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    5479 results match your criteria Cellular and molecular life sciences : CMLS[Journal]

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    Reprogramming the metabolome rescues retinal degeneration.
    Cell Mol Life Sci 2018 Jan 13. Epub 2018 Jan 13.
    Jonas Children's Vision Care and Bernard & Shirlee Brown Glaucoma Laboratory, Department of Ophthalmology, Columbia University, New York, NY, USA.
    Metabolomics studies in the context of ophthalmology have largely focused on identifying metabolite concentrations that characterize specific retinal diseases. Studies involving mass spectrometry (MS) and nuclear magnetic resonance (NMR) spectroscopy have shown that individuals suffering from retinal diseases exhibit metabolic profiles that markedly differ from those of control individuals, supporting the notion that metabolites may serve as easily identifiable biomarkers for specific conditions. An emerging branch of metabolomics resulting from biomarker studies, however, involves the study of retinal metabolic dysfunction as causes of degeneration. Read More

    Structural insights into the function of Elongator.
    Cell Mol Life Sci 2018 Jan 13. Epub 2018 Jan 13.
    Department of Biochemistry and Molecular Biology, The University of British Columbia, Vancouver, BC, V6T 1Z3, Canada.
    Conserved from yeast to humans, Elongator is a protein complex implicated in multiple processes including transcription regulation, α-tubulin acetylation, and tRNA modification, and its defects have been shown to cause human diseases such as familial dysautonomia. Elongator consists of two copies of six core subunits (Elp1, Elp2, Elp3, Elp4, Elp5, and Elp6) that are organized into two subcomplexes: Elp1/2/3 and Elp4/5/6 and form a stable assembly of ~ 850 kDa in size. Although the catalytic subunit of Elongator is Elp3, which contains a radical S-adenosyl-L-methionine (SAM) domain and a putative histone acetyltransferase domain, the Elp4/5/6 subcomplex also possesses ATP-modulated tRNA binding activity. Read More

    The role of the thioredoxin/thioredoxin reductase system in the metabolic syndrome: towards a possible prognostic marker?
    Cell Mol Life Sci 2018 Jan 11. Epub 2018 Jan 11.
    Research Department, Innlandet Hospital Trust, Brumunddal, Norway.
    Mammalian thioredoxin reductase (TrxR) is a selenoprotein with three existing isoenzymes (TrxR1, TrxR2, and TrxR3), which is found primarily intracellularly but also in extracellular fluids. The main substrate thioredoxin (Trx) is similarly found (as Trx1 and Trx2) in various intracellular compartments, in blood plasma, and is the cell's major disulfide reductase. Thioredoxin reductase is necessary as a NADPH-dependent reducing agent in biochemical reactions involving Trx. Read More

    An MD2-derived peptide promotes LPS aggregation, facilitates its internalization in THP-1 cells, and inhibits LPS-induced pro-inflammatory responses.
    Cell Mol Life Sci 2018 Jan 8. Epub 2018 Jan 8.
    Molecular and Structural Biology Division, CSIR-Central Drug Research Institute, Sector 10, Jankipuram Extension, Sitapur Road, Lucknow, 226031, India.
    MD2, a 160-residue accessory glycoprotein, is responsible for the recognition and binding of Gram-negative bacterial membrane component, lipopolysaccharide (LPS). Internalization of pathogen inside the mononuclear phagocytes has also been attributed to MD2 which leads to the clearance of pathogens from the host. However, not much is known about the segments in MD2 that are responsible for LPS interaction or internalization of pathogen inside the defense cells. Read More

    Molecular function of the novel α7β2 nicotinic receptor.
    Cell Mol Life Sci 2018 Jan 8. Epub 2018 Jan 8.
    Instituto de Investigaciones Bioquímicas de Bahía Blanca, Departamento de Biología, Bioquímica y Farmacia, Universidad Nacional del Sur-Consejo Nacional de Investigaciones Científicas y Técnicas (UNS-CONICET), 8000, Bahía Blanca, Argentina.
    The α7 nicotinic receptor is a promising drug target for neurological and inflammatory disorders. Although it is the homomeric member of the family, a novel α7β2 heteromeric receptor has been discovered. To decipher the functional contribution of the β2 subunit, we generated heteromeric receptors with fixed stoichiometry by two different approaches comprising concatenated and unlinked subunits. Read More

    Therapeutic approaches for induction of tolerance and immune quiescence in corneal allotransplantation.
    Cell Mol Life Sci 2018 Jan 6. Epub 2018 Jan 6.
    Schepens Eye Research Institute, Massachusetts Eye and Ear Infirmary, Harvard Medical School, Boston, MA, USA.
    The cornea is the most commonly transplanted tissue in the body. Corneal grafts in low-risk recipients enjoy high success rates, yet over 50% of high-risk grafts (with inflamed and vascularized host beds) are rejected. As our understanding of the cellular and molecular pathways that mediate rejection has deepened, a number of novel therapeutic strategies have been unveiled. Read More

