121 results match your criteria triggering exit

Coordination of asparagine uptake and asparagine synthetase expression modulates CD8+ T cell activation.

JCI Insight 2021 Apr 6. Epub 2021 Apr 6.

Leeds Institute of Medical Research at St. James's, University of Leeds, St. James's University HospitalFaculty of Medicine and, Leeds, United Kingdom.

T cell receptor (TCR) triggering by antigen results in metabolic reprogramming that, in turn, facilitates T cells' exit from quiescence. The increased nutrient requirements of activated lymphocytes are met in part by upregulation of cell surface transporters and enhanced uptake of amino acids, fatty acids and glucose from the environment. However, the role of intracellular pathways of amino acid biosynthesis in T cell activation is relatively unexplored. Read More

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OGP46 Induces Differentiation of Acute Myeloid Leukemia Cells via Different Optimal Signaling Pathways.

Front Cell Dev Biol 2021 4;9:652972. Epub 2021 Mar 4.

Department of Pharmaceutical Sciences, College of Pharmacy and Health Sciences, St. John's University, New York, NY, United States.

Acute myelogenous leukemia (AML) is characterized by blockage of cell differentiation leading to the accumulation of immature cells, which is the most prevalent form of acute leukemia in adults. It is well known that all-trans retinoic acid (ATRA) and arsenic trioxide (ATO) are the preferred drugs for acute promyelocytic leukemia (APL). However, they can lead to irreversible resistance which may be responsible for clinical failure after complete remission (CR). Read More

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Myosins, an Underestimated Player in the Infectious Cycle of Pathogenic Bacteria.

Int J Mol Sci 2021 Jan 9;22(2). Epub 2021 Jan 9.

CIRI, Centre International de Recherche en Infectiologie, Legionella Pathogenesis Group, Université de Lyon, 69007 Lyon, France.

Myosins play a key role in many cellular processes such as cell migration, adhesion, intracellular trafficking and internalization processes, making them ideal targets for bacteria. Through selected examples, such as enteropathogenic (EPEC), , , , or , this review aims to illustrate how bacteria target and hijack host cell myosins in order to adhere to the cell, to enter the cell by triggering their internalization, to evade from the cytosolic autonomous cell defense, to promote the biogenesis of intracellular replicative niche, to disseminate in tissues by cell-to-cell spreading, to exit out the host cell, and also to evade from macrophage phagocytosis. It highlights the diversity and sophistication of the strategy evolved by bacteria to manipulate one of their privileged targets, the actin cytoskeleton. Read More

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January 2021

In Vivo Pre-Instructed HSCs Robustly Execute Asymmetric Cell Divisions In Vitro.

Int J Mol Sci 2020 Nov 3;21(21). Epub 2020 Nov 3.

Institute of Bioengineering, Laboratory of Stem Cell Bioengineering, Ecole Polytechnique Fédérale de Lausanne (EPFL), CH-1015 Lausanne, Switzerland.

Hematopoietic stem cells (HSCs) are responsible for life-long production of all mature blood cells. Under homeostasis, HSCs in their native bone marrow niches are believed to undergo asymmetric cell divisions (ACDs), with one daughter cell maintaining HSC identity and the other committing to differentiate into various mature blood cell types. Due to the lack of key niche signals, in vitro HSCs differentiate rapidly, making it challenging to capture and study ACD. Read More

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November 2020

Ordered dephosphorylation initiated by the selective proteolysis of cyclin B drives mitotic exit.

Elife 2020 09 1;9. Epub 2020 Sep 1.

Department of Biochemistry, University of Oxford, Oxford, United Kingdom.

APC/C-mediated proteolysis of cyclin B and securin promotes anaphase entry, inactivating CDK1 and permitting chromosome segregation, respectively. Reduction of CDK1 activity relieves inhibition of the CDK1-counteracting phosphatases PP1 and PP2A-B55, allowing wide-spread dephosphorylation of substrates. Meanwhile, continued APC/C activity promotes proteolysis of other mitotic regulators. Read More

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September 2020

Anti-Müllerian hormone (Amh/amh) plays dual roles in maintaining gonadal homeostasis and gametogenesis in zebrafish.

Mol Cell Endocrinol 2020 11 31;517:110963. Epub 2020 Jul 31.

