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https://www.readbyqxmd.com/read/29109164/zika-virus-zikv-replication-is-substantially-inhibited-by-novel-favipiravir-and-interferon-alpha-combination-regimens
#1
Camilly P Pires de Mello, Xun Tao, Tae Hwan Kim, Jürgen B Bulitta, Jaime L Rodriquez, Justin J Pomeroy, Ashley N Brown
Zika virus (ZIKV) is a major public health concern due to its overwhelming spread into the Americas. Currently there are neither licensed vaccines nor antiviral therapies available for the treatment of ZIKV. We aimed to identify and rationally optimize effective therapeutic regimens for ZIKV by evaluating the antiviral potential of approved broad-spectrum antiviral agents favipiravir (FAV), interferon-alpha (IFN), and ribavirin (RBV) as single agent and combinations. For these studies, Vero cells were infected with ZIKV in the presence of increasing concentrations of FAV, IFN, or/and RBV for four days...
November 6, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/29089042/membrane-dynamics-and-organelle-biogenesis-lipid-pipelines-and-vesicular-carriers
#2
EDITORIAL
Christopher J Stefan, William S Trimble, Sergio Grinstein, Guillaume Drin, Karin Reinisch, Pietro De Camilli, Sarah Cohen, Alex M Valm, Jennifer Lippincott-Schwartz, Tim P Levine, David B Iaea, Frederick R Maxfield, Clare E Futter, Emily R Eden, Delphine Judith, Alexander R van Vliet, Patrizia Agostinis, Sharon A Tooze, Ayumu Sugiura, Heidi M McBride
Discoveries spanning several decades have pointed to vital membrane lipid trafficking pathways involving both vesicular and non-vesicular carriers. But the relative contributions for distinct membrane delivery pathways in cell growth and organelle biogenesis continue to be a puzzle. This is because lipids flow from many sources and across many paths via transport vesicles, non-vesicular transfer proteins, and dynamic interactions between organelles at membrane contact sites. This forum presents our latest understanding, appreciation, and queries regarding the lipid transport mechanisms necessary to drive membrane expansion during organelle biogenesis and cell growth...
October 31, 2017: BMC Biology
https://www.readbyqxmd.com/read/29083305/single-molecule-force-spectroscopy-of-protein-membrane-interactions
#3
Lu Ma, Yiying Cai, Yanghui Li, Junyi Jiao, Zhenyong Wu, Ben O'Shaughnessy, Pietro De Camilli, Erdem Karatekin, Yongli Zhang
Many biological processes rely on protein-membrane interactions in the presence of mechanical forces, yet high resolution methods to quantify such interactions are lacking. Here, we describe a single-molecule force spectroscopy approach to quantify membrane binding of C2 domains in Synaptotagmin-1 (Syt1) and Extended Synaptotagmin-2 (E-Syt2). Syts and E-Syts bind the plasma membrane via multiple C2 domains, bridging the plasma membrane with synaptic vesicles or endoplasmic reticulum to regulate membrane fusion or lipid exchange, respectively...
October 30, 2017: ELife
https://www.readbyqxmd.com/read/29079337/oseltamivir-zanamivir-combination-therapy-suppresses-drug-resistant-h1n1-influenza-a-viruses-in-the-hollow-fiber-infection-model-hfim-system
#4
Camilly P Pires de Mello, George L Drusano, Jonathan R Adams, Matthew Shudt, Robert Kulawy, Ashley N Brown
Drug-resistant influenza is a significant threat to global public health. Until new antiviral agents with novel mechanisms of action become available, there is a pressing need for alternative treatment strategies with available influenza antivirals. Our aims were to evaluate the antiviral activity of two neuraminidase inhibitors (oseltamivir and zanamivir) as combination therapy against H1N1 influenza A viruses, as these agents bind to the neuraminidase active site differently: oseltamivir requires a conformational change for binding whereas zanamivir does not...
October 25, 2017: European Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/28933693/structural-inhibition-of-dynamin-mediated-membrane-fission-by-endophilin
#5
Annika Hohendahl, Nathaniel Talledge, Valentina Galli, Peter S Shen, Frédéric Humbert, Pietro De Camilli, Adam Frost, Aurélien Roux
Dynamin, which mediates membrane fission during endocytosis, binds endophilin and other members of the Bin-Amphiphysin-Rvs (BAR) protein family. How endophilin influences endocytic membrane fission is still unclear. Here, we show that dynamin-mediated membrane fission is potently inhibited in vitro when an excess of endophilin co-assembles with dynamin around membrane tubules. We further show by electron microscopy that endophilin intercalates between turns of the dynamin helix and impairs fission by preventing trans interactions between dynamin rungs that are thought to play critical roles in membrane constriction...
