| 1. |
- Safavi, Setareh, et al.
(author)
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HSP90 inhibition blocks ERBB3 and RET phosphorylation in myxoid/round cell liposarcoma and causes massive cell death in vitro and in vivo
- 2016
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In: OncoTarget. - : Impact Journals, LLC. - 1949-2553. ; 7:1, s. 433-445
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Journal article (peer-reviewed)abstract
- Myxoid sarcoma (MLS) is one of the most common types of malignant soft tissue tumors. MLS is characterized by the FUS-DDIT3 or EWSR1-DDIT3 fusion oncogenes that encode abnormal transcription factors. The receptor tyrosine kinase (RTK) encoding RET was previously identified as a putative downstream target gene to FUS-DDIT3 and here we show that cultured MLS cells expressed phosphorylated RET together with its ligand Persephin. Treatment with RET specific kinase inhibitor Vandetanib failed to reduce RET phosphorylation and inhibit cell growth, suggesting that other RTKs may phosphorylate RET. A screening pointed out EGFR and ERBB3 as the strongest expressed phosphorylated RTKs in MLS cells. We show that ERBB3 formed nuclear and cytoplasmic complexes with RET and both RTKs were previously reported to form complexes with EGFR. The formation of RTK hetero complexes could explain the observed Vandetanib resistence in MLS. EGFR and ERBB3 are clients of HSP90 that help complex formation and RTK activation. Treatment of cultured MLS cells with HSP90 inhibitor 17-DMAG, caused loss of RET and ERBB3 phosphorylation and lead to rapid cell death. Treatment of MLS xenograft carrying Nude mice resulted in massive necrosis, rupture of capillaries and hemorrhages in tumor tissues. We conclude that complex formation between RET and other RTKs may cause RTK inhibitor resistance. HSP90 inhibitors can overcome this resistance and are thus promising drugs for treatment of MLS/RCLS.
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| 2. |
- Abdallah, Nancy, et al.
(author)
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Topology of posets with special partial matchings
- 2019
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In: Advances in Mathematics. - : Academic Press. - 0001-8708 .- 1090-2082. ; 348, s. 255-276
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Journal article (peer-reviewed)abstract
- Special partial matchings (SPMs) are a generalisation of Brentis special matchings. Let a pircon be a poset in which every non-trivial principal order ideal is finite and admits an SPM. Thus pircons generalise Mariettis zircons. We prove that every open interval in a pircon is a PL ball or a PL sphere. It is then demonstrated that Bruhat orders on certain twisted identities and quasiparabolic W-sets constitute pircons. Together, these results extend a result of Can, Cherniaysky, and Twelbeck, prove a conjecture of Hultman, and confirm a claim of Rains and Vazirani.
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| 3. |
- Bridel, Claire, et al.
(author)
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Diagnostic Value of Cerebrospinal Fluid Neurofilament Light Protein in Neurology : A Systematic Review and Meta-analysis
- 2019
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In: JAMA Neurology. - : American Medical Association (AMA). - 2168-6149 .- 2168-6157. ; 76:9, s. 1035-1048
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Research review (peer-reviewed)abstract
- Importance Neurofilament light protein (NfL) is elevated in cerebrospinal fluid (CSF) of a number of neurological conditions compared with healthy controls (HC) and is a candidate biomarker for neuroaxonal damage. The influence of age and sex is largely unknown, and levels across neurological disorders have not been compared systematically to date.Objectives To assess the associations of age, sex, and diagnosis with NfL in CSF (cNfL) and to evaluate its potential in discriminating clinically similar conditions.Data Sources PubMed was searched for studies published between January 1, 2006, and January 1, 2016, reporting cNfL levels (using the search terms neurofilament light and cerebrospinal fluid) in neurological or psychiatric conditions and/or in HC.Study Selection Studies reporting NfL levels measured in lumbar CSF using a commercially available immunoassay, as well as age and sex.Data Extraction and Synthesis Individual-level data were requested from study authors. Generalized linear mixed-effects models were used to estimate the fixed effects of age, sex, and diagnosis on log-transformed NfL levels, with cohort of origin modeled as a random intercept.Main Outcome and Measure The cNfL levels adjusted for age and sex across diagnoses.Results Data were collected for 10 059 individuals (mean [SD] age, 59.7 [18.8] years; 54.1% female). Thirty-five diagnoses were identified, including inflammatory diseases of the central nervous system (n = 2795), dementias and predementia stages (n = 4284), parkinsonian disorders (n = 984), and HC (n = 1332). The cNfL was elevated compared with HC in a majority of neurological conditions studied. Highest levels were observed in cognitively impaired HIV-positive individuals (iHIV), amyotrophic lateral sclerosis, frontotemporal dementia (FTD), and Huntington disease. In 33.3% of diagnoses, including HC, multiple sclerosis, Alzheimer disease (AD), and Parkinson disease (PD), cNfL was higher in men than women. The cNfL increased with age in HC and a majority of neurological conditions, although the association was strongest in HC. The cNfL overlapped in most clinically similar diagnoses except for FTD and iHIV, which segregated from other dementias, and PD, which segregated from atypical parkinsonian syndromes.Conclusions and Relevance These data support the use of cNfL as a biomarker of neuroaxonal damage and indicate that age-specific and sex-specific (and in some cases disease-specific) reference values may be needed. The cNfL has potential to assist the differentiation of FTD from AD and PD from atypical parkinsonian syndromes.
