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1.	Nord, Helena, 1980- (author) Application of Genomic and Expression Arrays for Identification of new Cancer Genes 2010 Doctoral thesis (other academic/artistic)abstract Copy number variation (CNV) comprises a recently discovered kind of variation involving deletion and duplication of DNA segments of variable size, ranging from a few hundred basepairs to several million. By altering gene dosage levels or disrupting proximal or distant regulatory elements CNVs create human diversity. They represent also an important factor in human evolution and play a role in many disorders including cancer. Array-based comparative genomic hybridization as well as expression arrays are powerful and suitable methods for determination of copy number variations or gene expression changes in the human genome. In paper I we established a 32K clone-based genomic array, covering 99% of the current assembly of the human genome with high resolution and applied it in the profiling of 71 healthy individuals from three ethnic groups. Novel and previously reported CNVs, involving ~3.5% of the genome, were identified. Interestingly, 87% of the detected CNV regions overlapped with known genes indicating that they probably have phenotypic consequences. In papers II through IV we applied this platform to different tumor types, namely two collections of brain tumors, glioblastoma (paper II) and medulloblastoma (paper III), and a set of bladder carcinoma (paper IV) to identify chromosomal alterations at the level of DNA copy number that could be related to tumor initiation/progression. Tumors of the central nervous system represent a heterogeneous group of both benign and malignant neoplasms that affect both children and adults. Glioblastoma and medulloblastoma are two malignant forms. Glioblastoma often affects adults while the embryonal tumor medulloblastoma is the most common malignant brain tumor among children. The detailed profiling of 78 glioblastomas, allowed us to identify a complex pattern of aberrations including frequent and high copy number amplicons (detected in 79% of samples) as well as a number of homozygously deleted loci. These regions encompassed not only previously reported oncogenes and tumor suppressor genes but also numerous novel genes. In paper III, a subset of 26 medulloblastomas was analyzed using the same genomic array. We observed that alterations involving chromosome 17, especially isochromosome 17q, were the most common genomic aberrations in this tumor type, but copy number alterations involving other chromosomes: 1, 7 and 8 were also frequent. Focal amplifications, on chromosome 1 and 3, not previously described, were also detected. These loci may encompass novel genes involved in medulloblastoma development. In paper IV we examined for the presence of DNA copy number alterations and their effect on gene expression in a subset of 21 well-characterized Ta bladder carcinomas, selected for the presence or absence of recurrences. We identified a number of novel genes as well as a significant association between amplifications and high-grade and recurrent tumors which might be clinically useful. The results derived from these studies increase our understanding of the genetic alterations leading to the development of these tumor forms and point out candidate genes that may be used in future as targets for new diagnostic and therapeutic strategies.
2.	Andersson, Robin, et al. (author) A Segmental Maximum A Posteriori Approach to Genome-wide Copy Number Profiling 2008 In: Bioinformatics. - : Oxford University Press (OUP). - 1367-4803 .- 1367-4811. ; 24:6, s. 751-758 Journal article (other academic/artistic)abstract MOTIVATION: Copy number profiling methods aim at assigning DNA copy numbers to chromosomal regions using measurements from microarray-based comparative genomic hybridizations. Among the proposed methods to this end, Hidden Markov Model (HMM)-based approaches seem promising since DNA copy number transitions are naturally captured in the model. Current discrete-index HMM-based approaches do not, however, take into account heterogeneous information regarding the genomic overlap between clones. Moreover, the majority of existing methods are restricted to chromosome-wise analysis. RESULTS: We introduce a novel Segmental Maximum A Posteriori approach, SMAP, for DNA copy number profiling. Our method is based on discrete-index Hidden Markov Modeling and incorporates genomic distance and overlap between clones. We exploit a priori information through user-controllable parameterization that enables the identification of copy number deviations of various lengths and amplitudes. The model parameters may be inferred at a genome-wide scale to avoid overfitting of model parameters often resulting from chromosome-wise model inference. We report superior performances of SMAP on synthetic data when compared with two recent methods. When applied on our new experimental data, SMAP readily recognizes already known genetic aberrations including both large-scale regions with aberrant DNA copy number and changes affecting only single features on the array. We highlight the differences between the prediction of SMAP and the compared methods and show that SMAP accurately determines copy number changes and benefits from overlap consideration.
3.	Backman, Samuel, et al. (author) The Evolutionary History of Metastatic Pancreatic Neuroendocrine Tumours Reveals a Therapy Driven Route to High-Grade Transformation. 2024 In: medRxiv : the preprint server for health sciences. Journal article (peer-reviewed)abstract Tumour evolution with acquisition of more aggressive disease characteristics is a hallmark of disseminated cancer. Metastatic pancreatic neuroendocrine tumours (PanNETs) in particular, show frequent progression from a low/intermediate to a high-grade disease. To understand the molecular mechanisms underlying this phenomenon, we performed multi-omics analysis of 32 longitudinal samples from six metastatic PanNET patients. Following MEN1 inactivation, PanNETs exhibit genetic heterogeneity on both spatial and temporal dimensions with parallel and convergent tumuor evolution involving the ATRX/DAXX and mTOR pathways. Following alkylating chemotherapy treatment, some PanNETs develop mismatch repair deficiency and acquire a hypermutator phenotype. This DNA hypermutation phenotype was only found in cases that also showed transformation into a high-grade PanNET. Overall, our findings contribute to broaden the understanding of metastatic PanNET, and suggests that therapy driven disease evolution is an important hallmark of this disease.
4.	Cavalli, Marco, et al. (author) Allele-specific transcription factor binding in liver and cervix cells unveils many likely drivers of GWAS signals 2016 In: Genomics. - : Elsevier BV. - 0888-7543 .- 1089-8646. ; 107:6, s. 248-254 Journal article (peer-reviewed)abstract Genome-wide association studies (GWAS) point to regions with associated genetic variants but rarely to a specific gene and therefore detailed knowledge regarding the genes contributing to complex traits and diseases remains elusive. The functional role of GWAS-SNPs is also affected by linkage disequilibrium with many variants on the same haplotype and sometimes in the same regulatory element almost equally likely to mediate the effect. Using ChIP-seq data on many transcription factors, we pinpointed genetic variants in HepG2 and HeLa-S3 cell lines which show a genome-wide significant difference in binding between alleles. We identified a collection of 3713 candidate functional regulatory variants many of which are likely drivers of GWAS signals or genetic difference in expression. A recent study investigated many variants before finding the functional ones at the GALNT2 locus, which we found in our genome-wide screen in HepG2. This illustrates the efficiency of our approach.
