| 1. |
- Hamidi, Anahita, et al.
(författare)
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TGF-β promotes PI3K-AKT signaling and prostate cancer cell migration through the TRAF6-mediated ubiquitylation of p85α
- 2017
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Ingår i: Science Signaling. - : American Association for the Advancement of Science. - 1945-0877 .- 1937-9145. ; 10:486
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- TGF-β signaling stimulates various intracellular pathways that can promote migration in tumor cells. These pathways are generally thought to be either dependent or independent of transcription factors called SMADs. One of the SMAD-independent pathways (PI3K-AKT) is mediated by a direct interaction between PI3K and the TGF-β type I receptor. However, Hamidi et al. found that the TGF-β–induced activation of PI3K depends on another ubiquitin ligase–mediated mechanism and a SMAD protein but is independent of the kinase function of TβRI. The binding of TGF-β to its receptor triggered the recruitment of PI3K and the ubiquitin ligase TRAF6, which polyubiquitylated the regulatory PI3K subunit p85α, thus enabling phosphorylation of the catalytic PI3K subunit p110, but only in the presence of SMAD7. The abundance of ubiquitylated p85α correlated with migration in cultured cells and prostate tumor grade in patient samples. TRAF6 mediates activation of the other “SMAD-independent” (JNK) pathway. These data suggest that, although distinct, the TGF-β signaling pathways are not as insulated from each other as was once thought.
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| 2. |
- Mattsson, Niklas, 1979, et al.
(författare)
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Age and diagnostic performance of Alzheimer disease CSF biomarkers.
- 2012
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Ingår i: Neurology. - : American Academy of Neurology (AAN). - 1526-632X .- 0028-3878. ; 78:7, s. 468-76
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Tidskriftsartikel (refereegranskat)abstract
- Core CSF changes in Alzheimer disease (AD) are decreased amyloid β(1-42), increased total tau, and increased phospho-tau, probably indicating amyloid plaque accumulation, axonal degeneration, and tangle pathology, respectively. These biomarkers identify AD already at the predementia stage, but their diagnostic performance might be affected by age-dependent increase of AD-type brain pathology in cognitively unaffected elderly.
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| 3. |
- Semb, Gunvor, et al.
(författare)
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A Scandcleft randomised trials of primary surgery for unilateral cleft lip and palate: 1. Planning and management.
- 2017
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Ingår i: Journal of Plastic Surgery and Hand Surgery. - : Taylor & Francis. - 2000-656X .- 2000-6764. ; 51:1, s. 2-13
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND AND AIMS: Longstanding uncertainty surrounds the selection of surgical protocols for the closure of unilateral cleft lip and palate, and randomised trials have only rarely been performed. This paper is an introduction to three randomised trials of primary surgery for children born with complete unilateral cleft lip and palate (UCLP). It presents the protocol developed for the trials in CONSORT format, and describes the management structure that was developed to achieve the long-term engagement and commitment required to complete the project.METHOD: Ten established national or regional cleft centres participated. Lip and soft palate closure at 3-4 months, and hard palate closure at 12 months served as a common method in each trial. Trial 1 compared this with hard palate closure at 36 months. Trial 2 compared it with lip closure at 3-4 months and hard and soft palate closure at 12 months. Trial 3 compared it with lip and hard palate closure at 3-4 months and soft palate closure at 12 months. The primary outcomes were speech and dentofacial development, with a series of perioperative and longer-term secondary outcomes.RESULTS: Recruitment of 448 infants took place over a 9-year period, with 99.8% subsequent retention at 5 years.CONCLUSION: The series of reports that follow this introductory paper include comparisons at age 5 of surgical outcomes, speech outcomes, measures of dentofacial development and appearance, and parental satisfaction. The outcomes recorded and the numbers analysed for each outcome and time point are described in the series.TRIAL REGISTRATION: ISRCTN29932826.
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| 4. |
- Thakur, Noopur, et al.
(författare)
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TGF beta-induced invasion of prostate cancer cells is promoted by c-Jun-dependent transcriptional activation of Snail1
- 2014
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Ingår i: Cell Cycle. - : Informa UK Limited. - 1538-4101 .- 1551-4005. ; 13:15, s. 2400-2414
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Tidskriftsartikel (refereegranskat)abstract
- High levels of transforming growth factor-beta (TGF beta) correlate with poor prognosis for patients with prostate cancer and other cancers. TGF beta is a multifunctional cytokine and crucial regulator of cell fate, such as epithelial to mesenchymal transition (EMT), which is implicated in cancer invasion and progression. TGF beta conveys its signals upon binding to type I and type II serine/threonine kinase receptors (T beta RI/II); phosphorylation of Smad2 and Smad3 promotes their association with Smad4, which regulates expression of targets genes, such as Smad7, p21, and c-Jun. TGF beta also activates the ubiquitin ligase tumor necrosis factor receptor-associated factor 6 (TRAF6), which associates with T beta RI and activates the p38 mitogen-activated protein kinase (MAPK) pathway. Snail1 is a key transcription factor, induced by TGF beta that promotes migration and invasion of cancer cells. In this study, we have identified a novel binding site for c-Jun in the promoter of the Snail1 gene and report that the activation of the TGF beta-TRAF6-p38 MAPK pathway promotes both c-Jun expression and its activation via p38a-dependent phosphorylation of c-Jun at Ser63. The TRAF6-dependent activation of p38 also leads to increased stability of c-Jun, due to p38-dependent inactivation of glycogen synthase kinase (GSK) 3 beta by phosphorylation at Ser9. Thus, our findings elucidate a novel role for the p38 MAPK pathway in stimulated cells, leading to activation of c-Jun and its binding to the promoter of Snail1, thereby triggering motility and invasiveness of aggressive human prostate cancer cells.
