| 1. |
- Bensch, Staffan, et al.
(författare)
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The genome of Haemoproteus tartakovskyi and its relationship to human malaria parasites
- 2016
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Ingår i: Genome Biology and Evolution. - : Oxford University Press (OUP). - 1759-6653. ; 8:5, s. 73-1361
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Tidskriftsartikel (refereegranskat)abstract
- The phylogenetic relationships among hemosporidian parasites, including the origin of Plasmodium falciparum, the most virulent malaria parasite of humans, have been heavily debated for decades. Studies based on multiple-gene sequences have helped settle many of these controversial phylogenetic issues. However, denser taxon sampling and genome-wide analyses are needed to confidently resolve the evolutionay relationships among hemosporidian parasites. Genome sequences of several Plasmodium parasites are available but only for species infecting primates and rodents. To root the phylogenetic tree of Plasmodium, genomic data from related parasites of birds or reptiles are required. Here, we use a novel approach to isolate parasite DNA from microgametes and describe the first genome of a bird parasite in the sister genus to Plasmodium, Haemoproteus tartakovskyi Similar to Plasmodium parasites, H. tartakovskyi has a small genome (23.2 Mb, 5,990 genes) and a GC content (25.4%) closer to P. falciparum (19.3%) than to Plasmodium vivax (42.3%). Combined with novel transcriptome sequences of the bird parasite Plasmodium ashfordi, our phylogenomic analyses of 1,302 orthologous genes demonstrate that mammalian-infecting malaria parasites are monophyletic, thus rejecting the repeatedly proposed hypothesis that the ancestor of Laverania parasites originated from a secondary host shift from birds to humans. Genes and genomic features previously found to be shared between P. falciparum and bird malaria parasites, but absent in other mammal malaria parasites, are therefore signatures of maintained ancestral states. We foresee that the genome of H. tartakovskyi will open new directions for comparative evolutionary analyses of malarial adaptive traits.
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| 2. |
- Cardell, Lars-Olaf, et al.
(författare)
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TOTALL: high cost of allergic rhinitis-a national Swedish population-based questionnaire study.
- 2016
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Ingår i: NPJ primary care respiratory medicine. - : Springer Science and Business Media LLC. - 2055-1010. ; 26
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Tidskriftsartikel (refereegranskat)abstract
- Allergic rhinitis is a global illness with a well-recognised impact on quality of life and work performance. Comparatively little is known about the extent of its economic impact on society. The TOTALL study estimates the total cost of allergic rhinitis using a sample representing the entire Swedish population of working age. A questionnaire focused on allergic rhinitis was mailed out to a random population of Swedish residents, aged 18-65 years. Health-care contacts, medications, absenteeism (absence from work) and presenteeism (reduced working capacity at work) were assessed, and the direct and indirect costs of allergic rhinitis were calculated. Medication use was evaluated in relation to the ARIA guidelines. In all, 3,501 of 8,001 (44%) answered the questionnaire, and 855 (24%) of these reported allergic rhinitis. The mean annual direct and indirect costs because of allergic rhinitis were €210.3 and €750.8, respectively, resulting in a total cost of €961.1 per individual/year. Presenteeism represented 70% of the total cost. Antihistamines appear to be used in excess in relation to topical steroids, and the use of nasal decongestants was alarmingly high. The total cost of allergic rhinitis in Sweden, with a population of 9.5 million, was estimated at €1.3 billion annually. These unexpectedly high costs could be related to the high prevalence of disease, in combination with the previously often underestimated indirect costs. Improved adherence to guidelines might ease the economic burden on society.
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| 3. |
- Chapman, Joanne R., et al.
