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https://www.readbyqxmd.com/read/28636387/novel-kiteplatin-pyrophosphate-derivatives-with-improved-efficacy
#1
Alessandra Curci, Valentina Gandin, Cristina Marzano, James D Hoeschele, Giovanni Natile, Nicola Margiotta
Two new Pt(II) derivatives of kiteplatin ([PtCl2(cis-1,4-DACH)]) with pyrophosphate as carrier ligand, one mononuclear (1) and one dinuclear (2), were synthesized with the aim of potentiating the efficacy of kiteplatin. Complex 1 resulted to be remarkably stable at physiological pH, but it undergoes a fast hydrolysis reaction at acidic pH releasing free pyrophosphate and (aquated) kiteplatin. The dinuclear compound 2 resulted to be less stable than 1 at both neutral and acidic pH forming 1 and (aquated) kiteplatin as first step...
June 21, 2017: Inorganic Chemistry
https://www.readbyqxmd.com/read/28636257/covalent-attachment-and-pro-pro-endopeptidase-ppep-1-mediated-release-of-clostridium-difficile-cell-surface-proteins-involved-in-adhesion
#2
REVIEW
Jeroen Corver, Valentina Cordo', Hans C van Leeuwen, Oleg I Klychnikov, Paul J Hensbergen
In the past decade, Clostridium difficile has emerged as an important gut pathogen. This anaerobic, Gram-positive bacterium is the main cause of infectious nosocomial diarrhea. Whereas much is known about the mechanism through which the C. difficile toxins cause diarrhea, relatively little is known about the dynamics of adhesion and motility, which is mediated by cell surface proteins. This review will discuss the recent advances in our understanding of the sortase-mediated covalent attachment of cell surface (adhesion) proteins to the peptidoglycan layer of C...
June 21, 2017: Molecular Microbiology
https://www.readbyqxmd.com/read/28636034/upregulation-of-heme-oxygenase-1-mediates-the-anti-inflammatory-activity-of-casein-glycomacropeptide-gmp-hydrolysates-in-lps-stimulated-macrophages
#3
Tiange Li, Xue Cheng, Min Du, Bin Chen, Xueying Mao
Recently, we have shown that casein glycomacropeptide hydrolysates (GHP) exhibit both anti-inflammatory and anti-oxidative activities in vitro. However, whether heme oxygenase-1 (HO-1) is involved in the cytoprotective effect of GHP against the inflammatory status remains unclear. Therefore, we hypothesized that HO-1 is a potential target of GHP, which mediates its anti-inflammatory effect. Here, GHP inhibited the intracellular reactive oxygen species (ROS) accumulation and NADPH oxidase 2 (NOX2) expression and enhanced reduced glutathione (GSH) levels in LPS-stimulated RAW264...
June 21, 2017: Food & Function
https://www.readbyqxmd.com/read/28635593/the-protein-slr1143-is-an-active-diguanylate-cyclase-in-synechocystis-sp-pcc-6803-and-interacts-with-the-photoreceptor-cph2
#4
Veronika Angerer, Philipp Schwenk, Thomas Wallner, Volkhard Kaever, Andreas Hiltbrunner, Annegret Wilde
Cyclic-di-GMP is an ubiquitous second messenger in bacteria. Several c-di-GMP receptor proteins have been identified to date, and downstream signalling pathways are often mediated through protein-protein interactions. The photoreceptor Cph2 from the cyanobacterium Synechocystis sp. PCC 6803 comprises three domains related to c-di-GMP metabolism: two GGDEF and one EAL domain. It has been shown that the C-terminal GGDEF domain acts as blue-light triggered c-di-GMP producer thereby inhibiting motility of the cells in blue light...
June 21, 2017: Microbiology
https://www.readbyqxmd.com/read/28632757/molecular-mechanism-of-drp1-assembly-studied-in-vitro-by-cryo-electron-microscopy
#5
Kaustuv Basu, Driss Lajoie, Tristan Aumentado-Armstrong, Jin Chen, Roman I Koning, Blaise Bossy, Mihnea Bostina, Attila Sik, Ella Bossy-Wetzel, Isabelle Rouiller
Mitochondria are dynamic organelles that continually adapt their morphology by fusion and fission events. An imbalance between fusion and fission has been linked to major neurodegenerative diseases, including Huntington's, Alzheimer's, and Parkinson's diseases. A member of the Dynamin superfamily, dynamin-related protein 1 (DRP1), a dynamin-related GTPase, is required for mitochondrial membrane fission. Self-assembly of DRP1 into oligomers in a GTP-dependent manner likely drives the division process. We show here that DRP1 self-assembles in two ways: i) in the presence of the non-hydrolysable GTP analog GMP-PNP into spiral-like structures of ~36 nm diameter; and ii) in the presence of GTP into rings composed of 13-18 monomers...
