Finland, Norway and Sweden we have analyzed 200 isolates from different fields using nine simple-sequence repeat (SSR) markers. Forty-nine alleles were detected among the nine SSR loci and isolates from all four Nordic countries shared the most common alleles across the loci. In total 169 multilocus genotypes (based on seven loci) were identified among 191 isolates. The genotypic diversities, quantified by a normalized Shannons diversity index (H(s)), were 0.95 for the four Nordic countries. The low F(ST) value of 0.04 indicates that the majority of variation is found within the four Nordic countries. The large number of genotypes and the frequency distribution of mating types (60% A1) support the hypothesis that sexual reproduction is contributing notably to the genetic variation of P. infestans in the Nordic countries.
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An unbiased metagenomic search for infectious agents using monozygotic twins discordant for chronic fatigue.
BMC Microbiol.
PUBLISHED: 01-02-2011
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Chronic fatigue syndrome is an idiopathic syndrome widely suspected of having an infectious or immune etiology. We applied an unbiased metagenomic approach to try to identify known or novel infectious agents in the serum of 45 cases with chronic fatigue syndrome or idiopathic chronic fatigue. Controls were the unaffected monozygotic co-twins of cases, and serum samples were obtained at the same place and time.
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Protein profiling identified dissociations between growth hormone-mediated longitudinal growth and bone mineralization in short prepubertal children.
J Proteomics
PUBLISHED: 08-24-2010
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Growth hormone (GH) promotes longitudinal growth and bone mineralization. In this study, a proteomic approach was used to analyze the association between serum protein expression pattern and height-adjusted bone mineralization in short prepubertal children receiving GH treatment. Patterns of protein expression were compared with those associated with longitudinal bone growth. Specific protein expression patterns associated with changes in height-adjusted bone mineralization in response to GH treatment were identified. Out of the 37 peaks found in significant regression models, 27 were uniquely present in models correlated with changes in bone mineralization and 7 peaks were uniquely present in models correlated with changes in height. The peaks identified corresponded to apolipoproteins, transthyretin, serum amyloid A4 and hemoglobin beta. We conclude that a proteomic approach could be used to identify specific protein expression patterns associated with bone mineralization in response to GH treatment and that height-adjusted bone mineralization and longitudinal bone growth are regulated partly by the same and partly by different mechanisms. Protein isoforms with different post-translational modifications might be of importance in the regulation of these processes. However, further validation is needed to assess the clinical significance of the results.
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Can prolonged QTc and cTNT level predict the acute and long-term prognosis of stroke?
Int. J. Cardiol.
PUBLISHED: 07-14-2010
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Previous studies in patients with stroke indicate that QTc prolongation and elevated cTNT are related to increased risk of all-cause and cardiovascular mortality.
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Dynamics of HIV-1 quasispecies during antiviral treatment dissected using ultra-deep pyrosequencing.
PLoS ONE
PUBLISHED: 05-26-2010
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Ultra-deep pyrosequencing (UDPS) allows identification of rare HIV-1 variants and minority drug resistance mutations, which are not detectable by standard sequencing.
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Classification of DNA sequences using Bloom filters.
Bioinformatics
PUBLISHED: 05-13-2010
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New generation sequencing technologies producing increasingly complex datasets demand new efficient and specialized sequence analysis algorithms. Often, it is only the novel sequences in a complex dataset that are of interest and the superfluous sequences need to be removed.
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Genome analysis and comparative genomics of a Giardia intestinalis assemblage E isolate.
BMC Genomics
PUBLISHED: 04-07-2010
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Giardia intestinalis is a protozoan parasite that causes diarrhea in a wide range of mammalian species. To further understand the genetic diversity between the Giardia intestinalis species, we have performed genome sequencing and analysis of a wild-type Giardia intestinalis sample from the assemblage E group, isolated from a pig.
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Analyses of an expressed sequence tag library from Taenia solium, Cysticerca.