September 21, 2017: ELife
https://www.readbyqxmd.com/read/28913412/addition-of-wollastonite-fibers-to-calcium-phosphate-cement-increases-cell-viability-and-stimulates-differentiation-of-osteoblast-like-cells
#6
Juliana Almeida Domingues, Mariana Motisuke, Celso Aparecido Bertran, Moema A Hausen, Eliana Aparecida de Rezende Duek, José Angelo Camilli
Calcium phosphate cement (CPC) that is based on α-tricalcium phosphate (α-TCP) is considered desirable for bone tissue engineering because of its relatively rapid degradation properties. However, such cement is relatively weak, restricting its use to areas of low mechanical stress. Wollastonite fibers (WF) have been used to improve the mechanical strength of biomaterials. However, the biological properties of WF remain poorly understood. Here, we tested the response of osteoblast-like cells to being cultured on CPC reinforced with 5% of WF (CPC-WF)...
2017: TheScientificWorldJournal
https://www.readbyqxmd.com/read/28797619/mechanical-ventilation-weaning-protocol-improves-medical-adherence-and-results
#7
Luís Guilherme Alegretti Borges, Augusto Savi, Cassiano Teixeira, Roselaine Pinheiro de Oliveira, Marcio Luiz Ferreira De Camillis, Ricardo Wickert, Sérgio Fernando Monteiro Brodt, Túlio Frederico Tonietto, Ricardo Cremonese, Leonardo Silveira da Silva, Fernanda Gehm, Eubrando Silvestre Oliveira, Jose Herve Diel Barth, Juçara Gasparetto Macari, Cíntia Dias de Barros, Sílvia Regina Rios Vieira
INTRODUCTION: Implementation of a weaning protocol is related to better patient prognosis. However, new approaches may take several years to become the standard of care in daily practice. We conducted a prospective cohort study to investigate the effectiveness of a multifaceted strategy to implement a protocol to wean patients from mechanical ventilation (MV) and to evaluate the weaning success rate as well as practitioner adherence to the protocol. METHODS: We investigated all consecutive MV-dependent subjects admitted to a medical-surgical intensive care unit (ICU) for >24h over 7years...
October 2017: Journal of Critical Care
https://www.readbyqxmd.com/read/28716556/impact-of-pneumococcal-conjugate-vaccine-pcv7-and-pcv13-on-pneumococcal-invasive-diseases-in-italian-children-and-insight-into-evolution-of-pneumococcal-population-structure
#8
Romina Camilli, Fabio D'Ambrosio, Maria Del Grosso, Fernanda Pimentel de Araujo, Maria Grazia Caporali, Martina Del Manso, Giovanni Gherardi, Fortunato D'Ancona, Annalisa Pantosti
BACKGROUND: The use of PCV7 for children immunization was gradually implemented in the Italian regions starting from 2006 and was replaced by PCV13 in 2010-2011. In this study we aimed to assess the PCV impact on invasive pneumococcal diseases (IPD) incidence, serotype distribution and antibiotic resistance in Italian children under 5years old. METHODS: All IPD cases in children from 5 Italian regions (Emilia-Romagna, Lombardia, A. P. Bolzano, A. P. Trento, and Piemonte) reported through the nationwide surveillance system during 2008-2014 were included in this study...
August 16, 2017: Vaccine
https://www.readbyqxmd.com/read/28681646/sleeve-gastrectomy-efficacy-on-metabolic-and-cardiovascular-dysfunction-with-a-focus-on-the-role-of-comorbidities
#9
Maria Anastasia Ricci, Stefano Ministrini, Stefano De Vuono, Matteo Camilli, Alessandra Gentili, Giulia Daviddi, Marcello Boni, Graziana Lupattelli
We evaluated the effects of sleeve gastrectomy (SG) on metabolic/cardiovascular parameters according to weight loss, visceral fat area (VFA), and homeostasis model assessment (HOMA)-insulin resistance index; we also assessed the influence of SG on comorbidities (diabetes/hypertension). At baseline and 10 to 12 months after SG, we assessed anthropometric and biochemical parameters, bioimpedentiometry, ultrasonographic VFA, liver steatosis, flow-mediated dilation, and echocardiography in 110 patients with obesity...
January 1, 2017: Angiology
https://www.readbyqxmd.com/read/28657621/ultrafast-dynamics-in-the-dna-building-blocks-thymidine-and-thymine-initiated-by-ionizing-radiation
#10
E P Månsson, S De Camillis, M C Castrovilli, M Galli, M Nisoli, F Calegari, J B Greenwood
Understanding how energetic charged particles damage DNA is crucial for improving radiotherapy techniques such as hadron therapy and for the development of new radiosensitizer drugs. In the present study, the damage caused by energetic particles was simulated by measuring the action of extreme ultraviolet (XUV) attosecond pulses on the DNA building blocks thymine and thymidine. This allowed the ultrafast processes triggered by direct ionization to be probed with an optical pulse with a time resolution of a few femtoseconds...
