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https://www.readbyqxmd.com/read/28102121/inflammasomes-in-myeloid-cells-warriors-within
#1
Sushmita Jha, W June Brickey, Jenny Pan-Yun Ting
The inflammasome is a large multimeric protein complex comprising an effector protein that demonstrates specificity for a variety of activators or ligands; an adaptor molecule; and procaspase-1, which is converted to caspase-1 upon inflammasome activation. Inflammasomes are expressed primarily by myeloid cells and are located within the cell. The macromolecular inflammasome structure can be visualized by cryo-electron microscopy. This complex has been found to play a role in a variety of disease models in mice, and several have been genetically linked to human diseases...
January 2017: Microbiology Spectrum
https://www.readbyqxmd.com/read/28094775/nanotechnologies-in-delivery-of-mrna-therapeutics-using-nonviral-vector-based-delivery-systems
#2
REVIEW
S Guan, J Rosenecker
Due to its safe and effective protein expression profile, in vitro transcribed messenger RNA (IVT-mRNA) represents a promising candidate in the development of novel therapeutics for genetic diseases, vaccines or gene editing strategies, especially when its inherent shortcomings (e.g. instability and immunogenicity) have been partially addressed via structural modifications. However, numerous unsolved technical difficulties in successful in vivo delivery of IVT-mRNA have greatly hindered the applications of IVT-mRNA in clinical development...
January 17, 2017: Gene Therapy
https://www.readbyqxmd.com/read/28090287/transcription-factors-transcriptional-coregulators-and-epigenetic-modulation-in-the-control-of-pulmonary-vascular-cell-phenotype-therapeutic-implications-for-pulmonary-hypertension-2015-grover-conference-series
#3
REVIEW
Soni S Pullamsetti, Frédéric Perros, Prakash Chelladurai, Jason Yuan, Kurt Stenmark
Pulmonary hypertension (PH) is a complex and multifactorial disease involving genetic, epigenetic, and environmental factors. Numerous stimuli and pathological conditions facilitate severe vascular remodeling in PH by activation of a complex cascade of signaling pathways involving vascular cell proliferation, differentiation, and inflammation. Multiple signaling cascades modulate the activity of certain sequence-specific DNA-binding transcription factors (TFs) and coregulators that are critical for the transcriptional regulation of gene expression that facilitates PH-associated vascular cell phenotypes, as demonstrated by several studies summarized in this review...
December 2016: Pulmonary Circulation
https://www.readbyqxmd.com/read/28088905/update-on-recent-developments-in-small-molecular-hiv-1-rnase-h-inhibitors-2013-2016-opportunities-and-challenges
#4
Xueshun Wang, Ping Gao, Luis Menéndez-Arias, Xinyong Liu, Peng Zhan
Combinations of antiretroviral drugs are successfully used to treat HIV-infected patients. However, drug resistance is a major problem that makes discovery of new antiretroviral drugs an ongoing priority. The ribonuclease H (RNase H) activity of the HIV-1 reverse transcriptase catalyzes the selective hydrolysis of the RNA strand of RNA:DNA heteroduplex replication intermediates, and represents an attractive unexploited target for drug development. This review reports on recent progress in the characterization of HIV-1 RNase H inhibitors from 2013 to 2016, describing their chemical structures, structure-activity relationship and binding modes...
January 13, 2017: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/28087410/repair-of-8-oxog-a-mismatches-by-the-mutyh-glycosylase-mechanism-metals-medicine
#5
REVIEW
Douglas M Banda, Nicole N Nuñez, Michael A Burnside, Katie M Bradshaw, Sheila S David
Reactive oxygen and nitrogen species (RONS) may infringe on the passing of pristine genetic information by inducing DNA inter- and intra-strand crosslinks, protein-DNA crosslinks, and chemical alterations to the sugar or base moieties of DNA. 8-Oxo-7,8-dihydroguanine (8-oxoG) is one of the most prevalent DNA lesions formed by RONS and is repaired through the base excision repair (BER) pathway involving the DNA repair glycosylases OGG1 and MUTYH in eukaryotes. MUTYH removes adenine (A) from 8-oxoG:A mispairs, thus mitigating the potential of G:C to T:A transversion mutations from occurring in the genome...
