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Amino Acid Therapy

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https://www.readbyqxmd.com/read/27935841/the-cytoplasmic-tail-domain-of-epstein-barr-virus-gh-regulates-membrane-fusion-activity-through-altering-gh-binding-to-gp42-and-epithelial-cell-attachment
#1
Jia Chen, Theodore S Jardetzky, Richard Longnecker
: Epstein-Barr virus (EBV) is associated with infectious mononucleosis and a variety of cancers as well as lymphoproliferative disorders in immunocompromised patients. EBV mediates viral entry into epithelial and B cells using fusion machinery composed of four glycoproteins: gB, the gH/gL complex, and gp42. gB and gH/gL are required for both epithelial and B cell fusion. The specific role of gH/gL in fusion has been the most elusive among the required herpesvirus entry glycoproteins. Previous mutational studies have focused on the ectodomain of EBV gH and not on the gH cytoplasmic tail domain (CTD)...
November 15, 2016: MBio
https://www.readbyqxmd.com/read/27934069/blood-brain-barrier-penetrating-albumin-nanoparticles-for-biomimetic-drug-delivery-via-albumin-binding-protein-pathways-for-antiglioma-therapy
#2
Tingting Lin, Pengfei Zhao, Yifan Jiang, Yisi Tang, Hongyue Jin, Zhenzhen Pan, Huining He, Victor C Yang, Yongzhuo Huang
Nutrient transporters have been explored for biomimetic delivery targeting the brain. The albumin-binding proteins (e.g., SPARC and gp60) are overexpressed in many tumors for transport of albumin as an amino acid and an energy source for fast-growing cancer cells. However, their application in brain delivery has rarely been investigated. In this work, SPARC and gp60 overexpression was found on glioma and tumor vessel endothelium; therefore, such pathways were explored for use in brain-targeting biomimetic delivery...
November 22, 2016: ACS Nano
https://www.readbyqxmd.com/read/27932423/integrated-genomic-analysis-of-survival-outliers-in-glioblastoma
#3
Sen Peng, Harshil Dhurv, Brock Armstrong, Bodour Salhia, Christophe Legendre, Jeffrey Kiefer, Julianna Parks, Selene Virk, Andrew E Sloan, Quinn T Ostrom, Jill S Barnholtz-Sloan, Nhan L Tran, Michael E Berens
BACKGROUND: To elucidate molecular features associated with disproportionate survival of glioblastoma (GB) patients, we conducted deep genomic comparative analysis of a cohort of patients receiving standard therapy (surgery plus concurrent radiation and temozolomide); "GB outliers" were identified: long-term survivor of 33 months (LTS; n = 8) versus short-term survivor of 7 months (STS; n = 10). METHODS: We implemented exome, RNA, whole genome sequencing, and DNA methylation for collection of deep genomic data from STS and LTS GB patients...
December 8, 2016: Neuro-oncology
https://www.readbyqxmd.com/read/27932276/the-why-and-how-of-amino-acid-analytics-in-cancer-diagnostics-and-therapy
#4
REVIEW
Friederike Manig, Konstantin Kuhne, Cläre von Neubeck, Uwe Schwarzenbolz, Zhanru Yu, Benedikt M Kessler, Jens Pietzsch, Leoni A Kunz-Schughart
Pathological alterations in cell functions are frequently accompanied by metabolic reprogramming including modifications in amino acid metabolism. Amino acid detection is thus integral to the diagnosis of many hereditary metabolic diseases. The development of malignant diseases as metabolic disorders comes along with a complex dysregulation of genetic and epigenetic factors affecting metabolic enzymes. Cancer cells might transiently or permanently become auxotrophic for non-essential or semi-essential amino acids such as asparagine or arginine...
