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    99943 results match your criteria Biochimica et Biophysica Acta[Journal]

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    The endoscopist and malignant and non-malignant biliary obstruction.
    Biochim Biophys Acta 2017 Sep 17. Epub 2017 Sep 17.
    Department of Gastroenterology, University College London NHS Foundation Trust, London, UK.
    Patients with biliary strictures often represent a diagnostic and therapeutic challenge, due to the site and complexity of biliary obstruction and wide differential diagnosis. Multidisciplinary decision making is required to reach an accurate and timely diagnosis and to plan optimal care. Developments in endoscopic ultrasound and peroral cholangioscopy have advanced the diagnostic yield of biliary endoscopy, and novel optical imaging techniques are emerging. Read More

    BMP7-induced-Pten inhibits Akt and prevents renal fibrosis.
    Biochim Biophys Acta 2017 Sep 15. Epub 2017 Sep 15.
    UCD Diabetes Complications Research Centre, School of Medicine, Conway Institute, University College Dublin, Belfield, Dublin 4, Ireland.
    Bone morphogenetic protein-7 (BMP-7) counteracts pro-fibrotic effects of TGFβ1 in cultured renal cells and protects from fibrosis in acute and chronic renal injury models. Using the unilateral ureteral obstruction (UUO) model of chronic renal fibrosis, we investigated the effect of exogenous-rhBMP-7 on pro-fibrotic signaling pathways mediated by TGFβ1 and hypoxia. Mice undergoing UUO were treated with vehicle or rhBMP-7 (300μg/kg i. Read More

    Modulation of the picosecond dynamics of troponin by the cardiomyopathy-causing mutation K247R of troponin T observed by quasielastic neutron scattering.
    Biochim Biophys Acta 2017 Sep 15. Epub 2017 Sep 15.
    Quantum Beam Science Research Directorate, National Institutes for Quantum and Radiological Science and Technology, Tokai, Ibaraki 319-1106, Japan.. Electronic address:
    Troponin (Tn), consisting of three subunits (TnC, TnI, and TnT), regulates cardiac muscle contraction in a Ca(2+)-dependent manner. Various point mutations of human cardiac Tn are known to cause familial hypertrophic cardiomyopathy due to aberration of the regulatory function. In this study, we investigated the effects of one of these mutations, K247R of TnT, on the picosecond dynamics of the Tn core domain (Tn-CD), consisting of TnC, TnI and TnT2 (183-288 residues of TnT), by carrying out the quasielastic neutron scattering measurements on the reconstituted Tn-CD containing either the wild-type TnT2 (wtTn-CD) or the mutant TnT2 (K247R-Tn-CD) in the absence and presence of Ca(2+). Read More

    Selecting of a cytochrome P450cam SeSaM library with 3-Chloroindole and Endosulfan - Identification of mutants that Dehalogenate 3-Chloroindole.
    Biochim Biophys Acta 2017 Sep 15. Epub 2017 Sep 15.
    Department of Chemistry, Simon Fraser University, 8888 University Drive, Burnaby, BC, Canada - V5A 1S6. Electronic address:
    Cytochrome P450cam (a camphor hydroxylase) from the soil bacterium Pseudomonas putida shows potential importance in environmental applications such as the degradation of chlorinated organic pollutants. Seven P450cam mutants generated from Sequence Saturation Mutagenesis (SeSaM) and isolated by selection on minimal media with either 3-chloroindole or the insecticide endosulfan were studied for their ability to oxidize of 3-chloroindole to isatin. The wild-type enzyme did not accept 3-chloroindole as a substrate. Read More

    The roles of ubiquitin modifying enzymes in neoplastic disease.
    Biochim Biophys Acta 2017 Sep 15. Epub 2017 Sep 15.
    Cancer Science Institute of Singapore, National University of Singapore, 117599, Singapore; Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, 117597, Singapore. Electronic address:
    The initial experiments performed by Rose, Hershko, and Ciechanover describing the identification of a specific degradation signal in short-lived proteins paved the way to the discovery of the ubiquitin mediated regulation of numerous physiological functions required for cellular homeostasis. Since their discovery of ubiquitin and ubiquitin function over 30years ago it has become wholly apparent that ubiquitin and their respective ubiquitin modifying enzymes are key players in tumorigenesis. The human genome encodes approximately 600 putative E3 ligases and 80 deubiquitinating enzymes and in the majority of cases these enzymes exhibit specificity in sustaining either pro-tumorigenic or tumour repressive responses. Read More

    AKAP-Lbc mediates protection against doxorubicin-induced cardiomyocyte toxicity.
    Biochim Biophys Acta 2017 Sep 16. Epub 2017 Sep 16.
    Département de Pharmacologie et de Toxicologie, Faculté de Biologie et de Médecine, Lausanne 1005, Switzerland. Electronic address:
    Doxorubicin (DOX) is a chemotherapic agent that is widely used to treat hematological and solid tumors. Despite its efficacy, DOX displays significant cardiac toxicity associated with cardiomyocytes death and heart failure. Cardiac toxicity is mainly associated with the ability of DOX to alter mitochondrial function. Read More