    Inhibitors of protein translocation across membranes of the secretory pathway: novel antimicrobial and anticancer agents.
    Cell Mol Life Sci 2018 Jan 5. Epub 2018 Jan 5.
    Laboratory of Virology and Chemotherapy, Department of Microbiology and Immunology, Rega Institute for Medical Research, KU Leuven - University of Leuven, 3000, Leuven, Belgium.
    Proteins routed to the secretory pathway start their journey by being transported across biological membranes, such as the endoplasmic reticulum. The essential nature of this protein translocation process has led to the evolution of several factors that specifically target the translocon and block translocation. In this review, various translocation pathways are discussed together with known inhibitors of translocation. Read More

    Primary cilia proteins: ciliary and extraciliary sites and functions.
    Cell Mol Life Sci 2018 Jan 5. Epub 2018 Jan 5.
    Department of Neuroscience and Experimental Therapeutics, Albany Medical College, 47 New Scotland Avenue, MC-136, Albany, NY, 12208, USA.
    Primary cilia are immotile organelles known for their roles in development and cell signaling. Defects in primary cilia result in a range of disorders named ciliopathies. Because this organelle can be found singularly on almost all cell types, its importance extends to most organ systems. Read More

    Furin promotes dendritic morphogenesis and learning and memory in transgenic mice.
    Cell Mol Life Sci 2018 Jan 4. Epub 2018 Jan 4.
    Department of Neurology, The First Affiliated Hospital of Chongqing Medical University, Chongqing Key Laboratory of Neurology, 1 Youyi Road, Chongqing, 400016, China.
    Furin is a proprotein convertase implicated in a variety of pathological processes including neurodegenerative diseases. However, the role of furin in neuronal plasticity and learning and memory remains to be elucidated. Here, we report that in brain-specific furin transgenic (Furin-Tg) mice, the dendritic spine density and proliferation of neural progenitor cells were significantly increased. Read More

    Structure and function of the Nppa-Nppb cluster locus during heart development and disease.
    Cell Mol Life Sci 2018 Jan 4. Epub 2018 Jan 4.
    Department of Medical Biology, Academic Medical Center, University of Amsterdam, Meibergdreef 15, 1105 AZ, Amsterdam, The Netherlands.
    Atrial natriuretic factor and brain natriuretic peptide are two important biomarkers in clinical cardiology. These two natriuretic peptide hormones are encoded by the paralogous genes Nppa and Nppb, which are evolutionary conserved. Both genes are predominantly expressed by the heart muscle during the embryonic and fetal stages, and in particular Nppa expression is strongly reduced in the ventricles after birth. Read More

    Evidence of G-protein-coupled receptor and substrate transporter heteromerization at a single molecule level.
    Cell Mol Life Sci 2017 Dec 30. Epub 2017 Dec 30.
    Institut für Experimentelle Pädiatrische Endokrinologie, Charité - Universitätsmedizin Berlin, 13353, Berlin, Germany.
    G-protein-coupled receptors (GPCRs) can constitute complexes with non-GPCR integral membrane proteins, while such interaction has not been demonstrated at a single molecule level so far. We here investigated the potential interaction between the thyrotropin receptor (TSHR) and the monocarboxylate transporter 8 (MCT8), a member of the major facilitator superfamily (MFS), using fluorescence cross-correlation spectroscopy (FCCS). Both the proteins are expressed endogenously on the basolateral plasma membrane of the thyrocytes and are involved in stimulation of thyroid hormone production and release. Read More

    Tight co-twin similarity of monozygotic twins for hTERT protein level of T cell subsets, for telomere length and mitochondrial DNA copy number, but not for telomerase activity.
    Cell Mol Life Sci 2017 Dec 30. Epub 2017 Dec 30.
    Department of Genetics, Cell- and Immunobiology, Semmelweis University, Budapest, Hungary.
    Our study analyzed lymphocyte subpopulations of 32 monozygotic twins and compared the level of the catalytic reverse transcriptase protein subunit (hTERT) in T lymphocytes (Tly), helper- (Th), cytotoxic- (Tc) and regulatory T cell (Treg) subgroups. Four variables related to telomere and mitochondrial biology were simultaneously assessed, applying multi-parametric flow cytometry, TRAP-ELISA assay and qPCR standard curve method on peripheral blood mononuclear cell (PBMC) samples of genetically matched individuals. Twin data of telomerase activity (TA), hTERT protein level, telomere length (TL) and mitochondrial DNA copy number (mtDNAcn) were analyzed for co-twin similarity. Read More