5.	Cavalli, Marco, et al. (author) Allele-specific transcription factor binding to common and rare variants associated with disease and gene expression 2016 In: Human Genetics. - : Springer Science and Business Media LLC. - 0340-6717 .- 1432-1203. ; 135:5, s. 485-497 Journal article (peer-reviewed)abstract Genome-wide association studies (GWAS) have identified a large number of disease-associated SNPs, but in few cases the functional variant and the gene it controls have been identified. To systematically identify candidate regulatory variants, we sequenced ENCODE cell lines and used public ChIP-seq data to look for transcription factors binding preferentially to one allele. We found 9962 candidate regulatory SNPs, of which 16 % were rare and showed evidence of larger functional effect than common ones. Functionally rare variants may explain divergent GWAS results between populations and are candidates for a partial explanation of the missing heritability. The majority of allele-specific variants (96 %) were specific to a cell type. Furthermore, by examining GWAS loci we found >400 allele-specific candidate SNPs, 141 of which were highly relevant in our cell types. Functionally validated SNPs support identification of an SNP in SYNGR1 which may expose to the risk of rheumatoid arthritis and primary biliary cirrhosis, as well as an SNP in the last intron of COG6 exposing to the risk of psoriasis. We propose that by repeating the ChIP-seq experiments of 20 selected transcription factors in three to ten people, the most common polymorphisms can be interrogated for allele-specific binding. Our strategy may help to remove the current bottleneck in functional annotation of the genome.
6.	Cavalli, Marco, et al. (author) Genetic prevention of hepatitis C virus-induced liver fibrosis by allele-specific downregulation of MERTK 2017 In: Hepatology Research. - : Wiley. - 1386-6346 .- 1872-034X. ; 47:8, s. 826-830 Journal article (peer-reviewed)abstract AIM: Infection by hepatitis C virus (HCV) can result in the development of liver fibrosis and may eventually progress into cirrhosis and hepatocellular carcinoma. However, the molecular mechanisms for this process are not fully known. Several genome-wide association studies have been carried out to pinpoint causative variants in HCV-infected patient cohorts, but these variants are usually not the functional ones. The aim of this study was to identify the regulatory single nucleotide polymorphism associated with the risk of HCV-induced liver fibrosis and elucidate its molecular mechanism.METHODS: We utilized a bioinformatics approach to identify a non-coding regulatory variant, located in an intron of the MERTK gene, based on differential transcription factor binding between the alleles. We validated the results using expression reporter assays and electrophoresis mobility shift assays.RESULTS: Chromatin immunoprecipitation sequencing indicated that transcription factor(s) bind stronger to the A allele of rs6726639. Electrophoresis mobility shift assays supported these findings and suggested that the transcription factor is interferon regulatory factor 1 (IRF1). Luciferase report assays showed lower enhancer activity from the A allele and that IRF1 may act as a repressor.CONCLUSIONS: Treatment of hepatitis C with interferon-α results in increased IRF1 levels and our data suggest that this leads to an allele-specific downregulation of MERTK mediated by an allelic effect on the regulatory element containing the functional rs6726639. This variant also shows the hallmarks for being the driver of the genome-wide association studies for reduced risk of liver fibrosis and non-alcoholic fatty liver disease at MERTK.
7.	Cavalli, Marco, et al. (author) Looking beyond GWAS : allele-specific transcription factor binding drives the association of GALNT2 to HDL-C plasma levels 2016 In: Lipids in Health and Disease. - : Springer Science and Business Media LLC. - 1476-511X. ; 15 Journal article (peer-reviewed)abstract Background: Plasma levels of high-density lipoprotein cholesterol (HDL-C) have been associated to cardiovascular disease. The high heritability of HDL-C plasma levels has been an incentive for several genome wide association studies (GWASs) which identified, among others, variants in the first intron of the GALNT2 gene strongly associated to HDL-C levels. However, the lead GWAS SNP associated to HDL-C levels in this genomic region, rs4846914, is located outside of transcription factor (TF) binding sites defined by chromatin immunoprecipitation followed by DNA sequencing (ChIP-seq) experiments in the ENCODE project and is therefore unlikely to be functional. In this study we apply a bioinformatics approach which rely on the premise that ChIP-seq reads can identify allele specific binding of a TF at cell specific regulatory elements harboring allele specific SNPs (AS-SNPs). EMSA and luciferase assays were used to validate the allele specific binding and to test the enhancer activity of the regulatory element harboring the AS-SNP rs4846913 as well as the neighboring rs2144300 which are in high LD with rs4846914. Findings: Using luciferase assays we found that rs4846913 and the neighboring rs2144300 displayed allele specific enhancer activity. We propose that an inhibitor binds preferentially to the rs4846913-C allele with an inhibitory boost from the synergistic binding of other TFs at the neighboring SNP rs2144300. These events influence the transcription level of GALNT2. Conclusions: The results suggest that rs4846913 and rs2144300 drive the association to HDL-C plasma levels through an inhibitory regulation of GALNT2 rather than the reported lead GWAS SNP rs4846914.
8.	Cavalli, Marco, et al. (author) Novel regulatory variant detected on the VKORC1 haplotype that is associated with warfarin dose 2016 In: Pharmacogenomics (London). - : Future Medicine Ltd. - 1462-2416 .- 1744-8042. ; 17:12, s. 1305-1314 Journal article (peer-reviewed)abstract Aim: Warfarin dose requirement is associated with VKORC1 rs9923231, and we studied whether it is a functional variant.Materials & methods: We selected variants in linkage disequilibrium with rs9923231 that bind transcription factors in an allele-specific way. Representative haplotypes were cloned or constructed, nuclear protein binding and transcriptional activity were evaluated.Results: rs56314408C>T and rs2032915C>T were detected in a liver enhancer in linkage disequilibrium with rs9923231. The rs56314408-rs2032915 C-C haplotype preferentially bound nuclear proteins and had higher transcriptional activity than T-T and the African-specific T-C. A motif for TFAP2A/C was disrupted by rs56314408T. No difference in transcriptional activity was detected for rs9923231G>A.Conclusion: Our results supported an activating role for rs56314408C, while rs9923231G>A had no evidence of being functional.