(författare)
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The Evolution of Innate Immune Genes : Purifying and Balancing Selection on beta-Defensins in Waterfowl
- 2016
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Ingår i: Molecular biology and evolution. - : Oxford University Press (OUP). - 0737-4038 .- 1537-1719. ; 33:12, s. 3075-3087
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Tidskriftsartikel (refereegranskat)abstract
- In disease dynamics, high immune gene diversity can confer a selective advantage to hosts in the face of a rapidly evolving and diverse pathogen fauna. This is supported empirically for genes involved in pathogen recognition and signalling. In contrast, effector genes involved in pathogen clearance may be more constrained. beta-Defensins are innate immune effector genes; their main mode of action is via disruption of microbial membranes. Here, five beta-defensin genes were characterized in mallards (Anas platyrhynchos) and other waterfowl; key reservoir species for many zoonotic diseases. All five genes showed remarkably low diversity at the individual-, population-, and species-level. Furthermore, there was widespread sharing of identical alleles across species divides. Thus, specific beta-defensin alleles were maintained not only spatially but also over long temporal scales, with many amino acid residues being fixed across all species investigated. Purifying selection to maintain individual, highly efficacious alleles was the primary evolutionary driver of these genes in waterfowl. However, we also found evidence for balancing selection acting on the most recently duplicated beta-defensin gene (AvBD3b). For this gene, we found that amino acid replacements were more likely to be radical changes, suggesting that duplication of beta-defensin genes allows exploration of wider functional space. Structural conservation to maintain function appears to be crucial for avian beta-defensin effector molecules, resulting in low tolerance for new allelic variants. This contrasts with other types of innate immune genes, such as receptor and signalling molecules, where balancing selection to maintain allelic diversity has been shown to be a strong evolutionary force.
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| 4. |
- Garcia-Longoria, Luz, et al.
(författare)
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Detecting transmission areas of malaria parasites in a migratory bird species.
- 2015
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Ingår i: Parasitology. - 1469-8161. ; 142:9, s. 1215-1220
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Tidskriftsartikel (refereegranskat)abstract
- The identification of the regions where vector-borne diseases are transmitted is essential to study transmission patterns and to recognize future changes in environmental conditions that may potentially influence the transmission areas. SGS1, one of the lineages of Plasmodium relictum, is known to have active transmission in tropical Africa and temperate regions of Europe. Nuclear sequence data from isolates infected with SGS1 (based on merozoite surface protein 1 (MSP1) allelic diversity) have provided new insights on the distribution and transmission areas of these allelic variants. For example, MSP1 alleles transmitted in Africa differ from those transmitted in Europe, suggesting the existence of two populations of SGS1 lineages. However, no study has analysed the distribution of African and European transmitted alleles in Afro-Palearctic migratory birds. With this aim, we used a highly variable molecular marker to investigate whether juvenile house martins become infected in Europe before their first migration to Africa. We explored the MSP1 allelic diversity of P. relictum in adult and juvenile house martins. We found that juveniles were infected with SGS1 during their first weeks of life, confirming active transmission of SGS1 to house martins in Europe. Moreover, we found that all the juveniles and most of adults were infected with one European transmitted MSP1 allele, whereas two adult birds were infected with two African transmitted MSP1 alleles. These findings suggest that house martins are exposed to different strains of P. relictum in their winter and breeding quarters.
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| 5. |
- Gustafsson, O., et al.
(författare)
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Reversing air-source heat pumps - Noise at defrost initiation and a noise reducing strategy
- 2016
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Ingår i: International Journal of Refrigeration. - : Elsevier BV. - 0140-7007 .- 1879-2081. ; 62, s. 137-144
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Tidskriftsartikel (refereegranskat)abstract
- With the increasing use of air source heat pumps, noise disturbance can be a barrier for further market growth and acceptance. Both steady state noise level and noise events influence reported noise disturbance. In this study one of the transient noise events was investigated: the noise initiated when the heat pump shifts to defrost mode. The results show that noise from a heat pump at defrost initiation was strongly dependent on the pressure differences in the system at the time of the shift. A reduced pressure difference resulted in a lower noise level. A control strategy that adds an idling time for the heat pump just before the shift of the 4-way valve is therefore suggested. This will have a small negative effect (<3%) on the heat capacity of the heat pump but the effect upon the COP will be negligible. (C) 2016 Elsevier Ltd and International Institute of Refrigeration. All rights reserved.
