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https://www.readbyqxmd.com/read/29150937/cgmp-production-and-analysis-of-bg505-sosip-664-an-extensively-glycosylated-trimeric-hiv-1-envelope-glycoprotein-vaccine-candidate
#1
Antu K Dey, Albert Cupo, Gabriel Ozorowski, Vaneet K Sharma, Anna-Janina Behrens, Eden P Go, Thomas J Ketas, Anila Yasmeen, Per J Klasse, Eddy Sayeed, Heather Desaire, Max Crispin, Ian A Wilson, Rogier W Sanders, Thomas Hassell, Andrew Ward, John P Moore
We describe the properties of BG505 SOSIP.664 HIV-1 envelope glycoprotein trimers produced under current Good Manufacturing Practice (cGMP) conditions. These proteins are the first of a new generation of native-like trimers that are the basis for many structure-guided immunogen development programs aimed at devising how to induce broadly neutralizing antibodies (bNAbs) to HIV-1 by vaccination. The successful translation of this prototype demonstrates the feasibility of producing similar immunogens on an appropriate scale and of an acceptable quality for Phase I experimental medicine clinical trials...
November 18, 2017: Biotechnology and Bioengineering
https://www.readbyqxmd.com/read/29150935/generation-of-insulin-producing-cells-from-human-adipose-derived-mesenchymal-stem-cells-on-pva-scaffold-by-optimized-differentiation-protocol
#2
Seyed Ehsan Enderami, Masoud Soleimani, Yousef Mortazavi, Samad Nadri, Ali Salimi
The studies have been done on patient-specific human adipose-derived from mesenchymal stem cells (hADSCs) like a series of autologous growth factors and nanofibrous scaffolds (3D culture) will probably have many benefits for regenerative medicine in type 1 diabetes mellitus (TIDM) patients in the future. For this purpose, we established a polyvinyl alcohol (PVA) scaffold and a differentiation protocol by adding platelet-rich plasma (PRP) that induces the hADSCs into insulin-producing cells (IPCs). The Characteristics of the derived IPCs in 3D culture were compared with conventional culture (2D) groups evaluated at the mRNA and protein levels...
November 18, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/29150926/viral-short-orfs-and-their-possible-functions
#3
REVIEW
Yaara Finkel, Noam Stern-Ginossar, Michal Schwartz
Definition of functional genomic elements is one of the greater challenges of the genomic era. Traditionally, putative short Open Reading Frames (sORFs) coding for less than 100 amino acids were disregarded due to computational and experimental limitations, however it has become clear over the past several years that translation of sORFs is pervasive and serves diverse functions. The development of ribosome profiling, allowing identification of translated sequences genome-wide, revealed wide-spread, previously unidentified translation events...
November 18, 2017: Proteomics
https://www.readbyqxmd.com/read/29150896/stereospecific-control-of-peptide-gas-phase-ion-chemistry-with-cis-and-trans-cyclo-ornithine-residues
#4
Aleš Marek, Huong T H Nguyen, Břetislav Brož, František Tureček
We report non-chiral amino acid residues cis- and trans-1,4-diaminocyclohexane-1-carboxylic acid (cyclo-ornithine, cO) that exhibit unprecedented stereospecific control of backbone dissociations of singly charged peptide cations and hydrogen-rich cation radicals produced by electron-transfer dissociation (ETD). Upon collision-induced dissociation (CID) in the slow heating regime, peptide cations containing trans-cO residues undergo facile backbone cleavages of amide bonds C-terminal to trans-cO. In contrast, peptides with cis-cO residues undergo dissociations at several amide bonds along the peptide ion backbone...
November 18, 2017: Journal of Mass Spectrometry: JMS
https://www.readbyqxmd.com/read/29150857/a-randomized-double-blind-placebo-controlled-dose-finding-trial-with-lolium-perenne-peptide-immunotherapy
#5
Ralph Mösges, Elena M Kasche, Esther Raskopf, Jaswinder Singh, Lea Sohlich, Anatoli Astvatsatourov, Kija Shah-Hosseini, Sabine Pirotton, Ludo Haazen, Stephen R Durham, Thierry Legon, Gregor Zadoyan, Mohamed H Shamji
BACKGROUND: A novel subcutaneous allergen immunotherapy formulation (gpASIT+(™) ) containing Lolium perenne peptides (LPP) and having a short up-dosing phase has been developed to treat grass pollen-induced seasonal allergic rhinoconjunctivitis. We investigated peptide immunotherapy containing the hydrolysate from perennial ryegrass allergens for the optimum dose in terms of clinical efficacy, immunogenicity, and safety. METHODS: This prospective, double-blind, placebo-controlled, phase IIb, parallel, four-arm, dose-finding study randomized 198 grass pollen-allergic adults to receive placebo or cumulative doses of 70, 170, or 370 μg LPP...
