| 1. |
- Cannerfelt, B., et al.
(författare)
-
White matter lesions and brain atrophy in systemic lupus erythematosus patients : correlation to cognitive dysfunction in a cohort of systemic lupus erythematosus patients using different definition models for neuropsychiatric systemic lupus erythematosus
- 2018
-
Ingår i: Lupus. - : SAGE Publications. - 0961-2033 .- 1477-0962. ; 27:7, s. 1140-1149
-
Tidskriftsartikel (refereegranskat)abstract
- Aim: The aim of this study was to evaluate the extent of white matter lesions, atrophy of the hippocampus and corpus callosum, and their correlation with cognitive dysfunction (CD), in patients diagnosed with systemic lupus erythematosus (SLE). Methods: Seventy SLE patients and 25 healthy individuals (HIs) were included in the study. To evaluate the different SLE and neuropsychiatric SLE (NPSLE) definition schemes, patients were grouped both according to the American College of Rheumatology (ACR) definition, as well as the more stringent ACR-Systemic Lupus International Collaborating Clinics definition. Patients and HIs underwent a 3 Tesla brain MRI and a standardized neuropsychological test. MRI data were evaluated for number and volume of white matter lesions and atrophy of the hippocampus and corpus callosum. Differences between groups and subgroups were evaluated for significance. Number and volume of white matter lesions and atrophy of the hippocampus and corpus callosum were correlated to cognitive dysfunction. Results: The total volume of white matter lesions was significantly larger in SLE patients compared to HIs (p = 0.004). However, no significant differences were seen between the different SLE subgroups. Atrophy of the bilateral hippocampus was significantly more pronounced in patients with NPSLE compared to those with non-NPSLE (right: p = 0.010; left p = 0.023). Significant negative correlations between cognitive test scores on verbal memory and number and volume of white matter lesions were present. Conclusion: SLE patients have a significantly larger volume of white matter lesions on MRI compared to HIs and the degree of white matter lesion volume correlates to cognitive dysfunction, specifically to verbal memory. No significant differences in the number or volume of white matter lesions were identified between subgroups of SLE patients regardless of the definition model used.
|
|
| 2. |
- Ahlinder, J., et al.
(författare)
-
Use of metagenomic microbial source tracking to investigate the source of a foodborne outbreak of cryptosporidiosis
- 2022
-
Ingår i: FOOD AND WATERBORNE PARASITOLOGY. - : Elsevier. - 2405-6766. ; 26
-
Tidskriftsartikel (refereegranskat)abstract
- Cryptosporidium is a protozoan parasite of global public health importance that causes gastroenteritis in a variety of vertebrate hosts, with many human outbreaks reported yearly, often from ingestion of contaminated water or food. Despite the major public health implications, little is typically known about sources of contamination of disease outbreaks caused by Cryptosporidium. Here, we study a national foodborne outbreak resulted from infection with Cryptosporidium parvum via romaine lettuce, with the main goal to trace the source of the parasite. To do so, we combined traditional outbreak investigation methods with molecular detection and characterization methods (i.e. PCR based typing, amplicon and shotgun sequencing) of romaine lettuce samples collected at the same farm from which the contaminated food was produced. Using 18S rRNA typing, we detected C. parvum in two out of three lettuce samples, which was supported by detections in the metagenome analysis. Microbial source tracking analysis of the lettuce samples suggested sewage water as a likely source of the contamination, albeit with some uncertainty. In addition, the high degree of overlap in bacterial species content with a public human gut microbial database corroborated the source tracking results. The combination of traditional and molecular based methods applied here is a promising tool for future source tracking investigations of food- and waterborne outbreaks of Cryptosporidium spp. and can help to control and mitigate contamination risks.
|
|
| 3. |
- Gioti, Anastasia, et al.
