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Johan Ankarklev

Bio: Johan Ankarklev is an academic researcher from Stockholm University. The author has contributed to research in topics: Giardia & Gene. The author has an hindex of 13, co-authored 22 publications receiving 1371 citations. Previous affiliations of Johan Ankarklev include Uppsala University & Karolinska Institutet.

Papers
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Journal ArticleDOI
TL;DR: This Review discusses recent discoveries in the molecular cell biology and pathogenesis of G. intestinalis and suggests that the disease mechanisms are still poorly understood.
Abstract: The eukaryotic intestinal parasite Giardia intestinalis was first described in 1681, when Antonie van Leeuwenhoek undertook a microscopic examination of his own diarrhoeal stool. Nowadays, although G. intestinalis is recognized as a major worldwide contributor to diarrhoeal disease in humans and other mammals, the disease mechanisms are still poorly understood. Owing to its reduced complexity and proposed early evolutionary divergence, G. intestinalis is used as a model eukaryotic system for studying many basic cellular processes. In this Review we discuss recent discoveries in the molecular cell biology and pathogenesis of G. intestinalis.

337 citations

Journal ArticleDOI
TL;DR: 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.
Abstract: 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 16× 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.

260 citations

Journal ArticleDOI
TL;DR: These findings provide a mechanistic link between EVs and vascular dysfunction during malaria infection and show that EVs are efficiently internalized by endothelial cells, where the miRNA-Argonaute 2 complexes modulate target gene expression and barrier properties.
Abstract: Malaria remains one of the greatest public health challenges worldwide, particularly in sub-Saharan Africa. The clinical outcome of individuals infected with Plasmodium falciparum parasites depends on many factors including host systemic inflammatory responses, parasite sequestration in tissues and vascular dysfunction. Production of pro-inflammatory cytokines and chemokines promotes endothelial activation as well as recruitment and infiltration of inflammatory cells, which in turn triggers further endothelial cell activation and parasite sequestration. Inflammatory responses are triggered in part by bioactive parasite products such as hemozoin and infected red blood cell-derived extracellular vesicles (iRBC-derived EVs). Here we demonstrate that such EVs contain functional miRNA-Argonaute 2 complexes that are derived from the host RBC. Moreover, we show that EVs are efficiently internalized by endothelial cells, where the miRNA-Argonaute 2 complexes modulate target gene expression and barrier properties. Altogether, these findings provide a mechanistic link between EVs and vascular dysfunction during malaria infection.

174 citations

Journal ArticleDOI
TL;DR: Compared genomics of the three diverse Giardia intestinalis isolates P15, GS and WB to define a core proteome for this species complex and to identify lineage-specific genes were used to identify novel members of the VSP, NEK Kinase and HCMP gene families.
Abstract: 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. We identified 5012 protein coding genes, the majority of which are conserved compared to the previously sequenced genomes of the WB and GS strains in terms of microsynteny and sequence identity. Despite this, there is an unexpectedly large number of chromosomal rearrangements and several smaller structural changes that are present in all chromosomes. Novel members of the VSP, NEK Kinase and HCMP gene families were identified, which may reveal possible mechanisms for host specificity and new avenues for antigenic variation. We used comparative genomics of the three diverse Giardia intestinalis isolates P15, GS and WB to define a core proteome for this species complex and to identify lineage-specific genes. Extensive analyses of polymorphisms in the core proteome of Giardia revealed differential rates of divergence among cellular processes. Our results indicate that despite a well conserved core of genes there is significant genome variation between Giardia isolates, both in terms of gene content, gene polymorphisms, structural chromosomal variations and surface molecule repertoires. This study improves the annotation of the Giardia genomes and enables the identification of functionally important variation.

132 citations

Journal ArticleDOI
TL;DR: Results suggest that women are more exposed to T. gondii infection than men in China and argue for deeper investigations for the potential risk factors that threat the female populations.
Abstract: Toxoplasmosis is an important zoonotic parasitic disease worldwide. In immune competent individuals, Toxoplasma gondii preferentially infects tissues of central nervous systems, which might be an adding factor of certain psychiatric disorders. Congenital transmission of T. gondii during pregnancy has been regarded as a risk factor for the health of newborn infants. While in immune-compromised individuals, the parasite can cause life-threatening infections. This study aims to investigate the prevalence of T. gondii infection among clinically healthy individuals and patients with psychiatric disorders in China and to identify the potential risk factors related to the vulnerability of infection in the population. Serum samples from 2634 healthy individuals and 547 patients with certain psychiatric disorders in Changchun and Daqing in the northeast, and in Shanghai in the south of China were examined respectively for the levels of anti-T. gondii IgG by indirect ELISA and a direct agglutination assay. Prevalence of T. gondii infection in the Chinese population in respect of gender, age, residence and health status was systematically analyzed. The overall anti-T. gondii IgG prevalence in the study population was 12.3%. In the clinically healthy population 12.5% was sero-positive and in the group with psychiatric disorders 11.3% of these patients were positive with anti-T. gondii IgG. A significant difference (P = 0.004) was found between male and female in the healthy population, the seroprevalence was 10.5% in men versus 14.3% in women. Furthermore, the difference of T. gondii infection rate between male and female in the 20-19 year's group was more obvious, with 6.4% in male population and 14.6% in female population. A significant higher prevalence of T. gondii infection was observed in female in the clinically healthy population. No correlation was found between T. gondii infection and psychiatric disorders in this study. Results suggest that women are more exposed to T. gondii infection than men in China. The data argue for deeper investigations for the potential risk factors that threat the female populations.

