| 1. |
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| 2. |
- Carlenor, E, et al.
(författare)
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On the presence of a nicotinamide nucleotide transhydrogenase in mitochondria from potato tuber
- 1988
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Ingår i: Plant Physiology. - 0032-0889 .- 1532-2548. ; 88, s. 303-308
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Tidskriftsartikel (refereegranskat)abstract
- Mitochondria isolated from potato (Solanum tuberosum L.) tuber wereinvestigated for the presence of a nicotinamide nucleotide transhydrogenaseactivity. Submitochondrial particles derived from these mitochondriaby sonication catalyzed a reduction of NAD' or 3-acetylpyridine-NAD'by NADPH, which showed a maximum of about 50 to 150 nanomoles/minute. milligram protein at pH 5 to 6. The Km values for 3-acetylpyridine-NAD' and NADPH were about 24 and 55 micromolar, respectively.Intact mitochondria showed a negligible activity in the absence of detergents.However, in the presence of detergents the specific activity approachedabout 30% of that seen with submitochondrial particles. Thepotato mitochondria transhydrogenase activity was sensitive to trypsinand phenylarsine oxide, both agents that are known to inhibit the mammaliantranshydrogenase. Antibodies raised against rat liver transhydrogenasecrossreacted with two peptides in potato tuber mitochondrialmembranes with a molecular mass of 100 to 115 kilodaltons. Theobserved transhydrogenase activities may be due to an unspecific activityof dehydrogenases and/or to a genuine transhydrogenase. The activitycontributions by NADH dehydrogenases and transhydrogenase to thetotal transhydrogenase activity were investigated by determining theirrelative sensitivities to trypsin. It is concluded that, at high or neutralpH, the observed transhydrogenase activity in potato tuber submitochondrialparticles is due to the presence of a genuine and specific highmolecular weight transhydrogenase. At low pH an unspecific reaction ofan NADH dehydrogenase with NADPH contributes to the total transhydrogenaseactivity.
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| 3. |
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| 4. |
- Clyne, N, et al.
(författare)
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The intracellular distribution of cobalt in exposed and unexposed rat myocardium
- 1990
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Ingår i: Scandinavian Journal of Clinical and Laboratory Investigation. - 0036-5513 .- 1502-7686. ; 50:6, s. 605-609
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Tidskriftsartikel (refereegranskat)abstract
- The intracellular distribution of cobalt was analysed in the myocardium of exposed and unexposed rats. The exposed rats were given a dietary cobalt supplementation of 40 mg CoS04-7 H20/kg body weight for 8 weeks. The mitochondrial fraction showed the greatest relative increase in cobalt: 0.09 ng/mg protein in the unexposed rats to 8.43 ng/mg protein in the exposed rats. In the exposed rats the submitochondrial particles had the highest levels of cobalt: 19.43 ng/mg protein, followed by the sarcoplasmatic reticulum: 12.3 ng/mg protein. The microsomal 44 000g supernatant also showed an increase, although the levels remained low (0.51 ng/mg protein in the exposed animals). Apparently the calcium-storing organelles had the highest levels of cobalt. This could affect calcium flux in myocardial cells and, secondarily, tension development in cardiac muscle.
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| 5. |
- Chauvin, Maxime, et al.
(författare)
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The design and flight performance of the PoGOLite Pathfinder balloon-borne hard X-ray polarimeter
- 2016
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Ingår i: Experimental astronomy. - : Springer Science and Business Media LLC. - 0922-6435 .- 1572-9508. ; 41:1, s. 17-41
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Tidskriftsartikel (refereegranskat)abstract
- In the 50 years since the advent of X-ray astronomy there have been many scientific advances due to the development of new experimental techniques for detecting and characterising X-rays. Observations of X-ray polarisation have, however, not undergone a similar development. This is a shortcoming since a plethora of open questions related to the nature of X-ray sources could be resolved through measurements of the linear polarisation of emitted X-rays. The PoGOLite Pathfinder is a balloon-borne hard X-ray polarimeter operating in the 25-240 keV energy band from a stabilised observation platform. Polarisation is determined using coincident energy deposits in a segmented array of plastic scintillators surrounded by a BGO anticoincidence system and a polyethylene neutron shield. The PoGOLite Pathfinder was launched from the SSC Esrange Space Centre in July 2013. A near-circumpolar flight was achieved with a duration of approximately two weeks. The flight performance of the Pathfinder design is discussed for the three Crab observations conducted. The signal-to-background ratio for the observations is shown to be 0.25 ±0.03 and the Minimum Detectable Polarisation (99 % C.L.) is (28.4 ±2.2) %. A strategy for the continuation of the PoGOLite programme is outlined based on experience gained during the 2013 maiden flight.