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| 4. |
- Enqvist, Martin, 1976-, et al.
(author)
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The CDIO Initiative from an Automatic Control Project Course Perspective
- 2005
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In: Proceedings of the 16th IFAC World Congress. - 9783902661753 ; , s. 2283-2283
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Conference paper (peer-reviewed)abstract
- The CDIO (Conceive Design Implement Operate) Initiative is explained, and some of the results at the Applied Physics and Electrical Engineering program at Linköping University, Sweden, are presented. A project course in Automatic Control is used as an example. The projects within the course are carried out using the LIPS (Linköping interactive project steering) model. An example of a project, the golf playing industrial robot, and the results from this project are also covered.
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| 5. |
- Gourdon, Pontus Emanuel, 1978, et al.
(author)
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Optimized in vitro and in vivo expression of proteorhodopsin: A seven-transmembrane proton pump
- 2008
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In: Protein Expression and Purification. - : Elsevier BV. - 1096-0279 .- 1046-5928. ; 58:1, s. 103-113
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Journal article (peer-reviewed)abstract
- Proteorhodopsin is an integral membrane light-harvesting proton pump that is found in bacteria distributed throughout global surface waters. Here, we present a protocol for functional in vitro production of pR using a commercial cell-free synthesis system yielding 1.0 mg purified protein per milliliter of cell lysate. We also present an optimized protocol for in vivo over-expression of pR in Escherichia coli, and a two-step purification yielding 5 mg of essentially pure functional protein per liter of culture. Both approaches are straightforward, rapid, and easily scalable. Thus either may facilitate the exploitation of pR for commercial biotechnological applications. Finally, the implications of some observations of the in vitro synthesis behavior, as well as preliminary results towards a structural determination of pR are discussed.
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| 6. |
- Hansson, Caroline, 1981, et al.
(author)
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Risk factors for suicide in bipolar disorder: a cohort study of 12 850 patients
- 2018
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In: Acta Psychiatrica Scandinavica. - : Wiley. - 0001-690X .- 1600-0447. ; 138:5, s. 456-463
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Journal article (peer-reviewed)abstract
- ObjectiveMethodBipolar disorder carries a high risk of suicide. Identification of risk factors is important. The aim of this study was to study risk factors for suicide in a large cohort of men and women with bipolar disorder. A prospective cohort study using clinical data from the Swedish National Quality Register for Bipolar Affective Disorder (BipolaR). The outcome variable was suicide captured in the Cause of Death Register between 2004 and 2014. Hazard ratios (HR) were calculated using Cox proportional hazards models. ResultsConclusionsOf 12 850 persons (4844 men and 8006 women) with bipolar disorder, 90 (55 men and 35 women) died by suicide during the follow-up period (between 1 and 10 years). Male sex (HR 2.56), living alone (HR 2.45), previous suicide attempts (HR 4.10), comorbid psychiatric disorder (HR 2.64), recent affective episodes (HR 2.39), criminal conviction (HR 4.43), psychiatric inpatient care (HR 2.79), and involuntary commitment (HR 3.50) were significant risk factors for suicide. Several of the statistically significant risk factors for suicide in bipolar disorder differed between men and women. Risk factors for suicide in bipolar disorder include factors associated with suicide in general, but also diagnosis-specific factors.
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| 7. |
- Hansson, Mattias, et al.
(author)
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Artifactual insulin release from differentiated embryonic stem cells.