    Structural and kinetics characterization of the F1F0-ATP synthase dimer. New repercussion of monomer-monomer contact.
    Biochim Biophys Acta 2017 Sep 14. Epub 2017 Sep 14.
    Departamento de Bioquímica, Facultad de Medicina, Universidad Nacional Autónoma de México. 04510, México City, Mexico. Electronic address:
    Ustilago maydis is an aerobic basidiomycete that fully depends on oxidative phosphorylation for its supply of ATP, pointing to mitochondria as a key player in the energy metabolism of this organism. Mitochondrial F1F0-ATP synthase occurs in supramolecular structures. In this work, we isolated the monomer (640kDa) and the dimer (1280kDa) and characterized their subunit composition and kinetics of ATP hydrolysis. Read More

    Hydrogen and oxygen trapping at the H-cluster of [FeFe]‑hydrogenase revealed by site-selective spectroscopy and QM/MM calculations.
    Biochim Biophys Acta 2017 Sep 14. Epub 2017 Sep 14.
    Department of Physics, Biophysics of Metalloenzymes, Freie Universität Berlin, 14195, Berlin, Germany. Electronic address:
    [FeFe]‑hydrogenases are superior hydrogen conversion catalysts. They bind a cofactor (H-cluster) comprising a four‑iron and a diiron unit with three carbon monoxide (CO) and two cyanide (CN(-)) ligands. Hydrogen (H2) and oxygen (O2) binding at the H-cluster was studied in the C169A variant of [FeFe]‑hydrogenase HYDA1, in comparison to the active oxidized (Hox) and CO-inhibited (Hox-CO) species in wildtype enzyme. Read More

    Cholesterol modulates the cellular localization of Orai1 channels and its disposition among membrane domains.
    Biochim Biophys Acta 2017 Sep 12. Epub 2017 Sep 12.
    Departamento de Biología Celular y del Desarrollo, Instituto de Fisiología Celular, Universidad Nacional Autónoma de México, Mexico. Electronic address:
    Store Operated Calcium Entry (SOCE) is one of the most important mechanisms for calcium mobilization in to the cell. Two main proteins sustain SOCE: STIM1 that acts as the calcium sensor in the endoplasmic reticulum (ER) and Orai1 responsible for calcium influx upon depletion of ER. There are many studies indicating that SOCE is modulated by the cholesterol content of the plasma membrane (PM). Read More

    FABP1 knockdown in human enterocytes impairs proliferation and alters lipid metabolism.
    Biochim Biophys Acta 2017 Sep 12. Epub 2017 Sep 12.
    Instituto de Investigaciones Bioquímicas de La Plata, Facultad de Ciencias Médicas, Universidad Nacional de La Plata, La Plata, Buenos Aires, Argentina. Electronic address:
    Fatty Acid-Binding Proteins (FABPs) are abundant intracellular proteins that bind long chain fatty acids (FA) and have been related with inmunometabolic diseases. Intestinal epithelial cells express two isoforms of FABPs: liver FABP (LFABP or FABP1) and intestinal FABP (IFABP or FABP2). They are thought to be associated with intracellular dietary lipid transport and trafficking towards diverse cell fates. Read More

    Atorvastatin reduces lipid accumulation in the liver by activating protein kinase A-mediated phosphorylation of perilipin 5.
    Biochim Biophys Acta 2017 Sep 12. Epub 2017 Sep 12.
    Department of Pathology, Xijing Hospital, Fourth Military Medical University, Xi'an 710032, China. Electronic address:
    Statins have been proven to be effective in treating non-alcoholic fatty liver disease (NAFLD). Recently, it was reported that statins decreased the hepatic expression of perilipin 5 (Plin5), a lipid droplet (LD)-associated protein, which plays critical roles in regulating lipid accumulation and lipolysis in liver. However, the function and regulation mechanism of Plin5 have not yet been well-established in NAFLD treatment with statins. Read More

    Assignment of the absolute configuration of hepatoprotective highly oxygenated triterpenoids using X-ray, ECD, NMR J-based configurational analysis and HSQC overlay experiments.
    Biochim Biophys Acta 2017 Sep 14. Epub 2017 Sep 14.
    Department of Drug Discovery and Biomedical Sciences, College of Pharmacy, Medical University of South Carolina, Charleston, SC 29425, United States. Electronic address:
    Background: The plants of the genus Kadsura are widely distributed in China, South Korea, and Japan. Their roots and stems are traditionally used to treat blood diseases and pain. The main bioactive constituents of Kadsura longipedunculata comprise highly oxygenated triterpenoids. Read More

    Hepatic stellate cell-specific deletion of SIRT1 exacerbates liver fibrosis in mice.
    Biochim Biophys Acta 2017 Sep 14. Epub 2017 Sep 14.
    Key Laboratory of Cardiovascular Disease and Molecular Intervention and Key Laboratory of Human Functional Genomics of Jiangsu Province, Department of Pathophysiology, Nanjing Medical University, Nanjing, China. Electronic address:
    Liver fibrosis is widely perceived as a host defense mechanism that aids tissue repair following liver injury. Excessive fibrogenesis, however, serves to disrupts normal liver structure and precedes such irrevocable human pathologies as cirrhosis and hepatocellular carcinoma. Activation of hepatic stellate cells (HSCs) is a hallmark event during liver fibrosis. Read More