Centre of Reproduction, Development and Aging (CRDA), Faculty of Health Sciences, University of Macau, Taipa, Macau. Electronic address:

Anti-Müllerian hormone (AMH/Amh) plays a role in gonadal differentiation and function across vertebrates. In zebrafish we demonstrated that Amh deficiency caused severe gonadal dysgenesis and dysfunction. The mutant gonads showed extreme hypertrophy with accumulation of early germ cells in both sexes, namely spermatogonia in the testis and primary growth oocytes in the ovary. Read More

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November 2020

Adult Human Glioblastomas Harbor Radial Glia-like Cells.

Stem Cell Reports 2020 02 30;14(2):338-350. Epub 2020 Jan 30.

Department of Neurosurgery, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA. Electronic address:

Radial glia (RG) cells are the first neural stem cells to appear during embryonic development. Adult human glioblastomas harbor a subpopulation of RG-like cells with typical RG morphology and markers. The cells exhibit the classic and unique mitotic behavior of normal RG in a cell-autonomous manner. Read More

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February 2020

Engaging with change: Information and communication technology professionals' perspectives on change at the mid-point in the UK/EU Brexit process.

PLoS One 2020 6;15(1):e0227089. Epub 2020 Jan 6.

Department of Computer and Information Sciences, iSchool, Northumbria University, Newcastle-Upon-Tyne, England, United Kingdom.

Background: Information and Communication Technology (ICT) has been a key agent of change in the 21st century. Given the role of ICT in changing society, this research explores the responses and attitudes to change over time from ICT professionals and ICT academics in dealing with the potentially far reaching political challenge triggered by the UK's 2016 European Union Referendum and its decision to leave the European Union (Brexit). Whilst the vote was a UK based decision its ramifications have global implications and as such the research was not confined to the UK. Read More

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Exploring Reactive Conformations of Coenzyme A during Binding and Unbinding to Pyruvate Formate-Lyase.

J Phys Chem A 2019 Oct 17;123(43):9345-9356. Epub 2019 Oct 17.

Group for Computational Life Sciences, Division for Physical Chemistry , Ruđer Bošković Institute , Bijenička cesta 54 , 10000 Zagreb , Croatia.

Pyruvate formate-lyase (PFL) is a glycyl radical enzyme that converts pyruvate and coenzyme A (CoA) into formate and acetyl-CoA in two half-reactions. Recently, we showed that the acetylation of the PFL active site in the first half-reaction induces subtle conformational changes, leading to the opening of a potential channel for CoA entry. Entry of CoA into the active site is crucial for the second half-reaction, involving the acetyl transfer to CoA, and the completion of the catalytic cycle. Read More

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October 2019

The autophagic protein LC3 translocates to the nucleus and localizes in the nucleolus associated to NUFIP1 in response to cyclic mechanical stress.

Autophagy 2020 07 16;16(7):1248-1261. Epub 2019 Sep 16.

Department of Ophthalmology, Duke Eye Center, Duke University , Durham, NC, USA.

The trabecular meshwork (TM) is a key regulatory tissue of intraocular pressure (IOP) in the anterior chamber of eye. Dysfunction of the TM causes resistance to outflow of aqueous humor, which in turn leads to elevated IOP, a main risk factor of glaucomatous neurodegeneration. Due to variations in IOP, TM cells are continuously exposed to mechanical deformations. Read More

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Expression of Mammalian BM88/CEND1 in Drosophila Affects Nervous System Development by Interfering with Precursor Cell Formation.

Neurosci Bull 2019 Dec 11;35(6):979-995. Epub 2019 May 11.

"Alexander Fleming" Biomedical Sciences Research Centre, 16672, Athens, Greece.

We used Drosophila melanogaster as an experimental model to express mouse and pig BM88/CEND1 (cell cycle exit and neuronal differentiation 1) in order to investigate its potential functional effects on Drosophila neurogenesis. BM88/CEND1 is a neuron-specific protein whose function is implicated in triggering cells to exit from the cell cycle and differentiate towards a neuronal phenotype. Transgenic flies expressing either mouse or pig BM88/CEND1 in the nervous system had severe neuronal phenotypes with variable expressivity at various stages of embryonic development. Read More

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December 2019

Imbalance of the spindle-assembly checkpoint promotes spindle poison-mediated cytotoxicity with distinct kinetics.

Cell Death Dis 2019 04 5;10(4):314. Epub 2019 Apr 5.

Division of Life Science, Center for Cancer Research, and State Key Laboratory of Molecular Neuroscience, Hong Kong University of Science and Technology, Clear Water Bay, Hong Kong.

