5,604 results match your criteria Cellular and molecular life sciences : CMLS[Journal]


Targeting epigenetics using synthetic lethality in precision medicine.

Authors:
Ee Sin Chen

Cell Mol Life Sci 2018 Jul 12. Epub 2018 Jul 12.

Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, 117597, Singapore.

Technological breakthroughs in genomics have had a significant impact on clinical therapy for human diseases, allowing us to use patient genetic differences to guide medical care. The "synthetic lethal approach" leverages on cancer-specific genetic rewiring to deliver a therapeutic regimen that preferentially targets malignant cells while sparing normal cells. The utility of this system is evident in several recent studies, particularly in poor prognosis cancers with loss-of-function mutations that become "treatable" when two otherwise discrete and unrelated genes are targeted simultaneously. Read More

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July 2018
1 Read

The mesenchymoangioblast, mesodermal precursor for mesenchymal and endothelial cells.

Cell Mol Life Sci 2018 Jul 10. Epub 2018 Jul 10.

Wisconsin National Primate Research Center, University of Wisconsin, 1220 Capitol Ct., Madison, WI, 53715, USA.

Mesenchymoangioblast (MB) is the earliest precursor for endothelial and mesenchymal cells originating from APLNRPDGFRαKDR mesoderm in human pluripotent stem cell cultures. MBs are identified based on their capacity to form FGF2-dependent compact spheroid colonies in a serum-free semisolid medium. MBs colonies are composed of PDGFRβCD271EMCNDLK1CD73 primitive mesenchymal cells which are generated through endothelial/angioblastic intermediates (cores) formed during first 3-4 days of clonogenic cultures. Read More

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July 2018
1 Read

A126 in the active site and TI167/168 in the TI loop are essential determinants of the substrate specificity of PTEN.

Cell Mol Life Sci 2018 Jul 9. Epub 2018 Jul 9.

Institute of Physiology and Pathophysiology, Philipps-University Marburg, Deutschhausstr. 1-2, 35037, Marburg, Germany.

PTEN prevents tumor genesis by antagonizing the PI3 kinase/Akt pathway through D3 site phosphatase activity toward PI(3,4)P and PI(3,4,5)P. The structural determinants of this important specificity remain unknown. Interestingly, PTEN shares remarkable homology to voltage-sensitive phosphatases (VSPs) that dephosphorylate D5 and D3 sites of PI(4,5)P, PI(3,4)P, and PI(3,4,5)P. Read More

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Voltage-gated sodium currents in cerebellar Purkinje neurons: functional and molecular diversity.

Cell Mol Life Sci 2018 Jul 7. Epub 2018 Jul 7.

Department of Developmental Biology, Washington University School of Medicine, St. Louis, MO, 63110, USA.

Purkinje neurons, the sole output of the cerebellar cortex, deliver GABA-mediated inhibition to the deep cerebellar nuclei. To subserve this critical function, Purkinje neurons fire repetitively, and at high frequencies, features that have been linked to the unique properties of the voltage-gated sodium (Nav) channels expressed. In addition to the rapidly activating and inactivating, or transient, component of the Nav current (I) present in many types of central and peripheral neurons, Purkinje neurons, also expresses persistent (I) and resurgent (I) Nav currents. Read More

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Dsg2 via Src-mediated transactivation shapes EGFR signaling towards cell adhesion.

Cell Mol Life Sci 2018 Jul 6. Epub 2018 Jul 6.

Department I, Institute of Anatomy and Cell Biology, Ludwig Maximilians University Munich, Pettenkoferstr. 11, 80336, Munich, Germany.

Rapidly renewing epithelial tissues such as the intestinal epithelium require precise tuning of intercellular adhesion and proliferation to preserve barrier integrity. Here, we provide evidence that desmoglein 2 (Dsg2), an adhesion molecule of desmosomes, controls cell adhesion and proliferation via epidermal growth factor receptor (EGFR) signaling. Dsg2 is required for EGFR localization at intercellular junctions as well as for Src-mediated EGFR activation. Read More

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July 2018
1 Read

Crosstalk between metabolism and epigenetic modifications in autoimmune diseases: a comprehensive overview.

Cell Mol Life Sci 2018 Jul 4. Epub 2018 Jul 4.

Department of Dermatology, The Second Xiangya Hospital, Central South University, Hunan Key Laboratory of Medical Epigenomics, No. 139 Renmin Middle Rd, Changsha, 410011, Hunan, China.

Little information is available regarding mechanistic links between epigenetic modifications and autoimmune diseases. It seems plausible to surmise that aberrant gene expression and energy metabolism would disrupt immune tolerance, which could ultimately result in autoimmune responses. Metaboloepigenetics is an emerging paradigm that defines the interrelationships between metabolism and epigenetics. Read More

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July 2018
1 Read

Trans-spliced long non-coding RNA: an emerging regulator of pluripotency.