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| 6. |
- Hellgren, Olof
(författare)
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Allelic variation at innate immune genes (avian beta-defensins), within a natural population of great tits
- 2015
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Ingår i: Journal of Avian Biology. - : Wiley. - 0908-8857. ; 46:1, s. 113-118
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Tidskriftsartikel (refereegranskat)abstract
- In order to fully understand pathogen induced natural variation in fitness in wild animal populations it is important to identify and study the degree of non-synonymous alleles in genes that code for components of the immune system. This study investigates the degree of natural genetic variation at 6 innate immune genes belonging to the -defensin family within a single population of birds, the great tits Parus major. In 40 adult individuals, all belonging to the same local population in Wytham Woods, Oxford, UK, screened across 6 different -defensin genes, all but one individual showed non-synonymous heterozygosity within the exon coding for the mature defensin peptide. The non-synonomous variation was thus associated with the part of the defensin gene that directly interacts with potential pathogens. Within the sample, 31 different genotypes were identified across the 6 different loci. Much of the found allelic variation affected the amino acid composition, which in turn alter the net charge and hydrophilicity of the produced peptide; properties associated with the efficiency of binding to and rupture pathogens. This study demonstrates that non-synonymous genetic variation exists at -defensins genes, a part of the immune system that forms an important first line of defence against various pathogens. Understanding the degree of underlying genetic variation at different parts of the immune system will help achieve a holistic view of the reasons behind individual variation in pathogen susceptibility, as well as why individuals are affected differently once they become infected.
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| 7. |
- Hellgren, Olof, et al.
(författare)
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De novo synthesis of thiamine (vitamin B1) is the ancestral state in Plasmodium parasites – evidence from avian haemosporidians
- 2018
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Ingår i: Parasitology. - 0031-1820. ; 145:8, s. 1084-1089
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Tidskriftsartikel (refereegranskat)abstract
- Parasites often have reduced genomes as their own genes become redundant when utilizing their host as a source of metabolites, thus losing their own de novo production of metabolites. Primate malaria parasites can synthesize vitamin B1 (thiamine) de novo but rodent malaria and other genome-sequenced apicomplexans cannot, as the three essential genes responsible for this pathway are absent in their genomes. The unique presence of functional thiamine synthesis genes in primate malaria parasites and their sequence similarities to bacterial orthologues, have led to speculations that this pathway was horizontally acquired from bacteria. Here we show that the genes essential for the de novo synthesis of thiamine are found also in avian Plasmodium species. Importantly, they are also present in species phylogenetically basal to all mammalian and avian Plasmodium parasites, i.e. Haemoproteus. Furthermore, we found that these genes are expressed during the blood stage of the avian malaria infection, indicating that this metabolic pathway is actively transcribed. We conclude that the ability to synthesize thiamine is widespread among haemosporidians, with a recent loss in the rodent malaria species.
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| 8. |
- Hellgren, Olof, et al.
(författare)
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De novo synthesis of thiamine (vitamin B1) is the ancestral state in Plasmodium parasites – evidence from avian haemosporidians
- 2017
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Ingår i: Parasitology. - : Cambridge University Press (CUP). - 0031-1820 .- 1469-8161. ; 145:8, s. 1084-1089
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Tidskriftsartikel (refereegranskat)abstract
- Parasites often have reduced genomes as their own genes become redundant when utilizing their host as a source of metabolites, thus losing their own de novo production of metabolites. Primate malaria parasites can synthesize vitamin B1 (thiamine) de novo but rodent malaria and other genome-sequenced apicomplexans cannot, as the three essential genes responsible for this pathway are absent in their genomes. The unique presence of functional thiamine synthesis genes in primate malaria parasites and their sequence similarities to bacterial orthologues, have led to speculations that this pathway was horizontally acquired from bacteria. Here we show that the genes essential for the de novo synthesis of thiamine are found also in avian Plasmodium species. Importantly, they are also present in species phylogenetically basal to all mammalian and avian Plasmodium parasites, i.e. Haemoproteus. Furthermore, we found that these genes are expressed during the blood stage of the avian malaria infection, indicating that this metabolic pathway is actively transcribed. We conclude that the ability to synthesize thiamine is widespread among haemosporidians, with a recent loss in the rodent malaria species.
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| 9. |
- Hellgren, Olof, et al.
