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https://www.readbyqxmd.com/read/28727999/drug-ion-co-delivery-multi-functional-nanocarrier-to-regenerate-infected-tissue-defect
#1
Jung-Hwan Lee, Ahmed El-Fiqi, Nandin Mandakhbayar, Hae-Hyoung Lee, Hae-Won Kim
Regeneration of infected tissues is a globally challenging issue in medicine and dentistry. Common clinical therapies involving a complete removal of infected areas together with a treatment of antimicrobial drugs are often suboptimal. Biomaterials with anti-bacterial and pro-regenerative potential can offer a solution to this. Here we design a novel nanocarrier based on a mesoporous silicate-calcium glass by doping with Ag ions and simultaneously loading antimicrobial drugs onto mesopores. The nanocarriers could controllably release multiple ions (silver, calcium, and silicate) and drugs (tetracycline or chlorohexidine) to levels therapeutically relevant, and effectively internalize to human dental stem cells (∼90%) with excellent viability, ultimately stimulating odontogenic differentiation...
July 12, 2017: Biomaterials
https://www.readbyqxmd.com/read/28726068/cardiac-complications-of-congenital-disorders-of-glycosylation-cdg-a-systematic-review-of-the-literature
#2
REVIEW
D Marques-da-Silva, R Francisco, D Webster, V Dos Reis Ferreira, J Jaeken, T Pulinilkunnil
Congenital disorders of glycosylation (CDG) are inborn errors of metabolism due to protein and lipid hypoglycosylation. This rapidly growing family of genetic diseases comprises 103 CDG types, with a broad phenotypic diversity ranging from mild to severe poly-organ -system dysfunction. This literature review summarizes cardiac involvement, reported in 20% of CDG. CDG with cardiac involvement were divided according to the associated type of glycosylation: N-glycosylation, O-glycosylation, dolichol synthesis, glycosylphosphatidylinositol (GPI)-anchor biosynthesis, COG complex, V-ATPase complex, and other glycosylation pathways...
July 19, 2017: Journal of Inherited Metabolic Disease
https://www.readbyqxmd.com/read/28724633/conformationally-organized-lysine-isosteres-in-streptococcus-pyogenes-m-protein-mediate-direct-high-affinity-binding-to-human-plasminogen
#3
Yue Yuan, Jaroslav Zajicek, Cunjia Qiu, Vishwanatha Chandrahas, Shaun W Lee, Victoria A Ploplis, Francis J Castellino
The binding of human plasminogen (hPg) to the surface of the human pathogen Streptococcus pyogenes (GAS) and subsequent hPg activation to the protease plasmin generate a proteolytic surface that GAS employs to circumvent host innate immunity. Direct high-affinity binding of hPg/plasmin to pattern D GAS is fully recapitulated by the hPg kringle 2 domain (K2hPg) and a short internal peptide region (a1a2) of a specific subtype of bacterial surface M protein, present in all GAS pattern D strains. To better understand the nature of this binding, critical to the virulence of many GAS skin-tropic strains, we used high-resolution NMR to define the interaction of recombinant K2hPg with recombinant a1a2 (VKK38) of the M protein from GAS isolate NS455...
July 19, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28723944/application-of-mass-spectrometry-to-elucidate-the-pathophysiology-of-encephalitozoon-cuniculi-infection-in-rabbits
#4
Guillaume Desoubeaux, Maria Del Carmen Piqueras, Ana Pantin, Sanjoy K Bhattacharya, Roman Peschke, Anja Joachim, Carolyn Cray
Encephalitozoon cuniculi is a microsporidian species which can induce subclinical to serious disease in mammals including rabbits, a definitive natural host. The pathophysiology of infection has not been comprehensively elucidated. In this exploratory study, we utilized two mass spectrometry approaches: first, the analysis of the humoral response by profiling the microsporidian antigens as revealed by Western blot screening, and second, implementing the iTRAQ®-labeling protocol to focus on the changes within the host proteome during infection...
2017: PloS One
https://www.readbyqxmd.com/read/28722511/grwd1-a-new-player-among-oncogenesis-related-ribosomal-nucleolar-proteins
#5
Takuya Takafuji, Kota Kayama, Nozomi Sugimoto, Masatoshi Fujita
Increasing attention has been paid to certain ribosomal or ribosome biosynthesis-related proteins involved in oncogenesis. Members of one group are classified as "tumor suppressive factors" represented by RPL5 and RPL11; loss of their functions leads to cancer predisposition. RPL5 and RPL11 prevent tumorigenesis by binding to and inhibiting the MDM2 ubiquitin ligase and thereby up-regulating p53. Many other candidate tumor suppressive ribosomal/nucleolar proteins have been suggested. However, it remains to be experimentally clarified whether many of these factors can actually prevent tumorigenesis and if so, how they do so...
