| 1. |
- Allentoft, Morten E., et al.
(författare)
-
100 ancient genomes show repeated population turnovers in Neolithic Denmark
- 2024
-
Ingår i: Nature. - 0028-0836 .- 1476-4687. ; 625, s. 329-337
-
Tidskriftsartikel (refereegranskat)abstract
- Major migration events in Holocene Eurasia have been characterized genetically at broad regional scales1–4. However, insights into the population dynamics in the contact zones are hampered by a lack of ancient genomic data sampled at high spatiotemporal resolution5–7. Here, to address this, we analysed shotgun-sequenced genomes from 100 skeletons spanning 7,300 years of the Mesolithic period, Neolithic period and Early Bronze Age in Denmark and integrated these with proxies for diet (13C and 15N content), mobility (87Sr/86Sr ratio) and vegetation cover (pollen). We observe that Danish Mesolithic individuals of the Maglemose, Kongemose and Ertebølle cultures form a distinct genetic cluster related to other Western European hunter-gatherers. Despite shifts in material culture they displayed genetic homogeneity from around 10,500 to 5,900 calibrated years before present, when Neolithic farmers with Anatolian-derived ancestry arrived. Although the Neolithic transition was delayed by more than a millennium relative to Central Europe, it was very abrupt and resulted in a population turnover with limited genetic contribution from local hunter-gatherers. The succeeding Neolithic population, associated with the Funnel Beaker culture, persisted for only about 1,000 years before immigrants with eastern Steppe-derived ancestry arrived. This second and equally rapid population replacement gave rise to the Single Grave culture with an ancestry profile more similar to present-day Danes. In our multiproxy dataset, these major demographic events are manifested as parallel shifts in genotype, phenotype, diet and land use.
|
|
| 2. |
- Allentoft, Morten E., et al.
(författare)
-
Population genomics of post-glacial western Eurasia
- 2024
-
Ingår i: Nature. - 0028-0836 .- 1476-4687. ; 625:7994, s. 301-311
-
Tidskriftsartikel (refereegranskat)abstract
- Western Eurasia witnessed several large-scale human migrations during the Holocene1–5. Here, to investigate the cross-continental effects of these migrations, we shotgun-sequenced 317 genomes—mainly from the Mesolithic and Neolithic periods—from across northern and western Eurasia. These were imputed alongside published data to obtain diploid genotypes from more than 1,600 ancient humans. Our analyses revealed a ‘great divide’ genomic boundary extending from the Black Sea to the Baltic. Mesolithic hunter-gatherers were highly genetically differentiated east and west of this zone, and the effect of the neolithization was equally disparate. Large-scale ancestry shifts occurred in the west as farming was introduced, including near-total replacement of hunter-gatherers in many areas, whereas no substantial ancestry shifts happened east of the zone during the same period. Similarly, relatedness decreased in the west from the Neolithic transition onwards, whereas, east of the Urals, relatedness remained high until around 4,000 bp, consistent with the persistence of localized groups of hunter-gatherers. The boundary dissolved when Yamnaya-related ancestry spread across western Eurasia around 5,000 bp, resulting in a second major turnover that reached most parts of Europe within a 1,000-year span. The genetic origin and fate of the Yamnaya have remained elusive, but we show that hunter-gatherers from the Middle Don region contributed ancestry to them. Yamnaya groups later admixed with individuals associated with the Globular Amphora culture before expanding into Europe. Similar turnovers occurred in western Siberia, where we report new genomic data from a ‘Neolithic steppe’ cline spanning the Siberian forest steppe to Lake Baikal. These prehistoric migrations had profound and lasting effects on the genetic diversity of Eurasian populations.
|
|
| 3. |
- Brander, Søren, et al.
(författare)
-
Biochemical evidence of both copper chelation and oxygenase activity at the histidine brace
- 2020
-
Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322 .- 2045-2322. ; 10:1
-
Tidskriftsartikel (refereegranskat)abstract
- Lytic polysaccharide monooxygenase (LPMO) and copper binding protein CopC share a similar mononuclear copper site. This site is defined by an N-terminal histidine and a second internal histidine side chain in a configuration called the histidine brace. To understand better the determinants of reactivity, the biochemical and structural properties of a well-described cellulose-specific LPMO from Thermoascus aurantiacus (TaAA9A) is compared with that of CopC from Pseudomonas fluorescens (PfCopC) and with the LPMO-like protein Bim1 from Cryptococcus neoformans. PfCopC is not reduced by ascorbate but is a very strong Cu(II) chelator due to residues that interacts with the N-terminus. This first biochemical characterization of Bim1 shows that it is not redox active, but very sensitive to H2O2, which accelerates the release of Cu ions from the protein. TaAA9A oxidizes ascorbate at a rate similar to free copper but through a mechanism that produce fewer reactive oxygen species. These three biologically relevant examples emphasize the diversity in how the proteinaceous environment control reactivity of Cu with O2.
|
|
| 4. |
- Christensen, Christian Kolle, et al.