December 5, 2016: Journal of Biotechnology
https://www.readbyqxmd.com/read/27929116/a-proteolytic-modification-of-aim-promotes-its-renal-excretion
#5
Tomoko Yamazaki, Ryoichi Sugisawa, Emiri Hiramoto, Ryosuke Takai, Ayaka Matsumoto, Yoshie Senda, Katsuhiko Nakashima, Peter S Nelson, Jared M Lucas, Andrew Morgan, Zhenghua Li, Ken-Ichi Yamamura, Satoko Arai, Toru Miyazaki
Apoptosis inhibitor of macrophage (AIM, encoded by cd5l) is a multi-functional circulating protein that has a beneficial role in the regulation of a broad range of diseases, some of which are ameliorated by AIM administration in mice. In blood, AIM is stabilized by association with IgM pentamers and maintains its high circulating levels. The mechanism regulating the excessive accumulation of blood AIM remains unknown, although it is important, since a constitutive increase in AIM levels promotes chronic inflammation...
December 8, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27928027/five-coordinate-h64q-neuroglobin-as-a-ligand-trap-antidote-for-carbon-monoxide-poisoning
#6
Ivan Azarov, Ling Wang, Jason J Rose, Qinzi Xu, Xueyin N Huang, Andrea Belanger, Ying Wang, Lanping Guo, Chen Liu, Kamil B Ucer, Charles F McTiernan, Christopher P O'Donnell, Sruti Shiva, Jesús Tejero, Daniel B Kim-Shapiro, Mark T Gladwin
Carbon monoxide (CO) is a leading cause of poisoning deaths worldwide, with no available antidotal therapy. We introduce a potential treatment paradigm for CO poisoning, based on near-irreversible binding of CO by an engineered human neuroglobin (Ngb). Ngb is a six-coordinate hemoprotein, with the heme iron coordinated by two histidine residues. We mutated the distal histidine to glutamine (H64Q) and substituted three surface cysteines with less reactive amino acids to form a five-coordinate heme protein (Ngb-H64Q-CCC)...
December 7, 2016: Science Translational Medicine
https://www.readbyqxmd.com/read/27925690/purification-and-characterization-of-a-platelet-aggregation-inhibitor-and-anticoagulant-cc-5_ntase-cd-73-like-from-cerastes-cerastes-venom
#7
Samah Saoud, Fatah Chérifi, Traki Benhassine, Fatima Laraba-Djebari
The present study is the first attempt to report the characterization of a nucleotidase from Cerastes cerastes venom. A 70 kDa 5'-nucleotidase (Cc-5'NTase) was purified to homogeneity. The amino acid sequence of Cc-5'NTase displayed high homology with many nucleotidases. Its activity was optimal at pH 7 with a specific hydrolytic activity toward mono-, di-, and triphosphate adenylated nucleotides. Cc-5'NTase preferentially hydrolyzed ADP and obeyed Michaelis-Menten kinetics. Among the metals and inhibitors tested, Ni(2+) and Mg(2+) completely potentiated enzyme activity, whereas EGTA, PMSF, iodoacetamide, vanillic acid, vanillyl mandelic acid, and 1,10-phenanthroline partially abolished its activity...
December 7, 2016: Journal of Biochemical and Molecular Toxicology
https://www.readbyqxmd.com/read/27921081/a-fungus-specific-protein-domain-is-essential-for-rasa-mediated-morphogenetic-signaling-in-aspergillus-fumigatus
#8
Qusai Al Abdallah, Tiffany S Norton, Amy M Hill, Lawrence L LeClaire, Jarrod R Fortwendel
Ras proteins function as conserved regulators of eukaryotic growth and differentiation and are essential signaling proteins orchestrating virulence in pathogenic fungi. Here, we report the identification of a novel N-terminal domain of the RasA protein in the filamentous fungus Aspergillus fumigatus. Whereas this domain is absent in Ras homologs of higher eukaryotes, the N-terminal extension is conserved among fungi and is characterized by a short string of two to eight amino acids terminating in an invariant arginine...