Cell Mol Life Sci 2018 Jun 30. Epub 2018 Jun 30.

Institute of Cellular and Organismic Biology, Academia Sinica, No. 128, Sec. 2, Academia Road, Nankang, Taipei, 11529, Taiwan.

With dual capacities for unlimited self-renewal and pluripotent differentiation, pluripotent stem cells (PSCs) give rise to many cell types in our body and PSC culture systems provide an unparalleled opportunity to study early human development and disease. Accumulating evidence indicates that the molecular mechanisms underlying pluripotency maintenance in PSCs involve many factors. Among these regulators, recent studies have shown that long non-coding RNAs (lncRNAs) can affect the pluripotency circuitry by cooperating with master pluripotency-associated factors. Read More

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Transcriptional regulation of murine natural killer cell development, differentiation and maturation.

Cell Mol Life Sci 2018 Jun 29. Epub 2018 Jun 29.

Department of Oncology UNIL CHUV, University of Lausanne, Ch. des Boveresses 155, 1066, Epalinges, Switzerland.

Natural killer (NK) cells are innate cytotoxic effector cells that play important protective roles against certain pathogens as well as against pathogen-infected and transformed host cells. NK cells continuously arise from adult bone marrow-resident haematopoietic progenitors. Their generation can be sub-divided into three phases. Read More

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Inhibition of SRC family kinases facilitates anti-CTLA4 immunotherapy in head and neck squamous cell carcinoma.

Cell Mol Life Sci 2018 Jun 28. Epub 2018 Jun 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, 237 Luoyu Road, Wuhan, 430079, China.

The immune system plays a critical role in the establishment, development, and progression of head and neck squamous cell carcinoma (HNSCC). As treatment with single-immune checkpoint agent results in a lower response rate in patients, it is important to investigate new strategies to maintain favorable anti-tumor immune response. Herein, the combination immunotherapeutic value of CTLA4 blockade and SFKs inhibition was assessed in transgenic HNSCC mouse model. Read More

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June 2018
2 Reads

Coordination of microtubule acetylation and the actin cytoskeleton by formins.

Cell Mol Life Sci 2018 Jun 15. Epub 2018 Jun 15.

Department of Cell Biology and Immunology, Centro de Biología Molecular Severo Ochoa, Consejo Superior de Investigaciones Científicas and Universidad Autónoma, Madrid, Spain.

The acetylation of the lysine 40 residue of α-tubulin was described more than 30 years ago and has been the subject of intense research ever since. Although the exact function of this covalent modification of tubulin in the cell remains unknown, it has been established that tubulin acetylation confers resilience to mechanical stress on the microtubules. Formins have a dual role in the fate of the actin and tubulin cytoskeletons. Read More

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June 2018
1 Read

Mechanisms of protein toxicity in neurodegenerative diseases.

Cell Mol Life Sci 2018 Jun 12. Epub 2018 Jun 12.

Department of Brain and Cognitive Sciences, DGIST, Daegu, 42988, Republic of Korea.

Protein toxicity can be defined as all the pathological changes that ensue from accumulation, mis-localization, and/or multimerization of disease-specific proteins. Most neurodegenerative diseases manifest protein toxicity as one of their key pathogenic mechanisms, the details of which remain unclear. By systematically deconstructing the nature of toxic proteins, we aim to elucidate and illuminate some of the key mechanisms of protein toxicity from which therapeutic insights may be drawn. Read More

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OSBP-related protein-2 (ORP2): a novel Akt effector that controls cellular energy metabolism.

Cell Mol Life Sci 2018 Jun 12. Epub 2018 Jun 12.

Minerva Foundation Institute for Medical Research, Biomedicum 2U, Tukholmankatu 8, 00290, Helsinki, Finland.

ORP2 is a ubiquitously expressed OSBP-related protein previously implicated in endoplasmic reticulum (ER)-lipid droplet (LD) contacts, triacylglycerol (TG) metabolism, cholesterol transport, adrenocortical steroidogenesis, and actin-dependent cell dynamics. Here, we characterize the role of ORP2 in carbohydrate and lipid metabolism by employing ORP2-knockout (KO) hepatoma cells (HuH7) generated by CRISPR-Cas9 gene editing. The ORP2-KO and control HuH7 cells were subjected to RNA sequencing, analyses of Akt signaling, carbohydrate and TG metabolism, the extracellular acidification rate, and the lipidome, as well as to transmission electron microscopy. Read More

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Targeting Nrf-2 is a promising intervention approach for the prevention of ethanol-induced liver disease.