January 10, 2017: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/28078793/insights-into-nuclear-dynamics-using-live-cell-imaging-approaches
#6
REVIEW
Rachel B Bigley, Alexander Y Payumo, Jeffrey M Alexander, Guo N Huang
The nucleus contains the genetic blueprint of the cell and myriad interactions within this subcellular structure are required for gene regulation. In the current scientific era, characterization of these gene regulatory networks through biochemical techniques coupled with systems-wide 'omic' approaches has become commonplace. However, these strategies are limited because they represent a mere snapshot of the cellular state. To obtain a holistic understanding of nuclear dynamics, relevant molecules must be studied in their native contexts in living systems...
January 12, 2017: Wiley Interdisciplinary Reviews. Systems Biology and Medicine
https://www.readbyqxmd.com/read/28078514/the-molecular-basis-of-the-organization-of-repetitive-dna-containing-constitutive-heterochromatin-in-mammals
#7
REVIEW
Gohei Nishibuchi, Jérôme Déjardin
Constitutive heterochromatin is composed mainly of repetitive elements and represents the typical inert chromatin structure in eukaryotic cells. Approximately half of the mammalian genome is made of repeat sequences, such as satellite DNA, telomeric DNA, and transposable elements. As essential genes are not present in these regions, most of these repeat sequences were considered as junk DNA in the past. However, it is now clear that these regions are essential for chromosome stability and the silencing of neighboring genes...
January 11, 2017: Chromosome Research
https://www.readbyqxmd.com/read/28075396/translesion-synthesis-insights-into-the-selection-and-switching-of-dna-polymerases
#8
REVIEW
Linlin Zhao, M Todd Washington
DNA replication is constantly challenged by DNA lesions, noncanonical DNA structures and difficult-to-replicate DNA sequences. Two major strategies to rescue a stalled replication fork and to ensure continuous DNA synthesis are: (1) template switching and recombination-dependent DNA synthesis; and (2) translesion synthesis (TLS) using specialized DNA polymerases to perform nucleotide incorporation opposite DNA lesions. The former pathway is mainly error-free, and the latter is error-prone and a major source of mutagenesis...
January 10, 2017: Genes
https://www.readbyqxmd.com/read/28069354/bufadienolides-from-amphibians-a-promising-source-of-anticancer-prototypes-for-radical-innovation-apoptosis-triggering-and-na-k-atpase-inhibition
#9
REVIEW
Lívia Queiroz de Sousa, Kátia da Conceição Machado, Samara Ferreira de Carvalho Oliveira, Lidiane da Silva Araújo, Evaldo Dos Santos Monção-Filho, Ana Amélia de Carvalho Melo-Cavalcante, Gerardo Magela Vieira-Júnior, Paulo Michel Pinheiro Ferreira
Amphibians present pharmacologically active aliphatic, aromatic and heterocyclic molecules in their skin as defense against microorganisms, predators and infections, such as steroids, alkaloids, biogenic amines, guanidine derivatives, proteins and peptides. Based on the discovered bioactive potential of bufadienolides, this work reviewed the contribution of amphibians, especially from members of Bufonidae family, as source of new cytotoxic and antitumor molecules, highlighting the mechanisms responsible for such amazing biological potentialities...
January 6, 2017: Toxicon: Official Journal of the International Society on Toxinology
https://www.readbyqxmd.com/read/28069312/centromeres-drive-a-hard-bargain
#10
REVIEW
Leah F Rosin, Barbara G Mellone
Centromeres are essential chromosomal structures that mediate the accurate distribution of genetic material during meiotic and mitotic cell divisions. In most organisms, centromeres are epigenetically specified and propagated by nucleosomes containing the centromere-specific H3 variant, centromere protein A (CENP-A). Although centromeres perform a critical and conserved function, CENP-A and the underlying centromeric DNA are rapidly evolving. This paradox has been explained by the centromere drive hypothesis, which proposes that CENP-A is undergoing an evolutionary tug-of-war with selfish centromeric DNA...
