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https://www.readbyqxmd.com/read/29040995/role-of-immune-checkpoint-blockade-in-the-treatment-for-human-hepatocellular-carcinoma
#1
Naoshi Nishida, Masatoshi Kudo
With the development of molecular targeting therapy, several treatment options for advanced hepatocellular carcinoma (HCC) have become available in cases where curative and other palliative treatments, such as radiofrequency ablation, surgical resection, and transarterial chemoembolization, are not applicable. However, with the detection of a variety of mutations in cancer-related genes in a single tumor, molecular heterogeneity is commonly observed in HCC. Therefore, mutations in the major cellular signaling pathways underlie the development of resistance to molecular targeting agents...
2017: Digestive Diseases
https://www.readbyqxmd.com/read/29040977/gene-microarray-integrated-with-high-throughput-proteomics-for-the-discovery-of-transthyretin-in-rhabdomyolysis-induced-acute-kidney-injury
#2
Ou Li, Xiaodong Geng, Qian Ma, Weiwei Wang, Ran Liu, Zhong Yin, Siyang Wang, Guangyan Cai, Xiangmei Chen, Quan Hong
BACKGROUND/AIMS: Rhabdomyolysis, one of the leading causes of acute kidney injury (AKI), develops after trauma, drug toxicity, infections, burns, and physical exertion. The aim of this study was to investigate differences in gene and protein expression to elucidate the pathogenesis of rhabdomyolysis (RM)-induced AKI. METHODS: In this study, we used glycerol induced renal injury as a model of RM-induced AKI. Affymetrix U133 plus 2.0 microarrays were used to perform gene microarray analysis...
October 18, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/29040870/parkin-absence-accelerates-microtubule-aging-in-dopaminergic-neurons
#3
Daniele Cartelli, Alida Amadeo, Alessandra Maria Calogero, Francesca Vittoria Marialuisa Casagrande, Carmelita De Gregorio, Mariarosa Gioria, Naoko Kuzumaki, Ilaria Costa, Jenny Sassone, Andrea Ciammola, Nobutaka Hattori, Hideyuki Okano, Stefano Goldwurm, Laurent Roybon, Gianni Pezzoli, Graziella Cappelletti
Loss-of-function caused by mutations in the parkin gene (PARK2) lead to early-onset familial Parkinson's disease. Recently, mechanistic studies proved the ability of parkin in regulating mitochondria homeostasis and microtubule (MT) stability. Looking at these systems during aging of PARK2 knockout mice, we found that loss of parkin induced an accelerated (over)acetylation of MT system both in dopaminergic neuron cell bodies and fibers, localized in the substantia nigra and corpus striatum, respectively. Interestingly, in PARK2 knockout mice, changes of MT stability preceded the alteration of mitochondria transport...
September 20, 2017: Neurobiology of Aging
https://www.readbyqxmd.com/read/29040859/the-fks-family-genes-cause-changes-in-cell-wall-morphology-resulted-in-regulation-of-anti-autolytic-ability-in-saccharomyces-cerevisiae
#4
Jinjing Wang, Jiangchuan Mao, Ge Yang, Feiyun Zheng, Chengtuo Niu, Yongxian Li, Chunfeng Liu, Qi Li
The aim of this study was to discuss the functions of FKS family genes which encode β-1, 3-glucan synthase regarding the viability and autolysis of yeast strain. Loss of FKS1 gene severely influences the viability and anti-autolytic ability of yeast. Mutation of FKS1 and FKS2 genes led to cell reconstruction, resulting in a sharp shrinkage of cell volume and decreased stress resistance, viability, and anti-autolytic ability. Deletion of FKS3 gene did not clearly influence the synthesis of β-1, 3-glucan of yeast but increased the strain's stress resistance, viability, and anti-autolytic ability...
September 21, 2017: Bioresource Technology
https://www.readbyqxmd.com/read/29040803/synthesis-and-characterization-of-fatty-acid-grafted-chitosan-polymer-and-their-nanomicelles-for-non-viral-gene-delivery-applications
#5
Divya Sharma, Jagdish Singh
The aim of this study was to synthesize and characterize fatty acid-grafted-chitosan (fatty acid-g-CS) polymer and their nanomicelles for using as carriers for gene delivery. CS was hydrophobically modified using saturated fatty acids of increasing fatty acyl chain length. Carbodiimide along with N-hydroxysuccinimide was used for coupling carboxyl group of fatty acids with amine groups of CS. Proton nuclear magnetic resonance and Fourier transform-infrared spectroscopy were used to quantify fatty acyl substitution onto CS backbone...