July 19, 2017: Cell Cycle
https://www.readbyqxmd.com/read/28721844/cd81-large-extracellular-loop-containing-fusion-proteins-with-a-dominant-negative-effect-on-hcv-cell-spread-and-replication
#6
Boyan Grigorov, Jennifer Molle, Eric Rubinstein, Fabien Zoulim, Birke Bartosch
The roles of CD81 in the hepatitis C virus (HCV) life cycle are multiple but remain ill characterized. CD81 is known to interact with the HCV glycoproteins as an attachment factor. It also has an important role in the post-attachment entry process. Its interaction with claudin-1, for example, is vital for viral uptake and trafficking. Furthermore, CD81 and its role in membrane organization and trafficking are thought to play a pivotal role in HCV replication. Some of these functions are particularly limited to human CD81; others can be substituted with CD81 molecules from other species...
July 18, 2017: Journal of General Virology
https://www.readbyqxmd.com/read/28720148/multifocal-gastric-adenocarcinoma-in-a-patient-with-lrba-deficiency
#7
Nina Bratanič, Jernej Kovač, Katka Pohar, Katarina Trebušak Podkrajšek, Alojz Ihan, Tadej Battelino, Magdalena Avbelj Stefanija
BACKGROUND: Lipopolysaccharide-responsive, beige-like anchor protein (LRBA) deficiency is characterized by primary immunodeficiency and autoimmunity. Cancer may present another feature of LRBA deficiency. We describe a case history of a young adult with LRBA deficiency and two independent malignancies. METHODS: Family-trio whole exome sequencing with unbiased phenotype ontology approach was used for identification of causative mutations of a primary immune deficiency disorder...
July 18, 2017: Orphanet Journal of Rare Diseases
https://www.readbyqxmd.com/read/28718807/melanin-and-melanin-related-polymers-as-materials-with-biomedical-and-biotechnological-applications-cuttlefish-ink-and-mussel-foot-proteins-as-inspired-biomolecules
#8
REVIEW
Francisco Solano
The huge development of bioengineering during the last years has boosted the search for new bioinspired materials, with tunable chemical, mechanical, and optoelectronic properties for the design of semiconductors, batteries, biosensors, imaging and therapy probes, adhesive hydrogels, tissue restoration, photoprotectors, etc. These new materials should complement or replace metallic or organic polymers that cause cytotoxicity and some adverse health effects. One of the most interesting biomaterials is melanin and synthetic melanin-related molecules...
July 18, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28718762/sec17-sec18-act-twice-enhancing-membrane-fusion-and-then-disassembling-cis-snare-complexes
#9
Hongki Song, Amy S Orr, Mengtong Duan, Alexey J Merz, William T Wickner
At physiological protein levels, the slow HOPS- and SNARE-dependent fusion which occurs upon complete SNARE zippering is stimulated by Sec17 and Sec18:ATP without requiring ATP hydrolysis. To stimulate, Sec17 needs its central residues which bind the 0-layer of the SNARE complex and its N-terminal apolar loop. Adding a transmembrane anchor to the N-terminus of Sec17 bypasses this requirement for apolarity of the Sec17 loop, suggesting that the loop functions for membrane binding rather than to trigger bilayer rearrangement...
July 18, 2017: ELife
https://www.readbyqxmd.com/read/28718265/haemoglobinuria-and-portal-venous-thrombosis-in-a-young-male
#10
Zain Ul Abideen, Munnam Sohail Jafar, Nasir Hameed, Ahmad Malik
Paroxysmal nocturnal haemoglobinuria is a non-malignant stem cell disorder due to acquired somatic mutations in cell surface anchored proteins CD55 and CD59. Both have a compliment inhibitory role and their deficiency leads to intravascular haemolysis. This paper reports a challenging case of a 25 years old male who presented with generalized weakness, exertional dyspnoea and episodic early morning haematuria. Recently, he started developing progressive abdominal distention and dull generalized abdominal pain...
