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https://www.readbyqxmd.com/read/28102005/blind-prediction-of-deleterious-amino-acid-variations-with-snps-go
#1
Emidio Capriotti, Pier Luigi Martelli, Piero Fariselli, Rita Casadio
: SNPs&GO is a machine learning method for predicting the association of single amino acid variations (SAVs) to disease, considering protein functional annotation. The method is a binary classifier that implements a Support Vector Machine algorithm to discriminate between disease-related and neutral SAVs. SNPs&GO combines information from protein sequence with functional annotation encoded by Gene Ontology terms. Tested in sequence mode on more than 38,000 SAVs from the SwissVar dataset, our method reached 81% overall accuracy and an area under the receiving operating characteristic curve (AUC) of 0...
January 19, 2017: Human Mutation
https://www.readbyqxmd.com/read/28100881/transporters-for-the-intestinal-absorption-of-cholesterol-vitamin-e-and-vitamin-k
#2
Yoshihide Yamanashi, Tappei Takada, Ryoya Kurauchi, Yusuke Tanaka, Toko Komine, Hiroshi Suzuki
Humans cannot synthesize fat-soluble vitamins such as vitamin E and vitamin K. For this reason, they must be obtained from the diet via intestinal absorption. As the deficiency or excess of these vitamins has been reported to cause several types of diseases and disorders in humans, the intestinal absorption of these nutrients must be properly regulated to ensure good health. However, the mechanism of their intestinal absorption remains poorly understood. Recent studies on cholesterol using genome-edited mice, genome-wide association approaches, gene mutation analyses, and the development of cholesterol absorption inhibitors have revealed that several membrane proteins play crucial roles in the intestinal absorption of cholesterol...
January 17, 2017: Journal of Atherosclerosis and Thrombosis
https://www.readbyqxmd.com/read/28100701/self-cytoplasmic-dna-upregulates-the-mutator-enzyme-apobec3a-leading-to-chromosomal-dna-damage
#3
Rodolphe Suspène, Bianka Mussil, Hélène Laude, Vincent Caval, Noémie Berry, Mohamed S Bouzidi, Valérie Thiers, Simon Wain-Hobson, Jean-Pierre Vartanian
Foreign and self-cytoplasmic DNA are recognized by numerous DNA sensor molecules leading to the production of type I interferons. Such DNA agonists should be degraded otherwise cells would be chronically stressed. Most human APOBEC3 cytidine deaminases can initiate catabolism of cytoplasmic mitochondrial DNA. Using the human myeloid cell line THP-1 with an interferon inducible APOBEC3A gene, we show that cytoplasmic DNA triggers interferon α and β production through the RNA polymerase III transcription/RIG-I pathway leading to massive upregulation of APOBEC3A By catalyzing C→U editing in single stranded DNA fragments, the enzyme prevents them from re-annealing so attenuating the danger signal...
January 18, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28100636/centriole-splitting-caused-by-loss-of-the-centrosomal-linker-protein-c-nap1-reduces-centriolar-satellite-density-and-impedes-centrosome-amplification
#4
Anne-Marie Flanagan, Elena Stavenschi, Shivakumar Basavaraju, David Gaboriau, David A Hoey, Ciaran G Morrison
Duplication of the centrosomes is a tightly regulated process. Abnormal centrosome numbers can impair cell division and cause changes in how cells migrate. Duplicated centrosomes are held together by a proteinaceous linker made up of rootletin filaments anchored to the centrioles by C-NAP1. This linker is removed in a NEK2A kinase-dependent manner as mitosis begins. To explore C-NAP1 activities in regulating centrosome activities, we used genome editing to ablate it. C-NAP1 null cells were viable and had an increased frequency of premature centriole separation, accompanied by reduced density of the centriolar satellites, with re-expression of C-NAP1 rescuing both these phenotypes...