October 17, 2017: Bioconjugate Chemistry
https://www.readbyqxmd.com/read/29040791/roles-of-mmu_pir_003399-in-microcystin-leucine-arginine-mc-lr-induced-reproductive-toxicity-in-the-spermatogonial-cells-and-testis
#6
Ling Zhang, Xiannan Meng, Zou Xiang, Dongmei Li, Xiaodong Han
Our previous work has demonstrated that microcystin-leucine arginine (MC-LR) is a potent toxin for the reproductive system of male mice and it exerts cytotoxicity in spermatogonial cells, resulting in the constitutional and functional changes of the mouse testis. The present study was designed to investigate the functions of P-element-induced wimpy (piwi)-interacting RNAs (piRNAs) in MC-LR-induced reproductive toxicity in male mice. We observed an increase in the mmu_piR_003399 level in spermatogonial cells and mouse testicular tissues following treatment with MC-LR...
October 12, 2017: Toxicological Sciences: An Official Journal of the Society of Toxicology
https://www.readbyqxmd.com/read/29040785/engineering-a-temperature-sensitive-tobacco-etch-virus-protease
#7
J Wong, X Chen, K Truong
Since tobacco etch virus protease (TEVp) has a high specificity and efficiency in cleaving its target substrates, many groups have attempted to engineer conditional control of its activity. Temperature induction is widely used for modulating gene function because it has fast temporal response, good penetrability and applicability to many model organisms. Here, we engineered a temperature sensitive TEVp (tsTEVp) by using N-terminal truncations to TEVp that achieved efficient proteolysis on a timescale of 4 h after 30°C induction, while remaining relatively inactive at 37°C...
October 13, 2017: Protein Engineering, Design & Selection: PEDS
https://www.readbyqxmd.com/read/29040782/egfr-heterogeneity-and-implications-for-therapeutic-intervention-in-glioblastoma
#8
Eskil Eskilsson, Gro V Røsland, Gergely Solecki, Qianghu Wang, Patrick N Harter, Grazia Graziani, Roel G W Verhaak, Frank Winkler, Rolf Bjerkvig, Hrvoje Miletic
Patients with glioblastoma (GBM) have a universally poor prognosis and are in urgent need of effective treatment strategies. Recent advances in sequencing techniques unraveled the complete genomic landscape of GBMs and revealed profound heterogeneity of individual tumors even at the single cell level. Genomic profiling has detected epidermal growth factor receptor (EGFR) gene alterations in more than half of GBMs. Major genetic events include amplification and mutation of EGFR. Yet, treatment strategies targeting EGFR have thus far failed in clinical trials...
October 10, 2017: Neuro-oncology
https://www.readbyqxmd.com/read/29040774/assessing-the-between-background-stability-of-metabolic-effects-arising-from-lignin-related-transgenic-modifications-in-two-populus-hybrids-using-non-targeted-metabolomics
#9
Andrew R Robinson, Rebecca Dauwe, Shawn D Mansfield
The advances in 'high-throughput' biology have significantly expanded our fundamental understanding of complex biological processes inherent to tree growth and development. Relative to the significant achievements attained with whole genome re-sequencing and transcriptomics efforts, the development and power of post-transcriptional tools such as proteomics and metabolomics continue to lag behind in tree biology. However, the inclusion of these powerful functional genomics platforms should substantially enable systems biology assessments of tree development, physiology and response(s) to biotic and abiotic stresses...
October 10, 2017: Tree Physiology
https://www.readbyqxmd.com/read/29040729/csra-maximizes-expression-of-the-acrab-multidrug-resistance-transporter
#10
Vito Ricci, Victoria Attah, Tim Overton, David C Grainger, Laura J V Piddock
Carbon Storage Regulator A (CsrA) is an RNA binding protein that acts as a global regulator of diverse genes. Using a combination of genetics and biochemistry we show that CsrA binds directly to the 5' end of the transcript encoding AcrAB. Deletion of csrA or mutagenesis of the CsrA binding sites reduced production of both AcrA and AcrB. Nucleotide substitutions at the 5' UTR of acrA mRNA that could potentially weaken the inhibitory RNA secondary structure, allow for more efficient translation of the AcrAB proteins...