122 citations


Cited by
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Journal ArticleDOI
TL;DR: The authors' efforts in characterizing the molecular epidemiology of giardiasis are compromised by the lack of case-control and longitudinal cohort studies and the sampling and testing of humans and animals living in the same community, the frequent occurrence of infections with mixed genotypes and subtypes.
Abstract: Summary: Molecular diagnostic tools have been used recently in assessing the taxonomy, zoonotic potential, and transmission of Giardia species and giardiasis in humans and animals. The results of these studies have firmly established giardiasis as a zoonotic disease, although host adaptation at the genotype and subtype levels has reduced the likelihood of zoonotic transmission. These studies have also identified variations in the distribution of Giardia duodenalis genotypes among geographic areas and between domestic and wild ruminants and differences in clinical manifestations and outbreak potentials of assemblages A and B. Nevertheless, our efforts in characterizing the molecular epidemiology of giardiasis and the roles of various animals in the transmission of human giardiasis are compromised by the lack of case-control and longitudinal cohort studies and the sampling and testing of humans and animals living in the same community, the frequent occurrence of infections with mixed genotypes and subtypes, and the apparent heterozygosity at some genetic loci for some G. duodenalis genotypes. With the increased usage of multilocus genotyping tools, the development of next-generation subtyping tools, the integration of molecular analysis in epidemiological studies, and an improved understanding of the population genetics of G. duodenalis in humans and animals, we should soon have a better appreciation of the molecular epidemiology of giardiasis, the disease burden of zoonotic transmission, the taxonomy status and virulences of various G. duodenalis genotypes, and the ecology of environmental contamination.

986 citations

01 Jan 2009
TL;DR: In this article, a review outlines the current understanding of miRNA target recognition in animals and discusses the widespread impact of miRNAs on both the expression and evolution of protein-coding genes.
Abstract: MicroRNAs (miRNAs) are endogenous ∼23 nt RNAs that play important gene-regulatory roles in animals and plants by pairing to the mRNAs of protein-coding genes to direct their posttranscriptional repression. This review outlines the current understanding of miRNA target recognition in animals and discusses the widespread impact of miRNAs on both the expression and evolution of protein-coding genes.

646 citations

Journal ArticleDOI
TL;DR: The gene distribution across lineages reflects the presence of anaerobic energy metabolism in the eukaryote common ancestor and differential loss during the specialization of some lineages to oxic niches, just as oxphos capabilities have been differentially lost in specialization to anoxic niches and the parasitic life-style.
Abstract: Major insights into the phylogenetic distribution, biochemistry, and evolutionary significance of organelles involved in ATP synthesis (energy metabolism) in eukaryotes that thrive in anaerobic environments for all or part of their life cycles have accrued in recent years. All known eukaryotic groups possess an organelle of mitochondrial origin, mapping the origin of mitochondria to the eukaryotic common ancestor, and genome sequence data are rapidly accumulating for eukaryotes that possess anaerobic mitochondria, hydrogenosomes, or mitosomes. Here we review the available biochemical data on the enzymes and pathways that eukaryotes use in anaerobic energy metabolism and summarize the metabolic end products that they generate in their anaerobic habitats, focusing on the biochemical roles that their mitochondria play in anaerobic ATP synthesis. We present metabolic maps of compartmentalized energy metabolism for 16 well-studied species. There are currently no enzymes of core anaerobic energy metabolism that are specific to any of the six eukaryotic supergroup lineages; genes present in one supergroup are also found in at least one other supergroup. The gene distribution across lineages thus reflects the presence of anaerobic energy metabolism in the eukaryote common ancestor and differential loss during the specialization of some lineages to oxic niches, just as oxphos capabilities have been differentially lost in specialization to anoxic niches and the parasitic life-style. Some facultative anaerobes have retained both aerobic and anaerobic pathways. Diversified eukaryotic lineages have retained the same enzymes of anaerobic ATP synthesis, in line with geochemical data indicating low environmental oxygen levels while eukaryotes arose and diversified.

638 citations

Journal ArticleDOI
TL;DR: Smart-seq2 as discussed by the authors improved reverse transcription, template switching and preamplification to increase both yield and length of cDNA libraries generated from individual cells, which have improved detection, coverage, bias and accuracy compared to Smart-seq libraries and are generated with off-the-shelf reagents at lower cost.
Abstract: Single-cell gene expression analyses hold promise for characterizing cellular heterogeneity, but current methods compromise on either the coverage, the sensitivity or the throughput. Here, we introduce Smart-seq2 with improved reverse transcription, template switching and preamplification to increase both yield and length of cDNA libraries generated from individual cells. Smart-seq2 transcriptome libraries have improved detection, coverage, bias and accuracy compared to Smart-seq libraries and are generated with off-the-shelf reagents at lower cost.

553 citations

01 Jan 1982
TL;DR: A pesar de los riesgos tan elevados que supone el contraer la toxoplasmosis for estos grupos and de que un individuo se pueda infectar después de una trasfusión sanguínea, ésta no es una enfermedad de declaración obligatoria.
Abstract: OFFARM 123 E reservorio principal de Toxoplasma gondii es el gato doméstico (Felis catus), que por medio de los ooquistes que elimina con las heces, disemina la infección en el medio ambiente pudiendo transmitirla a multitud de animales, al hombre o incluso a pájaros y peces. La infección causada por este parásito pasa, en el hombre sano, casi inadvertida, pero no sucede lo mismo en individuos inmunodeprimidos en los que puede llegar a provocar la muerte. También el contraer la toxoplasmosis durante el embarazo entraña para la mujer, y principalmente para su feto, daños que pueden ser fatales pudiendo ocasionar abortos espontáneos o daños irreversibles en el sistema nervioso central del neonato. A pesar de los riesgos tan elevados que supone el contraer la toxoplasmosis para estos grupos y de que un individuo se pueda infectar después de una trasfusión sanguínea, ésta no es una enfermedad de declaración obligatoria.

533 citations