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1.
  • Segerholm, Kristoffer, et al. (författare)
  • Micromorphology, moisture sorption and mechanical properties of a biocomposite based on acetylated wood particles and cellulose ester
  • 2007
  • Ingår i: Wood Material Science and Engineering. - : Informa UK Limited. - 1748-0272 .- 1748-0280. ; 3-4:2, s. 106-117
  • Tidskriftsartikel (refereegranskat)abstract
    • One of the major issues in a long-term perspective for the use of wood-plastic composites (WPCs) in outdoor applications is the moisture sensitivity of the wood component and the consequent dimensional instability and susceptibility to biological degradation of the composite. In this work, the effects of using an acetylated wood component and a cellulose ester as matrix on the micromorphology, mechanical performance and moisture uptake of injection-moulded WPCs have been studied. Composites based on unmodified and acetylated wood particles, specially designed with a length-to-width ratio of about 5-7, combined with both cellulose acetate propionate (CAP) and polypropylene (PP) matrices were studied. The size and shape of the wood particles were studied before and after the processing using light microscopy, and the micromorphology of the composites was studied using a newly developed surface preparation technique based on ultraviolet laser irradiation combined with low-vacuum scanning electron microscopy (LV-SEM). The water vapour sorption in the composites and the effect of accelerated weathering were measured using thin samples which were allowed to reach equilibrium moisture content (EMC). The length-to-diameter ratio was only slightly decreased for the acetylated particles after compounding and injection moulding, although both the unmodified and the acetylated particles were smaller in size after the processing steps. The tensile strength was about 40% higher for the composite based on acetylated wood than for the composite with unmodified wood using either CAP or PP as matrix, whereas the notched impact strength of the composite based on acetylated wood was about 20% lower than those of the corresponding unmodified composites. The sorption experiments showed that the EMC was 50% lower in the composites with an acetylated wood component than in the composites with an unmodified wood component. The choice of matrix material strongly affected the moisture absorptivity of the WPC. The composites with CAP as matrix gained moisture more rapidly than the composites with PP as matrix. It was also found that accelerated ageing in a Weather-Ometer® significantly increased the moisture sensitivity of the PP-based composites.
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  • Adhikari, Deepak, et al. (författare)
  • Inhibitory phosphorylation of Cdk1 mediates prolonged prophase I arrest in female germ cells and is essential for female reproductive lifespan
  • 2016
  • Ingår i: Cell Research. - : Springer Science and Business Media LLC. - 1001-0602 .- 1748-7838. ; 26, s. 1212-1225
  • Tidskriftsartikel (refereegranskat)abstract
    • © 2016 IBCB, SIBS, CAS. A unique feature of female germ cell development in mammals is their remarkably long arrest at the prophase of meiosis I, which lasts up to 50 years in humans. Both dormant and growing oocytes are arrested at prophase I and completely lack the ability to resume meiosis. Here, we show that the prolonged meiotic arrest of female germ cells is largely achieved via the inhibitory phosphorylation of Cdk1 (cyclin-dependent kinase 1). In two mouse models where we have introduced mutant Cdk1 T14AY15F which cannot be inhibited by phosphorylation (Cdk1AF) in small meiotically incompetent oocytes, the prophase I arrest is interrupted, leading to a premature loss of female germ cells. We show that in growing oocytes, Cdk1AF leads to premature resumption of meiosis with condensed chromosomes and germinal vesicle breakdown followed by oocyte death, whereas in dormant oocytes, Cdk1AF leads to oocyte death directly, and both situations damage the ovarian reserve that maintains the female reproductive lifespan, which should be around 1 year in mice. Furthermore, interruption of the inhibitory phosphorylation of Cdk1 results in DNA damage, which is accompanied by induction of the Chk2 (checkpoint kinase 2)-p53/p63-dependent cell death pathway, which eventually causes global oocyte death. Together, our data demonstrate that the phosphorylation-mediated suppression of Cdk1 activity is one of the crucial factors that maintain the lengthy prophase arrest in mammalian female germ cells, which is essential for preserving the germ cell pool and reproductive lifespan in female mammals.
