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1.	Blomberg, Helena, 1970-, et al. (author) Extremistisk ideologi i den retoriska kampen om sanningen : fallet Nordiska motståndsrörelsen på sociala medier och i lokalpress 2018 Reports (other academic/artistic)
2.	Blomberg, Jonas, et al. (author) Effects of semi-isostatic densification of wood on the variation in strength properties with density 2005 In: Wood Science and Technology. - : Springer Science and Business Media LLC. - 0043-7719 .- 1432-5225. ; 39:5, s. 339-350 Journal article (peer-reviewed)abstract The variation in strength properties with density was compared between semi-isostatically densified and non-densified wood. Strength properties were compared with published data from earlier studies using other methods for densification. Small clear specimens of eight species were analysed for compression strength in axial, radial and tangential direction, three-point bending and Brinell hardness. After densification, all tested strength properties increased with density, but especially strength perpendicular to grain became lower than expected from the density of non-densified wood. Strength of densified wood relative to what could be expected for non-densified wood of similar density was denoted as 'strength potential index'. For axial compression strength and bending strength, strength potential index of individual wood species varied between 0.7 and 1.0, i.e. densified wood is slightly weaker than what could be expected from its density. Strength potential index was lower for properties much determined by strength perpendicular to grain. In radial direction, densified wood was rubbery with low modulus of elasticity and nearly no proportional limit or modulus of rupture. Generally, wood was apparently weakened in proportion to the degree of compression in respective direction. Strength potential index also increased with increasing original density of the species.
3.	Blomberg, Jonas, et al. (author) No evidence for xenotropic murine leukemia-related virus infection in Sweden using internally controlled multiepitope suspension array serology 2012 In: Clinical and Vaccine Immunology. - : American Society for Microbiology. - 1556-6811 .- 1556-679X. ; 19:9, s. 1399-1410 Journal article (peer-reviewed)abstract Many syndromes have a large number of differential diagnoses, a situation which calls for multiplex diagnostic systems. Myalgic encephalomyelitis (ME), also named chronic fatigue syndrome (CFS), is a common disease of unknown etiology. A mouse retrovirus, xenotropic murine leukemia-related virus (XMRV), was found in ME/CFS patients and blood donors, but this was not corroborated. However, the paucity of serological investigations on XMRV in humans prompted us to develop a serological assay which cover many aspects of XMRV antigenicity. It is a novel suspension array method, using a multiplex IgG assay with nine recombinant proteins from the env and gag genes of XMRV and 38 peptides based on known epitopes of vertebrate gamma-retroviruses. IgG antibodies were sought in 520 blood donors and 85 ME/CFS patients and in positive-and negative-control sera from animals. We found no differences in seroreactivity between blood donors and ME/CFS patients for any of the antigens. This did not support an association between ME/CFS and XMRV infection. The multiplex serological system had several advantages: (i) biotinylated protein G allowed us to run both human and animal sera, which is essential because of a lack of XMRV-positive humans; (ii) a novel quality control was a pan-peptide positive-control rabbit serum; and (iii) synthetic XMRV Gag peptides with degenerate positions covering most of the variation of murine leukemia-like viruses did not give higher background than nondegenerate analogs. The principle may be used for creation of variant tolerant peptide serologies. Thus, our system allows rational large-scale serological assays with built-in quality control.
4.	Blomberg, Jonas, et al. (author) Phylogeny-directed search for murine leukemia virus-like retroviruses in vertebrate genomes and in patients suffering from myalgic encephalomyelitis/chronic fatigue syndrome and prostate cancer 2011 In: Advances in Virology. - : Hindawi Limited. - 1687-8639 .- 1687-8647. ; 2011, s. 341294- Review (peer-reviewed)abstract Gammaretrovirus-like sequences occur in most vertebrate genomes. Murine Leukemia Virus (MLV) like retroviruses (MLLVs) are a subset, which may be pathogenic and spread cross-species. Retroviruses highly similar to MLLVs (xenotropic murine retrovirus related virus (XMRV) and Human Mouse retrovirus-like RetroViruses (HMRVs)) reported from patients suffering from prostate cancer (PC) and myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) raise the possibility that also humans have been infected. Structurally intact, potentially infectious MLLVs occur in the genomes of some mammals, especially mouse. Mouse MLLVs contain three major groups. One, MERV G3, contained MLVs and XMRV/HMRV. Its presence in mouse DNA, and the abundance of xenotropic MLVs in biologicals, is a source of false positivity. Theoretically, XMRV/HMRV could be one of several MLLV transspecies infections. MLLV pathobiology and diversity indicate optimal strategies for investigating XMRV/HMRV in humans and raise ethical concerns. The alternatives that XMRV/HMRV may give a hard-to-detect "stealth" infection, or that XMRV/HMRV never reached humans, have to be considered.
5.	Frisk, Peter, et al. (author) Coxsackievirus B3 infection affects metal-binding/transporting proteins and trace elements in the pancreas in mice 2007 In: Pancreas. - : Ovid Technologies (Wolters Kluwer Health). - 0885-3177 .- 1536-4828. ; 35:3, s. e37-e44 Journal article (peer-reviewed)abstract Objective: The trigger of juvenile diabetes has been suggested to be an interaction between a virus and trace elements, where enteroviruses, including coxsackievirus B3 (CVB3), have been discussed as potential initiators. The aim of this study was to investigate the effects in the pancreas on gene expressions of metallothionein 1 (MT1), divalent metal transporter 1 (DMT1), and zinc transporter 5 (ZnT-5) and concomitant changes in iron (Fe), copper (Cu), and zinc (Zn) in serum and pancreas of Balb/c mice on days 3, 6, and 9 of CVB3 infection. Methods: Trace elements were measured through inductively coupled plasma-mass spectrometry, and CVB3, MT1, DMT1, and ZnT-5 were measured by reverse transcription/polymerase chain reaction. Results: Virus was found in the pancreas on all days, with a peak on day 3. Infection tended to increase Fe in both serum and the pancreas. The Cu/Zn ratio in the pancreas increased early in the infection because of a great decrease in Zn. In serum, the Cu/Zn ratio was not increased until day 9 of the disease. In the pancreas, MT1 decreased, whereas DMT1 tended to increase on day 6, and ZnT-5 increased progressively during the course of the disease. Conclusions: Virus-induced changes in trace elements, MT1, DMT1, and ZnT-5 in the pancreas may reflect early stages of the development of pancreatitis and prestages of diabetic disease.
6.	Ilbäck, Nils-Gunnar, et al. (author) Gastrointestinal uptake of trace elements are changed during the course of a common human viral (Coxsackievirus B3) infection in mice 2008 In: Journal of Trace Elements in Medicine and Biology. - : Elsevier BV. - 0946-672X .- 1878-3252. ; 22:2, s. 120-30 Journal article (peer-reviewed)abstract Most infectious diseases are accompanied by a change in levels of several trace elements in the blood. However, it is not known whether changes in the gastrointestinal uptake of trace elements contribute to this event. Coxsackievirus B3 (CVB3), adapted to Balb/c mice, was used to study whether infection induces gene expression of metallothionein (MT1) and divalent-metal transporter 1 (DMT1) in the intestine and liver and hepcidin in the liver, as well as whether trace elements in these tissues are changed accordingly. Quantitative expression of CVB3, MT1, DMT1 and hepcidin was measured by real-time RT-PCR and six trace elements by ICP-MS on days 3, 6 and 9 of the infection. The copper/zinc (Cu/Zn) ratio in serum increased as a response to the infection. High concentrations of virus were found in the intestine and liver on day 3 and in the intestine on day 6. MT1 in the intestine and liver increased on days 3 and 6. The increase of MT1 in the liver correlated positively with Cu and Zn. Hepcidin in the liver showed a non-significant increase on days 3 and 6 of the infection, whereas DMT1 in the intestine decreased on day 9. Accordingly, iron (Fe) in the liver increased progressively during the disease, whereas in the intestine DMT1 was negatively correlated to Fe. Arsenic (As), cadmium (Cd) and mercury (Hg) were found to decrease to various degrees in the intestine, serum and liver. Thus, enteroviral infections, and possibly many other infections, may cause a change in the gastrointestinal uptake of both non-essential and essential trace elements.