(författare)
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Global phylogeography of the avian malaria pathogen Plasmodium relictum based on MSP1 allelic diversity
- 2015
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Ingår i: Ecography. - : Wiley. - 1600-0587 .- 0906-7590. ; 38:8, s. 842-850
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Tidskriftsartikel (refereegranskat)abstract
- Knowing the genetic variation that occurs in pathogen populations and how it is distributed across geographical areas is essential to understand parasite epidemiology, local patterns of virulence, and evolution of host-resistance. In addition, it is important to identify populations of pathogens that are evolutionarily independent and thus free' to adapt to hosts and environments. Here, we investigated genetic variation in the globally distributed, highly invasive avian malaria parasite Plasmodium relictum, which has several distinctive mitochondrial haplotyps (cyt b lineages, SGS1, GRW11 and GRW4). The phylogeography of P. relictum was accessed using the highly variable nuclear gene merozoite surface protein 1 (MSP1), a gene linked to the invasion biology of the parasite. We show that the lineage GRW4 is evolutionarily independent of GRW11 and SGS1 whereas GRW11 and SGS1 share MSP1 alleles and thus suggesting the presence of two distinct species (GRW4 versus SGS1 and GRW11). Further, there were significant differences in the global distribution of MSP1 alleles with differences between GRW4 alleles in the New and the Old World. For SGS1, a lineage formerly believed to have both tropical and temperate transmission, there were clear differences in MSP1 alleles transmitted in tropical Africa compared to the temperate regions of Europe and Asia. Further, we highlight the occurrence of multiple MSP1 alleles in GRW4 isolates from the Hawaiian Islands, where the parasite has contributed to declines and extinctions of endemic forest birds since it was introduced. This study stresses the importance of multiple independent loci for understanding patterns of transmission and evolutionary independence across avian malaria parasites.
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| 10. |
- Huang, Xi, et al.
(författare)
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The success of sequence capture in relation to phylogenetic distance from a reference genome : a case study of avian haemosporidian parasites
- 2018
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Ingår i: International Journal for Parasitology. - : Elsevier BV. - 0020-7519. ; 48:12, s. 947-954
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Tidskriftsartikel (refereegranskat)abstract
- Genomic sequencing of avian haemosporidian parasites (Haemosporida) has been challenging due to excessive contamination from host DNA. In this study, we developed a cost-effective protocol to obtain parasite sequences from naturally infected birds, based on targeted sequence capture and next generation sequencing. With the genomic data of Haemoproteus tartakovskyi as a reference, we successfully sequenced up to 1000 genes from each of the 15 selected samples belonging to nine different cytochrome b lineages, eight of which belong to Haemoproteus and one to Plasmodium. The targeted sequences were enriched to ∼104-fold, and mixed infections were identified as well as the proportions of each mixed lineage. We found that the total number of reads and the proportions of exons sequenced decreased when the parasite lineage became more divergent from the reference genome. For each of the samples, the recovery of sequences from different exons varied with the function and GC content of the exon. From the obtained sequences, we detected within-lineage variation in both mitochondrial and nuclear genes, which may be a result of local adaptation to different host species and environmental conditions. This targeted sequence capture protocol can be applied to a broader range of species and will open a new door for further studies on disease diagnostics and comparative analysis of haemosporidians evolution.
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| 11. |
- Huang, Xi, et al.