Disrupting microtubule dynamics with spindle poisons activates the spindle-assembly checkpoint (SAC) and induces mitotic cell death. However, mitotic exit can occur prematurely without proper chromosomal segregation or cytokinesis by a process termed mitotic slippage. It remains controversial whether mitotic slippage increases the cytotoxicity of spindle poisons or the converse. Read More

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Triggering the Resolution of Immune Mediated Inflammatory Diseases: Can Targeting Leukocyte Migration Be the Answer?

Front Pharmacol 2019 1;10:184. Epub 2019 Mar 1.

Rheumatology Research Group, Arthritis Research UK Centre of Excellence in the Pathogenesis of Rheumatoid Arthritis, Institute of Inflammation and Ageing, University of Birmingham, Birmingham, United Kingdom.

Leukocyte recruitment is a pivotal process in the regulation and resolution of an inflammatory episode. It is vital for the protective responses to microbial infection and tissue damage, but is the unwanted reaction contributing to pathology in many immune mediated inflammatory diseases (IMIDs). Indeed, it is now recognized that patients with IMIDs have defects in at least one, if not multiple, check-points regulating the entry and exit of leukocytes from the inflamed site. Read More

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Impressionist portraits of mitotic exit: APC/C, K11-linked ubiquitin chains and Cezanne.

Cell Cycle 2019 Mar - Apr;18(6-7):652-660. Epub 2019 Mar 28.

a Lineberger Comprehensive Cancer Center , University of North Carolina , Chapel Hill , NC , USA.

The Anaphase-Promoting Complex/Cyclosome (APC/C) is an E3 ubiquitin ligase and a key regulator of cell cycle progression. By triggering the degradation of mitotic cyclins, APC/C controls cell cycle-dependent oscillations in cyclin-dependent kinase (CDK) activity. Thus, the dynamic activities of both APC/C and CDK sit at the core of the cell cycle oscillator. Read More

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CD62L Is a Functional and Phenotypic Marker for Circulating Innate Lymphoid Cell Precursors.

J Immunol 2019 01 30;202(1):171-182. Epub 2018 Nov 30.

Department of Molecular Cell Biology and Immunology, VU University Medical Center, 1081AZ Amsterdam, the Netherlands;

Innate lymphoid cells (ILCs) guard epithelial tissue integrity during homeostasis, but can be potent immune effector cells during inflammation. Precursors to all ILC subsets (ILC precursors [ILCP]) have been identified in human peripheral blood (PB). We found that during homeostasis, ILCP in PB of mouse and human expressed homing receptors for secondary lymphoid organs, mainly CD62L. Read More

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January 2019

Mitosis inhibitors in anticancer therapy: When blocking the exit becomes a solution.

Cancer Lett 2019 01 9;440-441:64-81. Epub 2018 Oct 9.

CESPU, Instituto de Investigação e Formação Avançada Em Ciências e Tecnologias da Saúde, Instituto Universitário de Ciências da Saúde, Gandra PRD, Portugal; Centro Interdisciplinar de Investigação Marinha e Ambiental (CIIMAR/CIMAR), Universidade Do Porto, Porto, Portugal. Electronic address:

Current microtubule-targeting agents (MTAs) remain amongst the most important antimitotic drugs used against a broad range of malignancies. By perturbing spindle assembly, MTAs activate the spindle assembly checkpoint (SAC), which induces mitotic arrest and subsequent apoptosis. However, besides toxic side effects and resistance, mitotic slippage and failure in triggering apoptosis in various cancer cells are limiting factors of MTAs efficacy. Read More

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January 2019

Regulation of Leukocytes by TspanC8 Tetraspanins and the "Molecular Scissor" ADAM10.

Front Immunol 2018 2;9:1451. Epub 2018 Jul 2.

School of Biosciences, College of Life and Environmental Sciences, University of Birmingham, Birmingham, United Kingdom.

A disintegrin and metalloproteinase 10 (ADAM10) is a ubiquitous transmembrane protein that functions as a "molecular scissor" to cleave the extracellular regions from its transmembrane target proteins. ADAM10 is well characterized as the ligand-dependent activator of Notch proteins, which control cell fate decisions. Indeed, conditional knockouts of ADAM10 in mice reveal impaired B-, T-, and myeloid cell development and/or function. Read More

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Minimally invasive thread trigger digit release: a preliminary report on 34 digits of the adult hands.

J Hand Surg Eur Vol 2018 Nov 15;43(9):942-947. Epub 2018 May 15.

