| 1. |
- Ch'ng, Jun-Hong, et al.
(författare)
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Epitopes of anti-RIFIN antibodies and characterization of rif-expressing Plasmodium falciparum parasites by RNA sequencing
- 2017
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Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 7
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Tidskriftsartikel (refereegranskat)abstract
- Variable surface antigens of Plasmodium falciparum have been a major research focus since they facilitate parasite sequestration and give rise to deadly malaria complications. Coupled with its potential use as a vaccine candidate, the recent suggestion that the repetitive interspersed families of polypeptides (RIFINs) mediate blood group A rosetting and influence blood group distribution has raised the research profile of these adhesins. Nevertheless, detailed investigations into the functions of this highly diverse multigene family remain hampered by the limited number of validated reagents. In this study, we assess the specificities of three promising polyclonal anti-RIFIN antibodies that were IgG-purified from sera of immunized animals. Their epitope regions were mapped using a 175,000-peptide microarray holding overlapping peptides of the P. falciparum variable surface antigens. Through immunoblotting and immunofluorescence imaging, we show that different antibodies give varying results in different applications/assays. Finally, we authenticate the antibody-based detection of RIFINs in two previously uncharacterized non-rosetting parasite lines by identifying the dominant rif transcripts using RNA sequencing.
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| 2. |
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| 3. |
- Gorcenco, Sorina, et al.
(författare)
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Ataxia-pancytopenia syndrome with SAMD9L mutations
- 2017
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Ingår i: Neurology: Genetics. - 2376-7839. ; 3:5
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: We describe the neurologic, neuroradiologic, and ophthalmologic phenotype of 1 Swedish and 1 Finnish family with autosomal dominant ataxia-pancytopenia (ATXPC) syndrome and SAMD9L mutations.METHODS: Members of these families with germline SAMD9L c.2956C>T, p.Arg986Cys, or c.2672T>C, p.Ile891Thr mutations underwent structured interviews and neurologic and ophthalmologic examinations. Neuroimaging was performed, and medical records were reviewed. Previous publications on SAMD9L-ATXPC were reviewed.RESULTS: Twelve individuals in both families were affected clinically. All mutation carriers examined had balance impairment, although severity was very variable. All but 1 had nystagmus, and all but 1 had pyramidal tract signs. Neurologic features were generally present from childhood on and progressed slowly. Two adult patients, who experienced increasing clumsiness, glare, and difficulties with gaze fixation, had paracentral retinal dysfunction verified by multifocal electroretinography. Brain MRI showed early, marked cerebellar atrophy in most carriers and variable cerebral periventricular white matter T2 hyperintensities. Two children were treated with hematopoietic stem cell transplantation for hematologic malignancies, and the neurologic symptoms of one of these worsened after treatment. Three affected individuals had attention deficit hyperactivity disorder or cognitive problems. Retinal dysfunction was not previously reported in individuals with ATXPC.CONCLUSIONS: The neurologic phenotype of this syndrome is defined by balance or gait impairment, nystagmus, hyperreflexia in the lower limbs and, frequently, marked cerebellar atrophy. Paracentral retinal dysfunction may contribute to glare, reading problems, and clumsiness. Timely diagnosis of ATXPC is important to address the risk for severe hemorrhage, infection, and hematologic malignancies inherent in this syndrome; regular hematologic follow-up might be beneficial.
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| 4. |
- Muralidharan, Somsundar Veppil, et al.
(författare)
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BET bromodomain inhibitors synergize with ATR inhibitors in melanoma in melanoma.
- 2017
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Ingår i: Cell Death & Disease. - 2041-4889. ; 8:8, s. 1-7
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Tidskriftsartikel (refereegranskat)abstract
- Metastatic malignant melanoma continues to be a challenging disease despite clinical translation of the comprehensive understanding of driver mutations and how melanoma cells evade immune attack. In Myc-driven lymphoma, efficacy of epigenetic inhibitors of the bromodomain and extra-terminal domain (BET) family of bromodomain proteins can be enhanced by combination therapy with inhibitors of the DNA damage response kinase ATR. Whether this combination is active in solid malignancies like melanoma, and how it relates to immune therapy, has not previously investigated. To test efficacy and molecular consequences of combination therapies cultured melanoma cells were used. To assess tumor responses to therapies in vivo we use patient-derived xenografts and B6 mice transplanted with B16F10 melanoma cells. Concomitant inhibition of BET proteins and ATR of cultured melanoma cells resulted in similar effects as recently shown in lymphoma, such as induction of apoptosis and p62, implicated in autophagy, senescence-associated secretory pathway and ER stress. In vivo, apoptosis and suppression of subcutaneous growth of patient-derived melanoma and B16F10 cells were observed. Our data suggest that ATRI/BETI combination therapies are effective in melanoma.
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| 5. |
- Wicher, Grzegorz K., et al.