    Forward and reverse genetics approaches to uncover metabolic aging pathways in Caenorhabditis elegans.
    Biochim Biophys Acta 2017 Sep 14. Epub 2017 Sep 14.
    Laboratory Genetic Metabolic Diseases, Academic Medical Center of Amsterdam, 1105, AZ, Amsterdam, The Netherlands. Electronic address:
    The biological mechanisms of aging have been studied in depth and prominent findings in this field promote the development of new therapies for age-associated disorders. Various model organisms are used for research on aging; among these, the nematode Caenorhabditis elegans has been widely used and has provided valuable knowledge in determining the regulatory mechanisms driving the aging process. Many genes involved in lifespan regulation are associated with metabolic pathways and are influenced by genetic and environmental factors. Read More

    Suspension state increases reattachment of breast cancer cells by up-regulating lamin A/C.
    Biochim Biophys Acta 2017 Sep 14. Epub 2017 Sep 14.
    Key Laboratory of Biorheological Science and Technology, Ministry of Education, Bioengineering College, Chongqing University, Chongqing 400044, PR China; Mechanobiology and Regenerative Medicine Laboratory, Bioengineering College, Chongqing University, Chongqing 400044, PR China. Electronic address:
    Extravasation is a rate-limiting step of tumor metastasis, for which adhesion to endothelium of circulating tumor cells (CTCs) is the prerequisite. The suspension state of CTCs undergoing detachment from primary tumor is a persistent biomechanical cue, which potentially regulates the biophysical characteristics and cellular behaviors of tumor cells. In this study, breast tumor cells MDA-MB-231 in suspension culture condition were used to investigate the effect of suspension state on reattachment of CTCs. Read More

    Fluorophore labeling of a cell-penetrating peptide induces differential effects on its cellular distribution and affects cell viability.
    Biochim Biophys Acta 2017 Sep 14. Epub 2017 Sep 14.
    Section for Biologics, Department of Pharmacy, Faculty of Health and Medical Sciences, University of Copenhagen. Electronic address:
    Cell-penetrating peptides constitute efficient delivery vectors, and studies of their uptake and mechanism of translocation typically involve fluorophore-labeled conjugates. In the present study, the influence of a number of specific fluorophores on the physico-chemical properties and uptake-related characteristics of penetratin were studied. An array of seven fluorophores belonging to distinct structural classes was examined, and the impact of fluorophore labeling on intracellular distribution and cytotoxicity was correlated to the physico-chemical properties of the conjugates. Read More

    Characterizing pathology in erythrocytes using morphological and biophysical membrane properties: Relation to impaired hemorheology and cardiovascular function in rheumatoid arthritis.
    Biochim Biophys Acta 2017 Sep 14. Epub 2017 Sep 14.
    Department of Physiological Sciences, Stellenbosch University, Private Bag X1, Matieland, 7602, RSA, South Africa. Electronic address:
    The inflammatory burden of the complex Rheumatoid Arthritis (RA) disease affects several organ-systems, including rheological properties of blood and its formed elements. Red blood cells (RBCs) are constantly exposed to circulating dysregulated inflammatory molecules that are co-transported within the vasculature; and their membranes may be particularly vulnerable to the accompanying oxidative stress. In the current study, we investigate biophysical and ultrastructural characteristics of RBCs obtained from a cohort of patients using atomic force microscopy (AFM), scanning electron microscopy (SEM) and confocal microscopy (CM). Read More

    On the importance of protein diffusion in biological systems: The example of the Bicoid morphogen gradient.
    Biochim Biophys Acta 2017 Sep 13. Epub 2017 Sep 13.
    Dept. of Physics and Astronomy, McMaster University, 1280 Main St W., Hamilton, ON L8S 4M1, Canada.
    Morphogens are proteins that form concentration gradients in embryos and developing tissues, where they act as postal codes, providing cells with positional information and allowing them to behave accordingly. Bicoid was the first discovered morphogen, and remains one of the most studied. It regulates segmentation in flies, forming a striking exponential gradient along the anterior-posterior axis of early Drosophila embryos, and activating the transcription of multiple target genes in a concentration-dependent manner. Read More

    Netrins & Semaphorins: Novel regulators of the immune response.
    Biochim Biophys Acta 2017 Sep 13. Epub 2017 Sep 13.
    Division of Vascular Surgery, Department of Surgery, New York University School of Medicine, 530 First Avenue, New York, NY 10016, USA; Department of Cell Biology, New York University School of Medicine, 530 First Avenue, New York, NY 10016, USA. Electronic address:
    Netrins and semaphorins, members of the neuronal guidance cue family, exhibit a rich biology with significant roles that extend beyond chemotactic guidance of the axons to build the neuronal patterns of the body. Screening of adult tissues and specific cellular subsets have illuminated that these proteins are also abundantly expressed under both steady state and pathological scenarios. This observation suggests that, in addition to their role in the development of the axonal tree, these proteins possess additional novel functions in adult physiopathology. Read More

