| 1. |
- Kanai, M, et al.
(författare)
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- 2023
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swepub:Mat__t
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| 2. |
- Niemi, MEK, et al.
(författare)
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- 2021
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swepub:Mat__t
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| 3. |
- Duffy, DL, et al.
(författare)
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Publisher Correction: Novel pleiotropic risk loci for melanoma and nevus density implicate multiple biological pathways
- 2019
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Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 10:1, s. 299-
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Tidskriftsartikel (refereegranskat)abstract
- The original version of this Article contained errors in the spelling of the authors Fan Liu and M. Arfan Ikram, which were incorrectly given as Fan Lui and Arfan M. Ikram. In addition, the original version of this Article also contained errors in the author affiliations which are detailed in the associated Publisher Correction.
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| 17. |
- Gao, Y, et al.
(författare)
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Ancestral SARS-CoV-2-specific T cells cross-recognize the Omicron variant
- 2022
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Ingår i: Nature medicine. - : Springer Science and Business Media LLC. - 1546-170X .- 1078-8956. ; 28:3, s. 472-
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Tidskriftsartikel (refereegranskat)abstract
- The emergence of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron (B.1.1.529) variant of concern (VOC) has destabilized global efforts to control the impact of coronavirus disease 2019 (COVID-19). Recent data have suggested that B.1.1.529 can readily infect people with naturally acquired or vaccine-induced immunity, facilitated in some cases by viral escape from antibodies that neutralize ancestral SARS-CoV-2. However, severe disease appears to be relatively uncommon in such individuals, highlighting a potential role for other components of the adaptive immune system. We report here that SARS-CoV-2 spike-specific CD4+ and CD8+ T cells induced by prior infection or BNT162b2 vaccination provide extensive immune coverage against B.1.1.529. The median relative frequencies of SARS-CoV-2 spike-specific CD4+ T cells that cross-recognized B.1.1.529 in previously infected or BNT162b2-vaccinated individuals were 84% and 91%, respectively, and the corresponding median relative frequencies for SARS-CoV-2 spike-specific CD8+ T cells were 70% and 92%, respectively. Pairwise comparisons across groups further revealed that SARS-CoV-2 spike-reactive CD4+ and CD8+ T cells were functionally and phenotypically similar in response to the ancestral strain or B.1.1.529. Collectively, our data indicate that established SARS-CoV-2 spike-specific CD4+ and CD8+ T cell responses, especially after BNT162b2 vaccination, remain largely intact against B.1.1.529.
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| 18. |
- Grant, MA, et al.
(författare)
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The metal-free and calcium-bound structures of a gamma-carboxyglutamic acid-containing contryphan from Conus marmoreus, glacontryphan-M
- 2004
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Ingår i: Journal of Biological Chemistry. - 1083-351X. ; 279:31, s. 32464-32473
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Tidskriftsartikel (refereegranskat)abstract
- Glacontryphan-M, a novel calcium-dependent inhibitor of L-type voltage-gated Ca2+ channels expressed in mouse pancreatic beta-cells, was recently isolated from the venom of the cone snail Conus marmoreus (Hansson, K., Ma, X., Eliasson, L., Czerwiec, E., Furie, B., Furie, B. C., Rorsman, P., and Stenflo, J. ( 2004) J. Biol. Chem. 278, 32453-32463). The conserved disulfide-bonded loop of the contryphan family of conotoxins including a D-Trp is present; however, unique to glacontryphan-M is a histidine within the intercysteine-loop and two gamma-carboxy-glutamic acid (Gla) residues, formed by post-translational modification of glutamic acid. The two calcium-binding Gla residues are located in a four residue N-terminal extension of this contryphan. To better understand the structural and functional significance of these residues, we have determined the structure of glacontryphan-M using two-dimensional H-1 NMR spectroscopy in the absence and presence of calcium. Comparisons of the glacontryphan-M structures reveal that calcium binding induces structural perturbations within the Gla-containing N terminus and the Cys(11)-Cys(5)-Pro(6) region of the intercysteine loop. The backbone of N-terminal residues perturbed by calcium, Gla(2) and Ser(3), moves away from the His(8) and Trp(10) aromatic rings and the alignment of the D-Trp(7) and His(8) aromatic rings with respect to the Trp(10) rings is altered. The blockage of L-type voltage-gated Ca2+ channel currents by glacontryphan-M requires calcium binding to N-terminal Gla residues, where presumably histidine and tryptophan may be accessible for interaction with the channel. The backbone Calpha conformation of the intercysteine loop of calcium-bound glacontryphan-M superimposes on known structures of contryphan-R and Vn (0.83 and 0.66 Angstrom, respectively). Taken together these data identify that glacontryphan-M possesses the canonical contryphan intercysteine loop structure, yet possesses critical determinants necessary for a calcium-induced functionally required conformation.