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| 6. |
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| 7. |
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| 8. |
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| 9. |
- Kullander, Klas, et al.
(författare)
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Role of EphA4 and EphrinB3 in local neuronal circuits that control walking
- 2003
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Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 299:5614, s. 1889-1892
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Tidskriftsartikel (refereegranskat)abstract
- Local circuits in the spinal cord that generate locomotion are termed central pattern generators (CPGs). These provide coordinated bilateral control over the normal limb alternation that underlies walking. The molecules that organize the mammalian CPG are unknown. Isolated spinal cords from mice lacking either the EphA4 receptor or its ligand ephrinB3 have lost left-right limb alternation and instead exhibit synchrony. We identified EphA4-positive neurons as an excitatory component of the locomotor CPG. Our study shows that dramatic locomotor changes can occur as a consequence of local genetic rewiring and identifies genes required for the development of normal locomotor behavior.
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| 10. |
- Martner, Anna, 1979, et al.
(författare)
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NK cell expression of natural cytotoxicity receptors may determine relapse risk in older AML patients undergoing immunotherapy for remission maintenance.
- 2015
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Ingår i: Oncotarget. - : Impact Journals, LLC. - 1949-2553. ; 6:40, s. 42569-74
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Tidskriftsartikel (refereegranskat)abstract
- In a phase IV trial, eighty-four patients (age 18-79) with acute myeloid leukemia (AML) in first complete remission (CR) received cycles of immunotherapy with histamine dihydrochloride (HDC) and low-dose human recombinant interleukin-2 (IL-2) to prevent relapse in the post-consolidation phase. Aspects of natural killer (NK) cell biology were analyzed before and during immunotherapy with focus on outcome in older patients. In younger (<60 years old, n = 37) and older patients (>60 years old, n = 47), treatment with HDC/IL-2 resulted in an expansion of CD56bright and CD16+ NK cells in blood along with an increased NK cell expression of the natural cytotoxicity receptors (NCR) NKp30 and NKp46. In older patients, a high expression of NKp30 or NKp46 on CD16+ NK cells before and during therapy predicted leukemia-free and overall survival. These results suggest that NK cell functions determine relapse risk and survival in older AML patients and point to biomarkers of efficacy in protocols for remission maintenance.
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| 11. |
- Martner, Anna, 1979, et al.
(författare)
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Role of natural killer cell subsets and natural cytotoxicity receptors for the outcome of immunotherapy in acute myeloid leukemia
- 2016
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Ingår i: Oncoimmunology. - : Informa UK Limited. - 2162-402X. ; 5:1
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Tidskriftsartikel (refereegranskat)abstract
- In a phase IV trial, 84 patients (age 18-79) with acute myeloid leukemia (AML) in first complete remission (CR) received cycles of immunotherapy with histamine dihydrochloride (HDC) and low-dose human recombinant interleukin 2 (IL-2) for 18 months to prevent leukemic relapse. During cycles, the treatment resulted in expansion of CD56(bright) (CD3 /16 /56(bright)) and CD16(+) (CD3 /16(+)/56(+)) natural killer (NK) cells in the blood along with increased NK cell expression of the natural cytotoxicity receptors (NCRs) NKp30 and NKp46. Multivariate analyses correcting for age and risk group demonstrated that high CD56(bright) NK cell counts and high expression of NKp30 or NKp46 on CD16(+) NK cells independently predicted leukemia-free survival (LFS) and overall survival (OS). Our results suggest that the dynamics of NK cell subsets and their NCR expression may determine the efficiency of relapse-preventive immunotherapy in AML.
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| 12. |
- Martner, Anna, et al.
(författare)
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Role of natural killer cell subsets and natural cytotoxicity receptors for the outcome of immunotherapy in acute myeloid leukemia.