2017: PloS One
https://www.readbyqxmd.com/read/28629761/cytokines-for-the-induction-of-antitumor-effectors-the-paradigm-of-cytokine-induced-killer-cik-cells
#6
Elisa Cappuzzello, Roberta Sommaggio, Paola Zanovello, Antonio Rosato
Cytokine-Induced killer (CIK) cells are raising growing interest in cellular antitumor therapy, as they can be easily expanded with a straightforward and inexpensive protocol, and are safe requiring only GMP-grade cytokines to obtain very high amounts of cytotoxic cells. CIK cells do not need antigen-specific stimuli to be activated and proliferate, as they recognize and destroy tumor cells in an HLA-independent fashion through the engagement of NKG2D. In several preclinical studies and clinical trials, CIK cells showed a reduced alloreactivity compared to conventional T cells, even when challenged across HLA-barriers; only in a few patients, a mild GVHD occurred after treatment with allogeneic CIK cells...
June 3, 2017: Cytokine & Growth Factor Reviews
https://www.readbyqxmd.com/read/28626601/long-term-efficacy-of-gmp-grade-xeno-free-hesc-derived-rpe-cells-following-transplantation
#7
Trevor J McGill, Osnat Bohana-Kashtan, Jonathan W Stoddard, Michael D Andrews, Neelay Pandit, Lior R Rosenberg-Belmaker, Ofer Wiser, Limor Matzrafi, Eyal Banin, Benjamin Reubinoff, Nir Netzer, Charles Irving
PURPOSE: Retinal pigment epithelium (RPE) dysfunction underlies the retinal degenerative process in age-related macular degeneration (AMD), and thus RPE cell replacement provides an optimal treatment target. We characterized longitudinally the efficacy of RPE cells derived under xeno-free conditions from clinical and xeno-free grade human embryonic stem cells (OpRegen) following transplantation into the subretinal space of Royal College of Surgeons (RCS) rats. METHODS: Postnatal (P) day 20 to 25 RCS rats (n = 242) received a single subretinal injection of 25,000 (low)-, 100,000 (mid)-, or 200,000 (high)-dose xeno-free RPE cells...
June 2017: Translational Vision Science & Technology
https://www.readbyqxmd.com/read/28620360/cytr-homolog-of-pectobacterium-carotovorum-subsp-carotovorum-controls-air-liquid-biofilm-formation-by-regulating-multiple-genes-involved-in-cellulose-production-c-di-gmp-signaling-motility-and-type-iii-secretion-system-in-response-to-nutritional-and-environmental
#8
M M Haque, M M H Oliver, Kamrun Nahar, Mohammad Z Alam, Hisae Hirata, Shinji Tsuyumu
Pectobacterium carotovorum subsp. carotovorum [Pcc (formerly Erwinia carotovora subsp. carotovora)] PC1 causes soft-rot disease in a wide variety of plant species by secreting multiple pathogenicity-related traits. In this study, regulatory mechanism of air-liquid (AL) biofilm formation was studied using a cytR homolog gene deletion mutant (ΔcytR) of Pcc PC1. Compared to the wild type (Pcc PC1), the ΔcytR mutant produced fragile and significantly (P < 0.001) lower amounts of AL biofilm on salt-optimized broth plus 2% glycerol (SOBG), yeast peptone dextrose adenine, and also on King's B at 27°C after 72 h incubation in static condition...
2017: Frontiers in Microbiology
https://www.readbyqxmd.com/read/28620207/dengue-virus-activates-cgas-through-the-release-of-mitochondrial-dna
#9
Bo Sun, Karin B Sundström, Jun Jie Chew, Pradeep Bist, Esther S Gan, Hwee Cheng Tan, Kenneth C Goh, Tanu Chawla, Choon Kit Tang, Eng Eong Ooi
Cyclic GMP-AMP synthetase (cGAS) is a DNA-specific cytosolic sensor, which detects and initiates host defense responses against microbial DNA. It is thus curious that a recent study identified cGAS as playing important roles in inhibiting positive-sense single-stranded RNA (+ssRNA) viral infection, especially since RNA is not known to activate cGAS. Using a dengue virus serotype 2 (DENV-2) vaccine strain (PDK53), we show that infection creates an endogenous source of cytosolic DNA in infected cells through the release of mitochondrial DNA (mtDNA) to drive the production of cGAMP by cGAS...
