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https://www.readbyqxmd.com/read/27882195/design-and-synthesis-of-tesirine-a-clinical-antibody-drug-conjugate-pyrrolobenzodiazepine-dimer-payload
#1
Arnaud C Tiberghien, Jean-Noel Levy, Luke A Masterson, Neki V Patel, Lauren R Adams, Simon Corbett, David G Williams, John A Hartley, Philip W Howard
Pyrrolobenzodiazepine dimers are an emerging class of warhead in the field of antibody-drug conjugates (ADCs). Tesirine (SG3249) was designed to combine potent antitumor activity with desirable physicochemical properties such as favorable hydrophobicity and improved conjugation characteristics. One of the reactive imines was capped with a cathepsin B-cleavable valine-alanine linker. A robust synthetic route was developed to allow the production of tesirine on clinical scale, employing a flexible, convergent strategy...
November 10, 2016: ACS Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/27492011/plasmid-ppcp1-derived-srna-hmsa-promotes-biofilm-formation-of-yersinia-pestis
#2
Zizhong Liu, Xiaofang Gao, Hongduo Wang, Haihong Fang, Yanfeng Yan, Lei Liu, Rong Chen, Dongsheng Zhou, Ruifu Yang, Yanping Han
BACKGROUND: The ability of Yersinia pestis to form a biofilm is an important characteristic in flea transmission of this pathogen. Y. pestis laterally acquired two plasmids (pPCP1and pMT1) and the ability to form biofilms when it evolved from Yersinia pseudotuberculosis. Small regulatory RNAs (sRNAs) are thought to play a crucial role in the processes of biofilm formation and pathogenesis. RESULTS: A pPCP1-derived sRNA HmsA (also known as sR084) was found to contribute to the enhanced biofilm formation phenotype of Y...
2016: BMC Microbiology
https://www.readbyqxmd.com/read/27387855/the-rna-chaperone-hfq-is-essential-for-virulence-and-modulates-the-expression-of-four-adhesins-in-yersinia-enterocolitica
#3
Tamara Katharina Kakoschke, Sara Carina Kakoschke, Catharina Zeuzem, Hicham Bouabe, Kristin Adler, Jürgen Heesemann, Ombeline Rossier
In Enterobacteriaceae, the RNA chaperone Hfq mediates the interaction of small RNAs with target mRNAs, thereby modulating transcript stability and translation. This post-transcriptional control helps bacteria adapt quickly to changing environmental conditions. Our previous mutational analysis showed that Hfq is involved in metabolism and stress survival in the enteropathogen Yersinia enterocolitica. In this study we demonstrate that Hfq is essential for virulence in mice and influences production of surface pathogenicity factors, in particular lipopolysaccharide and adhesins mediating interaction with host tissue...
2016: Scientific Reports
https://www.readbyqxmd.com/read/27276911/enzymatic-synthesis-of-bioactive-compounds-with-high-potential-for-cosmeceutical-application
#4
REVIEW
Io Antonopoulou, Simona Varriale, Evangelos Topakas, Ulrika Rova, Paul Christakopoulos, Vincenza Faraco
Cosmeceuticals are cosmetic products containing biologically active ingredients purporting to offer a pharmaceutical therapeutic benefit. The active ingredients can be extracted and purified from natural sources (botanicals, herbal extracts, or animals) but can also be obtained biotechnologically by fermentation and cell cultures or by enzymatic synthesis and modification of natural compounds. A cosmeceutical ingredient should possess an attractive property such as anti-oxidant, anti-inflammatory, skin whitening, anti-aging, anti-wrinkling, or photoprotective activity, among others...
August 2016: Applied Microbiology and Biotechnology
https://www.readbyqxmd.com/read/27127171/a-toll-like-receptor-2-agonist-fused-antigen-enhanced-antitumor-immunity-by-increasing-antigen-presentation-and-the-cd8-memory-t-cells-population
#5
Chiao-Chieh Wu, Shih-Jen Liu, Hsin-Wei Chen, Kuan-Yin Shen, Chih-Hsiang Leng
The induction of long-lived effector CD8+ T cells is key to the development of efficient cancer vaccines. In this study, we demonstrated that a Toll-like receptor 2 (TLR2) agonist-fused antigen increased antigen presentation via TLR2 signaling and induced effector memory-like CD8+ T cells against cancer after immunization. The N-terminus of ovalbumin (OVA) was biologically fused with a bacterial lipid moiety TLR2 agonist to produce a recombinant lipidated ovalbumin (rlipo-OVA). We demonstrated that rlipo-OVA activated bone marrow-derived dendritic cells (BM-DCs) maturation and increased antigen presentation by major histocompatibility complex (MHC) class I via TLR2...