- 2015
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Ingår i: OncoImmunology. - 2162-4011. ; 5:1, s. 1041701-1041701
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Tidskriftsartikel (refereegranskat)abstract
- In a phase IV trial, 84 patients (age 18-79) with acute myeloid leukemia (AML) in first complete remission (CR) received cycles of immunotherapy with histamine dihydrochloride (HDC) and low-dose human recombinant interleukin 2 (IL-2) for 18 months to prevent leukemic relapse. During cycles, the treatment resulted in expansion of CD56(bright) (CD3(-)/16(-)/56(bright)) and CD16(+) (CD3(-)/16(+)/56(+)) natural killer (NK) cells in the blood along with increased NK cell expression of the natural cytotoxicity receptors (NCRs) NKp30 and NKp46. Multivariate analyses correcting for age and risk group demonstrated that high CD56(bright) NK cell counts and high expression of NKp30 or NKp46 on CD16(+) NK cells independently predicted leukemia-free survival (LFS) and overall survival (OS). Our results suggest that the dynamics of NK cell subsets and their NCR expression may determine the efficiency of relapse-preventive immunotherapy in AML.
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| 13. |
- Pearce, Mark, et al.
(författare)
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Balloon-borne hard X-ray polarimetry with PoGOLite
- 2012
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Ingår i: 2012 IEEE Nuclear Science Symposium and Medical Imaging Conference Record (NSS/MIC). - : IEEE. - 9781467320306 ; , s. 1885-1892
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Konferensbidrag (refereegranskat)abstract
- PoGOLite is a hard X-ray polarimeter operating in the 25-100 keV energy band. The instrument design is optimised for the observation of compact astrophysical sources. Observations are conducted from a stabilised stratospheric balloon platform at an altitude of approximately 40 km. The primary targets for first balloon flights of a reduced effective area instrument are the Crab and Cygnus-X1. The polarisation of incoming photons is determined using coincident Compton scattering and photo-absorption events reconstructed in an array of plastic scintillator detector cells surrounded by a bismuth germanate oxide (BGO) side anticoincidence shield and a polyethylene neutron shield. A custom attitude control system keeps the polarimeter field-of-view aligned to targets of interest, compensating for sidereal motion and perturbations such as torsional forces in the balloon rigging. An overview of the PoGOLite project is presented and the outcome of the ill-fated maiden balloon flight is discussed.
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| 14. |
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| 15. |
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| 16. |
- Sander, Frida Ewald, et al.
(författare)
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Dynamics of cytotoxic T cell subsets during immunotherapy predicts outcome in acute myeloid leukemia
- 2016
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Ingår i: Oncotarget. - : Impact Journals, LLC. - 1949-2553. ; 7:7, s. 7586-7596
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Tidskriftsartikel (refereegranskat)abstract
- Preventing relapse after chemotherapy remains a challenge in acute myeloid leukemia (AML). Eighty-four non-transplanted AML patients in first complete remission received relapse-preventive immunotherapy with histamine dihydrochloride and low-dose interleukin-2 in an international phase IV trial (ClinicalTrials.gov; NCT01347996). Blood samples were drawn during cycles of immunotherapy and analyzed for CD8(+) (cytotoxic) T cell phenotypes in blood. During the first cycle of therapy, a re-distribution of cytotoxic T cells was observed comprising a reduction of T effector memory cells and a concomitant increase of T effector cells. The dynamics of T cell subtypes during immunotherapy prognosticated relapse and survival, in particular among older patients and remained significantly predictive of clinical outcome after correction for potential confounders. Presence of CD8(+) T cells with specificity for leukemia-associated antigens identified patients with low relapse risk. Our results point to novel aspects of T cell-mediated immunosurveillance in AML and provide conceivable biomarkers in relapse-preventive immunotherapy.
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| 17. |
- Sander, Frida Ewald, et al.