June 15, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28619510/crystal-structure-of-brlr-with-c-di-gmp
#10
Harikiran Raju, Rohan Sharma
The transcriptional regulator BrlR is a member of the MerR family of multidrug transport activators in Pseudomonas aeruginosa. Recent study indicates that BrlR is a novel 3',5'-cyclic diguanylic acid (c-di-GMP) receptor and can be activated by c-di- GMP. To gain insight into BrlR function, we determined the structure of BrlR with c-di-GMP complex structure to 2.5 Å. The structure and SEC data revealed BrlR forms a tetramer and each BrlR protomer consists of three parts, DNA-binding domain, a coiled-coil region and GyrI-like domain...
June 12, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28619035/an-evolutionary-optimization-of-a-rhodopsin-based-phototrophic-metabolism-in-escherichia-coli
#11
Hyun Aaron Kim, Hyun Ju Kim, Jihoon Park, Ah Reum Choi, Kyoo Heo, Haeyoung Jeong, Kwang-Hwan Jung, Yeong-Jae Seok, Pil Kim, Sang Jun Lee
BACKGROUND: The expression of the Gloeobacter rhodopsin (GR) in a chemotrophic Escherichia coli enables the light-driven phototrophic energy generation. Adaptive laboratory evolution has been used for acquiring desired phenotype of microbial cells and for the elucidation of basic mechanism of molecular evolution. To develop an optimized strain for the artificially acquired phototrophic metabolism, an ancestral E. coli expressing GR was adaptively evolved in a chemostat reactor with constant illumination and limited glucose conditions...
June 15, 2017: Microbial Cell Factories
https://www.readbyqxmd.com/read/28614771/mantidis-ootheca-induces-vascular-relaxation-through-pi3k-akt-mediated-nitric-oxide-cyclic-gmp-protein-kinase-g-signaling-in-endothelial-cells
#12
H Y Kim, Y J Lee, B H Han, J J Yoon, Y M Ahn, M H Hong, R Tan, D G Kang, H S Lee
Mantidis ootheca (Sang Piao Xiao) is well known mantis eggs in a foamy pouch. The purpose of the present study was to investigate the underlying cellular mechanisms of the nitric oxide (NO)-releasing property of the aqueous extract of Mantidis ootheca (AMO) in rat aorta and vascular endothelial cells. AMO was examined for its vascular relaxant effect in isolated phenylephrine-precontracted rat thoracic aortic rings. The roles of the nitric oxide (NO) signaling in the AMO-induced effects were tested in human umbilical vein endothelial cells (HUVECs)...
April 2017: Journal of Physiology and Pharmacology: An Official Journal of the Polish Physiological Society
https://www.readbyqxmd.com/read/28611507/a-proinflammatory-effect-of-the-%C3%AE-glucan-from-pleurotus-cornucopiae-mushroom-on-macrophage-action
#13
Ken-Ichiro Minato, Akihiro Ohara, Masashi Mizuno
PCPS from P. citrinopileatus mushroom extract is a β-1,6-glucan possessing a proinflammatory effect on innate immune cells. The PCPS stimulated THP-1 macrophages to secrete significant levels of TNF. Moreover, the mRNA expressions of TNF and IL-1β were significantly enhanced by PCPS treatment. However, the PCPS did not induce to express both IL-12 and IL-10 mRNA in the macrophages. Next, the P. cornucopiae extract (containing mainly PCPS) treatment against mice showed significant increases in TNF and IL-1β mRNA expressions in the peritoneal macrophages of them...
2017: Mediators of Inflammation
https://www.readbyqxmd.com/read/28611182/the-lost-language-of-the-rna-world
#14
REVIEW
James W Nelson, Ronald R Breaker
The possibility of an RNA World is based on the notion that life on Earth passed through a primitive phase without proteins, a time when all genomes and enzymes were composed of ribonucleic acids. Numerous apparent vestiges of this ancient RNA World remain today, including many nucleotide-derived coenzymes, self-processing ribozymes, metabolite-binding riboswitches, and even ribosomes. Many of the most common signaling molecules and second messengers used by modern organisms are also formed from RNA nucleotides or their precursors...
June 13, 2017: Science Signaling
https://www.readbyqxmd.com/read/28609666/the-hippeastrum-hybridum-pepr1-gene-hppepr1-encodes-a-functional-guanylyl-cyclase-and-is-involved-in-early-response-to-fungal-infection
#15
Brygida Świeżawska, Krzysztof Jaworski, Maria Duszyn, Agnieszka Pawełek, Adriana Szmidt-Jaworska
It is generally known that cyclic GMP widespread in prokaryotic and eukaryotic cells, is involved in essential cellular processes and stress signal transduction. However, in contrast to animals the knowledge about plant guanylyl cyclases (GCs) which catalyze the formation of cGMP from GTP is still quite obscure. Recent studies of plant GCs are focused on identification and functional analysis of a new family of membrane proteins called "moonlighting kinases with GC activity" with guanylyl cyclase catalytic center encapsulated within intracellular kinase domain...
