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https://www.readbyqxmd.com/read/28550310/a-to-i-editing-in-human-mirnas-is-enriched-in-seed-sequence-influenced-by-sequence-contexts-and-significantly-hypoedited-in-glioblastoma-multiforme
#1
Deepanjan Paul, Ashis Narayan Sinha, Arjun Ray, Megha Lal, Subhashree Nayak, Anchal Sharma, Bharati Mehani, Debasish Mukherjee, Saurabh V Laddha, Ashish Suri, Chitra Sarkar, Arijit Mukhopadhyay
Editing in microRNAs, particularly in seed can significantly alter the choice of their target genes. We show that out of 13 different human tissues, different regions of brain showed higher adenosine to inosine (A-to-I) editing in mature miRNAs. These events were enriched in seed sequence (73.33%), which was not observed for cytosine to uracil (17.86%) editing. More than half of the edited miRNAs showed increased stability, 72.7% of which had ΔΔG values less than -6.0 Kcal/mole and for all of them the edited adenosines mis-paired with cytosines on the pre-miRNA structure...
May 26, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28549865/application-of-crispr-cas9-to-the-study-of-brain-development-and-neuropsychiatric-disease
#2
REVIEW
S K Powell, J Gregory, S Akbarian, K J Brennand
CRISPR/Cas9 technology has transformed our abilities to manipulate the genome and epigenome, as applications have expanded from efficient genomic editing to include the targeted localization of effectors to specific genomic loci. By facilitating the manipulation of DNA- and histone-modifying enzyme activities, activation or repression of gene expression, and targeting of transcriptional regulators to defined loci, it is now possible to directly probe the role of gene-regulatory and epigenetic pathways in order to examine their roles in basic biology and disease processes...
May 23, 2017: Molecular and Cellular Neurosciences
https://www.readbyqxmd.com/read/28549203/polymorphisms-in-the-melatonin-receptor-gene-promoter-and-their-associations-with-fertility-characteristics-in-buffalo-herd-in-eastern-amazon
#3
E M Barbosa, B B Souza, R C Guimarães, L K N Silva, J S N Azevedo, E C Gonçalves, H F L Ribeiro, S T Rolim Filho, E Silva Filho
Buffalo production is spreading globally because of its economic advantage. Then, it has become necessary to improve the reproductive and productive efficiency of these animals, as well as to look for genetic factors that increase this efficiency. The objectives of this study were to characterize the promoter region of the melatonin 1A receptor gene (MTRN1A), to detect possible SNPs and associate them with fertility characteristics, and identify binding sites of transcription factors involved in the regulation of genetic expression in buffaloes in the Amazon...
May 25, 2017: Genetics and Molecular Research: GMR
https://www.readbyqxmd.com/read/28545148/mitochondrial-genome-evolution-in-alismatales-size-reduction-and-extensive-loss-of-ribosomal-protein-genes
#4
Gitte Petersen, Argelia Cuenca, Athanasios Zervas, Gregory T Ross, Sean W Graham, Craig F Barrett, Jerrold I Davis, Ole Seberg
The order Alismatales is a hotspot for evolution of plant mitochondrial genomes characterized by remarkable differences in genome size, substitution rates, RNA editing, retrotranscription, gene loss and intron loss. Here we have sequenced the complete mitogenomes of Zostera marina and Stratiotes aloides, which together with previously sequenced mitogenomes from Butomus and Spirodela, provide new evolutionary evidence of genome size reduction, gene loss and transfer to the nucleus. The Zostera mitogenome includes a large portion of DNA transferred from the plastome, yet it is the smallest known mitogenome from a non-parasitic plant...
2017: PloS One
https://www.readbyqxmd.com/read/28543738/crispr-editing-in-biological-and-biomedical-investigation
#5
Xing-Da Ju, Jing Xu, Zhong Sheng Sun
The CRISPR (clustered regularly interspaced short palindromic repeat)-Cas (CRISPR--associated protein) system, a prokaryotic RNA-based adaptive immune system against viral infection, is emerging as a powerful genome editing tool in broad research areas. To further improve and expand its functionality, various CRISPR delivery strategies have been tested and optimized, and key CRISPR system components such as Cas protein have been engineered with different purposes. Benefiting from more in-depth understanding and further development of CRISPR, versatile CRISPR-based platforms for genome editing have been rapidly developed to advance investigations in biology and biomedicine...
