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https://www.readbyqxmd.com/read/28530678/the-complex-genetics-of-hypoplastic-left-heart-syndrome
#1
Xiaoqin Liu, Hisato Yagi, Shazina Saeed, Abha S Bais, George C Gabriel, Zhaohan Chen, Kevin A Peterson, You Li, Molly C Schwartz, William T Reynolds, Manush Saydmohammed, Brian Gibbs, Yijen Wu, William Devine, Bishwanath Chatterjee, Nikolai T Klena, Dennis Kostka, Karen L de Mesy Bentley, Madhavi K Ganapathiraju, Phillip Dexheimer, Linda Leatherbury, Omar Khalifa, Anchit Bhagat, Maliha Zahid, William Pu, Simon Watkins, Paul Grossfeld, Stephen A Murray, George A Porter, Michael Tsang, Lisa J Martin, D Woodrow Benson, Bruce J Aronow, Cecilia W Lo
Congenital heart disease (CHD) affects up to 1% of live births. Although a genetic etiology is indicated by an increased recurrence risk, sporadic occurrence suggests that CHD genetics is complex. Here, we show that hypoplastic left heart syndrome (HLHS), a severe CHD, is multigenic and genetically heterogeneous. Using mouse forward genetics, we report what is, to our knowledge, the first isolation of HLHS mutant mice and identification of genes causing HLHS. Mutations from seven HLHS mouse lines showed multigenic enrichment in ten human chromosome regions linked to HLHS...
May 22, 2017: Nature Genetics
https://www.readbyqxmd.com/read/28530655/a-quantitative-and-multiplexed-approach-to-uncover-the-fitness-landscape-of-tumor-suppression-in-vivo
#2
Zoë N Rogers, Christopher D McFarland, Ian P Winters, Santiago Naranjo, Chen-Hua Chuang, Dmitri Petrov, Monte M Winslow
Cancer growth is a multistage, stochastic evolutionary process. While cancer genome sequencing has been instrumental in identifying the genomic alterations that occur in human tumors, the consequences of these alterations on tumor growth remain largely unexplored. Conventional genetically engineered mouse models enable the study of tumor growth in vivo, but they are neither readily scalable nor sufficiently quantitative to unravel the magnitude and mode of action of many tumor-suppressor genes. Here, we present a method that integrates tumor barcoding with ultradeep barcode sequencing (Tuba-seq) to interrogate tumor-suppressor function in mouse models of human cancer...
May 22, 2017: Nature Methods
https://www.readbyqxmd.com/read/28530652/cd34-cells-from-dental-pulp-stem-cells-with-a-zfn-mediated-and-homology-driven-repair-mediated-locus-specific-knock-in-of-an-artificial-%C3%AE-globin-gene
#3
S Chattong, O Ruangwattanasuk, W Yindeedej, A Setpakdee, K Manotham
In humans, mutations in the β-globin gene (HBB) have two important clinical manifestations: β-thalassemia and sickle cell disease. The progress in genome editing and stem cell research may be relevant to the treatment of β-globin-related diseases. In this work, we employed zinc finger nuclease (ZFN)-mediated gene integration of synthetic β-globin cDNA into HBB loci, thus correcting almost all β-globin mutations. The integration was achieved in both HEK 293 cells and isolated dental pulp stem cell (DPSCs)...
May 22, 2017: Gene Therapy
https://www.readbyqxmd.com/read/28530648/mechanism-of-human-somatic-reprogramming-to-ips-cell
#4
Rika Teshigawara, Junkwon Cho, Masahiro Kameda, Takashi Tada
Somatic reprogramming to induced pluripotent stem cells (iPSC) was realized in the year 2006 in mice, and in 2007 in humans, by transiently forced expression of a combination of exogenous transcription factors. Human and mouse iPSCs are distinctly reprogrammed into a 'primed' and a 'naïve' state, respectively. In the last decade, puzzle pieces of somatic reprogramming have been collected with difficulty. Collectively, dissecting reprogramming events and identification of the hallmark of sequentially activated/silenced genes have revealed mouse somatic reprogramming in fragments, but there is a long way to go toward understanding the molecular mechanisms of human somatic reprogramming, even with developing technologies...