9.	de Ståhl, Teresita Díaz, et al. (author) Profiling of copy number variations (CNVs) in healthy individuals from three ethnic groups using a human genome 32 K BAC-clone-based array 2008 In: Human Mutation. - : Hindawi Limited. - 1059-7794 .- 1098-1004. ; 29:3, s. 398-408 Journal article (peer-reviewed)abstract To further explore the extent of structural large-scale variation in the human genome, we assessed copy number variations (CNVs) in a series of 71 healthy subjects from three ethnic groups. CNVs were analyzed using comparative genomic hybridization (CGH) to a BAC array covering the human genome, using DNA extracted from peripheral blood, thus avoiding any culture-induced rearrangements. By applying a newly developed computational algorithm based on Hidden Markov modeling, we identified 1,078 autosomal CNVs, including at least two neighboring/overlapping BACs, which represent 315 distinct regions. The average size of the sequence polymorphisms was approximately 350 kb and involved in total approximately 117 Mb or approximately 3.5% of the genome. Gains were about four times more common than deletions, and segmental duplications (SDs) were overrepresented, especially in larger deletion variants. This strengthens the notion that SDs often define hotspots of chromosomal rearrangements. Over 60% of the identified autosomal rearrangements match previously reported CNVs, recognized with various platforms. However, results from chromosome X do not agree well with the previously annotated CNVs. Furthermore, data from single BACs deviating in copy number suggest that our above estimate of total variation is conservative. This report contributes to the establishment of the common baseline for CNV, which is an important resource in human genetics.
10.	Edskär, Ida (author) Modal Analysis, Dynamic Properties and Horizontal Stabilisation of Timber Buildings 2019 Doctoral thesis (other academic/artistic)abstract Engineers face new challenges as taller timber buildings are constructed. According to Eurocode 1-4, both horizontal deformations from static wind and acceleration levels shall be limited. Due to the low self-weight of wood, dynamic vibrations and acceleration levels cancause problems. The current knowledge in the field is limited and there is a need for increasing the understanding of dynamic properties in tall timber buildings. This research project has been a collaboration between Luleå Technical University and Sweco Structures AB, where the author has gained practical experience as a designer in parallel to the research studies.The purpose of this research is to understand and describe the dynamic behaviour of tall timber buildings using FE-simulations , studying their dynamic properties, and comparing acceleration levels to comfort criteria. By varying different parameters, dynamic properties have been studied and compared with assumptions and recommendations in Eurocode 1-4.In this study, buildings with cross-laminated timber panels (CLT) have been studied but also post-and-beam systems with trusses. Depending on the shape, layout and materials of the building, the dynamic properties of the building will vary: natural frequency, mode shape, modal mass, and modal stiffness. To assess the comfort of the building, the standard ISO 10137 has been used evaluating the natural frequency of the building and its peak acceleration. Simulations have been performed using finite element (FE) software where modal analyses have been performed. Over 250 simulations have been performed in this study.Adding mass reduces the natural frequency and the acceleration level of the building, which is an appropriate measure if the building has a frequency below 1 Hz. Increased stiffness increases the natural frequency and reduces the acceleration level, which is suitable for buildings with a natural frequency over 2 Hz.The empirical expression f = 46 / h should be used with caution as it is based onmeasurements of concrete and steel buildings. The recommendation is to perform FEsimulations until the empirical knowledge base is sufficient for timber buildings.The placement of the stabilizing system is important for creating a balanced (symmetrical) system resulting in pure translation modes. Eurocode 1-4 presupposes 2D modes in the plane while asymmetry can create diagonal and even torsional modes, which Eurocode 1-4 cannot handle. Openings and asymmetry in the floor plan affect the dynamic properties of the building. The assumption that the building can be modelled as a homogeneous beam where the mass is evenly distributed can result in an over- or underestimation of the equivalent mass, which in turn can lead to an underestimation of the acceleration level, around 20% - 30%. It is recommended that the equivalent mass is calculated from FE generated modal mass and mode shapes.Acceleration levels vary over the building height depending on the mode shape. Timber buildings with a slenderness <3.9 have more or less a pure shear mode and with increasing height it shifts to a linear mode. For timber buildings, it is recommended to use the generated mode shape from FE simulations, and not those prescribed in Eurocode 1-4 as these can underestimate the acceleration levels, around 30 %.
11.	Elfving, Hedvig, et al. (author) Evaluation of NTRK immunohistochemistry as a screening method for NTRK gene fusion detection in non-small cell lung cancer 2021 In: Lung Cancer. - : Elsevier. - 0169-5002 .- 1872-8332. ; 151, s. 53-59 Journal article (peer-reviewed)abstract Purpose: The small molecule inhibitors larotrectinib and entrectinib have recently been approved as cancer agnostic drugs in patients with tumours harbouring a rearrangement of the neurotrophic tropomyosin receptor kinase (NTRK). These oncogenic fusions are estimated to occur in 0.1-3 % of non-small cell lung cancers (NSCLC). Although molecular techniques are most reliable for fusion detection, immunohistochemical analysis is considered valuable for screening. Therefore, we evaluated the newly introduced diagnostic immunohistochemical assay (clone EPR17341) on a representative NSCLC cohort.Methods: Cancer tissue from 688 clinically and molecularly extensively annotated NSCLC patients were comprised on tissue microarrays and stained with the pan-TRK antibody clone EPR17341. Positive cases were further analysed with the TruSight Tumor 170 RNA assay (Illumina). Selected cases were also tested with a NanoString NTRK fusion assay. For 199 cases, NTRK RNA expression data were available from previous RNA sequencing analysis.Results: Altogether, staining patterns for 617 NSCLC cases were evaluable. Of these, four cases (0.6 %) demonstrated a strong diffuse cytoplasmic and membranous staining, and seven cases a moderate staining (1.1 %). NanoString or TST170-analysis could not confirm an NTRK fusion in any of the IHC positive cases, or any of the cases with high mRNA levels. In the four cases with strong staining intensity in the tissue microarray, whole section staining revealed marked heterogeneity of NTRK protein expression.Conclusion: The presence of NTRK fusion genes in non-small cell lung cancer is exceedingly rare. The use of the immunohistochemical NTRK assay will result in a small number of false positive cases. This should be considered when the assay is applied as a screening tool in clinical diagnostics.