November 18, 2017: Allergy
https://www.readbyqxmd.com/read/29150631/effect-of-long-term-incretin-based-therapies-on-ischemic-heart-diseases-in-patients-with-type-2-diabetes-mellitus-a-network-meta-analysis
#6
Che-Yi Chou, Ying-Tzu Chang, Jia-Lian Yang, Jiun-Yi Wang, Tsui-Er Lee, Ruey-Yun Wang, Chin-Chuan Hung
Patients with type 2 diabetes mellitus (T2DM) experience many cardiovascular complications. Several studies have demonstrated the cardioprotective effects of incretin-based therapies; however, there are few studies on the effects of long-term incretin-based therapies on cardiovascular events. Therefore, the present study conducted a systematic review and network meta-analysis to evaluate the effects of long-term incretin-based therapies on ischaemic diseases. We searched PubMed, CENTRAL, and Clinicaltrial.gov to retrieve randomised control trials reported until December 2016 and enrolled only RCTs with more than a 1-year follow-up...
November 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29150621/pnpla3-variant-and-portal-periportal-histological-pattern-in-patients-with-biopsy-proven-non-alcoholic-fatty-liver-disease-a-possible-role-for-oxidative-stress
#7
Guido Carpino, Daniele Pastori, Francesco Baratta, Diletta Overi, Giancarlo Labbadia, Licia Polimeni, Alessia Di Costanzo, Gaetano Pannitteri, Roberto Carnevale, Maria Del Ben, Marcello Arca, Francesco Violi, Francesco Angelico, Eugenio Gaudio
Pathogenesis of non-alcoholic fatty liver disease (NAFLD) is influenced by predisposing genetic variations, dysmetabolism, systemic oxidative stress, and local cellular and molecular cross-talks. Patatin-like phospholipase domain containing 3 (PNPLA3) gene I148M variant is a known determinant of NAFLD. Aims were to evaluate whether PNPLA3 I148M variant was associated with a specific histological pattern, hepatic stem/progenitor cell (HpSC) niche activation and serum oxidative stress markers. Liver biopsies were obtained from 54 NAFLD patients...
November 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29150562/the-role-of-mhc-e-in-t-cell-immunity-is-conserved-among-humans-rhesus-macaques-and-cynomolgus-macaques
#8
Helen L Wu, Roger W Wiseman, Colette M Hughes, Gabriela M Webb, Shaheed A Abdulhaqq, Benjamin N Bimber, Katherine B Hammond, Jason S Reed, Lina Gao, Benjamin J Burwitz, Justin M Greene, Fidel Ferrer, Alfred W Legasse, Michael K Axthelm, Byung S Park, Simon Brackenridge, Nicholas J Maness, Andrew J McMichael, Louis J Picker, David H O'Connor, Scott G Hansen, Jonah B Sacha
MHC-E is a highly conserved nonclassical MHC class Ib molecule that predominantly binds and presents MHC class Ia leader sequence-derived peptides for NK cell regulation. However, MHC-E also binds pathogen-derived peptide Ags for presentation to CD8(+) T cells. Given this role in adaptive immunity and its highly monomorphic nature in the human population, HLA-E is an attractive target for novel vaccine and immunotherapeutic modalities. Development of HLA-E-targeted therapies will require a physiologically relevant animal model that recapitulates HLA-E-restricted T cell biology...
November 17, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/29150511/sulfolobus-acidocaldarius-uptakes-pentoses-via-a-cut2-type-abc-transporter-and-metabolizes-them-through-the-aldolase-independent-weimberg-pathway
#9
Michaela Wagner, Lu Shen, Andreas Albersmeier, Nienke van der Kolk, Sujin Kim, Jaeho Cha, Christopher Bräsen, Jörn Kalinowski, Bettina Siebers, Sonja-Verena Albers
Sulfolobus spp. possess a great metabolic versatility and grow heterotrophically on various carbon sources such as different sugars and peptides. Known sugar transporters in Archaea predominantly belong to ABC transport systems. Although several ABC transporters for sugar uptake have been characterized in the crenarchaeon Sulfolobus solfataricus, only one homologue of these transporters, the maltose/maltooligomer transporter, could be identified in the closely related Sulfolobus acidocaldarius Comparison of the transcriptome of S...
