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Sökning: WFRF:(SzeKely L)

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  • Prentice, S. J., et al. (författare)
  • SN 2016coi/ASASSN-16fp : an example of residual helium in a type Ic supernova?
  • 2018
  • Ingår i: Monthly notices of the Royal Astronomical Society. - : Oxford University Press (OUP). - 0035-8711 .- 1365-2966. ; 478:3, s. 4162-4192
  • Tidskriftsartikel (refereegranskat)abstract
    • The optical observations of Ic-4 supernova (SN) 2016coi/ASASSN-16fp, from similar to 2 to similar to 450 d after explosion, are presented along with analysis of its physical properties. The SN shows the broad lines associated with SNe Ic-3/4 but with a key difference. The early spectra display a strong absorption feature at similar to 5400 angstrom which is not seen in other SNe Ic-3/4 at this epoch. This feature has been attributed to He I in the literature. Spectral modelling of the SN in the early photospheric phase suggests the presence of residual He in a C/O dominated shell. However, the behaviour of the He I lines is unusual when compared with He-rich SNe, showing relatively low velocities and weakening rather than strengthening over time. The SN is found to rise to peak similar to 16 d after core-collapse reaching a bolometric luminosity of L-p similar to 3 x 10(42) erg s(-1). Spectral models, including the nebular epoch, show that the SN ejected 2.5-4M(circle dot) of material, with similar to 1.5M(circle dot) below 5000 km s(-1), and with a kinetic energy of (4.5-7) x 10(51) erg. The explosion synthesized similar to 0.14M(circle dot) of Ni-56. There are significant uncertainties in E(B - V)(host) and the distance, however, which will affect L-p and M-Ni. SN 2016coi exploded in a host similar to the Large Magellanic Cloud (LMC) and away from star-forming regions. The properties of the SN and the host-galaxy suggest that the progenitor had M-ZAMS of 23-28M(circle dot) and was stripped almost entirely down to its C/O core at explosion.
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  • Flaberg, E., et al. (författare)
  • High-throughput live cell imaging reveals differential inhibition of tumor cell proliferation by human fibroblasts
  • 2011
  • Ingår i: International Journal of Cancer. - : Wiley-Blackwell. - 0020-7136 .- 1097-0215. ; 128:12, s. 2793-2802
  • Tidskriftsartikel (refereegranskat)abstract
    • Increasing evidence indicates that cancer development requires changes both in the precancerous cells and in their microenvironment. To study one aspect of the microenvironmental control, we departed from Michael Stoker's observation (Stroker et al, J Cell Sci 1966;1:297-310) that normal fibroblasts can inhibit the growth of admixed cancer cells (neighbour suppression). We have developed a high-throughput microscopy and image analysis system permitting the examination of live mixed cell cultures growing on 384-well plates, at the single cell level and over time. We have tested the effect of 107 samples of low passage number (<5) primary human fibroblasts from pediatric and adult donors, on the growth of six human tumor cell lines. Three of the lines were derived from prostate carcinomas, two from lung carcinomas and one was an EBV transformed lymphoblastoid line. Labeled tumor cells were grown in the presence of unlabeled fibroblasts. The majority of the tested fibroblasts inhibited the proliferation of the tumor cells, compared to the control cultures where labeled tumor cells were co-cultured with unlabeled tumor cells. The proliferation inhibiting effect of the fibroblasts differed depending on their site of origin and the age of the donor. Inhibition required direct cell contact. Mouse 3T3 fibroblasts inhibited the growth of SV40-transformed 3T3 cells and human tumor cells, showing that the inhibitory effect could prevail across the species barrier. Our high-throughput system allows the quantitative analysis of the inhibitory effect of fibroblasts on the population level and the exploration of differences depending on the source of the normal cells.