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  • Carlson, Lena-Maria, et al. (författare)
  • Differentiation induced by physiological and pharmacological stimuli leads to increased antigenicity of human neuroblastoma cells
  • 2008
  • Ingår i: Cell Research. - : Springer Science and Business Media LLC. - 1748-7838 .- 1001-0602. ; 18:3, s. 398-411
  • Tidskriftsartikel (refereegranskat)abstract
    • Sympathetic neuronal differentiation is associated with favorable prognosis of neuroblastoma (NB), the most common extra-cranial solid tumor of early childhood. Differentiation agents have proved useful in clinical protocols of NB treatment, but using them as a sole treatment is not sufficient to induce tumor elimination in patients. Therefore, complementary approaches, such as immunotherapy, are warranted. Here we demonstrate that differentiation of NB cell lines and ex vivo isolated tumor cells in response to physiological or pharmacological stimuli is associated with acquisition of increased antigenicity. This manifests as increased expression of surface major histocompatibility class I complexes and ICAM-1 molecules and translates into increased sensitivity of NB cells to lysis by cytotoxic T lymphocytes (CTLs) and natural killer (NK) cells. The latter is paralleled by enhanced ability of differentiated cells to form immune conjugates and bind increased amounts of granzyme B to the cell surface. We demonstrate, for the first time, that, regardless of the stimulus applied, the differentiation state in NBs is associated with increased tumor antigenicity that enables more efficient elimination of tumor cells by cytotoxic lymphocytes and paves the way for combined application of differentiation-inducing agents and immunotherapy as an auxiliary approach in NB patients.
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  • Djupedal, Ingela, et al. (författare)
  • Epigenetics : heterochromatin meets RNAi
  • 2009
  • Ingår i: Cell Research. - : Springer Science and Business Media LLC. - 1001-0602 .- 1748-7838. ; 19:3, s. 282-295
  • Tidskriftsartikel (refereegranskat)abstract
    • The term epigenetics refers to heritable changes not encoded by DNA. The organization of DNA into chromatin fibers affects gene expression in a heritable manner and is therefore one mechanism of epigenetic inheritance. Large parts of eukaryotic genomes consist of constitutively highly condensed heterochromatin, important for maintaining genome integrity but also for silencing of genes within. Small RNA, together with factors typically associated with RNA interference (RNAi) targets homologous DNA sequences and recruits factors that modify the chromatin, commonly resulting in formation of heterochromatin and silencing of target genes. The scope of this review is to provide an overview of the roles of small RNA and the RNAi components, Dicer, Argonaute and RNA dependent polymerases in epigenetic inheritance via heterochromatin formation, exemplified with pathways from unicellular eukaryotes, plants and animals.
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7.
  • Fucikova, J, et al. (författare)
  • Calreticulin and cancer
  • 2021
  • Ingår i: Cell research. - : Springer Science and Business Media LLC. - 1748-7838 .- 1001-0602. ; 31:1, s. 5-16
  • Tidskriftsartikel (refereegranskat)
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8.
  • Ghavami, Saeid, et al. (författare)
  • S100A8/A9 induces autophagy and apoptosis via ROS-mediated cross-talk between mitochondria and lysosomes that involves BNIP3
  • 2010
  • Ingår i: Cell Research. - : Springer Science and Business Media LLC. - 1001-0602 .- 1748-7838. ; 20:3, s. 314-331
  • Tidskriftsartikel (refereegranskat)abstract
    • The complex formed by two members of the S100 calcium-binding protein family, S100A8/A9, exerts apoptosis-inducing activity in various cells of different origins. Here, we present evidence that the underlying molecular mechanisms involve both programmed cell death I (PCD I, apoptosis) and PCD II (autophagy)-like death. Treatment of cells with S100A8/A9 caused the increase of Beclin-1 expression as well as Atg12-Atg5 formation. S100A8/A9-induced cell death was partially inhibited by the specific PI3-kinase class III inhibitor, 3-methyladenine (3-MA), and by the vacuole H+-ATPase inhibitor, bafilomycin-A1 (Baf-A1). S100A8/A9 provoked the translocation of BNIP3, a BH3 only pro-apoptotic Bcl2 family member, to mitochondria. Consistent with this finding, ΔTM-BNIP3 overexpression partially inhibited S100A8/A9-induced cell death, decreased reactive oxygen species (ROS) generation, and partially protected against the decrease in mitochondrial transmembrane potential in S100A8/A9-treated cells. In addition, either ΔTM-BNIP3 overexpression or N-acetyl-L-cysteine co-treatment decreased lysosomal activation in cells treated with S100A8/A9. Our data indicate that S100A8/A9-promoted cell death occurs through the cross-talk of mitochondria and lysosomes via ROS and the process involves BNIP3.
