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- Chen, Min-Wei, et al.
(författare)
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H3K9 histone methyltransferase G9a promotes lung cancer invasion and metastasis by silencing the cell adhesion molecule Ep-CAM
- 2010
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Ingår i: Cancer Research. - : American Association for Cancer Research. - 0008-5472 .- 1538-7445. ; 70:20, s. 7830-7840
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Tidskriftsartikel (refereegranskat)abstract
- G9a is a mammalian histone methyltransferase that contributes to the epigenetic silencing of tumor suppressor genes. Emerging evidence suggests that G9a is required to maintain the malignant phenotype, but the role of G9a function in mediating tumor metastasis has not been explored. Here, we show that G9a is expressed in aggressive lung cancer cells, and its elevated expression correlates with poor prognosis. RNAi-mediated knockdown of G9a in highly invasive lung cancer cells inhibited cell migration and invasion in vitro and metastasis in vivo. Conversely, ectopic G9a expression in weakly invasive lung cancer cells increased motility and metastasis. Mechanistic investigations suggested that repression of the cell adhesion molecule Ep-CAM mediated the effects of G9a. First, RNAi-mediated knockdown of Ep-CAM partially relieved metastasis suppression imposed by G9a suppression. Second, an inverse correlation between G9a and Ep-CAM expression existed in primary lung cancer. Third, Ep-CAM repression was associated with promoter methylation and an enrichment for dimethylated histone H3K9. G9a knockdown reduced the levels of H3K9 dimethylation and decreased the recruitment of the transcriptional cofactors HP1, DNMT1, and HDAC1 to the Ep-CAM promoter. Our findings establish a functional contribution of G9a overexpression with concomitant dysregulation of epigenetic pathways in lung cancer progression.
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- Desjardins, Kewin, et al.
(författare)
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Characterization of a back-illuminated CMOS camera for soft x-ray coherent scattering
- 2019
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Ingår i: Proceedings of the 13th International Conference on Synchrotron Radiation Instrumentation, SRI 2018. - : Author(s). - 9780735417823 ; 2054
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Konferensbidrag (refereegranskat)abstract
- A commercial scientific camera has been adapted and characterized at the SOLEIL Synchrotron with the aim to improve the acquisition capabilities on the soft X-ray coherent scattering experimental station at SEXTANTS beamline. This device is equipped by the last generation of back side illuminated scientific CMOS (BSI-sCMOS) of 2048 by 2048 pixels of 11 μm2 able to acquire low noise images with a frame rate up to 48 Hz. The camera's performance measurements have been done and shows a good level of readout noise, a large full-well capacity, a medium dark current and a good homogeneity, respectively, 1.6 e- rms (in High Gain mode), 80 000 e- (in Low Gain mode),<5 e-/pixel/s and ∼ 1%. The quantum efficiency (QE) measurement has been performed at the soft x-ray branch of the METROLOGIE beamline and gives a relatively good agreement with the expected theoretical values. Finally, the demonstration of the camera's efficiency and of the gain in useful time measurement related to the high frame rate have been performed with a series of Airy patterns images compared with an image recorded using the standard BSI-CDD already in operation at the SEXTANTS beamline.
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- Griesmayer, E., et al.
(författare)
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Applications of single-crystal CVD diamond XBPM detectors with nanometre x-ray beams
- 2019
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Ingår i: Proceedings of the 13th International Conference on Synchrotron Radiation Instrumentation, SRI 2018. - : Author(s). - 9780735417823 ; 2054
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Konferensbidrag (refereegranskat)abstract
- Measurements with a Diamond XBPM were carried out at the MAX IV Laboratory, Lund, Sweden, at the NanoMAX beam line. This was the first investigation of a Diamond XBPM detector with nanometre beams. The effect of diffusion, as well as the position resolution at the smallest available beam sizes were studied.
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- Marcouille, O., et al.