7.	Muradrasoli, Shaman, et al. (author) Prevalence and phylogeny of coronaviruses in wild birds from the Bering Strait area (Beringia) 2010 In: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 5:10 Journal article (peer-reviewed)abstract Coronaviruses (CoVs) can cause mild to severe disease in humans and animals, their host range and environmental spread seem to have been largely underestimated, and they are currently being investigated for their potential medical relevance. Infectious bronchitis virus (IBV) belongs to gamma-coronaviruses and causes a costly respiratory viral disease in chickens. The role of wild birds in the epidemiology of IBV is poorly understood. In the present study, we examined 1,002 cloacal and faecal samples collected from 26 wild bird species in the Beringia area for the presence of CoVs, and then we performed statistical and phylogenetic analyses. We detected diverse CoVs by RT-PCR in wild birds in the Beringia area. Sequence analysis showed that the detected viruses are gamma-coronaviruses related to IBV. These findings suggest that wild birds are able to carry gamma-coronaviruses asymptomatically. We concluded that CoVs are widespread among wild birds in Beringia, and their geographic spread and frequency is higher than previously realised. Thus, Avian CoV can be efficiently disseminated over large distances and could be a genetic reservoir for future emerging pathogenic CoVs. Considering the great animal health and economic impact of IBV as well as the recent emergence of novel coronaviruses such as SARS-coronavirus, it is important to investigate the role of wildlife reservoirs in CoV infection biology and epidemiology.
8.	Oldgren, Jonas, 1964-, et al. (author) Systematic Coronary Risk Evaluation estimated risk and prevalent subclinical atherosclerosis in coronary and carotid arteries: A population-based cohort analysis from the Swedish Cardiopulmonary Bioimage Study 2021 In: European Journal of Preventive Cardiology. - : Oxford University Press (OUP). - 2047-4873 .- 2047-4881. ; 28:3, s. 250-259 Journal article (peer-reviewed)abstract Background It is not clear if the European Systematic Coronary Risk Evaluation algorithm is useful for identifying prevalent subclinical atherosclerosis in a population of apparently healthy individuals. Our aim was to explore the association between the risk estimates from Systematic Coronary Risk Evaluation and prevalent subclinical atherosclerosis. Design The design of this study was as a cross-sectional analysis from a population-based study cohort. Methods From the general population, the Swedish Cardiopulmonary Bioimage Study randomly invited individuals aged 50-64 years and enrolled 13,411 participants mean age 57 (standard deviation 4.3) years; 46% males between November 2013-December 2016. Associations between Systematic Coronary Risk Evaluation risk estimates and coronary artery calcification and plaques in the carotid arteries by using imaging data from a computed tomography of the heart and ultrasonography of the carotid arteries were examined. Results Coronary calcification was present in 39.5% and carotid plaque in 56.0%. In men, coronary artery calcium score >0 ranged from 40.7-65.9% and presence of carotid plaques from 54.5% to 72.8% in the age group 50-54 and 60-65 years, respectively. In women, the corresponding difference was from 17.1-38.9% and from 41.0-58.4%. A doubling of Systematic Coronary Risk Evaluation was associated with an increased probability to have coronary artery calcium score >0 (odds ratio: 2.18 (95% confidence interval 2.07-2.30)) and to have >1 carotid plaques (1.67 (1.61-1.74)). Conclusion Systematic Coronary Risk Evaluation estimated risk is associated with prevalent subclinical atherosclerosis in two major vascular beds in a general population sample without established cardiovascular disease or diabetes mellitus. Thus, the Systematic Coronary Risk Evaluation risk chart may be of use for estimating the risk of subclinical atherosclerosis.
9.	Rönnberg, Bengt, et al. (author) Compensating for cross-reactions using avidity and computation in a suspension multiplex immunoassay for serotyping of Zika versus other flavivirus infections 2017 In: Medical Microbiology and Immmunology. - : SPRINGER. - 0300-8584 .- 1432-1831. ; 206:5, s. 383-401 Journal article (peer-reviewed)abstract The recent spread of Zika virus (ZIKV) in the Americas and Asia necessitates an increased preparedness for improved maternal and perinatal health and blood safety. However, serological cross-reactions, especially to Dengue virus (DENV), complicate ZIKV antibody serodiagnosis. A novel "pan-Flavi" suspension multiplex immunoassay (PFSMIA) using 25 antigens, whole virus (WV), non-structural protein 1 (NS1), and envelope (E) proteins, from 7 zoonotic flaviviruses for specific detection of ZIKV and DENV IgM and IgG was developed. Patterns of antibody cross-reactivity, avidity, and kinetics were established in 104 sera from returning travelers with known ZIKV and DENV infections. PFSMIA gave IgM- and IgG-sensitivities for both viruses of 96-100%, compared to an immunofluorescence assay. Main IgM cross-reactions were to NS1, for IgG to the E and WV antigens. Infecting virus yielded reactivity to several antigens of the homologous virus, while cross-reactions tended to occur only to a single antigen from heterologous virus(es). A specificity-enhancing computer procedure took into account antibody isotype, number of antibody-reactive antigens per virus, avidity, average degree of cross-reactivity to heterologous flavivirus antigens, and reactivity changes in serial sera. It classified all 50 cases correctly. Applied to sera from 200 pregnant women and 173 blood donors from Sweden, one blood donor was found ZIKV NS1 IgM positive, and another as ZIKV NS1 IgG positive. These samples did not react with other ZIKV antigens and were thereby judged as false-positives. PFSMIA provided sensitive and specific ZIKV and DENV serology, warranting high-throughput serological surveillance and a minimized need for laborious and expensive virus neutralization assays.
10.	Scholz, Saskia, et al. (author) Human hantavirus infection elicits pronounced redistribution of mononuclear phagocytes in peripheral blood and airways 2017 In: PLoS Pathogens. - : Public library science. - 1553-7366 .- 1553-7374. ; 13:6 Journal article (peer-reviewed)abstract Hantaviruses infect humans via inhalation of virus-contaminated rodent excreta. Infection can cause severe disease with up to 40% mortality depending on the viral strain. The virus primarily targets the vascular endothelium without direct cytopathic effects. Instead, exaggerated immune responses may inadvertently contribute to disease development. Mononuclear phagocytes (MNPs), including monocytes and dendritic cells (DCs), orchestrate the adaptive immune responses. Since hantaviruses are transmitted via inhalation, studying immunological events in the airways is of importance to understand the processes leading to immunopathogenesis. Here, we studied 17 patients infected with Puumala virus that causes a mild form of hemorrhagic fever with renal syndrome (HFRS). Bronchial biopsies as well as longitudinal blood draws were obtained from the patients. During the acute stage of disease, a significant influx of MNPs expressing HLA-DR, CD11c or CD123 was detected in the patients' bronchial tissue. In parallel, absolute numbers of MNPs were dramatically reduced in peripheral blood, coinciding with viremia. Expression of CCR7 on the remaining MNPs in blood suggested migration to peripheral and/or lymphoid tissues. Numbers of MNPs in blood subsequently normalized during the convalescent phase of the disease when viral RNA was no longer detectable in plasma. Finally, we exposed blood MNPs in vitro to Puumala virus, and demonstrated an induction of CCR7 expression on MNPs. In conclusion, the present study shows a marked redistribution of blood MNPs to the airways during acute hantavirus disease, a process that may underlie the local immune activation and contribute to immunopathogenesis in hantavirus-infected patients.
11.	Sheikholvaezin, Ali, et al. (author) Rational recombinant XMRV antigen preparation and bead coupling for multiplex serology in a suspension array 2011 In: Protein Expression and Purification. - : Elsevier BV. - 1046-5928 .- 1096-0279. ; 80:2, s. 176-184 Journal article (peer-reviewed)abstract Diagnosis of infectious diseases often requires demonstration of antibodies to the microbe (serology). A large set of antigens, covering viruses, bacteria, fungi and parasites may be needed. Recombinant proteins have a prime role in serological tests. Suspension arrays offer high throughput for simultaneous measurement of many different antibodies. We here describe a rational process for preparation, purification and coupling to beads of recombinant proteins prepared in Escherichia coli derivate Origami B, to be used in a serological Luminex suspension array. All six Gag and Env proteins (p10, p12, p15, p30, gp70 and p15E), from the xenotropic murine leukemia virus-related virus (XMRV), were prepared, allowing the creation of a multiepitope XMRV antibody assay. The procedure is generic and allows production of protein antigens ready for serological testing in a few working days. Instability and aggregation problems were circumvented by expression of viral proteins fused to a carrier protein (thioredoxin A; TrxA), purification via inclusion body formation, urea solubilization, His tag affinity chromatography and direct covalent coupling to microspheres without removal of the elution buffer. The yield of one preparation (2-10 mg fusion protein per 100 ml culture) was enough for 20-100 coupling reactions, sufficing for tests of many tens of thousands of sera. False serological positivity due to antibodies binding to TrxA and to traces of E. coil proteins remaining in the preparation could be reduced by preabsorption of sera with free TrxA and E. coli extract. The recombinant antigens were evaluated using anti-XMRV antibodies. Although hybrid proteins expressed in E. coli in this way will not have the entire tertiary structure and posttranslational modifications of the native proteins, they contain a large subset of the epitopes associated with them. The described strategy is simple, quick, efficient and cheap. It should be applicable for suspension array serology in general.