January 18, 2017: Molecular Biology of the Cell
https://www.readbyqxmd.com/read/28100240/reactivation-of-dormant-anti-tumor-immunity-a-clinical-perspective-of-therapeutic-immune-checkpoint-modulation
#5
REVIEW
Richard Greil, Evelyn Hutterer, Tanja Nicole Hartmann, Lisa Pleyer
In favor of their outgrowth, cancer cells must resist immune surveillance and edit the immune response. Cancer immunoediting is characterized by fundamental changes in the cellular composition and the inflammatory cytokine profiles in the microenvironment of the primary tumor and metastatic niches, with an ever increasing complexity of interactions between tumor cells and the immune system. Recent data suggest that genetic instability and immunoediting are not necessarily disparate processes. Increasing mutational load may be associated with multiple neoepitopes expressed by the tumor cells and thus increased chances for the immune system to recognize and combat these cells...
January 19, 2017: Cell Communication and Signaling: CCS
https://www.readbyqxmd.com/read/28100080/the-commercialization-of-genome-editing-technologies
#6
Katelyn Brinegar, Ali K Yetisen, Sun Choi, Emily Vallillo, Guillermo U Ruiz-Esparza, Anand M Prabhakar, Ali Khademhosseini, Seok-Hyun Yun
The emergence of new gene-editing technologies is profoundly transforming human therapeutics, agriculture, and industrial biotechnology. Advances in clustered regularly interspaced short palindromic repeats (CRISPR) have created a fertile environment for mass-scale manufacturing of cost-effective products ranging from basic research to translational medicine. In our analyses, we evaluated the patent landscape of gene-editing technologies and found that in comparison to earlier gene-editing techniques, CRISPR has gained significant traction and this has established dominance...
January 18, 2017: Critical Reviews in Biotechnology
https://www.readbyqxmd.com/read/28099519/crispr-cas9-mediated-nox4-knockout-inhibits-cell-proliferation-and-invasion-in-hela-cells
#7
Naser Jafari, Hyunju Kim, Rackhyun Park, Liqing Li, Minsu Jang, Andrew J Morris, Junsoo Park, Cai Huang
Increased expression of NOX4 protein is associated with cancer progression and metastasis but the role of NOX4 in cell proliferation and invasion is not fully understood. We generated NOX4 knockout HeLa cell lines using the CRISPR-Cas9 gene editing system to explore the cellular functions of NOX4. After transfection of CRISPR-Cas9 construct, we performed T7 endonuclease 1 assays and DNA sequencing to generate and identify insertion and deletion of the NOX4 locus. We confirmed the knockout of NOX4 by Western blotting...
2017: PloS One
https://www.readbyqxmd.com/read/28096358/repair-shielding-of-platinum-dna-lesions-in-testicular-germ-cell-tumors-by-high-mobility-group-box-protein-4-imparts-cisplatin-hypersensitivity
#8
Samuel G Awuah, Imogen A Riddell, Stephen J Lippard
Cisplatin is the most commonly used anticancer drug for the treatment of testicular germ cell tumors (TGCTs). The hypersensitivity of TGCTs to cisplatin is a subject of widespread interest. Here, we show that high-mobility group box protein 4 (HMGB4), a protein preferentially expressed in testes, uniquely blocks excision repair of cisplatin-DNA adducts, 1,2-intrastrand cross-links, to potentiate the sensitivity of TGCTs to cisplatin therapy. We used CRISPR/Cas9-mediated gene editing to knockout the HMGB4 gene in a testicular human embryonic carcinoma and examined cellular responses...
January 17, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28096221/efficient-crispr-cas9-assisted-gene-targeting-enables-rapid-and-precise-genetic-manipulation-of-mammalian-neural-stem-cells
#9
Raul Bardini Bressan, Pooran Singh Dewari, Maria Kalantzaki, Ester Gangoso, Mantas Matjusaitis, Claudia Garcia-Diaz, Carla Blin, Vivien Grant, Harry Bulstrode, Sabine Gogolok, William C Skarnes, Steven M Pollard
Mammalian neural stem (NS) cell lines provide a tractable model for discovery across stem cell and developmental biology, regenerative medicine and neuroscience. They can be derived from foetal or adult germinal tissues and continuously propagated in vitro as adherent monolayers. NS cells are clonally expandable, genetically stable, and easily transfectable - experimental attributes compatible with targeted genetic manipulations. However, gene targeting - so critical for functional studies of embryonic stem cells - has not been exploited to date in NS cells...