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| 19. |
- Hansson, AC, et al.
(författare)
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Biphasic autoregulation of mineralocorticoid receptor mRNA in the medial septal nucleus by aldosterone
- 2002
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Ingår i: Neuroendocrinology. - : S. Karger AG. - 0028-3835 .- 1423-0194. ; 75:6, s. 358-366
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Tidskriftsartikel (refereegranskat)abstract
- The time-dependent action of aldosterone was analyzed on the regulation of mineralocorticoid receptor (MR) and glucocorticoid receptor (GR) mRNAs in the brain. Bilaterally adrenalectomized rats were injected subcutaneously with a single low dose of aldosterone (0.01 mg/kg, s.c.). By means of in situ hybridization MR and GR mRNA levels were studied in autoradiograms 2, 4, 8 and 24 h after the hormone injection in brain regions related to stress responses, i.e. subregions of the dorsal hippocampus (CA1 to CA4 and dentate gyrus), the hypothalamic paraventricular nucleus, and the septum. The findings show a biphasic regulation of MR mRNA levels in the medial septal nucleus with substantial increases after 4 h (79% increase) followed by substantial decreases in MR mRNA levels after 24 h (71% decrease), whereas no changes in MR mRNA levels were observed in the lateral septal nucleus. A negative autoregulation of hippocampal MR mRNA levels was observed only in the CA2 subregion (38% decrease) at the 8-hour time interval. Over the same time interval a negative cross-regulation of GR mRNA by aldosterone was observed in all hippocampal subfields (32–57% decrease) except in CA2. No changes in GR mRNA levels were found in the hypothalamic paraventricular nucleus. The time-dependent action of corticosterone (10 mg/kg, s.c.) was analyzed in the same animal model revealing no changes in MR mRNA levels in the medial and lateral septal nuclei. The present findings suggest that the medial septal nucleus shows a unique responsiveness to aldosterone in the adrenalectomized model in terms of biphasic changes in MR mRNA levels. Activated MR in the medial septal nucleus may therefore take part in the regulation of septo-hippocampal cholinergic pathways and thus of limbic circuits.
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| 20. |
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| 21. |
- Hansson, AC, et al.
(författare)
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Dissociation of antidepressant-like activity of escitalopram and nortriptyline on behaviour and hippocampal BDNF expression in female rats
- 2011
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Ingår i: Journal of psychopharmacology (Oxford, England). - : SAGE Publications. - 1461-7285 .- 0269-8811. ; 25:10, s. 1378-1387
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Tidskriftsartikel (refereegranskat)abstract
- A major hypothesis of depression postulates that a dysregulation of the neurotrophin systems is directly involved in the pathophysiology of depression, and that restoration of such deficits may underlie the therapeutic efficacy of antidepressant treatment. One key finding supporting this hypothesis is upregulation of brain derived neurotrophic factor (BDNF) in the hippocampus after antidepressant treatment. Here, we further test the hypothesis of BDNF involvement in antidepressant action in a genetic rat model of depression after chronic oral treatment with escitalopram, nortriptyline or placebo. Active treatments had significant behavioural antidepressant-like actions in female rats of the Flinders Sensitive Line (FSL) and non-selected Sprague Dawley (SD) rats, while Flinders Resistant Line (FRL) rats were unaffected. Escitalopram, but not nortriptyline, markedly reduced BDNF mRNA levels in the dentate gyrus of FSL rats. The BDNF downregulation was common to the four major promoters of the gene. Treatments did not affect BDNF expression in FRL or SD strains. We conclude that the antidepressant effects of escitalopram and nortriptyline, two common drugs with different pharmacological profiles, appear to be unrelated to the regulation of hippocampal BDNF expression in female rats. These results indicate that the tropic hypothesis of depression has limitations and emphasize the need for validated disease models of depression to assess potential treatment targets.
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| 27. |
- Hansson, B, et al.