(författare)
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Role of regulatory T cells in acute myeloid leukemia patients undergoing relapse-preventive immunotherapy
- 2017
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Ingår i: Cancer Immunology Immunotherapy. - : Springer Science and Business Media LLC. - 0340-7004 .- 1432-0851. ; 66:11, s. 1473-1484
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Tidskriftsartikel (refereegranskat)abstract
- Regulatory T cells - (Tregs) have been proposed to dampen functions of anti-neoplastic immune cells and thus promote cancer progression. In a phase IV trial (Re: Mission Trial, NCT01347996, http://www.clinicaltrials.gov) 84 patients (age 18-79) with acute myeloid leukemia (AML) in first complete remission (CR) received ten consecutive 3-week cycles of immunotherapy with histamine dihydrochloride (HDC) and low-dose interleukin-2 (IL-2) to prevent relapse of leukemia in the post-consolidation phase. This study aimed at defining the features, function and dynamics of Foxp3(+)CD25(high)CD4(+) T-regs during immunotherapy and to determine the potential impact of T-regs on relapse risk and survival. We observed a pronounced increase in T-reg counts in peripheral blood during initial cycles of HDC/IL-2. The accumulating T-regs resembled thymic-derived natural T-regs (nT(regs)), showed augmented expression of CTLA-4 and suppressed the cell cycle proliferation of conventional T cells ex vivo. Relapse of AML was not prognosticated by T-reg counts at onset of treatment or after the first cycle of immunotherapy. However, the magnitude of T-reg induction was diminished in subsequent treatment cycles. Exploratory analyses implied that a reduced expansion of T-regs in later treatment cycles and a short T-reg telomere length were significantly associated with a favorable clinical outcome. Our results suggest that immunotherapy with HDC/IL-2 in AML entails induction of immunosuppressive T-regs that may be targeted for improved anti-leukemic efficiency.
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| 18. |
- Sindi, S., et al.
(författare)
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Multimodal Preventive Trial for Alzheimer’s Disease : MIND-ADmini Pilot Trial Study Design and Progress
- 2022
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Ingår i: The Journal of Prevention of Alzheimer's Disease. - : Serdi-Editions. - 2274-5807 .- 2426-0266. ; 9:1, s. 30-39
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Tidskriftsartikel (refereegranskat)abstract
- Background: Interventions simultaneously targeting multiple risk factors and mechanisms are most likely to be effective in preventing cognitive impairment. This was indicated in the Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability (FINGER) testing a multidomain lifestyle intervention among at-risk individuals. The importance of medical food at the early symptomatic disease stage, prodromal Alzheimer’s disease (AD), was emphasized in the LipiDiDiet trial. The feasibility and effects of multimodal interventions in prodromal AD are unclear. Objectives: To evaluate the feasibility of an adapted FINGER-based multimodal lifestyle intervention, with or without medical food, among individuals with prodromal AD. Methods: MIND-ADmini is a multinational proof-of-concept 6-month randomized controlled trial (RCT), with four trial sites (Sweden, Finland, Germany, France). The trial targeted individuals with prodromal AD defined using the International Working Group-1 criteria, and with vascular or lifestyle-related risk factors. The parallel-group RCT includes three arms: 1) multimodal lifestyle intervention (nutritional guidance, exercise, cognitive training, vascular/metabolic risk management and social stimulation); 2) multimodal lifestyle intervention+medical food (Fortasyn Connect); and 3) regular health advice/ care (control group). Primary outcomes are feasibility and adherence. Secondary outcomes are adherence to the individual intervention domains and healthy lifestyle changes. Results: Screening began on 28 September 2017 and was completed on 21 May 2019. Altogether 93 participants were randomized and enrolled. The intervention proceeded as planned. Conclusions: For the first time, this pilot trial tests the feasibility and adherence to a multimodal lifestyle intervention, alone or combined with medical food, among individuals with prodromal AD. It can serve as a model for combination therapy trials (non-pharma, nutrition-based and/or pharmacological interventions).
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| 19. |
- Sjöström, Annika E., 1963-, et al.