Cell Mol Life Sci 2018 Jun 11. Epub 2018 Jun 11.

Institute of Toxicology, School of Public Health, Shandong University, 44 Wenhua West Road, Jinan, 250012, Shandong, China.

Alcoholic liver disease (ALD) remains to be a worldwide health problem. It is generally accepted that oxidative stress plays critical roles in the pathogenesis of ALD, and antioxidant therapy represents a logical strategy for the prevention and treatment of ALD. Nuclear factor erythroid-derived 2-like 2 (NFE2L2 or Nrf-2) is essential for the antioxidant responsive element (ARE)-mediated induction of endogenous antioxidant enzymes such as heme oxygenase 1 (HO-1) and glutamate-cysteine ligase [GCL, the rate-limiting enzyme in the synthesis of glutathione (GSH)]. Read More

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June 2018
5 Reads

Caveolar targeting links Kv1.3 with the insulin-dependent adipocyte physiology.

Cell Mol Life Sci 2018 Jun 11. Epub 2018 Jun 11.

Molecular Physiology Laboratory, Dpt. de Bioquímica i Biomedicina Molecular, Universitat de Barcelona, Av. Diagonal 643, 08028, Barcelona, Spain.

The voltage-dependent potassium channel Kv1.3 participates in peripheral insulin sensitivity. Genetic ablation of Kv1. Read More

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June 2018
2 Reads

Response of vascular mesenchymal stem/progenitor cells to hyperlipidemia.

Cell Mol Life Sci 2018 Jun 26. Epub 2018 Jun 26.

Department of Cardiology, The First Affiliated Hospital, School of Medicine, Zhejiang University, Zhejiang, China.

Hyperlipidemia is a risk factor for atherosclerosis that is characterized by lipid accumulation, inflammatory cell infiltration, and smooth muscle cell proliferation. It is well known that hyperlipidemia is a stimulator for endothelial dysfunction and smooth muscle cell migration during vascular disease development. Recently, it was found that vessel wall contains a variable number of mesenchymal stem cells (MSCs) that are quiescent in physiological conditions, but can be activated by a variety of stimuli, e. Read More

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June 2018
2 Reads

Pivotal role of LBD16 in root and root-like organ initiation.

Cell Mol Life Sci 2018 Jun 25. Epub 2018 Jun 25.

National Key Laboratory of Plant Molecular Genetics, CAS Center for Excellence in Molecular Plant Sciences, Shanghai Institute of Plant Physiology and Ecology, Chinese Academy of Sciences, Shanghai, China.

In the post-embryonic stage of Arabidopsis thaliana, roots can be initiated from the vascular region of the existing roots or non-root organs; they are designated as lateral roots (LRs) and adventitious roots (ARs), respectively. Some root-like organs can also be initiated from the vasculature. In tissue culture, auxin-induced callus, which is a group of pluripotent root-primordium-like cells, is formed via the rooting pathway. Read More

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Neuronal GAP-Porf-2 transduces EphB1 signaling to brake axon growth.

Cell Mol Life Sci 2018 Jun 25. Epub 2018 Jun 25.

Department of Neurosurgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, No. 280 Mo-He Road, Shanghai, 201900, China.

Axonal outgrowth and guidance require numerous extracellular cues and intracellular mediators that transduce signals in the growth cone to regulate cytoskeletal dynamics. However, the way in which cytoskeletal effectors respond to these signals remains elusive. Here, we demonstrate that Porf-2, a neuron-expressed RhoGTPase-activating protein, plays an essential role in the inhibition of initial axon growth by restricting the expansion of the growth cone in a cell-autonomous manner. Read More

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June 2018
1 Read

Molecular mechanisms of hepatic lipid accumulation in non-alcoholic fatty liver disease.

Cell Mol Life Sci 2018 Jun 23. Epub 2018 Jun 23.

Department of Veterinary and Animal Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Ridebanevej 9, 1870, Frederiksberg C, Denmark.

Non-alcoholic fatty liver disease (NAFLD) is currently the world's most common liver disease, estimated to affect up to one-fourth of the population. Hallmarked by hepatic steatosis, NAFLD is associated with a multitude of detrimental effects and increased mortality. This narrative review investigates the molecular mechanisms of hepatic steatosis in NAFLD, focusing on the four major pathways contributing to lipid homeostasis in the liver. Read More

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Galectin-8 induces functional disease markers in human osteoarthritis and cooperates with galectins-1 and -3.

Cell Mol Life Sci 2018 Jun 22. Epub 2018 Jun 22.

Institute of Physiological Chemistry, Faculty of Veterinary Medicine, Ludwig-Maximilians-University Munich, Munich, Germany.

