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https://www.readbyqxmd.com/read/28438927/the-role-of-psl-genes-in-antibiotic-tolerance-of-adherent-pseudomonas-aeruginosa
#1
Keiji Murakami, Tsuneko Ono, Darija Viducic, Yoko Somiya, Reiko Kariyama, Kenji Hori, Takashi Amoh, Katsuhiko Hirota, Hiromi Kumon, Matthew R Parsek, Yoichiro Miyake
Bacteria attached to a surface are generally more tolerant to antibiotics than their planktonic counterparts, even without the formation of a biofilm. The mechanism of antibiotic tolerance in biofilm communities is multifactorial, and the genetic backgound underlying this antibiotic tolerance has not yet been fully elucidated. Using transposon mutagenesis, we isolated a mutant with reduced tolerance to biapenem (relative to the wild-type) from adherent cells. Sequencing analysis revealed a mutation in the pslL gene, which is a part of the polysaccharide biosynthesis operon...
April 24, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28436027/production-and-characterization-of-active-recombinant-human-factor-ii-with-consistent-sialylation
#2
Jeong H Lee, Jason Reier, Kelley M Heffner, Christopher Barton, David Spencer, Albert E Schmelzer, Raghavan Venkat
Coagulation factor II (prothrombin; FII) is the pre-proteolyzed precursor to thrombin in the coagulation cascade. It has ten sites of gamma-carboxylation, which are required for its bioactivity, and is N-glycosylated at three of four putative sites. Production of recombinant human FII (rhFII) using a platform fed-batch process designed for monoclonal antibody production resulted in low levels of gamma-carboxylation and sialylation. There have not been any prior reports of successful process development and clinical manufacture of rhFII with optimal, consistent gamma-carboxylation and sialylation...
April 24, 2017: Biotechnology and Bioengineering
https://www.readbyqxmd.com/read/28419759/regulation-of-burkholderia%C3%A2-cenocepacia-biofilm-formation-by-rpon-and-the-c-di-gmp-effector-berb
#3
Mustafa Fazli, Morten Rybtke, Elisabeth Steiner, Elisabeth Weidel, Jens Berthelsen, Julie Groizeleau, Wu Bin, Boo Zhao Zhi, Zhang Yaming, Volkhard Kaever, Michael Givskov, Rolf W Hartmann, Leo Eberl, Tim Tolker-Nielsen
Knowledge about the molecular mechanisms that are involved in the regulation of biofilm formation is essential for the development of biofilm-control measures. It is well established that the nucleotide second messenger cyclic diguanosine monophosphate (c-di-GMP) is a positive regulator of biofilm formation in many bacteria, but more knowledge about c-di-GMP effectors is needed. We provide evidence that c-di-GMP, the alternative sigma factor RpoN (σ54), and the enhancer-binding protein BerB play a role in biofilm formation of Burkholderia cenocepacia by regulating the production of a biofilm-stabilizing exopolysaccharide...
April 16, 2017: MicrobiologyOpen
https://www.readbyqxmd.com/read/28417968/rational-development-of-a-protective-p-vivax-vaccine-evaluated-with-transgenic-rodent-parasite-challenge-models
#4
Ahmed M Salman, Eduardo Montoya-Díaz, Heather West, Amar Lall, Erwan Atcheson, Cesar Lopez-Camacho, Jai Ramesar, Karolis Bauza, Katharine A Collins, Florian Brod, Fernando Reis, Leontios Pappas, Lilia González-Cerón, Chris J Janse, Adrian V S Hill, Shahid M Khan, Arturo Reyes-Sandoval
Development of a protective and broadly-acting vaccine against the most widely distributed human malaria parasite, Plasmodium vivax, will be a major step towards malaria elimination. However, a P. vivax vaccine has remained elusive by the scarcity of pre-clinical models to test protective efficacy and support further clinical trials. In this study, we report the development of a highly protective CSP-based P. vivax vaccine, a virus-like particle (VLP) known as Rv21, able to provide 100% sterile protection against a stringent sporozoite challenge in rodent models to malaria, where IgG2a antibodies were associated with protection in absence of detectable PvCSP-specific T cell responses...
April 18, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28407821/-association-between-platelet-activating-factor-acetylhydrolase-gene-polymorphisms-and-gastrointestinal-bleeding-in-children-with-henoch-sch%C3%A3-nlein-purpura
#5
Bao-Xiang Wang, Hong Mei, Han-Ming Peng, Yuan Gao, Yan Ding
OBJECTIVE: To study the association between the single nucleotide polymorphisms (SNPs) of the ninth exon Val279Phe of platelet-activating factor acetylhydrolase (PAF-AH) gene and gastrointestinal bleeding in children with Henoch-Schönlein purpura (HSP). METHODS: A total 516 children with HSP were enrolled, among whom 182 had gastrointestinal bleeding and 334 had no gastrointestinal bleeding. PCR was used to investigate the distribution of genotypes and alleles in the SNPs of Val97Phe...