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  • Liu, Z. G., et al. (författare)
  • Hemizygous variants in protein phosphatase 1 regulatory subunit 3F (PPP1R3F) are associated with a neurodevelopmental disorder characterized by developmental delay, intellectual disability and autistic features
  • 2023
  • Ingår i: Human Molecular Genetics. - 0964-6906 .- 1460-2083. ; 32:20, s. 2981-2995
  • Tidskriftsartikel (refereegranskat)abstract
    • Protein phosphatase 1 regulatory subunit 3F (PPP1R3F) is a member of the glycogen targeting subunits (GTSs), which belong to the large group of regulatory subunits of protein phosphatase 1 (PP1), a major eukaryotic serine/threonine protein phosphatase that regulates diverse cellular processes. Here, we describe the identification of hemizygous variants in PPP1R3F associated with a novel X-linked recessive neurodevelopmental disorder in 13 unrelated individuals. This disorder is characterized by developmental delay, mild intellectual disability, neurobehavioral issues such as autism spectrum disorder, seizures and other neurological findings including tone, gait and cerebellar abnormalities. PPP1R3F variants segregated with disease in affected hemizygous males that inherited the variants from their heterozygous carrier mothers. We show that PPP1R3F is predominantly expressed in brain astrocytes and localizes to the endoplasmic reticulum in cells. Glycogen content in PPP1R3F knockout astrocytoma cells appears to be more sensitive to fluxes in extracellular glucose levels than in wild-type cells, suggesting that PPP1R3F functions in maintaining steady brain glycogen levels under changing glucose conditions. We performed functional studies on nine of the identified variants and observed defects in PP1 binding, protein stability, subcellular localization and regulation of glycogen metabolism in most of them. Collectively, the genetic and molecular data indicate that deleterious variants in PPP1R3F are associated with a new X-linked disorder of glycogen metabolism, highlighting the critical role of GTSs in neurological development. This research expands our understanding of neurodevelopmental disorders and the role of PP1 in brain development and proper function.
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  • Pastorello, A., et al. (författare)
  • ESC and KAIT observations of the transitional type Ia SN 2004eo
  • 2007
  • Ingår i: Monthly notices of the Royal Astronomical Society. - : Oxford University Press (OUP). - 0035-8711 .- 1365-2966. ; 377:4, s. 1531-1552
  • Tidskriftsartikel (refereegranskat)abstract
    • We present optical and infrared observations of the unusual Type Ia supernova (SN) 2004eo. The light curves and spectra closely resemble those of the prototypical SN 1992A, and the luminosity at maximum (M-B = -19.08) is close to the average for a Type Ia supernova (SN Ia). However, the ejected Ni-56 mass derived by modelling the bolometric light curve (about 0.45M(circle dot)) lies near the lower limit of the Ni-56 mass distribution observed in normal SNe Ia. Accordingly, SN 2004eo shows a relatively rapid post-maximum decline in the light curve [Delta m(15)(B)(true) = 1.46], small expansion velocities in the ejecta and a depth ratio Si II lambda 5972/ Si II lambda 6355 similar to that of SN 1992A. The physical properties of SN 2004eo cause it to fall very close to the boundary between the faint, low-velocity gradient and high-velocity gradient subgroups proposed by Benetti et al. Similar behaviour is seen in a few other SNe Ia. Thus, there may in fact exist a few SNe Ia with intermediate physical properties.
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  • Tommasini, R., et al. (författare)
  • Accepted Tutorials at The Web Conference 2022
  • 2022
  • Ingår i: WWW 2022 - Companion Proceedings of the Web Conference 2022. - New York, NY, USA : Association for Computing Machinery (ACM). ; , s. 391-399
  • Konferensbidrag (refereegranskat)abstract
    • This paper summarizes the content of the 20 tutorials that have been given at The Web Conference 2022: 85% of these tutorials are lecture style, and 15% of these are hands on. 
