| 1. |
- Ambrosi, Aurelie, et al.
(författare)
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Development of heart block in children of SSA/SSB-autoantibody-positive women is associated with maternal age and displays a season-of-birth pattern
- 2012
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Ingår i: Annals of the Rheumatic Diseases. - London : BMJ Publishing Group. - 0003-4967 .- 1468-2060. ; 71:3, s. 334-340
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Tidskriftsartikel (refereegranskat)abstract
- Objective Congenital heart block may develop in the fetuses of Ro/SSA-positive and La/SSB-positive mothers. Recurrence rates of only 10-20% despite persisting maternal antibodies indicate that additional factors are critical for the establishment of heart block. The authors investigated the influence of other maternal and fetal factors on heart block development in a Swedish population-based cohort. less thanbrgreater than less thanbrgreater thanMethods The influence of fetal gender, maternal age, parity and time of birth on heart block development was analysed in 145 families, including Ro/La-positive (n=190) and Ro/La-negative (n=165) pregnancies. less thanbrgreater than less thanbrgreater thanResults There was a recurrence rate of 12.1% in Ro/La-positive women, and no recurrence in Ro/La-negative women. Fetal gender and parity did not influence the development of heart block in either group. Maternal age in Ro/La-positive pregnancies with a child affected by heart block was, however, significantly higher than in pregnancies resulting in babies without heart block (pandlt;0.05). Seasonal timing of pregnancy influenced the outcome. Gestational susceptibility weeks 18-24 occurring during January-March correlated with a higher proportion of children with heart block and lower vitamin D levels during the same period in a representative sample of Swedish women and a corresponding higher proportion of children with heart block born in the summer (pandlt;0.02). Maternal age or seasonal timing of pregnancy did not affect the outcome in Ro/La-negative pregnancies. less thanbrgreater than less thanbrgreater thanConclusion This study identifies maternal age and seasonal timing of pregnancy as novel risk factors for heart block development in children of Ro/La-positive women. These observations may be useful for counselling when pregnancy is considered.
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| 2. |
- Eriksson Skog, Amanda, et al.
(författare)
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Interaction of a Histidine-Rich Antimicrobial Saliva Peptide with Model Cell Membranes : The Role of Histidines
- 2023
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Ingår i: Langmuir : the ACS journal of surfaces and colloids. - 0743-7463. ; 39:22, s. 7694-7706
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Tidskriftsartikel (refereegranskat)abstract
- Histatin 5 is a histidine-rich, intrinsically disordered, multifunctional saliva protein known to act as a first line of defense against oral candidiasis caused by Candida albicans. An earlier study showed that, upon interaction with a common model bilayer, a protein cushion spontaneously forms underneath the bilayer. Our hypothesis is that this effect is of electrostatic origin and that the observed behavior is due to proton charge fluctuations of the histidines, promoting attractive electrostatic interactions between the positively charged proteins and the anionic surfaces, with concomitant counterion release. Here we are investigating the role of the histidines in more detail by defining a library of variants of the peptide, where the former have been replaced by the pH-insensitive amino acid glutamine. By using experimental techniques such as circular dichroism, small angle X-ray scattering, quartz crystal microbalance with dissipation monitoring, and neutron reflectometry, it was determined that changing the number of histidines in the peptide sequence did not affect the structure of the peptide dissolved in solution. However, it was shown to affect the penetration depth of the peptide into the bilayer, where all variants except the one with zero histidines were found below the bilayer. A decrease in the number of histidine from the original seven to zero decreases the ability of the peptide to penetrate the bilayer, and the peptide is then also found residing within the bilayer. We hypothesize that this is due to the ability of the histidines to charge titrate, which charges up the peptide, and enables it to penetrate and translocate through the lipid bilayer.
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| 3. |
- Gerelli, Yuri, et al.
(författare)
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Spontaneous Formation of Cushioned Model Membranes Promoted by an Intrinsically Disordered Protein
- 2020
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Ingår i: Langmuir. - : American Chemical Society (ACS). - 0743-7463 .- 1520-5827. ; 36:15, s. 3997-4004
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Tidskriftsartikel (refereegranskat)abstract
- In this article, it is shown that by exposing commonly used lipids for biomembrane mimicking studies, to a solution containing the histidine-rich intrinsically disordered protein histatin 5, a protein cushion spontaneously forms underneath the bilayer. The underlying mechanism is attributed to have an electrostatic origin, and it is hypothesized that the observed behavior is due to proton charge fluctuations promoting attractive electrostatic interactions between the positively charged proteins and the anionic surfaces, with concomitant counterion release. Hence, we anticipate that this novel "green" approach of forming cushioned bilayers can be an important tool to mimic the cell membrane without the disturbance of the solid substrate, thereby achieving a further understanding of protein-cell interactions.