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9.
  • Guo, Jingtao, et al. (författare)
  • The adult human testis transcriptional cell atlas
  • 2018
  • Ingår i: Cell Research. - : INST BIOCHEMISTRY & CELL BIOLOGY. - 1001-0602 .- 1748-7838. ; 28, s. 1141-1157
  • Tidskriftsartikel (refereegranskat)abstract
    • Human adult spermatogenesis balances spermatogonial stem cell (SSC) self-renewal and differentiation, alongside complex germ cell-niche interactions, to ensure long-term fertility and faithful genome propagation. Here, we performed single-cell RNA sequencing of similar to 6500 testicular cells from young adults. We found five niche/somatic cell types (Leydig, myoid, Sertoli, endothelial, macrophage), and observed germline-niche interactions and key human-mouse differences. Spermatogenesis, including meiosis, was reconstructed computationally, revealing sequential coding, non-coding, and repeat-element transcriptional signatures. Interestingly, we identified five discrete transcriptional/developmental spermatogonial states, including a novel early SSC state, termed State 0. Epigenetic features and nascent transcription analyses suggested developmental plasticity within spermatogonial States. To understand the origin of State 0, we profiled testicular cells from infants, and identified distinct similarities between adult State 0 and infant SSCs. Overall, our datasets describe key transcriptional and epigenetic signatures of the normal adult human testis, and provide new insights into germ cell developmental transitions and plasticity.
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  • Jiang, Lei, et al. (författare)
  • Arabidopsis STO/BBX24 negatively regulates UV-B signaling by interacting with COP1 and repressing HY5 transcriptional activity
  • 2012
  • Ingår i: Cell Research. - : Springer Science and Business Media LLC. - 1748-7838 .- 1001-0602. ; 22, s. 1046-1057
  • Tidskriftsartikel (refereegranskat)abstract
    • UV-B (280-315 nm) is an integral part of solar radiation and can act either as a stress inducer or as a developmental signal. In recent years, increasing attention has been paid to the low-fluence UV-B-induced photomorphogenic response and several key players in this response have been identified, which include UVR8 (a UV-B-specific photoreceptor), COP1 (a WD40-repeat-containing RING finger protein), HY5 (a basic zipper transcription factor), and RUP1/2 (two UVR8-interacting proteins). Here we report that Arabidopsis SALT TOLERANCE (STO/BBX24), a known regulator for light signaling in plants, defines a new signaling component in UV-B-mediated photomorphogenesis. The bbx24 mutant is hypersensitive to UV-B radiation and becomes extremely dwarfed under UV-B treatment. By contrast, BBX24 overexpression transgenic lines respond much more weakly to UV-B than the bbx24 and wild-type plants. BBX24 expression is UV-B-inducible and its accumulation under UV-B requires COP1. Co-immunoprecipitation experiments indicate that BBX24 interacts with COP1 in planta upon UV-B illumination. Moreover, BBX24 interacts with HY5 and acts antagonistically with HY5 in UV-B-induced inhibition of hypocotyl elongation. Furthermore, BBX24 attenuates UV-B-induced HY5 accumulation and suppresses its transcription-activation activity. Taken together, our results reveal a previously uncharacterized function of the light-regulated BBX24 in UV-B responses and demonstrate that BBX24 functions as a negative regulator of photomorphogenic UV-B responses by interacting with both COP1 and HY5. The UV-B-inducible expression pattern and its suppression of HY5 activity suggest that BBX24 could be a new component of the feedback regulatory module of UV-B signaling in plants.