The reading of glycan-encoded signals by tissue lectins is considered a major route of the flow of biological information in many (patho)physiological processes. The arising challenge for current research is to proceed from work on a distinct protein to family-wide testing of lectin function. Having previously identified homodimeric galectin-1 and chimera-type galectin-3 as molecular switches in osteoarthritis progression, we here provide proof-of-principle evidence for an intra-network cooperation of galectins with three types of modular architecture. Read More

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Histones and heart failure in diabetes.

Cell Mol Life Sci 2018 Jun 22. Epub 2018 Jun 22.

Keenan Research Centre for Biomedical Science and Li Ka Shing Knowledge Institute of St. Michael's Hospital, 6-151, 61 Queen Street East, Toronto, ON, M5C 2T2, Canada.

Although heart failure is now accepted as being a major long-term complication of diabetes, many of the recent advances in our understanding of the pathobiology of diabetes complications have come about through the study of more traditional microvascular or macrovascular diseases. This has been the case, for example, in the evolving field of the epigenetics of diabetes complications and, in particular, the post-translational modification of histone proteins. However, histone modifications also occur in human heart failure and their perturbation also occurs in diabetic hearts. Read More

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June 2018
1 Read

Megalin mediates plasma membrane to mitochondria cross-talk and regulates mitochondrial metabolism.

Cell Mol Life Sci 2018 Jun 9. Epub 2018 Jun 9.

Division of Nephrology, Department of Medicine, Selzman Institute for Kidney Health, Baylor College of Medicine, One Baylor Plaza, ABBR R706, M/S BCM395, Houston, TX, 77030-3498, USA.

Mitochondrial intracrines are extracellular signaling proteins, targeted to the mitochondria. The pathway for mitochondrial targeting of mitochondrial intracrines and actions in the mitochondria remains unknown. Megalin/LRP2 mediates the uptake of vitamins and proteins, and is critical for clearance of amyloid-β protein from the brain. Read More

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June 2018
2 Reads

Correction to: Cellular mechanisms responsible for cell-to-cell spreading of prions.

Cell Mol Life Sci 2018 Jul;75(14):2575

Insitut NeuroMyoGène, CNRS UMR5310, INSERM U1217, Faculté de Médecine Rockefeller, Université Claude Bernard Lyon I, 8 Avenue Rockefeller, 69373, Lyon Cedex 08, France.

In the original publication, part of acknowledgement text was missing. The complete acknowledgement section should read as follows. Read More

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July 2018
1 Read

The role of survival motor neuron protein (SMN) in protein homeostasis.

Cell Mol Life Sci 2018 Jun 5. Epub 2018 Jun 5.

Euan MacDonald Centre for Motor Neurone Disease Research, University of Edinburgh, Edinburgh, UK.

Ever since loss of survival motor neuron (SMN) protein was identified as the direct cause of the childhood inherited neurodegenerative disorder spinal muscular atrophy, significant efforts have been made to reveal the molecular functions of this ubiquitously expressed protein. Resulting research demonstrated that SMN plays important roles in multiple fundamental cellular homeostatic pathways, including a well-characterised role in the assembly of the spliceosome and biogenesis of ribonucleoproteins. More recent studies have shown that SMN is also involved in other housekeeping processes, including mRNA trafficking and local translation, cytoskeletal dynamics, endocytosis and autophagy. Read More

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June 2018
5 Reads

Regulating the human HECT E3 ligases.

Cell Mol Life Sci 2018 Jun 1. Epub 2018 Jun 1.

Department of Medical Biochemistry, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.

Ubiquitination, the covalent attachment of ubiquitin to proteins, by E3 ligases of the HECT (homologous to E6AP C terminus) family is critical in controlling diverse physiological pathways. Stringent control of HECT E3 ligase activity and substrate specificity is essential for cellular health, whereas deregulation of HECT E3s plays a prominent role in disease. The cell employs a wide variety of regulatory mechanisms to control HECT E3 activity and substrate specificity. Read More

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June 2018
1 Read

The adhesion receptor GPR56 is activated by extracellular matrix collagen III to improve β-cell function.

Cell Mol Life Sci 2018 May 31. Epub 2018 May 31.

Department of Diabetes, School of Life Course Sciences, King's College London, Guy's Campus, London, SE1 1UL, UK.

Aims: G-protein coupled receptor 56 (GPR56) is the most abundant islet-expressed G-protein coupled receptor, suggesting a potential role in islet function. This study evaluated islet expression of GPR56 and its endogenous ligand collagen III, and their effects on β-cell function.