    Regulation of mitochondrial bioenergetics by the non-canonical roles of mitochondrial dynamics proteins in the heart.
    Biochim Biophys Acta 2017 Sep 13. Epub 2017 Sep 13.
    Center for Translational Medicine, Department of Medicine, Sidney Kimmel Medical College, Thomas Jefferson University, Philadelphia, PA 19107, USA. Electronic address:
    Recent advancement in mitochondrial research has significantly extended our knowledge on the role and regulation of mitochondria in health and disease. One important breakthrough is the delineation of how mitochondrial morphological changes, termed mitochondrial dynamics, are coupled to the bioenergetics and signaling functions of mitochondria. In general, it is believed that fusion leads to an increased mitochondrial respiration efficiency and resistance to stress-induced dysfunction while fission does the contrary. Read More

    Identification of potential allosteric communication pathways between functional sites of the bacterial ribosome by graph and elastic network models.
    Biochim Biophys Acta 2017 Sep 13. Epub 2017 Sep 13.
    Department of Chemical Engineering, Istanbul Technical University, Istanbul, Turkey. Electronic address:
    Background: Accumulated evidence indicates that bacterial ribosome employs allostery throughout its structure for protein synthesis. The nature of the allosteric communication between remote functional sites remains unclear, but the contact topology and dynamics of residues may play role in transmission of a perturbation to distant sites.

    Methods/results: We employ two computationally efficient approaches - graph and elastic network modeling to gain insights about the allosteric communication in ribosome. Read More

    Differential effects of FXR or TGR5 activation in cholangiocarcinoma progression.
    Biochim Biophys Acta 2017 Sep 12. Epub 2017 Sep 12.
    Department of Liver and Gastrointestinal Diseases, Biodonostia Research Institute - Donostia University Hospital -, University of the Basque Country (UPV/EHU), San Sebastián, Spain; National Institute for the Study of Liver and Gastrointestinal Diseases (CIBERehd, Instituto de Salud Carlos III), Madrid, Spain; IKERBASQUE, Basque Foundation for Science, Bilbao, Spain. Electronic address:
    Background And Aims: Cholangiocarcinoma (CCA) is an aggressive tumor type affecting cholangiocytes. CCAs frequently arise under certain cholestatic liver conditions. Intrahepatic accumulation of bile acids may facilitate cocarcinogenic effects by triggering an inflammatory response and cholangiocyte proliferation. Read More

    The role of a new class of long noncoding RNAs transcribed from ultraconserved regions in cancer.
    Biochim Biophys Acta 2017 Sep 12. Epub 2017 Sep 12.
    Institute of Genetics and Biophysics "A. Buzzati Traverso", National Research Council (CNR), Naples, Italy. Electronic address:
    Ultraconserved regions (UCRs) represent a relatively new class of non-coding genomic sequences highly conserved between human, rat and mouse genomes. These regions can reside within exons of protein-coding genes, despite the vast majority of them localizes within introns or intergenic regions. Several studies have undoubtedly demonstrated that most of these regions are actively transcribed in normal cells/tissues, where they contribute to regulate many cellular processes. Read More

    PP2A Regulates signaling through hormonal receptors in breast cancer with important therapeutic implications.
    Biochim Biophys Acta 2017 Sep 12. Epub 2017 Sep 12.
    Translational Oncology Division, Oncohealth Institute, IIS-Fundacion Jimenez Diaz, UAM, University Hospital "Fundacion Jimenez Diaz", Madrid, Spain. Electronic address:
    The functional inhibition of protein phosphatase 2A (PP2A) has emerged in the last years as a common alteration in breast cancer that determines poor outcome and contributes to disease progression and aggressiveness. Furthermore, expression of estrogen receptor (ER) is a high relevant molecular event with key therapeutic implications in breast cancer, and androgen receptor (AR) signaling is involved in the pathogenesis of breast cancer and represents a novel target with crescent importance in this disease. In this review, we summarize the role of the tumor suppressor PP2A in modulating ER and AR signaling in breast cancer, the molecular mechanisms involved, and its biological and therapeutic impact. Read More

    In vivo multimodal tumor imaging and photodynamic therapy with novel theranostic agents based on the porphyrazine framework-chelated gadolinium (III) cation.
    Biochim Biophys Acta 2017 Sep 12. Epub 2017 Sep 12.
    Nizhny Novgorod State Medical Academy, 10/1 Minin and Pozharsky Sq., 603005 Nizhny Novgorod, Russia.
    Background: A promising strategy for cancer diagnosis and therapy is the development of an agent for multimodal imaging and treatment. In the present paper we report on two novel multifunctional agents prepared on the porphyrazine pigment platform using a gadolinium (III) cation chelated by red-fluorescent tetrapyrrole macrocycles (GdPz1 and GdPz2).