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| 4. |
- Neiman, Daniel, et al.
(författare)
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Multiplexing DNA methylation markers to detect circulating cell-free DNA derived from human pancreatic β cells
- 2020
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Ingår i: JCI Insight. - : American Society for Clinical Investigation. - 2379-3708. ; 5:14
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Tidskriftsartikel (refereegranskat)abstract
- It has been proposed that unmethylated insulin promoter fragments in plasma derive exclusively from β cells, reflect their recent demise, and can be used to assess β cell damage in type 1 diabetes. Herein we describe an ultrasensitive assay for detection of a β cell–specific DNA methylation signature, by simultaneous assessment of 6 DNA methylation markers, that identifies β cell DNA in mixtures containing as little as 0.03% β cell DNA (less than 1 β cell genome equivalent). Based on this assay, plasma from nondiabetic individuals (N = 218, aged 4–78 years) contained on average only 1 β cell genome equivalent/mL. As expected, cell-free DNA (cfDNA) from β cells was significantly elevated in islet transplant recipients shortly after transplantation. We also detected β cell cfDNA in a patient with KATP congenital hyperinsulinism, in which substantial β cell turnover is thought to occur. Strikingly, in contrast to previous reports, we observed no elevation of β cell–derived cfDNA in autoantibody-positive subjects at risk for type 1 diabetes (N = 32), individuals with recent-onset type 1 diabetes (<4 months, N = 92), or those with long-standing disease (>4 months, N = 38). We discuss the utility of sensitive β cell cfDNA analysis and potential explanations for the lack of a β cell cfDNA signal in type 1 diabetes.
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| 5. |
- Skog, Amanda
(författare)
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Being born with congenital heart block : risk factors, growth and development
- 2013
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Congenital heart block (CHB) is a rare but life-threatening disease associated with the presence of Ro and La autoantibodies in the mother of the child affected. CHB is one of the manifestations of neonatal lupus erythematosus (NLE) that may also include several other manifestations such as a skin rash and cytopenias. Although the link between Ro and La autoantibodies and the risk for CHB has been recognized for decades, a recurrence rate of 12-17% in subsequent pregnancies suggests that other risk factors also contribute to disease pathogenesis. Furthermore, as CHB is rare disease, little is known about outcome and health in these children. The aim of this thesis was therefore to investigate outcome, health and antibody levels in children with CHB as well as risk factors for CHB development. In our results we reveal that increased maternal age and seasonal timing of birth are novel risk factors for CHB in autoantibody-positive pregnancies. Furthermore, when analyzing antibody levels in children born to mothers with Ro/SSA autoantibodies, we have demonstrated that maternal autoantibodies decrease rapidly in the infant circulation during the first few weeks of life among both breast-fed and non-breast-fed infants and are not correlated to NLE skin manifestations. We have also demonstrated that an autoantibody-associated complete CHB diagnosis after the neonatal period is possible, advocating testing of maternal serology at the time of diagnosis. Our results demonstrate that newborns with fetal signs of atrioventricular block (AVB) II-III have a significantly lower weight at birth than those with AVB I or normal conduction and do not show signs of catch-up during the first 12 months of life. Fetuses with AVB I or normal atrioventricular conduction have significant but smaller weight retardation at birth, but showed a rapid catch-up during the first two postnatal months, indicating that they have a good prognosis. Looking at long-term growth, we demonstrate that children with complete CHB are weight restricted both in comparison to their siblings without CHB and the Swedish reference standards from birth to 2-3 years of age, when a catch-up is initiated. From the age of 9-11 they have normal body measurements as a group and do not significantly deviate from the reference standards. When investigating neurodevelopment, our data indicate that in addition to well established factors such as male sex and being born preterm, both maternal SLE and CHB may influence neurodevelopment as learning impairment was significantly influenced by maternal SLE (p < 0.005), while attention deficits was influenced by both maternal SLE (p < 0.05) and CHB in the child (p < 0.05). In conclusion, our results indicate that maternal age and seasonal timing of birth are risk factors for CHB development, information that may be useful to consider when pregnancy is planned. As antibody levels decreased in the infants and were not correlated to NLE skin manifestations, we conclude that there is no reason not to recommend breast feeding in children born to anti-Ro and or La positive women. Although children with CHB are weight retarded during their first years of life, they appeared to spontaneously initiate a catch-up in weight around the age of 2-3 years. However, as the group of children with CHB did not reach the reference standards until the age of 9-11, careful follow-up of individuals with CHB regarding nutrition and growth is recommended. In addition, follow-up of neurodevelopment should be considered for children with CHB, especially if the mother is diagnosed with SLE. An early diagnosis is one way to help these children overcome their difficulties during childhood and school years and make sure that they obtain the support needed.
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