    Delta opioid receptors recycle to the membrane after sorting to the degradation path.
    Cell Mol Life Sci 2017 Dec 29. Epub 2017 Dec 29.
    Department of Pharmacology, University of Montreal, Montreal, Quebec, H3T 1J4, Canada.
    Soon after internalization delta opioid receptors (DOPrs) are committed to the degradation path by G protein-coupled receptor (GPCR)-associated binding protein. Here we provide evidence that this classical post-endocytic itinerary may be rectified by downstream sorting decisions which allow DOPrs to regain to the membrane after having reached late endosomes (LE). The LE sorting mechanism involved ESCRT accessory protein Alix and the TIP47/Rab9 retrieval complex which supported translocation of the receptor to the TGN, from where it subsequently regained the cell membrane. Read More

    Clostridium difficile-related postinfectious IBS: a case of enteroglial microbiological stalking and/or the solution of a conundrum?
    Cell Mol Life Sci 2017 Dec 28. Epub 2017 Dec 28.
    Department of Experimental Medicine, University of Perugia Medical School, Perugia, Italy.
    Post-infectious irritable bowel syndrome is a well-defined pathological entity that develops in about one-third of subjects after an acute infection (bacterial, viral) or parasitic infestation. Only recently it has been documented that an high incidence of post-infectious irritable bowel syndrome occurs after Clostridium difficile infection. However, until now it is not known why in some patients recovered from this infection the gastrointestinal disturbances persist for months or years. Read More

    Bacterial LPX motif-harboring virulence factors constitute a species-spanning family of cell-penetrating effectors.
    Cell Mol Life Sci 2017 Dec 28. Epub 2017 Dec 28.
    Institute of Infectiology, Center for Molecular Biology of Inflammation (ZMBE), University of Münster, Von-Esmarch-Str. 56, 48149, Münster, Germany.
    Effector proteins are key virulence factors of pathogenic bacteria that target and subvert the functions of essential host defense mechanisms. Typically, these proteins are delivered into infected host cells via the type III secretion system (T3SS). Recently, however, several effector proteins have been found to enter host cells in a T3SS-independent manner thereby widening the potential range of these virulence factors. Read More

    Identification of a novel lncRNA induced by the nephrotoxin ochratoxin A and expressed in human renal tumor tissue.
    Cell Mol Life Sci 2017 Dec 27. Epub 2017 Dec 27.
    Julius Bernstein Institute of Physiology, Martin Luther University Halle-Wittenberg, Magdeburgerstrasse 6, 06112, Halle (Saale), Germany.
    Long non-coding RNAs represent a fraction of the transcriptome that is being increasingly recognized. For most of them no function has been allocated so far. Here, we describe the nature and function of a novel non-protein-coding transcript, named WISP1-AS1, discovered in human renal proximal tubule cells exposed to the carcinogenic nephrotoxin ochratoxin A. Read More

    Neuroprotective effects of the gliopeptide ODN in an in vivo model of Parkinson's disease.
    Cell Mol Life Sci 2017 Dec 20. Epub 2017 Dec 20.
    Laboratory of Neuronal and Neuroendocrine Communication and Differentiation, Institute for Research and Innovation in Biomedicine (IRIB), Normandy University, UNIROUEN, INSERM, U1239, 76821, Mont-Saint-Aignan, France.
    Parkinson's disease (PD) is a neurodegenerative disorder characterized by a progressive loss of dopamine (DA) neurons through apoptotic, inflammatory and oxidative stress mechanisms. The octadecaneuropeptide (ODN) is a diazepam-binding inhibitor (DBI)-derived peptide, expressed by astrocytes, which protects neurons against oxidative cell damages and apoptosis in an in vitro model of PD. The present study reveals that a single intracerebroventricular injection of 10 ng ODN 1 h after the last administration of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) prevented the degeneration of DA neurons induced by the toxin in the substantia nigra pars compacta of mice, 7 days after treatment. Read More

    iPSCs-based generation of vascular cells: reprogramming approaches and applications.
    Cell Mol Life Sci 2017 Dec 14. Epub 2017 Dec 14.
    Institute for Cell Biology (Cancer Research), University Hospital Essen, University of Duisburg-Essen, Virchowstr. 173, 45122, Essen, Germany.
    Recent advances in the field of induced pluripotent stem cells (iPSCs) research have opened a new avenue for stem cell-based generation of vascular cells. Based on their growth and differentiation potential, human iPSCs constitute a well-characterized, generally unlimited cell source for the mass generation of lineage- and patient-specific vascular cells without any ethical concerns. Human iPSCs-derived vascular cells are perfectly suited for vascular disease modeling studies because patient-derived iPSCs possess the disease-causing mutation, which might be decisive for full expression of the disease phenotype. Read More