May 20, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/28543417/toward-public-bioethics
#6
EDITORIAL
Gregory E Kaebnick
This issue of the Hastings Center Report (May-June 2017) features a couple of interesting takes on the governance challenges of emerging technologies. In an essay on the National Academies of Science, Engineering, and Medicine report published this February on human germ-line gene editing, Eric Juengst, a philosopher at the University of North Carolina, argues that the NASEM committee did not manage to rethink the rules. Juengst reaches what he calls an "eccentric conclusion": "The committee's 2017 consensus report has been widely interpreted as 'opening the door' to inheritable human genetic modification and holding a line against enhancement interventions...
May 2017: Hastings Center Report
https://www.readbyqxmd.com/read/28543411/crowdsourcing-the-moral-limits-of-human-gene-editing
#7
Eric T Juengst
In 2015, a flourish of "alarums and excursions" by the scientific community propelled CRISPR/Cas9 and other new gene-editing techniques into public attention. At issue were two kinds of potential gene-editing experiments in humans: those making inheritable germ-line modifications and those designed to enhance human traits beyond what is necessary for health and healing. The scientific consensus seemed to be that while research to develop safe and effective human gene editing should continue, society's moral uncertainties about these two kinds of experiments needed to be better resolved before clinical trials of either type should be attempted...
May 2017: Hastings Center Report
https://www.readbyqxmd.com/read/28542349/crispr-cas9-mediated-targeted-mutagenesis-in-grape
#8
Ikuko Nakajima, Yusuke Ban, Akifumi Azuma, Noriyuki Onoue, Takaya Moriguchi, Toshiya Yamamoto, Seiichi Toki, Masaki Endo
RNA-guided genome editing using the CRISPR/Cas9 CRISPR (clustered regularly interspaced short palindromic repeats)/Cas9 (CRISPR-associated protein 9) system has been applied successfully in several plant species. However, to date, there are few reports on the use of any of the current genome editing approaches in grape-an important fruit crop with a large market not only for table grapes but also for wine. Here, we report successful targeted mutagenesis in grape (Vitis vinifera L., cv. Neo Muscat) using the CRISPR/Cas9 system...
2017: PloS One
https://www.readbyqxmd.com/read/28542197/deep-rna-sequencing-reveals-the-smallest-known-mitochondrial-micro-exon-in-animals-the-placozoan-cox1-single-base-pair-exon
#9
Hans-Jürgen Osigus, Michael Eitel, Bernd Schierwater
The phylum Placozoa holds a key position for our understanding of the evolution of mitochondrial genomes in Metazoa. Placozoans possess large mitochondrial genomes which harbor several remarkable characteristics such as a fragmented cox1 gene and trans-splicing cox1 introns. A previous study also suggested the existence of cox1 mRNA editing in Trichoplax adhaerens, yet the only formally described species in the phylum Placozoa. We have analyzed RNA-seq data of the undescribed sister species, Placozoa sp. H2 ("Panama" clone), with special focus on the mitochondrial mRNA...
2017: PloS One
https://www.readbyqxmd.com/read/28542170/human-mutations-in-integrator-complex-subunits-link-transcriptome-integrity-to-brain-development
#10
Renske Oegema, David Baillat, Rachel Schot, Leontine M van Unen, Alice Brooks, Sima Kheradmand Kia, A Jeannette M Hoogeboom, Zheng Xia, Wei Li, Matteo Cesaroni, Maarten H Lequin, Marjon van Slegtenhorst, William B Dobyns, Irenaeus F M de Coo, Frans W Verheijen, Andreas Kremer, Peter J van der Spek, Daphne Heijsman, Eric J Wagner, Maarten Fornerod, Grazia M S Mancini
Integrator is an RNA polymerase II (RNAPII)-associated complex that was recently identified to have a broad role in both RNA processing and transcription regulation. Importantly, its role in human development and disease is so far largely unexplored. Here, we provide evidence that biallelic Integrator Complex Subunit 1 (INTS1) and Subunit 8 (INTS8) gene mutations are associated with rare recessive human neurodevelopmental syndromes. Three unrelated individuals of Dutch ancestry showed the same homozygous truncating INTS1 mutation...