May 24, 2016: Oncotarget
https://www.readbyqxmd.com/read/27115878/pharmacological-development-of-target-specific-delocalized-lipophilic-cation-functionalized-carboranes-for-cancer-therapy
#6
Eirini D Tseligka, Aikaterini Rova, Elsa P Amanatiadou, Gianpiero Calabrese, John Tsibouklis, Dimitrios G Fatouros, Ioannis S Vizirianakis
PURPOSE: Tumor cell heterogeneity and microenvironment represent major hindering factors in the clinical setting toward achieving the desired selectivity and specificity to malignant tissues for molecularly targeted cancer therapeutics. In this study, the cellular and molecular evaluation of several delocalized lipophilic cation (DLC)-functionalized carborane compounds as innovative anticancer agents is presented. METHODS: The anticancer potential assessment of the DLC-carboranes was performed in established normal (MRC-5, Vero), cancer (U-87 MG, HSC-3) and primary glioblastoma cancer stem (EGFR(pos), EGFR(neg)) cultures...
August 2016: Pharmaceutical Research
https://www.readbyqxmd.com/read/27043513/effect-of-different-pretreatment-methods-on-birch-outer-bark-new-biorefinery-routes
#7
Anthi Karnaouri, Ulrika Rova, Paul Christakopoulos
A comparative study among different pretreatment methods used for the fractionation of the birch outer bark components, including steam explosion, hydrothermal and organosolv treatments based on the use of ethanol/water media, is reported. The residual solid fractions have been characterized by ATR-FTIR, (13)C-solid-state NMR and morphological alterations after pretreatment were detected by scanning electron microscopy. The general chemical composition of the untreated and treated bark including determination of extractives, suberin, lignin and monosaccharides was also studied...
2016: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/26994015/catalytic-upgrading-of-butyric-acid-towards-fine-chemicals-and-biofuels
#8
Magnus Sjöblom, Leonidas Matsakas, Paul Christakopoulos, Ulrika Rova
Fermentation-based production of butyric acid is robust and efficient. Modern catalytic technologies make it possible to convert butyric acid to important fine chemicals and biofuels. Here, current chemocatalytic and biocatalytic conversion methods are reviewed with a focus on upgrading butyric acid to 1-butanol or butyl-butyrate. Supported Ruthenium- and Platinum-based catalyst and lipase exhibit important activities which can pave the way for more sustainable process concepts for the production of green fuels and chemicals...
April 2016: FEMS Microbiology Letters
https://www.readbyqxmd.com/read/26984293/reciprocal-regulation-of-yersinia-pestis-biofilm-formation-and-virulence-by-rovm-and-rova
#9
Lei Liu, Haihong Fang, Huiying Yang, Yiquan Zhang, Yanping Han, Dongsheng Zhou, Ruifu Yang
RovA is known to enhance Yersinia pestis virulence by directly upregulating the psa loci. This work presents a complex gene regulatory paradigm involving the reciprocal regulatory action of RovM and RovA on the expression of biofilm and virulence genes as well as on their own genes. RovM and RovA enhance and inhibit Y. pestis biofilm production, respectively, whereas RovM represses virulence in mice. RovM directly stimulates the transcription of hmsT, hmsCDE and rovM, while indirectly enhancing hmsHFRS transcription...
March 2016: Open Biology
https://www.readbyqxmd.com/read/26909078/development-of-thermophilic-tailor-made-enzyme-mixtures-for-the-bioconversion-of-agricultural-and-forest-residues
#10
Anthi Karnaouri, Leonidas Matsakas, Evangelos Topakas, Ulrika Rova, Paul Christakopoulos
Even though the main components of all lignocellulosic feedstocks include cellulose, hemicellulose, as well as the protective lignin matrix, there are some differences in structure, such as in hardwoods and softwoods, which may influence the degradability of the materials. Under this view, various types of biomass might require a minimal set of enzymes that has to be tailor-made. Partially defined complex mixtures that are currently commercially used are not adapted to efficiently degrade different materials, so novel enzyme mixtures have to be customized...