November 17, 2017: Applied and Environmental Microbiology
https://www.readbyqxmd.com/read/29150447/the-prototypical-proton-coupled-oligopeptide-transporter-ydgr-from-escherichia-coli-facilitates-chloramphenicol-uptake-into-bacterial-cells
#10
Bala K Prabhala, Nanda G Aduri, Neha Sharma, Aqsa Shaheen, Arpan Sharma, Mazhar Iqbal, Paul R Hansen, Christoffer Brasen, Michael Gajhede, Moazur Rahman, Osman Mirza
Chloramphenicol (Cam) is a broad-spectrum antibiotic used to combat bacterial infections in humans and animals. Cam export from bacterial cells is one of the mechanisms by which pathogens resist Cam's antibacterial effects, and several different proteins are known to facilitate this process. However, to date no report exists on any specific transport protein that facilitates Cam uptake. The proton-coupled oligopeptide transporter (POT) YdgR from Escherichia coli is a prototypical member of the POT family, functioning in proton-coupled uptake of di- and tripeptides...
November 17, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29150441/co-ii-and-ni-ii-binding-of-the-escherichia-coli-transcriptional-repressor-rcnr-orders-its-n-terminus-alters-helix-dynamics-and-reduces-dna-affinity
#11
Hsin-Ting Huang, Cedric E Bobst, Jeffrey S Iwig, Peter T Chivers, Igor A Kaltashov, Michael J Maroney
RcnR, a transcriptional regulator in Escherichia coli, derepresses the expression of the export proteins RcnAB upon binding Ni(II) or Co(II). Lack of structural information has precluded elucidation of the allosteric basis for the decreased DNA affinity in RcnR's metal-bound states. Here, using hydrogen-deuterium exchange coupled with MS (HDX-MS), we probed the RcnR structure in the presence of DNA, the cognate metal ions Ni(II) and Co(II), or the noncognate metal ion Zn(II). We found that cognate metal binding altered the flexibility from the N-terminus through helix 1 and modulated the RcnR-DNA interaction...
November 17, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29150334/a-routinely-used-protein-staining-dye-acts-as-an-inhibitor-of-wild-type-and-mutant-alpha-synuclein-aggregation-and-modulator-of-neurotoxicity
#12
Nuzhat Ahsan, Ibrar Ahmed Siddique, Sarika Gupta, Avadhesha Surolia
Inhibition of amyloid formation along with modulation of toxicity employing small molecules is emerging as a potential therapeutic approach for protein misfolding disorders which includes Parkinson's disease, Alzheimer's disease and Multiple System Atrophy etc. Countless current interventional strategies for treating α-synucleinopathies consider using peptidic and non-peptidic inhibitors for arresting fibrillisation, disrupting existing fibrils and reducing associated toxicity. One group of molecules less exploited in this regard are triphenylmethane dyes...
October 12, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29150267/can-memory-exist-outside-of-brain-and-be-transferred-historical-review-issues-ways-forward
#13
Ghulam Abbas, Wajahat Mahmood, Faisal Khan
Learning and memory are among the executive functions attributed to intelligent forms of life. Unfortunately, there is a lack of clear understanding regarding the underlying mechanisms governing these functions. Most of the modern day scientists attribute these functions solely to brain. However, in the latter half of last century, a number of reports suggested existence of extra-cranial memory and potential of its transfer between animals. Some have linked this phenomenon to RNA while others believed that peptides were responsible...
November 2017: Medical Hypotheses
https://www.readbyqxmd.com/read/29150249/accuracy-of-the-cobas-egfr-mutation-assay-in-non-small-cell-lung-cancer-compared-with-three-laboratory-developed-tests
#14
Haruhiko Nakamura, Hirotaka Koizumi, Hiroki Sakai, Hiroyuki Kimura, Tomoyuki Miyazawa, Hideki Marushima, Hisashi Saji, Masayuki Takagi
BACKGROUND: The reliability of the cobas EGFR assay to detect epidermal growth factor receptor (EGFR) mutations in non-small-cell lung cancer (NSCLC) as an in vitro diagnostic test was compared with 3 laboratory-developed tests (LDTs). MATERIALS AND METHODS: After screening for EGFR mutations using formalin-fixed-paraffin-embedded NSCLC tissue sections using the cobas EGFR assay, 151 samples were further tested with 3 LDTs; the peptide nucleic acid-locked nucleic acid polymerase chain reaction (PCR) clamp, PCR invader, and Cycleave assays...
October 28, 2017: Clinical Lung Cancer
https://www.readbyqxmd.com/read/29150238/a-t-cell-receptor-locus-harbors-a-malaria-specific-immune-response-gene
#15
Natalija Van Braeckel-Budimir, Stephanie Gras, Kristin Ladell, Tracy M Josephs, Lecia Pewe, Stina L Urban, Kelly L Miners, Carine Farenc, David A Price, Jamie Rossjohn, John T Harty
Immune response (Ir) genes, originally proposed by Baruj Benacerraf to explain differential antigen-specific responses in animal models, have become synonymous with the major histocompatibility complex (MHC). We discovered a non-MHC-linked Ir gene in a T cell receptor (TCR) locus that was required for CD8(+) T cell responses to the Plasmodium berghei GAP5040-48 epitope in mice expressing the MHC class I allele H-2D(b). GAP5040-48-specific CD8(+) T cell responses emerged from a very large pool of naive Vβ8...