(författare)
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Skeletal muscle signaling responses to resistance exercise of the elbow extensors are not compromised by a preceding bout of aerobic exercise
- 2019
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Ingår i: American journal of physiology. Regulatory, integrative and comparative physiology. - : American Physiological Society. - 1522-1490 .- 0363-6119. ; 317:1, s. R83-R92
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Tidskriftsartikel (refereegranskat)abstract
- The current study examined the effects of a preceding bout of aerobic exercise (AE) on subsequent molecular signaling to resistance exercise (RE) of the elbow extensors. Eleven men performed unilateral elbow-extensor AE (~45 min at 70% peak workload) followed by unilateral RE (4 × 7 maximal repetitions) for both arms. Thus, one arm performed AE+RE interspersed with 15 min recovery, whereas the other arm conducted RE alone. Muscle biopsies were taken from the triceps brachii of each arm immediately before (PRE) and 15 min (POST1) and 3 h (POST2) after RE. Molecular markers involved in translation initiation, protein breakdown, mechanosignaling, and ribosome biogenesis were analyzed. Peak power during RE was reduced by 24% (±19%) when preceded by AE ( P < 0.05). Increases in PGC1a and MuRF1 expression were greater from PRE to POST2 in AE+RE compared with RE (18- vs. 3.5- and 4- vs. 2-fold, respectively, interaction, P < 0.05). Myostatin mRNA decreased in both arms ( P < 0.05). Phosphorylation of AMPK (Thr172) increased (2.5-fold), and 4E-BP1 (Thr37/46) decreased (2.0-fold), after AE (interactions, P < 0.05). p70 S6K, yes-associated protein, and c-Jun NH2-terminal kinase phosphorylation were unaltered, whereas focal adhesion kinase decreased ~1.5-fold, and β1-integrin increased ~1.3- to 1.5-fold, (time effect, P < 0.05). Abundance of 45S pre-ribosomal (r)RNA (internally transcribed spacer, ITS) decreased (~30%) after AE (interaction, P < 0.05), whereas CMYC mRNA was greater in AE+RE compared with RE (12-fold, P < 0.05). POLR1B abundance increased after both AE+RE and RE. All together, our results suggest that a single bout of AE leads to an immediate decrease in signaling for translation initiation and ribosome biogenesis. Yet, this did not translate into altered RE-induced signaling during the 3-h postexercise recovery period.
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| 28. |
- Kang, J, et al.
(författare)
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Total chemical synthesis and NMR characterization of the glycopeptide tx5a, a heavily post-translationally modified conotoxin, reveals that the glycan structure is alpha-D-Gal-(1 -> 3)-alpha-D-GalNAc
- 2004
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Ingår i: European Journal of Biochemistry. - : Wiley. - 0014-2956 .- 1432-1033. ; 271:23-24, s. 4939-4949
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Tidskriftsartikel (refereegranskat)abstract
- The 13-amino acid glycopeptide tx5a (Gla-Cys-Cys-Gla-Asp-Gly-Trp*-Cys-Cys-Thr*-Ala-Ala-Hyp-OH, where Trp* = 6-bromotryptophan and Thr* = Gal-GalNAc-threonine), isolated from Conus textile, causes hyperactivity and spasticity when injected intracerebral ventricularly into mice. It contains nine post-translationally modified residues: four cysteine residues, two gamma-carboxyglutamic acid residues, and one residue each of 6-bromotryptophan, 4-trans-hydroxyproline and glycosylated threonine. The chemical nature of each of these has been determined with the exception of the glycan linkage pattern on threonine and the stereochemistry of the 6-bromotryptophan residue. Previous investigations have demonstrated that tx5a contains a disaccharide composed of N-acetylgalactosamine (GalNAc) and galactose (Gal), but the interresidue linkage was not characterized. We hypothesized that tx5a contained the T-antigen, beta-D-Gal-(1-->3)-alpha-D-GalNAc, one of the most common O-linked glycan structures, identified previously in another Conus glycopeptide, contalukin-G. We therefore utilized the peracetylated form of this glycan attached to Fmoc-threonine in an attempted synthesis. While the result-ing synthetic peptide (Gla-Cys-Cys-Gla-Asp-Gly-Trp*-Cys-Cys-Thr*-Ala-Ala-Hyp-OH, where Trp* =6-bromotryptophan and Thr* = beta-D-Gal-(1-->3)-alpha-D-GalNAc-threonine) and the native peptide had almost identical mass spectra, a comparison of their RP-HPLC chromatograms suggested that the two forms were not identical. Two-dimensional H-1 homonuclear and C-13-H-1 heteronuclear NMR spectroscopy of native tx5a isolated from Conus textile was then used to determine that the glycan present on tx5a indeed is not the aforementioned T-antigen, but rather alpha-D-Gal-(1-->3)-alpha-D-GalNAc.
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| 29. |
- Leeksma, AC, et al.
