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https://www.readbyqxmd.com/read/28732364/a-novel-heterozygous-germline-deletion-in-msh2-gene-in-a-five-generation-chinese-family-with-lynch-syndrome
#1
Bin Wu, Wuyang Ji, Shengran Liang, Chao Ling, Yan You, Lai Xu, Min-Er Zhong, Yi Xiao, Hui-Zhong Qiu, Jun-Yang Lu, Santasree Banerjee
Lynch syndrome (LS) is one of the most common familial forms of colorectal cancer predisposing syndrome with an autosomal dominant mode of inheritance. LS is caused by the germline mutations in DNA mismatch repair (MMR) genes including MSH2, MLH1, MSH6and PMS2. Clinically, LS is characterized by high incidence of early-onset colorectal cancer as well as endometrial, small intestinal and urinary tract cancers, usually occur in the third to fourth decade of the life. Here we describe a five generation Chinese family with LS clinically diagnosed according to the Amsterdam II criteria...
July 14, 2017: Oncotarget
https://www.readbyqxmd.com/read/28732357/profiling-cancer-related-gene-mutations-in-oral-squamous-cell-carcinoma-from-japanese-patients-by-targeted-amplicon-sequencing
#2
Takafumi Nakagaki, Miyuki Tamura, Kenta Kobashi, Ryota Koyama, Hisayo Fukushima, Tomoko Ohashi, Masashi Idogawa, Kazuhiro Ogi, Hiroyoshi Hiratsuka, Takashi Tokino, Yasushi Sasaki
Somatic mutation analysis is a standard practice in the study of human cancers to identify mutations that cause therapeutic sensitization and resistance. We performed comprehensive genomic analyses that used PCR target enrichment and next-generation sequencing on Ion Proton semiconductor sequencers. Forty-seven oral squamous cell carcinoma (OSCC) samples and their corresponding noncancerous tissues were used for multiplex PCR amplification to obtain targeted coverage of the entire coding regions of 409 cancer-related genes (covered regions: 95...
July 15, 2017: Oncotarget
https://www.readbyqxmd.com/read/28732288/lncrna-hotair-alleviates-rheumatoid-arthritis-by-targeting-mir-138-and-inactivating-nf-%C3%AE%C2%BAb-pathway
#3
Hong-Ju Zhang, Qiao-Feng Wei, Shu-Jun Wang, Hong-Jie Zhang, Xiu-Ying Zhang, Qin Geng, Yan-Hui Cui, Xiu-Hua Wang
Rheumatoid arthritis (RA) is a chronic and autoimmune-mediated inflammatory disease. We aimed to investigate the regulation of lncRNA HOTAIR in LPS-treated chondrocytes and RA mouse. Our results showed that HOTAIR expression was significantly reduced in LPS-treated chondrocytes. The HOTAIR was then over-expressed in chondrocytes by transfecting recombinant lentivirus carrying sequences encoding HOTAIR. The LPS-induced reduction of cell proliferation rate and production of two inflammatory factors interleukin (IL)-17, IL-23 were markedly inhibited...
July 18, 2017: International Immunopharmacology
https://www.readbyqxmd.com/read/28732207/a-crispr-resource-for-individual-combinatorial-or-multiplexed-gene-knockout
#4
Nicolas Erard, Simon R V Knott, Gregory J Hannon
We have combined a machine-learning approach with other strategies to optimize knockout efficiency with the CRISPR/Cas9 system. In addition, we have developed a multiplexed sgRNA expression strategy that promotes the functional ablation of single genes and allows for combinatorial targeting. These strategies have been combined to design and construct a genome-wide, sequence-verified, arrayed CRISPR library. This resource allows single-target or combinatorial genetic screens to be carried out at scale in a multiplexed or arrayed format...
July 20, 2017: Molecular Cell
https://www.readbyqxmd.com/read/28732084/increased-parb-level-affects-expression-of-stress-response-adaptation-and-virulence-operons-and-potentiates-repression-of-promoters-adjacent-to-the-high-affinity-binding-sites-pars3-and-pars4-in-pseudomonas-aeruginosa
#5
Adam Kawalek, Krzysztof Glabski, Aneta Agnieszka Bartosik, Anna Fogtman, Grazyna Jagura-Burdzy
Similarly to its homologs in other bacteria, Pseudomonas aeruginosa partitioning protein ParB facilitates segregation of newly replicated chromosomes. Lack of ParB is not lethal but results in increased frequency of anucleate cells production, longer division time, cell elongation, altered colony morphology and defective swarming and swimming motility. Unlike in other bacteria, inactivation of parB leads to major changes of the transcriptome, suggesting that, directly or indirectly, ParB plays a role in regulation of gene expression in this organism...