November 2016: MSphere
https://www.readbyqxmd.com/read/27920481/new-real-time-pcr-method-to-identify-single-point-mutations-in-hepatitis-c-virus
#9
Qian Chen, Irene Belmonte, Maria Buti, Leonardo Nieto, Damir Garcia-Cehic, Josep Gregori, Celia Perales, Laura Ordeig, Meritxell Llorens, Maria Eugenia Soria, Rafael Esteban, Juan Ignacio Esteban, Francisco Rodriguez-Frias, Josep Quer
AIM: To develop a fast, low-cost diagnostic strategy to identify single point mutations in highly variable genomes such as hepatitis C virus (HCV). METHODS: In patients with HCV infection, resistance-associated amino acid substitutions within the viral quasispecies prior to therapy can confer decreased susceptibility to direct-acting antiviral agents and lead to treatment failure and virological relapse. One such naturally occurring mutation is the Q80K substitution in the HCV-NS3 protease gene, which confers resistance to PI inhibitors, particularly simeprevir...
November 21, 2016: World Journal of Gastroenterology: WJG
https://www.readbyqxmd.com/read/27919007/challenges-in-assignment-of-allosteric-effects-in-cytochrome-p450-catalyzed-substrate-oxidations-to-structural-dynamics-in-the-hemoprotein-architecture
#10
Peter Hlavica
Cytochrome P450s (CYP) represent a superfamily of b-type hemoproteins catalyzing NAD(P)H-dependent oxidative biotransformation of a vast array of natural and xenobiotic compounds. Many eu- and prokaryotic members of this class of monooxygenases display complex non-Michaelis-Menten saturation kinetics, suggestive of homo-/heterotropic cooperativity arising from substrate-/effector-induced allosteric interactions. Here, the paradigm of multiple-ligand occupancy of the catalytic pocket in combination with enzyme oligomerization provides the most favored explanations for the atypical kinetic patterns...
November 25, 2016: Journal of Inorganic Biochemistry
https://www.readbyqxmd.com/read/27914526/jiawei-erzhiwan-improves-menopausal-metabolic-syndrome-by-enhancing-insulin-secretion-in-pancreatic-%C3%AE-cells
#11
Xiao-Meng Wan, Mu Zhang, Pei Zhang, Zhi-Shen Xie, Feng-Guo Xu, Ping Zhou, Shi-Ping Ma, Xiao-Jun Xu
Menopausal metabolic syndrome (MMS) is a series of syndrome caused by ovarian function decline and hormone insufficiency, and is a high risk factor for cardiovascular diseases (CVD) and type II diabetes mellitus (T2DM). Erzhiwan (EZW), composed of Herba Ecliptae and Fructus Ligustri Lucidi, is a traditional Chinese herbal formula that has been used to treat menopausal syndrome for many years. We added Herba Epimedii, Radix Rehmanniae, and Fructus Corni into EZW, to prepare a new formula, termed Jiawei Erzhiwan (JE)...
November 2016: Chinese Journal of Natural Medicines
https://www.readbyqxmd.com/read/27913515/cellular-immune-responses-in-red-blood-cell-alloimmunization
#12
James C Zimring, Krystalyn E Hudson
In excess of 340 blood group antigens have now been described that vary between individuals. Thus, any unit of blood that is nonautologous represents a significant dose of alloantigen. Most blood group antigens are proteins, which differ by a single amino acid between donors and recipients. Approximately 1 out of every 70 individuals are transfused each year (in the United States alone), which leads to antibody responses to red blood cell (RBC) alloantigens in some transfusion recipients. When alloantibodies are formed, in many cases, RBCs expressing the antigen in question can no longer be safely transfused...
