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Inhibiting PARP as a Strategic Target in Cancer

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Book Series: Frontiers Research Topics ISSN: 16648714 ISBN: 9782889199556 Year: Pages: 97 DOI: 10.3389/978-2-88919-955-6 Language: English
Publisher: Frontiers Media SA
Subject: Medicine (General) --- Oncology
Added to DOAB on : 2016-01-19 14:05:46
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Poly-ADP ribose polymerase (PARP) proteins are critical mediators of DNA repair. Many traditional anti-cancer chemotherapy agents overwhelm a cell’s ability to repair DNA damage in order to kill proliferating malignant cells. Recent evidence suggests that cancers within and across tissue types have specific defects in DNA repair pathways, and that these defects may predispose for sensitivity and resistance to various classes of cytotoxic agents. Breast, ovarian and other cancers develop in the setting of inherited DNA repair deficiency, and these cancers may be more sensitive to cytotoxic agents that induce DNA strand breaks, as well as to inhibitors of PARP activity. A series of recent clinical trials has tested whether PARP inhibitors can achieve synthetic lethality in hereditary DNA repair-deficient tumors. At the current time, mutation of BRCA serves as a potential, but not comprehensive, biomarker to predict response to PARP inhibitor therapy. Mechanisms of resistance to PARP inhibitors are only recently being uncovered. Future studies seek to identify sporadic cancers that harbor genomic instability rendering susceptibility to PARP inhibitors that compound lethal DNA damage.

Epigenetics of B Cells and Antibody Responses

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Book Series: Frontiers Research Topics ISSN: 16648714 ISBN: 9782889197903 Year: Pages: 121 DOI: 10.3389/978-2-88919-790-3 Language: English
Publisher: Frontiers Media SA
Subject: Allergy and Immunology --- Medicine (General)
Added to DOAB on : 2017-02-03 17:04:57
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Epigenetics is the study of changes in gene activity that are heritable but not caused by changes in the DNA sequence. By modulating gene activities, epigenetic changes regulate cell functions. They include DNA methylation, histone posttranslational modifications and gene silencing by the action of non-coding RNAs, particularly microRNAs. It is now clear that epigenetic changes regulate B cell development. By acting in concert with networks of transcription factors, they modulate the activation of B cell lineage specific gene programs and repress inappropriate gene transcription in particular B cell differentiation states. A hallmark of B cell development in the bone marrow is the assembly of the B cell receptor (BCR) for antigen through rearrangement of immunoglobulin heavy (IgH) and light (IgL) chain V(D)J genes, as mediated by RAG1/RAG2 recombinases. Ig V(D)J rearrangement critically times the progression from pro-B cell to pre-B cell and, finally, mature B cell. Such progression is modulated by epigenetic marks, such as DNA methylation and histone posttranslational modifications, that increase chromatin accessibility and target RAG/RAG2 to V, D and J DNA. It is also dependent on the expression of multiple microRNAs. Mice deficient in Ago2, which is essential for microRNA biogenesis and function, have B cell development blocked at the pro-B cell stage. In agreement with this, B cell specific ablation of microRNA by B cell-specific knockout of Dicer virtually blocks B cell differentiation at the pro-B to pre-B cell transition. After mature B cells encounter antigen, changes of the epigenetic landscape are induced by the same stimuli that drive the antibody response; such epigenetic changes underpin the maturation of the antibody response itself. They instruct those B cell differentiation processes, somatic hypermutation (SHM), class switch DNA recombination (CSR) and plasma cell differentiation, that are central to the maturation of the antibody response as well as differentiation of memory B cells. Inducible histone modifications, together with DNA methylation and microRNAs modulate the transcriptome, particularly the expression of activation-induced cytidine deaminase (AID), central to SHM and CSR, and B lymphocyte-induced maturation protein-1 (Blimp-1), which is central to plasma cell differentiation. Combinatorial histone modifications also function as histone codes in the targeting of the CSR and, possibly, the SHM machinery to the Ig locus by recruiting specific adaptors (histone code readers) that can in turn target and/or stabilize CSR/SHM factors. Epigenetic alterations in memory B cells contribute to their functionally distinction from their naive counterparts. Memory B cells inherit epigenetic information from their precursors and acquire new epigenetic marks, which make these resting B cells poised to promptly respond to antigen. The cross/feedback regulation of different epigenetic modifications/elements further increases the complexity of the B cell epigenome, which interacts with the genetic information for precise modulation of gene expression. It is increasingly evident that epigenetic dysregulation in B cells, including aberrant expression of microRNAs, can result in aberrant antibody responses to microbial pathogens, emergence of pathogenic autoantibodies or B cell neoplastic transformation. Epigenetic marks are potential targets for new therapeutics in autoimmunity and B cell malignancy.