(författare)
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Production of high energy photons with in vacuum wigglers : From SOLEIL wiggler to MAXIV wiggler
- 2019
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Ingår i: Proceedings of the 13th International Conference on Synchrotron Radiation Instrumentation, SRI 2018. - : Author(s). - 9780735417823 ; 2054
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Konferensbidrag (refereegranskat)abstract
- Small gap wigglers become more and more attractive to produce high photon fluxes in the hard X-ray photon range. They use magnet blocks of high magnetization which resists much better to heating (baking, synchrotron radiation) than in the past, produce high magnetic field with numerous periods and are very compact. They also are a very good alternative to superconducting technology which requires special infrastructure, heavy maintenance and is not running cost free. SOLEIL, operating presently at 2.75 GeV has designed and built an in-vacuum wiggler of 38 periods of 50 mm producing 2.1 T at a minimum gap of 5.5 mm to delivered photon beam between 20 keV and 50 keV. Already in operation, further improvements are presently in progress to push photons towards higher energy, in particular thanks to the operation at lower gap (4.5 mm). MAX IV and SOLEIL, in the frame of collaboration, ave built an upgraded version of the existing SOLEIL wiggler with the target to extend the spectral range at high energy (above 50 keV) but also at low energy (4 keV) with the same insertion device. The design of the existing magnetic system has been modified to reach 2.4 T at a minimum gap of 4.2 mm and includes taper operation to avoid undulator structure in the radiated spectrum at low energy.
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- Plivelic, Tomás S., et al.
(författare)
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X-ray tracing, design and construction of an optimized optics scheme for CoSAXS, the small angle x-ray scattering beamline at MAX IV laboratory
- 2019
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Ingår i: Proceedings of the 13th International Conference on Synchrotron Radiation Instrumentation, SRI 2018. - : Author(s). - 9780735417823 ; 2054
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Konferensbidrag (refereegranskat)abstract
- A novel optical design for a flexible SAXS beamline at a modern synchrotron has been implemented for the CoSAXS beamline at the 3GeV ring at the MAX TV Laboratory. The performance of the beamline has been simulated through combined ray tracing and wave propagation with the code xrt taking into account the low emittance and highly coherent beam of MAX TV and the short inter-optics distances of the beamline. The total photon flux is estimated to be 1012-1013 ph/s with the coherent flux portion up to 10 % at 7.1 keV. The inhomogeneities in the X-ray beam arising from use of real (non-idealised) mirror surfaces are also modelled using the measured slope profiles of the mirrors. Strategies to mitigate these inhomogeneities are discussed. The optical components for CoSAXS have been constructed and beamline commissioning will start in 2019.
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- Docherty, Anna R, et al.
(författare)
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GWAS Meta-Analysis of Suicide Attempt: Identification of 12 Genome-Wide Significant Loci and Implication of Genetic Risks for Specific Health Factors.
- 2023
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Ingår i: The American journal of psychiatry. - : American Psychiatric Association Publishing. - 1535-7228 .- 0002-953X. ; 180:10, s. 723-738
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Tidskriftsartikel (refereegranskat)abstract
- Suicidal behavior is heritable and is a major cause of death worldwide. Two large-scale genome-wide association studies (GWASs) recently discovered and cross-validated genome-wide significant (GWS) loci for suicide attempt (SA). The present study leveraged the genetic cohorts from both studies to conduct the largest GWAS meta-analysis of SA to date. Multi-ancestry and admixture-specific meta-analyses were conducted within groups of significant African, East Asian, and European ancestry admixtures.This study comprised 22 cohorts, including 43,871 SA cases and 915,025 ancestry-matched controls. Analytical methods across multi-ancestry and individual ancestry admixtures included inverse variance-weighted fixed-effects meta-analyses, followed by gene, gene-set, tissue-set, and drug-target enrichment, as well as summary-data-based Mendelian randomization with brain expression quantitative trait loci data, phenome-wide genetic correlation, and genetic causal proportion analyses.Multi-ancestry and European ancestry admixture GWAS meta-analyses identified 12 risk loci at p values <5×10-8. These loci were mostly intergenic and implicated DRD2, SLC6A9, FURIN, NLGN1, SOX5, PDE4B, and CACNG2. The multi-ancestry SNP-based heritability estimate of SA was 5.7% on the liability scale (SE=0.003, p=5.7×10-80). Significant brain tissue gene expression and drug set enrichment were observed. There was shared genetic variation of SA with attention deficit hyperactivity disorder, smoking, and risk tolerance after conditioning SA on both major depressive disorder and posttraumatic stress disorder. Genetic causal proportion analyses implicated shared genetic risk for specific health factors.This multi-ancestry analysis of suicide attempt identified several loci contributing to risk and establishes significant shared genetic covariation with clinical phenotypes. These findings provide insight into genetic factors associated with suicide attempt across ancestry admixture populations, in veteran and civilian populations, and in attempt versus death.