April 2017: Zhongguo Dang Dai Er Ke za Zhi, Chinese Journal of Contemporary Pediatrics
https://www.readbyqxmd.com/read/28405517/hematopoietic-stem-cell-derived-myeloid-and-plasmacytoid-dc-based-vaccines-are-highly-potent-inducers-of-tumor-reactive-t-cell-and-nk-cell-responses-ex-vivo
#6
Soley Thordardottir, Nicolaas Schaap, Elja Louer, Michel G D Kester, J H Frederik Falkenburg, Joop Jansen, Timothy R D Radstake, Willemijn Hobo, Harry Dolstra
Because of the potent graft-versus-tumor (GVT) effect, allogeneic stem cell transplantation (alloSCT) can be a curative therapy for hematological malignancies. However, relapse remains the most frequent cause of treatment failure, illustrating the necessity for development of adjuvant post-transplant therapies to boost GVT immunity. Dendritic cell (DC) vaccination is a promising strategy in this respect, in particular, where distinct biologic functions of naturally occurring DC subsets, i.e. myeloid DCs (mDCs) and plasmacytoid DCs (pDCs), are harnessed...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28405029/protein-kinase-enzymes-in-the-human-vagina-relation-to-key-mediators-of-the-cyclic-amp-and-cyclic-gmp-pathways
#7
S Ückert, J Sonnenberg, J E Sonnenberg, W Kauffels, K Albrecht, M A Kuczyk, P Hedlund
Aside from phosphodiesterase (PDE) isoenzymes, protein kinases (cAK=cyclic AMP-binding protein kinase, cGK=cyclic GMP-binding protein kinase) have also been identified as important receptors for cyclic nucleotides. A significance of protein kinases in the control of the function of the male and female reproductive tract has been suggested; however, up until today, only a few approaches have addressed these enzymes in female genital tissues. The present study aimed to investigate by means of biochemical and immunohistochemical methods the expression of cAK and cGK...
April 13, 2017: International Journal of Impotence Research
https://www.readbyqxmd.com/read/28404873/sulfhydration-associated-phosphodiesterase-5a-dimerization-mediates-vasorelaxant-effect-of-hydrogen-sulfide
#8
Yan Sun, Yaqian Huang, Wen Yu, Siyao Chen, Qiuyu Yao, Chunyu Zhang, Dingfang Bu, Chaoshu Tang, Junbao Du, Hongfang Jin
The study was designed to examine if the vasorelaxant effect of hydrogen sulfide was mediated by sulfhydration-associated phosphodiesterase (PDE) 5A dimerization. The thoracic aorta of rat was separated and the vasorelaxant effects were examined with in vitro vascular perfusion experiments. The dimerization and sulfhydration of PDE 5A and soluble guanylatecyclase (sGC) were measured. PDE 5A and protein kinase G (PKG) activities were tested. Intracellular cGMP content was detected by enzyme-linked immunosorbent assay (ELISA)...
March 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/28403796/riboswitches-as-potential-targets-for-the-development-of-anti-biofilm-drugs
#9
José A Reyes-Darias, Tino Krell
In nature, bacteria can exist as single motile cells or as sessile cellular community, known as microbial biofilms. Bacteria within biofilms are embedded in a self-produced extracellular matrix that makes them more resistant to antibiotic treatment and responses of the host immune system. Microbial biofilms are very important in medicine since they are associated with several human diseases such as dental caries, periodontitis, otitis media, infective endocarditis, infectious kidney stones, osteomyelitis or prostatitis...
April 7, 2017: Current Topics in Medicinal Chemistry
https://www.readbyqxmd.com/read/28403539/gmp-polyamine-hybrid-hydrogels-enhanced-gel-strength-probed-by-z-spectroscopy
#10
Juan A Aguilar, Raquel Belda, Enrique García-España, Gareth A Morris, Jonathan W Steed
The self-assembling tendencies of guanosine-5'-monophosphate (GMP) can be drastically increased using polyamines, with potential applications in the production of biocompatible smart materials, as well as for the design of anti-tumoral drugs based on G-quadruplex stabilization. Results from scanning electron microscopy (SEM), wide angle X-ray scattering (WAXS), rheology and nuclear magnetic resonance (NMR) z-spectroscopy studies are presented.