June 1, 2017: Journal of Plant Physiology
https://www.readbyqxmd.com/read/28607158/the-two-component-signal-transduction-system-vxrab-positively-regulates-vibrio-cholerae-biofilm-formation
#16
Jennifer K Teschler, Andrew T Cheng, Fitnat H Yildiz
Two-component signal transduction systems (TCSs), typically composed of a sensor histidine kinase (HK) and a response regulator (RR), are the primary mechanism by which pathogenic bacteria sense and respond to extracellular signals. The pathogenic bacterium Vibrio cholerae is no exception and encodes for 52 RR genes. Using in frame deletion mutants of each RR gene, we performed a systematic analysis of their role in V. cholerae biofilm formation. We determined that 7 RRs impacted expression of an essential biofilm gene and found that the recently characterized RR, VxrB, regulates expression of key structural and regulatory biofilm-genes in V...
June 12, 2017: Journal of Bacteriology
https://www.readbyqxmd.com/read/28607054/electron-shuttling-antibiotics-structure-bacterial-communities-by-modulating-cellular-levels-of-c-di-gmp
#17
Chinweike Okegbe, Blanche L Fields, Stephanie J Cole, Christopher Beierschmitt, Chase J Morgan, Alexa Price-Whelan, Richard C Stewart, Vincent T Lee, Lars E P Dietrich
Diverse organisms secrete redox-active antibiotics, which can be used as extracellular electron shuttles by resistant microbes. Shuttle-mediated metabolism can support survival when substrates are available not locally but rather at a distance. Such conditions arise in multicellular communities, where the formation of chemical gradients leads to resource limitation for cells at depth. In the pathogenic bacterium Pseudomonas aeruginosa PA14, antibiotics called phenazines act as oxidants to balance the intracellular redox state of cells in anoxic biofilm subzones...
June 12, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28605431/matrix-exopolysaccharides-the-sticky-side-of-biofilm-formation
#18
Eve Maunders, Martin Welch
The Gram-negative pathogen Pseudomonas aeruginosa is found ubiquitously within the environment and is recognised as an opportunistic human pathogen that commonly infects burn wounds and immunocompromised individuals, or patients suffering from the autosomal recessive disorder cystic fibrosis (CF). During chronic infection, P. aeruginosa is thought to form structured aggregates known as biofilms characterised by a self-produced matrix which encases the bacteria, protecting them from anti-microbial attack and the host immune response...
June 12, 2017: FEMS Microbiology Letters
https://www.readbyqxmd.com/read/28605194/discovery-of-two-bacterial-nitric-oxide-responsive-proteins-and-their-roles-in-bacterial-biofilm-regulation
#19
Sajjad Hossain, Lisa-Marie Nisbett, Elizabeth M Boon
Bacterial biofilms form when bacteria adhere to a surface and produce an exopolysaccharide matrix ( Costerton Science 1999 , 284 , 1318 ; Davies Science 1998 , 280 , 295 ; Flemming Nat. Rev. Microbiol. 2010 , 8 , 623 ). Because biofilms are resistant to antibiotics, they are problematic in many aspects of human health and welfare, causing, for instance, persistent fouling of medical implants such as catheters and artificial joints ( Brunetto Chimia 2008 , 62 , 249 ). They are responsible for chronic infections in the lungs of cystic fibrosis patients and in open wounds, such as those associated with burns and diabetes...
June 12, 2017: Accounts of Chemical Research
https://www.readbyqxmd.com/read/28604167/adaptation-to-copper-stress-influences-biofilm-formation-in-alteromonas-macleodii
#20
Kathleen D Cusick, Jason R Dale, Lisa A Fitzgerald, Brenda J Little, Justin C Biffinger
An Alteromonas macleodii strain was isolated from copper-containing coupons incubated in surface seawater (Key West, FL, USA). In addition to the original isolate, a copper-adapted mutant was created and maintained with 0.78 mM Cu(2+). Biofilm formation was compared between the two strains under copper-amended and low-nutrient conditions. Biofilm formation was significantly increased in the original isolate under copper amendment, while biofilm formation was significantly higher in the mutant under low-nutrient conditions...
July 2017: Biofouling
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