December 2, 2016: Hematology—the Education Program of the American Society of Hematology
https://www.readbyqxmd.com/read/27912794/a-genetic-risk-score-composed-of-rheumatoid-arthritis-risk-alleles-hla-drb1-haplotypes-and-response-to-tnfi-therapy-results-from-a-swedish-cohort-study
#13
Xia Jiang, Johan Askling, Saedis Saevarsdottir, Leonid Padyukov, Lars Alfredsson, Sebastien Viatte, Thomas Frisell
BACKGROUND: To prevent debilitating and irreversible joint damage, rheumatoid arthritis (RA) is often treated with tumor necrosis factor inhibitor (TNFi), but many patients do not respond to this costly therapy. Few predictors for response are known, and it has been proposed that genetic factors which influence the development of RA may also influence disease severity and response to therapy. Several previous studies have attempted to confirm this but results remain inconclusive. We expand on previous studies by including more RA risk alleles, and maximize power by combining them into a genetic risk score...
December 3, 2016: Arthritis Research & Therapy
https://www.readbyqxmd.com/read/27908546/effects-of-branched-chain-amino-acid-supplementation-after-radiofrequency-ablation-for-hepatocellular-carcinoma-a-randomized-trial
#14
Shunsuke Nojiri, Kei Fujiwara, Noboru Shinkai, Etsuko Iio, Takashi Joh
OBJECTIVE: Maintenance of liver function is important for better outcomes after radiofrequency ablation (RFA) for hepatocellular carcinoma (HCC). The aim of this study was to examine the effects of oral branched-chain amino acid (BCAA) supplementation on liver function, intrahepatic recurrence rate, and incidence of complications after RFA for HCC. METHODS: Patients with cirrhosis who underwent RFA were enrolled between August 2009 and April 2012, randomized to oral supplementation with Aminoleban EN (BCAA group) or diet alone (control group), and followed to determine changes in serum parameters and health status...
January 2017: Nutrition
https://www.readbyqxmd.com/read/27908295/dopamine-2-receptor-extracellular-n-terminus-regulates-receptor-surface-availability-and-is-the-target-of-human-pathogenic-antibodies-from-children-with-movement-and-psychiatric-disorders
#15
Nese Sinmaz, Fiona Tea, Deepti Pilli, Alicia Zou, Mazen Amatoury, Tina Nguyen, Vera Merheb, Sudarshini Ramanathan, Sandra T Cooper, Russell C Dale, Fabienne Brilot
Anti-Dopamine-2 receptor (D2R) antibodies have been recently identified in a subgroup of children with autoimmune movement and psychiatric disorders, however the epitope(s) and mechanism of pathogenicity remain unknown. Here we report a major biological role for D2R extracellular N-terminus as a regulator of receptor surface availability, and as a major epitope targeted and impaired in brain autoimmunity. In transfected human cells, purified anti-D2R antibody from patients specifically and significantly reduced human D2R surface levels...
December 1, 2016: Acta Neuropathologica Communications
https://www.readbyqxmd.com/read/27906990/surveillance-of-helicobacter-pylori-antibiotic-susceptibility-in-indonesia-different-resistance-types-among-regions-and-with-novel-genetic-mutations
#16
Muhammad Miftahussurur, Ari Fahrial Syam, Iswan Abbas Nusi, Dadang Makmun, Langgeng Agung Waskito, Lukman Hakim Zein, Fardah Akil, Willy Brodus Uwan, David Simanjuntak, I Dewa Nyoman Wibawa, Jimmy Bradley Waleleng, Alexander Michael Joseph Saudale, Fauzi Yusuf, Syifa Mustika, Pangestu Adi, Ummi Maimunah, Hasan Maulahela, Yudith Annisa Ayu Rezkitha, Phawinee Subsomwong, Nasronudin, Dadik Rahardjo, Rumiko Suzuki, Junko Akada, Yoshio Yamaoka
Information regarding Helicobacter pylori antibiotic resistance in Indonesia was previously inadequate. We assessed antibiotic susceptibility for H. pylori in Indonesia, and determined the association between virulence genes or genetic mutations and antibiotic resistance. We recruited 849 dyspeptic patients who underwent endoscopy in 11 cities in Indonesia. E-test was used to determine the minimum inhibitory concentration of five antibiotics. PCR-based sequencing assessed mutations in 23S rRNA, rdxA, gyrA, gyrB, and virulence genes...
