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- Hildebrand, S, et al.
(författare)
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The E-cadherin/AmotL2 complex organizes actin filaments required for epithelial hexagonal packing and blastocyst hatching
- 2017
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Ingår i: Scientific reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 7:1, s. 9540-
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Tidskriftsartikel (refereegranskat)abstract
- Epithelial cells connect via cell-cell junctions to form sheets of cells with separate cellular compartments. These cellular connections are essential for the generation of cellular forms and shapes consistent with organ function. Tissue modulation is dependent on the fine-tuning of mechanical forces that are transmitted in part through the actin connection to E-cadherin as well as other components in the adherens junctions. In this report we show that p100 amotL2 forms a complex with E-cadherin that associates with radial actin filaments connecting cells over multiple layers. Genetic inactivation or depletion of amotL2 in epithelial cells in vitro or zebrafish and mouse in vivo, resulted in the loss of contractile actin filaments and perturbed epithelial packing geometry. We further showed that AMOTL2 mRNA and protein was expressed in the trophectoderm of human and mouse blastocysts. Genetic inactivation of amotL2 did not affect cellular differentiation but blocked hatching of the blastocysts from the zona pellucida. These results were mimicked by treatment with the myosin II inhibitor blebbistatin. We propose that the tension generated by the E-cadherin/AmotL2/actin filaments plays a crucial role in developmental processes such as epithelial geometrical packing as well as generation of forces required for blastocyst hatching.
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- Jouhilahti, EM, et al.
(författare)
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The human PRD-like homeobox gene LEUTX has a central role in embryo genome activation
- 2016
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Ingår i: Development (Cambridge, England). - : The Company of Biologists. - 1477-9129 .- 0950-1991. ; 143:19, s. 3459-3469
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Tidskriftsartikel (refereegranskat)abstract
- Leucine twenty homeobox gene (LEUTX) is a PAIRED (PRD)-like homeobox gene that is expressed nearly exclusively in human preimplantation embryos. We previously identified a novel transcription start site for the predicted human LEUTX gene based on the transcriptional analysis of human preimplantation embryos. The novel variant encodes a protein with a complete homeodomain. Here we provide a detailed description of the molecular cloning of the complete homeodomain-containing LEUTX. Using a human embryonic stem cell overexpression model we show that the complete homeodomain isoform is functional and sufficient to activate the transcription of a large fraction of the genes found upregulated in human embryo genome activation, whereas the previously predicted partial homeodomain isoform is largely inactive. Another PRD-like transcription factor, DPRX, appears as a powerful repressor of transcription. We propose a two-stage model of human EGA in which LEUTX acts as a transcriptional activator at 4-cell stage, and DPRX as a balancing repressor at 8-cell stage. We conclude that LEUTX is a candidate regulator of human embryo genome activation.
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- Wagner, M, et al.
(författare)
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Single-cell analysis of human ovarian cortex identifies distinct cell populations but no oogonial stem cells
- 2020
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Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 11:1, s. 1147-
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Tidskriftsartikel (refereegranskat)abstract
- The human ovary orchestrates sex hormone production and undergoes monthly structural changes to release mature oocytes. The outer lining of the ovary (cortex) has a key role in defining fertility in women as it harbors the ovarian reserve. It has been postulated that putative oogonial stem cells exist in the ovarian cortex and that these can be captured by DDX4 antibody isolation. Here, we report single-cell transcriptomes and cell surface antigen profiles of over 24,000 cells from high quality ovarian cortex samples from 21 patients. Our data identify transcriptional profiles of six main cell types; oocytes, granulosa cells, immune cells, endothelial cells, perivascular cells, and stromal cells. Cells captured by DDX4 antibody are perivascular cells, not oogonial stem cells. Our data do not support the existence of germline stem cells in adult human ovaries, thereby reinforcing the dogma of a limited ovarian reserve.
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- Parmigiani, Francesca, et al.
(författare)
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All-Optical Phase Regeneration of 40Gbit/s DPSK Signals in a Black‐Box Phase Sensitive Amplifier
- 2010
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Ingår i: 2010 Conference on Optical Fiber Communication, Collocated National Fiber Optic Engineers Conference, OFC/NFOEC 2010; San Diego, CA; United States; 21 March 2010 through 25 March 2010. - 9781557528841 ; , s. PDPC3-
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Konferensbidrag (refereegranskat)abstract
- We present a black‐box four wave mixingbased bit‐rate‐flexible phase sensitive amplifier and use it in the first demonstration of 40 Gbit/s DPSK phaseregeneration.
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- Bloise, E, et al.