January 17, 2017: Development
https://www.readbyqxmd.com/read/28095751/crispr-based-epigenome-editing-of-cytokine-receptors-for-the-promotion-of-cell-survival-and-tissue-deposition-in-inflammatory-environments
#10
Niloofar Farhang, Jonathan M Brunger, Joshua D Stover, Pratiksha I Thakore, Brandon Lawrence, Farshid Guilak, Charles A Gersbach, Lori A Setton, Robert D Bowles
Musculoskeletal diseases have been associated with inflammatory cytokine action, particularly action by TNF-α and IL-1β. These inflammatory cytokines promote apoptosis and senescence of cells in diseased tissue and extracellular matrix breakdown. Stem cell-based therapies are being considered for the treatment of musculoskeletal diseases, but the presence of these inflammatory cytokines will have similar deleterious action on therapeutic cells delivered to these environments. Methods that prevent inflammatory-induced apoptosis and pro-inflammatory signaling, in cell and pathway specific manners are needed...
January 17, 2017: Tissue Engineering. Part A
https://www.readbyqxmd.com/read/28094982/bacterial-genome-editing-via-a-designed-toxin-antitoxin-cassette
#11
Jie Wu, Aihua Deng, Qinyun Sun, Hua Bai, Zhaopeng Sun, Xiuling Shang, Yun Zhang, Qian Liu, Yong Liang, Shuwen Liu, Yongsheng Che, Tingyi Wen
Manipulating the bacterial genomes in an efficient manner is essential to biological and biotechnological research. Despite usage of various modules for genomic editing with counter-selectable markers including the toxin genes, an easy-to-use and highly designable toxin-antitoxin (TA) cassette without causing any leakages is urgently needed for efficient genome editing of the Gram-positive bacteria. Here, we reprogramed the bacterial TA systems as a toxin counter-selectable cassette regulated by an antitoxin switch (TCCRAS) for genetic modifications in the extensively studied and utilized Gram-positive bacteria, B...
January 17, 2017: ACS Synthetic Biology
https://www.readbyqxmd.com/read/28094775/nanotechnologies-in-delivery-of-mrna-therapeutics-using-nonviral-vector-based-delivery-systems
#12
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/28093068/potential-of-gene-drives-with-genome-editing-to-increase-genetic-gain-in-livestock-breeding-programs
#13
Serap Gonen, Janez Jenko, Gregor Gorjanc, Alan J Mileham, C Bruce A Whitelaw, John M Hickey
BACKGROUND: This paper uses simulation to explore how gene drives can increase genetic gain in livestock breeding programs. Gene drives are naturally occurring phenomena that cause a mutation on one chromosome to copy itself onto its homologous chromosome. METHODS: We simulated nine different breeding and editing scenarios with a common overall structure. Each scenario began with 21 generations of selection, followed by 20 generations of selection based on true breeding values where the breeder used selection alone, selection in combination with genome editing, or selection with genome editing and gene drives...
January 4, 2017: Genetics, Selection, Evolution: GSE
https://www.readbyqxmd.com/read/28089161/genome-wide-gene-expression-patterns-in-dikaryon-of-the-basidiomycete-fungus-pleurotus-ostreatus
#14
Tianxiang Liu, Huiru Li, Yatong Ding, Yuancheng Qi, Yuqian Gao, Andong Song, Jinwen Shen, Liyou Qiu
Dikarya is a subkingdom of fungi that includes Ascomycota and Basidiomycota. The gene expression patterns of dikaryon are poorly understood. In this study, we bred a dikaryon DK13×3 by mating monokaryons MK13 and MK3, which were from the basidiospores of Pleurotus ostreatus TD300. Using RNA-Seq, we obtained the transcriptomes of the three strains. We found that the total transcript numbers in the transcriptomes of the three strains were all more than ten thousand, and the expression profile in DK13×3 was more similar to MK13 than MK3...
January 3, 2017: Brazilian Journal of Microbiology: [publication of the Brazilian Society for Microbiology]
https://www.readbyqxmd.com/read/28088010/challenges-and-opportunities-for-improving-food-quality-and-nutrition-through-plant-biotechnology
#15
REVIEW
David Francis, John J Finer, Erich Grotewold
Plant biotechnology has been around since the advent of humankind, resulting in tremendous improvements in plant cultivation through crop domestication, breeding and selection. The emergence of transgenic approaches involving the introduction of defined DNA sequences into plants by humans has rapidly changed the surface of our planet by further expanding the gene pool used by plant breeders for plant improvement. Transgenic approaches in food plants have raised concerns on the merits, social implications, ecological risks and true benefits of plant biotechnology...
