| 1. |
- Zuntini, Alexandre R., et al.
(author)
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Phylogenomics and the rise of the angiosperms
- 2024
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In: NATURE. - 0028-0836 .- 1476-4687. ; 629, s. 843-850
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Journal article (peer-reviewed)abstract
- Angiosperms are the cornerstone of most terrestrial ecosystems and human livelihoods(1,2). A robust understanding of angiosperm evolution is required to explain their rise to ecological dominance. So far, the angiosperm tree of life has been determined primarily by means of analyses of the plastid genome(3,4). Many studies have drawn on this foundational work, such as classification and first insights into angiosperm diversification since their Mesozoic origins(5-7). However, the limited and biased sampling of both taxa and genomes undermines confidence in the tree and its implications. Here, we build the tree of life for almost 8,000 (about 60%) angiosperm genera using a standardized set of 353 nuclear genes(8). This 15-fold increase in genus-level sampling relative to comparable nuclear studies(9) provides a critical test of earlier results and brings notable change to key groups, especially in rosids, while substantiating many previously predicted relationships. Scaling this tree to time using 200 fossils, we discovered that early angiosperm evolution was characterized by high gene tree conflict and explosive diversification, giving rise to more than 80% of extant angiosperm orders. Steady diversification ensued through the remaining Mesozoic Era until rates resurged in the Cenozoic Era, concurrent with decreasing global temperatures and tightly linked with gene tree conflict. Taken together, our extensive sampling combined with advanced phylogenomic methods shows the deep history and full complexity in the evolution of a megadiverse clade.
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| 2. |
- Mortazavi, Susanne E., et al.
(author)
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Acquisition of complement fixing antibodies targeting Plasmodium falciparum merozoites in infants and their mothers in Uganda
- 2023
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In: Frontiers in Immunology. - 1664-3224. ; 14
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Journal article (peer-reviewed)abstract
- Background: Antibody-mediated complement fixation has previously been associated with protection against malaria in naturally acquired immunity. However, the process of early-life development of complement-fixing antibodies in infants, both in comparison to their respective mothers and to other immune parameters, remains less clear. Results: We measured complement-fixing antibodies in newborns and their mothers in a malaria endemic area over 5 years follow-up and found that infants’ complement-fixing antibody levels were highest at birth, decreased until six months, then increased progressively until they were similar to birth at five years. Infants with high levels at birth experienced a faster decay of complement-fixing antibodies but showed similar levels to the low response group of newborns thereafter. No difference was observed in antibody levels between infant cord blood and mothers at delivery. The same result was found when categorized into high and low response groups, indicating placental transfer of antibodies. Complement-fixing antibodies were positively correlated with total schizont-specific IgG and IgM levels in mothers and infants at several time points. At nine months, complement-fixing antibodies were negatively correlated with total B cell frequency and osteopontin concentrations in the infants, while positively correlated with atypical memory B cells and P. falciparum-positive atypical memory B cells. Conclusion: This study indicates that complement-fixing antibodies against P. falciparum merozoites are produced in the mothers and placentally-transferred, and they are acquired in infants over time during the first years of life. Understanding early life immune responses is crucial for developing a functional, long lasting malaria vaccine.
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| 3. |
- Mortazavi, Susanne E., et al.
(author)
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Osteopontin and malaria : no direct effect on parasite growth, but correlation with P. falciparum-specific B cells and BAFF in a malaria endemic area
- 2021
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In: BMC Microbiology. - : Springer Science and Business Media LLC. - 1471-2180. ; 21:1
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Journal article (peer-reviewed)abstract
- Background: The dysregulation of B cell activation is prevalent during naturally acquired immunity against malaria. Osteopontin (OPN), a protein produced by various cells including B cells, is a phosphorylated glycoprotein that participates in immune regulation and has been suggested to be involved in the immune response against malaria. Here we studied the longitudinal concentrations of OPN in infants and their mothers living in Uganda, and how OPN concentrations correlated with B cell subsets specific for P. falciparum and B cell activating factor (BAFF). We also investigated the direct effect of OPN on P. falciparum in vitro. Results: The OPN concentration was higher in the infants compared to the mothers, and OPN concentration in infants decreased from birth until 9 months. OPN concentration in infants during 9 months were independent of OPN concentrations in corresponding mothers. OPN concentrations in infants were inversely correlated with total atypical memory B cells (MBCs) as well as P. falciparum-specific atypical MBCs. There was a positive correlation between OPN and BAFF concentrations in both mothers and infants. When OPN was added to P. falciparum cultured in vitro, parasitemia was unaffected regardless of OPN concentration. Conclusions: The concentrations of OPN in infants were higher and independent of the OPN concentrations in corresponding mothers. In vitro, OPN does not have a direct effect on P. falciparum growth. Our correlation analysis results suggest that OPN could have a role in the B cell immune response and acquisition of natural immunity against malaria.