(författare)
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Interleukin-33 Promotes Recruitment of Microglia/Macrophages in Response to Traumatic Brain Injury
- 2017
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Ingår i: Journal of Neurotrauma. - : Mary Ann Liebert Inc. - 0897-7151 .- 1557-9042. ; 34:22, s. 3173-3182
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Tidskriftsartikel (refereegranskat)abstract
- Traumatic brain injury (TBI) is a devastating condition, often leading to life-long consequences for patients. Even though modern neurointensive care has improved functional and cognitive outcomes, efficient pharmacological therapies are still lacking. Targeting peripherally derived, or resident inflammatory, cells that are rapid responders to brain injury is promising, but complex, given that the contribution of inflammation to exacerbation versus improved recovery varies with time post-injury. The injury-induced inflammatory response is triggered by release of alarmins, and in the present study we asked whether interleukin-33 (IL-33), an injury-associated nuclear alarmin, is involved in TBI. Here, we used samples from human TBI microdialysate, tissue sections from human TBI, and mouse models of central nervous system injury and found that expression of IL-33 in the brain was elevated from nondetectable levels, reaching a maximum after 72 h in both human samples and mouse models. Astrocytes and oligodendrocytes were the main producers of IL-33. Post-TBI, brains of mice deficient in the IL-33 receptor, ST2, contained fewer microglia/macrophages in the injured region than wild-type mice and had an altered cytokine/chemokine profile in response to injury. These observations indicate that IL-33 plays a role in neuroinflammation with microglia/macrophages being cellular targets for this interleukin post-TBI.
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| 6. |
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| 7. |
- Alves, Andreia, et al.
(författare)
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Case Study on Screening Emerging Pollutants in Urine and Nails
- 2017
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Ingår i: Environmental Science and Technology. - : American Chemical Society (ACS). - 0013-936X .- 1520-5851. ; 51:7, s. 4046-4053
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Tidskriftsartikel (refereegranskat)abstract
- Alternative plasticizers and flame retardants (FRs) have been introduced as replacements for banned or restricted chemicals, but much is still unknown about their metabolism and occurrence in humans. We identified the metabolites formed in vitro for four alternative plasticizers (acetyltributyl citrate (ATBC), bis(2-propylheptyl) phthalate (DPHP), bis(2-ethylhexyl) terephthalate (DEHTP), bis(2ethylhexyl) adipate (DEHA)), and one FR (2,2-bis (chloromethyl)-propane-1,3-diyltetrakis(2-chloroethyl) bisphosphate (V6)). Further, these compounds and their metabolites were investigated by LC/ESI-Orbitrap-MS in urine and finger nails collected from a Norwegian cohort. Primary and secondary ATBC metabolites had detection frequencies (% DF) in finger nails ranging from 46 to 95%. V6 was identified for the first time in finger nails, suggesting that this matrix may also indicate past exposure to FRs as well as alternative plasticizers. Two isomeric forms of DEHTP primary metabolite were highly detected in urine (97% DF) and identified in finger nails, while no DPHP metabolites were detected in vivo. Primary and secondary DEHA metabolites were identified in both matrices, and the relative proportion of the secondary metabolites was higher in urine than in finger nails; the opposite was observed for the primary metabolites. As many of the metabolites present in in vitro extracts were further identified in vivo in urine and finger nail samples, this suggests that in vitro assays can reliably mimic the in vivo processes. Finger nails may be a useful noninvasive matrix for human biomonitoring of specific organic contaminants, but further validation is needed.
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| 8. |
- Ameur, Adam, et al.
(författare)
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SweGen : a whole-genome data resource of genetic variability in a cross-section of the Swedish population
- 2017
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Ingår i: European Journal of Human Genetics. - : NATURE PUBLISHING GROUP. - 1018-4813 .- 1476-5438. ; 25:11, s. 1253-1260
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Tidskriftsartikel (refereegranskat)abstract
- Here we describe the SweGen data set, a comprehensive map of genetic variation in the Swedish population. These data represent a basic resource for clinical genetics laboratories as well as for sequencing-based association studies by providing information on genetic variant frequencies in a cohort that is well matched to national patient cohorts. To select samples for this study, we first examined the genetic structure of the Swedish population using high-density SNP-array data from a nation-wide cohort of over 10 000 Swedish-born individuals included in the Swedish Twin Registry. A total of 1000 individuals, reflecting a cross-section of the population and capturing the main genetic structure, were selected for whole-genome sequencing. Analysis pipelines were developed for automated alignment, variant calling and quality control of the sequencing data. This resulted in a genome-wide collection of aggregated variant frequencies in the Swedish population that we have made available to the scientific community through the website https://swefreq.nbis.se. A total of 29.2 million single-nucleotide variants and 3.8 million indels were detected in the 1000 samples, with 9.9 million of these variants not present in current databases. Each sample contributed with an average of 7199 individual-specific variants. In addition, an average of 8645 larger structural variants (SVs) were detected per individual, and we demonstrate that the population frequencies of these SVs can be used for efficient filtering analyses. Finally, our results show that the genetic diversity within Sweden is substantial compared with the diversity among continental European populations, underscoring the relevance of establishing a local reference data set.