April 12, 2017: Chemistry: a European Journal
https://www.readbyqxmd.com/read/28402990/the-use-of-gmp-produced-bone-marrow-derived-stem-cells-in-combination-with-extra-corporeal-membrane-oxygenation-in-ards-an-animal-model
#11
Ergin Kocyildirim, Nayra Cárdenes, Antony Ting, Eder Cáceres, Christian Bermúdez, Mauricio Rojas
RDS is the result of a wide variety of disorders, which can be associated with different clinical disorders or systemic diseases directly affecting the lungs. Currently, the only existing therapy is limited to supportive care. In a 6-hour pilot study, we analyzed the use of the combination of both stem cell and ECMO strategies to prevent or treat severe lung injury. A total of 11 sheep were used. 5 sheep received E. coli endotoxin as a control group (Group 1). 3 sheep that received E. coli endotoxin were treated with veno-venous ECMO support in Group 2...
April 11, 2017: ASAIO Journal: a Peer-reviewed Journal of the American Society for Artificial Internal Organs
https://www.readbyqxmd.com/read/28402322/nutritional-status-in-patients-with-phenylketonuria-using-glycomacropeptide-as-their-major-protein-source
#12
A Pinto, M F Almeida, P C Ramos, S Rocha, A Guimas, R Ribeiro, E Martins, A Bandeira, A MacDonald, J C Rocha
BACKGROUND/OBJECTIVES: Low phenylalanine (PHE), glycomacropeptide-based protein substitute (GMP) is an alternative to traditional L-amino acid supplements (AA) used in the dietary management of phenylketonuria (PKU). In a retrospective, longitudinal study, we report the nutritional status of PKU patients taking AA and GMP. SUBJECTS/METHODS: Eleven PKU patients aged 27±10 years (1 HPA, 4 mild and 6 classical PKU) on dietary treatment were evaluated (anthropometry, body composition, blood pressure measurements, biochemical markers including vitamin, mineral, lipids, carbohydrates and protein status/metabolism, and nutritional intake assessment) at two different annual reviews...
April 12, 2017: European Journal of Clinical Nutrition
https://www.readbyqxmd.com/read/28401358/mrna-cancer-vaccines-messages-that-prevail
#13
Christian Grunwitz, Lena M Kranz
During the last decade, mRNA became increasingly recognized as a versatile tool for the development of new innovative therapeutics. Especially for vaccine development, mRNA is of outstanding interest and numerous clinical trials have been initiated. Strikingly, all of these studies have proven that large-scale GMP production of mRNA is feasible and concordantly report a favorable safety profile of mRNA vaccines. Induction of T-cell immunity is a multi-faceted process comprising antigen acquisition, antigen processing and presentation, as well as immune stimulation...
March 31, 2017: Current Topics in Microbiology and Immunology
https://www.readbyqxmd.com/read/28401257/ido-and-galectin-3-hamper-the-ex-vivo-generation-of-clinical-grade-tumor-specific-t-cells-for-adoptive-cell-therapy-in-metastatic-melanoma
#14
Sara M Melief, Marten Visser, Sjoerd H van der Burg, Els M E Verdegaal
Adoptive T cell transfer (ACT) with ex vivo-expanded tumor-reactive T cells proved to be successful for the treatment of metastatic melanoma patients. Mixed lymphocyte tumor cell cultures (MLTC) can be used to generate tumor-specific T cells for ACT; however, in a number of cases tumor-reactive T cell, expansion is far from optimal. We hypothesized that this is due to tumor intrinsic and extrinsic factors and aimed to identify and manipulate these factors so to optimize our clinical, GMP-compliant MLTC protocol...
April 11, 2017: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/28400091/metabolomic-changes-demonstrate-reduced-bioavailability-of-tyrosine-and-altered-metabolism-of-tryptophan-via-the-kynurenine-pathway-with-ingestion-of-medical-foods-in-phenylketonuria
#15
Denise M Ney, Sangita G Murali, Bridget M Stroup, Nivedita Nair, Emily A Sawin, Fran Rohr, Harvey L Levy
BACKGROUND: Deficiencies of the monoamine neurotransmitters, such as dopamine synthesized from Tyr and serotonin synthesized from Trp, are of concern in PKU. Our objective was to utilize metabolomics analysis to assess monoamine metabolites in subjects with PKU consuming amino acid medical foods (AA-MF) and glycomacropeptide medical foods (GMP-MF). METHODS: Subjects with PKU consumed a low-Phe diet combined with AA-MF or GMP-MF for 3weeks each in a randomized, controlled, crossover study...