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| 4. |
- Fasanya, Adebimpe, et al.
(author)
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Anti-phosphatidylserine antibody levels are low in multigravid pregnant women in a malaria-endemic area in Nigeria, and do not correlate with anti-VAR2CSA antibodies
- 2023
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In: Frontiers in cellular and infection microbiology. - : Frontiers Media SA. - 2235-2988. ; 13
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Journal article (peer-reviewed)abstract
- Anemia is a common malaria-associated complication in pregnant women in endemic regions. Phosphatidylserine (PS) is exposed to the immune system during the massive destruction of red blood cells (RBCs) that accompany malaria, and antibodies against PS have been linked to anemia through destruction of uninfected RBCs. We determined levels of anti-PS IgG antibodies in pregnant women in Ibadan, Nigeria and correlated them to parameters of importance in development of anemia and immunity. Anti-PS correlated inversely with Packed Cell Volume (PCV), indicating that the antibodies could contribute to anemia. There was no correlation with anti-VAR2CSA IgG, haptoglobin or parasitemia, indicating that the modulation of anti-PS response is multifactorial in nature. Anti-PS levels were lowest in multigravidae compared to both primigravidae and secundigravidae and correlated inversely with age. In conclusion, lower levels of anti-PS in multigravidae could be beneficial in avoiding anemia.
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| 5. |
- Ivarsson, Anna Clara, et al.
(author)
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Head-to-head comparison of two loop-mediated isothermal amplification (LAMP) kits for diagnosis of malaria in a non-endemic setting
- 2023
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In: Malaria Journal. - 1475-2875. ; 22:1
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Journal article (peer-reviewed)abstract
- Background: Light microscopy and rapid diagnostic tests (RDT) have long been the recommended diagnostic methods for malaria. However, in recent years, loop-mediated isothermal amplification (LAMP) techniques have been shown to offer superior performance, in particular concerning low-grade parasitaemia, by delivering higher sensitivity and specificity with low laboratory capacity requirements in little more than an hour. In this study, the diagnostic performance of two LAMP kits were assessed head-to-head, compared to highly sensitive quantitative real time PCR (qPCR), in a non-endemic setting. Methods: In this retrospective validation study two LAMP kits; Alethia® Illumigene Malaria kit and HumaTurb Loopamp™ Malaria Pan Detection (PDT) kit, were evaluated head-to-head for detection of Plasmodium-DNA in 133 biobanked blood samples from suspected malaria cases at the Clinical Microbiology Laboratory of Region Skåne, Sweden to determine their diagnostic performance compared to qPCR. Results: Of the 133 samples tested, qPCR detected Plasmodium DNA in 41 samples (defined as true positives), and the two LAMP methods detected 41 and 37 of those, respectively. The results from the HumaTurb Loopamp™ Malaria PDT kit were in complete congruence with the qPCR, with a sensitivity of 100% (95% CI 91.40–100%) and specificity of 100% (95% CI 96.07–100%). The Alethia® Illumigene Malaria kit had a sensitivity of 90.24% (95% CI 76.87–97.28) and a specificity of 95.65% (95% CI 89.24–98.80) as compared to qPCR. Conclusions: This head-to-head comparison showed higher performance indicators of the HumaTurb Loopamp™ Malaria PDT kit compared to the Alethia® illumigene Malaria kit for detection of malaria.
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| 6. |
- Jongruamklang, Philaiphon, et al.