October 13, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/29040720/genome-wide-prediction-of-minor-groove-electrostatic-potential-enables-biophysical-modeling-of-protein-dna-binding
#11
Tsu-Pei Chiu, Satyanarayan Rao, Richard S Mann, Barry Honig, Remo Rohs
Protein-DNA binding is a fundamental component of gene regulatory processes, but it is still not completely understood how proteins recognize their target sites in the genome. Besides hydrogen bonding in the major groove (base readout), proteins recognize minor-groove geometry using positively charged amino acids (shape readout). The underlying mechanism of DNA shape readout involves the correlation between minor-groove width and electrostatic potential (EP). To probe this biophysical effect directly, rather than using minor-groove width as an indirect measure for shape readout, we developed a methodology, DNAphi, for predicting EP in the minor groove and confirmed the direct role of EP in protein-DNA binding using massive sequencing data...
October 11, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/29040713/human-argonaute3-has-slicer-activity
#12
Mi Seul Park, Hong-Duc Phan, Florian Busch, Samantha H Hinckley, James A Brackbill, Vicki H Wysocki, Kotaro Nakanishi
Of the four human Argonaute (AGO) paralogs, only AGO2 has been shown to have slicer activity. The others (AGO1, AGO3 and AGO4) have been thought to assemble with microRNAs to form slicer-independent effector complexes that bind target mRNAs and silence gene expression through translational repression and deadenylation but not cleavage. Here, we report that recombinant AGO3 loaded with miR-20a cleaves complementary target RNAs, whereas AGO3 loaded with let-7a, miR-19b or miR-16 does not, indicating that AGO3 has slicer activity but that this activity depends on the guide RNA...
October 11, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/29040675/fluctuation-localization-imaging-based-fluorescence-in-situ-hybridization-flifish-for-accurate-detection-and-counting-of-rna-copies-in-single-cells
#13
Yi Cui, Dehong Hu, Lye Meng Markillie, William B Chrisler, Matthew J Gaffrey, Charles Ansong, Lori Sussel, Galya Orr
Quantitative gene expression analysis in intact single cells can be achieved using single molecule-based fluorescence in situ hybridization (smFISH). This approach relies on fluorescence intensity to distinguish between true signals, emitted from an RNA copy hybridized with multiple oligonucleotide probes, and background noise. Thus, the precision in smFISH is often compromised by partial or nonspecific probe binding and tissue autofluorescence, especially when only a small number of probes can be fitted to the target transcript...
October 4, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/29040610/the-biological-impact-of-blood-pressure-associated-genetic-variants-in-the-natriuretic-peptide-receptor-c-gene-on-human-vascular-smooth-muscle
#14
Meixia Ren, Fu Liang Ng, Helen Warren, Kate Witkowska, Michael Baron, Zhilong Jia, Claudia Cabrera, Ruoxin Zhang, Borbala Mifsud, Patricia B Munroe, Qingzhong Xiao, Andrea Townsend-Nicholson, Adrian Hobbs, Shu Ye, Mark Caulfield
Elevated blood pressure (BP) is a major global risk factor for cardiovascular disease. Genome-wide association studies have identified several genetic variants at the NPR3 locus associated with BP, but the functional impact of these variants remains to be determined. Here we confirmed, by a genome-wide association study within UK Biobank, the existence of two independent BP-related signals within NPR3 locus. Using human primary vascular smooth muscle cells and endothelial cells from different individuals, we found that the BP-elevating alleles within one linkage disequilibrium block identified by the sentinel variant rs1173771 was associated with lower endogenous NPR3 mRNA and protein levels in vascular smooth muscle cells, together with reduced levels in open chromatin and nuclear protein binding...