12.	Fadl, Helena E., 1965-, et al. (author) Randomized controlled study in pregnancy on treatment of marked hyperglycemia that is short of overt diabetes 2015 In: Acta Obstetricia et Gynecologica Scandinavica. - : Wiley-Blackwell. - 0001-6349 .- 1600-0412. ; 94:11, s. 1181-1187 Journal article (peer-reviewed)abstract Introduction: A randomized multicenter study was conducted in the Stockholm-orebro areas in Sweden to evaluate how treatment aiming at normoglycemia affects fetal growth, pregnancy and neonatal outcome in pregnant women with severe hyperglycemia.Material and methods: Pregnant women with hyperglycemia defined as fasting capillary plasma glucose <7.0 mmol/L and a two-hour plasma glucose value 10.0 and <12.2 mmol/L following a 75-g oral glucose tolerance test (OGTT) diagnosed before 34 weeks of gestation were randomized to treatment (n=33) or controls (n=36). Women assigned to the control group were blinded for the OGTT results and received routine care. The therapeutic goal was fasting plasma glucose 4-5 mmol/L, and <6.5 mmol/L after a meal. Primary outcomes were size at birth and number of large-for-gestational age (>90th percentile) neonates. Secondary outcomes were pregnancy complications, neonatal morbidity and glycemic control.Results: The planned number of participating women was not reached. There was a significantly reduced rate of large-for-gestational age neonates, 21 vs. 47%, P<0.05. Group differences in pregnancy complications and neonatal morbidity were not detected because of limited statistical power. In total, 66.7% of the women in the intervention group received insulin. Of all measured plasma glucose values, 64.1% were in the target range, 7.2% in the hypoglycemic range and 28.7% above target values. There were no cases of severe hypoglycemia.Conclusions: Aiming for normalized glycemia in a pregnancy complicated by severe hyperglycemia reduces fetal growth but is associated with an increased rate of mild hypoglycemia.
13.	Gisselsson Nord, David, et al. (author) Unique cytological features and chromosome aberrations in chondroid lipoma: a case report based on fine-needle aspiration cytology, histopathology, electron microscopy, chromosome banding, and molecular cytogenetics 1999 In: American Journal of Surgical Pathology. - 1532-0979. ; 23:10, s. 1300-1300 Journal article (peer-reviewed)abstract Chondroid lipoma is a rare, benign tumor that may mimic soft-tissue sarcoma clinically. Its histopathologic features may resemble hibernoma, myxoid liposarcoma, myxoid chondrosarcoma, and other lipomatous or chondroid neoplasms. In this study, a chondroid lipoma was analyzed by fine-needle aspiration cytology, histopathology, electron microscopy, chromosome banding, and metaphase fluorescence in situ hybridization. The results demonstrate that chondroid lipoma exhibits a characteristic pattern by fine-needle aspiration cytology, including a mixture of benign adipose tissue with lipoblastlike cells, and chondroblastlike cells with a fibrochondroid matrix. Cytogenetically, a three-way rearrangement between chromosomes 1, 2, and 5 was found, together with an 11;16 translocation with a breakpoint in 11q13, approximately 1 Mb proximal to the MEN1 region shown to be rearranged frequently in hibernoma. The presence of a karyotype of low complexity, but without any of the genetic aberrations characteristic for other types of soft-tissue tumors, indicate that chondroid lipoma develops along a unique pathogenetic pathway.
14.	Hallikainen, J., et al. (author) The Wording of Telephone Guided CPRAffect on Senior Citizens Performance : A Simulation Study 2018 In: Journal of Clinical Medicine. - : SM Group. - 2077-0383. ; 4:1 Journal article (peer-reviewed)abstract Objectives: To assess how senior citizens followed Telephone CPR (T-CPR) instructions in a simulated cardiac arrest scenario. Methods: Twenty-two voluntary senior citizens were studied in a simulated cardiac arrest scenario following the instructions given to them by an Emergency Medical Dispatcher. The phone calls and the CPR performance were recorded and analyzed. Results: The rescuers reported that they had performed better than the analysis of video and phone call recordings showed. When asked after the scenario the rescuers felt that they had coped with the situation well 72% and quite well 28% of the cases. Every participant evaluated the given telephone CPR instructions as very easy to understand. 35% of the participants thought that performing CPR was physically quite easy. The unexpected result was the EMDs’ bad protocol compliance. Protocol was not strictly followed by the dispatchers. They gave more straight forward instructions without the full knowledge of the situation, than they should have. From the 12 analyzed instructions that the dispatchers should have given to the rescuer, only three instructions (give two deep rescue breaths, correct positioning of the rescuers arms and to compress 15 times) were totally as in the protocol. Conclusions: The quality of CPR given by the senior citizens was inadequate in this study. The EMDs had bad protocol compliance. Standardized and feasible T-CPR instructions by the dispatcher are not seen in this study, even if the rescuers stated that the instructions were clear and easy to understand.
15.	Lawrenson, Kate, et al. (author) Functional mechanisms underlying pleiotropic risk alleles at the 19p13.1 breast-ovarian cancer susceptibility locus 2016 In: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 7 Journal article (peer-reviewed)abstract A locus at 19p13 is associated with breast cancer (BC) and ovarian cancer (OC) risk. Here we analyse 438 SNPs in this region in 46,451 BC and 15,438 OC cases, 15,252 BRCA1 mutation carriers and 73,444 controls and identify 13 candidate causal SNPs associated with serous OC (P=9.2 × 10-20), ER-negative BC (P=1.1 × 10-13), BRCA1-associated BC (P=7.7 × 10-16) and triple negative BC (P-diff=2 × 10-5). Genotype-gene expression associations are identified for candidate target genes ANKLE1 (P=2 × 10-3) and ABHD8 (P<2 × 10-3). Chromosome conformation capture identifies interactions between four candidate SNPs and ABHD8, and luciferase assays indicate six risk alleles increased transactivation of the ADHD8 promoter. Targeted deletion of a region containing risk SNP rs56069439 in a putative enhancer induces ANKLE1 downregulation; and mRNA stability assays indicate functional effects for an ANKLE1 3′-UTR SNP. Altogether, these data suggest that multiple SNPs at 19p13 regulate ABHD8 and perhaps ANKLE1 expression, and indicate common mechanisms underlying breast and ovarian cancer risk.
16.	Lind, Carl, et al. (author) RAMP: Risk Management Assessment Tool for Manual Handling Proactively 2014 In: HUMAN FACTORS IN ORGANIZATIONAL DESIGN AND MANAGEMENT – XINORDIC ERGONOMICS SOCIETY ANNUAL CONFERENCE – 46. ; , s. 107-110 Conference paper (peer-reviewed)abstract This paper presents an IT-based risk management tool called RAMP, risk assessment management tool for manual handling proactively. The tool consists of a checklist (RAMP I) and an assessment tool (RAMP II) which can be used to assess physicalrisk factors associated with manual handling activities in the production industry. The tool provides guidance for action plans and evaluations to promote improvement of occupational health and safety work at company level. Examples of the tool, its development and evaluation are presented.