January 6, 2017: Trends in Genetics: TIG
https://www.readbyqxmd.com/read/28068556/organizing-dna-repair-in-the-nucleus-dsbs-hit-the-road
#11
REVIEW
Aline Marnef, Gaëlle Legube
In the past decade, large-scale movements of DNA double strand breaks (DSBs) have repeatedly been identified following DNA damage. These mobility events include clustering, anchoring or peripheral movement at subnuclear structures. Recent work suggests roles for motion in homology search and in break sequestration to preclude deleterious outcomes. Yet, the precise functions of these movements still remain relatively obscure, and the same holds true for the determinants. Here we review recent advances in this exciting area of research, and highlight that a recurrent characteristic of mobile DSBs may lie in their inability to undergo rapid repair...
January 6, 2017: Current Opinion in Cell Biology
https://www.readbyqxmd.com/read/28067843/maintenance-of-genome-integrity-how-mammalian-cells-orchestrate-genome-duplication-by-coordinating-replicative-and-specialized-dna-polymerases
#12
REVIEW
Ryan Barnes, Kristin Eckert
Precise duplication of the human genome is challenging due to both its size and sequence complexity. DNA polymerase errors made during replication, repair or recombination are central to creating mutations that drive cancer and aging. Here, we address the regulation of human DNA polymerases, specifically how human cells orchestrate DNA polymerases in the face of stress to complete replication and maintain genome stability. DNA polymerases of the B-family are uniquely adept at accurate genome replication, but there are numerous situations in which one or more additional DNA polymerases are required to complete genome replication...
January 6, 2017: Genes
https://www.readbyqxmd.com/read/28067410/the-photolyase-cryptochrome-family-of-proteins-as-dna-repair-enzymes-and-transcriptional-repressors
#13
REVIEW
Ibrahim Halil Kavakli, Ibrahim Baris, Mehmet Tardu, Şeref Gül, Haşimcan Öner, Sibel Çal, Selma Bulut, Darya Yarparvar, Çağlar Berkel, Pınar Ustaoğlu, Cihan Aydın
Light is a very important environmental factor that governs many cellular responses in organisms. As a consequence, organisms possess different kinds of light-sensing photoreceptors to regulate their physiological variables and adapt to a given habitat. The cryptochrome/photolyase family (CPF) includes photoreceptors that perform different functions in different organisms. Photolyases repair ultraviolet-induced DNA damage by a process known as photoreactivation using photons absorbed from the blue end of the light spectrum...
November 16, 2016: Photochemistry and Photobiology
https://www.readbyqxmd.com/read/28067384/nanocaged-platforms-modification-drug-delivery-and-nanotoxicity-opening-synthetic-cages-to-release-the-tiger
#14
REVIEW
Parham Sahandi Zangabad, Mahdi Karimi, Fatemeh Mehdizadeh, Hedieh Malekzad, Alireza Ghasemi, Sajad Bahrami, Hossein Zare, Mohsen Moghoofei, Amin Hekmatmanesh, Michael R Hamblin
Nanocages (NCs) have emerged as a new class of drug-carriers, with a wide range of possibilities in multi-modality medical treatments and theranostics. Nanocages can overcome such limitations as high toxicity caused by anti-cancer chemotherapy or by the nanocarrier itself, due to their unique characteristics. These properties consist of: (1) a high loading-capacity (spacious interior); (2) a porous structure (analogous to openings between the bars of the cage); (3) enabling smart release (a key to unlock the cage); and (4) a low likelihood of unfavorable immune responses (the outside of the cage is safe)...
January 9, 2017: Nanoscale
https://www.readbyqxmd.com/read/28064387/the-role-of-histone-modifications-and-telomere-alterations-in-the-pathogenesis-of-diffuse-gliomas-in-adults-and-children
#15
REVIEW
Julieann Lee, D A Solomon, Tarik Tihan
Genetic profiling is an increasingly useful tool for sub-classification of gliomas in adults and children. Specific gene mutations, structural rearrangements, DNA methylation patterns, and gene expression profiles are now recognized to define molecular subgroups of gliomas that arise in distinct anatomic locations and patient age groups, and also provide a better prediction of clinical outcomes for glioma patients compared to histologic assessment alone. Understanding the role of these distinctive genetic alterations in gliomagenesis is also important for the development of potential targeted therapeutic interventions...