PLoS Negl Trop Dis
PUBLISHED: 03-31-2010
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Neurocysticercosis is a disease caused by the oral ingestion of eggs from the human parasitic worm Taenia solium. Although drugs are available they are controversial because of the side effects and poor efficiency. An expressed sequence tag (EST) library is a method used to describe the gene expression profile and sequence of mRNA from a specific organism and stage. Such information can be used in order to find new targets for the development of drugs and to get a better understanding of the parasite biology.
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Toll-like receptor 4 promoter polymorphisms: common TLR4 variants may protect against severe urinary tract infection.
PLoS ONE
PUBLISHED: 02-08-2010
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Polymorphisms affecting Toll-like receptor (TLR) structure appear to be rare, as would be expected due to their essential coordinator role in innate immunity. Here, we assess variation in TLR4 expression, rather than structure, as a mechanism to diversify innate immune responses.
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Plasmodium falciparum multidrug resistance protein 1 and artemisinin-based combination therapy in Africa.
J. Infect. Dis.
PUBLISHED: 10-08-2009
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Plasmodium falciparum response mechanisms to the major artemisinin-based combination therapies (ACTs) are largely unknown. Multidrug-resistance protein (MRP)-like adenosine triphosphate (ATP)-binding cassette transporters are known to be related to multidrug resistance in many organisms. Therefore, we hypothesized that sequence variation in pfmrp1 can contribute to decreased parasite sensitivity to ACT. Through sequencing of the pfmrp1 open reading frame for 103 geographically diverse P. falciparum infections, we identified 27 single-nucleotide polymorphisms (SNPs), of which 21 were nonsynonymous and 6 synonymous. Analyses of clinical efficacy trials with artesunate-amodiaquine and artemether-lumefantrine detected a specific selection of the globally prevalent I876V SNP in recurrent infections after artemether-lumefantrine treatment. Additional in silico studies suggested an influence of variation in amino acid 876 on the ATP hydrolysis cycle of pfMRP1 with potential impact on protein functionality. Our data suggest for the first time, to our knowledge, the involvement of pfMRP1 in P. falciparum in vivo response to ACT.
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Proteins related to lipoprotein profile were identified using a pharmaco-proteomic approach as markers for growth response to growth hormone (GH) treatment in short prepubertal children.
Proteome Sci
PUBLISHED: 08-20-2009
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The broad range in growth observed in response to growth hormone (GH) treatment is mainly caused by individual variations in both GH secretion and GH sensitivity. Individual GH responsiveness can be estimated using evidence-based models that predict the response to GH treatment; however, these models can be improved. High-throughput proteomics techniques can be used to identify proteins that may potentially be used as variables in such models in order to improve their predictive ability. Previously we have reported that proteomic analyses can identify biomarkers that discriminate between short prepubertal children with idiopathic short stature (ISS) who show good or poor growth in response to GH treatment. In this study we used a pharmaco-proteomic approach to identify novel factors that correlate with the growth response to GH treatment in prepubertal children who are short due to GH deficiency or ISS. The study included 128 short prepubertal children receiving GH treatment, of whom 39 were GH-deficient and 89 had ISS. Serum protein expression profiles at study start and after 1 year of GH treatment were analyzed using SELDI-TOF. Cross-validated regression and random permutation analyses were performed to identify significant correlations between protein expression patterns and the 2-year growth response to GH treatment.
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Selective and irreversible inhibitors of mosquito acetylcholinesterases for controlling malaria and other mosquito-borne diseases.