(författare)
-
Beam damage in operando X-ray diffraction studies of Li-ion batteries
- 2023
-
Ingår i: Journal of Synchrotron Radiation. - 0909-0495. ; 30:Pt 3, s. 561-570
-
Tidskriftsartikel (refereegranskat)abstract
- Operando powder X-ray diffraction (PXRD) is a widely employed method for the investigation of structural evolution and phase transitions in electrodes for rechargeable batteries. Due to the advantages of high brilliance and high X-ray energies, the experiments are often carried out at synchrotron facilities. It is known that the X-ray exposure can cause beam damage in the battery cell, resulting in hindrance of the electrochemical reaction. This study investigates the extent of X-ray beam damage during operando PXRD synchrotron experiments on battery materials with varying X-ray energies, amount of X-ray exposure and battery cell chemistries. Battery cells were exposed to 15, 25 or 35 keV X-rays (with varying dose) during charge or discharge in a battery test cell specially designed for operando experiments. The observed beam damage was probed by μPXRD mapping of the electrodes recovered from the operando battery cell after charge/discharge. The investigation reveals that the beam damage depends strongly on both the X-ray energy and the amount of exposure, and that it also depends strongly on the cell chemistry, i.e. the chemical composition of the electrode.
|
|
| 5. |
|
|
| 6. |
- Fromm, Bastian, et al.
(författare)
-
MirGeneDB 2.0 : the metazoan microRNA complement
- 2020
-
Ingår i: Nucleic Acids Research. - : Oxford University Press (OUP). - 0305-1048 .- 1362-4962. ; 48:D1, s. D132-D141
-
Tidskriftsartikel (refereegranskat)abstract
- Small non-coding RNAs have gained substantial attention due to their roles in animal development and human disorders. Among them, microRNAs are special because individual gene sequences are conserved across the animal kingdom. In addition, unique and mechanistically well understood features can clearly distinguish bona fide miRNAs from the myriad other small RNAs generated by cells. However, making this distinction is not a common practice and, thus, not surprisingly, the heterogeneous quality of available miRNA complements has become a major concern in microRNA research. We addressed this by extensively expanding our curated microRNA gene database - MirGeneDB - to 45 organisms, encompassing a wide phylogenetic swath of animal evolution. By consistently annotating and naming 10,899 microRNA genes in these organisms, we show that previous microRNA annotations contained not only many false positives, but surprisingly lacked >2000 bona fide microRNAs. Indeed, curated microRNA complements of closely related organisms are very similar and can be used to reconstruct ancestral miRNA repertoires. MirGeneDB represents a robust platform for microRNA-based research, providing deeper and more significant insights into the biology and evolution of miRNAs as well as biomedical and biomarker research.
|
|
| 7. |
- Goldbrunner, Roland, et al.
(författare)
-
EANO guidelines for the diagnosis and treatment of meningiomas
- 2016
-
Ingår i: The Lancet Oncology. - 1470-2045 .- 1474-5488. ; 17:9, s. E383-E391
-
Forskningsöversikt (refereegranskat)abstract
- Although meningiomas are the most common intracranial tumours, the level of evidence to provide recommendations for the diagnosis and treatment of meningiomas is low compared with other tumours such as high-grade gliomas. The meningioma task force of the European Association of Neuro-Oncology (EANO) assessed the scientific literature and composed a framework of the best possible evidence-based recommendations for health professionals. The provisional diagnosis of meningioma is mainly made by MRI. Definitive diagnosis, including histological classification, grading, and molecular profiling, requires a surgical procedure to obtain tumour tissue. Therefore, in many elderly patients, observation is the best therapeutic option. If therapy is deemed necessary, the standard treatment is gross total surgical resection including the involved dura. As an alternative, radiosurgery can be done for small tumours, or fractionated radiotherapy in large or previously treated tumours. Treatment concepts combining surgery and radiosurgery or fractionated radiotherapy, which enable treatment of the complete tumour volume with low morbidity, are being developed. Pharmacotherapy for meningiomas has remained largely experimental. However, antiangiogenic drugs, peptide receptor radionuclide therapy, and targeted agents are promising candidates for future pharmacological approaches to treat refractory meningiomas across all WHO grades.
|
|
| 8. |
- Gunst, Jesper D., et al.