November 10, 2017: Immunity
https://www.readbyqxmd.com/read/29150171/similar-pro-nt-and-pro-rlx2-levels-after-preeclampsia-and-after-uncomplicated-pregnancy
#16
G A Gerbrand Zoet, B B Bas van Rijn, M Miriam Rehfeldt, A Arie Franx, A H E M Angela Maas
OBJECTIVE: Women are at increased risk of developing cardiovascular disease (CVD) after preeclampsia. Proneurotensin 1-117 (pro-NT) and prorelaxin 2 connecting peptide (pro-RLX2) have recently emerged as potential biomarkers for CVD risk in women. We assessed pro-NT and pro-RLX2 levels in women with and without a history of preeclampsia. STUDY DESIGN: 339 women with a history of early-onset preeclampsia and 327 women with an uncomplicated pregnancy underwent cardiovascular screening 10 years after delivery (the Preeclampsia Risk EValuation in FEMales (PREVFEM) cohort)...
December 2017: Maturitas
https://www.readbyqxmd.com/read/29150077/unique-arginine-array-improves-cytosolic-localization-of-hydrocarbon-stapled-peptides
#17
Kim Quach, Jonathan LaRochelle, Xiao-Han Li, Elizabeth Rhoades, Alanna Schepartz
We have previously reported that miniature proteins containing a distinct array of 5 arginine residues on a folded α-helix - a penta-arg motif - traffic with high efficiency from endosomes into the cytosol and nucleus of mammalian cells. Here we evaluate whether a penta-arg motif can improve the intracellular trafficking of an otherwise impermeant hydrocarbon-stapled peptide, SAH-p53-4(Rho). We prepared a panel of SAH-p53-4(Rho) variants containing penta-arg sequences with different spacings and axial arrangement and evaluated their overall uptake (as judged by flow cytometry) and their intracellular access (as determined by fluorescence correlation spectroscopy, FCS)...
November 7, 2017: Bioorganic & Medicinal Chemistry
https://www.readbyqxmd.com/read/29150049/generation-of-advanced-glycation-end-products-ages-by-glycoxidation-mediated-by-copper-and-ros-in-a-human-serum-albumin-hsa-model-peptide-reaction-mechanism-and-damage-in-motor-neuron-cells
#18
Caroline Martins Sandanielo Marques, Emilene Arusievicz Nunes, Larissa Lago, Cibele Nicolaski Pedron, Tânia Maria Manieri, Roseli Hiromi Sato, Vani Xavier Oliveira, Giselle Cerchiaro
Glucose, in the presence of reactive oxygen species (ROS), acts as an as an oxidative agent and drives deleterious processes in Diabetes Mellitus. We have studied the mechanism and the toxicological effects of glucose-dependent glycoxidation reactions driven by copper and ROS, using a model peptide based on the exposed sequence of Human Serum Albumin (HSA) and containing a lysine residue susceptible to copper complexation. The main products of these reactions are Advanced Glycation End-products (AGEs). Carboxymethyl lysine and pyrraline condensed on the model peptide, generating a Modified Peptide (MP)...
December 2017: Mutation Research
https://www.readbyqxmd.com/read/29149813/structural-analysis-of-cd59-of-chinese-tree-shrew-a-new-reference-molecule-for-human-immune-system-specific-cd59-drug-discovery
#19
Subhamay Panda, Leena Kumari, Santamay Panda
BACKGROUND: Chinese tree shrews (Tupaia belangeri chinensis) bear several characteristics that are considered to be very crucial for utilizing in animal experimental models in biomedical research. Subsequent to the identification of key aspects and signaling pathways in nervous and immune systems, it is revealed that tree shrews acquires shared common as well as unique characteristics, and hence offers a genetic basis for employing this animal as a prospective model for biomedical research...
November 17, 2017: Current Drug Discovery Technologies
https://www.readbyqxmd.com/read/29149812/architectures-and-mechanical-properties-of-drugs-and-complexes-of-surface-active-compounds-at-air-water-and-oil-water-interfaces
#20
Dipak K Sarker
BACKGROUND: Drugs can represents a multitude of compounds from proteins and peptides, such as growth hormones and insulin and on to simple organic molecules such as flurbiprofen, ibuprofen and lidocaine. Given the chemical nature of these compounds two features are always present. A portion or portions of the molecule that has little affinity for apolar surfaces and media and the opposite a series of part or one large part that has considerable affinity for hydrophilic, polar or charged media and surfaces...
November 17, 2017: Current Drug Discovery Technologies
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