April 6, 2017: Molecular Genetics and Metabolism
https://www.readbyqxmd.com/read/28399655/cyclic-gmp-amp-as-an-endogenous-second-messenger-in-innate-immune-signaling-by-cytosolic-dna
#16
Kazuki Kato, Hiroki Omura, Ryuichiro Ishitani, Osamu Nureki
The innate immune system functions as the first line of defense against invading bacteria and viruses. In this context, the cGAS/STING [cyclic guanosine monophosphate (GMP)-adenosine monophosphate (AMP) synthase/ STING] signaling axis perceives the nonself DNA associated with bacterial and viral infections, as well as the leakage of self DNA by cellular dysfunction and stresses, to elicit the host's immune responses. In this pathway, the noncanonical cyclic dinucleotide 2',3'-cyclicGMP-AMP(2',3'-cGAMP) functions as a second messenger for signal transduction: 2',3'-cGAMP is produced by the enzyme cGAS upon its recognition of double-stranded DNA, and then the 2',3'-cGAMP is recognized by the receptor STING to induce the phosphorylation of downstream factors, including TBK1 (TANK binding kinase 1) and IRF3 (interferon regulatory factor 3)...
April 7, 2017: Annual Review of Biochemistry
https://www.readbyqxmd.com/read/28396343/cyclic-dinucleotides-modulate-induced-type-i-ifn-responses-in-innate-immune-cells-by-degradation-of-sting
#17
Christine Rueckert, Ulfert Rand, Urmi Roy, Bahram Kasmapour, Till Strowig, Carlos A Guzmán
The cyclic dinucleotides, GMP-AMP (cGAMP) and c-di-AMP [bis-(3',5')-cyclic dimeric AMP], are potent type I IFN inducers via STING-TBK1-IRF3 cascade. They are promising adjuvants that promote antigen-specific humoral and cellular immune responses in different preclinical models; however, an optimal outcome of vaccination depends on a balanced immune activation. Here, we characterize the process of IFN-β induction by c-di-AMP and cGAMP in an in vitro model on the basis of primary mouse dendritic cells. Results obtained show decreased IFN-β production upon prolonged cell stimulation...
April 10, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28396341/bioactivity-of-oral-linaclotide-in-human-colorectum-for-cancer-chemoprevention
#18
David S Weinberg, Jieru E Lin, Nathan R Foster, Gary J Della'Zanna, Asad Umar, Drew K Seisler, Walter K Kraft, David M Kastenberg, Leo C Katz, Paul J Limburg, Scott A Waldman
Guanylate cyclase C (GUCY2C) is a tumor suppressing receptor silenced by loss of expression of its luminocrine hormones guanylin and uroguanylin early in colorectal carcinogenesis. This observation suggests oral replacement with a GUCY2C agonist may be an effective targeted chemoprevention agent. Linaclotide is an FDA approved oral GUCY2C agonist formulated for gastric release, inducing fluid secretion into the small bowel to treat chronic idiopathic constipation. The ability of oral linaclotide to induce a pharmacodynamic response in epithelial cells of the colorectum in humans remains undefined...
April 10, 2017: Cancer Prevention Research
https://www.readbyqxmd.com/read/28395097/artesunate-to-treat-severe-malaria-in-travellers-review-of-efficacy-and-safety-and-practical-implications
#19
Camille Roussel, Eric Caumes, Marc Thellier, Papa Alioune Ndour, Pierre A Buffet, Stéphane Jauréguiberry
Background: Artesunate (AS) is the WHO first-line treatment of severe malaria in endemic countries, in adults and children. However, despite solid evidence that AS is safe and more effective than quinine in endemic areas, its deployment in non-endemic areas has been slow, due in part to the absence of a full good manufacturing practice (GMP) qualification (although prequalification has been granted in 2010). Prospective comparative trials were not conducted in travellers, but several retrospective studies and case reports are providing insights into the efficacy and safety of AS in imported severe malaria...
March 1, 2017: Journal of Travel Medicine
https://www.readbyqxmd.com/read/28393936/effect-of-counterions-on-the-micellization-and-monolayer-behaviour-of-cationic-gemini-surfactants
#20
M S Islam, S M Shortall, G M Mekhail, S P Callender, O Madkhali, Z Bharwani, D Ayyash, K Kobernyk, S D Wettig
The effect of various inorganic and organic counterions on the aggregation behavior of gemini surfactants was examined to investigate the dominant influence of the anions on their micellization and aggregation behavior. This study included eight ethanediyl-α,ω-bis-(dimethylhexadecylammonium) gemini surfactants (GS, also known as 16-2-16) having counterions of chloride (Cl(-)), bromide (Br(-)), malate, tartrate, adenosine monophosphate (AMP), guanosine monophosphate (GMP), cytidine monophosphate (CMP), and uridine monophosphate (UMP)...
April 10, 2017: Physical Chemistry Chemical Physics: PCCP
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