    Junctional adhesion molecule-A: functional diversity through molecular promiscuity.
    Cell Mol Life Sci 2017 Dec 14. Epub 2017 Dec 14.
    Institute-Associated Research Group: Cell Adhesion and Cell Polarity, Institute of Medical Biochemistry, ZMBE, University of Münster, Von-Esmarch-Str. 56, 48149, Münster, Germany.
    Cell adhesion molecules (CAMs) of the immunoglobulin superfamily (IgSF) regulate important processes such as cell proliferation, differentiation and morphogenesis. This activity is primarily due to their ability to initiate intracellular signaling cascades at cell-cell contact sites. Junctional adhesion molecule-A (JAM-A) is an IgSF-CAM with a short cytoplasmic tail that has no catalytic activity. Read More

    Cardiomyokines from the heart.
    Cell Mol Life Sci 2017 Dec 13. Epub 2017 Dec 13.
    Department of Cell Biology, National Cerebral and Cardiovascular Center Research Institute, 5-7-1 Fujishirodai, Suita, Osaka, 565-8565, Japan.
    The heart is regarded as an endocrine organ as well as a pump for circulation, since atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) were discovered in cardiomyocytes to be secreted as hormones. Both ANP and BNP bind to their receptors expressed on remote organs, such as kidneys and blood vessels; therefore, the heart controls the circulation by pumping blood and by secreting endocrine peptides. Cardiomyocytes secrete other peptides besides natriuretic peptides. Read More

    Role of the microenvironment in myeloid malignancies.
    Cell Mol Life Sci 2017 Dec 8. Epub 2017 Dec 8.
    Haematopoietic Stem Cell Laboratory, The Francis Crick Institute, 1, Midland Road, London, NW1 1AT, UK.
    The bone marrow microenvironment (BMM) regulates the fate of hematopoietic stem cells (HSCs) in homeostatic and pathologic conditions. In myeloid malignancies, new insights into the role of the BMM and its cellular and molecular actors in the progression of the diseases have started to emerge. In this review, we will focus on describing the major players of the HSC niche and the role of the altered niche function in myeloid malignancies, more specifically focusing on the mesenchymal stroma cell compartment. Read More

    Membrane-shed vesicles from the parasite Trichomonas vaginalis: characterization and their association with cell interaction.
    Cell Mol Life Sci 2017 Dec 8. Epub 2017 Dec 8.
    Laboratorio de Parásitos Anaerobios Instituto de Investigaciones Biotecnológicas-Instituto Tecnológico Chascomús (IIB-INTECH), CONICET-UNSAM, Intendente Marino KM 8.200 Chascomús, B7130IWA, Chascomús, Provincia de Buenos Aires, Argentina.
    Trichomonas vaginalis is a common sexually transmitted parasite that colonizes the human urogenital tract, where it remains extracellular and adheres to epithelial cells. Infections range from asymptomatic to highly inflammatory, depending on the host and the parasite strain. Despite the serious consequences associated with trichomoniasis disease, little is known about parasite or host factors involved in attachment of the parasite-to-host epithelial cells. Read More

    Regulation of myelopoiesis by proinflammatory cytokines in infectious diseases.
    Cell Mol Life Sci 2017 Dec 7. Epub 2017 Dec 7.
    Department of Immunoregulation, Institute of Medical Science, Tokyo Medical University, 6-1-1 Shinjuku, Shinjuku-ku, Tokyo, 160-8402, Japan.
    Hematopoiesis is hierarchically orchestrated by a very small population of hematopoietic stem cells (HSCs) that reside in the bone-marrow niche and are tightly regulated to maintain homeostatic blood production. HSCs are predominantly quiescent, but they enter the cell cycle in response to inflammatory signals evoked by severe systemic infection or injury. Thus, hematopoietic stem and progenitor cells (HSPCs) can be activated by pathogen recognition receptors and proinflammatory cytokines to induce emergency myelopoiesis during infection. Read More

    The SH3-binding domain of Cx43 participates in loop/tail interactions critical for Cx43-hemichannel activity.
    Cell Mol Life Sci 2017 Dec 7. Epub 2017 Dec 7.
    Laboratory of Molecular and Cellular Signaling, Department Cellular and Molecular Medicine, KU Leuven, Campus Gasthuisberg O/N-1 Bus 802, Herestraat 49, 3000, Louvain, Belgium.
    Connexin 43 (Cx43) hemichannels establish local signaling networks via the release of ATP and other molecules, but their excessive opening may result in cell death. Hence, the activity of Cx43-hemichannels ought to be critically controlled. This involves interactions between the C-terminal tail (CT) and the cytoplasmic loop (CL), more particularly the L2 domain within CL. Read More