    Methods: Spectral and magnetic properties of the compounds were analyzed. Read More

    Dissection of membrane-binding and -remodeling regions in two classes of bacterial phospholipid N-methyltransferases.
    Biochim Biophys Acta 2017 Sep 11. Epub 2017 Sep 11.
    Microbial Biology, Faculty of Biology, Ruhr University Bochum, Bochum, Germany. Electronic address:
    Bacterial phospholipid N-methyltransferases (Pmts) catalyze the formation of phosphatidylcholine (PC) via successive N-methylation of phosphatidylethanolamine (PE). They are classified into Sinorhizobium-type and Rhodobacter-type enzymes. The Sinorhizobium-type PmtA protein from the plant pathogen Agrobacterium tumefaciens is recruited to anionic lipids in the cytoplasmic membrane via two amphipathic helices called αA and αF. Read More

    Membrane perturbing activities and structural properties of the frog-skin derived peptide Esculentin-1a(1-21)NH2 and its Diastereomer Esc(1-21)-1c: Correlation with their antipseudomonal and cytotoxic activity.
    Biochim Biophys Acta 2017 Sep 11. Epub 2017 Sep 11.
    Laboratory affiliated to Pasteur Italia-Fondazione Cenci Bolognetti, Department of Biochemical Sciences, Sapienza University of Rome, Rome, via degli Apuli, 9, 00185, Italy. Electronic address:
    Antimicrobial peptides (AMPs) represent new alternatives to cope with the increasing number of multi-drug resistant microbial infections. Recently, a derivative of the frog-skin AMP esculentin-1a, Esc(1-21), was found to rapidly kill both the planktonic and biofilm forms of the Gram-negative bacterium Pseudomonas aeruginosa with a membrane-perturbing activity as a plausible mode of action. Lately, its diastereomer Esc(1-21)-1c containing two d-amino acids i. Read More

    Cholesterol affects the interaction between an ionic liquid and phospholipid vesicles. A study by differential scanning calorimetry and nanoplasmonic sensing.
    Biochim Biophys Acta 2017 Sep 11. Epub 2017 Sep 11.
    Department of Chemistry, P. O. Box 55, FIN-00014 University of Helsinki, Helsinki, Finland. Electronic address:
    The present work aims at studying the interactions between cholesterol-rich phosphatidylcholine-based lipid vesicles and trioctylmethylphosphonium acetate ([P8881][OAc]), a biomass dissolving ionic liquid (IL). The effect of cholesterol was assayed by using differential scanning calorimetry (DSC) and nanoplasmonic sensing (NPS) measurement techniques. Cholesterol-enriched dipalmitoyl-phosphatidylcholine vesicles were exposed to different concentrations of the IL, and the derived membrane perturbation was monitored by DSC. Read More

    Importance of the REM (Ras exchange) domain for membrane interactions by RasGRP3.
    Biochim Biophys Acta 2017 Sep 11. Epub 2017 Sep 11.
    Laboratory of Cancer Biology and Genetics, Center for Cancer Research, National Cancer Institute, Bethesda, MD 20892, United States. Electronic address:
    RasGRP comprises a family of guanine nucleotide exchange factors, regulating the dissociation of GDP from Ras GTPases to enhance the formation of the active GTP-bound form. RasGRP1 possesses REM (Ras exchange), GEF (catalytic), EF-hand, C1, SuPT (suppressor of PT), and PT (plasma membrane-targeting) domains, among which the C1 domain drives membrane localization in response to diacylglycerol or phorbol ester and the PT domain recognizes phosphoinositides. The homologous family member RasGRP3 shows less plasma membrane localization. Read More

    Influence of omega-3 fatty acids on bovine luteal cell plasma membrane dynamics.
    Biochim Biophys Acta 2017 Sep 11. Epub 2017 Sep 11.
    Department of Chemistry, Colorado State University, Fort Collins, Colorado 80523.
    Fish oil is a rich source of omega-3 fatty acids which disrupt lipid microdomain structure and affect mobility of the prostaglandin F2α (FP) receptor in bovine luteal cells. The objectives of this study were to determine the effects of individual omega-3 fatty acids, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) on 1) membrane fatty acid composition, 2) lipid microdomain structure, and 3) lateral mobility of the FP receptor in bovine luteal cells. Ovaries were collected from a local abattoir (n=5/experiment). Read More

    Antimicrobial peptides are degraded by the cytosolic proteases of human erythrocytes.
    Biochim Biophys Acta 2017 Sep 11. Epub 2017 Sep 11.
    Department of Biochemistry and Molecular Biology, Tulane University School of Medicine, New Orleans, LA 70112, USA. Electronic address:
    Well-studied and promising antimicrobial peptides (AMPs), with potent bactericidal activity, in vitro, have yet to have a significant impact in human medicine beyond topical applications. We previously showed that interactions of AMPs with concentrated human erythrocytes inhibit many of them, and suggested that screens and assays should be done in their presence to mimic host cell inhibition. Here, we use AMPs to characterize the activity of proteases that are associated with human erythrocytes. Read More

    Assessing the mechanisms of cholesteryl ester transfer protein inhibitors.
    Biochim Biophys Acta 2017 Sep 11. Epub 2017 Sep 11.
    Molecular Foundry, Lawrence Berkeley National Laboratory, Berkeley, CA 94720, USA. Electronic address:
    Cholesteryl ester transfer protein (CETP) inhibitors are a new class of therapeutics for dyslipidemia that simultaneously improve two major cardiovascular disease (CVD) risk factors: elevated low-density lipoprotein (LDL) cholesterol and decreased high-density lipoprotein (HDL) cholesterol. However, the detailed molecular mechanisms underlying their efficacy are poorly understood, as are any potential mechanistic differences among the drugs in this class. Herein, we used electron microscopy (EM) to investigate the effects of three of these agents (Torcetrapib, Dalcetrapib and Anacetrapib) on CETP structure, CETP-lipoprotein complex formation and CETP-mediated cholesteryl ester (CE) transfer. Read More