(författare)
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Within-Lineage Divergence of Avian Haemosporidians : A Case Study to Reveal the Origin of a Widespread Haemoproteus Parasite
- 2019
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Ingår i: The Journal of Parasitology. - 0022-3395. ; 105:3, s. 414-422
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Tidskriftsartikel (refereegranskat)abstract
- Avian haemosporidian parasites are particularly diverse and widespread. To date, more than 3,000 distinct cytochrome b lineages have been recorded, of which some present extremely wide geographical distributions, even including multiple continents. Whether these isolates represent one or several cryptic species remains unknown. Here we carried out a case study of SISKIN1, a common haemosporidian parasite lineage belonging to the morphologically described species Haemoproteus tartakovskyi. To shed light on its evolutionary origin, we investigated the divergence between SISKIN1 isolates obtained from siskins and redpolls in Europe (Russia and Sweden) and house finches in North America (Mexico). First, we used sequence capture of a small data set (2 Russian isolates and 1 Mexican isolate) to investigate the genetic structure based on the full-length mitochondrial genome and ∼1,000 genes. The mitochondrial genomes of Russian isolates were identical with each other but differed from the Mexican one at 6 positions. The nuclear divergence between Russian and Mexican isolates was on average 2.8%, close to what has been observed between 2 species of malaria parasites that respectively infect humans (Plasmodium falciparum) and gorillas (Plasmodium praefalciparum). Second, we used the expanded data set (15 samples in total) to investigate the genetic structure in 3 genes known to be involved in host invasion. The European isolates were identical across all sequenced genes, whereas the Mexican isolates were highly diverse. The lack of shared alleles between European and Mexican populations suggests that they might have diverged in isolation without gene flow. From the MalAvi database we examined the lineages most similar to the SISKIN1 barcode fragment (part of the cyt b gene) and found that most of them had been recorded in North and South America. This suggests that the lineage SISKIN1 originated in North America and subsequently spread to Europe. Our analyses support that the cyt b gene barcoding region is a useful marker for identification of avian haemosporidian lineages that can classify them into clusters of closely related parasites, but to further investigate species limits and evolutionary history, molecular data from multiple faster-evolving genes are required.
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| 12. |
- Ricklefs, Robert E, et al.
(författare)
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Avian migration and the distribution of malaria parasites in New World passerine birds
- 2017
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Ingår i: Journal of Biogeography. - : Wiley. - 0305-0270 .- 1365-2699. ; 44:5, s. 1113-1123
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Tidskriftsartikel (refereegranskat)abstract
- Aim: Migrating birds transport their parasites, often over long distances, but little is known about the transfer of these parasites to resident hosts in either the wintering or breeding ranges of the migratory host populations. We investigated the haemosporidian parasite faunas of migratory and resident birds to determine connections among distant parasite faunas, plausibly brought about by migratory host populations. Location: Samples were obtained, primarily during or shortly after the local breeding season, throughout the Americas, from the United States through the Caribbean Basin and into northern South America. Methods: Infections were identified by PCR and sequencing of parasite DNA in avian blood samples. The analyses were based on c. 4700 infections representing 79 parasite lineages of Plasmodium and Haemoproteus spp. Geographical connections of lineages between regions in the Americas were compared to those in the Euro-African migration system, where migration distances are longer for many host species and the migrant and resident avifaunas in the wintering areas are phylogenetically more divergent. Results: Haemosporidian lineages exhibited considerable variation in distribution in the Americas, and patterns of distribution differ markedly between the Americas and the Euro-African migration system. In particular, few lineages were recovered from resident species in both temperate and tropical latitudes, particularly in the Euro-African system, in which a large proportion of lineages were restricted to migrants. Parasite lineages in the Euro-African system exhibited considerable phylogenetic conservatism in their distributions, that is, a tendency of related lineages to exhibit similar geographical distributions. In contrast, clades of parasites in the Americas displayed more geographical diversity, with four of 12 clades exhibiting all four of the distribution types representing the combinations of resident and migrant host species in both temperate and tropical latitudes. Main conclusions: Long-distance migrants connect communities of avian haemosporidian parasites in breeding and wintering areas with disparate avifaunas and different vector communities. The degree of parasite lineage sharing between migrants and residents in breeding and wintering areas appears to reflect, to a large degree, the taxonomic similarity of migrants to the resident species in both areas.
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| 13. |
- Simonson, Oscar E., et al.