1 BayCare Clinic, Green Bay, WI, USA.

The trigger finger release was performed in 34 digits (11 thumbs and 23 fingers) of 24 patients through the thread transecting technique with the tip-to-tip approach, in which a 22-gauge needle inserts into a 18-gauge needle when both needles are inside the hand, guiding the 22-gauge needle to exit the hand at the same access point of 18-gauge needle. We prospectively evaluated the effectiveness and functional recovery of these patients. In all 34 digits, triggering and locking were resolved, and complete extension and flexion occurred immediately following the release. Read More

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November 2018

Focal ablation for atrial tachycardia from the double-exit of the Marshall bundle inducing atrial fibrillation.

J Arrhythm 2017 Aug 2;33(4):324-327. Epub 2017 Jan 2.

Division of Cardiology, Eulji University Hospital, Eulji University School of Medicine, Daejeon, Republic of Korea.

Atrial fibrillation (AF) from the ligament/vein of Marshall (LOM/VOM) has previously been described. We report the case of a 23-year-old woman with an antiarrhythmic drug-resistant AF induced by two distinct atrial tachycardias (ATs). Focal ablation of these ATs from the double-exit of the Marshall bundle using a three-dimensional map eliminated AF triggering, even though pulmonary vein electrical isolation is the cornerstone for paroxysmal AF. Read More

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The Ribosomal Protein uL22 Modulates the Shape of the Protein Exit Tunnel.

Structure 2017 08 6;25(8):1233-1241.e3. Epub 2017 Jul 6.

Department of Structural Biology, The Weizmann Institute of Science, Rehovot 7610001, Israel. Electronic address:

Erythromycin is a clinically useful antibiotic that binds to an rRNA pocket in the ribosomal exit tunnel. Commonly, resistance to erythromycin is acquired by alterations of rRNA nucleotides that interact with the drug. Mutations in the β hairpin of ribosomal protein uL22, which is rather distal to the erythromycin binding site, also generate resistance to the antibiotic. Read More

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Dimerization Efficiency of Canine Distemper Virus Matrix Protein Regulates Membrane-Budding Activity.

J Virol 2017 08 27;91(16). Epub 2017 Jul 27.

Division of Neurological Sciences, DCR-VPH, Vetsuisse Faculty, University of Bern, Bern, Switzerland

Paramyxoviruses rely on the matrix (M) protein to orchestrate viral assembly and budding at the plasma membrane. Although the mechanistic details remain largely unknown, structural data suggested that M dimers and/or higher-order oligomers may facilitate membrane budding. To gain functional insights, we employed a structure-guided mutagenesis approach to investigate the role of canine distemper virus (CDV) M protein self-assembly in membrane-budding activity. Read More

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Ångstrom-size exocytotic fusion pore: Implications for pituitary hormone secretion.

Mol Cell Endocrinol 2018 03 27;463:65-71. Epub 2017 Apr 27.

Laboratory of Neuroendocrinology-Molecular Cell Physiology, Faculty of Medicine, University of Ljubljana, Zaloška 4, 1000 Ljubljana, Slovenia; Celica Biomedical, Tehnološki Park 24, 1000 Ljubljana, Slovenia. Electronic address:

In the past, vesicle content release was thought to occur immediately and completely after triggering of exocytosis. However, vesicles may merge with the plasma membrane to form an Ångstrom diameter fusion pore that prevents the exit of secretions from the vesicle lumen. The advantage of such a narrow pore is to minimize the delay between the trigger and the release. Read More

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Physical exercise rescues defective neural stem cells and neurogenesis in the adult subventricular zone of Btg1 knockout mice.

Brain Struct Funct 2017 Aug 28;222(6):2855-2876. Epub 2017 Feb 28.

Institute of Cell Biology and Neurobiology, National Research Council, Fondazione Santa Lucia, via del Fosso di Fiorano 64, 00143, Rome, Italy.

Adult neurogenesis occurs throughout life in the dentate gyrus (DG) and the subventricular zone (SVZ), where glia-like stem cells generate new neurons. Voluntary running is a powerful neurogenic stimulus triggering the proliferation of progenitor cells in the DG but, apparently, not in the SVZ. The antiproliferative gene Btg1 maintains the quiescence of DG and SVZ stem cells. Read More

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Tumor specific regulatory T cells in the bone marrow of breast cancer patients selectively upregulate the emigration receptor S1P1.

Cancer Immunol Immunother 2017 May 21;66(5):593-603. Epub 2017 Feb 21.

Division of Translational Immunology, National Center for Tumor Diseases (NCT), DKFZ, Heidelberg, Germany.