    Functional dynamics in cyclic nucleotide signaling and amyloid inhibition.
    Biochim Biophys Acta 2017 Sep 11. Epub 2017 Sep 11.
    Department of Chemistry and Chemical Biology, McMaster University, Hamilton, Ontario, Canada; Department of Biochemistry and Biomedical Sciences, McMaster University, Hamilton, Ontario, Canada. Electronic address:
    It is now established that understanding the molecular basis of biological function requires atomic resolution maps of both structure and dynamics. Here, we review several illustrative examples of functional dynamics selected from our work on cyclic nucleotide signaling and amyloid inhibition. Although fundamentally diverse, a central aspect common to both fields is that function can only be rationalized by considering dynamic equilibria between distinct states of the accessible free energy landscape. Read More

    Relationships between residue Voronoi volume and sequence conservation in proteins.
    Biochim Biophys Acta 2017 Sep 11. Epub 2017 Sep 11.
    Institute of Bioinformatics and Systems Biology, National Chiao Tung University, HsinChu 30050, Taiwan, R.O.C. Electronic address:
    Background: Functional and biophysical constraints can cause different levels of sequence conservation in proteins. Previously, structural properties, e.g. Read More

    Multi-scale mechanical characterization of prostate cancer cell lines: Relevant biological markers to evaluate the cell metastatic potential.
    Biochim Biophys Acta 2017 Sep 9. Epub 2017 Sep 9.
    Univ Lyon, CNRS, Molecular and Supramolecular Chemistry and Biochemistry Institute ICBMS UMR 5246, F-69622 Lyon, France. Electronic address:
    Background: Considering the importance of cellular mechanics in the birth and evolution of cancer towards increasingly aggressive stages, we compared nano-mechanical properties of non-tumoral (WPMY-1) and highly aggressive metastatic (PC-3) prostate cell lines both on cell aggregates, single cells, and membrane lipids.

    Methods: Cell aggregate rheological properties were analyzed during dynamic compression stress performed on a homemade rheometer. Single cell visco-elasticity measurements were performed by Atomic Force Microscopy using a cantilever with round tip on surface-attached cells. Read More

    The translocator protein ligand XBD173 improves clinical symptoms and neuropathological markers in the SJL/J mouse model of multiple sclerosis.
    Biochim Biophys Acta 2017 Sep 9. Epub 2017 Sep 9.
    Biopathologie de la Myéline, Neuroprotection et Stratégies Thérapeutiques, INSERM U1119, Fédération de Médecine Translationnelle de Strasbourg (FMTS), Université de Strasbourg, Bâtiment 3 de la Faculté de Médecine, 11 rue Humann, 67 000 Strasbourg, France. Electronic address:
    Multiple sclerosis (MS) is a severe autoimmune disease characterized by inflammatory, demyelinating and neurodegenerative components causing motor, sensory, visual and/or cognitive symptoms. The relapsing-remitting MS affecting 85% of patients is reliably mimicked by the proteolipid-protein (PLP)-induced experimental autoimmune encephalomyelitis (EAE) SJL/J-mouse model. Significant progress was made for MS treatment but the development of effective therapies devoid of severe side-effects remains a great challenge. Read More

    Transcription factor CUX1 is required for intestinal epithelial wound healing and targets the VAV2-RAC1 Signalling complex.
    Biochim Biophys Acta 2017 Sep 8. Epub 2017 Sep 8.
    Département d'anatomie et biologie cellulaire, Faculté de médecine et des sciences de la santé, Pavillon de recherche appliquée sur le cancer, Université de Sherbrooke, Sherbrooke, QC, CANADA, J1E 4K8. Electronic address:
    Intestinal epithelial cells form a protective barrier in limiting gut luminal content potentially harmful to the host. Upon gut epithelium injury, several signals instruct epithelial cells to undergo a rapid healing process. Defects in this process induce inflammatory responses and can further evolve into chronic gut inflammatory diseases. Read More

    The ILK-MMP9-MRTF axis is crucial for EndMT differentiation of endothelial cells in a tumor microenvironment.
    Biochim Biophys Acta 2017 Sep 8. Epub 2017 Sep 8.
    Department of Medical Cell Mechanisms, Medical University of Lodz, Mazowiecka 6/8, 92-216 Lodz, Poland. Electronic address:
    Increasing evidence indicates that the tumor microenvironment is a critical factor supporting cancer progression, chemoresistance and metastasis. Recently, cancer-associated fibroblasts (CAFs) have been recognized as a crucial tumor stromal component promoting cancer growth and invasiveness via modulation of the extracellular matrix (ECM) structure, tumor metabolism and immune reprogramming. One of the main sources of CAFs are endothelial cells undergoing the endothelial-mesenchymal transition (EndMT). Read More