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| 5. |
- Ahl, Magnus, et al.
(författare)
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Effects of orthognathic surgery on respiratory function during sleep : A prospective longitudinal study
- 2024
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Ingår i: Orthodontics & craniofacial research. - : John Wiley & Sons. - 1601-6335 .- 1601-6343.
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Tidskriftsartikel (refereegranskat)abstract
- When treating patients with orthognathic surgery, there might be a risk of obstructive sleep apnoea (OSA) due to soft tissue changes in the upper airways, especially in patients treated with isolated mandibular setback or mandibular setback in combination with maxillary advancement. In the present study, we assessed respiratory function during sleep with home cardiorespiratory polygraphy in 62 patients who had not been previously been diagnosed with OSA at three times: prior to orthognathic surgery for aesthetic and functional indications, and then 3 months and 1 year after surgery. We evaluated surgical displacement based on measurements in three dimensions using pre- and post-operative computed tomography. There were only minor changes in the respiratory parameters such as the apnoea-hypopnoea index (AHI), the apnoea-hypopnoea index in the supine position (AHIsup), the oxygen saturation index (ODI) and the snore index. There was no significant correlation between surgical displacement and the AHI, AHIsup and ODI. There was a weak but significant correlation between vertical displacement of the anterior mandible and the snore index. Within the limitations of the present study, the risk for iatrogenic obstruction of the upper airways seems to be low in patients without OSA treated with orthognathic surgery.
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| 6. |
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| 7. |
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| 8. |
- Blennow, Kaj, 1958, et al.
(författare)
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No association between the alpha2-macroglobulin (A2M) deletion and Alzheimer's disease, and no change in A2M mRNA, protein, or protein expression.
- 2000
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Ingår i: Journal of neural transmission (Vienna, Austria : 1996). - : Springer Science and Business Media LLC. - 0300-9564 .- 1435-1463. ; 107:8-9, s. 1065-79
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Tidskriftsartikel (refereegranskat)abstract
- A polymorphism consisting of a deletion near the 5' splice site of exon 18 on the alpha2-macroglobulin (A2M) gene (A2M-2) has been suggested to be associated with Alzheimer's disease (AD) in family-based studies. We studied the A2M-2 allele together with the ApoE alleles in a large series on patients with AD (n = 449) and age-matched controls (n = 349). Neuropathologically confirmed diagnoses were available in 199 cases (94 AD and 107 control cases). We found no increase in A2M-2 genotype or allele frequencies in AD (27.5% and 14.6%) versus controls (26.4% and 14.9%). In contrast, a marked increase (p < 0.0001) in ApoE epsilon4 genotype or allele frequencies was found in AD (66.6% and 41.2%) as compared with controls (29.8% and 16.5%), suggesting sufficient statistical power in our sample. No relation was found between the A2M-2 and the ApoE epsilon4 allele. No change in A2M exon 17-18 mRNA size or sequence or A2M protein size was found in cases carrying the A2M-2 deletion, suggesting that there is no biological consequences of the A2M intronic deletion. No change in A2M protein level in cerebrospinal fluid was found in AD, suggesting that the A2M-2 allele does not effect the A2M protein expression in the brain. The lack of an association between the A2M-2 allele and AD in the present study, and the lack of abnormalities in the A2M mRNA or protein suggest that the A2M-2 allele is not associated with AD.
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| 9. |
- Duits, Flora H., et al.
(författare)
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The cerebrospinal fluid "Alzheimer profile": Easily said, but what does it mean?
- 2014
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Ingår i: Alzheimer's & Dementia. - : Elsevier. - 1552-5260 .- 1552-5279. ; 10:6, s. 713-723
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Tidskriftsartikel (refereegranskat)abstract
- Background: We aimed to identify the most useful definition of the "cerebrospinal fluid Alzheimer profile," based on amyloid-beta(1-42) (A beta(42)), total tau, and phosphorylated tau (p-tau), for diagnosis and prognosis of Alzheimers disease (AD). Methods: We constructed eight Alzheimer profiles with previously published combinations, including regression formulas and simple ratios. We compared their diagnostic accuracy and ability to predict dementia due to AD in 1385 patients from the Amsterdam Dementia Cohort. Results were validated in an independent cohort (n = 1442). Results: Combinations outperformed individual biomarkers. Based on the sensitivity of the best performing regression formulas, cutoffs were chosen at 0.52 for the tau/A beta(42) ratio and 0.08 for the p-tau/A beta(42) ratio. Ratios performed similar to formulas (sensitivity, 91%-93%; specificity, 81%-84%). The same combinations best predicted cognitive decline in mild cognitive impairment patients. Validation confirmed these results, especially regarding the tau/A beta(42) ratio. Conclusions: A tau/A beta(42) ratio of greater than0.52 constitutes a robust cerebrospinal fluid Alzheimer profile. We recommend using this ratio to combine biomarkers.
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