(författare)
-
Efficacy of the TMPRSS2 inhibitor camostat mesilate in patients hospitalized with Covid-19-a double-blind randomized controlled trial
- 2021
-
Ingår i: eClinicalMedicine. - : Elsevier. - 2589-5370. ; 35
-
Tidskriftsartikel (refereegranskat)abstract
- Background: The trans-membrane protease serine 2 (TMPRSS2) is essential for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) cell entry and infection. Efficacy and safety of TMPRSS2 inhibitors in patients with coronavirus disease 2019 (Covid-19) have not been evaluated in randomized trials.Methods: We conducted an investigator-initiated, double-blind, randomized, placebo-controlled multicenter trial in patients hospitalized with confirmed SARS-CoV-2 infection from April 4, to December 31, 2020. Within 48 h of admission, participants were randomly assigned in a 2:1 ratio to receive the TMPRSS2 inhibitor camostat mesilate 200 mg three times daily for 5 days or placebo. The primary outcome was time to discharge or clinical improvement measured as ≥2 points improvement on a 7-point ordinal scale. Other outcomes included 30-day mortality, safety and change in oropharyngeal viral load. ClinicalTrials.gov Identifier: NCT04321096. EudraCT Number: 2020-001,200-42.Findings: 137 patients were assigned to receive camostat mesilate and 68 to placebo. Median time to clinical improvement was 5 days (interquartile range [IQR], 3 to 7) in the camostat group and 5 days (IQR, 2 to 10) in the placebo group (P = 0·31). The hazard ratio for 30-day mortality in the camostat compared with the placebo group was 0·82 (95% confidence interval [CI], 0·24 to 2·79; P = 0·75). The frequency of adverse events was similar in the two groups. Median change in viral load from baseline to day 5 in the camostat group was -0·22 log10 copies/mL (p <0·05) and -0·82 log10 in the placebo group (P <0·05).Interpretation: Under this protocol, camostat mesilate treatment was not associated with increased adverse events during hospitalization for Covid-19 and did not affect time to clinical improvement, progression to ICU admission or mortality.
|
|
| 9. |
|
|
| 10. |
- Hernández-Rollán, Cristina, et al.
(författare)
-
LyGo : A Platform for Rapid Screening of Lytic Polysaccharide Monooxygenase Production
- 2021
-
Ingår i: ACS Synthetic Biology. - : American Chemical Society (ACS). - 2161-5063. ; 10:4, s. 897-906
-
Tidskriftsartikel (refereegranskat)abstract
- Environmentally friendly sources of energy and chemicals are essential constituents of a sustainable society. An important step toward this goal is the utilization of biomass to supply building blocks for future biorefineries. Lytic polysaccharide monooxygenases (LPMOs) are enzymes that play a critical role in breaking the chemical bonds in the most abundant polymers found in recalcitrant biomass, such as cellulose and chitin. To use them in industrial processes they need to be produced in high titers in cell factories. Predicting optimal strategies for producing LPMOs is often nontrivial, and methods allowing for screening several strategies simultaneously are therefore needed. Here, we present a standardized platform for cloning LPMOs. The platform allows users to combine gene fragments with 14 different expression vectors in a simple 15 min reaction, thus enabling rapid exploration of several gene contexts, hosts, and expression strategies in parallel. The open-source LyGo platform is accompanied by easy-to-follow online protocols for both cloning and expression. As a demonstration of its utility, we explore different strategies for expressing several different LPMOs in Escherichia coli, Bacillus subtilis, and Komagataella phaffii.
|
|
| 11. |
- Jakobsen, Stig S., et al.