12.	Abdeldaim, Guma, et al. (author) Duplex detection of the Mycobacterium tuberculosis complex and medically important non-tuberculosis mycobacteria by real-time PCR based on the rnpB gene 2016 In: Acta Pathologica, Microbiologica et Immunologica Scandinavica (APMIS). - : Wiley. - 0903-4641 .- 1600-0463. ; 124:11, s. 991-995 Journal article (peer-reviewed)abstract A duplex real-time PCR based on the rnpB gene was developed for Mycobacterium spp. The assay was specific for the Mycobacterium tuberculosis complex (MTB) and also detected all 19 tested species of non-tuberculous mycobacteria (NTM). The assay was evaluated on 404 clinical samples: 290 respiratory samples and 114 from tissue and other nonrespiratory body sites. M. tuberculosis was detected by culture in 40 samples and in 30 samples by the assay. The MTB assay showed a sensitivity similar to Roche Cobas Amplicor MTB-PCR (Roche Molecular Systems, Pleasanton, CA, USA). There were only nine samples with non-tuberculous mycobacteria detected by culture. Six of them were detected by the PCR assay.
13.	Abdeldaim, Guma, et al. (author) Is quantitative PCR for the pneumolysin (ply) gene useful for detection of pneumococcal lower respiratory tract infection? 2009 In: Clinical Microbiology and Infection. - : Elsevier BV. - 1198-743X .- 1469-0691. ; 15:6, s. 565-570 Journal article (peer-reviewed)abstract The pneumolysin (ply) gene is widely used as a target in PCR assays for Streptococcus pneumoniae in respiratory secretions. However, false-positive results with conventional ply-based PCR have been reported. The aim here was to study the performance of a quantitative ply-based PCR for the identification of pneumococcal lower respiratory tract infection (LRTI). In a prospective study, fibreoptic bronchoscopy was performed in 156 hospitalized adult patients with LRTI and 31 controls who underwent bronchoscopy because of suspicion of malignancy. Among the LRTI patients and controls, the quantitative ply-based PCR applied to bronchoalveolar lavage (BAL) fluid was positive at >/=10(3) genome copies/mL in 61% and 71% of the subjects, at >/=10(5) genome copies/mL in 40% and 58% of the subjects, and at >/=10(7) genome copies/mL in 15% and 3.2% of the subjects, respectively. Using BAL fluid culture, blood culture, and/or a urinary antigen test, S. pneumoniae was identified in 19 LRTI patients. As compared with these diagnostic methods used in combination, quantitative ply-based PCR showed sensitivities and specificities of 89% and 43% at a cut-off of 10(3) genome copies/mL, of 84% and 66% at a cut-off of 10(5) genome copies/mL, and of 53% and 90% at a cut-off of 10(7) genome copies/mL, respectively. In conclusion, a high cut-off with the quantitative ply-based PCR was required to reach acceptable specificity. However, as a high cut-off resulted in low sensitivity, quantitative ply-based PCR does not appear to be clinically useful. Quantitative PCR methods for S. pneumoniae using alternative gene targets should be evaluated.
14.	Abdeldaim, Guma M. K., et al. (author) Detection of Haemophilus influenzae in respiratory secretions from pneumonia patients by quantitative real-time polymerase chain reaction 2009 In: Diagnostic microbiology and infectious disease. - : Elsevier. - 0732-8893 .- 1879-0070. ; 64:4, s. 366-373 Journal article (peer-reviewed)abstract A quantitative real-time polymerase chain reaction (PCR) based on the omp P6 gene was developed to detect Haemophilus influenzae. Its specificity was determined by analysis of 29 strains of 11 different Haemophilus spp. and was compared with PCR assays having other target genes: rnpB, 16S rRNA, and bexA. The method was evaluated on nasopharyngeal aspirates from 166 adult patients with community-acquired pneumonia. When 104 DNA copies/mL was used as cutoff limit for the method, P6 PCR had a sensitivity of 97.5% and a specificity of 96.0% compared with the culture. Of 20 culture-negative but P6 PCR-positive cases, 18 were confirmed by fucK PCR as H. influenzae. Five (5.9%) of 84 nasopharyngeal aspirates from adult controls tested PCR positive. We conclude that the P6 real-time PCR is both sensitive and specific for identification of H. influenzae in respiratory secretions. Quantification facilitates discrimination between disease-causing H. influenzae strains and commensal colonization.
15.	Abdeldaim, Guma M. K. (author) PCR detection of Streptococcus pneumoniae and Haemophilus influenzae in pneumonia patients 2009 Doctoral thesis (other academic/artistic)abstract PCR is a rapid, reproducible method for nucleic acid detection. However, this technology displays significant deficiencies when applied in clinical microbiology. This work’s aim was to improve current diagnostics and provide sensitive and quantitative real-time PCRs. Paper I describes the development of a sensitive and specific quantitative real-time PCR for the detection of Streptococcus pneumoniae, based on the Spn9802 DNA fragment. Applied to nasopharyngeal aspirates from 166 pneumonia patients, Spn9802 PCR had a sensitivity of 94% and a specificity of 98%. In Paper II the performance of a ply gene PCR for identification of pneumococcal lower respiratory tract infection (LRTI) was evaluated on bronchoalveloar lavage fluids. At the detection limit 103 genome copies/mL, 89% sensitivity but only 43% specificity was achieved. Paper III shows that S. pneumoniae DNA is detectable in plasma from acutely febrile patients. Sensitivities were low (26-42%) for detection of pneumococcal pneumonia, for bacteraemic pneumococcal pneumonia they were 60-70%. Paper IV describes evaluation of four PCR targets for Haemophilus influenzae detection. A real-time PCR based on the P6 gene was developed and applied to 166 CAP patients, using cut-off of 104 genome copies/mL the assay had a sensitivity of 97% and a specificity of 96%. In paper V, the two real-time PCRs presented in papers I and IV were combined with a PCR for detection of Neisseriae meningitidis. The analytical sensitivity of this multiplex real-time PCR was not affected by using a mixture of reagents and a combined DNA standard (S. pneumoniae/H. influenzae) in single tubes. Applied to 156 LRTI patients, this PCR had sensitivities over 90% for S. pneumoniae and H. influenzae, and specificities of 89% and 96%, respectively. In conclusion, real-time PCR assays are useful for the diagnosis of S. pneumoniae and H. influenzae. They enable detection after antibiotic installation, and quantification increases the etiological specificity of pneumonia.
16.	Abdeldaim, Guma M. K., et al. (author) Quantitative fucK gene polymerase chain reaction on sputum and nasopharyngeal secretions to detect Haemophilus influenzae pneumonia 2013 In: Diagnostic microbiology and infectious disease. - : Elsevier. - 0732-8893 .- 1879-0070. ; 76:2, s. 141-146 Journal article (peer-reviewed)abstract A quantitative polymerase chain reaction (PCR) for the fucK gene was developed for specific detection of Haemophilus influenzae. The method was tested on sputum and nasopharyngeal aspirate (NPA) from 78 patients with community-acquired pneumonia (CAP). With a reference standard of sputum culture and/or serology against the patient's own nasopharyngeal isolate, H. influenzae etiology was detected in 20 patients. Compared with the reference standard, fucK PCR (using the detection limit 10(5) DNA copies/mL) on sputum and NPA showed a sensitivity of 95.0% (19/20) in both cases, and specificities of 87.9% (51/58) and 89.5% (52/58), respectively. In a receiver operating characteristic curve analysis, sputum fucK PCR was found to be significantly superior to sputum P6 PCR for detection of H. influenzae CAP. NPA fucK PCR was positive in 3 of 54 adult controls without respiratory symptoms. In conclusion, quantitative fucK real-time PCR provides a sensitive and specific identification of H. influenzae in respiratory secretions.