2017: PloS One
https://www.readbyqxmd.com/read/28732007/a-data-driven-modeling-approach-to-identify-disease-specific-multi-organ-networks-driving-physiological-dysregulation
#6
Warren D Anderson, Danielle DeCicco, James S Schwaber, Rajanikanth Vadigepalli
Multiple physiological systems interact throughout the development of a complex disease. Knowledge of the dynamics and connectivity of interactions across physiological systems could facilitate the prevention or mitigation of organ damage underlying complex diseases, many of which are currently refractory to available therapeutics (e.g., hypertension). We studied the regulatory interactions operating within and across organs throughout disease development by integrating in vivo analysis of gene expression dynamics with a reverse engineering approach to infer data-driven dynamic network models of multi-organ gene regulatory influences...
July 2017: PLoS Computational Biology
https://www.readbyqxmd.com/read/28731899/current-perspectives-on-invasive-nontyphoidal-salmonella-disease
#7
Andrea H Haselbeck, Ursula Panzner, Justin Im, Stephen Baker, Christian G Meyer, Florian Marks
PURPOSE OF REVIEW: We searched PubMed for scientific literature published in the past 2 years for relevant information regarding the burden of invasive nontyphoidal Salmonella disease and host factors associated with nontyphoidal Salmonella infection and discuss current knowledge on vaccine development. The following search terms were used: Salmonella, non typhoidal/nontyphoidal, NTS, disease, bloodstream infection, invasive, sepsis/septicaemia/septicemia, bacteraemia/bacteremia, gastroenteritis, incidence, prevalence, morbidity, mortality, case fatality, host/risk factor, vaccination, and prevention/control...
July 20, 2017: Current Opinion in Infectious Diseases
https://www.readbyqxmd.com/read/28731788/identification-of-osr2-transcriptional-target-genes-in-palate-development
#8
X Fu, J Xu, P Chaturvedi, H Liu, R Jiang, Y Lan
Previous studies have identified the odd-skipped related 2 (Osr2) transcription factor as a key intrinsic regulator of palatal shelf growth and morphogenesis. However, little is known about the molecular program acting downstream of Osr2 in the regulation of palatogenesis. In this study, we isolated palatal mesenchyme cells from embryonic day 12.5 (E12.5) and E13.5 Osr2(RFP/+) and Osr2(RFP/-) mutant mouse embryos and performed whole transcriptome RNA sequencing analyses. Differential expression analysis of the RNA sequencing datasets revealed that expression of 70 genes was upregulated and expression of 61 genes was downregulated by >1...
July 1, 2017: Journal of Dental Research
https://www.readbyqxmd.com/read/28731615/the-prevalence-of-ccr5-%C3%AE-32-mutation-in-a-cohort-of-saudi-stem-cell-donors
#9
M Alarifi, F Al-Amro, A Alalwan, A Al-Turki, H Fakhoury, N Atallah, M Al Muallimi, M Al-Balwi, M ALzahrani, A Alaskar, A Hajeer, D Jawdat
CCR5 is a chemokine receptor that also was found to be used by HIV as a co-receptor for entering target cells. A 32 bp deletion was described in certain people that rendered CCR5 non-functional. The mutant allele CCR5-Δ32 has been shown to prevent HIV infection. In addition, stem cell transplantation with the CCR5-Δ32 homozygous genotype can lead to clearance of HIV infection. In this study, our aim was to investigate the frequency of CCR5-Δ32 mutation in a cohort of stem cell donors from cord blood bank and stem cell donor registry...
July 21, 2017: HLA
https://www.readbyqxmd.com/read/28731526/drug-discovery-and-development-for-rare-genetic-disorders
#10
REVIEW
Wei Sun, Wei Zheng, Anton Simeonov
Approximately 7,000 rare diseases affect millions of individuals in the United States. Although rare diseases taken together have an enormous impact, there is a significant gap between basic research and clinical interventions. Opportunities now exist to accelerate drug development for the treatment of rare diseases. Disease foundations and research centers worldwide focus on better understanding rare disorders. Here, the state-of-the-art drug discovery strategies for small molecules and biological approaches for orphan diseases are reviewed...