(författare)
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In Vivo Effects of Mesenchymal Stromal Cells in Two Patients With Severe Acute Respiratory Distress Syndrome
- 2015
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Ingår i: Stem Cells Translational Medicine. - : Oxford University Press (OUP). - 2157-6564 .- 2157-6580. ; 4:10, s. 1199-1213
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Tidskriftsartikel (refereegranskat)abstract
- Mesenchymal stromal cells (MSCs) have been investigated as a treatment for various inflammatory diseases because of their immunomodulatory and reparative properties. However, many basic questions concerning their mechanisms of action after systemic infusion remain unanswered. We performed a detailed analysis of the immunomodulatory properties and proteomic profile of MSCs systemically administered to two patients with severe refractory acute respiratory distress syndrome (ARDS) on a compassionate use basis and attempted to correlate these with in vivo anti-inflammatory actions. Both patients received 2 x 10(6) cells per kilogram, and each subsequently improved with resolution of respiratory, hemodynamic, and multiorgan failure. In parallel, a decrease was seen in multiple pulmonary and systemic markers of inflammation, including epithelial apoptosis, alveolar-capillary fluid leakage, and proinflammatory cytokines, microRNAs, and chemokines. In vitro studies of the MSCs demonstrated a broad anti-inflammatory capacity, including suppression of T-cell responses and induction of regulatory phenotypes in T cells, monocytes, and neutrophils. Some of these in vitro potency assessments correlated with, and were relevant to, the observed in vivo actions. These experiences highlight both the mechanistic information that can be gained from clinical experience and the value of correlating in vitro potency assessments with clinical effects. The findings also suggest, but do not prove, a beneficial effect of lung protective strategies using adoptively transferred MSCs in ARDS. Appropriate randomized clinical trials are required to further assess any potential clinical efficacy and investigate the effects on in vivo inflammation. STEM CELLS TRANSLATIONAL MEDICINE 2015;4:1199-1213
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| 14. |
- Tinnert, Jon, et al.
(författare)
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Population genetic structure, differentiation, and diversity in Tetrix subulata pygmy grasshoppers : roles of population size and immigration
- 2016
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Ingår i: Ecology and Evolution. - : Wiley. - 2045-7758. ; 6:21, s. 7831-7846
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Tidskriftsartikel (refereegranskat)abstract
- Genetic diversity within and among populations and species is influenced by complex demographic and evolutionary processes. Despite extensive research, there is no consensus regarding how landscape structure, spatial distribution, gene flow, and population dynamics impact genetic composition of natural populations. Here, we used amplified fragment length polymorphisms (AFLPs) to investigate effects of population size, geographic isolation, immigration, and gene flow on genetic structure, divergence, and diversity in populations of Tetrix subulata pygmy grasshoppers (Orthoptera: Tetrigidae) from 20 sampling locations in southern Sweden. Analyses of 1564 AFLP markers revealed low to moderate levels of genetic diversity (PPL=59.5-90.1; Hj=0.23-0.32) within and significant divergence among sampling localities. This suggests that evolution of functional traits in response to divergent selection is possible and that gene flow is restricted. Genetic diversity increased with population size and with increasing proportion of long-winged phenotypes (a proxy of recent immigration) across populations on the island of oland, but not on the mainland. Our data further suggested that the open water separating oland from the mainland acts as a dispersal barrier that restricts migration and leads to genetic divergence among regions. Isolation by distance was evident for short interpopulation distances on the mainland, but gradually disappeared as populations separated by longer distances were included. Results illustrate that integrating ecological and molecular data is key to identifying drivers of population genetic structure in natural populations. Our findings also underscore the importance of landscape structure and spatial sampling scheme for conclusions regarding the role of gene flow and isolation by distance.
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| 15. |
- Videvall, Elin, et al.
(författare)
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Major shifts in gut microbiota during development and its relationship to growth in ostriches
- 2019
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Ingår i: Molecular Ecology. - : Wiley. - 0962-1083 .- 1365-294X. ; 28:10, s. 2653-2667
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Tidskriftsartikel (refereegranskat)abstract
- The development of gut microbiota during ontogeny is emerging as an important process influencing physiology, immunity and fitness in vertebrates. However, knowledge of how bacteria colonize the juvenile gut, how this is influenced by changes in the diversity of gut bacteria and to what extent this influences host fitness, particularly in nonmodel organisms, is lacking. Here we used 16S rRNA gene sequencing to describe the successional development of the faecal microbiome in ostriches (Struthio camelus, n = 66, repeatedly sampled) over the first 3 months of life and its relationship to growth. We found a gradual increase in microbial diversity with age that involved multiple colonization and extinction events and a major taxonomic shift in bacteria that coincided with the cessation of yolk absorption. Comparisons with the microbiota of adults (n = 5) revealed that the chicks became more similar in their microbial diversity and composition to adults as they aged. There was a five-fold difference in juvenile growth during development, and growth during the first week of age was strongly positively correlated with the abundance of the genus Bacteroides and negatively correlated with Akkermansia. After the first week, the abundances of six phylogenetically diverse families (Peptococcaceae, S24-7, Verrucomicrobiae, Anaeroplasmataceae, Streptococcaceae, Methanobacteriaceae) were associated with subsequent reductions in chick growth in an age-specific and transient manner. These results have broad implications for our understanding of the development of gut microbiota and its associations with animal growth.