April 2017: Journal of Ayub Medical College, Abbottabad: JAMC
https://www.readbyqxmd.com/read/28716937/altered-metabotropic-glutamate-receptor-5-markers-in-ptsd-in-vivo-and-postmortem-evidence
#11
Sophie E Holmes, Matthew J Girgenti, Margaret T Davis, Robert H Pietrzak, Nicole DellaGioia, Nabeel Nabulsi, David Matuskey, Steven Southwick, Ronald S Duman, Richard E Carson, John H Krystal, Irina Esterlis
Posttraumatic stress disorder (PTSD) is a prevalent and highly disabling disorder, but there is currently no targeted pharmacological treatment for it. Dysfunction of the glutamate system has been implicated in trauma and stress psychopathology, resulting in a growing interest in modulation of the glutamate system for the treatment of PTSD. Specifically, the metabotropic glutamate receptor 5 (mGluR5) represents a promising treatment target. We used [(18)F]FPEB, a radioligand that binds to the mGluR5, and positron emission tomography (PET) to quantify in vivo mGluR5 availability in human PTSD vs...
July 17, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28716744/a-heterozygous-mutation-in-got1-is-associated-with-familial-macro-aspartate-aminotransferase
#12
Maria Kulecka, Aldona Wierzbicka, Agnieszka Paziewska, Michal Mikula, Andrzej Habior, Wojciech Janczyk, Michalina Dabrowska, Jakub Karczmarski, Michal Lazniewski, Krzysztof Ginalski, Anna Czlonkowska, Piotr Socha, Jerzy Ostrowski
BACKGROUND & AIMS: Macro-aspartate aminotransferase (macro-AST) manifests as persistent elevation of AST levels, due to association of the protein with immunoglobulins in the circulation macro-AST is a rare, benign condition without a previously confirmed genetic basis. METHODS: Whole exome sequencing (WES)-based screening was performed on 32 participants with suspected familial macro-AST, while variants validation was performed on an extended cohort of 90 probands and 1644 healthy controls using Taqman genotyping...
July 14, 2017: Journal of Hepatology
https://www.readbyqxmd.com/read/28714993/a-two-helix-motif-positions-the-lysophosphatidic-acid-acyltransferase-active-site-for-catalysis-within-the-membrane-bilayer
#13
Rosanna M Robertson, Jiangwei Yao, Stefan Gajewski, Gyanendra Kumar, Erik W Martin, Charles O Rock, Stephen W White
Phosphatidic acid (PA), the central intermediate in membrane phospholipid synthesis, is generated by two acyltransferases in a pathway conserved in all life forms. The second step in this pathway is catalyzed by 1-acyl-sn-glycerol-3-phosphate acyltransferase, called PlsC in bacteria. Here we present the crystal structure of PlsC from Thermotoga maritima, revealing an unusual hydrophobic/aromatic N-terminal two-helix motif linked to an acyltransferase αβ-domain that contains the catalytic HX4D motif. PlsC dictates the acyl chain composition of the 2-position of phospholipids, and the acyl chain selectivity 'ruler' is an appropriately placed and closed hydrophobic tunnel...
July 17, 2017: Nature Structural & Molecular Biology
https://www.readbyqxmd.com/read/28714966/nanoscale-imaging-of-clinical-specimens-using-pathology-optimized-expansion-microscopy
#14
Yongxin Zhao, Octavian Bucur, Humayun Irshad, Fei Chen, Astrid Weins, Andreea L Stancu, Eun-Young Oh, Marcello DiStasio, Vanda Torous, Benjamin Glass, Isaac E Stillman, Stuart J Schnitt, Andrew H Beck, Edward S Boyden
Expansion microscopy (ExM), a method for improving the resolution of light microscopy by physically expanding a specimen, has not been applied to clinical tissue samples. Here we report a clinically optimized form of ExM that supports nanoscale imaging of human tissue specimens that have been fixed with formalin, embedded in paraffin, stained with hematoxylin and eosin, and/or fresh frozen. The method, which we call expansion pathology (ExPath), converts clinical samples into an ExM-compatible state, then applies an ExM protocol with protein anchoring and mechanical homogenization steps optimized for clinical samples...
July 17, 2017: Nature Biotechnology
https://www.readbyqxmd.com/read/28714554/type-ix-secretion-the-generation-of-bacterial-cell-surface-coatings-involved-in-virulence-gliding-motility-and-the-degradation-of-complex-biopolymers
#15
Paul D Veith, Michelle D Glew, Dhana G Gorasia, Eric C Reynolds
The Type IX Secretion System (T9SS) is present in over 1000 sequenced species/strains of the Fibrobacteres-Chlorobi-Bacteroidetes superphylum. Proteins secreted by the T9SS have an N-terminal signal peptide for translocation across the inner membrane via the SEC translocon and a C-terminal signal for secretion across the outer membrane via the T9SS. Nineteen protein components of the T9SS have been identified including three, SigP, PorX and PorY that are involved in regulation. The inner membrane proteins PorL and PorM and the outer membrane proteins PorK and PorN interact and a complex comprising PorK and PorN forms a large ring structure of 50 nm in diameter...