Methods: GPR56 and collagen III expression in mouse and human pancreas sections was determined by fluorescence immunohistochemistry. Read More

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May 2018
4 Reads

Immune stimuli shape the small non-coding transcriptome of extracellular vesicles released by dendritic cells.

Cell Mol Life Sci 2018 May 28. Epub 2018 May 28.

Department of Biochemistry and Cell Biology, Faculty of Veterinary Medicine, Utrecht University, Utrecht, The Netherlands.

The release and uptake of nano-sized extracellular vesicles (EV) is a highly conserved means of intercellular communication. The molecular composition of EV, and thereby their signaling function to target cells, is regulated by cellular activation and differentiation stimuli. EV are regarded as snapshots of cells and are, therefore, in the limelight as biomarkers for disease. Read More

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May 2018
9 Reads

Maternal eating behavior is a major synchronizer of fetal and postnatal peripheral clocks in mice.

Cell Mol Life Sci 2018 May 26. Epub 2018 May 26.

Université de Lyon, Université Claude Bernard Lyon 1, Ecole Normale Supérieure de Lyon; CNRS UMR 5242, Institut de Génomique Fonctionnelle de Lyon, 46 allée d'Italie, 69364, Lyon, France.

Most living organisms show circadian rhythms in physiology and behavior. These oscillations are generated by endogenous circadian clocks, present in virtually all cells where they control key biological processes. To study peripheral clocks in vivo, we developed an original model, the Rev-Luc mouse to follow noninvasively and longitudinally Rev-Luc oscillations in peripheral clocks using in vivo bioluminescence imaging. Read More

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May 2018
1 Read

MAP kinase signalling: interplays between plant PAMP- and effector-triggered immunity.

Cell Mol Life Sci 2018 Aug 22;75(16):2981-2989. Epub 2018 May 22.

Department of Botany, University of British Columbia, Vancouver, BC, V6T 1Z4, Canada.

In plants, mitogen-activated protein kinase (MAPK) cascades are involved in regulating many biological processes including immunity. They relay signals from membrane-residing immune receptors to downstream components for defense activation. Arabidopsis MPK3/6 and MPK4 are activated in two parallel MAPK cascades during PAMP-triggered immunity. Read More

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August 2018
1 Read

Role of peroxisome proliferator-activated receptors in non-alcoholic fatty liver disease inflammation.

Cell Mol Life Sci 2018 Aug 22;75(16):2951-2961. Epub 2018 May 22.

Laboratory of Ultrastructure, Aggeu Magalhães Institute (IAM), Avenida Professor Moraes Rego, s/n, Cidade Universitária, Recife, PE, 50670-420, Brazil.

Overweight and obesity have been identified as the most important risk factors for many diseases, including cardiovascular disease, type 2 diabetes and lipid disorders, such as non-alcoholic fatty liver disease (NAFLD). The metabolic changes associated with obesity are grouped to define metabolic syndrome, which is one of the main causes of morbidity and mortality in industrialized countries. NAFLD is considered to be the hepatic manifestation of metabolic syndrome and is one of the most prevalent liver diseases worldwide. Read More

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August 2018
1 Read

GLIS1-3 transcription factors: critical roles in the regulation of multiple physiological processes and diseases.

Authors:
Anton M Jetten

Cell Mol Life Sci 2018 May 19. Epub 2018 May 19.

Cell Biology Group, Immunity, Inflammation and Disease Laboratory, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC, 27709, USA.

Krüppel-like zinc finger proteins form one of the largest families of transcription factors. They function as key regulators of embryonic development and a wide range of other physiological processes, and are implicated in a variety of pathologies. GLI-similar 1-3 (GLIS1-3) constitute a subfamily of Krüppel-like zinc finger proteins that act either as activators or repressors of gene transcription. Read More

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May 2018
1 Read

Combining theoretical and experimental data to decipher CFTR 3D structures and functions.

Cell Mol Life Sci 2018 May 19. Epub 2018 May 19.

Sorbonne Université, Muséum National d'Histoire Naturelle, UMR CNRS 7590, IRD, Institut de Minéralogie, de Physique des Matériaux et de Cosmochimie, IMPMC, 75005, Paris, France.

Cryo-electron microscopy (cryo-EM) has recently provided invaluable experimental data about the full-length cystic fibrosis transmembrane conductance regulator (CFTR) 3D structure. However, this experimental information deals with inactive states of the channel, either in an apo, quiescent conformation, in which nucleotide-binding domains (NBDs) are widely separated or in an ATP-bound, yet closed conformation. Here, we show that 3D structure models of the open and closed forms of the channel, now further supported by metadynamics simulations and by comparison with the cryo-EM data, could be used to gain some insights into critical features of the conformational transition toward active CFTR forms. Read More

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May 2018
2 Reads

The potential importance of myeloid-derived suppressor cells (MDSCs) in the pathogenesis of Alzheimer's disease.