(författare)
-
Failure of total hip implants : metals and metal release in 52 cases
- 2014
-
Ingår i: Contact Dermatitis. - : Wiley. - 0105-1873 .- 1600-0536. ; 71:6, s. 319-325
-
Tidskriftsartikel (refereegranskat)abstract
- BackgroundThe pathogenesis of total joint replacement failure is multifactorial. One hypothesis suggests that corrosion and wear of alloys result in metal ion release, which may then cause sensitization and even implant failure, owing to the acquired immune reactivity. ObjectivesTo assess cobalt, nickel and chromium(VI) release from, and the metal composition of, failed metal-on-ethylene total hip replacements. Materials/methodsImplant components from 52 revision cases were evaluated with spot tests for free nickel, cobalt, and chromium (VI) ions. Implant composition was determined with X-ray fluorescence spectroscopy, and information on the reason for revision and complications in relation to surgery was collected from the medical charts when possible (72%). For 10 implants, corrosion was further characterized with scanning electron microscopy. ResultsWe detected cobalt release from three of 38 removed femoral heads and from one of 24 femoral stems. Nickel release was detected from one of 24 femoral stems. No chromium(VI) release was detected. ConclusionsWe found that cobalt and nickel were released from some failed total hip arthroplasties, and corrosion was frequently observed. Metal ions and particles corroded from metal-on-polyethylene may play a role in the complex aetiopathology of implant failure.
|
|
| 12. |
- Klionsky, Daniel J., et al.
(författare)
-
Guidelines for the use and interpretation of assays for monitoring autophagy
- 2012
-
Ingår i: Autophagy. - : Informa UK Limited. - 1554-8635 .- 1554-8627. ; 8:4, s. 445-544
-
Forskningsöversikt (refereegranskat)abstract
- In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Accordingly, it is important to update these guidelines for monitoring autophagy in different organisms. Various reviews have described the range of assays that have been used for this purpose. Nevertheless, there continues to be confusion regarding acceptable methods to measure autophagy, especially in multicellular eukaryotes. A key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers or volume of autophagic elements (e.g., autophagosomes or autolysosomes) at any stage of the autophagic process vs. those that measure flux through the autophagy pathway (i.e., the complete process); thus, a block in macroautophagy that results in autophagosome accumulation needs to be differentiated from stimuli that result in increased autophagic activity, defined as increased autophagy induction coupled with increased delivery to, and degradation within, lysosomes (in most higher eukaryotes and some protists such as Dictyostelium) or the vacuole (in plants and fungi). In other words, it is especially important that investigators new to the field understand that the appearance of more autophagosomes does not necessarily equate with more autophagy. In fact, in many cases, autophagosomes accumulate because of a block in trafficking to lysosomes without a concomitant change in autophagosome biogenesis, whereas an increase in autolysosomes may reflect a reduction in degradative activity. Here, we present a set of guidelines for the selection and interpretation of methods for use by investigators who aim to examine macroautophagy and related processes, as well as for reviewers who need to provide realistic and reasonable critiques of papers that are focused on these processes. These guidelines are not meant to be a formulaic set of rules, because the appropriate assays depend in part on the question being asked and the system being used. In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multiple assays to monitor autophagy. In these guidelines, we consider these various methods of assessing autophagy and what information can, or cannot, be obtained from them. Finally, by discussing the merits and limits of particular autophagy assays, we hope to encourage technical innovation in the field.
|
|
| 13. |
|
|
| 14. |
- Lokkegaard, Sanne, et al.
(författare)
-
MCM3 upregulation confers endocrine resistance in breast cancer and is a predictive marker of diminished tamoxifen benefit
- 2021
-
Ingår i: npj Breast Cancer. - : NATURE RESEARCH. - 2374-4677. ; 7:1
-
Tidskriftsartikel (refereegranskat)abstract
- Resistance to endocrine therapy in estrogen receptor-positive (ER+) breast cancer is a major clinical problem with poorly understood mechanisms. There is an unmet need for prognostic and predictive biomarkers to allow appropriate therapeutic targeting. We evaluated the mechanism by which minichromosome maintenance protein 3 (MCM3) influences endocrine resistance and its predictive/prognostic potential in ER+ breast cancer. We discovered that ER+ breast cancer cells survive tamoxifen and letrozole treatments through upregulation of minichromosome maintenance proteins (MCMs), including MCM3, which are key molecules in the cell cycle and DNA replication. Lowering MCM3 expression in endocrine-resistant cells restored drug sensitivity and altered phosphorylation of cell cycle regulators, including p53(Ser(315,33)), CHK1(Ser(317)), and cdc25b(Ser(323)), suggesting that the interaction of MCM3 with cell cycle proteins is an important mechanism of overcoming replicative stress and anti-proliferative effects of endocrine treatments. Interestingly, the MCM3 levels did not affect the efficacy of growth inhibitory by CDK4/6 inhibitors. Evaluation of MCM3 levels in primary tumors from four independent cohorts of breast cancer patients receiving adjuvant tamoxifen mono-therapy or no adjuvant treatment, including the Stockholm tamoxifen (STO-3) trial, showed MCM3 to be an independent prognostic marker adding information beyond Ki67. In addition, MCM3 was shown to be a predictive marker of response to endocrine treatment. Our study reveals a coordinated signaling network centered around MCM3 that limits response to endocrine therapy in ER+ breast cancer and identifies MCM3 as a clinically useful prognostic and predictive biomarker that allows personalized treatment of ER+ breast cancer patients.