(författare)
-
Genomic Insights into the Atopic Eczema-Associated Skin Commensal Yeast Malassezia sympodialis
- 2013
-
Ingår i: mBio. - 2161-2129 .- 2150-7511. ; 4:1, s. e00572-12-
-
Tidskriftsartikel (refereegranskat)abstract
- Malassezia commensal yeasts are associated with a number of skin disorders, such as atopic eczema/dermatitis and dandruff, and they also can cause systemic infections. Here we describe the 7.67-Mbp genome of Malassezia sympodialis, a species associated with atopic eczema, and contrast its genome repertoire with that of Malassezia globosa, associated with dandruff, as well as those of other closely related fungi. Ninety percent of the predicted M. sympodialis protein coding genes were experimentally verified by mass spectrometry at the protein level. We identified a relatively limited number of genes related to lipid biosynthesis, and both species lack the fatty acid synthase gene, in line with the known requirement of these yeasts to assimilate lipids from the host. Malassezia species do not appear to have many cell wall-localized glycosylphosphatidylinositol (GPI) proteins and lack other cell wall proteins previously identified in other fungi. This is surprising given that in other fungi these proteins have been shown to mediate interactions (e. g., adhesion and biofilm formation) with the host. The genome revealed a complex evolutionary history for an allergen of unknown function, Mala s 7, shown to be encoded by a member of an amplified gene family of secreted proteins. Based on genetic and biochemical studies with the basidiomycete human fungal pathogen Cryptococcus neoformans, we characterized the allergen Mala s 6 as the cytoplasmic cyclophilin A. We further present evidence that M. sympodialis may have the capacity to undergo sexual reproduction and present a model for a pseudobipolar mating system that allows limited recombination between two linked MAT loci. IMPORTANCE Malassezia commensal yeasts are associated with a number of skin disorders. The previously published genome of M. globosa provided some of the first insights into Malassezia biology and its involvement in dandruff. Here, we present the genome of M. sympodialis, frequently isolated from patients with atopic eczema and healthy individuals. We combined comparative genomics with sequencing and functional characterization of specific genes in a population of clinical isolates and in closely related model systems. Our analyses provide insights into the evolution of allergens related to atopic eczema and the evolutionary trajectory of the machinery for sexual reproduction and meiosis. We hypothesize that M. sympodialis may undergo sexual reproduction, which has important implications for the understanding of the life cycle and virulence potential of this medically important yeast. Our findings provide a foundation for the development of genetic and genomic tools to elucidate host-microbe interactions that occur on the skin and to identify potential therapeutic targets.
|
|
| 4. |
|
|
| 5. |
- Langensee, L, et al.
(författare)
-
Cognitive performance in systemic lupus erythematosus patients: a cross-sectional and longitudinal study
- 2022
-
Ingår i: BMC Rheumatology. - : Springer Science and Business Media LLC. - 2520-1026. ; 6, s. 1-11
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Previous research has provided evidence for cognitive dysfunction as a common symptom of systemic lupus erythematosus (SLE). In light of this, the primary goal of this study was to investigate how cognitive impairment in this patient group develops over time. In addition, the present dataset contributes to delineating the specific abilities that are impaired in SLE patients as well as answering the question whether the disease affects the cognition of SLE patients with neuropsychiatric manifestations (NPSLE) and without (non-NPSLE) in distinct ways.METHODS: 91 female participants (33 NPSLE, 29 non-NPSLE, 29 healthy controls (HC)) underwent standardized neurocognitive testing. A total of ten different cognitive abilities were assessed, among others executive function, memory, and attention. Some of the participants (30 NPSLE patients, 22 non-NPSLE, 13 HC) were tested twice (mean time between testing sessions: 50 months) to enable longitudinal tracking of cognitive abilities. Analyses of Variance (ANOVA) were conducted to determine whether cognitive performance differed cross-sectionally between the groups. Linear mixed effects models were fit to investigate performance differences between the groups over time.RESULTS: Cross-sectional analysis at follow-up demonstrated that the cognitive performance of both NPSLE and non-NPSLE was significantly lower than that of HC for the motor speed and the psychomotor speed domain. Additionally, NPSLE patients performed significantly weaker than HC in the complex attention domain. At the same time, the cross-sectional data did not yield any support for performance differences between NPSLE and non-NPSLE patients. Weak positive correlations between disease duration and psychomotor speed, motor speed and reaction time emerged. A temporal progression of cognitive dysfunction in SLE patients was not confirmed.CONCLUSIONS: Cognitive performance is affected in both non-NPSLE and NPSLE patients. However, a linear decline in performance over time could not be verified. More in-depth longitudinal assessments of cognition in SLE patients are needed to establish how cognitive abilities in this patient population develop over time.
