| 1. |
|
|
| 2. |
|
|
| 3. |
|
|
| 4. |
- Andersson, C., et al.
(författare)
-
Improved systems for hydrophobic tagging of recombinant immunogens for efficient iscom incorporation
- 2000
-
Ingår i: JIM - Journal of Immunological Methods. - 0022-1759 .- 1872-7905. ; 238:02-jan, s. 181-193
-
Tidskriftsartikel (refereegranskat)abstract
- We have previously reported a strategy for production in Escherichia coli of recombinant immunogens fused to a hydrophobic tag to improve their capacity to associate with an adjuvant formulation [Andersson et al., J. Immunol. Methods 222 (1999) 171]. Here, we describe a further development of the previous strategy and present significant improvements. In the novel system, the target immunogen is produced with an N-terminal affinity tag suitable for affinity purification, and a C-terminal hydrophobic tag, which should enable association through hydrophobic interactions of the immunogen with an adjuvant system, here being immunostimulating complexes (iscoms). Two different hydrophobic tags were evaluated: (i) a tag denoted M, derived from the membrane-spanning region of Staphylococcus aureus protein A (SpA), and (ii) a tag denoted MI consisting of the transmembrane region of hemagglutinin from influenza A virus. Furthermore, two alternative affinity tags were evaluated; the serum albumin-binding protein ABP, derived from streptococcal protein G, and the divalent IgG-binding ZZ-domains derived from SpA. A malaria peptide M5, derived from the central repeat region of the Plasmodium falciparum blood-stage antigen Pf155/RESA, served as model immunogen in this study. Four different fusion proteins, ABP-MS-M, ABP-MS-MI, ZZ-MS-M and ZZ-MS-MI, were thus produced, affinity purified and evaluated in iscom-incorporation experiments. All of the fusion proteins were found in the iscom fractions in analytical ultracentrifugation, indicating iscom incorporation. This was further supported by electron microscopy analysis showing that iscoms were formed. In addition, these iscom preparations were demonstrated to induce MS-specific antibody responses upon immunisation of mice, confirming the successful incorporation into iscoms. The novel system for hydrophobic tagging of immunogens, with optional affinity and hydrophobic tags, gave expression levels that were increased ten to fifty-fold, as compared to the earlier reported system. We believe that the presented strategy would be a convenient way to achieve efficient adjuvant association for recombinant immunogens.
|
|
| 5. |
- Bäckström, Torbjörn, et al.
(författare)
-
Paradoxical effects of GABA-A modulators may explain sex steroid induced negative mood symptoms in some persons
- 2011
-
Ingår i: Neuroscience. - Oxford : Elsevier BV. - 0306-4522 .- 1873-7544. ; 191:Special issue, s. 46-54
-
Forskningsöversikt (refereegranskat)abstract
- Some women have negative mood symptoms, caused by progestagens in hormonal contraceptives or sequential hormone therapy or by progesterone in the luteal phase of the menstrual cycle, which may be attributed to metabolites acting on the GABA-A receptor. The GABA system is the major inhibitory system in the adult CNS and most positive modulators of the GABA-A receptor (benzodiazepines, barbiturates, alcohol, GABA steroids), induce inhibitory (e.g. anesthetic, sedative, anticonvulsant, anxiolytic) effects. However, some individuals have adverse effects (seizures, increased pain, anxiety, irritability, aggression) upon exposure. Positive GABA-A receptor modulators induce strong paradoxical effects including negative mood in 3%-8% of those exposed, while up to 25% have moderate symptoms. The effect is biphasic: low concentrations induce an adverse anxiogenic effect while higher concentrations decrease this effect and show inhibitory, calming properties. The prevalence of premenstrual dysphoric disorder (PMDD) is also 3%-8% among women in fertile ages, and up to 25% have more moderate symptoms of premenstrual syndrome (PMS). Patients with PMDD have severe luteal phase-related symptoms and show changes in GABA-A receptor sensitivity and GABA concentrations. Findings suggest that negative mood symptoms in women with PMDD are caused by the paradoxical effect of allopregnanolone mediated via the GABA-A receptor, which may be explained by one or more of three hypotheses regarding the paradoxical effect of GABA steroids on behavior: (1) under certain conditions, such as puberty, the relative fraction of certain GABA-A receptor subtypes may be altered, and at those subtypes the GABA steroids may act as negative modulators in contrast to their usual role as positive modulators; (2) in certain brain areas of vulnerable women the transmembrane C1(-) gradient may be altered by factors such as estrogens that favor excitability; (3) inhibition of inhibitory neurons may promote disinhibition, and hence excitability. This article is part of a Special Issue entitled: Neuroactive Steroids: Focus on Human Brain. (C) 2011 Published by Elsevier Ltd on behalf of IBRO.
|
|
| 6. |
- Funkquist, Anders, 1977-, et al.