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  • Lian, XJ, et al. (författare)
  • The years of the monkey
  • 2013
  • Ingår i: Cell research. - : Springer Science and Business Media LLC. - 1748-7838 .- 1001-0602. ; 23:10, s. 1161-1162
  • Tidskriftsartikel (refereegranskat)
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  • Lönn, Peter, et al. (författare)
  • Regulating the stability of TGFβ receptors and Smads
  • 2009
  • Ingår i: Cell Research. - : IBCB, SIBS, CAS. - 1001-0602 .- 1748-7838. ; 19:1, s. 21-35
  • Forskningsöversikt (refereegranskat)abstract
    • Transforming growth factor beta (TGFbeta) controls cellular behavior in embryonic and adult tissues. TGFbeta binding to serine/threonine kinase receptors on the plasma membrane activates Smad molecules and additional signaling proteins that together regulate gene expression. In this review, mechanisms and models that aim at explaining the coordination between several components of the signaling network downstream of TGFbeta are presented. We discuss how the activity and duration of TGFbeta receptor/Smad signaling can be regulated by post-translational modifications that affect the stability of key proteins in the pathway. We highlight links between these mechanisms and human diseases, such as tissue fibrosis and cancer.
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  • Mazzurana, Luca, et al. (författare)
  • Tissue-specific transcriptional imprinting and heterogeneity in human innate lymphoid cells revealed by full-length single-cell RNA-sequencing
  • 2021
  • Ingår i: Cell Research. - : Springer Science and Business Media LLC. - 1748-7838 .- 1001-0602. ; 31:5, s. 554-568
  • Tidskriftsartikel (refereegranskat)abstract
    • The impact of the microenvironment on innate lymphoid cell (ILC)-mediated immunity in humans remains largely unknown. Here we used full-length Smart-seq2 single-cell RNA-sequencing to unravel tissue-specific transcriptional profiles and heterogeneity of CD127+ ILCs across four human tissues. Correlation analysis identified gene modules characterizing the migratory properties of tonsil and blood ILCs, and signatures of tissue-residency, activation and modified metabolism in colon and lung ILCs. Trajectory analysis revealed potential differentiation pathways from circulating and tissue-resident naïve ILCs to a spectrum of mature ILC subsets. In the lung we identified both CRTH2+ and CRTH2− ILC2 with lung-specific signatures, which could be recapitulated by alarmin-exposure of circulating ILC2. Finally, we describe unique TCR-V(D)J-rearrangement patterns of blood ILC1-like cells, revealing a subset of potentially immature ILCs with TCR-δ rearrangement. Our study provides a useful resource for in-depth understanding of ILC-mediated immunity in humans, with implications for disease.
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18.
  • Pang, KL, et al. (författare)
  • An App knock-in rat model for Alzheimer's disease exhibiting Aβ and tau pathologies, neuronal death and cognitive impairments
  • 2022
  • Ingår i: Cell research. - : Springer Science and Business Media LLC. - 1748-7838 .- 1001-0602. ; 32:2, s. 157-175
  • Tidskriftsartikel (refereegranskat)abstract
    • A major obstacle in Alzheimer’s disease (AD) research is the lack of predictive and translatable animal models that reflect disease progression and drug efficacy. Transgenic mice overexpressing amyloid precursor protein (App) gene manifest non-physiological and ectopic expression of APP and its fragments in the brain, which is not observed in AD patients. The App knock-in mice circumvented some of these problems, but they do not exhibit tau pathology and neuronal death. We have generated a rat model, with three familiar App mutations and humanized Aβ sequence knocked into the rat App gene. Without altering the levels of full-length APP and other APP fragments, this model exhibits pathologies and disease progression resembling those in human patients: deposit of Aβ plaques in relevant brain regions, microglia activation and gliosis, progressive synaptic degeneration and AD-relevant cognitive deficits. Interestingly, we have observed tau pathology, neuronal apoptosis and necroptosis and brain atrophy, phenotypes rarely seen in other APP models. This App knock-in rat model may serve as a useful tool for AD research, identifying new drug targets and biomarkers, and testing therapeutics.
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  • Parmar, Malin, et al. (författare)
  • Turning skin into dopamine neurons.