(författare)
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Acute Effects of Viral Exposure on P-Glycoprotein Function in the Mouse Fetal Blood-Brain Barrier
- 2017
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Ingår i: Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology. - : S. Karger AG. - 1421-9778. ; 41:3, s. 1044-1050
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Tidskriftsartikel (refereegranskat)abstract
- Background/Aims: Viral infection during pregnancy is known to affect the fetal brain. The toll-like receptor (TLR)-3 is a pattern recognition receptor activated by viruses known to elicit adverse fetal neurological outcomes. The P-glycoprotein (P-gp) efflux transporter protects the developing fetus by limiting the transfer of substrates across both the placenta and the fetal blood-brain barrier (BBB). As such, inhibition of P-gp at these blood-barrier sites may result in increased exposure of the developing fetus to environmental toxins and xenobiotics present in the maternal circulation. We hypothesized that viral exposure during pregnancy would impair P-gp function in the placenta and in the developing BBB. Here we investigated whether the TLR-3 ligand, polyinosinic:polycytidylic acid (PolyI:C), increased accumulation of one P-gp substrate in the fetus and in the developing fetal brain. Methods: Pregnant C57BL/6 mice (GD15.5) were injected (i.p.) with PolyI:C (5 mg/kg or 10 mg/kg) or vehicle (saline). [3H]digoxin (P-gp substrate) was injected (i.v.) 3 or 23h post-treatment and animals were euthanized 1h later. Maternal plasma, ‘fetal-units’ (fetal membranes, amniotic fluid and whole fetus), and fetal brains were collected. Results: PolyI:C exposure (4h) significantly elevated maternal plasma IL-6 (P<0.001) and increased [3H]digoxin accumulation in the fetal brain (P<0.05). In contrast, 24h after PolyI:C exposure, no effect on IL-6 or fetal brain accumulation of P-gp substrate was observed. Conclusion: Viral infection modeled by PolyI:C causes acute increases in fetal brain accumulation of P-gp substrates and by doing so, may increase fetal brain exposure to xenobiotics and environmental toxins present in the maternal circulation.
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- Chen, G, et al.
(författare)
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Single-cell analyses of X Chromosome inactivation dynamics and pluripotency during differentiation
- 2016
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Ingår i: Genome research. - : Cold Spring Harbor Laboratory. - 1549-5469 .- 1088-9051. ; 26:10, s. 1342-1354
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Tidskriftsartikel (refereegranskat)abstract
- Pluripotency, differentiation, and X Chromosome inactivation (XCI) are key aspects of embryonic development. However, the underlying relationship and mechanisms among these processes remain unclear. Here, we systematically dissected these features along developmental progression using mouse embryonic stem cells (mESCs) and single-cell RNA sequencing with allelic resolution. We found that mESCs grown in a ground state 2i condition displayed transcriptomic profiles diffused from preimplantation mouse embryonic cells, whereas EpiStem cells closely resembled the post-implantation epiblast. Sex-related gene expression varied greatly across distinct developmental states. We also identified novel markers that were highly enriched in each developmental state. Moreover, we revealed that several novel pathways, including PluriNetWork and Focal Adhesion, were responsible for the delayed progression of female EpiStem cells. Importantly, we “digitalized” XCI progression using allelic expression of active and inactive X Chromosomes and surprisingly found that XCI states exhibited profound variability in each developmental state, including the 2i condition. XCI progression was not tightly synchronized with loss of pluripotency and increase of differentiation at the single-cell level, although these processes were globally correlated. In addition, highly expressed genes, including core pluripotency factors, were in general biallelically expressed. Taken together, our study sheds light on the dynamics of XCI progression and the asynchronicity between pluripotency, differentiation, and XCI.
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| 38. |
- Ellis, A. D., et al.
(författare)
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Future Directions to Realize Ultra-High Bit-Rate Transmission Systems
- 2010
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Ingår i: Proceedings of OptoElectronics and Communications Conference, OECC 2010, Sapporo, Japan, 5-9 July 2010, invited paper..
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- In this paper we examine two potential future directions for the realization of ultra-high bit rate transmission systems.
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| 39. |
- Kumar, B, et al.
(författare)
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Polycomb repressive complex 2 shields naïve human pluripotent cells from trophectoderm differentiation
- 2022
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Ingår i: Nature cell biology. - : Springer Science and Business Media LLC. - 1476-4679 .- 1465-7392. ; 24:6, s. 845-
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Tidskriftsartikel (refereegranskat)abstract
- The first lineage choice in human embryo development separates trophectoderm from the inner cell mass. Naïve human embryonic stem cells are derived from the inner cell mass and offer possibilities to explore how lineage integrity is maintained. Here, we discover that polycomb repressive complex 2 (PRC2) maintains naïve pluripotency and restricts differentiation to trophectoderm and mesoderm lineages. Through quantitative epigenome profiling, we found that a broad gain of histone H3 lysine 27 trimethylation (H3K27me3) is a distinct feature of naïve pluripotency. We define shared and naïve-specific bivalent promoters featuring PRC2-mediated H3K27me3 concomitant with H3K4me3. Naïve bivalency maintains key trophectoderm and mesoderm transcription factors in a transcriptionally poised state. Inhibition of PRC2 forces naïve human embryonic stem cells into an ‘activated’ state, characterized by co-expression of pluripotency and lineage-specific transcription factors, followed by differentiation into either trophectoderm or mesoderm lineages. In summary, PRC2-mediated repression provides a highly adaptive mechanism to restrict lineage potential during early human development.