    Sorting nexin 3 mutation impairs development and neuronal function in Caenorhabditis elegans.
    Cell Mol Life Sci 2017 Dec 1. Epub 2017 Dec 1.
    School of Medicine, Life and Health Sciences Research Institute (ICVS), University of Minho, Campus Gualtar, 4710-057, Braga, Portugal.
    The sorting nexins family of proteins (SNXs) plays pleiotropic functions in protein trafficking and intracellular signaling and has been associated with several disorders, namely Alzheimer's disease and Down's syndrome. Despite the growing association of SNXs with neurodegeneration, not much is known about their function in the nervous system. The aim of this work was to use the nematode Caenorhabditis elegans that encodes in its genome eight SNXs orthologs, to dissect the role of distinct SNXs, particularly in the nervous system. Read More

    D2A sequence of the urokinase receptor induces cell growth through αvβ3 integrin and EGFR.
    Cell Mol Life Sci 2017 Nov 28. Epub 2017 Nov 28.
    Department of Molecular Biology and Functional Genomics, DIBIT, Università Vita-Salute San Raffaele, Via Olgettina 58, 20132, Milan, Italy.
    The urokinase receptor (uPAR) stimulates cell proliferation by forming a macromolecular complex with αvβ3 integrin and the epidermal growth factor receptor (EGFR, ErbB1 or HER1) that we name the uPAR proliferasome. uPAR transactivates EGFR, which in turn mediates uPAR-initiated mitogenic signal to the cell. EGFR activation and EGFR-dependent cell growth are blocked in the absence of uPAR expression or when uPAR activity is inhibited by antibodies against either uPAR or EGFR. Read More

    The TET enzymes.
    Cell Mol Life Sci 2017 Nov 28. Epub 2017 Nov 28.
    Faculty of Biochemistry and Molecular Medicine, Biocenter Oulu, Oulu Center for Cell-Matrix Research, University of Oulu, 90014, Oulu, Finland.
    During the past decade, we have learnt that the most common DNA modification, 5-methylcytosine (5mC), playing crucial roles in development and disease, is not stable but can be actively reversed to its unmodified form via enzymatic catalysis involving the TET enzymes. These ground-breaking discoveries have been achieved thanks to technological advances in the detection of the oxidized forms of 5mC and to the boldness of individual scientists. The TET enzymes require molecular oxygen for their catalysis, making them important targets for hypoxia research. Read More

    Blockage of the NLRP3 inflammasome by MCC950 improves anti-tumor immune responses in head and neck squamous cell carcinoma.
    Cell Mol Life Sci 2017 Nov 28. Epub 2017 Nov 28.
    The State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei-MOST) and Key Laboratory of Oral Biomedicine Ministry of Education, School and Hospital of Stomatology, Wuhan University, Wuhan, China.
    The NLRP3 inflammasome is a critical innate immune pathway responsible for producing active interleukin (IL)-1β, which is associated with tumor development and immunity. However, the mechanisms regulating the inflammatory microenvironment, tumorigenesis and tumor immunity are unclear. Herein, we show that the NLRP3 inflammasome was over-expressed in human HNSCC tissues and that the IL-1β concentration was increased in the peripheral blood of HNSCC patients. Read More

    Liver cell therapy: is this the end of the beginning?
    Cell Mol Life Sci 2017 Nov 27. Epub 2017 Nov 27.
    MRC Centre for Regenerative Medicine, University of Edinburgh, 5 Little France Drive, Edinburgh, EH16 4UU, UK.
    The prevalence of liver diseases is increasing globally. Orthotopic liver transplantation is widely used to treat liver disease upon organ failure. The complexity of this procedure and finite numbers of healthy organ donors have prompted research into alternative therapeutic options to treat liver disease. Read More

    Structural variations in wheat HKT1;5 underpin differences in Na+ transport capacity.
    Cell Mol Life Sci 2017 Nov 27. Epub 2017 Nov 27.
    Australian Research Council Centre of Excellence in Plant Energy Biology, Waite Research Precinct, University of Adelaide, Glen Osmond, SA, 5064, Australia.
    An important trait associated with the salt tolerance of wheat is the exclusion of sodium ions (Na+) from the shoot. We have previously shown that the sodium transporters TmHKT1;5-A and TaHKT1;5-D, from Triticum monoccocum (Tm) and Triticum aestivum (Ta), are encoded by genes underlying the major shoot Na+-exclusion loci Nax1 and Kna1, respectively. Here, using heterologous expression, we show that the affinity (K m) for the Na+ transport of TmHKT1;5-A, at 2. Read More