June 28, 2017: Physical Chemistry Chemical Physics: PCCP
https://www.readbyqxmd.com/read/28599006/long-term-cryopreservation-of-decellularised-oesophagi-for-tissue-engineering-clinical-application
#11
Luca Urbani, Panagiotis Maghsoudlou, Anna Milan, Maria Menikou, Charlotte Klara Hagen, Giorgia Totonelli, Carlotta Camilli, Simon Eaton, Alan Burns, Alessandro Olivo, Paolo De Coppi
Oesophageal tissue engineering is a therapeutic alternative when oesophageal replacement is required. Decellularised scaffolds are ideal as they are derived from tissue-specific extracellular matrix and are non-immunogenic. However, appropriate preservation may significantly affect scaffold behaviour. Here we aim to prove that an effective method for short- and long-term preservation can be applied to tissue engineered products allowing their translation to clinical application. Rabbit oesophagi were decellularised using the detergent-enzymatic treatment (DET), a combination of deionised water, sodium deoxycholate and DNase-I...
2017: PloS One
https://www.readbyqxmd.com/read/28559323/contacts-between-the-endoplasmic-reticulum-and-other-membranes-in-neurons
#12
Yumei Wu, Christina Whiteus, C Shan Xu, Kenneth J Hayworth, Richard J Weinberg, Harald F Hess, Pietro De Camilli
Close appositions between the membrane of the endoplasmic reticulum (ER) and other intracellular membranes have important functions in cell physiology. These include lipid homeostasis, regulation of Ca(2+) dynamics, and control of organelle biogenesis and dynamics. Although these membrane contacts have previously been observed in neurons, their distribution and abundance have not been systematically analyzed. Here, we have used focused ion beam-scanning electron microscopy to generate 3D reconstructions of intracellular organelles and their membrane appositions involving the ER (distance ≤30 nm) in different neuronal compartments...
June 13, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28466468/loss-of-dynamin-2-gtpase-function-results-in-microcytic-anaemia
#13
Fiona C Brown, Michael Collett, Cedric S Tremblay, Gerhard Rank, Pietro De Camilli, Carmen J Booth, Marc Bitoun, Phillip J Robinson, Benjamin T Kile, Stephen M Jane, David J Curtis
In a dominant mouse ethylnitrosurea mutagenesis screen for genes regulating erythropoiesis, we identified a pedigree with a novel microcytic hypochromia caused by a V235G missense mutation in Dynamin 2 (Dnm2). Mutations in Dnm2, a GTPase, are highly disease-specific and have been implicated in four forms of human diseases: centronuclear myopathy, Charcot-Marie Tooth neuropathy and, more recently, T-cell leukaemia and Hereditary Spastic Paraplegia, but red cell abnormalities have not been reported to date. The V235G mutation lies within a crucial GTP nucleotide-binding pocket of Dnm2, and resulted in defective GTPase activity and incompatibility with life in the homozygous state...
August 2017: British Journal of Haematology
https://www.readbyqxmd.com/read/28363589/the-extended-synaptotagmins
#14
REVIEW
Yasunori Saheki, Pietro De Camilli
The extended-synaptotagmins (tricalbins in yeast) derive their name from their partial domain structure similarity to the synaptotagmins, which are characterized by an N-terminal membrane anchor and cytosolically exposed C2 domains. However, they differ from the synaptotagmins in localization and function. The synaptotagmins tether secretory vesicles, including synaptic vesicles, to the plasma membrane (PM) via their C2 domains and regulate their Ca(2+) triggered exocytosis. In contrast, the extended-synaptotagmins are resident proteins of the endoplasmic reticulum (ER), which tether this organelle to the plasma membrane via their C2 domains, but not as a premise to fusion of the two membranes...
September 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28301744/endoplasmic-reticulum-plasma-membrane-contact-sites
#15
REVIEW
Yasunori Saheki, Pietro De Camilli
The endoplasmic reticulum (ER) has a broad localization throughout the cell and forms direct physical contacts with all other classes of membranous organelles, including the plasma membrane (PM). A number of protein tethers that mediate these contacts have been identified, and study of these protein tethers has revealed a multiplicity of roles in cell physiology, including regulation of intracellular Ca(2+) dynamics and signaling as well as control of lipid traffic and homeostasis. In this review, we discuss the cross talk between the ER and the PM mediated by direct contacts...