    Structural and functional characterization of a highly secreted α-L-arabinofuranosidase (GH62) from Aspergillus nidulans grown on sugarcane bagasse.
    Biochim Biophys Acta 2017 Sep 7. Epub 2017 Sep 7.
    Institute of Biology, University of Campinas - UNICAMP, Campinas, SP, Brazil - CEP 13083-862. Electronic address:
    Carbohydrate-Active Enzymes are key enzymes for biomass-to-bioproducts conversion. α-L-Arabinofuranosidases that belong to the Glycoside Hydrolase family 62 (GH62) have important applications in biofuel production from plant biomass by hydrolyzing arabinoxylans, found in both the primary and secondary cell walls of plants. In this work, we identified a GH62 α-L-arabinofuranosidase (AnAbf62Awt) that was highly secreted when Aspergillus nidulans was cultivated on sugarcane bagasse. Read More

    Aggregation properties of a disordered protein are tunable by pH and depend on its net charge per residue.
    Biochim Biophys Acta 2017 Sep 8;1861(11 Pt A):2543-2550. Epub 2017 Sep 8.
    Department of Biotechnology and Biosciences, State University of Milano-Bicocca, Milano, Italy. Electronic address:
    Intrinsically disordered proteins (IDPs) possess a peculiar amino acid composition that makes them very soluble. Nevertheless, they can encounter aggregation in physiological and pathological contexts. In this work, we addressed the issue of how electrostatic charges can influence aggregation propensity by using the N-terminus moiety of the measles virus phosphoprotein, PNT, as a model IDP. Read More

    Deglycosylating enzymes acting on N-glycans in fungi: Insights from a genome survey.
    Biochim Biophys Acta 2017 Sep 7;1861(11 Pt A):2551-2558. Epub 2017 Sep 7.
    Glycometabolome Team, Systems Glycobiology Research Group, RIKEN Global Research Cluster, Wako, Saitama 351-0198, Japan. Electronic address:
    Background: N-Glycosylation, one of the most prominent post-translational modifications of proteins, is found in all domains of life, i.e. eukaryotes, bacteria and archaea, and has been shown to play a crucial role in modulating the physicochemical/physiological properties of carrier proteins. Read More

    Regulated expression of the TPβ isoform of the human T Prostanoid receptor by the tumour suppressors FOXP1 and NKX3.1: Implications for the role of Thromboxane in Prostate Cancer.
    Biochim Biophys Acta 2017 Sep 8. Epub 2017 Sep 8.
    UCD School of Biomolecular and Biomedical Sciences, UCD Conway Institute of Biomolecular and Biomedical Research, University College Dublin, Belfield, Dublin 4, Ireland.
    The prostanoid thromboxane (TX)A2 signals through the TPα and TPβ isoforms of T Prostanoid receptor (TP) that are transcriptionally regulated by distinct promoters termed Prm1 and Prm3, respectively, within the TBXA2R gene. We recently demonstrated that expression of TPα and TPβ is increased in PCa, differentially correlating with Gleason grade and with altered CpG methylation of the individual Prm1/Prm3 regions within the TBXA2R. The current study sought to localise the sites of CpG methylation within Prm1 and Prm3, and to identify the main transcription factors regulating TPβ expression through Prm3 in the prostate adenocarcinoma PC-3 and LNCaP cell lines. Read More

    MiR-525-3p mediates antiviral defense to rotavirus infection by targeting nonstructural protein 1.
    Biochim Biophys Acta 2017 Sep 7. Epub 2017 Sep 7.
    Institute of Immunology, PLA, Third Military Medical University, Chongqing, China.. Electronic address:
    MicroRNAs (miRNAs) are short RNAs of approximately 22 nucleotides that post-transcriptionally regulate gene expression by controlling mRNA stability or translation. They play critical roles in intricate networks of host-pathogen interactions and innate immunity. Rotaviruses (RVs) are the leading cause of severe diarrhea among infants and young children worldwide. Read More

    Histone methyltransferase SETDB1 maintains survival of mouse spermatogonial stem/progenitor cells via PTEN/AKT/FOXO1 pathway.
    Biochim Biophys Acta 2017 Sep 7. Epub 2017 Sep 7.
    College of Animal Science and Technology, Northwest A&F University, Shaanxi 712100, China. Electronic address:
    Spermatogonial stem cells (SSCs) possess the capacity of self-renewal and differentiation, which are the basis of spermatogenesis. In maintenance of SSC homeostasis, intrinsic/extrinsic factors and various signaling pathways tightly control the fate of SSCs. Methyltransferase SETDB1 (Set domain, bifurcated 1) catalyzes histone H3 lysine 9 (H3K9) trimethylation and represses gene expression. Read More

    Kinetic analysis of the inhibition of the drug efflux protein AcrB using surface plasmon resonance.
    Biochim Biophys Acta 2017 Sep 7. Epub 2017 Sep 7.
    School of Pharmacy and Medical Sciences, Sansom Institute for Health Research, University of South Australia, SA 5000, Australia. Electronic address:
    Multidrug efflux protein complexes such as AcrAB-TolC from Escherichia coli are paramount in multidrug resistance in Gram-negative bacteria and are also implicated in other processes such as virulence and biofilm formation. Hence efflux pump inhibition, as a means to reverse antimicrobial resistance in clinically relevant pathogens, has gained increased momentum over the past two decades. Significant advances in the structural and functional analysis of AcrB have informed the selection of efflux pump inhibitors (EPIs). Read More