17.	Abdeldaim, Guma M. K., et al. (author) Toward a quantitative DNA-based definition of pneumococcal pneumonia : a comparison of Streptococcus pneumoniae target genes, with special reference to the Spn9802 fragment 2008 In: Diagnostic microbiology and infectious disease. - : Elsevier BV. - 0732-8893 .- 1879-0070. ; 60:2, s. 143-150 Journal article (peer-reviewed)abstract The current shift from phenotypically toward genotypically based microbial diagnosis is not unproblematic. A novel quantitative real-time polymerase chain reaction (PCR) assay based on the Spn9802 DNA fragment was therefore developed for detection of Streptococcus pneumoniae. Out of 44 bacterial species, only S. pneumoniae and Streptococcus pseudopneumoniae were positive in Spn9802 PCR. In an evaluation on nasopharyngeal aspirates from 166 patients with community-acquired pneumonia, the assay was positive in 49 of 50 culture-positive cases. Of 19 culture-negative but Spn9802 PCR-positive cases, 12 were confirmed as S. pneumoniae by rnpB sequence analysis. With an expanded reference standard, including culture and rnpB sequencing, Spn9802 had a sensitivity of 94% and a specificity of 98%. A cutoff for clinically significant positivity was 10(4) DNA copies/mL, giving 71% sensitivity and 100% specificity. In conclusion, Spn9802 real-time PCR is highly sensitive and specific. The quantification it provides enables differentiation between pneumococcal pathogenicity and commensalism.
18.	Abdeldaim, Guma, 1969-, et al. (author) Multiplex quantitative PCR for detection of lower respiratory tract infection and meningitis caused by Streptococcus pneumoniae, Haemophilus influenzae and Neisseria meningitidis 2010 In: BMC Microbiology. - : Springer Science and Business Media LLC. - 1471-2180. ; 10, s. 310- Journal article (peer-reviewed)abstract Background. Streptococcus pneumoniae and Haemophilus influenzae cause pneumonia and as Neisseria meningitidis they are important agents of meningitis. Although several PCR methods have been described for these bacteria the specificity is an underestimated problem. Here we present a quantitative multiplex real-time PCR (qmPCR) for detection of S. pneumoniae (9802 gene fragment), H. influenzae (omp P6 gene) and N. meningitidis (ctrA gene). The method was evaluated on bronchoalveolar lavage (BAL) samples from 156 adults with lower respiratory tract infection (LRTI) and 31 controls, and on 87 cerebrospinal fluid (CSF) samples from meningitis patients. Results. The analytical sensitivity was not affected by using a combined mixture of reagents and a combined DNA standard (S. pneumoniae/H. influenzae/N. meningitidis) in single tubes. By blood- and BAL-culture and S. pneumoniae urinary antigen test, S. pneumoniae and H. influenzae were aetiological agents in 21 and 31 of the LTRI patients, respectively. These pathogens were identified by qmPCR in 52 and 72 of the cases, respectively, yielding sensitivities and specificities of 95% and 75% for S. pneumoniae, and 90% and 65% for H. influenzae, respectively. When using a cut-off of 105 genome copies/mL for clinical positivity the sensitivities and specificities were 90% and 80% for S. pneumoniae, and 81% and 85% for H. influenzae, respectively. Of 44 culture negative but qmPCR positive for H. influenzae, 41 were confirmed by fucK PCR as H. influenzae. Of the 103 patients who had taken antibiotics prior to sampling, S. pneumoniae and H. influenzae were identified by culture in 6% and 20% of the cases, respectively, and by the qmPCR in 36% and 53% of the cases, respectively. In 87 CSF samples S. pneumoniae and N. meningitidis were identified by culture and/or 16 S rRNA in 14 and 10 samples and by qmPCR in 14 and 10 samples, respectively, giving a sensitivity of 100% and a specificity of 100% for both bacteria. Conclusions. The PCR provides increased sensitivity and the multiplex format facilitates diagnosis of S. pneumoniae, H. influenzae and N. meningitidis and the assay enable detection after antibiotic treatment has been installed. Quantification increases the specificity of the etiology for pneumonia.
19.	Abdeldaim, Guma, et al. (author) Usefulness of real-time PCR for lytA, ply, and Spn9802 on plasma samples for the diagnosis of pneumococcal pneumonia 2010 In: Clinical Microbiology and Infection. - : Elsevier BV. - 1198-743X .- 1469-0691. ; 16:8, s. 1135-1141 Journal article (peer-reviewed)abstract In the present study, we evaluated rapid real-time PCR assays for ply, Spn9802, and lytA applied to plasma samples for the detection of Streptococcus pneumoniae in patients with community-acquired pneumonia (CAP). In a prospective study of CAP aetiology, an EDTA plasma sample was collected together with blood culture in 92 adult CAP patients and 91 adult controls. Among the 92 CAP patients, lytA PCR was positive in eight (9%), Spn9802 PCR was positive in 11 (12%) and ply PCR was positive in 19 (21%) cases. Of 91 controls, the ply PCR was positive in eight cases (9%), but no positive cases were noted by Spn9802 or lytA PCRs. Ten CAP patients had pneumococcal bacteraemia. Compared to blood culture, PCR for lytA, Spn9802 and ply had sensitivities of 70% (7/10), 60% (6/10) and 70% (7/10), and specificities of 96% (79/82), 94% (77/82) and 85% (70/82) respectively. With blood culture and/or culture of representative sputum, and/or urinary antigen detection, S. pneumoniae was identified in 31 CAP patients. Compared to these tests in combination, PCR for lytA, Spn9802 and ply showed sensitivities of 26% (8/31), 32% (10/31) and 42% (13/31), and specificities of 100% (61/61), 98% (60/61) and 90% (55/61) respectively. We conclude that Spn9802 and lytA PCRs may be useful for the rapid detection of bacteraemic pneumococcal pneumonia, whereas ply PCR is not specific enough for routine use and blood PCR with small plasma volumes is not useful for the detection of nonbacteraemic pneumococcal pneumonia.