- 2004
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In: Diabetes. - 0012-1797. ; 53:10, s. 2603-9
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Journal article (peer-reviewed)abstract
- Several recent reports claim the generation of insulin-producing cells from embryonic stem cells via the differentiation of progenitors that express nestin. Here, we investigate further the properties of these insulin-containing cells. We find that although differentiated cells contain immunoreactive insulin, they do not contain proinsulin-derived C-peptide. Furthermore, we find variable insulin release from these cells upon glucose addition, but C-peptide release is never detected. In addition, many of the insulin-immunoreactive cells are undergoing apoptosis or necrosis. We further show that cells cultured in the presence of a phosphoinositide 3-kinase inhibitor, which previously was reported to facilitate the differentiation of insulin(+) cells, are not C-peptide immunoreactive but take up fluorescein isothiocyanate-labeled insulin from the culture medium. Together, these data suggest that nestin(+) progenitor cells give rise to a population of cells that contain insulin, not as a result of biosynthesis but from the uptake of exogenous insulin. We conclude that C-peptide biosynthesis and secretion should be demonstrated to claim insulin production from embryonic stem cell progeny.
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| 8. |
- Hansson, Mikael, 1975-
(author)
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En kommentar till privaträttsliga diskrimineringsförbud med utgångspunkt i DCFR bok II kapitel 2
- 2012
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In: Svensk Juristtidning. - Uppsala : Iustus förlag. - 0039-6591. ; :10, s. 941-961
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Journal article (peer-reviewed)abstract
- I artikeln presenteras och kommenteras diskrimineringsförbuden i DCFR. Trots att de är en praktiskt taget oumbärlig del av det föreslagna regelverket är de lite säregna, och de innebär därmed vissa utmaningar för DCFR i sin helhet. Till sitt innehåll påminner de mycket om motsvarande regler i EU-rätten och i tvingande svensk rätt, och de kan därför användas till att diskutera diskrimineringsförbud i privaträttsliga sammanhang också utanför DCFR. De föreslagna modellreglerna överensstämmer dock inte nödvändigtvis helt och hållet med EU-rätten och svensk rätt, men i diskrepansen ryms potential att bidra till rättsutvecklingen — åtminstone i delar i en riktning som författaren till artikeln finner tilltalande.
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| 9. |
- Jansson, Hanna, 1975, et al.
(author)
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The crystal structure of the spinach plastocyanin double mutant G8D/L12E gives insight into its low reactivity towards photosystem 1 and cytochrome f
- 2003
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In: Biochimica et Biophysica Acta. - : Elsevier BV. - 0005-2728 .- 1879-2650. ; 1607:2-3, s. 203-210
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Journal article (peer-reviewed)abstract
- Plastocyanin (Pc) is a copper-containing protein, which functions as an electron carrier between the cytochrome b6f and photosystem 1 (PS1) complexes in the photosynthetic electron transfer (ET) chain. The ET is mediated by His87 situated in the hydrophobic surface in the north region of Pc. Also situated in this region is Leu12, which mutated to other amino acids severely disturbs the ET from cytochrome f and to PS1, indicating the importance of the hydrophobic surface. The crystal structure of the Pc double mutant G8D/L12E has been determined to 2.0 Å resolution, with a crystallographic R-factor of 18.3% (Rfree=23.2%). A comparison with the wild-type structure reveals that structural differences are limited to the sites of the mutations. In particular, there is a small but significant change in the hydrophobic surface close to His87. Evidently, this leads to a mismatch in the reactive complex with the redox partners. For PS1 this results in a 20 times weaker binding and an eightfold slower ET as determined by kinetic measurements. The mutations that have been introduced do not affect the optical absorption spectrum. However, there is a small change in the EPR spectrum, which can be related to changes in the copper coordination geometry.
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| 10. |
- Lautner, Ronald, et al.
(author)
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Apolipoprotein e genotype and the diagnostic accuracy of cerebrospinal fluid biomarkers for Alzheimer disease.
- 2014
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In: JAMA psychiatry. - : American Medical Association (AMA). - 2168-6238 .- 2168-622X. ; 71:10, s. 1183-91
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Journal article (peer-reviewed)abstract
- Several studies suggest that the apolipoprotein E (APOE) ε4 allele modulates cerebrospinal fluid (CSF) levels of β-amyloid 42 (Aβ42). Whether this effect is secondary to the association of the APOE ε4 allele with cortical Aβ deposition or whether APOE ε4 directly influences CSF levels of Aβ42 independently of Aβ pathology remains unknown.
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