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| 40. |
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| 41. |
- Liu, S., et al.
(författare)
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OTDM to WDM format conversion based on cascaded SHG/DFG in a single PPLN waveguide
- 2010
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Ingår i: Optics InfoBase Conference Papers. - Washington, D.C. : Optical Society of America (OSA).
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Konferensbidrag (refereegranskat)abstract
- We propose and experimentally demonstrate error-free OTDM to WDM format conversion based on cSHG/DFG within a 30mm-long PPLN waveguide and a time-to-frequency domain conversion approach, which relies upon switching a linearly chirped pulse.
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| 45. |
- Marhic, M. E., et al.
(författare)
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Fiber optical parametric amplifiers in optical communication systems
- 2015
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Ingår i: Laser and Photonics Reviews. - : Wiley. - 1863-8899 .- 1863-8880. ; 9:1, s. 50-74
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Forskningsöversikt (refereegranskat)abstract
- The prospects for using fiber optical parametric amplifiers (OPAs) in optical communication systems are reviewed. Phase-insensitive amplifiers (PIAs) and phase-sensitive amplifiers (PSAs) are considered. Low-penalty amplification at/or near 1 Tb/s has been achieved, for both wavelength- and time-division multiplexed formats. High-quality mid-span spectral inversion has been demonstrated at 0.64 Tb/s, avoiding electronic dispersion compensation. All-optical amplitude regeneration of amplitude-modulated signals has been performed, while PSAs have been used to demonstrate phase regeneration of phase-modulated signals. A PSA with 1.1-dB noise figure has been demonstrated, and preliminary wavelength-division multiplexing experiments have been performed with PSAs. 512Gb/s have been transmitted over 6,000km by periodic phase conjugation. Simulations indicate that PIAs could reach data rate x reach products in excess of 14,000 Tb/s x km in realistic wavelength-division multiplexed long-haul networks. Technical challenges remaining to be addressed in order for fiber OPAs to become useful for long-haul communication networks are discussed.
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| 46. |
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| 47. |
- Petropoulos, F., et al.
(författare)
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Operational Research : methods and applications
- 2024
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Ingår i: Journal of the Operational Research Society. - : Taylor and Francis Ltd.. - 0160-5682 .- 1476-9360.
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Forskningsöversikt (refereegranskat)abstract
- Throughout its history, Operational Research has evolved to include methods, models and algorithms that have been applied to a wide range of contexts. This encyclopedic article consists of two main sections: methods and applications. The first summarises the up-to-date knowledge and provides an overview of the state-of-the-art methods and key developments in the various subdomains of the field. The second offers a wide-ranging list of areas where Operational Research has been applied. The article is meant to be read in a nonlinear fashion and used as a point of reference by a diverse pool of readers: academics, researchers, students, and practitioners. The entries within the methods and applications sections are presented in alphabetical order. The authors dedicate this paper to the 2023 Turkey/Syria earthquake victims. We sincerely hope that advances in OR will play a role towards minimising the pain and suffering caused by this and future catastrophes.
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| 48. |
- Petropoulos, Fotios, et al.
(författare)
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Operational Research : methods and applications
- 2024
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Ingår i: Journal of the Operational Research Society. - : Taylor & Francis Group. - 0160-5682 .- 1476-9360. ; 75:3, s. 423-617
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Forskningsöversikt (refereegranskat)abstract
- Throughout its history, Operational Research has evolved to include methods, models and algorithms that have been applied to a wide range of contexts. This encyclopedic article consists of two main sections: methods and applications. The first summarises the up-to-date knowledge and provides an overview of the state-of-the-art methods and key developments in the various subdomains of the field. The second offers a wide-ranging list of areas where Operational Research has been applied. The article is meant to be read in a nonlinear fashion and used as a point of reference by a diverse pool of readers: academics, researchers, students, and practitioners. The entries within the methods and applications sections are presented in alphabetical order. The authors dedicate this paper to the 2023 Turkey/Syria earthquake victims. We sincerely hope that advances in OR will play a role towards minimising the pain and suffering caused by this and future catastrophes.
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