17.	Ljungquist, Helena Nord, et al. (author) Communication and protocol compliance and their relation to the quality of cardiopulmonary resuscitation (CPR) : a mixed-methods study of simulated telephone-assisted CPR 2015 In: International Emergency Nursing. - : Elsevier. - 1755-599X .- 1878-013X. ; 23:3, s. 254-259 Research review (peer-reviewed)abstract Background: In the event of a cardiac arrest, emergency medical dispatchers (EMDs) play a critical role by providing telephone-assisted cardiopulmonary resuscitation (T-CPR) to laypersons. The aim of our investigation was to describe compliance with the T-CPR protocol, the performance of the laypersons in a simulated T-CPR situation, and the communication between laypersons and EMDs during these actions. Methods: We conducted a retrospective observational study by analysing 20 recorded video and audio files. In a simulation, EMDs provided laypersons with instructions following T-CPR protocols. These were then analysed using a mixed method with convergent parallel design. Results: If the EMDs complied with the T-CPR protocol, the laypersons performed the correct procedures in 71% of the actions. The single most challenging instruction of the T-CPR protocol, for both EMDs and laypersons, was airway control. Mean values for compression depth and frequency did not reach established guideline goals for CPR. Conclusion: Proper application of T-CPR protocols by EMDs resulted in better performance by laypersons in CPR. The most problematic task for EMDs as well for laypersons was airway management. The study results did not establish that the quality of communication between EMDs and laypersons performing CPR in a cardiac arrest situation led to statistically different outcomes, as measured by the quality and effectiveness of the CPR delivered.
18.	Ljungquist, Helena Nord, et al. (author) Have communication and compliance to the telephone-assisted cardiopulmonary resuscitations protocol any importance for the quality of CPR? : A mixed method study 2014 In: International Emergency Nursing. - 1755-599X .- 1878-013X. ; 22:4, s. 266- Journal article (peer-reviewed)
19.	Nord, Helena, et al. (author) Characterization of novel and complex genomic aberrations in glioblastoma using a 32K BAC array 2009 In: Neuro-Oncology. - : Oxford University Press (OUP). - 1522-8517 .- 1523-5866. ; 11:6, s. 803-818 Journal article (peer-reviewed)abstract Glioblastomas (GBs) are malignant CNS tumors often associated with devastating symptoms. Patients with GB have a very poor prognosis, and despite treatment, most of them die within 12 months from diagnosis. Several pathways, such as the RAS, tumor protein 53 (TP53), and phosphoinositide kinase 3 (PIK3) pathways, as well as the cell cycle control pathway, have been identified to be disrupted in this tumor. However, emerging data suggest that these aberrations represent only a fraction of the genetic changes involved in gliomagenesis. In this study, we have applied a 32K clone-based genomic array, covering 99% of the current assembly of the human genome, to the detailed genetic profiling of a set of 78 GBs. Complex patterns of aberrations, including high and narrow copy number amplicons, as well as a number of homozygously deleted loci, were identified. Amplicons that varied both in number (three on average) and in size (1.4 Mb on average) were frequently detected (81% of the samples). The loci encompassed not only previously reported oncogenes (EGFR, PDGFRA, MDM2, and CDK4) but also numerous novel oncogenes as GRB10, MKLN1, PPARGC1A, HGF, NAV3, CNTN1, SYT1, and ADAMTSL3. BNC2, PTPLAD2, and PTPRE, on the other hand, represent novel candidate tumor suppressor genes encompassed within homozygously deleted loci. Many of these genes are already linked to several forms of cancer; others represent new candidate genes that may serve as prognostic markers or even as therapeutic targets in the future. The large individual variation observed between the samples demonstrates the underlying complexity of the disease and strengthens the demand for an individualized therapy based on the genetic profile of the patient.
20.	Nord, Helena, et al. (author) Focal amplifications are associated with high grade and recurrences in stage Ta bladder carcinoma 2010 In: International Journal of Cancer. - : Wiley. - 0020-7136 .- 1097-0215. ; 126:6, s. 1390-1402 Journal article (peer-reviewed)abstract Urinary bladder cancer is a heterogeneous disease with tumors ranging from papillary noninvasive (stage Ta) to solid muscle infiltrating tumors (stage T2+). The risk of progression and death for the most frequent diagnosed type, Ta, is low, but the high incidence of recurrences has a significant effect on the patients' quality of life and poses substantial costs for health care systems. Consequently, the purpose of this study was to search for predictive factors of recurrence on the basis of genetic profiling. A clinically well characterized cohort of Ta bladder carcinomas, selected by the presence or absence of recurrences, was evaluated by an integrated analysis of DNA copy number changes and gene expression (clone-based 32K, respectively, U133Plus2.0 arrays). Only a few chromosomal aberrations have previously been defined in superficial bladder cancer. Surprisingly, the profiling of Ta tumors with a high-resolution array showed that DNA copy alterations are relatively common in this tumor type. Furthermore, we observed an overrepresentation of focal amplifications within high-grade and recurrent cases. Known (FGFR3, CCND1, MYC, MDM2) and novel candidate genes were identified within the loci. For example, MYBL2, a nuclear transcription factor involved in cell-cycle progression; YWHAB, an antiapoptotic protein; and SDC4, an important component of focal adhesions represent interesting candidates detected within two amplicons on chromosome 20, for which DNA amplification correlated with transcript up-regulation. The observed overrepresentation of amplicons within high-grade and recurrent cases may be clinically useful for the identification of patients who will benefit from a more aggressive therapy.
21.	Nord, Helena, 1980-, et al. (author) Novel amplicons in pediatric medulloblastoma identified by high-resolution genomic analysis : Genetic aberrations in medulloblastoma Other publication (other academic/artistic)abstract Medulloblastoma (MB) is an aggressive and invasive embryonal CNS tumor that mainly affects children. Despite treatment, ~30% of the patients die within 2 years from diagnosis. MB patients are currently categorized into high- or standard-risk based on the clinical criteria, with high-risk group including patients <3 years, with incomplete tumor resection or with concomitant metastatic disease at presentation. However, these clinical parameters do not always predict patient outcome and additional biomarkers are desirable. In this study we have profiled a series of 25 MB samples with a high-resolution 32K BAC-array covering 99% of the current assembly of the human genome for the identification of genetic copy number alterations. The most frequent observed alteration was the combination of 17p loss and 17q gain, indicative of an isochromosome 17q, which was identified in 40% of the patients. This aberration was detected in both high- and standard-risk groups and was not associated with worse outcome. We also defined minimal overlapping regions of aberrations, including 16 regions of gains and 18 regions of loss in different chromosomes. Noteworthy, are a few very narrow amplified loci identified on autosomes 1, 3 and 8, aberrations that were verified with an alternative platform (Illumina 610Q chips). Several genes as CYR61, LMO4, EOMES, and MLH1 encompassed within these loci were also found to present with transcript up-regulation. These genes represent novel candidate genes most probably involved in MB development.