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| 9. |
- Burström, Bo, et al.
(författare)
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Equity aspects of the Primary Health Care Choice Reform in Sweden - a scoping review
- 2017
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Ingår i: International Journal for Equity in Health. - : Springer Science and Business Media LLC. - 1475-9276. ; 16
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Tidskriftsartikel (refereegranskat)abstract
- Background: Good health and equal health care are the cornerstones of the Swedish Health and Medical Service Act. Recent studies show that the average level of health, measured as longevity, improves in Sweden, however, social inequalities in health remain a major issue. An important issue is how health care services can contribute to reducing inequalities in health, and the impact of a recent Primary Health Care (PHC) Choice Reform in this respect. This paper presents the findings of a review of the existing evidence on impacts of these reforms. Methods: We reviewed the published accounts (reports and scientific articles) which reported on the impact of the Swedish PHC Choice Reform of 2010 and changes in reimbursement systems, using Donabedian's framework for assessing quality of care in terms of structure, process and outcomes. Results: Since 2010, over 270 new private PHC practices operating for profit have been established throughout the country. One study found that the new establishments had primarily located in the largest cities and urban areas, in socioeconomically more advantaged populations. Another study, adjusting for socioeconomic composition found minor differences. The number of visits to PHC doctors has increased, more so among those with lesser needs of health care. The reform has had a negative impact on the provision of services for persons with complex needs. Opinions of doctors and staff in PHC are mixed, many state that persons with lesser needs are prioritized. Patient satisfaction is largely unchanged. The impact of PHC on population health may be reduced. Conclusions: The PHC Choice Reform increased the average number of visits, but particularly among those in more affluent groups and with lower health care needs, and has made integrated care for those with complex needs more difficult. Resource allocation to PHC has become more dependent on provider location, patient choice and demand, and less on need of care. On the available evidence, the PHC Choice Reform may have damaged equity of primary health care provision, contrary to the tenets of the Swedish Health and Medical Service Act. This situation needs to be carefully monitored.
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| 10. |
- Carlson-Nilsson, Ulrika
(författare)
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Facilitation of introgressive hybridization of wild polyploid mexican potato species using DNA markers of R genes and of different cytoplasmic types
- 2017
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Ingår i: Agricultural biology. - : Sel'skokhozyaistvennaya Biologiya Editorial Office (SBEO), NPO. - 2412-0324. ; 52, s. 964-975
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Tidskriftsartikel (refereegranskat)abstract
- Nowadays potato breeding is targeting to develop genetically divers high yielding varieties with multiple pathogen resistance traits. Interspecific hybridization jointed with marker-Assistantselection (MAS) can effectively combine the R genes from different resistance sources. Additionally to effective pyramiding the target genes, MAS allows to restrict introgression of genetic factors conferring the undesirable traits, for example, male sterility of interspecific hybrids associated with Solanum stoloniferum-derived W/gamma cytoplasm that complicate the traditional breeding. Current study is targeting to search for the opportunities to improve the efficiency of introgressive hybridization between common potato and Mexican polyploid species Solanum. neoantipoviczii (=S. stoloniferum) and S. guerreroense using MAS with DNA markers for different cytoplasmic types and markers associated with major R-genes to the most harmful potato pathogens. DNA-based markers of genes for late blight resistance (R2 like, R3a, Rpi-blb1, Rpi-sto1), for extreme resistance to Potato virus Y (PVY) (Ryadg, Rysto, Ry-fsto) and for H1 gene for resistance to the root cyst nematode (Globodera rostochiensis, pathotype Ro1) were used in this study. Based on the MAS, hybrid genotypes with different combinations of these markers were selected. Among them, there were the clones with high field resistance to late blight and to PVY. Of 29 hybrid clones from different combinations of crossing with polyploid Mexican species used as the maternal forms, 15 had a W/α cytoplasmic type and were male sterile; both these traits were maternally inherited. The remaining hybrids with W/γ cytoplasm produced fertile pollen and were used in interspecific crosses as pollinators. Selection of resistant clones with W/alpha cytoplasm and elimination of genotypes with sterile W/γ cytoplasm among wild species germplasm could increase the probability of obtaining male fertile introgressive lines. This approach allows to obtain the multi-species hybrid genotypes that combine R genes for resistance to pathogens from different Mexican species and to avoid various types of male sterility in breeding. The joint use of two systems of DNA markers, i.e. nuclear markers associated to R genes, and cytoplasmic markers for male sterility factors, could reduce costs and increase efficiency of target gene pyramiding programs.
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