2016: PloS One
https://www.readbyqxmd.com/read/27901085/wide-variation-in-susceptibility-of-transmitted-founder-hiv-1-subtype-c-isolates-to-protease-inhibitors-and-association-with-in-vitro-replication-efficiency
#17
Katherine A Sutherland, Dami A Collier, Daniel T Claiborne, Jessica L Prince, Martin J Deymier, Richard A Goldstein, Eric Hunter, Ravindra K Gupta
The gag gene is highly polymorphic across HIV-1 subtypes and contributes to susceptibility to protease inhibitors (PI), a critical class of antiretrovirals that will be used in up to 2 million individuals as second-line therapy in sub Saharan Africa by 2020. Given subtype C represents around half of all HIV-1 infections globally, we examined PI susceptibility in subtype C viruses from treatment-naïve individuals. PI susceptibility was measured in a single round infection assay of full-length, replication competent MJ4/gag chimeric viruses, encoding the gag gene and 142 nucleotides of pro derived from viruses in 20 patients in the Zambia-Emory HIV Research Project acute infection cohort...
November 30, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27896994/human-kinases-display-mutational-hotspots-at-cognate-positions-within-cancer
#18
Jonathan Gallion, Angela D Wilkins, Olivier Lichtarge
The discovery of driver genes is a major pursuit of cancer genomics, usually based on observing the same mutation in different patients. But the heterogeneity of cancer pathways plus the high background mutational frequency of tumor cells often cloud the distinction between less frequent drivers and innocent passenger mutations. Here, to overcome these disadvantages, we grouped together mutations from close kinase paralogs under the hypothesis that cognate mutations may functionally favor cancer cells in similar ways...
2016: Pacific Symposium on Biocomputing
https://www.readbyqxmd.com/read/27896591/design-and-in-vitro-evaluation-of-bispecific-complexes-and-drug-conjugates-of-anticancer-peptide-lyp-1-in-human-breast-cancer
#19
Selin Seda Timur, Prashant Bhattarai, Reyhan Neslihan Gürsoy, İmran Vural, Ban-An Khaw
PURPOSE: LyP-1, a nine-amino-acid tumor homing peptide, selectively binds to its cognate receptor, p32. Overexpression of p32 in certain tumors should allow use of LyP-1 as a targeting agent for the delivery of therapeutic or diagnostic agents. Peptide conjugates are developed for enhanced pre-targeting of MDA-MB-231 breast cancer cells with peptide-antibody bispecific complexes and targeting with multiple-drug/-fluorophore-conjugated nano-polymers. METHODS: LyP-1-anti-DTPA bispecific antibody complexes (LyP-1-bsAbCx) were generated by conjugation of anti-DTPA antibody and LyP-1...
November 28, 2016: Pharmaceutical Research
https://www.readbyqxmd.com/read/27894862/hiv-drug-resistance-testing-among-patients-failing-second-line-antiretroviral-therapy-comparison-of-in-house-and-commercial-sequencing
#20
Benjamin Chimukangara, Bhavini Varyani, Tinei Shamu, Junior Mutsvangwa, Justen Manasa, Elizabeth White, Cleophas Chimbetete, Ruedi Luethy, David Katzenstein
INTRODUCTION: HIV genotyping is often unavailable in low and middle-income countries due to infrastructure requirements and cost. We compared genotype resistance testing in patients with virologic failure, by amplification of HIV pol gene, followed by "in-house" sequencing and commercial sequencing. METHODS: Remnant plasma samples from adults and children failing second-line ART were amplified and sequenced using in-house and commercial di-deoxysequencing, and analyzed in Harare, Zimbabwe and at Stanford, U...
November 25, 2016: Journal of Virological Methods
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