  • 2011
  • Ingår i: Cell Research. - : Springer Science and Business Media LLC. - 1748-7838 .- 1001-0602. ; 21, s. 1386-1387
  • Tidskriftsartikel (refereegranskat)
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  • Vitale, I, et al. (författare)
  • Spontaneous DNA damage propels tumorigenicity
  • 2017
  • Ingår i: Cell research. - : Springer Science and Business Media LLC. - 1748-7838 .- 1001-0602. ; 27:6, s. 720-721
  • Tidskriftsartikel (refereegranskat)
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36.
  • Wang, Guo-Dong, et al. (författare)
  • Out of southern East Asia : the natural history of domestic dogs across the world
  • 2016
  • Ingår i: Cell Research. - : Nature Publishing Group. - 1001-0602 .- 1748-7838. ; 26:1, s. 21-33
  • Tidskriftsartikel (refereegranskat)abstract
    • The origin and evolution of the domestic dog remains a controversial question for the scientific community, with basic aspects such as the place and date of origin, and the number of times dogs were domesticated, open to dispute. Using whole genome sequences from a total of 58 canids (12 gray wolves, 27 primitive dogs from Asia and Africa, and a collection of 19 diverse breeds from across the world), we find that dogs from southern East Asia have significantly higher genetic diversity compared to other populations, and are the most basal group relating to gray wolves, indicating an ancient origin of domestic dogs in southern East Asia 33 000 years ago. Around 15 000 years ago, a subset of ancestral dogs started migrating to the Middle East, Africa and Europe, arriving in Europe at about 10 000 years ago. One of the out of Asia lineages also migrated back to the east, creating a series of admixed populations with the endemic Asian lineages in northern China before migrating to the New World. For the first time, our study unravels an extraordinary journey that the domestic dog has traveled on earth.
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  • Zhu, RJ, et al. (författare)
  • Mesenchymal stem cell treatment improves outcome of COVID-19 patients via multiple immunomodulatory mechanisms
  • 2021
  • Ingår i: Cell research. - : Springer Science and Business Media LLC. - 1748-7838 .- 1001-0602. ; 31:12, s. 1244-1262
  • Tidskriftsartikel (refereegranskat)abstract
    • The infusion of coronavirus disease 2019 (COVID-19) patients with mesenchymal stem cells (MSCs) potentially improves clinical symptoms, but the underlying mechanism remains unclear. We conducted a randomized, single-blind, placebo-controlled (29 patients/group) phase II clinical trial to validate previous findings and explore the potential mechanisms. Patients treated with umbilical cord-derived MSCs exhibited a shorter hospital stay (P = 0.0198) and less time required for symptoms remission (P = 0.0194) than those who received placebo. Based on chest images, both severe and critical patients treated with MSCs showed improvement by day 7 (P = 0.0099) and day 21 (P = 0.0084). MSC-treated patients had fewer adverse events. MSC infusion reduced the levels of C-reactive protein, proinflammatory cytokines, and neutrophil extracellular traps (NETs) and promoted the maintenance of SARS-CoV-2-specific antibodies. To explore how MSCs modulate the immune system, we employed single-cell RNA sequencing analysis on peripheral blood. Our analysis identified a novel subpopulation of VNN2+ hematopoietic stem/progenitor-like (HSPC-like) cells expressing CSF3R and PTPRE that were mobilized following MSC infusion. Genes encoding chemotaxis factors — CX3CR1 and L-selectin — were upregulated in various immune cells. MSC treatment also regulated B cell subsets and increased the expression of costimulatory CD28 in T cells in vivo and in vitro. In addition, an in vivo mouse study confirmed that MSCs suppressed NET release and reduced venous thrombosis by upregulating kindlin-3 signaling. Together, our results underscore the role of MSCs in improving COVID-19 patient outcomes via maintenance of immune homeostasis.
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42.
  • Zitvogel, L, et al. (författare)
  • Interferon-γ induces cancer cell ferroptosis
  • 2019
  • Ingår i: Cell research. - : Springer Science and Business Media LLC. - 1748-7838 .- 1001-0602. ; 29:9, s. 692-693
  • Tidskriftsartikel (refereegranskat)
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