October 10, 2017: Human Molecular Genetics
https://www.readbyqxmd.com/read/29040522/behavioral-and-transcriptomic-analysis-of-trem2-null-mice-not-all-knockout-mice-are-created-equal
#15
Silvia S Kang, Aishe Kurti, Kelsey E Baker, Chia-Chen Liu, Marco Colonna, Jason D Ulrich, David M Holtzman, Guojun Bu, John D Fryer
It is clear that innate immune system status is altered in numerous neurodegenerative diseases. Human genetic studies have demonstrated that Triggering Receptor Expressed in Myeloid cells 2 (TREM2) coding variants have a strong association with Alzheimer's disease (AD) and other neurodegenerative diseases. To more thoroughly understand the impact of TREM2 in vivo, we studied the behavioral and cognitive functions of wild-type (WT) and Trem2-/- (KO) mice during basal conditions and brain function in the context of innate immune stimulation with peripherally administered lipopolysaccharide (LPS)...
October 11, 2017: Human Molecular Genetics
https://www.readbyqxmd.com/read/29040422/pharmacogenetics-a-general-review-on-progress-to-date
#16
Ann K Daly
Background: Pharmacogenetics is not a new subject area but its relevance to drug prescribing has become clearer in recent years due to developments in gene cloning and DNA genotyping and sequencing. Sources of data: There is a very extensive published literature concerned with a variety of different genes and drugs. Areas of agreement: There is general agreement that pharmacogenetic testing is essential for the safe use of drugs such as the thiopurines and abacavir...
October 11, 2017: British Medical Bulletin
https://www.readbyqxmd.com/read/29040406/matam-reconstruction-of-phylogenetic-marker-genes-from-short-sequencing-reads-in-metagenomes
#17
Pierre Pericard, Yoann Dufresne, Loïc Couderc, Samuel Blanquart, Hélène Touzet
Motivation: Advances in the sequencing of uncultured environmental samples, dubbed metagenomics, raise a growing need for accurate taxonomic assignment. Accurate identification of organisms present within a community is essential to understanding even the most elementary ecosystems. However, current high-throughput sequencing technologies generate short reads which partially cover full-length marker genes and this poses difficult bioinformatic challenges for taxonomy identification at high resolution...
October 11, 2017: Bioinformatics
https://www.readbyqxmd.com/read/29040381/the-cug-translated-wt1-not-aug-wt1-is-an-oncogene
#18
Kun Yeong Lee, Young Jin Jeon, Hong Gyum Kim, Joohyun Ryu, Do Young Lim, Sung Keun Jung, Dong Hoon Yu, Hanyong Chen, Ann M Bode, Zigang Dong
The Wilms' tumor 1 (WT1) gene is believed to act as a canonical tumor suppressor. However, it has also been reported to function as an oncogene. Germline WT1 deletion is associated with Wilms' tumor and exogenous WT1 cDNA introduction into cells induces the transcriptional suppression of its oncogenic target genes. In contrast, high WT1 expression is associated with poor prognosis in patients with various cancers. Why WT1 acts as a tumor suppressor under certain conditions, but as an oncogene under other conditions is unknown...
October 10, 2017: Carcinogenesis
https://www.readbyqxmd.com/read/29040309/targeted-pth4-expressing-cell-ablation-impairs-skeletal-mineralization-in-zebrafish
#19
Paula Suarez-Bregua, Ankur Saxena, Marianne E Bronner, Josep Rotllant
Skeletal development and mineralization are essential processes driven by the coordinated action of neural signals, circulating molecules and local factors. Our previous studies revealed that the novel neuropeptide Pth4, synthesized by hypothalamic cells, was involved in bone metabolism via phosphate regulation in adult zebrafish. Here, we investigate the role of pth4 during skeletal development using single-cell resolution, two-photon laser ablation of Pth4:eGFP-expressing cells and confocal imaging in vivo...
2017: PloS One
https://www.readbyqxmd.com/read/29040258/prognostic-and-therapeutic-implications-of-dna-repair-gene-mutations-in-advanced-prostate-cancer
#20
Michael T Schweizer, Emmanuel S Antonarakis
Recent work directed toward understanding the molecular features of advanced prostate cancers has revealed a relatively high incidence of both germline and somatic alterations in genes involved in DNA damage repair (DDR). Many of these alterations likely play a critical role in the pathogenesis of more aggressive prostate cancers-leading to genomic instability and an increased probability of the development of lethal disease. However, because the ability to repair DNA damage with a high degree of fidelity is critical to an individual cell's survival, tumor cells harboring alterations in DDR pathway genes are also more susceptible to drugs that induce DNA damage or impair alternative DNA repair pathways...
October 2017: Clinical Advances in Hematology & Oncology: H&O
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