June 20, 2017: Annual Review of Biochemistry
https://www.readbyqxmd.com/read/28279363/synaptic-vesicle-clusters-at-synapses-a-distinct-liquid-phase
#16
REVIEW
Dragomir Milovanovic, Pietro De Camilli
Phase separation in the cytoplasm is emerging as a major principle in intracellular organization. In this process, sets of macromolecules assemble themselves into liquid compartments that are distinct from the surrounding medium but are not delimited by membrane boundaries. Here, we discuss how phase separation, in which a component of one of the two phases is vesicles rather than macromolecules, could underlie the formation of synaptic vesicle (SV) clusters in proximity to presynaptic sites. The organization of SVs into a liquid phase could explain how SVs remain tightly clustered without being stably bound to a scaffold so that they can be efficiently recruited to release site by active zone components...
March 8, 2017: Neuron
https://www.readbyqxmd.com/read/28231468/parkinson-sac-domain-mutation-in-synaptojanin-1-impairs-clathrin-uncoating-at-synapses-and-triggers-dystrophic-changes-in-dopaminergic-axons
#17
Mian Cao, Yumei Wu, Ghazaleh Ashrafi, Amber J McCartney, Heather Wheeler, Eric A Bushong, Daniela Boassa, Mark H Ellisman, Timothy A Ryan, Pietro De Camilli
Synaptojanin 1 (SJ1) is a major presynaptic phosphatase that couples synaptic vesicle endocytosis to the dephosphorylation of PI(4,5)P2, a reaction needed for the shedding of endocytic factors from their membranes. While the role of SJ1's 5-phosphatase module in this process is well recognized, the contribution of its Sac phosphatase domain, whose preferred substrate is PI4P, remains unclear. Recently a homozygous mutation in its Sac domain was identified in early-onset parkinsonism patients. We show that mice carrying this mutation developed neurological manifestations similar to those of human patients...
February 22, 2017: Neuron
https://www.readbyqxmd.com/read/28209843/lipid-transport-by-tmem24-at-er-plasma-membrane-contacts-regulates-pulsatile-insulin-secretion
#18
Joshua A Lees, Mirko Messa, Elizabeth Wen Sun, Heather Wheeler, Federico Torta, Markus R Wenk, Pietro De Camilli, Karin M Reinisch
Insulin is released by β cells in pulses regulated by calcium and phosphoinositide signaling. Here, we describe how transmembrane protein 24 (TMEM24) helps coordinate these signaling events. We showed that TMEM24 is an endoplasmic reticulum (ER)-anchored membrane protein whose reversible localization to ER-plasma membrane (PM) contacts is governed by phosphorylation and dephosphorylation in response to oscillations in cytosolic calcium. A lipid-binding module in TMEM24 transports the phosphatidylinositol 4,5-bisphosphate [PI(4,5)P2] precursor phosphatidylinositol between bilayers, allowing replenishment of PI(4,5)P2 hydrolyzed during signaling...
February 17, 2017: Science
https://www.readbyqxmd.com/read/28035045/multiphasic-dynamics-of-phosphatidylinositol-4-phosphate-during-phagocytosis
#19
Roni Levin, Gerald R V Hammond, Tamas Balla, Pietro De Camilli, Gregory D Fairn, Sergio Grinstein
We analyzed the distribution, fate, and functional role of phosphatidylinositol 4-phosphate (PtdIns4P) during phagosome formation and maturation. To this end, we used genetically encoded probes consisting of the PtdIns4P-binding domain of the bacterial effector SidM. PtdIns4P was found to undergo complex, multiphasic changes during phagocytosis. The phosphoinositide, which is present in the plasmalemma before engagement of the target particle, is transiently enriched in the phagosomal cup. Soon after the phagosome seals, PtdIns4P levels drop precipitously due to the hydrolytic activity of Sac2 and phospholipase C, becoming undetectable for ∼10 min...
January 1, 2017: Molecular Biology of the Cell
https://www.readbyqxmd.com/read/27895154/kidney-tubular-ablation-of-ocrl-inpp5b-phenocopies-lowe-syndrome-tubulopathy
#20
Kazunori Inoue, Daniel M Balkin, Lijuan Liu, Ramiro Nandez, Yumei Wu, Xuefei Tian, Tong Wang, Robert Nussbaum, Pietro De Camilli, Shuta Ishibe
Lowe syndrome and Dent disease are two conditions that result from mutations of the inositol 5-phosphatase oculocerebrorenal syndrome of Lowe (OCRL) and share the feature of impaired kidney proximal tubule function. Genetic ablation of Ocrl in mice failed to recapitulate the human phenotypes, possibly because of the redundant functions of OCRL and its paralog type 2 inositol polyphosphate-5-phosphatase (INPP5B). Germline knockout of both paralogs in mice results in early embryonic lethality. We report that kidney tubule-specific inactivation of Inpp5b on a global Ocrl-knockout mouse background resulted in low molecular weight proteinuria, phosphaturia, and acidemia...
May 2017: Journal of the American Society of Nephrology: JASN
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