Regulatory T cells (Treg) hamper anti-tumor T-cell responses resulting in reduced survival and failure of cancer immunotherapy. Among lymphoid organs, the bone marrow (BM) is a major site of Treg residence and recirculation. However, the process governing the emigration of Treg from BM into the circulation remains elusive. Read More

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Multiple Roles of MYC in Integrating Regulatory Networks of Pluripotent Stem Cells.

Front Cell Dev Biol 2017 3;5. Epub 2017 Feb 3.

Department of Epigenetics, Fondazione Istituto Nazionale di Genetica Molecolare "Romeo ed Enrica Invernizzi" (INGM)Milan, Italy; Division of Pathology, Fondazione IRCCS Ca' Granda, Ospedale Maggiore PoliclinicoMilan, Italy.

Pluripotent stem cells (PSCs) are defined by their self-renewal potential, which permits their unlimited propagation, and their pluripotency, being able to generate cell of the three embryonic lineages. These properties render PSCs a valuable tool for both basic and medical research. To induce and stabilize the pluripotent state, complex circuitries involving signaling pathways, transcription regulators and epigenetic mechanisms converge on a core transcriptional regulatory network of PSCs, thus determining their cell identity. Read More

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February 2017

APC/C and APC/C play pivotal roles in the process of embryonic development in Artemia sinica.

Sci Rep 2016 12 19;6:39047. Epub 2016 Dec 19.

Department of Biology, Dalian Medical University, Dalian 116044, China.

Anaphase Promoting Complex or Cyclosome (APC/C) is a representative E3 ubiquitin ligase, triggering the transition of metaphase to anaphase by regulating degradation and ensures the exit from mitosis. Cell division cycle 20 (CDC20) and Cell division cycle 20 related protein 1 (CDH1), as co-activators of APC/C, play significant roles in the spindle assembly checkpoint, guiding ubiquitin-mediated degradation, together with CDC23. During the embryonic development of the brine shrimp, Artemia sinica, CDC20, CDH1 and CDC23 participate in cell cycle regulation, but the specific mechanisms of their activities remain unknown. Read More

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December 2016

Strong antitumor synergy between DNA crosslinking and HSP90 inhibition causes massive premitotic DNA fragmentation in ovarian cancer cells.

Cell Death Differ 2017 02 11;24(2):300-316. Epub 2016 Nov 11.

Institute of Molecular Oncology, Göttingen Center of Molecular Biosciences (GZMB), University Medical Center Göttingen, Göttingen D-37077, Germany.

All current regimens for treating ovarian cancer center around carboplatin as standard first line. The HSP90 inhibitor ganetespib is currently being assessed in advanced clinical oncology trials. Thus, we tested the combined effects of ganetespib and carboplatin on a panel of 15 human ovarian cancer lines. Read More

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February 2017

Technical brief: Pump-probe paradigm in an integrating cavity to study photodecomposition processes.

Mol Vis 2016 5;22:953-8. Epub 2016 Aug 5.

OLIS, Inc. Bogart, GA.

Purpose: Assaying photodecomposition is challenging because light must be used to initiate the photodamage and light must be used to monitor the photodecomposition. The experimental requirements are as follows: 1) During exposure of the actinic beam, continuously monitor the spectral characteristics of the sample, 2) uniformly expose the reactants to the actinic source, 3) obtain informative spectra in the presence of light scatter, and 4) achieve sufficient sensitivity for dilute reactants. Traditional spectrophotometers cannot address these issues due to sample turbidity, the inability to uniformly expose the cuvette contents to the incident beam, the inability to simultaneously perform spectral scans, and inherent low sensitivity. Read More

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January 2018

PP1 initiates the dephosphorylation of MASTL, triggering mitotic exit and bistability in human cells.

J Cell Sci 2016 Apr 12;129(7):1340-54. Epub 2016 Feb 12.

The Kinghorn Cancer Centre, Garvan Institute of Medical Research, Darlinghurst, New South Wales 2010, Australia St. Vincent's Clinical School, Faculty of Medicine, UNSW, Darlinghurst 2010, New South Wales, Australia

Entry into mitosis is driven by the phosphorylation of thousands of substrates, under the master control of Cdk1. During entry into mitosis, Cdk1, in collaboration with MASTL kinase, represses the activity of the major mitotic protein phosphatases, PP1 and PP2A, thereby ensuring mitotic substrates remain phosphorylated. For cells to complete and exit mitosis, these phosphorylation events must be removed, and hence, phosphatase activity must be reactivated. Read More

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