(författare)
-
Low CSF/serum ratio of free T4 is associated with decreased quality of life in mild hypothyroidism – A pilot study : CSF/s-T4 associated with QoL in hypothyroidism
- 2020
-
Ingår i: Journal of Clinical and Translational Endocrinology. - Netherlands : Elsevier BV. - 2214-6237. ; 19
-
Tidskriftsartikel (refereegranskat)abstract
- Background & Objective: Patients with mild hypothyroidism often are depressed and have impaired quality of life despite serum free-T4 and T3 within reference values. Therefore, we investigated whether their symptoms were dependent on the concentrations of free -T4 and T3 in the circulation and cerebrospinal fluid (CSF). Methods: Twenty-five newly diagnosed, untreated hypothyroid subjects and as many age- and sex-matched healthy controls were investigated. Blood and CSF sampling was performed in the morning after an overnight fast. Quality of life (QoL) was assessed by a Likert scale. In the hypothyroid subjects, the MADRS rating scale was also used to evaluate symptoms of depression. Furthermore, the results obtained by the questionnaires were related to serum and CSF levels of free- T4 and T3 as well as the ratios between them in CSF and in serum. Results: Self-reported health was considerably lower in hypothyroid subjects. MADRS was considerably higher than the normal range for healthy individuals. Low CSF/serum free-T4 ratio was correlated with an increased depressed state according to MADRS (p < 0.01), and in addition, CSF/serum free-T4 ratio correlated positively with the self-reported general health Likert scale (p < 0.05). Concentrations of TSH, or free-T3 in serum or CSF, were not associated with an increased depressed state or self-reported general health. Conclusions: Low CSF/serum ratio of free-T4 was correlated with impaired general health and mood, in contrast to serum measurements not showing any correlations. These findings might partly explain why some patients with hypothyroidism suffer from mental symptoms, despite adequate serum levels of free-T4. However, the findings need to be confirmed in further and larger studies.
|
|
| 7. |
- Johansson, Jonathan S M, et al.
(författare)
-
Prediabetes and incident heart failure in hypertensive patients: Results from the Swedish Primary Care Cardiovascular Database.
- 2022
-
Ingår i: Nutrition, metabolism, and cardiovascular diseases : NMCD. - : Elsevier BV. - 1590-3729 .- 0939-4753. ; 32:12, s. 2803-2810
-
Tidskriftsartikel (refereegranskat)abstract
- The cardiovascular risk conferred by concomitant prediabetes in hypertension is unclear. We aimed to examine the impact of prediabetes on incident heart failure (HF) and all-cause mortality, and to describe time in therapeutic blood pressure range (TTR) in a hypertensive real-world primary care population.In this retrospective cohort study, 9628 hypertensive individuals with a fasting plasma glucose (FPG) in 2006-2010 but no diabetes, cardiovascular or renal disease were followed to 2016; median follow-up was 9 years. Prediabetes was defined as FPG 5.6-6.9mmol/L, and in a secondary analysis as 6.1-6.9mmol/L. Study outcomes were HF and all-cause mortality. Hazard ratios (HR) were compared for prediabetes with normoglycemia using Cox regression. All blood pressure values from 2001 to the index date (first FPG in 2006-2010) were used to calculate TTR. At baseline, 51.4% had prediabetes. The multivariable-adjusted HR (95% confidence intervals) was 0.86 (0.67-1.09) for HF and 1.06 (0.90-1.26) for all-cause mortality. For FPG defined as 6.1-6.9mmol/L, the multivariable-adjusted HR were 1.05 (0.80-1.39) and 1.42 (1.19-1.70), respectively. The prediabetic group had a lower TTR (p<0.05).Prediabetes was not independently associated with incident HF in hypertensive patients without diabetes, cardiovascular or renal disease. However, prediabetes was associated with all-cause mortality when defined as FPG 6.1-6.9mmol/L (but not as 5.6-6.9mmol/L). TTR was lower in the prediabetic group, suggesting room for improved blood pressure to reduce incident heart failure in prediabetes.
|
|
| 8. |
- Johansson, M, et al.
(författare)
-
HfO2 gate dielectrics on strained-Si and strained-SiGe layers
- 2003
-
Ingår i: Semiconductor Science and Technology. - : IOP Publishing. - 0268-1242 .- 1361-6641. ; 18:9, s. 820-826
-
Tidskriftsartikel (refereegranskat)abstract
- We report on materials and device characterization of polycrystalline HfO2 gate dielectrics grown by atomic layer deposition (ALD) at 600 degreesC on strained-Si and strained-SiGe layers. No change in the diffusion profile of Hf into the Si substrate was observed for temperatures in the range 900-1100 degreesC for 20 min. The strain status in the Si layer remained unaltered after HfO2 deposition and an interface state density of similar to1 x 10(11) cm(-2) eV(-1) was obtained for the thicker HfO2 films. The breakdown fields were in the range 2-5 MV cm(-1), which is high compared to HfO2 films grown at higher temperatures. The leakage current was reduced by more than five orders of magnitude for the thin HFO2 with an EOT of 1.25 nm and ultra-thin cap (2.5-3 nm) layers on Si0.77Ge0.23/Si, though high interface state densities (similar to1 x 10(12) cm(-2) eV(-1)) were observed. The carrier transport through these HfO2 films was found to follow Frenkel-Poole emission over a wide range of applied gate voltages.
|
|
| 9. |
|
|