2016: Frontiers in Microbiology
https://www.readbyqxmd.com/read/26609521/evaluation-of-mediterranean-agricultural-residues-as-a-potential-feedstock-for-the-production-of-biogas-via-anaerobic-fermentation
#11
Christos Nitsos, Leonidas Matsakas, Kostas Triantafyllidis, Ulrika Rova, Paul Christakopoulos
Hydrothermal, dilute acid, and steam explosion pretreatment methods, were evaluated for their efficiency to improve the methane production yield of three Mediterranean agricultural lignocellulosic residues such as olive tree pruning, grapevine pruning, and almond shells. Hydrothermal and dilute acid pretreatments provided low to moderate increase in the digestibility of the biomass samples, whereas steam explosion enabled the highest methane yields to be achieved for almond shells at 232.2 ± 13.0 mL CH4/gVS and olive pruning at 315...
2015: BioMed Research International
https://www.readbyqxmd.com/read/26539186/sequential-parametric-optimization-of-methane-production-from-different-sources-of-forest-raw-material
#12
Leonidas Matsakas, Ulrika Rova, Paul Christakopoulos
The increase in environmental problems and the shortage of fossil fuels have led to the need for action in the development of sustainable and renewable fuels. Methane is produced through anaerobic digestion of organic materials and is a biofuel with very promising characteristics. The success in using methane as a biofuel has resulted in the operation of several commercial-scale plants and the need to exploit novel materials to be used. Forest biomass can serve as an excellent candidate for use as raw material for anaerobic digestion...
2015: Frontiers in Microbiology
https://www.readbyqxmd.com/read/26462122/from-ecc-2015-lung-cancer-novelty-of-rova-t-first-targeted-agent-for-sclc
#13
(no author information available yet)
No abstract text is available yet for this article.
December 2015: Nature Reviews. Clinical Oncology
https://www.readbyqxmd.com/read/26348850/a-lysr-type-transcriptional-regulator-rovm-senses-nutritional-cues-suggesting-that-it-is-involved-in-metabolic-adaptation-of-yersinia-pestis-to-the-flea-gut
#14
Viveka Vadyvaloo, Angela K Hinz
Yersinia pestis has evolved as a clonal variant of Yersinia pseudotuberculosis to cause flea-borne biofilm-mediated transmission of the bubonic plague. The LysR-type transcriptional regulator, RovM, is highly induced only during Y. pestis infection of the flea host. RovM homologs in other pathogens regulate biofilm formation, nutrient sensing, and virulence; including in Y. pseudotuberculosis, where RovM represses the major virulence factor, RovA. Here the role that RovM plays during flea infection was investigated using a Y...
2015: PloS One
https://www.readbyqxmd.com/read/26234561/the-dual-transcriptional-regulator-rovm-regulates-the-expression-of-ar3-and-t6ss4-dependent-acid-survival-systems-in-response-to-nutritional-status-in-yersinia-pseudotuberculosis
#15
Yunhong Song, Xiao Xiao, Changfu Li, Tietao Wang, Ruoxi Zhao, Weipeng Zhang, Lei Zhang, Yao Wang, Xihui Shen
Coordinated regulation of various acid survival systems in response to environmental stimuli is crucial for the adaptation of enteropathogenic bacteria to acidic environments such as the stomach. In this study, we demonstrated that the RovM protein, a central regulator of the CsrABC-RovM-RovA cascade, conversely regulates the expression of two acid survival systems in Yersinia pseudotuberculosis by acting as a dual transcriptional regulator. RovM activated the expression of T6SS4, which is essential for bacterial survival under mild acidic conditions, by binding upstream of the T6SS4 promoter...