May 22, 2017: Laboratory Investigation; a Journal of Technical Methods and Pathology
https://www.readbyqxmd.com/read/28530317/-long-term-survival-of-dual-disorders-patients-after-mixed-care-in-dual-disorders-and-standard-wards-versus-care-only-in-dual-disorders-ward
#5
Yuri Gimelfarb, Aviva Wolf, Mashit Ben-Tzarfati
BACKGROUND: Dual disorders (co-occurring mental illness and substance abuse disorders in the same person) are extremely common among patients receiving mental health services. Integrated treatment has been proposed as the standard of care and it describes a flexible combination of treatments from the mental health and addiction fields that are blended together in the therapy. Scientific evidence for survival of dual disorders patients (DDPs), who had integrated dual disorders inpatient care, is lacking...
January 2017: Harefuah
https://www.readbyqxmd.com/read/28530235/hit-and-go-cas9-delivered-through-a-lentiviral-based-self-limiting-circuit
#6
Gianluca Petris, Antonio Casini, Claudia Montagna, Francesca Lorenzin, Davide Prandi, Alessandro Romanel, Jacopo Zasso, Luciano Conti, Francesca Demichelis, Anna Cereseto
In vivo application of the CRISPR-Cas9 technology is still limited by unwanted Cas9 genomic cleavages. Long-term expression of Cas9 increases the number of genomic loci non-specifically cleaved by the nuclease. Here we develop a Self-Limiting Cas9 circuit for Enhanced Safety and specificity (SLiCES) which consists of an expression unit for Streptococcus pyogenes Cas9 (SpCas9), a self-targeting sgRNA and a second sgRNA targeting a chosen genomic locus. The self-limiting circuit results in increased genome editing specificity by controlling Cas9 levels...
May 22, 2017: Nature Communications
https://www.readbyqxmd.com/read/28529900/immunotherapy-and-radiation-therapy-for-operable-early-stage-and-locally-advanced-non-small-cell-lung-cancer
#7
REVIEW
Neil K Taunk, Andreas Rimner, Melissa Culligan, Joseph S Friedberg, Julie Brahmer, Jamie Chaft
Non-small cell lung cancer (NSCLC) is the most common cause of cancer mortality. Although a significant proportion of patients can be cured with surgery, with or without adjuvant or neoadjuvant chemotherapy and radiation, a significant proportion of patients will fail, particularly distantly. Over fifty percent of patients present with stage IV disease. There are multiple forms of immunotherapy available including T-cell transfer, cytokine therapy, and oncolytic viruses. Checkpoint inhibitors have shown tremendous activity in NSCLC and are currently under intense study given promising data on response...
April 2017: Translational Lung Cancer Research
https://www.readbyqxmd.com/read/28529507/a-novel-and-efficient-method-for-bacteria-genome-editing-employing-both-crispr-cas9-and-an-antibiotic-resistance-cassette
#8
Hong Zhang, Qiu-Xiang Cheng, Ai-Min Liu, Guo-Ping Zhao, Jin Wang
As Cas9-mediated cleavage requires both protospacer and protospacer adjacent motif (PAM) sequences, it is impossible to employ the CRISPR/Cas9 system to directly edit genomic sites without available PAM sequences nearby. Here, we optimized the CRISPR/Cas9 system and developed an innovative two-step strategy for efficient genome editing of any sites, which did not rely on the availability of PAM sequences. An antibiotic resistance cassette was employed as both a positive and a negative selection marker. By integrating the optimized two-plasmid CRISPR/Cas system and donor DNA, we achieved gene insertion and point mutation with high efficiency in Escherichia coli, and importantly, obtained clean mutants with no other unwanted mutations...
2017: Frontiers in Microbiology
https://www.readbyqxmd.com/read/28529360/twelve-month-prevalence-and-treatment-gap-for-common-mental-disorders-findings-from-a-large-scale-epidemiological-survey-in-india
#9
Rajesh Sagar, Raman Deep Pattanayak, R Chandrasekaran, Pranit K Chaudhury, Balbir S Deswal, R K Lenin Singh, Savita Malhotra, S Haque Nizamie, Bharat N Panchal, T P Sudhakar, J K Trivedi, Mathew Varghese, Jagdish Prasad, Somnath Chatterji
BACKGROUND: Common mental disorders, such as mood, anxiety, and substance use disorders, are significant contributors to disability globally, including India. Available research is, however, limited by methodological issues and heterogeneities. AIM: The present paper focuses on the 12-month prevalence and 12-month treatment for anxiety, mood, and substance use disorders in India. MATERIALS AND METHODS: As part of the World Health Organization World Mental Health (WMH) Survey Initiative, in India, the study was conducted at eleven sites...