20.	Ahmadpour, Doryaneh, 1973, et al. (author) Robustness analysis of HOG pathway genes in Saccharomyces cerevisiae 2006 In: YSBN Meeting Nov. 14-16, 2006- Vienna- Austria. Conference paper (other academic/artistic)abstract Robustness analysis of HOG pathway genes in Saccharomyces cerevisiae Doryaneh Ahmadpour1, Lars-Göran Ottosson1, Markus Krantz2, Jonas Warringer1, Anders Blomberg1 and Stefan Hohmann1* 1Department of Cell and Molecular Biology/Microbiology, Göteborg University, S-405 30 Göteborg, Sweden 2 The Systems Biology Institute (SBI), Shibuya, Tokyo, Japan E-mail: doryaneh.ahmadpour@gmm.gu.se Robustness is a fundamental property of biological systems and crucial for their effective function under internal or external perturbations. For instance, it has been proposed that internal parameters such as gene expression have been optimized during evolution such that a given system has the observed robustness. The permissible ranges of internal parameters in the cells are not comprehensively understood since there has not been a technique to measure such parameters. “Genetic tug-of-war” (gTOW) [1] is a genetic screening method that allows the investigation of the upper limit copy number of genes, and thereby the upper permissible range of gene expression level. This method is based on a 2-micron plasmid vector containing the leu2d allele with a very weak complementation activity and the gene of interest inserted as target gene. When the leu2ura3 deletion yeast cells transformed with pTOW plasmid are cultured under leucine-limiting conditions, there will be a bias toward increasing the plasmid copy number to compensate for the lack of leucine. On the other hand there will be an opposing bias toward decreasing the plasmid copy number if the target gene inhibits growth or has a toxic effect when a certain copy number is exceeded (it reaches to its upper limit). Eventually as a result of the “tug-of-war” between these two selection biases cells with optimized plasmid copy number will be concentrated. In this study we have applied the gTOW method on 29 HOG pathway related genes in Saccharomyces cerevisiae. The high osmolarity glycerol (HOG) MAPK pathway is essential for yeast survival in high osmolarity condition and consists of two branches that activate a MAPK (Hog1) via a MAPKK (Pbs2) to orchestrate part of the transcriptional response. The HOG pathway is the best understood osmoresponsive system in eukaryotes and the quantitative data provided by the gTOW method collating with the existing computational models could be used to analyze the robustness and fragility of the pathway. 1. Hisao Moriya, Yuki Shimizu-Yoshida and Hiroaki Kitano, 2006, PLoS Genetics, 2:7
21.	Ahmadpour, Doryaneh, 1973, et al. (author) Robustness analysis of HOG pathway related genes in Saccharomyces cerevisiae 2007 In: FEBS-SysBio March 10-16, 2007- Gosau, Austria. Conference paper (other academic/artistic)abstract Robustness analysis of HOG pathway related genes in Saccharomyces cerevisiae Doryaneh Ahmadpour1, Lars-Göran Ottosson1, Markus Krantz2, Jonas Warringer1, Anders Blomberg1 and Stefan Hohmann1* 1Department of Cell and Molecular Biology/Microbiology, Göteborg University, S-405 30 Göteborg, Sweden 2 The Systems Biology Institute (SBI), Shibuya, Tokyo, Japan E-mail: doryaneh.ahmadpour@gmm.gu.se Robustness is a fundamental property of biological systems and crucial for their effective function under internal or external perturbations. For instance, it has been proposed that internal parameters such as gene expression have been optimized during evolution such that a given system has the observed robustness. The permissible ranges of internal parameters in the cells are not comprehensively understood since there has not been a technique to measure such parameters. “Genetic tug-of-war” (gTOW) [1] is a genetic screening approach that allows the determination of the upper limit copy number of genes, and thereby the upper permissible range of the level of gene expression. This method is based on a 2-micron plasmid vector containing the LEU2d allele with a very weak complementation activity and the gene of interest inserted as target gene. When the leu2 ura3 mutant yeast transformed with pTOW plasmids is cultured under leucine-limiting conditions, there will be a bias toward increasing the plasmid copy number to satisfy the requirement for leucine. On the other hand there will be an opposing bias toward decreasing the plasmid copy number if the target gene inhibits growth when a certain copy number is exceeded (i.e. it reaches its upper limit). Eventually as a result of the “tug-of-war” between these two selection biases cells with optimized plasmid copy number will accumulate. In this study we have applied the gTOW method on 29 HOG pathway genes in S. cerevisiae. The high osmolarity glycerol (HOG) MAPK pathway is essential for yeast survival in high osmolarity condition [2]. It consists of two branches that activate a MAPK (Hog1) to orchestrate part of the transcriptional response. The HOG pathway is the best understood osmoresponsive system in eukaryotes. The quantitative data provided by the gTOW method collating with the existing computational models [3] could be used to analyze the robustness and fragility of the pathway. 1. Moriya H, et al., (2006), PLoS Genet 2(7): e111 2. Hohmann S (2002), Microbiol Mol Biol Rev 66:300 3. Klipp E, et al., (2005), Nat Biotechnol 23:975
22.	Al Moubayed, Samer, et al. (author) Talking with Furhat - multi-party interaction with a back-projected robot head 2012 In: Proceedings of Fonetik 2012. - Gothenberg, Sweden. ; , s. 109-112 Conference paper (other academic/artistic)abstract This is a condensed presentation of some recent work on a back-projected robotic head for multi-party interaction in public settings. We will describe some of the design strategies and give some preliminary analysis of an interaction database collected at the Robotville exhibition at the London Science Museum
23.	Albinsson, Bo, et al. (author) Distinction between serological responses following tick-borne encephalitis virus (TBEV) infection vs vaccination, Sweden 2017 2018 In: Eurosurveillance. - 1025-496X .- 1560-7917. ; 23:3, s. 2-7 Journal article (peer-reviewed)abstract Tick-borne encephalitis virus (TBEV) is an important European vaccine-preventable pathogen. Discrimination of vaccine-induced antibodies from those elicited by infection is important. We studied anti-TBEV IgM/IgG responses, including avidity and neutralisation, by multiplex serology in 50 TBEV patients and 50 TBEV vaccinees. Infection induced antibodies reactive to both whole virus (WV) and non-structural protein 1 (NS1) in 48 clinical cases, whereas 47 TBEV vaccinees had WV, but not NS1 antibodies, enabling efficient discrimination of infection/vaccination.
24.	Andersson, Ann-Catrin, et al. (author) ERV3 and related sequences in humans : structure and RNA expression. 2005 In: J Virol. - 0022-538X. ; 79:14, s. 9270-84 Journal article (peer-reviewed)
25.	Andersson, Ann-Catrin, et al. (author) ERV3 and related sequences in humans; studies of RNA expression by real-time PCR and in situ hybridisation Other publication (other academic/artistic)
26.	Andersson, Ann-Catrin, et al. (author) ERV3 in relation to cell differentiation in normal and neoplastic monocytes Other publication (other academic/artistic)
27.	Andersson, ML, et al. (author) Differential expression of human endogenous retroviral sequences similar to mouse mammary tumour virus in normal peripheral blood mononuclear cells. 1996 In: AIDS research and Human Retroviruses. ; 12, s. 833- Journal article (peer-reviewed)
28.	Andersson, Marie-Louise, et al. (author) Differential expression of human endogenous retroviral sequences similar to mouse mammary tumor virus in normal peripheral blood mononuclear cells 1996 In: AIDS Research and Human Retroviruses. - 0889-2229 .- 1931-8405. ; 12:9, s. 833-40 Journal article (peer-reviewed)abstract Mouse mammary tumor virus (MMTV) is a retrovirus that causes breast cancer in certain strains of mice. In a previous study we identified, by sequencing clones from human lymphocytes, six groups with similarities to MMTV. Using a primer pair derived from pol sequences conserved within types A, B, and D retroviruses and probes from the six human MMTV-like (HML-1 to HML-6) groups in an internally controlled hybridization assay we investigated the normal variation of expression in PBMCs. Variations occurred within all groups but was most significant within group HML-1, where hybridization signals differed by more than 500-fold between individuals. Groups HML-2 and HML-3 showed consistently stronger hybridization signals than groups HML-1 and HML-5, while group HML-6 resulted in weak signals for all individuals. Stringent hybridization of the amplified cDNA to 20 individual HML clones also demonstrated a marked heterogeneity of expression. Hybridization signals from some groups and sequences were found to be correlated, either in a positive or negative fashion. RNA isolated from PBMCs collected from two donors at four different time points (in the morning and in the afternoon on the same day, repeated 1 week later) was also analyzed using the six hml probes. A small variation in hybridization signals was seen in samples collected on the same day, but a larger difference was observed in samples taken 1 week later. The correlations and the differences in the expression of HMLs between individuals implicate a complex transcriptional regulation system of these sequences.
29.	Andersson, M-L, et al. (author) Human mouse mammary tumour virus (MMTV) related sequences 1998 In: J Gen Virol (accepted). Journal article (peer-reviewed)
30.	Arvidsson, Alf, et al. (author) Computer games as meeting places and as fiction 2008 In: Arv. Nordic Yearbook of Folklore. - Uppsala : Kungl. Gustav Adolfs akademien. - 0066-8176 .- 2002-4185. ; , s. 47-59 Journal article (peer-reviewed)
31.	Babazadeh, Roja, et al. (author) The Ashbya gossypiiEF-1α promoter of the ubiquitously used MX cassettes is toxic to Saccharomyces cerevisiae. 2011 In: FEBS letters. - : Wiley. - 1873-3468 .- 0014-5793. Journal article (peer-reviewed)abstract Protein overexpression based on introduction of multiple gene copies is well established. To improve purification or quantification, proteins are typically fused to peptide tags. In Saccharomyces cerevisiae, this has been hampered by multicopy toxicity of the TAP and GFP cassettes used in the global strain collections. Here, we show that this effect is due to the EF-1α promoter in the HIS3MX marker cassette rather than the tags per se. This promoter is frequently used in heterologous marker cassettes, including HIS3MX, KanMX, NatMX, PatMX and HphMX. Toxicity could be eliminated by promoter replacement or exclusion of the marker cassette. To our knowledge, this is the first report of toxicity caused by introduction of a heterologous promoter alone.