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  • Bier, Raven L., et al. (författare)
  • Effects of ecosystem size-induced environmental fluctuations on the temporal dynamics of community assembly mechanisms
  • 2022
  • Ingår i: The ISME Journal. - : Springer Nature. - 1751-7362 .- 1751-7370. ; 16:12, s. 2635-2643
  • Tidskriftsartikel (refereegranskat)abstract
    • Understanding processes that determine community membership and abundance is important for many fields from theoretical community ecology to conservation. However, spatial community studies are often conducted only at a single timepoint despite the known influence of temporal variability on community assembly processes. Here we used a spatiotemporal study to determine how environmental fluctuation differences induced by mesocosm volumes (larger volumes were more stable) influence assembly processes of aquatic bacterial metacommunities along a press disturbance gradient. By combining path analysis and network approaches, we found mesocosm size categories had distinct relative influences of assembly process and environmental factors that determined spatiotemporal bacterial community composition, including dispersal and species sorting by conductivity. These processes depended on, but were not affected proportionately by, mesocosm size. Low fluctuation, large mesocosms primarily developed through the interplay of species sorting that became more important over time and transient priority effects as evidenced by more time-delayed associations. High fluctuation, small mesocosms had regular disruptions to species sorting and greater importance of ecological drift and dispersal limitation indicated by lower richness and higher taxa replacement. Together, these results emphasize that environmental fluctuations influence ecosystems over time and its impacts are modified by biotic properties intrinsic to ecosystem size.
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  • Bozoky, Benedek, et al. (författare)
  • Stabilization of the classical phenotype upon integration of pancreatic cancer cells into the duodenal epithelium
  • 2021
  • Ingår i: Neoplasia. - : Elsevier. - 1522-8002 .- 1476-5586. ; 23:12, s. 1300-1306
  • Tidskriftsartikel (refereegranskat)abstract
    • Introduction: Pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive solid tumors. Based on transcriptomic classifiers, basal-like and classical PDAC subtypes have been defined that differ in prognosis. Cells of both subtypes can coexist in individual tumors; however, the contribution of either clonal heterogeneity or microenvironmental cues to subtype heterogeneity is unclear. Here, we report the spatial tumor phenotype dynamics in a cohort of patients in whom PDAC infiltrated the duodenal wall, and identify the duodenal epithelium as a distinct PDAC microniche. Materials and methods: We used serial multiplex quantitative immunohistochemistry (smq-IHC) for 24 proteins to phenotypically chart PDAC tumor cells in patients whose tumors infiltrated the duodenal epithelium. Additionally, we used a genetically engineered mouse model to study the PDAC cell phenotype in the small intestinal epithelium in a controlled genetic background. Result: We show that pancreatic cancer cells revert to non-destructive growth upon integration into the duodenal epithelium, where they adopt traits of intestinal cell differentiation, associated with phenotypical stabilization of the classical subtype. The integrated tumor cells replace epithelial cells in an adenoma-like manner, as opposed to invasive growth in the submucosa. Finally, we show that this phenomenon is shared between species, by confirming duodenal integration and phenotypic switching in a genetic PDAC mouse model. Discussion: Our results identify the duodenal epithelium as a distinct PDAC microniche and tightly link microenvironmental cue to cancer transcriptional subtypes. The phenomenon of "intestinal mimicry" provides a unique opportunity for the systematic investigation of microenvironmental influences on pancreatic cancer plasticity.
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  • Feng, Shaohong, et al. (författare)
  • Dense sampling of bird diversity increases power of comparative genomics
  • 2020
  • Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 587:7833
  • Tidskriftsartikel (refereegranskat)abstract
    • Whole-genome sequencing projects are increasingly populating the tree of life and characterizing biodiversity(1-4). Sparse taxon sampling has previously been proposed to confound phylogenetic inference(5), and captures only a fraction of the genomic diversity. Here we report a substantial step towards the dense representation of avian phylogenetic and molecular diversity, by analysing 363 genomes from 92.4% of bird families-including 267 newly sequenced genomes produced for phase II of the Bird 10,000 Genomes (B10K) Project. We use this comparative genome dataset in combination with a pipeline that leverages a reference-free whole-genome alignment to identify orthologous regions in greater numbers than has previously been possible and to recognize genomic novelties in particular bird lineages. The densely sampled alignment provides a single-base-pair map of selection, has more than doubled the fraction of bases that are confidently predicted to be under conservation and reveals extensive patterns of weak selection in predominantly non-coding DNA. Our results demonstrate that increasing the diversity of genomes used in comparative studies can reveal more shared and lineage-specific variation, and improve the investigation of genomic characteristics. We anticipate that this genomic resource will offer new perspectives on evolutionary processes in cross-species comparative analyses and assist in efforts to conserve species. A dataset of the genomes of 363 species from the Bird 10,000 Genomes Project shows increased power to detect shared and lineage-specific variation, demonstrating the importance of phylogenetically diverse taxon sampling in whole-genome sequencing.