|
|
| 15. |
|
|
| 16. |
|
|
| 17. |
- Ottesen, Anett Hellebø, et al.
(författare)
-
Secretoneurin is a novel prognostic cardiovascular biomarker associated with cardiomyocyte calcium handling.
- 2015
-
Ingår i: Journal of the American College of Cardiology. - : Elsevier BV. - 0735-1097 .- 1558-3597. ; 65:4, s. 339-51
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Secretoneurin (SN) levels are increased in patients with heart failure (HF), but whether SN provides prognostic information and influences cardiomyocyte function is unknown.OBJECTIVES: This study sought to evaluate the merit of SN as a cardiovascular biomarker and assess effects of SN on cardiomyocyte Ca(2+) handling.METHODS: We assessed the association between circulating SN levels and mortality in 2 patient cohorts and the functional properties of SN in experimental models.RESULTS: In 143 patients hospitalized for acute HF, SN levels were closely associated with mortality (n = 66) during follow-up (median 776 days; hazard ratio [lnSN]: 4.63; 95% confidence interval: 1.93 to 11.11; p = 0.001 in multivariate analysis). SN reclassified patients to their correct risk strata on top of other predictors of mortality. In 155 patients with ventricular arrhythmia-induced cardiac arrest, SN levels were also associated with short-term mortality (n = 51; hazard ratio [lnSN]: 3.33; 95% confidence interval: 1.83 to 6.05; p < 0.001 in multivariate analysis). Perfusing hearts with SN yielded markedly increased myocardial levels and SN internalized into cardiomyocytes by endocytosis. Intracellularly, SN reduced Ca(2+)/calmodulin (CaM)-dependent protein kinase II δ (CaMKIIδ) activity via direct SN-CaM and SN-CaMKII binding and attenuated CaMKIIδ-dependent phosphorylation of the ryanodine receptor. SN also reduced sarcoplasmic reticulum Ca(2+) leak, augmented sarcoplasmic reticulum Ca(2+) content, increased the magnitude and kinetics of cardiomyocyte Ca(2+) transients and contractions, and attenuated Ca(2+) sparks and waves in HF cardiomyocytes.CONCLUSIONS: SN provided incremental prognostic information to established risk indices in acute HF and ventricular arrhythmia-induced cardiac arrest.
|
|
| 18. |
- Patterson, Allison, et al.
(författare)
-
Foraging range scales with colony size in high-latitude seabirds
- 2022
-
Ingår i: Current Biology. - : Elsevier BV. - 0960-9822 .- 1879-0445. ; 32:17, s. 3800-3807
-
Tidskriftsartikel (refereegranskat)abstract
- Density-dependent prey depletion around breeding colonies has long been considered an important factor controlling the population dynamics of colonial animals.1, 2, 3, 4 Ashmole proposed that as seabird colony size increases, intraspecific competition leads to declines in reproductive success, as breeding adults must spend more time and energy to find prey farther from the colony.1 Seabird colony size often varies over several orders of magnitude within the same species and can include millions of individuals per colony.5,6 As such, colony size likely plays an important role in determining the individual behavior of its members and how the colony interacts with the surrounding environment.6 Using tracking data from murres (Uria spp.), the world’s most densely breeding seabirds, we show that the distribution of foraging-trip distances scales to colony size0.33 during the chick-rearing stage, consistent with Ashmole’s halo theory.1,2 This pattern occurred across colonies varying in size over three orders of magnitude and distributed throughout the North Atlantic region. The strong relationship between colony size and foraging range means that the foraging areas of some colonial species can be estimated from colony sizes, which is more practical to measure over a large geographic scale. Two-thirds of the North Atlantic murre population breed at the 16 largest colonies; by extrapolating the predicted foraging ranges to sites without tracking data, we show that only two of these large colonies have significant coverage as marine protected areas. Our results are an important example of how theoretical models, in this case, Ashmole’s version of central-place-foraging theory, can be applied to inform conservation and management in colonial breeding species.
|
|
| 19. |
- Posserud, Maj-Britt, et al.