May 25, 2017: PLoS Genetics
https://www.readbyqxmd.com/read/28542129/adar1-mediated-3-utr-editing-and-expression-control-of-antiapoptosis-genes-fine-tunes-cellular-apoptosis-response
#11
Chang-Ching Yang, Yi-Tung Chen, Yi-Feng Chang, Hsuan Liu, Yu-Ping Kuo, Chieh-Tien Shih, Wei-Chao Liao, Hui-Wen Chen, Wen-Sy Tsai, Bertrand Chin-Ming Tan
Adenosine-to-inosine RNA editing constitutes a crucial component of the cellular transcriptome and critically underpins organism survival and development. While recent high-throughput approaches have provided comprehensive documentation of the RNA editome, its functional output remains mostly unresolved, particularly for events in the non-coding regions. Gene ontology analysis of the known RNA editing targets unveiled a preponderance of genes related to apoptosis regulation, among which proto-oncogenes XIAP and MDM2 encode two the most abundantly edited transcripts...
May 25, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28541477/mitochondrial-retroprocessing-promoted-functional-transfers-of-rpl5-to-the-nucleus-in-grasses
#12
Zhiqiang Wu, Daniel B Sloan, Colin W Brown, Mónica Rosenblueth, Jeffrey D Palmer, Han Chuan Ong
Functional gene transfers from the mitochondrion to the nucleus are ongoing in angiosperms and have occurred repeatedly for all 15 ribosomal protein genes, but it is not clear why some of these genes are transferred more often than others nor what the balance is between DNA- and RNA-mediated transfers. Although direct insertion of mitochondrial DNA into the nucleus occurs frequently in angiosperms, case studies of functional mitochondrial gene transfer have implicated an RNA-mediated mechanism that eliminates introns and RNA editing sites, which would otherwise impede proper expression of mitochondrial genes in the nucleus...
May 25, 2017: Molecular Biology and Evolution
https://www.readbyqxmd.com/read/28540737/investigational-drugs-in-phase-i-and-phase-ii-clinical-trials-for-thalassemia
#13
Irene Motta, Natalia Scaramellini, Maria Domenica Cappellini
Regular transfusion and iron chelation are the current treatment of severe forms of thalassemia. As a result of this demanding supportive treatment, there are several unmet therapeutic needs. Due to a deeper understanding in the pathophysiology of thalassemia, new therapeutic strategies have been developed that are now in pre-clinical and clinical trials. Areas covered: Activin receptor ligand traps (luspatercept and sotatercept), drugs targeting ineffective erythropoiesis, showed encouraging results in Phase I and II clinical trials...
May 25, 2017: Expert Opinion on Investigational Drugs
https://www.readbyqxmd.com/read/28540674/microrna-expression-protein-participants-in-microrna-regulation
#14
Valeria M King, Glen M Borchert
MiRNAs are ~20 nt small RNAs that regulate networks of proteins using a seed region of nucleotides 2-8 to complement the 3' UTR of target mRNAs. The biogenesis and function of miRNAs as translational repressors is facilitated by protein counterparts that process primary and precursor miRNAs to maturity (Drosha/DCGR8 and Dicer/TRBP respectively) and incorporate miRNAs into the protein complex RISC to recognize and repress target mRNAs (RISC proteins: Ago/TRBP1/TRBP2/DICER). Similarly, siRNAs through comparable mechanisms are loaded into the protein complex RITS to heterochromatin formation of DNA and suppress transcription of particular genes...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28539325/cd7-edited-t-cells-expressing-a-cd7-specific-car-for-the-therapy-of-t-cell-malignancies
#15
Diogo Gomes-Silva, Madhuwanti Srinivasan, Sandhya Sharma, Ciaran M Lee, Timothy H Davis, Rayne H Rouce, Gang Bao, Malcolm K Brenner, Maksim Mamonkin
Extending the success of CAR T cells to T-cell malignancies is problematic since most target antigens are shared between normal and malignant cells, leading to CAR T cell fratricide. CD7 is a transmembrane protein highly expressed in acute T cell leukemia (T-ALL) and in a subset of peripheral T-cell lymphomas. Normal expression of CD7 is largely confined to T- and NK cells reducing the risk of off-target-organ toxicity. Here, we show that the expression of a CD7-specific CAR impaired expansion of transduced T cells due to residual CD7 expression and the ensuing fratricide...
May 24, 2017: Blood
https://www.readbyqxmd.com/read/28538159/long-term-stochastic-editing-of-regenerative-anatomy-via-targeting-endogenous-bioelectric-gradients
#16
Fallon Durant, Junji Morokuma, Christopher Fields, Katherine Williams, Dany Spencer Adams, Michael Levin
We show that regenerating planarians' normal anterior-posterior pattern can be permanently rewritten by a brief perturbation of endogenous bioelectrical networks. Temporary modulation of regenerative bioelectric dynamics in amputated trunk fragments of planaria stochastically results in a constant ratio of regenerates with two heads to regenerates with normal morphology. Remarkably, this is shown to be due not to partial penetrance of treatment, but a profound yet hidden alteration to the animals' patterning circuitry...