(author)
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Platelets inhibit erythrocyte invasion by Plasmodium falciparum at physiological platelet:erythrocyte ratios
- 2022
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In: Transfusion Medicine. - : Wiley. - 0958-7578 .- 1365-3148. ; 32:2, s. 168-174
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Journal article (peer-reviewed)abstract
- OBJECTIVE: To evaluate the effect of platelet:erythrocyte (P:E) ratios on Plasmodium falciparum erythrocyte invasion.BACKGROUND: Recent reports have shown that platelets are directly involved in the immune response towards P. falciparum during erythrocyte invasion. However, the literature both supports and conflicts with a role for platelets in limiting invasion. Also, the effect of platelet numbers on invasion (parasitemia) has not been thoroughly investigated.METHODS/MATERIALS: The P. falciparum strains FCR3S1.2 and W2mef were cultured with group O erythrocytes. The cultures were synchronised and supplemented with pooled platelets at P:E ratios ranging from 1:100 to 1:2. Parasitemia was measured at 40 h by flow cytometry and by microscopy of blood smears.RESULTS: A linear relationship was observed between reduced invasion and increased platelet numbers at P:E ratios ranging from 1:100 to 1:20. However, this effect was reversed at lower ratios (1:10-1:2). Microscopic evaluation revealed aggregation and attachment of platelets to erythrocytes, but not specifically to parasitised erythrocytes.CONCLUSION: We have shown that under physiological P:E ratios (approx. 1:10-1:40), platelets inhibited P. falciparum invasion in a dose-dependent manner. At ratios of 1:10 and below, platelets did not further increase the inhibitory effect and, although the trend was reversed, inhibition was still maintained.
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| 7. |
- Reddy, Sreenivasulu B., et al.
(author)
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Direct contact between Plasmodium falciparum and human B-cells in a novel co-culture increases parasite growth and affects B-cell growth
- 2021
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In: Malaria Journal. - : Springer Science and Business Media LLC. - 1475-2875. ; 20:1
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Journal article (peer-reviewed)abstract
- Background: Plasmodium falciparum parasites cause malaria and co-exist in humans together with B-cells for long periods of time. Immunity is only achieved after repeated exposure. There has been a lack of methods to mimic the in vivo co-occurrence, where cells and parasites can be grown together for many days, and it has been difficult with long time in vitro studies. Methods and results: A new method for growing P. falciparum in 5% CO2 with a specially formulated culture medium is described. This knowledge was used to establish the co-culture of live P. falciparum together with human B-cells in vitro for 10 days. The presence of B-cells clearly enhanced parasite growth, but less so when Transwell inserts were used (not allowing passage of cells or merozoites), showing that direct contact is advantageous. B-cells also proliferated more in presence of parasites. Symbiotic parasitic growth was verified using CESS cell-line and it showed similar results, indicating that B-cells are indeed the cells responsible for the effect. In malaria endemic areas, people often have increased levels of atypical memory B-cells in the blood, and in this assay it was demonstrated that when parasites were present there was an increase in the proportion of CD19 + CD20 + CD27 − FCRL4 + B-cells, and a contraction of classical memory B-cells. This effect was most clearly seen when direct contact between B-cells and parasites was allowed. Conclusions: These results demonstrate that P. falciparum and B-cells undoubtedly can affect each other when allowed to multiply together, which is valuable information for future vaccine studies.
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| 8. |
- Rönnberg, Caroline, et al.