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  • Garcia, Sarahi L, et al. (författare)
  • Decreased Snow Cover Stimulates Under-Ice Primary Producers but Impairs Methanotrophic Capacity
  • 2019
  • Ingår i: mSphere. - : AMER SOC MICROBIOLOGY. - 2379-5042. ; 4:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Climate change scenarios anticipate decreased spring snow cover in boreal and subarctic regions. Forest lakes are abundant in these regions and substantial contributors of methane emissions. To investigate the effect of reduced snow cover, we experimentally removed snow from an anoxic frozen lake. We observed that the removal of snow increased light penetration through the ice, increasing water temperature and modifying microbial composition in the different depths. Chlorophyll a and b concentrations increased in the upper water column, suggesting activation of algal primary producers. At the same time, Chlorobiaceae, one of the key photosynthetic bacterial families in anoxic lakes, shifted to lower depths. Moreover, a decrease in the relative abundance of methanotrophs within the bacterial family Methylococcaceae was detected, concurrent with an increase in methane concentration in the water column. These results indicate that decreased snow cover impacts both primary production and methane production and/or consumption, which may ultimately lead to increased methane emissions after spring ice off. IMPORTANCE Small lakes are an important source of greenhouse gases in the boreal zone. These lakes are severely impacted by the winter season, when ice and snow cover obstruct gas exchange between the lake and the atmosphere and diminish light availability in the water column. Currently, climate change is resulting in reduced spring snow cover. A short-term removal of the snow from the ice stimulated algal primary producers and subsequently heterotrophic bacteria. Concurrently, the relative abundance of methanotrophic bacteria decreased and methane concentrations increased. Our results increase the general knowledge of microbial life under ice and, specifically, the understanding of the potential impact of climate change on boreal lakes.
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  • Ge, Z, et al. (författare)
  • Aberrant ARID5B expression and its association with Ikaros dysfunction in acute lymphoblastic leukemia
  • 2018
  • Ingår i: Oncogenesis. - : Springer Science and Business Media LLC. - 2157-9024. ; 7:11, s. 84-
  • Tidskriftsartikel (refereegranskat)abstract
    • Mutations and single nucleotide polymorphisms of AT-rich interactive domain-containing protein 5B (ARID5B) are involved in the oncogenesis of acute lymphoblastic leukemia (ALL) and treatment outcomes. However, ARID5B expression and clinical significance in ALL remain unclear. We found ARID5B is significantly down-regulated in ALL compared to healthy bone marrow controls. ARID5B also interacts with PHD finger protein 2 (PHF2). Low expression of ARID5B (ARID5Blow) or ARID5B and PHF2 (ARID5BlowPHF2low) is correlated with the markers of cell proliferation and poor prognosis in ALL patients. Ikaros directly regulates ARID5B expression in ALL. Restoring Ikaros function by Casein Kinase II inhibition also promotes ARID5B expression through recruitment of trimethylation of lysine 4 on histone H3 (H3K4me3) at its promoter region. In summary, our data show that aberrant expression of ARID5B and PHF2 is related to leukemic cell proliferation and several poor prognostic markers. Our data indicate ARID5Blow expression, particularly ARID5BlowPHF2low expression, is linked to Ikaros dysfunction and involved in the oncogenic effect of high-risk ALL, which may represent a high-risk subgroup of ALL.