(författare)
-
Influence of assessment instrument on ADHD diagnosis.
- 2014
-
Ingår i: European child & adolescent psychiatry. - : Springer Science and Business Media LLC. - 1435-165X .- 1018-8827. ; 23:4, s. 197-205
-
Tidskriftsartikel (refereegranskat)abstract
- We compared four instruments commonly used to screen for and diagnose Attention-Deficit/Hyperactivity Disorder (ADHD) in children. The Bergen Child Study included a DSM-IV ADHD symptom list and the Strengths and Difficulties Questionnaire (SDQ) as screen in Phase one. Phase two included the parent Development and Well-Being Assessment (DAWBA), whereas Phase three comprised in-depth clinical assessment, including the Schedule for Affective Disorders and Schizophrenia for School Aged Children (K-SADS). We compared ADHD as diagnosed by the four instruments in the children with normal intellectual functioning participating in all three phases (N=234). The DSM-IV ADHD symptom list showed moderate agreement with all other instruments (κ=0.53-0.57), whereas there was fair agreement between the K-SADS-DAWBA (κ=0.31) and between SDQ-DAWBA (κ=0.33). The DAWBA diagnosed fewer children with ADHD than did the other instruments. Implications for use of the instruments are discussed.
|
|
| 20. |
|
|
| 21. |
- Sandve, Geir K., et al.
(författare)
-
The differential disease regulome
- 2011
-
Ingår i: BMC Genomics. - : Springer Science and Business Media LLC. - 1471-2164. ; 12
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Transcription factors in disease-relevant pathways represent potential drug targets, by impacting a distinct set of pathways that may be modulated through gene regulation. The influence of transcription factors is typically studied on a per disease basis, and no current resources provide a global overview of the relations between transcription factors and disease. Furthermore, existing pipelines for related large-scale analysis are tailored for particular sources of input data, and there is a need for generic methodology for integrating complementary sources of genomic information.Results: We here present a large-scale analysis of multiple diseases versus multiple transcription factors, with a global map of over-and under-representation of 446 transcription factors in 1010 diseases. This map, referred to as the differential disease regulome, provides a first global statistical overview of the complex interrelationships between diseases, genes and controlling elements. The map is visualized using the Google map engine, due to its very large size, and provides a range of detailed information in a dynamic presentation format.The analysis is achieved through a novel methodology that performs a pairwise, genome-wide comparison on the cartesian product of two distinct sets of annotation tracks, e.g. all combinations of one disease and one TF.The methodology was also used to extend with maps using alternative data sets related to transcription and disease, as well as data sets related to Gene Ontology classification and histone modifications. We provide a web-based interface that allows users to generate other custom maps, which could be based on precisely specified subsets of transcription factors and diseases, or, in general, on any categorical genome annotation tracks as they are improved or become available.Conclusion: We have created a first resource that provides a global overview of the complex relations between transcription factors and disease. As the accuracy of the disease regulome depends mainly on the quality of the input data, forthcoming ChIP-seq based binding data for many TFs will provide improved maps. We further believe our approach to genome analysis could allow an advance from the current typical situation of one-time integrative efforts to reproducible and upgradable integrative analysis. The differential disease regulome and its associated methodology is available at © 2011 Sandve et al; licensee BioMed Central Ltd.
|
|
| 22. |
- Sandve, Geir K., et al.
(författare)
-
The Genomic HyperBrowser: Inferential genomics at the sequence level
- 2010
-
Ingår i: Genome Biology. - : Springer Science and Business Media LLC. - 1474-7596 .- 1474-760X .- 1465-6906. ; 11
-
Tidskriftsartikel (refereegranskat)abstract
- The immense increase in the generation of genomic scale data poses an unmet analytical challenge, due to a lack of established methodology with the required flexibility and power. We propose a first principled approach to statistical analysis of sequence-level genomic information. We provide a growing collection of generic biological investigations that query pairwise relations between tracks, represented as mathematical objects, along the genome. The Genomic HyperBrowser implements the approach and is available at http://hyperbrowser.uio.no.© 2010 Sandve et al.; licensee BioMed Central Ltd.
|
|
| 23. |
- Shakya, Ruchika, et al.