January 2017: Indian Journal of Psychiatry
https://www.readbyqxmd.com/read/28529298/an-aspect-of-the-history-of-medicine-in-ancient-korea-as-examined-through-silla-buddhist-monks-annotations-on-the-chapter-on-eliminating-disease-in-the-sutra-of-golden-light-suvarnabh%C3%A4-sa-s%C3%A5-tra
#10
Chaekun Oh, Jongwook Jeon, Dongwon Shin
Nearly nothing is known of medicine in ancient Korea due to insufficient materials. With several extant prescriptions and esoteric methods of treating diseases alone, it is impossible to gauge in depth the management of medicine during this period. If one exception were to be cited, that would be the fact that the annotations for understanding the contents on Indian medicine in the "Chapter on Eliminating Disease" in the Sutra of Golden Light, a Buddhist sutra originating from India, reflected the medical knowledge of Buddhist monks from Silla (57 BC-935 AD) who were active immediately after the nation's unification of the two other kingdoms on the Korean Peninsula (668 AD) such as Wonhyo (617-686 AD), Gyeongheung (620?-700? AD), and Seungjang (684-? AD)...
December 2016: Ŭi Sahak
https://www.readbyqxmd.com/read/28529161/genome-editing-for-human-osteoarthritis-a-perspective
#11
EDITORIAL
D Almarza, M Cucchiarini, J Loughlin
No abstract text is available yet for this article.
May 18, 2017: Osteoarthritis and Cartilage
https://www.readbyqxmd.com/read/28528876/modeling-covalent-modifier-drugs
#12
REVIEW
Ernest Awoonor-Williams, Andrew G Walsh, Christopher N Rowley
In this review, we present a summary of how computer modeling has been used in the development of covalent modifier drugs. Covalent modifier drugs bind by forming a chemical bond with their target. This covalent binding can improve the selectivity of the drug for a target with complementary reactivity and result in increased binding affinities due to the strength of the covalent bond formed. In some cases, this results in irreversible inhibition of the target, but some targeted covalent inhibitor (TCI) drugs bind covalently but reversibly...
May 18, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28528577/single-step-pcr-based-genetic-sex-determination-of-rat-tissues-and-cells
#13
Pramod Dhakal, Michael J Soares
The advent of genome editing strategies has expanded the range of animal models available for gene manipulation and renewed research interest in the rat. Gender is a key variable for in vivo gene function analyses. Here, we present a simple PCR-based method to determine genetic sex in the rat.
May 1, 2017: BioTechniques
https://www.readbyqxmd.com/read/28528574/esc-track-a-computer-workflow-for-4-d-segmentation-tracking-lineage-tracing-and-dynamic-context-analysis-of-escs
#14
Laura Fernández-de-Manúel, Covadonga Díaz-Díaz, Daniel Jiménez-Carretero, Miguel Torres, María C Montoya
Embryonic stem cells (ESCs) can be established as permanent cell lines, and their potential to differentiate into adult tissues has led to widespread use for studying the mechanisms and dynamics of stem cell differentiation and exploring strategies for tissue repair. Imaging live ESCs during development is now feasible due to advances in optical imaging and engineering of genetically encoded fluorescent reporters; however, a major limitation is the low spatio-temporal resolution of long-term 3-D imaging required for generational and neighboring reconstructions...