(author)
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A longitudinal study of plasma BAFF levels in mothers and their infants in Uganda, and correlations with subsets of B cells
- 2021
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In: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 16:1 January
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Journal article (peer-reviewed)abstract
- Malaria is a potentially life-threatening disease with approximately half of the world’s population at risk. Young children and pregnant women are hit hardest by the disease. B cells and antibodies are part of an adaptive immune response protecting individuals continuously exposed to the parasite. An infection with Plasmodium falciparum can cause dysregulation of B cell homeostasis, while antibodies are known to be key in controlling symptoms and parasitemia. BAFF is an instrumental cytokine for the development and maintenance of B cells. Pregnancy alters the immune status and renders previously clinically immune women at risk of severe malaria, potentially due to altered B cell responses associated with changes in BAFF levels. In this prospective study, we investigated the levels of BAFF in a malaria-endemic area in mothers and their infants from birth up to 9 months. We found that BAFF-levels are significantly higher in infants than in mothers. BAFF is highest in cord blood and then drops rapidly, but remains significantly higher in infants compared to mothers even at 9 months of age. We further correlated BAFF levels to P. falciparum-specific antibody levels and B cell frequencies and found a negative correlation between BAFF and both P. falciparum-specific and total proportions of IgG+ memory B cells, as well as CD27− memory B cells, indicating that exposure to both malaria and other diseases affect the development of B-cell memory and that BAFF plays a part in this. In conclusion, we have provided new information on how natural immunity against malaria is formed.
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| 9. |
- Saleh, Bandar Hasan, et al.
(author)
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Autoantibodies against red blood cell antigens are common in a Malaria endemic area
- 2023
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In: Microbes and Infection. - : Elsevier BV. - 1769-714X .- 1286-4579. ; 25:3
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Journal article (peer-reviewed)abstract
- Plasmodium falciparum malaria can cause severe anemia. Even after treatment, hematocrit can decrease. The role of autoantibodies against erythrocytes is not clearly elucidated and how common they are, or what they are directed against, is still largely unknown. We have investigated antibodies against erythrocytes in healthy adult men living in a highly malaria endemic area in Uganda. We found antibodies in more than half of the individuals, which is significantly more than in a non-endemic area (Sweden). Some of the Ugandan samples had a broad reactivity where it was not possible to determine the exact target of the autoantibodies, but we also found specific antibodies directed against erythrocyte surface antigens known to be of importance for merozoite invasion such as glycophorin A (anti-En a, anti-M) and glycophorin B (anti-U, anti-S). In addition, several autoantibodies had partial specificities against glycophorin C and the blood group systems Rh, Diego (located on Band 3), Duffy (located on ACKR1), and Cromer (located on CD55), all of which have been described to be important for malaria and therefore of interest for understanding how autoantibodies could potentially stop parasites from entering the erythrocyte. In conclusion, specific autoantibodies against erythrocytes are common in a malaria endemic area.
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| 10. |
- Svensson, Joel, et al.
(author)
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A Serosurvey of Tick-Borne Encephalitis Virus in Sweden: Different Populations and Geographical Locations
- 2021
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In: Vector-Borne and Zoonotic Diseases. - : Mary Ann Liebert Inc. - 1557-7759 .- 1530-3667. ; 21:8, s. 614-619
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Journal article (peer-reviewed)abstract
- AbstractBackground: New risk areas for tick-borne encephalitis (TBE) are emerging and the spread of disease and vaccine coverage is unclear in Sweden. We wanted to study the prevalence and levels of TBE-virus (TBEV) antibodies in southern Sweden, and to investigate whether there were individuals with undiagnosed TBE.Materials and Methods: Two cohorts of sera were collected: One group of anonymous individuals in rural areas (AIRA) in Skåne and one group of volunteers who often got tick-bites (tick-bitten individuals [TBI]). An enzyme-linked immunosorbent assay for TBEV IgM and IgG was performed, as well as a TBEV neutralization test (NT) in selected individuals.Results: In the AIRA group, there was an IgG seropositivity of 5.3%. There were individuals with high antibody levels both in areas previously considered as risk areas (Bromölla and Knislinge), as well as in another area (Tyringe). In the TBI group, 45% of the individuals were vaccinated according to the questionnaires and IgG seropositivity was 28%. A lower seroprevalence and levels of antibodies were seen in the middle-aged group (50–69 years) compared with younger or elderly study participants. A positive NT revealed several individuals with suspected undiagnosed episodes of TBE.Conclusion: Subclinical or misdiagnosed cases have probably occurred in Skåne. Middle-aged individuals had lower levels of IgG, which could indicate either less tick exposure or a lower vaccine response. Less than half of the TBI were vaccinated, an indication that more information about the disease and vaccine might be needed. We conclude that the study motivates an increased awareness of TBEV in the region.
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