22.	Nord, Helena, et al. (author) Novel amplifications in pediatric medulloblastoma identified by genome-wide copy number profiling 2012 In: Journal of Neuro-Oncology. - : Springer Science and Business Media LLC. - 0167-594X .- 1573-7373. ; 107:1, s. 37-49 Journal article (peer-reviewed)abstract Medulloblastoma (MB) is a WHO grade IV, invasive embryonal CNS tumor that mainly affects children. The aggressiveness and response to therapy can vary considerably between cases, and despite treatment, ~30% of patients die within 2 years from diagnosis. Furthermore, the majority of survivors suffer long-term side-effects due to severe management modalities. Several distinct morphological features have been associated with differences in biological behavior, but improved molecular-based criteria that better reflect the underlying tumor biology are in great demand. In this study, we profiled a series of 25 MB with a 32K BAC array covering 99% of the current assembly of the human genome for the identification of genetic copy number alterations possibly important in MB. Previously known aberrations as well as several novel focally amplified loci could be identified. As expected, the most frequently observed alteration was the combination of 17p loss and 17q gain, which was detected in both high- and standard-risk patients. We also defined minimal overlapping regions of aberrations, including 16 regions of gain and 18 regions of loss in various chromosomes. A few noteworthy narrow amplified loci were identified on autosomes 1 (38.89-41.97 and 84.89-90.76 Mb), 3 (27.64-28.20 and 35.80-43.50 Mb), and 8 (119.66-139.79 Mb), aberrations that were verified with an alternative platform (Illumina 610Q chips). Gene expression levels were also established for these samples using Affymetrix U133Plus2.0 arrays. Several interesting genes encompassed within the amplified regions and presenting with transcript upregulation were identified. These data contribute to the characterization of this malignant childhood brain tumor and confirm its genetic heterogeneity.
23.	Nord-Ljungquist, Helena, et al. (author) Lone and lonely in a double ambivalence situation as experienced by callers while waiting for the ambulance in a rural environment 2020 In: Scandinavian Journal of Caring Sciences. - : John Wiley & Sons. - 0283-9318 .- 1471-6712. ; 34:3, s. 566-574 Journal article (peer-reviewed)abstract BackgroundIn a rural environment where distances and access to ambulance resources in people’s immediate area are limited, other responders like firefighters dispatched to perform a first aid before ambulance arrives in areas where a longer response time exists; an assignment called ‘While Waiting for the Ambulance’ (WWFA). Knowledge is limited about the experience from a caller’s perspective when a person has a life‐threatening condition needing emergency help and both firefighters in a WWFA assignment and ambulance staff are involved.AimThe aim of the study is to describe the emergency situation involving a WWFA assignment in a rural environment from the caller's perspective.MethodA descriptive design using qualitative methodology with a reflective lifeworld research (RLR) approach was used for this study, including in‐depth interviews with eight callers.ResultsAn emergency situation involving WWFA assignment in a rural environment mean a sense of being lone and lonely with a vulnerability in while waiting to hand over responsibility for the affected person. Ambivalence in several dimensions arises with simultaneous and conflicting emotions. A tension between powerlessness and power of action where the throw between doubt and hope are abrupt with a simultaneous pendulum between being in a chaos and in a calm.ConclusionA double ambivalence emerges between, on one hand feeling alone in the situation and having full control, on the other hand, with trust handing over the responsibility, thereby losing control. Contact with the emergency medical dispatcher becomes a saving lifeline to hold onto, and access to emergency help in the immediate area of WWFA is valuable and important. Trust and confidence are experienced when callers are met with empathy, regardless of personal acquaintance with arriving responders.
24.	Nord-Ljungquist, Helena, et al. (author) ‘Time is our utmost enemy’ : First responders’ experiences of ‘While Waiting For the Ambulance’ assignments in rural environments – A phenomenological study 2022 In: Nordic journal of nursing research. - : Sage Publications. - 2057-1585 .- 2057-1593. ; 42:3, s. 166-174 Journal article (peer-reviewed)abstract Firefighters around the world have the ability to provide first aid before ambulance staff arrive. In Sweden, this assignment is called ‘While Waiting For the Ambulance’ (WWFA). There is limited knowledge about WWFA in rural environments, therefore the aim of this study was to describe the WWFA assignment in a rural environment from the perspective of the firefighters and the ambulance staff. A descriptive design was used with a reflective lifeworld approach, including 16 telephone interviews with firefighters and ambulance staff. The COREQ checklist was applied. A directed responsibility emerges towards affected persons with a situation-adapted attitude during alarms in a WWFA assignment. The firefighters and ambulance staff are each other’s support with a simultaneous need for support from involved organisations. To strengthen this support, training is required, consisting of interprofessional training, feedback from relevant organisations about first aid efforts and expansion of WWFA assignments. Finally, there is a need for a more coordinated picture in order to provide better conditions for future action by the organisations involved, with increased opportunities to save lives in individual local environments.
25.	Nord-Ljungquist, Helena, et al. (author) "Time that save lives" while waiting for ambulance in rural environments 2021 In: International Emergency Nursing. - : Elsevier. - 1755-599X .- 1878-013X. ; 59 Journal article (peer-reviewed)abstract AimFirefighters perform first aid before the ambulance arrives in areas with a long response time in Sweden; this is called ‘While Waiting for the Ambulance’ (WWFA). The aim was to describe WWFA assignments in rural environments, focusing on frequency, event time, actions and survival >30 days after cardiopulmonary resuscitation (CPR) was performed.MethodsRetrospective descriptive and comparative design.ResultsFirefighters in the northern part of Sweden were involved in 518 WWFA assignments between 2012 and 2016. From alarm call until ambulance dispatch, median time was 2:20 min; for firefighters, nearly four minutes. Median dispatch time at out-of-hospital cardiac arrests (OHCA) (n = 52) was 1:40 min for ambulance and three minutes for firefighters. Maximal dispatch time was nearly 10 min for ambulance and 44 min for firefighters. Firefighters arrived first at the scene, after 17 min’ median, for 95 % of assignments, while the ambulance took nearly twice the amount of time. In OHCA situations, time for firefighters was over 19 min versus ambulance at nearly twice the time. CPR was terminated by ambulance staff at 83% (n = 43) of 52 when firefighters performed prolonged CPR. Return to spontaneous circulation after OHCA was 17%, and 9% were alive after >30 days.ConclusionThe efficiency of incident time and utilisation rate for WWFA assignments can be increased for the benefit of affected persons, especially in OHCA.