Cell Mol Life Sci 2018 May 19. Epub 2018 May 19.

School of Pharmacy, Faculty of Health Sciences, University of Eastern Finland, P.O. Box 1627, 70211, Kuopio, Finland.

The exact cause of Alzheimer's disease (AD) is still unknown, but the deposition of amyloid-β (Aβ) plaques and chronic inflammation indicates that immune disturbances are involved in AD pathogenesis. Recent genetic studies have revealed that many candidate genes are expressed in both microglia and myeloid cells which infiltrate into the AD brains. Invading myeloid cells controls the functions of resident microglia in pathological conditions, such as AD pathology. Read More

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May 2018
3 Reads

Mitochondrial quality control in AMD: does mitophagy play a pivotal role?

Cell Mol Life Sci 2018 Aug 18;75(16):2991-3008. Epub 2018 May 18.

Department of Molecular Genetics, University of Łódź, Pomorska 141/143, 90-236, Łódź, Poland.

Age-related macular degeneration (AMD) is the predominant cause of visual loss in old people in the developed world, whose incidence is increasing. This disease is caused by the decrease in macular function, due to the degeneration of retinal pigment epithelium (RPE) cells. The aged retina is characterised by increased levels of reactive oxygen species (ROS), impaired autophagy, and DNA damage that are linked to AMD pathogenesis. Read More

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August 2018
1 Read

Roles of heat shock factor 1 beyond the heat shock response.

Cell Mol Life Sci 2018 Aug 17;75(16):2897-2916. Epub 2018 May 17.

Department of Genetics, Eötvös Loránd University, Pázmány Péter Stny. 1/C, Budapest, 1117, Hungary.

Various stress factors leading to protein damage induce the activation of an evolutionarily conserved cell protective mechanism, the heat shock response (HSR), to maintain protein homeostasis in virtually all eukaryotic cells. Heat shock factor 1 (HSF1) plays a central role in the HSR. HSF1 was initially known as a transcription factor that upregulates genes encoding heat shock proteins (HSPs), also called molecular chaperones, which assist in refolding or degrading injured intracellular proteins. Read More

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August 2018
6 Reads

Involvement of extrasynaptic glutamate in physiological and pathophysiological changes of neuronal excitability.

Authors:
Balázs Pál

Cell Mol Life Sci 2018 May 15. Epub 2018 May 15.

Department of Physiology, Faculty of Medicine, University of Debrecen, Nagyerdei krt 98, Debrecen, 4012, Hungary.

Glutamate is the most abundant neurotransmitter of the central nervous system, as the majority of neurons use glutamate as neurotransmitter. It is also well known that this neurotransmitter is not restricted to synaptic clefts, but found in the extrasynaptic regions as ambient glutamate. Extrasynaptic glutamate originates from spillover of synaptic release, as well as from astrocytes and microglia. Read More

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May 2018
1 Read

Imaging of oxygen and hypoxia in cell and tissue samples.

Cell Mol Life Sci 2018 May 14. Epub 2018 May 14.

School of Biochemistry and Cell Biology, University College Cork, Cavanagh Pharmacy Building, College Road, Cork, Ireland.

Molecular oxygen (O) is a key player in cell mitochondrial function, redox balance and oxidative stress, normal tissue function and many common disease states. Various chemical, physical and biological methods have been proposed for measurement, real-time monitoring and imaging of O concentration, state of decreased O (hypoxia) and related parameters in cells and tissue. Here, we review the established and emerging optical microscopy techniques allowing to visualize O levels in cells and tissue samples, mostly under in vitro and ex vivo, but also under in vivo settings. Read More

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Cellular mechanisms responsible for cell-to-cell spreading of prions.

Cell Mol Life Sci 2018 May 14. Epub 2018 May 14.

Insitut NeuroMyoGène, CNRS UMR5310, INSERM U1217, Faculté de Médecine Rockefeller, Université Claude Bernard Lyon I, 8 Avenue Rockefeller, 69373, Lyon Cedex 08, France.

Prions are infectious agents that cause fatal neurodegenerative diseases. Current evidence indicates that they are essentially composed of an abnormally folded protein (PrP). These abnormal aggregated PrP species multiply in infected cells by recruiting and converting the host PrP protein into new PrP. Read More

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May 2018
2 Reads

The capacity of oocytes for DNA repair.

Cell Mol Life Sci 2018 Aug 10;75(15):2777-2792. Epub 2018 May 10.

Ovarian Biology Laboratory, Department of Anatomy and Developmental Biology, Biomedicine Discovery Institute, Monash University, Melbourne, Australia.