32.	Backman, Helena, et al. (author) Lung function trajectories and associated mortality among adults with and without airway obstruction 2023 In: American Journal of Respiratory and Critical Care Medicine. - : American Thoracic Society. - 1073-449X .- 1535-4970. ; 208:10, s. 1063-1074 Journal article (peer-reviewed)abstract Rationale: Spirometry is essential for diagnosis and assessment of prognosis in COPD.Objectives: To identify FEV1 trajectories and their determinants, based on annual spirometry measurements among individuals with and without airway obstruction. Furthermore, to assess mortality in relation to trajectories.Methods: In 2002-04, individuals with airway obstruction (AO) (FEV1/VC<0.70, n=993) and age- and sex-matched non-obstructive (NO) referents were recruited from population-based cohorts. Annual spirometries until 2014 were utilized in joint-survival Latent Class Mixed Models to identify lung function trajectories. Mortality data were collected during 15 years of follow-up.Results: Three trajectories were identified among the AO-cases and two among the NO referents. Trajectory membership was driven by baseline FEV1%predicted (%pred) in both groups and additionaly, pack-years in AO and current smoking in NO. Longitudinal FEV1%pred level depended on baseline FEV1%pred, pack-years and obesity. The trajectories were distributed: 79.6% T1AO FEV1-high with normal decline, 12.8% T2AO FEV1-high with rapid decline, and 7.7% T3AO FEV1-low with normal decline (mean 27, 72 and 26 mL/year) among AO-individuals, and 96.7% T1NO FEV1-high with normal decline and 3.3% T2NO FEV1-high with rapid decline (mean 34 and 173 mL/year) among referents. Hazard for death was increased for T2AO (HR1.56) and T3AO (HR3.45) vs. T1AO, and for T2NO (HR2.99) vs. T1NO.Conclusions: Three different FEV1 trajectories were identified among those with airway obstruction and two among the referents, with different outcomes in terms of FEV1-decline and mortality. The FEV1 trajectories among airway obstructive and the relationship between low FVC and trajectory outcome are of particular clinical interest.
33.	Barrio, Alvaro Martínez, et al. (author) Annotation and visualization of endogenous retroviral sequences using the Distributed Annotation System (DAS) and eBioX 2009 In: BMC Bioinformatics. - : BioMed Central. - 1471-2105. ; 10 Suppl. 6, s. S18- Journal article (peer-reviewed)abstract BACKGROUND: The Distributed Annotation System (DAS) is a widely used network protocol for sharing biological information. The distributed aspects of the protocol enable the use of various reference and annotation servers for connecting biological sequence data to pertinent annotations in order to depict an integrated view of the data for the final user. RESULTS: An annotation server has been devised to provide information about the endogenous retroviruses detected and annotated by a specialized in silico tool called RetroTector. We describe the procedure to implement the DAS 1.5 protocol commands necessary for constructing the DAS annotation server. We use our server to exemplify those steps. Data distribution is kept separated from visualization which is carried out by eBioX, an easy to use open source program incorporating multiple bioinformatics utilities. Some well characterized endogenous retroviruses are shown in two different DAS clients. A rapid analysis of areas free from retroviral insertions could be facilitated by our annotations. CONCLUSION: The DAS protocol has shown to be advantageous in the distribution of endogenous retrovirus data. The distributed nature of the protocol is also found to aid in combining annotation and visualization along a genome in order to enhance the understanding of ERV contribution to its evolution. Reference and annotation servers are conjointly used by eBioX to provide visualization of ERV annotations as well as other data sources. Our DAS data source can be found in the central public DAS service repository, http://www.dasregistry.org, or at http://loka.bmc.uu.se/das/sources.
34.	Barrio, Alvaro Martinez, et al. (author) The First Sequenced Carnivore Genome Shows Complex Host-Endogenous Retrovirus Relationships 2011 In: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 6:5, s. e19832- Journal article (peer-reviewed)abstract Host-retrovirus interactions influence the genomic landscape and have contributed substantially to mammalian genome evolution. To gain further insights, we analyzed a female boxer (Canis familiaris) genome for complexity and integration pattern of canine endogenous retroviruses (CfERV). Intriguingly, the first such in-depth analysis of a carnivore species identified 407 CfERV proviruses that represent only 0.15% of the dog genome. In comparison, the same detection criteria identified about six times more HERV proviruses in the human genome that has been estimated to contain a total of 8% retroviral DNA including solitary LTRs. These observed differences in man and dog are likely due to different mechanisms to purge, restrict and protect their genomes against retroviruses. A novel group of gammaretrovirus-like CfERV with high similarity to HERV-Fc1 was found to have potential for active retrotransposition and possibly lateral transmissions between dog and human as a result of close interactions during at least 10.000 years. The CfERV integration landscape showed a non-uniform intra-and inter-chromosomal distribution. Like in other species, different densities of ERVs were observed. Some chromosomal regions were essentially devoid of CfERVs whereas other regions had large numbers of integrations in agreement with distinct selective pressures at different loci. Most CfERVs were integrated in antisense orientation within 100 kb from annotated protein-coding genes. This integration pattern provides evidence for selection against CfERVs in sense orientation relative to chromosomal genes. In conclusion, this ERV analysis of the first carnivorous species supports the notion that different mammals interact distinctively with endogenous retroviruses and suggests that retroviral lateral transmissions between dog and human may have occurred.
35.	Benachenhou, Farid, et al. (author) Conserved structure and inferred evolutionary history of long terminal repeats (LTRs) 2013 In: Mobile DNA. - : Springer Science and Business Media LLC. - 1759-8753. ; 4, s. 5- Journal article (peer-reviewed)abstract Background: Long terminal repeats (LTRs, consisting of U3-R-U5 portions) are important elements of retroviruses and related retrotransposons. They are difficult to analyse due to their variability. The aim was to obtain a more comprehensive view of structure, diversity and phylogeny of LTRs than hitherto possible. Results: Hidden Markov models (HMM) were created for 11 clades of LTRs belonging to Retroviridae (class III retroviruses), animal Metaviridae (Gypsy/Ty3) elements and plant Pseudoviridae (Copia/Ty1) elements, complementing our work with Orthoretrovirus HMMs. The great variation in LTR length of plant Metaviridae and the few divergent animal Pseudoviridae prevented building HMMs from both of these groups. Animal Metaviridae LTRs had the same conserved motifs as retroviral LTRs, confirming that the two groups are closely related. The conserved motifs were the short inverted repeats (SIRs), integrase recognition signals (5' TGTTRNR ... YNYAACA 3'); the polyadenylation signal or AATAAA motif; a GT-rich stretch downstream of the polyadenylation signal; and a less conserved AT-rich stretch corresponding to the core promoter element, the TATA box. Plant Pseudoviridae LTRs differed slightly in having a conserved TATA-box, TATATA, but no conserved polyadenylation signal, plus a much shorter R region. The sensitivity of the HMMs for detection in genomic sequences was around 50% for most models, at a relatively high specificity, suitable for genome screening. The HMMs yielded consensus sequences, which were aligned by creating an HMM model (a 'Superviterbi' alignment). This yielded a phylogenetic tree that was compared with a Pol-based tree. Both LTR and Pol trees supported monophyly of retroviruses. In both, Pseudoviridae was ancestral to all other LTR retrotransposons. However, the LTR trees showed the chromovirus portion of Metaviridae clustering together with Pseudoviridae, dividing Metaviridae into two portions with distinct phylogeny. Conclusion: The HMMs clearly demonstrated a unitary conserved structure of LTRs, supporting that they arose once during evolution. We attempted to follow the evolution of LTRs by tracing their functional foundations, that is, acquisition of RNAse H, a combined promoter/polyadenylation site, integrase, hairpin priming and the primer binding site (PBS). Available information did not support a simple evolutionary chain of events.
36.	Benachenhou, Farid, et al. (author) Evolutionary Conservation of Orthoretroviral Long Terminal Repeats (LTRs) and ab initio Detection of Single LTRs in Genomic Data 2009 In: PLos ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 4:4, s. e5179- Journal article (peer-reviewed)abstract BACKGROUND: Retroviral LTRs, paired or single, influence the transcription of both retroviral and non-retroviral genomic sequences. Vertebrate genomes contain many thousand endogenous retroviruses (ERVs) and their LTRs. Single LTRs are difficult to detect from genomic sequences without recourse to repetitiveness or presence in a proviral structure. Understanding of LTR structure increases understanding of LTR function, and of functional genomics. Here we develop models of orthoretroviral LTRs useful for detection in genomes and for structural analysis. PRINCIPAL FINDINGS: Although mutated, ERV LTRs are more numerous and diverse than exogenous retroviral (XRV) LTRs. Hidden Markov models (HMMs), and alignments based on them, were created for HML- (human MMTV-like), general-beta-, gamma- and lentiretroviruslike LTRs, plus a general-vertebrate LTR model. Training sets were XRV LTRs and RepBase LTR consensuses. The HML HMM was most sensitive and detected 87% of the HML LTRs in human chromosome 19 at 96% specificity. By combining all HMMs with a low cutoff, for screening, 71% of all LTRs found by RepeatMasker in chromosome 19 were found. HMM consensus sequences had a conserved modular LTR structure. Target site duplications (TG-CA), TATA (occasionally absent), an AATAAA box and a T-rich region were prominent features. Most of the conservation was located in, or adjacent to, R and U5, with evidence for stem loops. Several of the long HML LTRs contained long ORFs inserted after the second A rich module. HMM consensus alignment allowed comparison of functional features like transcriptional start sites (sense and antisense) between XRVs and ERVs. CONCLUSION: The modular conserved and redundant orthoretroviral LTR structure with three A-rich regions is reminiscent of structurally relaxed Giardia promoters. The five HMMs provided a novel broad range, repeat-independent, ab initio LTR detection, with prospects for greater generalisation, and insight into LTR structure, which may aid development of LTR-targeted pharmaceuticals.