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| 16. |
- Videvall, Elin, et al.
(författare)
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The Avian Transcriptome Response to Malaria Infection.
- 2015
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Ingår i: Molecular biology and evolution. - : Oxford University Press (OUP). - 0737-4038 .- 1537-1719. ; 32:5, s. 1255-1267
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Tidskriftsartikel (refereegranskat)abstract
- Malaria parasites are highly virulent pathogens which infect a wide range of vertebrates. Despite their importance, the way different hosts control and suppress malaria infections remains poorly understood. With recent developments in next generation sequencing techniques, however, it is now possible to quantify the response of the entire transcriptome to infections. We experimentally infected Eurasian siskins (Spinus spinus) with avian malaria parasites (Plasmodium ashfordi), and used high-throughput RNA-sequencing to measure the avian transcriptome in blood collected before infection (day 0), during peak parasitemia (day 21 post infection), and when parasitemia was decreasing (day 31). We found considerable differences in the transcriptomes of infected and uninfected individuals, with a large number of genes differentially expressed during both peak and decreasing parasitemia stages. These genes were overrepresented among functions involved in the immune system, stress response, cell death regulation, metabolism, and telomerase activity. Comparative analyses of the differentially expressed genes in our study to those found in other hosts of malaria (human and mouse), revealed a set of genes that are potentially involved in highly conserved evolutionary responses to malaria infection. By using RNA-sequencing we gained a more complete view of the host response, and were able to pinpoint not only well documented host genes, but also unannotated genes with clear significance during infection, such as microRNAs. This study shows how the avian blood transcriptome shifts in response to malaria infection, and we believe it will facilitate further research into the diversity of molecular mechanisms that hosts utilize to fight malaria infections.
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| 17. |
- Videvall, Elin, et al.
(författare)
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The transcriptome of the avian malaria parasite Plasmodium ashfordi displays host-specific gene expression
- 2017
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Ingår i: Molecular Ecology. - : Wiley. - 0962-1083 .- 1365-294X.
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Tidskriftsartikel (refereegranskat)abstract
- Malaria parasites (Plasmodium spp.) include some of the world's most widespread and virulent pathogens. Our knowledge of the molecular mechanisms these parasites use to invade and exploit hosts other than mice and primates is, however, extremely limited. It is therefore imperative to characterize transcriptome-wide gene expression from non-model malaria parasites and how this varies across host individuals. Here, we used high-throughput Illumina RNA-sequencing on blood from wild-caught Eurasian siskins experimentally infected with a clonal strain of the avian malaria parasite Plasmodium ashfordi (lineage GRW2). By using a multi-step approach to filter out host transcripts, we successfully assembled the blood-stage transcriptome of P. ashfordi. A total of 11 954 expressed transcripts were identified, and 7 860 were annotated with protein information. We quantified gene expression levels of all parasite transcripts across three hosts during two infection stages – peak and decreasing parasitemia. Interestingly, parasites from the same host displayed remarkably similar expression profiles during different infection stages, but showed large differences across hosts, indicating that P. ashfordi may adjust its gene expression to specific host individuals. We further show that the majority of transcripts are most similar to the human parasite Plasmodium falciparum, and a large number of red blood cell invasion genes were discovered, suggesting evolutionary conserved invasion strategies between mammalian and avian Plasmodium. The transcriptome of P. ashfordi and its host-specific gene expression advances our understanding of Plasmodium plasticity and is a valuable resource as it allows for further studies analysing gene evolution and comparisons of parasite gene expression.
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