26.	Nord-Ljungquist, Helena (author) Vem har och tar ansvar! : – I Väntan På Ambulans (IVPA)-uppdrag i Glesbygdsmiljö 2020 Doctoral thesis (other academic/artistic)abstract Aim: The overall aim was to explore and describe experiences from the perspective of different actors in While Waiting for Ambulance (WWFA) assignments in a rural environment. The four studies aimed: to describe WWFA and ambulance assignments in rural environments, focusing on frequency, event time and actions of firefighters before an ambulance arrives at the scene, and to evaluate these actions (I); to describe emergency situations involving WWFA assignment in a rural environment from the caller´s perspective (II); to describe compliance with the telephone-assisted cardiopulmonary resuscitation (T-CPR) protocol, the performance of the laypersons in a simulated T-CPR situation, and the communication between laypersons and EMDs during these actions (III); to describe WWFA assignment in a rural environment from the firefighters’ and the ambulance staff’s perspective (IV).Methods: The studies had a descriptive and comparative design. They were analysed with a qualitative and quantitative methods.Results: In event time showed the process time between ambulance staff and firefighters as significantly statistically different, to firefighters' disadvantage. Nevertheless, firefighters arrived first at the scene for 95 % of assignments after 17 minutes in the median, while ambulance staff took nearly twice the time. Access to help in the immediate area is experienced as valuable to the callers, but there is also a sense of being lone and lonely with vulnerability. Instructions from T-CPR protocol were difficult to comply with both from EMDs and laypersons, especially airway control. Regardless of the quality of communication between EMD and lay people, performance of CPR did not improve. Firefighters and ambulance staff experienced a directedness of responsibility towards affected persons; simultaneously, they were each other’s support. WWFA assignment is, itself, in a gray zone between the involved organisations, and strategies are lacking for the assignment.Conclusions: WWFA assignments are an underutilized resource in individual’s local environments, where a coordinated picture of identified organisational gray zones provide better conditions for future action by the organisations involved, with increased opportunities to save lives in people's local environments.
27.	Pan, Gang, et al. (author) PATZ1 down-regulates FADS1 by binding to rs174557 and is opposed by SP1/SREBP1c 2017 In: Nucleic Acids Research. - : Oxford University Press (OUP). - 0305-1048 .- 1362-4962. ; 45:5, s. 2408-2422 Journal article (peer-reviewed)abstract The FADS1 and FADS2 genes in the FADS cluster encode the rate-limiting enzymes in the synthesis of long-chain polyunsaturated fatty acids (LC-PUFAs). Genetic variation in this region has been associated with a large number of diseases and traits many of them correlated to differences in metabolism of PUFAs. However, the causative variants leading to these associations have not been identified. Here we find that the multiallelic rs174557 located in an AluYe5 element in intron 1 of FADS1 is functional and lies within a PATZ1 binding site. The derived allele of rs174557, which is the common variant in most populations, diminishes binding of PATZ1, a transcription factor conferring allele-specific downregulation of FADS1 The PATZ1 binding site overlaps with a SP1 site. The competitive binding between the suppressive PATZ1 and the activating complex of SP1 and SREBP1c determines the enhancer activity of this region, which regulates expression of FADS1.
28.	Rose, Linda, et al. (author) Development, Implementation and dissemination of RAMP : Risk management assessment tool for manual handling proactively 2011 In: 43rd Annual Nordic Ergonomics Society Conference. ; , s. 255-260 Conference paper (peer-reviewed)abstract This paper describes an on-going project with the main objective to develop, implement, and disseminate a freely accessible computer-based assessment tool for physical ergonomics, the Risk Management Assessment Tool for Manual Handling Proactively, RAMP. The project is conducted in seven steps, in close co-operation between researchers and key company stakeholders, using an interactive research methodology. Results include a specification of requirements that the RAMP should meet. Difficulties of developing models of this kind and possible benefits of using such a tool are discussed.
29.	Sandgren, Johanna, et al. (author) Recurrent genomic alterations in benign and malignant pheochromocytomas and paragangliomas revealed by whole-genome array comparative genomic hybridization analysis 2010 In: Endocrine-Related Cancer. - 1351-0088 .- 1479-6821. ; 17:3, s. 561-579 Journal article (peer-reviewed)abstract Pheochromocytomas and abdominal paragangliomas are adrenal and extra-adrenal catecholamine-producing tumours. They arise due to heritable cancer syndromes, or more frequently occur sporadically due to an unknown genetic cause. The majority of cases are benign, but malignant tumours are observed. Previous comparative genomic hybridization (CGH) and loss of heterozygosity studies have shown frequent deletions of chromosome arms 1p, 3q and 22q in pheochromocytomas. We applied high-resolution whole-genome array CGH on 53 benign and malignant pheochromocytomas and paragangliomas to narrow down candidate regions as well as to identify chromosomal alterations more specific to malignant tumours. Minimal overlapping regions (MORs) were identified on 16 chromosomes, with the most frequent MORs of deletion (> or = 32%) occurring on chromosome arms 1p, 3q, 11p/q, 17p and 22q, while the chromosome arms 1q, 7p, 12q and 19p harboured the most common MORs of gain (> or = 14%). The most frequent MORs (61-75%) in the pheochromocytomas were identified at 1p, and the four regions of common losses encompassed 1p36, 1p32-31, 1p22-21 and 1p13. Tumours that did not show 1p loss generally demonstrated aberrations on chromosome 11. Gain of chromosomal material was significantly more frequent among the malignant cases. Moreover, gain at 19q, trisomy 12 and loss at 11q were positively associated with malignant pheochromocytomas, while 1q gain was commonly observed in the malignant paragangliomas. Our study revealed novel and narrow recurrent chromosomal regions of loss and gain at several autosomes, a prerequisite for identifying candidate tumour suppressor genes and oncogenes involved in the development of adrenal and extra-adrenal catecholamine-producing tumours.
30.	Sundelöf, Andreas, et al. (author) Fisk- och skaldjursbestånd i hav och sötvatten 2021 : Resursöversikt 2022 Reports (other academic/artistic)abstract I rapporten kan du ta del av bedömningen som görs av situationen för bestånd som regleras inom ramen för EU:s gemensamma fiskeripolitik (GFP). Bedömningarna baseras på det forskningssamarbete och den rådgivning som sker inom det Internationella Havsforskningsrådet (ICES). Sammantaget redovisas tillståndet för 107 bestånd av 48 fisk- och skaldjursarter.De bestånd som förvaltas nationellt baseras på de biologiska underlagen, och rådgivningen i huvudsak på den forskning och övervakning samt analys som bedrivs av Institutionen för akvatiska resurser vid Sveriges lantbruksuniversitet (SLU Aqua) samt yrkesfiskets rapportering.Rapporten är en beställning från Havs- och vattenmyndigheten (HaV) till Sveriges lantbruksuniversitet (SLU) och utgör ett viktigt kunskapsunderlag till myndighetens arbete. Den uppfyller de krav som finns inom EU:s gemensamma fiskeripolitik om att basera förvaltningen på bästa tillgängliga vetenskap. Denna rapport är också ett stöd till det arbete som beskrivs närmare i strategin för framtidens fiske och tillhörande handlingsplaner för vattenbruk, yrkes- och fritidsfiske som HaV och Jordbruksverket har tagit fram i dialog med fiskets och vattenbrukets intressenter.