SPIG2018

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ISBN: 9783038978503 9783038978510 Year: Pages: 288 DOI: 10.3390/books978-3-03897-851-0 Language: eng
Publisher: MDPI - Multidisciplinary Digital Publishing Institute
Subject: Science (General) --- Physics (General) --- Nuclear Physics
Added to DOAB on : 2019-04-25 16:37:17
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This Special Issue covers a wide range of topics from fundamental studies to applications of ionized gases. It is dedicated to four topics of interest: 1. ATOMIC COLLISION PROCESSES (electron and photon interactions with atomic particles, heavy particle collisions, swarms, and transport phenomena); 2. PARTICLE AND LASER BEAM INTERACTION WITH SOLIDS (atomic collisions in solids, sputtering and deposition, and laser and plasma interactions with surfaces); 3. LOW TEMPERATURE PLASMAS (plasma spectroscopy and other diagnostic methods, gas discharges, and plasma applications and devices); 4. GENERAL PLASMAS (fusion plasmas, astrophysical plasmas, and collective phenomena). This Special Issue of Atoms will highlight the need for continued research on ionized gas physics in different topics ranging from fundamental studies to applications, and will review current investigations.

Keywords

strong-field physics --- attoscience --- bicircular field --- high-order harmonic generation --- above-threshold ionization --- spin-polarized electrons --- capacitively-coupled discharge --- oxygen --- particle-in-cell/Monte Carlo collision --- electron heating --- secondary electron emission --- Large Helical Device (LHD) --- deuterium experiment --- ion temperature of 10 keV --- plasma research --- spectroscopic study --- dispersion interferometer --- modified theories of gravity --- methods: analytical --- methods: numerical --- galaxies: elliptical --- galaxies: fundamental parameters --- non-equilibrium --- collisions --- radiation --- planetary atmospheric entry --- laser matter interaction --- laser-induced breakdown --- plasma --- spectroscopy --- streak camera --- plasma --- spectral lines --- Stark broadening --- oxygen --- silicon --- spectroscopy --- gas discharges --- plasma applications --- databases --- virtual observatory --- cross sections --- rate coefficients --- runway electron --- plasma current --- fusion plasma --- tokamak --- glow discharge --- argon --- nitrogen admixture --- discharge voltage --- diffuse discharge --- constricted discharge --- electrical theory of DBDs --- QV-plot --- instantaneous power --- rainbow scattering --- positron channeling effect --- time-dependent Schrödinger equation --- chiral single wall carbon nanotubes --- black hole physics --- cosmology --- quasar spectroscopy --- cosmological parameters --- ionized gas --- broad line region --- Rydberg atoms --- dynamic instability --- control of atomic states --- Förster resonance --- plasma spectroscopy --- Stark broadening --- plasma diagnostics --- line shape modeling --- Zeeman-Doppler broadening --- Balmer line series --- radiative recombination --- photoacoustic --- photothermal --- inverse problem --- thermal memory --- minimum volume cell --- neural networks --- thermal diffusivity --- conductivity --- linear coefficient of thermal extension --- AGN --- black holes --- gravitational waves --- binary black holes --- quasars --- photodetachment --- magnetically confined fusion --- neutral beam injection --- plasma heating --- optical cavity amplification --- low-energy electrons --- electron–molecule interactions --- astrochemistry --- laboratory plasma --- astrophysical plasma --- fusion plasma --- lasers --- stars --- extragalactic objects --- spectra --- spectroscopy --- scaling laws