    CREBBP and p300 lysine acetyl transferases in the DNA damage response.
    Cell Mol Life Sci 2017 Nov 23. Epub 2017 Nov 23.
    Istituto di Genetica Molecolare del CNR, Via Abbiategrasso 207, 27100, Pavia, Italy.
    The CREB-binding protein (CREBBP, or in short CBP) and p300 are lysine (K) acetyl transferases (KAT) belonging to the KAT3 family of proteins known to modify histones, as well as non-histone proteins, thereby regulating chromatin accessibility and transcription. Previous studies have indicated a tumor suppressor function for these enzymes. Recently, they have been found to acetylate key factors involved in DNA replication, and in different DNA repair processes, such as base excision repair, nucleotide excision repair, and non-homologous end joining. Read More

    Signaling pathways and mesenchymal transition in pediatric high-grade glioma.
    Cell Mol Life Sci 2017 Nov 21. Epub 2017 Nov 21.
    Departments of Pediatric Oncology/Hematology, Neuro-oncology Research Group, Cancer Center Amsterdam, VU University Medical Center, De Boelelaan 1117, 1081HV, Amsterdam, The Netherlands.
    Pediatric high-grade gliomas (pHGG), including diffuse intrinsic pontine gliomas (DIPG), are the most lethal types of cancer in children. In recent years, it has become evident that these tumors are driven by epigenetic events, mainly mutations involving genes encoding Histone 3, setting them apart from their adult counterparts. These tumors are exceptionally resistant to chemotherapy and respond only temporarily to radiotherapy. Read More

    Bacteriophages targeting intestinal epithelial cells: a potential novel form of immunotherapy.
    Cell Mol Life Sci 2017 Nov 21. Epub 2017 Nov 21.
    Department of Clinical Immunology, Transplantation Institute, Medical University of Warsaw, 02-006, Warsaw, Poland.
    In addition to their established role as a physical barrier to invading pathogens and other harmful agents, intestinal epithelial cells (IEC) are actively involved in local immune reactions. In the past years, evidence has accumulated suggesting the role of IEC in the immunopathology of intestinal inflammatory disorders (IBD). Recent advances in research on bacteriophages strongly suggest that-in addition to their established antibacterial activity-they have immunomodulating properties that are potentially useful in the clinic. Read More

    Early SIV and HIV infection promotes the LILRB2/MHC-I inhibitory axis in cDCs.
    Cell Mol Life Sci 2017 Nov 13. Epub 2017 Nov 13.
    CEA-Université Paris Sud 11-INSERM U1184, Immunology of Viral Infections and Autoimmune Diseases (IMVA), IDMIT Department, IBJF, DRF, Fontenay-aux-Roses, France.
    Classical dendritic cells (cDCs) play a pivotal role in the early events that tip the immune response toward persistence or viral control. In vitro studies indicate that HIV infection induces the dysregulation of cDCs through binding of the LILRB2 inhibitory receptor to its MHC-I ligands and the strength of this interaction was proposed to drive disease progression. However, the dynamics of the LILRB2/MHC-I inhibitory axis in cDCs during early immune responses against HIV are yet unknown. Read More

    The ancient claudin Dni2 facilitates yeast cell fusion by compartmentalizing Dni1 into a membrane subdomain.
    Cell Mol Life Sci 2017 Nov 13. Epub 2017 Nov 13.
    Departamento de Microbiología y Genética, Universidad de Salamanca, Calle Zacarías González 2, Lab P1.1, Edificio IBFG, 37007, Salamanca, Spain.
    Dni1 and Dni2 facilitate cell fusion during mating. Here, we show that these proteins are interdependent for their localization in a plasma membrane subdomain, which we have termed the mating fusion domain. Dni1 compartmentation in the domain is required for cell fusion. Read More

    Epigenetic differences between naïve and primed pluripotent stem cells.
    Cell Mol Life Sci 2017 Nov 13. Epub 2017 Nov 13.
    Laboratory for Developmental Epigenetics, RIKEN Center for Developmental Biology, 2-2-3 Minatojima-minamimachi, Chuo-ku, Kobe, 650-0047, Japan.
    It has been 8 years since the concept of naïve and primed pluripotent stem cell states was first proposed. Both are states of pluripotency, but exhibit slightly different properties. The naïve state represents the cellular state of the preimplantation mouse blastocyst inner cell mass, while the primed state is representative of the post-implantation epiblast cells. Read More

    BRD7 regulates the insulin-signaling pathway by increasing phosphorylation of GSK3β.
    Cell Mol Life Sci 2017 Nov 10. Epub 2017 Nov 10.
    Division of Endocrinology, Boston Children's Hospital, Harvard Medical School, Boston, MA, 02115, USA.
    Reduced hepatic expression levels of bromodomain-containing protein 7 (BRD7) have been suggested to play a role in the development of glucose intolerance in obesity. However, the molecular mechanism by which BRD7 regulates glucose metabolism has remained unclear. Here, we show that BRD7 increases phosphorylation of glycogen synthase kinase 3β (GSK3β) in response to activation of the insulin receptor-signaling pathway shortly after insulin stimulation and the nutrient-sensing pathway after feeding. Read More