(författare)
-
Inkoo and Sindbis viruses in blood sucking insects, and a serological study for Inkoo virus in semi-domesticated Eurasian tundra reindeer in Norway
- 2022
-
Ingår i: Virology Journal. - : Springer Nature. - 1743-422X. ; 19:1
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Mosquito-borne viruses pose a serious threat to humans worldwide. There has been an upsurge in the number of mosquito-borne viruses in Europe, mostly belonging to the families Togaviridae, genus Alphavirus (Sindbis, Chikungunya), Flaviviridae (West Nile, Usutu, Dengue), and Peribunyaviridae, genus Orthobunyavirus, California serogroup (Inkoo, Batai, Tahyna). The principal focus of this study was Inkoo (INKV) and Sindbis (SINV) virus circulating in Norway, Sweden, Finland, and some parts of Russia. These viruses are associated with morbidity in humans. However, there is a knowledge gap regarding reservoirs and transmission. Therefore, we aimed to determine the prevalence of INKV and SINV in blood sucking insects and seroprevalence for INKV in semi-domesticated Eurasian tundra reindeer (Rangifer tarandus tarandus) in Norway. Materials and methods: In total, 213 pools containing about 25 blood sucking insects (BSI) each and 480 reindeer sera were collected in eight Norwegian reindeer summer pasture districts during 2013–2015. The pools were analysed by RT-PCR to detect INKV and by RT-real-time PCR for SINV. Reindeer sera were analysed for INKV-specific IgG by an Indirect Immunofluorescence Assay (n = 480, IIFA) and a Plaque Reduction Neutralization Test (n = 60, PRNT). Results: Aedes spp. were the most dominant species among the collected BSI. Two of the pools were positive for INKV-RNA by RT-PCR and were confirmed by pyrosequencing. The overall estimated pool prevalence (EPP) of INKV in Norway was 0.04%. None of the analysed pools were positive for SINV. Overall IgG seroprevalence in reindeer was 62% positive for INKV by IIFA. Of the 60 reindeer sera- analysed by PRNT for INKV, 80% were confirmed positive, and there was no cross-reactivity with the closely related Tahyna virus (TAHV) and Snowshoe hare virus (SSHV). Conclusion: The occurrence and prevalence of INKV in BSI and the high seroprevalence against the virus among semi-domesticated reindeer in Norway indicate that further studies are required for monitoring this virus. SINV was not detected in the BSI in this study, however, human cases of SINV infection are yearly reported from other regions such as Rjukan in south-central Norway. It is therefore essential to monitor both viruses in the human population. Our findings are important to raise awareness regarding the geographical distribution of these mosquito-borne viruses in Northern Europe.
|
|
| 24. |
- Sjödin, Anna, et al.
(författare)
-
Secretoglobins in the human pituitary : high expression of lipophilin B and its down-regulation in pituitary adenomas
- 2005
-
Ingår i: Acta Neuropathologica. - : Springer Science and Business Media LLC. - 0001-6322 .- 1432-0533. ; 109:4, s. 381-386
-
Tidskriftsartikel (refereegranskat)abstract
- Secretoglobins are small secreted proteins, the expression of which has mostly been associated with secretory mucosal epithelia. Several secretoglobins have been implicated in the development of various human cancers. Allelic deletions of chromosome 11q13 correlates with the invasiveness of pituitary tumors. Intriguingly, several secretoglobin genes are located on 11q13; however, for most of these genes the expression in the pituitary and pituitary tumors have not been investigated. Antibodies specific for the secretoglobin lipophilin B (SCGB1D2, BU101) were developed and used in an immunohistochemical analysis of a human normal tissue microarray. Prominent lipophilin B immunoreactivity was found in the secretory cells of the anterior pituitary. Eight of nine analyzed pituitary adenomas showed a reduction in lipophilin B immunoreactivity compared to normal pituitary. However, there was no apparent association between lipophilin B immunoreactivity and hormone production or tumor invasiveness. Expression of eight different secretoglobin mRNAs were analyzed in normal pituitary and the pituitary adenoma cell line HP75 by highly specific quantitative real-time reverse transcription-PCR assays. Lipophilins B and C (SCGB2A1, mammaglobin B) were the most prominently expressed secretoglobin mRNAs in the pituitary. No secretoglobin mRNA was detected in the HP75 cells. The present report demonstrates, for the first time, lipophilin B expression in the pituitary and its apparent down-regulation in pituitary adenomas.
|
|
| 25. |
- Westra, Jelmer, et al.