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8. |
- Mullins, Niamh, et al.
(författare)
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Dissecting the Shared Genetic Architecture of Suicide Attempt, Psychiatric Disorders, and Known Risk Factors
- 2022
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Ingår i: Biological Psychiatry. - : Elsevier. - 0006-3223 .- 1873-2402. ; 91:3, s. 313-327
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Suicide is a leading cause of death worldwide, and nonfatal suicide attempts, which occur far more frequently, are a major source of disability and social and economic burden. Both have substantial genetic etiology, which is partially shared and partially distinct from that of related psychiatric disorders.METHODS: We conducted a genome-wide association study (GWAS) of 29,782 suicide attempt (SA) cases and 519,961 controls in the International Suicide Genetics Consortium (ISGC). The GWAS of SA was conditioned on psychiatric disorders using GWAS summary statistics via multitrait-based conditional and joint analysis, to remove genetic effects on SA mediated by psychiatric disorders. We investigated the shared and divergent genetic architectures of SA, psychiatric disorders, and other known risk factors.RESULTS: Two loci reached genome-wide significance for SA: the major histocompatibility complex and an intergenic locus on chromosome 7, the latter of which remained associated with SA after conditioning on psychiatric disorders and replicated in an independent cohort from the Million Veteran Program. This locus has been implicated in risk-taking behavior, smoking, and insomnia. SA showed strong genetic correlation with psychiatric disorders, particularly major depression, and also with smoking, pain, risk-taking behavior, sleep disturbances, lower educational attainment, reproductive traits, lower socioeconomic status, and poorer general health. After conditioning on psychiatric disorders, the genetic correlations between SA and psychiatric disorders decreased, whereas those with nonpsychiatric traits remained largely unchanged.CONCLUSIONS: Our results identify a risk locus that contributes more strongly to SA than other phenotypes and suggest a shared underlying biology between SA and known risk factors that is not mediated by psychiatric disorders.
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9. |
- Phukhamsakda, Chayanard, et al.
(författare)
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The numbers of fungi: contributions from traditional taxonomic studies and challenges of metabarcoding
- 2022
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Ingår i: Fungal diversity. - : Springer Science and Business Media LLC. - 1560-2745 .- 1878-9129. ; 114:1, s. 327-386
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Tidskriftsartikel (refereegranskat)abstract
- The global diversity of fungi has been estimated using several different approaches. There is somewhere between 2–11 million estimated species, but the number of formally described taxa is around 150,000, a tiny fraction of the total. In this paper, we examine 12 ascomycete genera as case studies to establish trends in fungal species descriptions, and introduce new species in each genus. To highlight the importance of traditional morpho-molecular methods in publishing new species, we introduce novel taxa in 12 genera that are considered to have low species discovery. We discuss whether the species are likely to be rare or due to a lack of extensive sampling and classification. The genera are Apiospora, Bambusicola, Beltrania, Capronia, Distoseptispora, Endocalyx, Neocatenulostroma, Neodeightonia, Paraconiothyrium, Peroneutypa, Phaeoacremonium and Vanakripa. We discuss host-specificity in selected genera and compare the number of species epithets in each genus with the number of ITS (barcode) sequences deposited in GenBank and UNITE. We furthermore discuss the relationship between the divergence times of these genera with those of their hosts. We hypothesize whether there might be more species in these genera and discuss hosts and habitats that should be investigated for novel species discovery.
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