Female fertility and offspring health are critically dependent on the maintenance of an adequate supply of high-quality oocytes. Like somatic cells, oocytes are subject to a variety of different types of DNA damage arising from endogenous cellular processes and exposure to exogenous genotoxic stressors. While the repair of intentionally induced DNA double strand breaks in gametes during meiotic recombination is well characterised, less is known about the ability of oocytes to repair pathological DNA damage and the relative contribution of DNA repair to oocyte quality is not well defined. Read More

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August 2018
1 Read

Control of excessive neural circuit excitability and prevention of epileptic seizures by endocannabinoid signaling.

Cell Mol Life Sci 2018 Aug 8;75(15):2793-2811. Epub 2018 May 8.

Department of Neurophysiology, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Tokyo, 113-0033, Japan.

Progress in research on endocannabinoid signaling has greatly advanced our understanding of how it controls neural circuit excitability in health and disease. In general, endocannabinoid signaling at excitatory synapses suppresses seizures by inhibiting glutamate release. In contrast, endocannabinoid signaling promotes seizures by inhibiting GABA release at inhibitory synapses. Read More

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August 2018
2 Reads

Engineering microbes for targeted strikes against human pathogens.

Cell Mol Life Sci 2018 May 7. Epub 2018 May 7.

Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, 8 Medical Drive, Singapore, 117596, Singapore.

Lack of pathogen specificity in antimicrobial therapy causes non-discriminant microbial cell killing that disrupts the microflora present. As a result, potentially helpful microbial cells are killed along with the pathogen, altering the biodiversity and dynamic interactions within the population. Moreover, the unwarranted exposure of antibiotics to microbes increases the likelihood of developing resistance and perpetuates the emergence of multidrug resistance. Read More

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May 2018
1 Read

Seed coat thickness in the evolution of angiosperms.

Cell Mol Life Sci 2018 Jul 5;75(14):2509-2518. Epub 2018 May 5.

Institut Jean-Pierre Bourgin, INRA, AgroParisTech, CNRS, University of Paris-Saclay, Route de St-Cyr (RD10), 78026, Versailles Cedex, France.

The seed habit represents a remarkable evolutionary advance in plant sexual reproduction. Since the Paleozoic, seeds carry a seed coat that protects, nourishes and facilitates the dispersal of the fertilization product(s). The seed coat architecture evolved to adapt to different environments and reproductive strategies in part by modifying its thickness. Read More

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July 2018
1 Read

Including the mitochondrial metabolism of L-lactate in cancer metabolic reprogramming.

Cell Mol Life Sci 2018 Aug 4;75(15):2763-2776. Epub 2018 May 4.

Istituto di Biomembrane, Bioenergetica e Biotecnologie Molecolari (IBIOM)-CNR, Via G. Amendola 165/A, 70126, Bari, Italy.

Glucose avidity, high glycolysis and L-lactate production, regardless of oxygen availability, are the main traits of cancer metabolic reprogramming. The idea that mitochondria are dysfunctional in cancer, thus causing a glycolysis increase for ATP production and L-lactate accumulation as a dead-end product of glucose catabolism, has oriented cancer research for many years. However, it was shown that mitochondrial metabolism is essential for cancer cell proliferation and tumorigenesis and that L-lactate is a fundamental energy substrate with tumor growth-promoting and signaling capabilities. Read More

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August 2018
1 Read

Why the impact of mechanical stimuli on stem cells remains a challenge.

Cell Mol Life Sci 2018 May 4. Epub 2018 May 4.

Helmholtz Institute for Biomedical Engineering, Stem Cell Biology and Cellular Engineering, RWTH Aachen University Medical School, Aachen, Germany.

Mechanical stimulation affects growth and differentiation of stem cells. This may be used to guide lineage-specific cell fate decisions and therefore opens fascinating opportunities for stem cell biology and regenerative medicine. Several studies demonstrated functional and molecular effects of mechanical stimulation but on first sight these results often appear to be inconsistent. Read More

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May 2018
1 Read

Proliferation of hippocampal progenitors relies on p27-dependent regulation of Cdk6 kinase activity.

Cell Mol Life Sci 2018 May 4. Epub 2018 May 4.

Laboratory of Developmental Neurobiology, GIGA-Neurosciences, Quartier Hôpital, University of Liège, Avenue Hippocrate 15, B36 +1, 4000, Liège, Belgium.

Neural stem cells give rise to granule dentate neurons throughout life in the hippocampus. Upon activation, these stem cells generate fast proliferating progenitors that complete several rounds of divisions before differentiating into neurons. Although the mechanisms regulating the activation of stem cells have been intensively studied, little attention has been given so far to the intrinsic machinery allowing the expansion of the progenitor pool. Read More

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May 2018
1 Read

The impact of phosphatases on proliferative and survival signaling in cancer.