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  • Jing, X, et al. (författare)
  • COVID-19 instigates adipose browning and atrophy through VEGF in small mammals
  • 2022
  • Ingår i: Nature metabolism. - : Springer Science and Business Media LLC. - 2522-5812. ; 4:12, s. 1674-
  • Tidskriftsartikel (refereegranskat)abstract
    • Patients with COVID-19 frequently manifest adipose atrophy, weight loss and cachexia, which significantly contribute to poor quality of life and mortality1,2. Browning of white adipose tissue and activation of brown adipose tissue are effective processes for energy expenditure3–7; however, mechanistic and functional links between SARS-CoV-2 infection and adipose thermogenesis have not been studied. In this study, we provide experimental evidence that SARS-CoV-2 infection augments adipose browning and non-shivering thermogenesis (NST), which contributes to adipose atrophy and body weight loss. In mouse and hamster models, SARS-CoV-2 infection activates brown adipose tissue and instigates a browning or beige phenotype of white adipose tissues, including augmented NST. This browning phenotype was also observed in post-mortem adipose tissue of four patients who died of COVID-19. Mechanistically, high levels of vascular endothelial growth factor (VEGF) in the adipose tissue induces adipose browning through vasculature–adipocyte interaction. Inhibition of VEGF blocks COVID-19-induced adipose tissue browning and NST and partially prevents infection-induced body weight loss. Our data suggest that the browning of adipose tissues induced by COVID-19 can contribute to adipose tissue atrophy and weight loss observed during infection. Inhibition of VEGF signaling may represent an effective approach for preventing and treating COVID-19-associated weight loss.
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  • Kashuba, E, et al. (författare)
  • EBV-encoded EBNA-6 binds and targets MRS18-2 to the nucleus, resulting in the disruption of pRb-E2F1 complexes
  • 2008
  • Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 1091-6490. ; 105:14, s. 5489-5494
  • Tidskriftsartikel (refereegranskat)abstract
    • Epstein–Barr virus (EBV), like other DNA tumor viruses, induces an S-phase in the natural host cell, the human B lymphocyte. This is linked with blast transformation. It is believed that the EBV-encoded nuclear antigen 6 (EBNA-6) is involved in the regulation of cell cycle entry. However, the possible mechanism of this regulation is not approached. In our current study, we found that EBNA-6 binds to a MRPS18-2 protein, and targets it to the nucleus. We found that MRPS18-2 binds to both hypo- and hyperphosphorylated forms of Rb protein specifically. This binding targets the small pocket of pRb, which is a site of interaction with E2F1. The MRPS18-2 competes with the binding of E2F1 to pRb, thereby raising the level of free E2F1. Our experimental data suggest that EBNA-6 may play a major role in the entry of EBV infected B cells into the S phase by binding to and raising the level of nuclear MRPS18-2, protein. This would inhibit pRb binding to E2F1 competitively and lift the block preventing S-phase entry.
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  • Kashuba, E, et al. (författare)
  • MRPS18-2 protein immortalizes primary rat embryonic fibroblasts and endows them with stem cell-like properties
  • 2009
  • Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 1091-6490. ; 106:47, s. 19866-19871
  • Tidskriftsartikel (refereegranskat)abstract
    • We report that the overexpression of mitochondrial ribosomal protein MRPS18–2 (S18–2) can immortalize primary rat embryonic fibroblasts (REFs). The immortalized cells (18IM) lose contact inhibition, form foci, and are capable of anchorage-independent growth. Concurrently, mesodermal markers, such as vimentin, smooth muscle actin, and Fut4, disappear completely. 18IM cells express embryonic stem cell markers, such as SSEA-1, Sox2, and Oct3/4. In confluent cultures, a portion of cells also express ectoderm- and endoderm-specific pan-keratin, ectoderm-specific beta-III-tubulin, mesoderm-specific MHC class II, and become stainable for fat with Oil red O. None of these changes was detected in c-myc+Ha-ras (MR)-transformed cells. In immunodeficient mice, 18IM cells formed small transiently growing tumors that have down-regulated SSEA-1 and showed pan-keratin staining. We conclude that S18–2 can immortalize REFs and induces them to express stem cell traits.
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