July 21, 2017: American Journal of Medical Genetics. Part A
https://www.readbyqxmd.com/read/28731468/a-role-for-the-cell-wall-protein-silacidin-in-cell-size-of-the-diatom-thalassiosira-pseudonana
#11
Amy R Kirkham, Patrick Richthammer, Katrin Schmidt, Martin Wustmann, Yoshiaki Maeda, René Hedrich, Eike Brunner, Tsuyoshi Tanaka, Karl-Heinz van Pée, Angela Falciatore, Thomas Mock
Diatoms contribute 20% of global primary production and form the basis of many marine food webs. Although their species diversity correlates with broad diversity in cell size, there is also an intraspecific cell-size plasticity owing to sexual reproduction and varying environmental conditions. However, despite the ecological significance of the diatom cell size for food-web structure and global biogeochemical cycles, our knowledge about genes underpinning the size of diatom cells remains elusive. Here, a combination of reverse genetics, experimental evolution and comparative RNA-sequencing analyses enabled us to identify a previously unknown genetic control of cell size in the diatom Thalassiosira pseudonana...
July 21, 2017: ISME Journal
https://www.readbyqxmd.com/read/28731405/pro-death-nmda-receptor-signaling-is-promoted-by-the-glun2b-c-terminus-independently-of-dapk1
#12
Jamie McQueen, Tomas J Ryan, Sean McKay, Katie Fm Marwick, Paul E Baxter, Sarah M Carpanini, Thomas M Wishart, Thomas H Gillingwater, Jean C Manson, David Ja Wyllie, Seth Gn Grant, Barry McColl, Noboru Komiyama, Giles E Hardingham
Aberrant NMDA receptor (NMDAR) activity contributes to several neurological disorders, but direct antagonism is poorly tolerated therapeutically. The GluN2B cytoplasmic C-terminal domain (CTD) represents an alternative therapeutic target since it potentiates excitotoxic signaling. The key GluN2B CTD-centred event in excitotoxicity is proposed to involve its phosphorylation at Ser-1303 by DAPK1, that is blocked by a neuroprotective cell-permeable peptide mimetic of the region. Contrary to this model, we find that excitotoxicity can proceed without increased Ser-1303 phosphorylation, and is unaffected by DAPK1 deficiency in vitro or following ischemia in vivo...
July 21, 2017: ELife
https://www.readbyqxmd.com/read/28731187/isolation-and-purification-of-novel-peptides-derived-from-sepia-ink-effects-on-apoptosis-of-prostate-cancer-cell-pc%C3%A2-3
#13
Fangfang Huang, Yinwen Jing, Guofang Ding, Zuisu Yang
Novel prostate cancer therapeutics are in high demand. In order to identify potential therapeutic targets, protein from sepia ink was hydrolyzed by utilizing pepsin in an orthogonal array design. Pepsin hydrolysate (SH) obtained at optimal conditions exhibited the highest antitumor activity. Subsequently, a novel antitumor peptide, which was termed SHP, was isolated through ultrafiltration, gel filtration chromatography and reversed phase high‑performance liquid chromatography. The amino acid sequence of SHP was identified as Leu‑Lys‑Glu‑Glu‑Asn‑Arg‑Arg‑Arg‑Arg‑Asp with a molecular mass of 1371...
July 21, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28731050/genomic-abnormalities-in-invasive-endocervical-adenocarcinoma-correlate-with-pattern-of-invasion-biologic-and-clinical-implications
#14
Anjelica Hodgson, Yutaka Amemiya, Arun Seth, Matthew Cesari, Bojana Djordjevic, Carlos Parra-Herran
The pattern-based classification system for HPV-related endocervical adenocarcinoma, which classifies tumors based on the destructiveness of stromal invasion, is predictive of the risk of nodal metastases and adverse outcome. Previous studies have demonstrated clinically important molecular alterations in endocervical adenocarcinoma, including KRAS and PIK3CA mutations; however, correlation between the molecular landscape and pathological variables including pattern of invasion has not been thoroughly explored...