37.	Benachenhou, Farid, 1966- (author) Retroviral long Terminal Repeats; Structure, Detection and Phylogeny 2010 Doctoral thesis (other academic/artistic)abstract Long terminal repeats (LTRs) are non-coding repeats flanking the protein-coding genes of LTR retrotransposons. The variability of LTRs poses a challenge in studying them. Hidden Markov models (HMMs), probabilistic models widely used in pattern recognition, are useful in dealing with this variability. The aim of this work was mainly to study LTRs of retroviruses and LTR retrotransposons using HMMs. Paper I describes the methodology of HMM modelling applied to different groups of LTRs from exogenous retroviruses (XRVs) and endogenous retroviruses (ERVs). The detection capabilities of HMMs were assessed and were found to be high for homogeneous groups of LTRs. The alignments generated by the HMMs displayed conserved motifs some of which could be related to known functions of XRVs. The common features of the different groups of retroviral LTRs were investigated by combining them into a single alignment. They were the short inverted terminal repeats TG and CA and three AT-rich stretches which provide retroviruses with TATA boxes and AATAAA polyadenylation signals. In Paper II, phylogenetic trees of three groups of retroviral LTRs were constructed by using HMM-based alignments. The LTR trees were consistent with trees based on other retroviral genes suggesting co-evolution between LTRs and these genes. In Paper III, the methods in Paper I and II were extended to LTRs from other retrotransposon groups, covering much of the diversity of all known LTRs. For the first time an LTR phylogeny could be achieved. There were no major disagreement between the LTR tree and trees based on three different domains of the Pol gene. The conserved LTR structure of paper I was found to apply to all LTRs. Putative Integrase recognition motifs extended up to 12 bp beyond the short inverted repeats TG/CA. Paper IV is a review article describing the use of sequence similarity and structural markers for the taxonomy of ERVs. ERVs were originally classified into three classes according to the length of the target site duplication. While this classification is useful it does not include all ERVs. A naming convention based on previous ERV and XRV nomenclature but taking into account newer information is advocated in order to provide a practical yet coherent scheme in dealing with new unclassified ERV sequences. Paper V gives an overview of bioinformatics tools for studies of ERVs and of retroviral evolution before and after endogenization. It gives some examples of recent integrations in vertebrate genomes and discusses pathogenicity of human ERVs including their possible relation to cancers. In conclusion, HMMs were able to successfully detect and align LTRs. Progress was made in understanding their conserved structure and phylogeny. The methods developed in this thesis could be applied to different kinds of non-coding DNA sequence element.
38.	Benachenhou, Farid, et al. (author) The phylogeny of orthoretroviral long terminal repeats (LTRs) 2009 In: Gene. - Amsterdam : Elsevier. - 0378-1119 .- 1879-0038. ; 448:2, s. 134-138 Journal article (peer-reviewed)abstract LTRs are sequence elements in retroviruses and retrotransposons which are difficult to align due to their variability. One way of handling such cases is to use Hidden Markov Models (HMMs). In this work HMMs of LTRs were constructed for three groups of orthoretroviruses: the betaretroviruslike human MMTV-like (HML) endogenous retroviruses, the lentiviruses, including HIV, and gammaretroviruslike human endogenous retroviruses (HERVs). The HMM-generated LTR alignments and the phylogenetic trees constructed from them were compared with trees based on alignments of the pol gene at the nucleic acid level. The majority of branches in the LTR and pol based trees had the same order for the three retroviral genera, showing that HMM methods are successful in aligning and constructing phylogenies of LTRs. The HML LTR tree deviated somewhat from the pol tree for the groups HML3, HML7 and HML6. Among the gammaretroviruslike proviruses, the exogenous Mouse Leukemia Virus (MLV) was highly related to HERV-T in the pol based tree, but not in the LTR based tree. Aside from these differences, the similarity between the trees indicates that LTRs and pol coevolved in a largely monophyletic way.
39.	Benachenhou, Farid, et al. (author) Universal structure and phylogeny of Long Terminal Repeats (LTRs) Other publication (other academic/artistic)abstract Long terminal repeats (LTRs) are important sequence elements of retroviruses and related retrotransposons. They are however difficult to analyse due to their variability. The aim of this work was to construct models of LTRs from all known groups of LTR retrotransposons and retroviruses, representative of the entire LTR diversity, making it possible for the first time to comprehensively study their phylogeny and to compare it to phylogenies of other retrotransposon genes. A general HMM describing all LTRs was built. Its associated Viterbi alignment showed a consistent basic structure with inverted repeats starting with TGTT at the 5´end, ending with AACA at the 3´ end, plus two conserved AT-rich areas, the first one often containing the TATA box and the second one containing the polyadenylation signal AATAAA. A less conserved AT-rich stretch was apparent in the likely U3 portion. R was harder to delineate. The polyadenylation signal was followed by a T rich area characteristic of U5. The modular LTR structure previously reported by us, with modules separated by clusters of insert states, was also observed in this pan-LTR setting The result attests to the highly conserved basic structure of LTRs, which must date over a billion years back. Hidden Markov models (HMM) were also created for 14 subgroups of LTRs. The HMMs yielded consensus sequences which were aligned to a "Superviterbi" alignment. The Superviterbi alignment yielded a phylogenetic tree which was consistent with a tree based on an alignment of concatenated RT, RNAse H and INT proteins. In particular it gave further support for the monophyly of retroviral LTRs. The phylogenetic reconstruction now allows inferences regarding the origin of LTR retrotransposons.
40.	Bengtsson, A, et al. (author) Selective antibody reactivity with peptides from human endogenous retroviruses and nonviral polyaminoacids in patients with systemic lupus erythematosus 1996 In: Arthritis and Rheumatism. ; 39, s. 1654- Journal article (peer-reviewed)
41.	Bengtsson, Ders, et al. (author) Selective antibody reactivity with peptides from human endogenous retroviruses and nonviral poly(amino acids) in patients with systemic lupus erythematosus 1996 In: Arthritis and Rheumatism. - : Wiley. - 0004-3591 .- 1529-0131. ; 39:10, s. 1654-1663 Journal article (peer-reviewed)abstract Objective. To investigate antibody responses to a broad panel of peptides derived from human endogenous retroviruses (HERVs) among unselected patients with systemic lupus erythematosus (SLE). Methods. In sera obtained from 69 patients with SLE and healthy blood donors, immunoassay was used to measure levels of antibody against synthetic peptides derived from HERVs, exogenous retroviruses, and nonviral poly(amino acids). Results. Measurement by immunoassay revealed increased frequencies of antiretroviral antibodies against 2 peptides derived from the env gene of the type C-like class, which includes ERV-9 and HERV-H, and against 2 peptides from the gag region of human T lymphotropic virus type I-related endogenous sequence 1, in patients with SLE. Antibodies to 2 nonviral peptides, polyhistidine and polyproline, were also overrepresented in patient sera. In 1 patient, longitudinal data obtained over a period of 12 years indicated that the concentrations of certain antiretroviral antibodies varied according to disease activity. Conclusion. Reactivity to certain type C HERV-derived antigens was found among patients with SLE. This reactivity could be explained by increased exposure to cross-reactive epitopes from essentially complete type C HERVs.