31.	Tsakonas, Georgios, et al. (author) An immune gene expression signature distinguishes central nervous system metastases from primary tumours in non-small-cell lung cancer 2020 In: European Journal of Cancer. - : ELSEVIER SCI LTD. - 0959-8049 .- 1879-0852. ; 132, s. 24-34 Journal article (peer-reviewed)abstract Background: Dissemination of non-small-cell lung cancer (NSCLC) in the central nervous system is a frequent and challenging clinical problem. Systemic or local therapies rarely prolong survival and have modest activity regarding local control. Alterations in gene expression in brain metastasis versus primary tumour may increase aggressiveness and impair therapeutic efforts.Methods: We identified 25 patients with surgically removed NSCLC brain metastases in two different patient cohorts. For 13 of these patients, primary tumour samples were available. Gene expression analysis using the nCounter (R) PanCancer Immune Profiling gene expression panel (nanoString technologies Inc.) was performed in brain metastases and primary tumour samples. Identification of differentially expressed genes was conducted on normalized data using the nSolver analysis software.Results: We compared gene expression patterns in brain metastases with primary tumours. Brain metastasis samples displayed a distinct clustering pattern compared to primary tumour samples with a statistically significant downregulation of genes related to immune response and immune cell activation. Results from KEGG term analysis on differentially expressed genes revealed a concomitant enrichment of multiple KEGG terms associated with the immune system. We identified a 12-gene immune signature that clearly separated brain metastases from primary tumours.Conclusions: We identified a unique gene downregulation pattern in brain metastases compared with primary tumours. This finding may explain the lower intracranial efficacy of systemic therapy, especially immunotherapy, in brain metastasis of patients with NSCLC.
32.	Tsakonas, Georgios, et al. (author) Matched Analyses of Brain Metastases versus Primary Non-Small Cell Lung Cancer Reveal a Unique microRNA Signature 2023 In: International Journal of Molecular Sciences. - : MDPI. - 1661-6596 .- 1422-0067. ; 24:1 Journal article (peer-reviewed)abstract Distant spreading of tumor cells to the central nervous system in non-small cell lung cancer (NSCLC) occurs frequently and poses major clinical issues due to limited treatment options. RNAs displaying differential expression in brain metastasis versus primary NSCLC may explain distant tumor growth and may potentially be used as therapeutic targets. In this study, we conducted systematic microRNA expression profiling from tissue biopsies of primary NSCLC and brain metastases from 25 patients. RNA analysis was performed using the nCounter Human v3 miRNA Expression Assay, NanoString technologies, followed by differential expression analysis and in silico target gene pathway analysis. We uncovered a panel of 11 microRNAs with differential expression and excellent diagnostic performance in brain metastasis versus primary NSCLC. Five microRNAs were upregulated in brain metastasis (miR-129-2-3p, miR-124-3p, miR-219a-2-3p, miR-219a-5p, and miR-9-5p) and six microRNAs were downregulated in brain metastasis (miR-142-3p, miR-150-5p, miR-199b-5p, miR-199a-3p, miR-199b-5p, and miR-199a-5p). The differentially expressed microRNAs were predicted to converge on distinct target gene networks originating from five to twelve core target genes. In conclusion, we uncovered a unique microRNA profile linked to two target gene networks. Our results highlight the potential of specific microRNAs as biomarkers for brain metastasis in NSCLC and indicate plausible mechanistic connections.
33.	Wallerman, Ola, et al. (author) lobChIP : from cells to sequencing ready ChIP libraries in a single day 2015 In: Epigenetics & Chromatin. - : Springer Science and Business Media LLC. - 1756-8935. ; 8 Journal article (peer-reviewed)abstract Background: ChIP-seq is the method of choice for genome-wide studies of protein-DNA interactions. We describe a new method for ChIP-seq sample preparation, termed lobChIP, where the library reactions are performed on crosslinked ChIP fragments captured on beads. Results: The lobChIP method was found both to reduce time and cost and to simplify the processing of many samples in parallel. lobChIP has an early incorporation of barcoded sequencing adaptors that minimizes the risk of sample cross-contamination and can lead to reduced amount of adaptor dimers in the sequencing libraries, while allowing for direct decross-linking and amplification of the sample. Conclusions: With results for histone modifications and transcription factors, we show that lobChIP performs equal to or better than standard protocols and that it makes it possible to go from cells to sequencing ready libraries within a single day.
34.	Ågerstam, Helena, et al. (author) Modeling the human 8p11-myeloproliferative syndrome in immunodeficient mice 2010 In: Blood. - : American Society of Hematology. - 1528-0020 .- 0006-4971. ; 116:12, s. 2103-2111 Journal article (peer-reviewed)abstract The 8p11 myeloproliferative syndrome (EMS), also referred to as stem cell leukemia/lymphoma, is a chronic myeloproliferative disorder that rapidly progresses into acute leukemia. Molecularly, EMS is characterized by fusion of various partner genes to the FGFR1 gene, resulting in constitutive activation of the tyrosine kinases in FGFR1. To date, no previous study has addressed the functional consequences of ectopic FGFR1 expression in the potentially most relevant cellular context, that of normal primary human hematopoietic cells. Herein, we report that expression of ZMYM2/FGFR1 (previously known as ZNF198/FGFR1) or BCR/FGFR1 in normal human CD34(+) cells from umbilicalcord blood leads to increased cellular proliferation and differentiation toward the erythroid lineage in vitro. In immunodeficient mice, expression of ZMYM2/FGFR1 or BCR/FGFR1 in human cells induces several features of human EMS, including expansion of several myeloid cell lineages and accumulation of blasts in bone marrow. Moreover, bone marrow fibrosis together with increased extramedullary hematopoiesis is observed. This study suggests that FGFR1 fusion oncogenes, by themselves, are capable of initiating an EMS-like disorder, and provides the first humanized model of a myeloproliferative disorder transforming into acute leukemia in mice. The established in vivo EMS model should provide a valuable tool for future studies of this disorder. (Blood. 2010;116(12):2103-2111)

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