|
|
| 6. |
|
|
| 7. |
|
|
| 8. |
- Zervides, Kristoffer A, et al.
(författare)
-
Plasma and cerebrospinal fluid neurofilament light concentrations reflect neuronal damage in systemic lupus Erythematosus
- 2022
-
Ingår i: BMC Neurology. - : Springer Science and Business Media LLC. - 1471-2377. ; 22:1
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Neuronal damage in systemic lupus erythematosus (SLE) is common, but the extent and mechanisms are unclear. Neurofilament light (NfL) concentrations rise in plasma and cerebrospinal fluid (CSF) during neuronal damage in various neurological disorders. In this cross-sectional study, plasma and CSF concentrations of NfL were explored as a marker of neuronal damage in SLE.METHODS: Seventy-two consecutive SLE out-patients and 26 healthy controls, all female, aged < 55 years, underwent magnetic resonance imaging (MRI) and neurocognitive testing. NfL concentrations in plasma from all individuals and in CSF from 32 patients were measured with single-molecule array technology. Patients were assessed by a rheumatologist and neurologist to define neuropsychiatric involvement (NPSLE) according to three attribution models: SLICC A, SLICC B and ACR.RESULTS: Plasma and CSF NfL concentrations correlated strongly (r = 0.72, p < 0.001). Both NPSLE and non-NPSLE patients in all attribution models had higher plasma NfL concentrations compared with healthy controls (log-NfL, pg/ml, mean (SD); healthy controls (0.71 (0.17)); SLICC A model: NPSLE (0.87 (0.13), p = 0.003), non-NPSLE (0.83 (0.18), p = 0.005); SLICC B model: NPSLE (0.87 (0.14), p = 0.001), non-NPSLE (0.83 (0.18), p = 0.008); ACR model: NPSLE (0.86 (0.16), p < 0.001), non-NPSLE (0.81 (0.17), p = 0.044)). Plasma and CSF NfL concentrations did not differ between NPSLE and non-NPSLE patients. Higher plasma NfL concentrations correlated with larger CSF volumes on MRI (r = 0.34, p = 0.005), and was associated with poorer cognitive performance in the domains of simple attention, psychomotor speed and verbal memory. SLICC/ACR-Damage Index ≥1 was independently associated with higher plasma NfL concentrations (β = 0.074, p = 0.038). Higher plasma creatinine concentrations, anti-dsDNA-positivity, low complement C3 levels, or a history of renal involvement were associated with higher plasma NfL concentrations (β = 0.003, p = 0.009; β = 0.072, p = 0.031; β = 0.077, p = 0.027; β = 0.069, p = 0.047, respectively).CONCLUSIONS: Higher plasma NfL concentrations in NPSLE and non-NPSLE patients may indicate a higher degree of neuronal damage in SLE in general, corresponding to cognitive impairment and organ damage development. Furthermore, our results may indicate a higher degree of neuronal breakdown in patients with active SLE, also without overt clinical symptoms. NfL may serve as an indicator of neuronal damage in SLE in further studies.
|
|
| 9. |
- Zervides, Kristoffer A, et al.
