| 1. |
|
|
| 2. |
- Ingman, Mikael, et al.
(författare)
-
Novel mutation in Hepatitis B virus preventing HBeAg production and resembling primate strains.
- 2006
-
Ingår i: Journal of General Virology. - : Microbiology Society. - 1465-2099 .- 0022-1317. ; 87, s. 307-310
-
Tidskriftsartikel (refereegranskat)abstract
- Chronic carriers of hepatitis B infection often harbour virus strains with mutations in the precore region. These mutations are temporally associated with the development of HBeAg loss and seroconversion to anti-HBe. The most common precore mutation is a stop codon at position 1896, but other mutations leading to abolished HBeAg secretion have been described. Here, a novel precore mutation introducing a lysine in the precore position 28, a sequence shared by non-human primates but not by other human isolates, is described. However, the insertion causes a frame-shift preventing the expression of HBeAg by introducing a stop codon 5 aa downstream of the mutation. Analysis of the predicted RNA secondary structure indicates that the insertion could occur without fatally affecting the stability of the stem–loop encapsidation signal.
|
|
| 3. |
- Kidd-Ljunggren, Karin, et al.
(författare)
-
High levels of hepatitis B virus DNA in body fluids from chronic carriers.
- 2006
-
Ingår i: Journal of Hospital Infection. - : Elsevier BV. - 0195-6701. ; 64:4, s. 352-357
-
Tidskriftsartikel (refereegranskat)abstract
- infection with hepatitis B virus (HBV) is a major global health problem. Transmission is mainly blood-borne, although the route of infection during horizontal transmission in childhood is unclear. Nosocomial outbreaks of HBV have been widely reported, but have mainly focused on blood-borne transmission. There is Limited knowledge of the viral Load Levels in other body fluids. In the present study, chronic HBV carriers were tested for the presence of HBV DNA in serum, saliva, nasopharyngeal fluid, urine and tears by means of qualitative and quantitative polymerase chain reaction (PCR) methods. Twenty-five patients who were positive for HBV DNA with both PCRs were included. Low titres in real-time PCR corresponded with weak bands in the qualitative assay. HBV DNA was found in two urine samples, 10 saliva samples, five nasopharyngeal, swabs and in tear fluid from four patients. One highly viraemic HBeAg-positive carrier with serum HBV DNA Levels of 7 x 10(9) genome copies had high copy numbers detected in both saliva and nasopharyngeal fluid. These results demonstrate that highly viraemic HBV carriers may have high titres of HBV DNA in other body fluids. This has particular importance for infection control programmes and regulations, underlining the importance of aiming towards regular HBV DNA testing and thus infectivity assessment of chronic carriers in order to prevent transmission. (c) 2006 The Hospital Infection Society. Published by Elsevier Ltd. All rights reserved.
|
|
| 4. |
- Lindqvist, Göran, et al.
(författare)
-
The role of clusters in smart specialisation strategies
- 2013
-
Rapport (övrigt vetenskapligt/konstnärligt)abstract
- This report investigates the potential contribution of clusters and cluster policies in the design and implementation of Smart Specialisation Strategies. Both cluster policies and Smart Specialisation Strategies are policy approaches with a place-based dimension, aiming at exploiting advantages of proximity to promote economic growth and competitiveness. With regions across Europe currently working on their Smart Specialisation Strategies, the question whether and how clusters and cluster policies can be used in this endeavour is highly relevant. Smart Specialisation Strategies are difficult to design and implement because they are based on a new and complex academic framework that now has to be translated into policy practice. The contention of this report is that lessons learnt from the rich history of cluster policies can provide concrete inputs into the development of Smart Specialisation Strategies (S3).
|
|
| 5. |
- Nordin, Maria, et al.
(författare)
-
Variability in the precore and core promoter region of the hepatitis B virus genome.
- 2014
-
Ingår i: Journal of Medical Virology. - : Wiley. - 1096-9071 .- 0146-6615. ; 86:3, s. 437-445
-
Tidskriftsartikel (refereegranskat)abstract
- There is increasing evidence that hepatitis B virus (HBV) infections with different genotypes and subgenotypes differ in response to treatment and long-term prognosis. The differences emerge from variability within the genomes that leads to structural deviations at the pregenomic level and to changes at the translational level. Naturally occurring HBV strains covering the four major genotypes A-D were obtained from 393 patients and part of the genome was amplified using polymerase chain reaction (PCR), sequenced, and analyzed for mutational differences in the precore and core promoter regions. The study confirmed that core promoter and precore mutations occur at key positions (A1762T, G1764A, G1896A, and G1899A), and that the proportions of strains with seroconvertion in patients differ between the four HBV genotypes. A rare double mutation (C1857T together with G1897A) was observed, and C1856T was found together with the emerging G1898A mutation, which itself was found to be more widespread geographically than previously described. We found a novel mutation (T1850C), never before observed in human HBV strains but known from woodchuck hepatitis virus (WHV). A novel association of mutation C1773T with G1764T, C1766A, and G1757A was also found within a site already suggested to be a putative binding site for HNF-3. This novel association is proposed by us to be of importance for additional binding of HNH-2 to this site and is a better indicator of the emergence of the double mutation G1764T and C1766A than the G1757A mutation proposed previously. J. Med. Virol. © 2013 Wiley Periodicals, Inc.
|
|
| 6. |
|
|
| 7. |
- Quere, Ronan, et al.
(författare)
-
SMAD4 binds HOXA9 in the cytoplasm and protects primitive hematopoietic cells against nuclear activation by HOXA9 and leukemia transformation.
- 2011
-
Ingår i: Blood. - : American Society of Hematology. - 1528-0020 .- 0006-4971. ; 117, s. 5918-5930
-
Tidskriftsartikel (refereegranskat)abstract
- We studied leukemic stem cells (LSCs) in a Smad4(-/-) mouse model of acute myelogenous leukemia (AML) induced either by the HOXA9 gene or by the fusion oncogene NUP98-HOXA9. While HOXA9-SMAD4 complexes accumulate in the cytoplasm of normal hematopoietic stem- and progenitor cells (HSPCs) transduced with these oncogenes, there is no cytoplasmic accumulation of HOXA9 in Smad4(-/-) HSPCs and as a consequence increased levels of HOXA9 accumulate in the nucleus leading to increased immortalization in vitro. Loss of Smad4 accelerates the development of leukemia in vivo due to an increase in transformation of HSPCs. Therefore, the cytoplasmic binding of HOXA9 by SMAD4 is a mechanism to protect HOXA9-induced transformation of normal HSPCs. Since Smad4 is a potent tumor suppressor involved in growth control, we developed a strategy to modify the subcellular distribution of SMAD4. We successfully disrupted the interaction between HOXA9 and SMAD4 to activate the TGF-beta pathway and apoptosis, leading to a loss of LSCs. Together, these findings reveal a major role for Smad4 in the negative regulation of leukemia initiation and maintenance induced by HOXA9/NUP98-HOXA9 and provide strong evidence that antagonizing SMAD4 stabilization by these oncoproteins might be a promising novel therapeutic approach in leukemia.
|
|
| 8. |
|
|