    Gain of function of TMEM16E/ANO5 scrambling activity caused by a mutation associated with gnathodiaphyseal dysplasia.
    Cell Mol Life Sci 2017 Nov 9. Epub 2017 Nov 9.
    Institute of Biophysics, Consiglio Nazionale delle Ricerche, Via de Marini 6, 16149, Genova, Italy.
    Mutations in the human TMEM16E (ANO5) gene are associated both with the bone disease gnathodiaphyseal dysplasia (GDD; OMIM: 166260) and muscle dystrophies (OMIM: 611307, 613319). However, the physiological function of TMEM16E has remained unclear. We show here that human TMEM16E, when overexpressed in mammalian cell lines, displayed partial plasma membrane localization and gave rise to phospholipid scrambling (PLS) as well as non-selective ionic currents with slow time-dependent activation at highly depolarized membrane potentials. Read More

    The β6/β7 region of the Hsp70 substrate-binding domain mediates heat-shock response and prion propagation.
    Cell Mol Life Sci 2017 Nov 9. Epub 2017 Nov 9.
    Department of Biology, Maynooth University, Maynooth, Co. Kildare, Ireland.
    Hsp70 is a highly conserved chaperone that in addition to providing essential cellular functions and aiding in cell survival following exposure to a variety of stresses is also a key modulator of prion propagation. Hsp70 is composed of a nucleotide-binding domain (NBD) and substrate-binding domain (SBD). The key functions of Hsp70 are tightly regulated through an allosteric communication network that coordinates ATPase activity with substrate-binding activity. Read More

    Mouse models for human intestinal microbiota research: a critical evaluation.
    Cell Mol Life Sci 2018 Jan 9;75(1):149-160. Epub 2017 Nov 9.
    Laboratory of Microbiology, Wageningen University, Stippeneng 4, Building 124, 6708 WE, Wageningen, The Netherlands.
    Since the early days of the intestinal microbiota research, mouse models have been used frequently to study the interaction of microbes with their host. However, to translate the knowledge gained from mouse studies to a human situation, the major spatio-temporal similarities and differences between intestinal microbiota in mice and humans need to be considered. This is done here with specific attention for the comparative physiology of the intestinal tract, the effect of dietary patterns and differences in genetics. Read More

    Re-evaluation of protein kinase CK2 pleiotropy: new insights provided by a phosphoproteomics analysis of CK2 knockout cells.
    Cell Mol Life Sci 2017 Nov 9. Epub 2017 Nov 9.
    Department of Biomedical Sciences, University of Padova, Via U. Bassi 58/B, Padua, Italy.
    CK2 denotes a ubiquitous and pleiotropic protein kinase whose holoenzyme is composed of two catalytic (α and/or α') and two regulatory β subunits. The CK2 consensus sequence, S/T-x-x-D/E/pS/pT is present in numerous phosphosites, but it is not clear how many of these are really generated by CK2. To gain information about this issue, advantage has been taken of C2C12 cells entirely deprived of both CK2 catalytic subunits by the CRISPR/Cas9 methodology. Read More

    The emerging role of galectins in high-fatality cancers.
    Cell Mol Life Sci 2017 Nov 8. Epub 2017 Nov 8.
    INRS-Institut Armand-Frappier, 531 Boul. des Prairies, Laval, QC, H7V 1B7, Canada.
    Although we witnessed considerable progress in the prevention and treatment of cancer during the past few decades, a number of cancers remain difficult to treat. The main reasons for this are a lack of effective biomarkers necessary for an early detection and inefficient treatments for cancer that are diagnosed at late stages of the disease. Because of their alarmin-like properties and their protumorigenic role during cancer progression, members of the galectin family are uniquely positioned to provide information that could be used for the exploration of possible avenues for the treatment of high fatality cancer (HFC). Read More

    Macropinocytosis, mTORC1 and cellular growth control.
    Cell Mol Life Sci 2017 Nov 8. Epub 2017 Nov 8.
    Department of Microbiology and Immunology, University of Michigan Medical School, Ann Arbor, MI, 48109-5620, USA.
    The growth and proliferation of metazoan cells are driven by cellular nutrient status and by extracellular growth factors. Growth factor receptors on cell surfaces initiate biochemical signals that increase anabolic metabolism and macropinocytosis, an actin-dependent endocytic process in which relatively large volumes of extracellular solutes and nutrients are internalized and delivered efficiently into lysosomes. Macropinocytosis is prominent in many kinds of cancer cells, and supports the growth of cells transformed by oncogenic K-Ras. Read More