Cell Mol Life Sci 2018 Aug 3;75(15):2695-2718. Epub 2018 May 3.

Case Western Reserve University, Cleveland, OH, USA.

The dynamic and stringent coordination of kinase and phosphatase activity controls a myriad of physiologic processes. Aberrations that disrupt the balance of this interplay represent the basis of numerous diseases. For a variety of reasons, early work in this area portrayed kinases as the dominant actors in these signaling events with phosphatases playing a secondary role. Read More

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August 2018
1 Read

Phosphatidylinositol-3,5-bisphosphate lipid-binding-induced activation of the human two-pore channel 2.

Cell Mol Life Sci 2018 Apr 28. Epub 2018 Apr 28.

Molecular Plant Physiology, Department of Biology, Friedrich-Alexander Universität Erlangen-Nürnberg, Erlangen, Germany.

Mammalian two-pore channels (TPCs) are activated by the low-abundance membrane lipid phosphatidyl-(3,5)-bisphosphate (PI(3,5)P) present in the endo-lysosomal system. Malfunction of human TPC1 or TPC2 (hTPC) results in severe organellar storage diseases and membrane trafficking defects. Here, we compared the lipid-binding characteristics of hTPC2 and of the PI(3,5)P-insensitive TPC1 from the model plant Arabidopsis thaliana. Read More

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April 2018
2 Reads

Fibroblast growth factor receptor 1 signaling transcriptionally regulates the axon guidance cue slit1.

Cell Mol Life Sci 2018 Apr 28. Epub 2018 Apr 28.

Department of Cell Biology and Anatomy, Hotchkiss Brain Institute, Alberta Children's Hospital Research Institute, Cumming School of Medicine, University of Calgary, 3330 Hospital Dr., NW, Calgary, AB, T2N 4N1, Canada.

Axons sense molecular cues in their environment to arrive at their post-synaptic targets. While many of the molecular cues have been identified, the mechanisms that regulate their spatiotemporal expression remain elusive. We examined here the transcriptional regulation of the guidance gene slit1 both in vitro and in vivo by specific fibroblast growth factor receptors (Fgfrs). Read More

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April 2018
2 Reads

Impact of late-onset Alzheimer's genetic risk factors on beta-amyloid endocytic production.

Cell Mol Life Sci 2018 Jul 27;75(14):2577-2589. Epub 2018 Apr 27.

Neuronal Trafficking in Aging Lab, CEDOC, Chronic Diseases Research Centre, NOVA Medical School|Faculdade de Ciências Médicas, Universidade NOVA de Lisboa, Campo Mártires da Pátria, 130, 1169-056, Lisbon, Portugal.

The increased production of the 42 aminoacids long beta-amyloid (Aβ42) peptide has been established as a causal mechanism of the familial early onset Alzheimer's disease (AD). In contrast, the causal mechanisms of the late-onset AD (LOAD), that affects most AD patients, remain to be established. Indeed, Aβ42 accumulation has been detected more than 30 years before diagnosis. Read More

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July 2018
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Functional characterisation of naturally occurring mutations in human melanopsin.

Cell Mol Life Sci 2018 Apr 26. Epub 2018 Apr 26.

Nuffield Laboratory of Ophthalmology, Sleep and Circadian Neuroscience Institute, Nuffield Department of Clinical Neurosciences, Sir William Dunn School of Pathology, University of Oxford, OMPI G, South Parks Road, Oxford, OX1 3RE, UK.

Melanopsin is a blue light-sensitive opsin photopigment involved in a range of non-image forming behaviours, including circadian photoentrainment and the pupil light response. Many naturally occurring genetic variants exist within the human melanopsin gene (OPN4), yet it remains unclear how these variants affect melanopsin protein function and downstream physiological responses to light. Here, we have used bioinformatic analysis and in vitro expression systems to determine the functional phenotypes of missense human OPN4 variants. Read More

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April 2018
2 Reads

PAR3-PAR6-atypical PKC polarity complex proteins in neuronal polarization.

Cell Mol Life Sci 2018 Aug 25;75(15):2735-2761. Epub 2018 Apr 25.

Department of Neurology, School of Medicine, Yale University, 300 George Street, New Haven, CT, 06511, USA.

Polarity is a fundamental feature of cells. Protein complexes, including the PAR3-PAR6-aPKC complex, have conserved roles in establishing polarity across a number of eukaryotic cell types. In neurons, polarity is evident as distinct axonal versus dendritic domains. Read More

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August 2018
7 Reads