PLoS ONE
PUBLISHED: 06-20-2009
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New insecticides are urgently needed because resistance to current insecticides allows resurgence of disease-transmitting mosquitoes while concerns for human toxicity from current compounds are growing. We previously reported the finding of a free cysteine (Cys) residue at the entrance of the active site of acetylcholinesterase (AChE) in some insects but not in mammals, birds, and fish. These insects have two AChE genes (AP and AO), and only AP-AChE carries the Cys residue. Most of these insects are disease vectors such as the African malaria mosquito (Anopheles gambiae sensu stricto) or crop pests such as aphids. Recently we reported a Cys-targeting small molecule that irreversibly inhibited all AChE activity extracted from aphids while an identical exposure caused no effect on the human AChE. Full inhibition of AChE in aphids indicates that AP-AChE contributes most of the enzymatic activity and suggests that the Cys residue might serve as a target for developing better aphicides. It is therefore worth investigating whether the Cys-targeting strategy is applicable to mosquitocides. Herein, we report that, under conditions that spare the human AChE, a methanethiosulfonate-containing molecule at 6 microM irreversibly inhibited 95% of the AChE activity extracted from An. gambiae s. str. and >80% of the activity from the yellow fever mosquito (Aedes aegypti L.) or the northern house mosquito (Culex pipiens L.) that is a vector of St. Louis encephalitis. This type of inhibition is fast ( approximately 30 min) and due to conjugation of the inhibitor to the active-site Cys of mosquito AP-AChE, according to our observed reactivation of the methanethiosulfonate-inhibited AChE by 2-mercaptoethanol. We also note that our sulfhydryl agents partially and irreversibly inhibited the human AChE after prolonged exposure (>4 hr). This slow inhibition is due to partial enzyme denaturation by the inhibitor and/or micelles of the inhibitor, according to our studies using atomic force microscopy, circular dichroism spectroscopy, X-ray crystallography, time-resolved fluorescence spectroscopy, and liquid chromatography triple quadrupole mass spectrometry. These results support our view that the mosquito-specific Cys is a viable target for developing new mosquitocides to control disease vectors and to alleviate resistance problems with reduced toxicity toward non-target species.
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Draft genome sequencing of giardia intestinalis assemblage B isolate GS: is human giardiasis caused by two different species?
PLoS Pathog.
PUBLISHED: 04-03-2009
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Giardia intestinalis is a major cause of diarrheal disease worldwide and two major Giardia genotypes, assemblages A and B, infect humans. The genome of assemblage A parasite WB was recently sequenced, and the structurally compact 11.7 Mbp genome contains simplified basic cellular machineries and metabolism. We here performed 454 sequencing to 16x coverage of the assemblage B isolate GS, the only Giardia isolate successfully used to experimentally infect animals and humans. The two genomes show 77% nucleotide and 78% amino-acid identity in protein coding regions. Comparative analysis identified 28 unique GS and 3 unique WB protein coding genes, and the variable surface protein (VSP) repertoires of the two isolates are completely different. The promoters of several enzymes involved in the synthesis of the cyst-wall lack binding sites for encystation-specific transcription factors in GS. Several synteny-breaks were detected and verified. The tetraploid GS genome shows higher levels of overall allelic sequence polymorphism (0.5 versus <0.01% in WB). The genomic differences between WB and GS may explain some of the observed biological and clinical differences between the two isolates, and it suggests that assemblage A and B Giardia can be two different species.
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Preclinical assessment of the treatment of second-stage African trypanosomiasis with cordycepin and deoxycoformycin.
PLoS Negl Trop Dis
PUBLISHED: 03-24-2009
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There is an urgent need to substitute the highly toxic compounds still in use for treatment of the encephalitic stage of human African trypanosomiasis (HAT). We here assessed the treatment with the doublet cordycepin and the deaminase inhibitor deoxycoformycin for this stage of infection with Trypanosoma brucei (T.b.).
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Molecular characterization of a novel Ljungan virus (Parechovirus; Picornaviridae) reveals a fourth genotype and indicates ancestral recombination.
J. Gen. Virol.
PUBLISHED: 03-04-2009
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Ljungan virus (LV) was discovered 20 years ago in Swedish bank voles (Myodes glareolus, previously referred to as Clethrionomys glareolus) during the search for an infectious agent causing lethal myocarditis in young athletes. To date, the genomes of four LV isolates, including the prototype 87-012 strain, have been characterized. Three of these LV strains were isolated from bank voles trapped in Sweden. Sequence analysis of an American virus (M1146), isolated from a montane vole (Microtus montanus) in western USA, indicates that this strain represents a genotype that is different from the Swedish strains. Here, we present genomic analyses of a fifth LV strain (64-7855) isolated from a southern red-backed vole (Myodes gapperi) trapped during arbovirus studies in New York state in the north-eastern USA in the 1960s. Sequence analysis of the 64-7855 genome showed an LV-like genome organization and sequence similarity to other LV strains. Genetic and phylogenetic analyses of the evolutionary relationship between the 64-7855 strain and other viruses within the family Picornaviridae, including previously published LV strains, demonstrated that the 64-7855 strain constitutes a new genotype within the LV species. Analyses also showed that different regions of the 64-7855 genome have different phylogenetic relationships with other LV strains, indicating that previous recombination events have been involved in the evolution of this virus.