July 17, 2017: Molecular Microbiology
https://www.readbyqxmd.com/read/28714313/artificial-metalloenzymes-reaction-scope-and-optimization-strategies
#16
Fabian Schwizer, Yasunori Okamoto, Tillmann Heinisch, Yifan Gu, Michela M Pellizzoni, Vincent Lebrun, Raphael Reuter, Valentin Köhler, Jared C Lewis, Thomas R Ward
The incorporation of a synthetic, catalytically competent metallocofactor into a protein scaffold to generate an artificial metalloenzyme (ArM) has been explored since the late 1970's. Progress in the ensuing years was limited by the tools available for both organometallic synthesis and protein engineering. Advances in both of these areas, combined with increased appreciation of the potential benefits of combining attractive features of both homogeneous catalysis and enzymatic catalysis, led to a resurgence of interest in ArMs starting in the early 2000's...
July 17, 2017: Chemical Reviews
https://www.readbyqxmd.com/read/28713858/life-stage-specific-cargo-receptors-facilitate-glycosylphosphatidylinositol-anchored-surface-coat-protein-transport-in-trypanosoma-brucei
#17
Emilia K Kruzel, George P Zimmett, James D Bangs
The critical virulence factor of bloodstream-form Trypanosoma brucei is the glycosylphosphatidylinositol (GPI)-anchored variant surface glycoprotein (VSG). Endoplasmic reticulum (ER) exit of VSG is GPI dependent and relies on a discrete subset of COPII machinery (TbSec23.2/TbSec24.1). In other systems, p24 transmembrane adaptor proteins selectively recruit GPI-anchored cargo into nascent COPII vesicles. Trypanosomes have eight putative p24s (TbERP1 to TbERP8) that are constitutively expressed at the mRNA level...
July 2017: MSphere
https://www.readbyqxmd.com/read/28712723/msp1-is-a-membrane-protein-dislocase-for-tail-anchored-proteins
#18
Matthew L Wohlever, Agnieszka Mateja, Philip T McGilvray, Kasey J Day, Robert J Keenan
Mislocalized tail-anchored (TA) proteins of the outer mitochondrial membrane are cleared by a newly identified quality control pathway involving the conserved eukaryotic protein Msp1 (ATAD1 in humans). Msp1 is a transmembrane AAA-ATPase, but its role in TA protein clearance is not known. Here, using purified components reconstituted into proteoliposomes, we show that Msp1 is both necessary and sufficient to drive the ATP-dependent extraction of TA proteins from the membrane. A crystal structure of the Msp1 cytosolic region modeled into a ring hexamer suggests that active Msp1 contains a conserved membrane-facing surface adjacent to a central pore...
July 8, 2017: Molecular Cell
https://www.readbyqxmd.com/read/28711825/autonomous-electrochemical-biosensors-a-new-vision-to-direct-methanol-fuel-cells
#19
M Goreti F Sales, Lúcia Brandão
A new approach to biosensing devices is demonstrated aiming an easier and simpler application in routine health care systems. Our methodology considered a new concept for the biosensor transducing event that allows to obtain, simultaneously, an equipment-free, user-friendly, cheap electrical biosensor. The use of the anode triple-phase boundary (TPB) layer of a passive direct methanol fuel cell (DMFC) as biosensor transducer is herein proposed. For that, the ionomer present in the anode catalytic layer of the DMFC is partially replaced by an ionomer with molecular recognition capability working as the biorecognition element of the biosensor...
July 11, 2017: Biosensors & Bioelectronics
https://www.readbyqxmd.com/read/28710958/japanese-encephalitis-virus-counteracts-bst2-restriction-via-its-envelope-protein-e
#20
Mei Li, Ping Wang, Zifeng Zheng, Kai Hu, Mudan Zhang, Xinmeng Guan, Ming Fu, Di Zhang, Wei Wang, Gengfu Xiao, Qinxue Hu, Yalan Liu
It has been well documented that BST2 restricts the release of enveloped viruses by cross-linking newly produced virions to the cell membrane. However, it is less clear whether and how BST2 inhibits the release of enveloped viruses which bud via the secretory pathway. Here, we demonstrated that BST2 restricts the release of Japanese encephalitis virus (JEV) whose budding occurs at the ER-Golgi intermediate compartment, and in turn, JEV infection downregulates BST2 expression. We further found that the JEV envelope protein E, but not other viral components, significantly downregulates BST2 with the viral protein M playing an auxiliary role in the process...
July 12, 2017: Virology
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