Mycoviruses

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ISBN: 9783038979968 / 9783038979975 Year: Pages: 350 DOI: 10.3390/books978-3-03897-997-5 Language: eng
Publisher: MDPI - Multidisciplinary Digital Publishing Institute
Added to DOAB on : 2019-06-26 08:44:06
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A virus (from the Latin word ‘v?rus’ meaning ‘venom’ or ‘poison’) is a microorganism invisible to the naked eye. Viruses can multiply exclusively by entering a cell and using the cell’s resources to create copies of themselves. As the origin of their name suggests, viruses are generally considered dangerous, harmful and often deadly. Some of the most well-studied and widely known viruses, such as HIV and influenza, infect humans. However, viruses can also infect animals, plants and microorganisms, including fungi. Many fungi are medically, ecologically and economically significant, for example, causing diseases to humans, plants and insects or being used in industry to produce bread, cheese, beer and wine. Viruses that infect fungi are called mycoviruses (from the Greek work ‘myco’, meaning ‘fungus’). Mycoviruses do not cause harm to or kill the infected fungus; in contrast, they are ‘friendly’ viruses and we can utilize them to control the growth, pathogenicity and toxin production of fungi. This book describes a range of different mycoviruses and their geographical distribution, transmission and evolution, together with their effects on the fungal hosts and how these are brought about.

Keywords

RNA silencing --- gemycircularvirus --- mycovirus --- antiviral --- dicer --- dsRNA mycoviruses --- multiplex PCR --- Aspergillus fumigatus chrysovirus --- Aspergillus fumigatus partitivirus-1 --- Aspergillus fumigatus tetramycovirus-1. --- Botrytis cinerea --- hypovirus --- fusarivirus --- hypovirulence --- infection cushion --- Botrytis cinerea --- Botrytis cinerea mymonavirus 1 --- Mymonaviridae --- dsRNA virus --- mycovirus --- capsid protein --- capsid structure --- virus evolution --- viral lineage --- ScV-L-A --- PcV --- PsV-F --- RnQV1 --- chrysovirus --- mycovirus --- Aspergillus --- A. fumigatus --- A. nidulans --- A. niger --- A. thermomutatus --- biocontrol --- Saccharomyces paradoxus --- Totiviridae --- dsRNA virus --- killer system --- Trichoderma atroviride --- Mycovirus --- Partitivirus --- Fusarium head blight --- mycovirus --- RNA genome --- mitovirus --- Tymovirales --- Ethiopia --- Sclerotinia minor --- endornavirus --- hypovirulence --- transmissibility --- biological control --- Chalara fraxinea --- Hymenoscyphus pseudoalbidus --- ash dieback --- Narnaviridae --- evolution --- invasive species --- horizontal virus transmission --- Brunchorstia pinea --- conifers --- mycovirus --- dsRNA --- ssRNA --- phylogeny --- evolution --- mycovirus --- Beauveria bassiana --- partitivirus --- victorivirus --- polymycovirus --- selection pressure --- recombination --- transmission --- mycovirus --- populations study --- Cryphonectria parasitica --- chestnut blight --- Castanea sativa --- biological control --- Mycovirus --- rice blast fungus --- Magnaporthe oryzae. chrysovirus 1 --- double-stranded RNA virus --- hypovirulence --- Rhizoctonia solani AG-1 IA --- mycovirus --- dsRNA --- Alphapartitivirus --- genomic structure analysis --- mycorrhizal fungi --- mycovirus --- mitovirus --- Rhizophagus --- hypovirus --- small RNA --- tRFs --- mycovirus --- fungal viruses --- dsRNA mycoviruses --- hypervirulence --- Leptosphaeria biglobosa quadrivirus --- Botrytis cinerea --- hypovirulence --- partitivirus --- conidiogenesis --- sclerogenesis --- mycovirus --- dsRNA --- sequencing --- killer toxin --- totivirus --- brown rot --- stone fruit --- Prunus --- mycovirus --- hypervirulence --- hypovirulence --- isogenic --- database mining --- Entomophthora --- Entomophthoromycotina --- fungal virus --- mitochondrion --- mycovirus --- virus discovery --- Mitovirus --- Narnaviridae --- n/a

Plant Genetics and Molecular Breeding

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ISBN: 9783039211753 / 9783039211760 Year: Pages: 628 DOI: 10.3390/books978-3-03921-176-0 Language: eng
Publisher: MDPI - Multidisciplinary Digital Publishing Institute
Subject: Science (General) --- Biology
Added to DOAB on : 2019-08-28 11:21:27
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The development of new plant varieties is a long and tedious process involving the generation of large seedling populations for the selection of the best individuals. While the ability of breeders to generate large populations is almost unlimited, the selection of these seedlings is the main factor limiting the generation of new cultivars. Molecular studies for the development of marker-assisted selection (MAS) strategies are particularly useful when the evaluation of the character is expensive, time-consuming, or with long juvenile periods. The papers published in the Special Issue “Plant Genetics and Molecular Breeding” report highly novel results and testable new models for the integrative analysis of genetic (phenotyping and transmission of agronomic characters), physiology (flowering, ripening, organ development), genomic (DNA regions responsible for the different agronomic characters), transcriptomic (gene expression analysis of the characters), proteomic (proteins and enzymes involved in the expression of the characters), metabolomic (secondary metabolites), and epigenetic (DNA methylation and histone modifications) approaches for the development of new MAS strategies. These molecular approaches together with an increasingly accurate phenotyping will facilitate the breeding of new climate-resilient varieties resistant to abiotic and biotic stress, with suitable productivity and quality, to extend the adaptation and viability of the current varieties.