    Ionophores at work: Exploring the interaction of guanosine-based amphiphiles with phospholipid membranes.
    Biochim Biophys Acta 2017 Sep 7. Epub 2017 Sep 7.
    CSGI, Consorzio Interuniversitario per lo Sviluppo dei Sistemi a Grande Interfase, Via della Lastruccia 3, 50019 Sesto Fiorentino, Florence, Italy; Department of Chemical Sciences, University of Naples Federico II, Complesso Universitario di Monte S. Angelo, via Cintia 4, 80126 Naples, Italy. Electronic address:
    An amphiphilic derivative of guanosine, carrying a myristoyl group at the 5'-position and two methoxy(triethylene glycol) appendages at the 2' and 3'-positions (1), endowed with high ionophoric activity, has been here studied in its interaction mode with a model lipid membrane along with its 5'-spin-labelled analogue 2, bearing the 5-doxyl-stearic in lieu of the myristic residue. Electron spin resonance spectra, carried out on the spin-labelled nucleolipid 2 in mixture with a DOPC/DOPG phospholipid bilayer, on one side, and on spin-labelled lipids mixed with 1, on the other, integrated with dynamic light scattering and neutron reflectivity measurements, allowed getting an in-depth picture of the effect of the ionophores on membrane structure, relevant to clarify the ion transport mechanism through lipid bilayers. Particularly, dehydration of lipid headgroups and lowering of both the local polarity and acyl chains order across the bilayer, due to the insertion of the oligo(ethylene glycol) chains in the bilayer hydrophobic core, have been found to be the main effects of the amphiphilic guanosines interaction with the membrane. Read More

    A γ-subunit point mutation in Chlamydomonas reinhardtii chloroplast F1Fo-ATP synthase confers tolerance to reactive oxygen species.
    Biochim Biophys Acta 2017 Sep 7. Epub 2017 Sep 7.
    Laboratory for Chemistry and Life Science, Tokyo Institute of Technology, Nagatsuta 4259-R1-8, Midori-ku, Yokohama 226-8503, Japan.
    The chloroplast F1Fo-ATP synthase (CF1Fo) drives ATP synthesis and the reverse reaction of ATP hydrolysis. The enzyme evolved in a cellular environment where electron transfer processes and molecular oxygen are abundant, and thiol modulation in the γ-subunit via thioredoxin is important for its ATPase activity regulation. Especially under high light, oxygen can be reduced and forms reactive oxygen species (ROS) which can oxidize CF1Fo among various other biomolecules. Read More

    LRRK2 functions as a scaffolding kinase of ASK1-mediated neuronal cell death.
    Biochim Biophys Acta 2017 Sep 6. Epub 2017 Sep 6.
    Hormone Research Center, School of Biological Sciences and Technology, Chonnam National University, Gwangju, Republic of Korea. Electronic address:
    Leucine-rich repeat kinase 2 (LRRK2), a multi-domain protein, is a key causative factor in Parkinson's disease (PD). Identification of novel substrates and the molecular mechanisms underlying the effects of LRRK2 are essential for understanding the pathogenesis of PD. In this study, we showed that LRRK2 played an important role in neuronal cell death by directly phosphorylating and activating apoptosis signal-regulating kinase 1 (ASK1). Read More

    Chemicals or mutations that target mitochondrial translation can rescue the respiratory deficiency of yeast bcs1 mutants.
    Biochim Biophys Acta 2017 Sep 6. Epub 2017 Sep 6.
    Institute of Integrative Biology of the Cell (I2BC), CEA, CNRS, Université Paris-Sud, Université Evry-Val d'Essonne, Université Paris-Saclay, 91198 Gif sur Yvette Cedex, France. Electronic address:
    Bcs1p is a chaperone that is required for the incorporation of the Rieske subunit within complex III of the mitochondrial respiratory chain. Mutations in the human gene BCS1L (BCS1-like) are the most frequent nuclear mutations resulting in complex III-related pathologies. In yeast, the mimicking of some pathogenic mutations causes a respiratory deficiency. Read More

    Noradrenaline, oxymetazoline and phorbol myristate acetate induce distinct functional actions and phosphorylation patterns of α1A-adrenergic receptors.
    Biochim Biophys Acta 2017 Sep 6. Epub 2017 Sep 6.
    Instituto de Fisiología Celular, Universidad Nacional Autónoma de México, Ap. Postal 70-248, Ciudad Universitaria, Ciudad de México 04510, Mexico. Electronic address:
    In LNCaP cells that stably express α1A-adrenergic receptors, oxymetazoline increased intracellular calcium and receptor phosphorylation, however, this agonist was a weak partial agonist, as compared to noradrenaline, for calcium signaling. Interestingly, oxymetazoline-induced receptor internalization and desensitization displayed greater effects than those induced by noradrenaline. Phorbol myristate acetate induced modest receptor internalization and minimal desensitization. Read More

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