42.	Bergman Ärlebäck, Jonas, 1972-, et al. (author) An instructional design perspective on data-modelling for learning statistics and modelling 2015 In: Development of mathematics teaching: Design, Scale, Effects. - Umeå : Svensk förening för MatematikDidaktisk Forskning - SMDF. ; , s. 37-46, s. 37-46 Conference paper (peer-reviewed)abstract This theoretical and methodological paper discusses the emerging theoretical framing and methodological considerations in our efforts to develop a theoretical approach supporting instructional design for teaching and learning statistics and mathematical modelling. From an instructional design point of view aligned with the goals in governing curricula documents and real classroom constraints, we argue for the integration of the models and modelling perspective on teaching and learning mathematics with a data-modelling approach to facilitate students’ learning statistics and mathematical modelling. An application of the framework is given and future research discussed.
43.	Bergman Ärlebäck, Jonas, et al. (author) An instructional design perspective on data-modelling for learning statistics and modelling 2015 Conference paper (peer-reviewed)
44.	Bergman Ärlebäck, Jonas, et al. (author) An instructional design perspective on datamodelling for learning statistics and modelling 2014 Conference paper (peer-reviewed)abstract This theoretical and methodological paper discusses the emerging theoretical framing and methodological considerations in our efforts to develop a theoretical approach supporting instructional design for teaching and learning statistics and mathematical modelling. From an instructional design point of view aligned with the goals in governing curricula documents and real classroom constraints, we argue for the integration of the models and modelling perspective on teaching and learning mathematics with a data-modelling approach to facilitate students’ learning statistics and mathematical modelling. An application of the framework is given and future research discussed.
45.	Bindra, Amarinder, et al. (author) Search for DNA of exogenous mouse mammary tumor virus-related virus in human breast cancer samples 2007 In: Journal of General Virology. - : Microbiology Society. - 0022-1317 .- 1465-2099. ; 88, s. 1806-1809 Journal article (peer-reviewed)abstract Earlier reports of a human exogenous retrovirus (HMTV) related closely to mouse mammary tumor virus (MMTV) led us to search for these viral sequences in breast cancer tissues and normal tissues. A real-time PCR was developed based on MMTV and published HMTV envelope sequences. The real-time PCR method can detect one to ten copies of MMTV target DNA. Tissue samples were collected prospectively from 18 breast cancer patients and 11 non-malignant control cases, as well as peripheral blood leukocytes from the same women. Despite the high sensitivity of the real-time PCR method used, none of the samples were positive for HMTV DNA or RNA. The absence of HMTV DNA in both breast cancer samples and controls indicates either that the concentration of putative HMTV DNA in the breast cancers was too low for detection or that it did not exist there.
46.	Blikstad, Vidar, et al. (author) Evolution of human endogenous retroviral sequences : a conceptual account 2008 In: Cellular and Molecular Life Sciences (CMLS). - : Springer Science and Business Media LLC. - 1420-682X .- 1420-9071. ; 65:21, s. 3348-3365 Research review (peer-reviewed)abstract Endogenous retroviruses (ERVs) most likely are remnants of ancient retroviral infections. ERVs preserve functions of exogenous retroviruses to a varying extent, and can be parasites, symbionts or more or less neutral genetic 'junk'.Their evolution has two facets, pre- and post-endogenization. Although the two are not clearly separated, the first pertains to retroviral evolution in general and the second to the fate of repetitive DNA and the evolution of the host organism and its genome. The study of ERVs provides much material for the understanding of retroviral evolution. This sequence archive reflects the history of successes and shortcomings of antiviral resistance, but also of strategic evolutionary decisions regarding genome organization and new gene acquisition. This review discusses retroviral evolution illustrated through HERVs, bioinformatic prerequisites for ERV studies, the endogenization process and HERV evolution post-endogenization, including relation to disease. (Part of a multi-author review).
47.	Blomberg, Carl, et al. (author) Randomized Trials of Systemic Medically-treated Malignant Mesothelioma : A Systematic Review 2015 In: Anticancer Research. - 0250-7005 .- 1791-7530. ; 35:5, s. 2493-2501 Research review (peer-reviewed)abstract Malignant pleural mesothelioma (MPM) is a rare but aggressive malignancy mainly localized to the pleura. Malignant mesothelioma grows highly invasive into surrounding tissue and has a low tendency to metastasize. The median overall survival (OS) of locally advanced or metastatic disease without treatment is 4-13 months but, during recent years, improvement in survival has been achieved since treatment for patients with mesothelioma has improved with better palliative care, systemic medical treatment, surgery and improved diagnostics methods. The present review aims at describing available data from randomized trials considering systemic medical treatment for this patient category.
48.	Blomberg, Frida, et al. (author) Emotional arousal and lexical specificity modulate response times differently depending on ear of presentation in a dichotic listening task 2015 In: The Mental Lexicon. - : John Benjamins Publishing Company. - 1871-1340 .- 1871-1375. ; 10:2, s. 221-246 Journal article (peer-reviewed)abstract We investigated possible hemispheric differences in the processing of four different lexical semantic categories: SPECIFIC (e.g. bird), GENERAL (e.g. animal), ABSTRACT (e.g. advice), and EMOTIONAL (e.g. love). These wordtypes were compared using a dichotic listening paradigm and a semantic category classification task. Response times (RTs) were measured when participants classified testwords as concrete or abstract. In line with previous findings, words were expected to be processed faster following right-ear presentation. However, lexical specificity and emotional arousal were predicted to modulate response times differently depending on the ear of presentation. For left-ear presentation, relatively faster RTs were predicted for SPECIFIC and EMOTIONAL words as opposed to GENERAL and ABSTRACT words. An interaction of ear and wordtype was found. For right-ear presentation, RTs increased as testwords’ imageability decreased along the span SPECIFIC–GENERAL–EMOTIONAL–ABSTRACT. In contrast, for left ear presentation, EMOTIONAL words were processed fastest, while SPECIFIC words gave rise to long RTs on par with those for ABSTRACT words. Thus, the prediction for EMOTIONAL words presented in the left ear was borne out, whereas the prediction for SPECIFIC words was not. This might be related to previously found differences in processing of stimuli at a global or local level.
49.	Blomberg, Helena, 1970-, et al. (author) A narrative study of newly graduated registered Swedish nurses' establishment in the profession and the portrayal of a healthcare organisation 2019 In: Journal of Health Organization and Management. - : Emerald Insight. - 1477-7266. ; 33:4, s. 413-425 Journal article (peer-reviewed)abstract Purpose The purpose of this paper is to investigate how the participants talk about their experiences as newly graduated nurses, managers and nursing colleagues in the context of "newcomers' establishment in the profession" and to identify how they portray the healthcare organisation in their narratives. Design/methodology/approach A narrative approach is used to reveal and illustrate three perspectives on the topic "new-comers' establishment". In total, 14 interviews are conducted with 4 managers, 4 nursing colleagues and 6 newly graduated registered nurses. The focus of this study is how a healthcare organisation embraces and retains newly graduated registered nurses and how this is perceived. Findings The newcomers' establishment is facilitated by an orientation programme and an orientation period, individual support provided by managers and colleagues, and the creation of trust to boost confidence in nursing situations. The organisation is portrayed as struggling with high workloads, nursing shortages, high levels of responsibility and showing concern and an interest in the newcomer. The parties criticise the university for not teaching the most basic knowledge, thereby revealing the existence of a theory-practice gap. Originality/value The research shows how building trust amongst the organisation's members is essential for creating a satisfying workplace and the retention of newly graduated registered nurses. Empirical descriptions of newly graduated nurses, managers and nursing colleagues experiences of "newcomers establishment" are rare, which is why the description of such "establishment" in this research increases the value of the paper.
50.	Blomberg, Helena, 1970-, et al. (author) Att vara kommunikativt låst : Professionellas berättande om (vanskliga) vårdrelationer 2016 In: Socialvetenskaplig tidskrift. - 1104-1420 .- 2003-5624. ; 23:1, s. 59-76 Journal article (peer-reviewed)abstract The aim of the article is to shed light on the social dynamic that characterizes communicative breakdowns. As a first stage, this has been explored through individual and group interviews with 34 healthcare professionals about situations where they claim there has been a communication breakdown. Based on the professionals’ testimonies, the research question was: how do professionals illustrate their experiences of communicative breakdowns? In terms of theory, the study draws upon an integrated approach to language and social interaction dynamics – for example how actors mediate positions and roles, but also present, negotiate and determine the course of action in patient cases. Findings show: (1) different degrees of severity in communicative breakdowns, and (2) that the professionals have developed and use both explicit and implicit strategies to handle ”delicate relationships” in this kind of interactions.

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