(författare)
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Genomic arrays identify high-risk chronic lymphocytic leukemia with genomic complexity: a multi-center study
- 2021
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Ingår i: Haematologica. - : Ferrata Storti Foundation (Haematologica). - 1592-8721 .- 0390-6078. ; 106:1, s. 87-97
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Tidskriftsartikel (refereegranskat)abstract
- Complex karyotype (CK) identified by chromosome-banding analysis (CBA) has shown prognostic value in chronic lymphocytic leukemia (CLL). Genomic arrays offer high-resolution genome-wide detection of copy-number alterations (CNAs) and could therefore be well equipped to detect the presence of a CK. Current knowledge on genomic arrays in CLL is based on outcomes of single center studies, in which different cutoffs for CNA calling were used. To further determine the clinical utility of genomic arrays for CNA assessment in CLL diagnostics, we retrospectively analyzed 2293 arrays from 13 diagnostic laboratories according to established standards. CNAs were found outside regions captured by CLL FISH probes in 34% of patients, and several of them including gains of 8q, deletions of 9p and 18p (p<0.01) were linked to poor outcome after correction for multiple testing. Patients (n=972) could be divided in three distinct prognostic subgroups based on the number of CNAs. Only high genomic complexity (high-GC), defined as ≥5 CNAs emerged as an independent adverse prognosticator on multivariable analysis for time to first treatment (Hazard ratio: 2.15, 95% CI: 1.36-3.41; p=0.001) and overall survival (Hazard ratio: 2.54, 95% CI: 1.54-4.17; p<0.001; n=528). Lowering the size cutoff to 1 Mb in 647 patients did not significantly improve risk assessment. Genomic arrays detected more chromosomal abnormalities and performed at least as well in terms of risk stratification compared to simultaneous chromosome banding analysis as determined in 122 patients. Our findings highlight genomic array as an accurate tool for CLL risk stratification.
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| 40. |
- Sun, ND, et al.
(författare)
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Modified VEGF-A mRNA induces sustained multifaceted microvascular response and accelerates diabetic wound healing
- 2018
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Ingår i: Scientific reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 8:1, s. 17509-
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Tidskriftsartikel (refereegranskat)abstract
- Capable of mediating efficient transfection and protein production without eliciting innate immune responses, chemically modified mRNA holds great potential to produce paracrine factors at a physiologically beneficial level, in a spatiotemporally controlled manner, and with low toxicity. Although highly promising in cardiovascular medicine and wound healing, effects of this emerging therapeutic on the microvasculature and its bioactivity in disease settings remain poorly understood. Here, we longitudinally and comprehensively characterize microvascular responses to AZD8601, a modified mRNA encoding vascular endothelial growth factor A (VEGF-A), in vivo. Using multi-parametric photoacoustic microscopy, we show that intradermal injection of AZD8601 formulated in a biocompatible vehicle results in pronounced, sustained and dose-dependent vasodilation, blood flow upregulation, and neovessel formation, in striking contrast to those induced by recombinant human VEGF-A protein, a non-translatable variant of AZD8601, and citrate/saline vehicle. Moreover, we evaluate the bioactivity of AZD8601 in a mouse model of diabetic wound healing in vivo. Using a boron nanoparticle-based tissue oxygen sensor, we show that sequential dosing of AZD8601 improves vascularization and tissue oxygenation of the wound bed, leading to accelerated re-epithelialization during the early phase of diabetic wound healing.
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| 41. |
- Tahera, Y, et al.
(författare)
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Glucocorticoid receptor and nuclear factor-kappa B interactions in restraint stress-mediated protection against acoustic trauma
- 2006
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Ingår i: Endocrinology. - : The Endocrine Society. - 0013-7227 .- 1945-7170. ; 147:9, s. 4430-4437
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Tidskriftsartikel (refereegranskat)abstract
- The role of glucocorticoid receptors (GRs) in the protective effect of restraint stress (RS) before acoustic trauma was studied in spiral ganglion neurons of CBA mice. RS increased corticosterone and protected against elevated auditory brain stem thresholds caused by acoustic trauma. This protection was inhibited by the pretreatment with a corticosterone synthesis inhibitor, metyrapone (MET), and a GR antagonist (RU486). RS followed by acoustic trauma caused an immediate increase in corticosterone that triggered nuclear translocation of GR, without a change in the expression of GR protein. RU486 + MET before RS and acoustic trauma caused an immediate increase in GR mRNA followed by increased GR protein expression (24 h after trauma). GR signaling was further characterized by analyzing nuclear factor-κB (NFκB) nuclear translocation and protein expression. NFκB nuclear translocation was reduced after acoustic trauma or pretreatment with RU486 + MET before RS and acoustic trauma. On the contrary, RS protected against the trauma-induced NFκB reduction of its nuclear translocation in inhibitory-κB (IκB)-dependent manner. RU486 + MET caused a simultaneous decreased IκB expression and NFκB nuclear translocation, demonstrating an interference with the IκB-mediated activation of NFκB. In summary, RS protects the cochlea from acoustic trauma by increasing corticosterone and activating GRs. These results emphasis how GR activity modulates hearing sensitivity and its importance for the rationale use of glucocorticoids in inner ear diseases.
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