Keywords

sugarcane --- cry2A gene --- particle bombardment --- stem borer --- resistance --- NPK fertilizers --- agronomic traits --- molecular markers --- quantitative trait loci --- common wild rice --- Promoter --- Green tissue-specific expression --- light-induced --- transgenic chrysanthemum --- WRKY transcription factor --- salt stress --- gene expression --- DgWRKY2 --- Cucumis sativus L. --- RNA-Seq --- DEGs --- sucrose --- ABA --- drought stress --- Aechmea fasciata --- squamosa promoter binding protein-like --- flowering time --- plant architecture --- bromeliad --- Oryza sativa --- endosperm development --- rice quality --- WB1 --- the modified MutMap method --- abiotic stress --- Cicer arietinum --- candidate genes --- genetics --- heat-stress --- molecular breeding --- metallothionein --- Brassica --- Brassica napus --- As3+ stress --- broccoli --- cytoplasmic male sterile --- bud abortion --- gene expression --- transcriptome --- RNA-Seq --- sesame --- genome-wide association study --- yield --- QTL --- candidate gene --- cabbage --- yellow-green-leaf mutant --- recombination-suppressed region --- bulk segregant RNA-seq --- differentially expressed genes --- marker–trait association --- haplotype block --- genes --- root traits --- D-genome --- genotyping-by-sequencing --- single nucleotide polymorphism --- durum wheat --- bread wheat --- complex traits --- Brassica oleracea --- Ogura-CMS --- iTRAQ --- transcriptome --- pollen development --- rice --- OsCDPK1 --- seed development, starch biosynthesis --- endosperm appearance --- Chimonanthus praecox --- nectary --- floral scent --- gene expression --- Prunus --- flowering --- bisulfite sequencing --- genomics --- epigenetics --- breeding --- AP2/ERF genes --- Bryum argenteum --- transcriptome --- gene expression --- stress tolerance --- SmJMT --- transgenic --- Salvia miltiorrhiza --- overexpression --- transcriptome --- phenolic acids --- Idesia polycarpa var --- glycine --- FAD2 --- linoleic acid --- oleic acid --- anther wall --- tapetum --- pollen accumulation --- OsGPAT3 --- rice --- cytoplasmic male sterility (CMS) --- phytohormones --- differentially expressed genes --- pollen development --- Brassica napus --- Rosa rugosa --- RrGT2 gene --- Clone --- VIGS --- Overexpression --- Tobacco --- Flower color --- Anthocyanin --- sugarcane --- WRKY --- subcellular localization --- gene expression pattern --- protein-protein interaction --- transient overexpression --- soybean --- branching --- genome-wide association study (GWAS) --- near-isogenic line (NIL) --- BRANCHED1 (BRC1) --- TCP transcription factor --- Zea mays L. --- MADS transcription factor --- ZmES22 --- starch --- flowering time --- gene-by-gene interaction --- Hd1 --- Ghd7 --- rice --- yield trait --- Oryza sativa L. --- leaf shape --- yield trait --- molecular breeding --- hybrid rice --- nutrient use efficiency --- quantitative trait loci (QTLs), molecular markers --- agronomic efficiency --- partial factor productivity --- P. suffruticosa --- R2R3-MYB --- overexpression --- anthocyanin --- transcriptional regulation --- ethylene-responsive factor --- Actinidia deliciosa --- AdRAP2.3 --- gene expression --- waterlogging stress --- regulation --- Chrysanthemum morifolium --- WUS --- CYC2 --- gynomonoecy --- reproductive organ --- flower symmetry --- Hs1pro-1 --- cZR3 --- gene pyramiding --- Heterodera schachtii --- resistance --- tomato --- Elongated Internode (EI) --- QTL --- GA2ox7 --- n/a

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