(författare)
-
Coronary Artery Stenosis Evaluation by Angiography-Derived FFR Validation by Positron Emission Tomography and Invasive Thermodilution
- 2023
-
Ingår i: JACC Cardiovascular Imaging. - : ELSEVIER SCIENCE INC. - 1936-878X .- 1876-7591. ; 16:10, s. 1321-1331
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND Fractional flow reserve (FFR) derived from invasive coronary angiography (QFR) is promising for evaluation of intermediate coronary artery stenosis. OBJECTIVES The authors aimed to compare the diagnostic performance of QFR and the guideline-recommended invasive FFR using 82Rubidium positron emission tomography (82Rb-PET) myocardial perfusion imaging as reference standard. METHODS This is a prospective, observational study of symptomatic patients with suspected obstructive coronary artery disease on coronary computed tomography angiography (>= 50% diameter stenosis in >= 1 vessel). All patients were referred to 82Rb-PET and invasive coronary angiography with FFR and QFR assessment of all intermediate (30%-90% diameter stenosis) stenoses. Main analyses included a comparison of the ability of QFR and FFR to identify reduced myocardial blood flow (<2 mL/g/min) during vasodilation and/or relative perfusion abnormalities (summed stress score >= 4 in >= 2 adjacent segments).RESULTS A total of 250 patients (320 vessels) with indication for invasive physiological assessment were included. The continuous relationship of 82Rb-PET stress myocardial blood flow per 0.10 increase in FFR was +0.14 mL/g/min (95% CI: 0.07-0.21 mL/g/min) and +0.08 mL/g/min (95% CI: 0.02-0.14 mL/g/min) per 0.10 QFR increase. Using 82Rb-PET as reference, QFR and FFR had similar diagnostic performance on both a per-patient level (accuracy: 73%; 95% CI: 67%-79%; vs accuracy: 71%; 95% CI: 64%-78%) and per-vessel level (accuracy: 70%; 95% CI: 64%-75%; vs accuracy: 68%; 95% CI: 62%-73%). The per-vessel feasibility was 84% (95% CI: 80%-88%) for QFR and 88% (95% CI: 85%-92%) for FFR by intention-to-diagnose analysis. CONCLUSIONS With 82Rb-PET as reference modality, the wire-free QFR solution showed similar diagnostic accuracy as invasive FFR in evaluation of intermediate coronary stenosis. (DAN-NICAD - Danish Study of Non-Invasive Diagnostic Testing in Coronary Artery Disease; NCT02264717) (J Am Coll Cardiol Img 2023;16:1321-1331) (c) 2023 by the American College of Cardiology Foundation.
|
|
| 26. |
- Wibom, Carl, 1977-, et al.
(författare)
-
Proteomic profiles differ between bone invasive and noninvasive benign meningiomas of fibrous and meningothelial subtype
- 2009
-
Ingår i: Journal of Neuro-Oncology. - : Springer Netherlands. - 0167-594X .- 1573-7373. ; 94:3, s. 321-331
-
Tidskriftsartikel (refereegranskat)abstract
- Meningiomas of WHO grade I can usually be cured by surgical resection. However, some tumors may, despite their benign appearance, display invasive growth behavior. These tumors constitute a difficult clinical problem to handle. By histology alone, bone invasive meningiomas may be indistinguishable from their noninvasive counterparts. In this study we have examined the protein spectra in a series of meningiomas in search of protein expression patterns that may distinguish between bone invasive and noninvasive meningiomas. Tumor tissue from 13 patients with fibrous (6 invasive and 7 noninvasive) and 29 with meningothelial (10 invasive and 19 noninvasive) grade I meningiomas were analyzed by surface-enhanced laser desorption/ionization time-of-flight mass spectrometry (SELDI). Multivariate statistical methods were applied for data analyses. Comparing the protein spectra from invasive and noninvasive fibrous meningioma we found 22 peaks whose intensities were significantly different between the two groups (P < 0.001). Based on the expression pattern of these peaks we were able to perfectly separate the two entities (area under ROC curve = 1.0). In meningothelial meningioma the same comparison yielded six significantly differentially expressed peaks (P < 0.001), which to a large degree separated the invasive from noninvasive tissue (area under ROC curve = 0.873). By analyzing the protein spectra in benign meningiomas we could differentiate between invasive and noninvasive growth behavior in both fibrous and meningothelial meningiomas of grade I. A possibility for early identification of invasive grade I meningiomas may have a strong influence on the follow-up policy and the issue of early or late radiotherapy.
|
|