(författare)
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Analysis of the sfaXII locus in the Escherichia coli meningitis isolate IHE3034 reveals two novel regulatory genes within the promoter-distal region of the main S fimbrial operon
- 2009
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Ingår i: Microbial Pathogenesis. - : Elsevier Ltd. - 0882-4010 .- 1096-1208. ; 46:3, s. 150-158
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Tidskriftsartikel (refereegranskat)abstract
- We describe the expression and regulation of the gene sfaXII located near the SfaII fimbrial determinant in the newborn meningitis Escherichia coli (NMEC) isolate IHE3034. sfaXII belongs to a gene family, the 17kDa genes, typically located downstream (300 – 3000 bp) of different fimbrial operons found in E. coli isolates of uropathogenic and newborn meningitis origin. Using transcriptional sfaXII reporter gene fusions we found that different environmental conditions commonly affecting expression of fimbrial genes also affected sfaXII expression. Analysis of the sfaXII transcripts showed that the gene is part of the main fimbrial operon as it is transcribed together with the rest of the fimbrial genes. In addition, the sfaXII gene can be expressed from a more proximal promoter and is found to be subject to strong down-regulation by the nucleoid protein H-NS. Studies with an sfaXII mutant derivative of IHE3034 did not reveal effects on SfaII fimbrial biogenesis as monitored by e.g. immunofluorescence microscopy. Nevertheless, a mutation in sfaXII resulted in altered expression of other surface components. Moreover, we define a new gene, sfaYII, coding for a putative phosphodiesterase that is located in between the sfaXII gene and the fimbrial biogenesis genes. Our studies by ectopic expression of sfaYII in Vibrio cholerae showed that the gene product caused reduced biofilm formation and it is proposed that sfaYII can influence cyclic-di-GMP turnover in the bacteria. Our findings demonstrate that the operons typical for S-fimbriae of extraintestinal pathogenic E. coli include previously unrecognized novel regulatory genes.
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| 20. |
- Sjöström, Annika E., 1963-, et al.
(författare)
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Analysis of the sfaXII locus in the Escherichia coli meningitis isolate IHE3034 reveals two novel regulatory genes within the promoter-distal region ofthe main S fimbrial operon
- 2009
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Ingår i: Microbial Pathogenesis. - : Elsevier Ltd. - 0882-4010 .- 1096-1208. ; 46:3, s. 150-158
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Tidskriftsartikel (refereegranskat)abstract
- We describe the expression and regulation of the gene sfaXII located near the SfaII fimbrial determinant inthe newborn meningitis Escherichia coli (NMEC) isolate IHE3034. sfaXII belongs to a gene family, the 17-kDa genes, typically located downstream (300–3000 bp) of different fimbrial operons found in E. coli isolates of uropathogenic and newborn meningitis origin. Using transcriptional sfaXII reporter genefusions we found that different environmental conditions commonly affecting expression of fimbrialgenes also affected sfaXII expression. Analysis of the sfaXII transcripts showed that the gene is part of themain fimbrial operon as it is transcribed together with the rest of the fimbrial genes. In addition, the sfaXII gene can be expressed from a more proximal promoter and is found to be subject to strong downregulationby the nucleoid protein H-NS. Studies with an sfaXII mutant derivative of IHE3034 did notreveal effects on SfaII fimbrial biogenesis as monitored by e.g. immunofluorescence microscopy. Nevertheless,a mutation in sfaXII resulted in altered expression of other surface components. Moreover, we define a new gene, sfaYII, coding for a putative phosphodiesterase that is located in between the sfaXII gene and the fimbrial biogenesis genes. Our studies by ectopic expression of sfaYII in Vibrio cholerae showed that the gene product caused reduced biofilm formation and it is proposed that sfaYII caninfluence cyclic-di-GMP turnover in the bacteria. Our findings demonstrate that the operons typical for S-fimbriae of extraintestinal pathogenic E. coli include previously unrecognized novel regulatory genes.
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| 21. |
- Wenzel, Ulf Alexander, 1975, et al.
(författare)
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Spontaneous colitis in Muc2-deficient mice reflects clinical and cellular features of active ulcerative colitis.
- 2014
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Ingår i: PloS one. - : Public Library of Science (PLoS). - 1932-6203. ; 9:6
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Tidskriftsartikel (refereegranskat)abstract
- The colonic mucus layer plays a critical role in intestinal homeostasis by limiting contact between luminal bacteria and the mucosal immune system. A defective mucus barrier in animal models allows bacterial contact with the intestinal epithelium and results in spontaneous colitis. A defective mucus barrier is also a key feature of active ulcerative colitis (UC). Alterations in the immune compartment due to intestinal bacterial breach in mice lacking the colon mucus barrier have not been characterized and correlated to active UC.
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