July 21, 2017: Modern Pathology: An Official Journal of the United States and Canadian Academy of Pathology, Inc
https://www.readbyqxmd.com/read/28731047/targeted-next-generation-sequencing-supports-epidermoid-metaplasia-of-the-esophagus-as-a-precursor-to-esophageal-squamous-neoplasia
#15
Aatur D Singhi, Christina A Arnold, Dora M Lam-Himlin, Marina N Nikiforova, Lysandra Voltaggio, Marcia I Canto, Kevin M McGrath, Elizabeth A Montgomery
Esophageal epidermoid metaplasia is a rare condition that involves the proximal-to-middle third of the esophagus. It is sharply demarcated and defined histologically by epithelial hyperplasia, a prominent granular cell layer, and superficial hyperorthokeratosis. In addition, preliminary studies have suggested an association between esophageal epidermoid metaplasia and esophageal squamous neoplasia (squamous dysplasia and esophageal squamous cell carcinoma). To further characterize esophageal epidermoid metaplasia and better define its relationship to squamous neoplasia of the esophagus, we performed targeted next-generation sequencing on uninvolved esophageal squamous mucosa and matching esophageal epidermoid metaplasia specimens from 18 patients...
July 21, 2017: Modern Pathology: An Official Journal of the United States and Canadian Academy of Pathology, Inc
https://www.readbyqxmd.com/read/28730537/lung-cancer-as-a-paradigm-for-precision-oncology-in-solid-tumours
#16
Simon Schallenberg, Sabine Merkelbach-Bruse, Reinhard Buettner
Non-small cell lung cancer (NSCLC) is the leading cause of cancer-related death in the western world. However, the combination of molecular genotyping and subsequent systematic treatment of decoded target structures is a prime example of precision oncology in solid tumours. In this review, current targets of approved therapeutics and potential targets in clinical and preclinical trials are outlined. Furthermore, immune checkpoint inhibitors, as promising new therapeutic options, which have already been applied successfully in cases of lung cancer, are introduced...
July 20, 2017: Virchows Archiv: An International Journal of Pathology
https://www.readbyqxmd.com/read/28730480/identification-and-validation-of-driver-kinases-from-next-generation-sequencing-data
#17
Andri Leonidou, Barrie Peck, Rachael Natrajan
It is well appreciated that activating mutations in kinase genes result in kinome reprogramming that leads to altered downstream signaling networks that drive tumor progression. Indeed small-molecule inhibition of activated kinases has heralded the wave of precision medicine in the past decade. The advent of next-generation sequencing has identified a plethora of potentially activating mutations and fusion genes in previously unreported kinase genes that can potentially be developed as targeted therapies. However, the bottleneck in the translation of these alterations into clinically useful therapies lies in their functional validation...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28730479/analysis-of-drug-resistance-using-kinome-wide-functional-screens
#18
Katherine R Singleton, Keith T Earley, Lynn E Heasley
The clinical success of tyrosine kinase inhibitors specific for BCR-ABL-, EGFR-, ALK-, and ROS1-driven cancers continues to spur the quest to match specific oncogene-defined tumor types with an appropriate molecularly targeted therapy. Unfortunately, responses to these agents are not durable with intrinsic or acquired resistance limiting benefit. Additionally, efforts to identify the appropriate targets of new drugs have focused on nonfunctional assays such as large-scale sequencing for somatic mutations or analysis of gene copy number...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28730450/crispr-cas-rna-scaffolds-for-transcriptional-programming-in-yeast
#19
Jesse G Zalatan
CRISPR scaffold RNAs (scRNAs) provide a modular system for locus-specific transcriptional programming. scRNAs are generated by extending CRISPR guide RNA sequences with domains that recruit RNA-binding proteins, thus physically linking DNA binding and protein recruitment activities. A single scRNA molecule encodes information about the target locus and instructions about what regulatory function to execute at that locus. Sets of scRNA constructs can be used to generate synthetic multigene transcriptional programs in which some genes are activated and others are repressed...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28730439/design-and-preparation-of-aptamer-sirna-chimeras-asics-for-targeted-cancer-therapy
#20
Sven Kruspe, Paloma H Giangrande
Conjugation of cell-internalizing DNA or RNA aptamers to tumor-suppressing siRNAs represents a novel promising approach for cancer therapy. Here we describe how to employ RNA aptamers that bind to cell surface receptors as carriers for cell-targeted siRNA (or miRNA) delivery. This protocol was optimized to improve the efficiency of the aptamer-siRNA/miRNA conjugates and facilitate its implementation in most molecular biology labs. The single working steps include (1) outlining the optimal sequences of the RNA strands bearing the aptamer and siRNA sequence, for which further (2) a dsDNA template is synthesized and then (3) transcribed into an RNA that will be (4) folded and annealed to a chemically synthesized siRNA complementary strand...
2017: Methods in Molecular Biology
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