January 7, 2017: Journal of Neuro-oncology
https://www.readbyqxmd.com/read/28062403/mutated-chromatin-regulatory-factors-as-tumor-drivers-in-cancer
#16
REVIEW
Carl Koschmann, Felipe J Nunez, Flor Mendez, Jacqueline A Brosnan-Cashman, Alan K Meeker, Pedro R Lowenstein, Maria G Castro
Genes encoding proteins that regulate chromatin structure and DNA modifications [i.e., chromatin regulatory factors (CRF)] and genes encoding histone proteins harbor recurrent mutations in most human cancers. These mutations lead to modifications in tumor chromatin and DNA structure and an altered epigenetic state that contribute to tumorigenesis. Mutated CRFs have now been identified in most types of cancer and are increasingly regarded as novel therapeutic targets. In this review, we discuss DNA alterations in CRFs and how these influence tumor chromatin structure and function, which in turn leads to tumorigenesis...
January 15, 2017: Cancer Research
https://www.readbyqxmd.com/read/28060558/the-connection-between-brg1-ctcf-and-topoisomerases-at-tad-boundaries
#17
A Rasim Barutcu, Jane B Lian, Janet L Stein, Gary S Stein, Anthony N Imbalzano
The eukaryotic genome is partitioned into topologically associating domains (TADs). Despite recent advances characterizing TADs and TAD boundaries, the organization of these structures is an important dimension of genome architecture and function that is not well understood. Recently, we demonstrated that knockdown of BRG1, an ATPase driving the chromatin remodeling activity of mammalian SWI/SNF enzymes, globally alters long-range genomic interactions and results in a reduction of TAD boundary strength. We provided evidence suggesting that this effect may be due to BRG1 affecting nucleosome occupancy around CTCF sites present at TAD boundaries...
January 6, 2017: Nucleus
https://www.readbyqxmd.com/read/28057257/have-nec-coat-will-travel-structural-basis-of-membrane-budding-during-nuclear-egress-in-herpesviruses
#18
REVIEW
J M Bigalke, E E Heldwein
Herpesviruses are unusual among enveloped viruses because they bud twice yet acquire a single envelope. Furthermore, unlike other DNA viruses that replicate in the nucleus, herpesviruses do not exit it by passing through the nuclear pores or by rupturing the nuclear envelope. Instead, herpesviruses have a complex mechanism of nuclear escape whereby nascent capsids bud at the inner nuclear membrane to form perinuclear virions that subsequently fuse with the outer nuclear membrane, releasing capsids into the cytosol...
2017: Advances in Virus Research
https://www.readbyqxmd.com/read/28048551/we-fg-brb-02-spatial-mapping-of-the-rbe-of-scanned-particle-beams
#19
D Grosshans
: The physical pattern of energy deposition and the enhanced relative biological effectiveness (RBE) of protons and carbon ions compared to photons offer unique and not fully understood or exploited opportunities to improve the efficacy of radiation therapy. Variations in RBE within a pristine or spread out Bragg peak and between particle types may be exploited to enhance cell killing in target regions without a corresponding increase in damage to normal tissue structures. In addition, the decreased sensitivity of hypoxic tumors to photon-based therapies may be partially overcome through the use of more densely ionizing radiations...
June 2016: Medical Physics
https://www.readbyqxmd.com/read/28048194/we-fg-brb-01-clinical-significance-of-rbe-variations-in-proton-therapy
#20
H Paganetti
: The physical pattern of energy deposition and the enhanced relative biological effectiveness (RBE) of protons and carbon ions compared to photons offer unique and not fully understood or exploited opportunities to improve the efficacy of radiation therapy. Variations in RBE within a pristine or spread out Bragg peak and between particle types may be exploited to enhance cell killing in target regions without a corresponding increase in damage to normal tissue structures. In addition, the decreased sensitivity of hypoxic tumors to photon-based therapies may be partially overcome through the use of more densely ionizing radiations...
June 2016: Medical Physics
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