May 23, 2017: Biophysical Journal
https://www.readbyqxmd.com/read/28537929/orphan-nuclear-receptor-nur77-inhibits-poly-i-c-triggered-acute-liver-inflammation-by-inducing-the-ubiquitin-editing-enzyme-a20
#17
Xiu-Ming Li, Tian-Yu Yang, Xiao-Shun He, Jing-Ru Wang, Wen-Juan Gan, Shen Zhang, Jian-Ming Li, Hua Wu
Inflammation is a key contributor to various types of acute and chronic liver disease. We recently reported that lack of Nur77, an orphan nuclear receptor, contributes to the pathogenesis of inflammatory diseases including inflammatory bowel disease and sepsis. However, whether Nur77 plays a critical role in liver inflammation remains to be fully understood. Employing in vivo acute liver inflammation model in wild-type (Nur77+/+) and Nur77-/- mice, we here found that Nur77 deficiency dramatically increased the production of pro-inflammatory cytokines and accelerated liver injury induced by Poly (I:C)/D-GalN in Nur77-/- mice...
May 9, 2017: Oncotarget
https://www.readbyqxmd.com/read/28536097/dynamic-regulation-of-vegf-inducible-genes-by-an-erk-erg-p300-transcriptional-network
#18
Jason E Fish, Manuel Cantu Gutierrez, Lan T Dang, Nadiya Khyzha, Zhiqi Chen, Shawn Veitch, Henry S Cheng, Melvin Khor, Lina Antounians, Makon-Sébastien Njock, Emilie Boudreau, Alexander M Herman, Alexander M Rhyner, Oscar E Ruiz, George T Eisenhoffer, Alejandra Medina-Rivera, Michael D Wilson, Joshua D Wythe
The transcriptional pathways activated downstream of Vascular Endothelial Growth Factor (VEGF) signaling during angiogenesis remain incompletely characterized. By assessing the signals responsible for induction of the Notch ligand, Delta-Like 4 (DLL4) in endothelial cells we find that activation of the MAPK/ERK pathway mirrors the rapid and dynamic induction of DLL4 transcription and that this pathway is required for DLL4 expression. Furthermore, VEGF/ERK signaling induces phosphorylation and activation of the ETS transcription factor ERG, a prerequisite for DLL4 induction...
May 23, 2017: Development
https://www.readbyqxmd.com/read/28536069/crispr-engineered-genome-editing-for-the-next-generation-neurological-disease-modeling
#19
REVIEW
Weijun Feng, Hai-Kun Liu, Daisuke Kawauchi
Neurological disorders often occur because of failure of proper brain development and/or appropriate maintenance of neuronal circuits. In order to understand roles of causative factors (e.g. genes, cell types) in disease development, generation of solid animal models has been one of straight-forward approaches. Recent next generation sequencing studies on human patient-derived clinical samples have identified various types of recurrent mutations in individual neurological diseases. While these discoveries have prompted us to evaluate contribution of mutated genes to these neurological diseases, a feasible but flexible genome editing tool had remained to be developed...
May 20, 2017: Progress in Neuro-psychopharmacology & Biological Psychiatry
https://www.readbyqxmd.com/read/28535794/mutation-site-and-context-dependent-effects-of-esr1-mutation-in-genome-edited-breast-cancer-cell-models
#20
Amir Bahreini, Zheqi Li, Peilu Wang, Kevin M Levine, Nilgun Tasdemir, Lan Cao, Hazel M Weir, Shannon L Puhalla, Nancy E Davidson, Andrew M Stern, David Chu, Ben Ho Park, Adrian V Lee, Steffi Oesterreich
BACKGROUND: Mutations in the estrogen receptor alpha (ERα) 1 gene (ESR1) are frequently detected in ER+ metastatic breast cancer, and there is increasing evidence that these mutations confer endocrine resistance in breast cancer patients with advanced disease. However, their functional role is not well-understood, at least in part due to a lack of ESR1 mutant models. Here, we describe the generation and characterization of genome-edited T47D and MCF7 breast cancer cell lines with the two most common ESR1 mutations, Y537S and D538G...
May 23, 2017: Breast Cancer Research: BCR
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