    Low density lipoprotein receptor-related protein 1 couples β1 integrin activation to degradation.
    Cell Mol Life Sci 2017 Nov 7. Epub 2017 Nov 7.
    Department of Biochemistry, Justus Liebig University, 35392, Giessen, Germany.
    Low density lipoprotein receptor-related protein (LRP) 1 modulates cell adhesion and motility under normal and pathological conditions. Previous studies documented that LRP1 binds several integrin receptors and mediates their trafficking to the cell surface and endocytosis. However, the mechanism by which LRP1 may regulate integrin activation remains unknown. Read More

    Molecular roles and function of circular RNAs in eukaryotic cells.
    Cell Mol Life Sci 2017 Nov 7. Epub 2017 Nov 7.
    Institute of Laboratory Medicine, University Hospital, LMU Munich, Marchioninistr. 15, 81377, Munich, Germany.
    Protein-coding and noncoding genes in eukaryotes are typically expressed as linear messenger RNAs, with exons arranged colinearly to their genomic order. Recent advances in sequencing and in mapping RNA reads to reference genomes have revealed that thousands of genes express also covalently closed circular RNAs. Many of these circRNAs are stable and contain exons, but are not translated into proteins. Read More

    Homologous recombination-mediated repair of DNA double-strand breaks operates in mammalian mitochondria.
    Cell Mol Life Sci 2017 Nov 7. Epub 2017 Nov 7.
    Department of Biochemistry, Indian Institute of Science, Bangalore, 560 012, India.
    Mitochondrial DNA is frequently exposed to oxidative damage, as compared to nuclear DNA. Previously, we have shown that while microhomology-mediated end joining can account for DNA deletions in mitochondria, classical nonhomologous DNA end joining, the predominant double-strand break (DSB) repair pathway in nucleus, is undetectable. In the present study, we investigated the presence of homologous recombination (HR) in mitochondria to maintain its genomic integrity. Read More

    The emerging roles for the chromatin structure regulators CTCF and cohesin in neurodevelopment and behavior.
    Cell Mol Life Sci 2017 Nov 6. Epub 2017 Nov 6.
    Molecular and Behavioral Neurosciences Laboratory, Faculty of Medicine in the Galilee, Bar-Ilan University, Hanrietta Sold 8, 1311502, Safed, Israel.
    Recent genetic and technological advances have determined a role for chromatin structure in neurodevelopment. In particular, compounding evidence has established roles for CTCF and cohesin, two elements that are central in the establishment of chromatin structure, in proper neurodevelopment and in regulation of behavior. Genetic aberrations in CTCF, and in subunits of the cohesin complex, have been associated with neurodevelopmental disorders in human genetic studies, and subsequent animal studies have established definitive, although sometime opposing roles, for these factors in neurodevelopment and behavior. Read More

    Master regulatory role of p63 in epidermal development and disease.
    Cell Mol Life Sci 2017 Nov 4. Epub 2017 Nov 4.
    Department of Molecular Developmental Biology, Faculty of Science, Radboud Institute for Molecular Life Sciences, Radboud University, 274, Postbus 9101, 6500HB, Nijmegen, The Netherlands.
    The transcription factor p63 is a master regulator of epidermal development. Mutations in p63 give rise to human developmental diseases that often manifest epidermal defects. In this review, we summarize major p63 isoforms identified so far and p63 mutation-associated human diseases that show epidermal defects. Read More

    RNA cytosine methyltransferase Nsun3 regulates embryonic stem cell differentiation by promoting mitochondrial activity.
    Cell Mol Life Sci 2017 Nov 4. Epub 2017 Nov 4.
    Division of Molecular Biology, Biocenter, Medical University of Innsbruck, Innrain 80-82, 6020, Innsbruck, Austria.
    Chemical modifications of RNA have been attracting increasing interest because of their impact on RNA fate and function. Therefore, the characterization of enzymes catalyzing such modifications is of great importance. The RNA cytosine methyltransferase NSUN3 was recently shown to generate 5-methylcytosine in the anticodon loop of mitochondrial tRNAMet. Read More

    SUMOylation controls stem cell proliferation and regional cell death through Hedgehog signaling in planarians.
    Cell Mol Life Sci 2017 Nov 2. Epub 2017 Nov 2.
    Department of Molecular and Cell Biology, University of California, 5200 North Lake Road, Merced, CA, 95343, USA.
    Mechanisms underlying anteroposterior body axis differences during adult tissue maintenance and regeneration are poorly understood. Here, we identify that post-translational modifications through the SUMO (Small Ubiquitin-like Modifier) machinery are evolutionarily conserved in the Lophotrocozoan Schmidtea mediterranea. Disruption of SUMOylation in adult animals by RNA-interference of the only SUMO E2 conjugating enzyme Ubc9 leads to a systemic increase in DNA damage and a remarkable regional defect characterized by increased cell death and loss of the posterior half of the body. Read More

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