(författare)
-
Serum S100A8/A9 concentrations are associated with neuropsychiatric involvement in systemic lupus erythematosus: a cross-sectional study
- 2022
-
Ingår i: BMC Rheumatology. - : Springer Science and Business Media LLC. - 2520-1026. ; 6:1
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Neuropsychiatric (NP) involvement and fatigue are major problems in systemic lupus erythematosus (SLE). S100A8/A9 is a marker of inflammation and responds to therapy in SLE patients. S100A8/A9 has an immunopathogenic role in various neurological diseases. We investigated S100A8/A9 in relation to NP-involvement and fatigue in SLE.METHODS: 72 consecutive SLE outpatients at a tertiary centre and 26 healthy controls were included in this cross-sectional study. NPSLE was determined by specialists in rheumatology and neurology and defined according to three attribution models: "ACR", "SLICC A" and "SLICC B". Cerebral MRI was assessed by a neuroradiologist and neurocognitive testing by a neuropsychologist. The individuals were assessed by scores of pain (VAS), fatigue (VAS and FSS), and depression (MADRS-S). Concentrations of S100A8/A9 in serum and cerebrospinal fluid were measured with ELISA. Statistical calculations were performed using non-parametric methods.RESULTS: Serum concentrations of S100A8/A9 were higher in SLE patients compared with controls (medians 1230 ng/ml; 790 ng/ml, p = 0.023). The concentrations were higher in NPSLE patients compared with non-NPSLE patients when applying the SLICC A and ACR models, but not significant when applying the SLICC B model (medians 1400 ng/ml; 920 ng/ml, p = 0.011; 1560 ng/ml; 1090 ng/ml, p = 0.050; 1460 ng/ml; 1090 ng/ml, p = 0.083, respectively). No differences of CSF S100A8/A9 concentrations were observed between NPSLE and non-NPSLE patients. SLE patients with depression or cognitive dysfunction as an ACR NPSLE manifestation had higher serum S100A8/A9 concentrations than non-NPSLE patients (median 1460 ng/ml, p = 0.007 and 1380 ng/ml, p = 0.013, respectively). Higher serum S100A8/A9 correlated with higher VAS fatigue (r = 0.31; p = 0.008) and VAS pain (r = 0.27, p = 0.021) in SLE patients. Serum S100A8/A9 was not independently associated with NPSLE when adjusting for scores of fatigue (FSS) and pain (VAS) (OR 1.86, 95% CI 0.93-3.73, p = 0.08).CONCLUSIONS: Serum S100A8/A9 concentrations may be associated with NPSLE and fatigue. S100A8/A9 may be of interest in evaluating NPSLE, although further investigations are needed.
|
|
| 10. |
- Zhu, Y., et al.
(författare)
-
Proteogenomics produces comprehensive and highly accurate protein-coding gene annotation in a complete genome assembly of Malassezia sympodialis
- 2017
-
Ingår i: Nucleic Acids Research. - : Oxford University Press. - 0305-1048 .- 1362-4962. ; 45:5, s. 2629-2643
-
Tidskriftsartikel (refereegranskat)abstract
- Complete and accurate genome assembly and annotation is a crucial foundation for comparative and functional genomics. Despite this, few complete eukaryotic genomes are available, and genome annotation remains a major challenge. Here, we present a complete genome assembly of the skin commensal yeast Malassezia sympodialis and demonstrate how proteogenomics can substantially improve gene annotation. Through long-read DNA sequencing, we obtained a gap-free genome assembly for M. sympodialis (ATCC 42132), comprising eight nuclear and one mitochondrial chromosome. We also sequenced and assembled four M. sympodialis clinical isolates, and showed their value for understanding Malassezia reproduction by confirming four alternative allele combinations at the two mating-type loci. Importantly, we demonstrated how proteomics data could be readily integrated with transcriptomics data in standard annotation tools. This increased the number of annotated protein-coding genes by 14% (from 3612 to 4113), compared to using transcriptomics evidence alone. Manual curation further increased the number of protein-coding genes by 9% (to 4493). All of these genes have RNA-seq evidence and 87% were confirmed by proteomics. The M. sympodialis genome assembly and annotation presented here is at a quality yet achieved only for a few eukaryotic organisms, and constitutes an important reference for future host-microbe interaction studies.
|
|