November 2015: Environmental Microbiology
https://www.readbyqxmd.com/read/25939507/comparison-of-models-for-bubonic-plague-reveals-unique-pathogen-adaptations-to-the-dermis
#16
Rodrigo J Gonzalez, Eric H Weening, M Chelsea Lane, Virginia L Miller
UNLABELLED: Vector-borne pathogens are inoculated in the skin of mammals, most likely in the dermis. Despite this, subcutaneous (s.c.) models of infection are broadly used in many fields, including Yersinia pestis pathogenesis. We expand on a previous report where we implemented intradermal (i.d.) inoculations to study bacterial dissemination during bubonic plague and compare this model with an s.c. MODEL: We found that i.d. inoculations result in faster kinetics of infection and that bacterial dose influenced mouse survival after i...
July 2015: Infection and Immunity
https://www.readbyqxmd.com/read/25890272/metabolic-engineering-of-escherichia-coli-for-enhanced-arginine-biosynthesis
#17
Mireille Ginesy, Jaroslav Belotserkovsky, Josefine Enman, Leif Isaksson, Ulrika Rova
BACKGROUND: Arginine is a high-value product, especially for the pharmaceutical industry. Growing demand for environmental-friendly and traceable products have stressed the need for microbial production of this amino acid. Therefore, the aim of this study was to improve arginine production in Escherichia coli by metabolic engineering and to establish a fermentation process in 1-L bioreactor scale to evaluate the different mutants. RESULTS: Firstly, argR (encoding an arginine responsive repressor protein), speC, speF (encoding ornithine decarboxylases) and adiA (encoding an arginine decarboxylase) were knocked out and the feedback-resistant argA214 or argA215 were introduced into the strain...
2015: Microbial Cell Factories
https://www.readbyqxmd.com/read/25776979/metabolic-engineering-of-escherichia-coli-for-enhanced-arginine-biosynthesis
#18
Mireille Ginesy, Jaroslav Belotserkovsky, Josefine Enman, Leif Isaksson, Ulrika Rova
BACKGROUND: Arginine is a high-value product, especially for the pharmaceutical industry. Growing demand for environmental-friendly and traceable products have stressed the need for microbial production of this amino acid. Therefore, the aim of this study was to improve arginine production in Escherichia coli by metabolic engineering and to establish a fermentation process in 1-L bioreactor scale to evaluate the different mutants. RESULTS: Firstly, argR (encoding an arginine responsive repressor protein), speC, speF (encoding ornithine decarboxylases) and adiA (encoding an arginine decarboxylase) were knocked out and the feedback-resistant argA214 or argA215 were introduced into the strain...
December 2015: Microbial Cell Factories
https://www.readbyqxmd.com/read/25673284/chlorate-reductase-is-cotranscribed-with-cytochrome-c-and-other-downstream-genes-in-the-gene-cluster-for-chlorate-respiration-of-ideonella-dechloratans
#19
Miriam Hellberg Lindqvist, Thomas Nilsson, Pontus Sundin, Maria Rova
The chlorate-respiring bacterium Ideonella dechloratans is a facultative anaerobe that can use both oxygen and chlorate as terminal electron acceptors. The genes for the enzymes chlorate reductase (clrABDC) and chlorite dismutase, necessary for chlorate metabolism and probably acquired by lateral gene transfer, are located in a gene cluster that also includes other genes potentially important for chlorate metabolism. Among those are a gene for cytochrome c (cyc) whose gene product may serve as an electron carrier during chlorate reduction, a cofactor biosynthesis gene (mobB) and a predicted transcriptional regulator (arsR)...
March 2015: FEMS Microbiology Letters
https://www.readbyqxmd.com/read/25632300/high-concentrations-of-dried-sorghum-stalks-as-a-biomass-feedstock-for-single-cell-oil-production-by-rhodosporidium-toruloides
#20
Leonidas Matsakas, Nemailla Bonturi, Everson Alves Miranda, Ulrika Rova, Paul Christakopoulos
BACKGROUND: Environmental crisis and concerns for energy security have made the research for renewable fuels that will substitute the usage of fossil fuels an important priority. Biodiesel is a potential substitute for petroleum, but its feasibility is hindered by the utilization of edible vegetable oil as raw material, which is responsible for a large fraction of the production cost and fosters the food versus fuel competition. Microbial oils are an interesting alternative as they do not compete with food production, and low cost renewable materials could serve as raw materials during cultivation of microorganisms...
2015: Biotechnology for Biofuels
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