January 11, 2017: Current Opinion in Biotechnology
https://www.readbyqxmd.com/read/28087895/crohn-disease-risk-prediction-best-practices-and-pitfalls-with-exome-data
#16
Manuel Giollo, David T Jones, Marco Carraro, Emanuela Leonardi, Carlo Ferrari, Silvio C E Tosatto
The Critical Assessment of Genome Interpretation (CAGI) experiment is the first attempt to evaluate the state-of-the-art in genetic data interpretation. Among the proposed challenges, Crohn disease (CD) risk prediction has become the most classic problem spanning three editions. The scientific question is very hard: can anybody assess the risk to develop CD given the exome data alone? This is one of the ultimate goals of genetic analysis, which motivated most CAGI participants to look for powerful new methods...
January 13, 2017: Human Mutation
https://www.readbyqxmd.com/read/28087666/dysregulation-of-b-cell-repertoire-formation-in-myasthenia-gravis-patients-revealed-through-deep-sequencing
#17
Jason A Vander Heiden, Panos Stathopoulos, Julian Q Zhou, Luan Chen, Tamara J Gilbert, Christopher R Bolen, Richard J Barohn, Mazen M Dimachkie, Emma Ciafaloni, Teresa J Broering, Francois Vigneault, Richard J Nowak, Steven H Kleinstein, Kevin C O'Connor
Myasthenia gravis (MG) is a prototypical B cell-mediated autoimmune disease affecting 20-50 people per 100,000. The majority of patients fall into two clinically distinguishable types based on whether they produce autoantibodies targeting the acetylcholine receptor (AChR-MG) or muscle specific kinase (MuSK-MG). The autoantibodies are pathogenic, but whether their generation is associated with broader defects in the B cell repertoire is unknown. To address this question, we performed deep sequencing of the BCR repertoire of AChR-MG, MuSK-MG, and healthy subjects to generate ∼518,000 unique VH and VL sequences from sorted naive and memory B cell populations...
January 13, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28087399/advances-with-using-crispr-cas-mediated-gene-editing-to-treat-infections-with-hepatitis-b-virus-and-hepatitis-c-virus
#18
REVIEW
Buhle Moyo, Kristie Bloom, Tristan Scott, Abdullah Ely, Patrick Arbuthnot
Chronic infections with hepatitis B and hepatitis C viruses (HBV and HCV) account for the majority of cases of cirrhosis and hepatocellular carcinoma. Current therapies for the infections have limitations and improved efficacy is necessary to prevent complications in carriers of the viruses. In the case of HBV persistence, the replication intermediate comprising covalently closed circular DNA (cccDNA) is particularly problematic. Licensed therapies have little effect on cccDNA and HBV replication relapses following treatment withdrawal...
January 10, 2017: Virus Research
https://www.readbyqxmd.com/read/28087249/nick-initiated-homologous-recombination-protecting-the-genome-one-strand-at-a-time
#19
REVIEW
Lianne E M Vriend, Przemek M Krawczyk
Homologous recombination (HR) is an essential, widely conserved mechanism that utilizes a template for accurate repair of DNA breaks. Some early HR models, developed over five decades ago, anticipated single-strand breaks (nicks) as initiating lesions. Subsequent studies favored a more double-strand break (DSB)-centered view of HR initiation and at present this pathway is primarily considered to be associated with DSB repair. However, mounting evidence suggests that nicks can indeed initiate HR directly, without first being converted to DSBs...
December 29, 2016: DNA Repair
https://www.readbyqxmd.com/read/28080208/a-research-program-for-the-socioeconomic-impacts-of-gene-editing-regulation
#20
Agustina I Whelan, Martin A Lema
Gene editing technologies are a group of recent innovations in plant breeding using molecular biology, which have in common the capability of introducing a site-directed mutation or deletion in the genome. The first cases of crops improved with these technologies are approaching the market; this has raised an international debate regarding if they should be regulated as genetically modified crops or just as another form of mutagenesis under conventional breeding. This dilemma for policymakers not only entails issues pertaining safety information and legal/regulatory definitions...
January 12, 2017: GM Crops & Food
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