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Genetic polymorphisms of glutathione S-transferase genes GSTP1, GSTM1, and GSTT1 and risk of esophageal and gastric cardia cancers.
Cancer Causes Control
PUBLISHED: 02-13-2009
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Glutathione S-transferase (GST) enzymes are known to metabolize tobacco-related carcinogens. Previous studies on the association of functional polymorphisms of GST genes with esophageal squamous cell carcinoma have yielded conflicting but overall null results. A few studies of esophageal adenocarcinoma were likewise conflicting, but the scarcity of data is striking. We aimed to study associations of the GSTM1 and GSTT1 null deletion polymorphisms as well as the GSTP1 Ile105Val polymorphism with risks for esophageal and gastric cardia cancers. DNA was prepared from 96 and 79 cases of esophageal adenocarcinoma and squamous cell carcinoma, respectively, 126 cardia cancer cases, and 471 population-based controls. Pyrosequencing typed the GSTP1 Ile105Val polymorphism, while multiplex PCR detected GSTM1 and GSTT1 deletions. Logistic regression modeling estimated odds ratios (ORs) with 95% confidence intervals (CIs). None of the studied polymorphisms were related to the risk of esophageal adenocarcinoma, but the variant GSTP1 Val(105) allele was associated with an increased risk of esophageal squamous cell carcinoma (OR = 1.7; 95% CI 1.0-2.9) and tended to be weakly, positively linked to cardia cancer (OR = 1.4; 95% CI 0.9-2.1). Finally, we performed a meta-analysis and found that GSTP1 polymorphism seems to be associated with the risk of esophageal squamous cell carcinoma among Caucasian population (OR = 1.4; 95% CI 1.0-2.2; p value for heterogeneity test 0.34).
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var gene transcription dynamics in Plasmodium falciparum patient isolates.
Mol. Biochem. Parasitol.
PUBLISHED: 02-03-2009
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A major feature of Plasmodium falciparum parasitized red blood cells (pRBC) is their capacity to sequester in the microcirculation. The binding is mediated by PfEMP1 (P. falciparum erythrocyte membrane protein 1), a variable protein encoded by the var gene family. P. falciparum avoids the host antibody response generated against previously used variants by switching the expression of PfEMP1, which may affect the disease outcome. We have here studied var gene transcription over time within the life cycle of the parasite by semi-quantitative PCR and sequencing by employing three sets of degenerate primers to the 5-prime end of the var genes (corresponding to the DBL1alpha-domain). To accurately determine transcript levels, subsequent in-depth analysis was made by amplifying the 10 most frequently expressed var sequences identified in each developmental stage by quantitative PCR (Q-PCR). The maximum peak in var gene transcription seems to vary in time among parasites. In five out of seven parasites, var gene transcription was found to be higher or equal at 22-26h post-invasion compared to 4-10h post-invasion. Our data indicate that the intra-isolate var gene transcription dominance order may change between different developmental stages. The transcription of var genes in field isolates is more complex than in laboratory strains and often changes after in vitro adaption of the parasite. By using semi-quantitative PCR employing degenerate primers combined with quantitative-PCR using specific primers it is possible to monitor var gene transcription in detail during the life cycle of the parasite. The work presented here suggests that trophozoite pRBC is likely to be the optimal source of RNA for predicting the translated var gene species.
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The effect of statins on acute and long-term outcome after ischemic stroke in the elderly.
Am J Geriatr Pharmacother
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Although treatment with statins has produced beneficial effects when used as secondary prevention, its primary protective role is still somewhat controversial. Moreover, few studies have evaluated the effect of statins in older patients with stroke.
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Comparative genomic analysis of human infective Trypanosoma cruzi lineages with the bat-restricted subspecies T. cruzi marinkellei.
BMC Genomics
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Trypanosoma cruzi marinkellei is a bat-associated parasite of the subgenus Schizotrypanum and it is regarded as a T. cruzi subspecies. Here we report a draft genome sequence of T. c. marinkellei and comparison with T. c. cruzi. Our aims were to identify unique sequences and genomic features, which may relate to their distinct niches.
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Reproducibility and accuracy of robot-assisted laparoscopic fertility sparing radical trachelectomy.
Gynecol. Oncol.
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To assess the accuracy and reproducibility of robot-assisted laparoscopic abdominal fertility sparing radical trachelectomy in women with early stage cervical cancer.
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Comparative evaluation of treatment with low-dose aspirin plus dipyridamole versus aspirin only in patients with acute ischaemic stroke.
BMC Neurol
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Previous studies have suggested that pre-stroke treatment with low-dose aspirin (A) could reduce the severity of acute ischaemic stroke, but less is known on the effect of pre-stroke treatment with a combination of aspirin and dipyridamole (A + D) and post-stroke effects of these drugs. The aim of the present study was to evaluate the effect of this drug combination on acute and long-term prognosis of ischaemic stroke.
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Multiple mitochondrial introgression events and heteroplasmy in trypanosoma cruzi revealed by maxicircle MLST and next generation sequencing.
PLoS Negl Trop Dis
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Mitochondrial DNA is a valuable taxonomic marker due to its relatively fast rate of evolution. In Trypanosoma cruzi, the causative agent of Chagas disease, the mitochondrial genome has a unique structural organization consisting of 20-50 maxicircles (?20 kb) and thousands of minicircles (0.5-10 kb). T. cruzi is an early diverging protist displaying remarkable genetic heterogeneity and is recognized as a complex of six discrete typing units (DTUs). The majority of infected humans are asymptomatic for life while 30-35% develop potentially fatal cardiac and/or digestive syndromes. However, the relationship between specific clinical outcomes and T. cruzi genotype remains elusive. The availability of whole genome sequences has driven advances in high resolution genotyping techniques and re-invigorated interest in exploring the diversity present within the various DTUs.
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Characterization of the viral microbiome in patients with severe lower respiratory tract infections, using metagenomic sequencing.
PLoS ONE
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The human respiratory tract is heavily exposed to microorganisms. Viral respiratory tract pathogens, like RSV, influenza and rhinoviruses cause major morbidity and mortality from respiratory tract disease. Furthermore, as viruses have limited means of transmission, viruses that cause pathogenicity in other tissues may be transmitted through the respiratory tract. It is therefore important to chart the human virome in this compartment. We have studied nasopharyngeal aspirate samples submitted to the Karolinska University Laboratory, Stockholm, Sweden from March 2004 to May 2005 for diagnosis of respiratory tract infections. We have used a metagenomic sequencing strategy to characterize viruses, as this provides the most unbiased view of the samples. Virus enrichment followed by 454 sequencing resulted in totally 703,790 reads and 110,931 of these were found to be of viral origin by using an automated classification pipeline. The snapshot of the respiratory tract virome of these 210 patients revealed 39 species and many more strains of viruses. Most of the viral sequences were classified into one of three major families; Paramyxoviridae, Picornaviridae or Orthomyxoviridae. The study also identified one novel type of Rhinovirus C, and identified a number of previously undescribed viral genetic fragments of unknown origin.
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What is Visualize?

JoVE Visualize is a tool created to match the last 5 years of PubMed publications to methods in JoVE's video library.

How does it work?

We use abstracts found on PubMed and match them to JoVE videos to create a list of 10 to 30 related methods videos.

Video X seems to be unrelated to Abstract Y...

In developing our video relationships, we compare around 5 million PubMed articles to our library of over 4,500 methods videos. In some cases the language used in the PubMed abstracts makes matching that content to a JoVE video difficult. In other cases, there happens not to be any content in our video library that is relevant to the topic of a given abstract. In these cases, our algorithms are trying their best to display videos with relevant content, which can sometimes result in matched videos with only a slight relation.