May 1, 2017: BioTechniques
https://www.readbyqxmd.com/read/28527830/crispr-cas9-mediated-precise-targeted-integration-in-vivo-using-a-double-cut-donor-with-short-homology-arms
#15
Xuan Yao, Xing Wang, Junlai Liu, Xinde Hu, Linyu Shi, Xiaowen Shen, Wenqin Ying, Xinyao Sun, Xin Wang, Pengyu Huang, Hui Yang
Precisely targeted genome editing is highly desired for clinical applications. However, the widely used homology-directed repair (HDR)-based genome editing strategies remain inefficient for certain in vivo applications. We here demonstrate a microhomology-mediated end-joining (MMEJ)-based strategy for precisely targeted gene integration in transfected neurons and hepatocytes in vivo with efficiencies up to 20%, much higher (up to 10 fold) than HDR-based strategy in adult mouse tissues. As a proof of concept of its therapeutic potential, we demonstrate the efficacy of MMEJ-based strategy in correction of Fah mutation and rescue of Fah(-/-) liver failure mice, offering an efficient approach for precisely targeted gene therapies...
May 11, 2017: EBioMedicine
https://www.readbyqxmd.com/read/28527816/adar1-is-targeted-by-mir-143-to-regulate-il-1%C3%AE-induced-endothelial-activation-through-the-nf%C3%AE%C2%BAb-pathway
#16
Yuanzhuo Chen, Hu Peng, Shuqin Zhou, Yugang Zhuang
Excessive endothelial activation by inflammatory mediators is a critical contributing factor of sepsis pathophysiology. ADAR1 (adenosine deaminase acting on RNA), an enzyme that binds and edits double-stranded RNAs, exhibits immune regulatory properties. Whether ADAR1 is involved in the pathophysiology of sepsis is unclear. In the present study, we used human umbilical endothelial cells (HUVECs) as an in vitro model system to investigate the roles of ADAR1 in interleukin (IL)-1β-induced endothelial activation...
May 17, 2017: International Journal of Biochemistry & Cell Biology
https://www.readbyqxmd.com/read/28527722/crispr-cas9-mediated-ccr5-ablation-in-human-hematopoietic-stem-progenitor-cells-confers-hiv-1-resistance-in%C3%A2-vivo
#17
Lei Xu, Huan Yang, Yang Gao, Zeyu Chen, Liangfu Xie, Yulin Liu, Ying Liu, Xiaobao Wang, Hanwei Li, Weifeng Lai, Yuan He, Anzhi Yao, Liying Ma, Yiming Shao, Bin Zhang, Chengyan Wang, Hu Chen, Hongkui Deng
Transplantation of hematopoietic stem cells (HSCs) with a naturally occurring CCR5 mutation confers a loss of detectable HIV-1 in the patient, making ablation of the CCR5 gene in HSCs an ideal therapy for an HIV-1 cure. Although CCR5 disruption has been attempted in CD4(+) T cells and hematopoietic stem/progenitor cells (HSPCs), efficient gene editing with high specificity and long-term therapeutic potential remains a major challenge for clinical translation. Here, we established a CRISPR/Cas9 gene editing system in human CD34(+) HSPCs and achieved efficient CCR5 ablation evaluated in long-term reconstituted NOD/Prkdc(scid)/IL-2Rγ(null) mice...
May 17, 2017: Molecular Therapy: the Journal of the American Society of Gene Therapy
https://www.readbyqxmd.com/read/28527668/imaging-mass-spectrometry-ims-of-cortical-lipids-from-preclinical-to-severe-stages-of-alzheimer-s-disease
#18
E Gónzalez de San Román, I Manuel, M T Giralt, I Ferrer, R Rodríguez-Puertas
Alzheimer's disease (AD) is a progressive neurodegenerative disease affecting millions of patients worldwide. Previous studies have demonstrated alterations in the lipid composition of lipid extracts from plasma and brain samples of AD patients. However, there is no consensus regarding the qualitative and quantitative changes of lipids in brains from AD patients. In addition, the recent developments in imaging mass spectrometry methods are leading to a new stage in the in situ analysis of lipid species in brain tissue slices from human postmortem samples...
May 17, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28527665/therapeutic-editing-of-hepatocyte-genome-in-vivo
#19
REVIEW
Marina Ruiz de Galarreta, Amaia Lujambio
The recent development of gene editing platforms enables making precise changes in the genome of eukaryotic cells. Programmable nucleases, such as meganucleases, zinc finger nucleases (ZFNs), transcription activator-like effector nucleases (TALENs), and clustered regularly interspaced short palindromic repeat (CRISPR)-associated nucleases, have revolutionized the way research is conducted as they facilitate the rapid production of mutant or knock-out cellular and animal models. These same genetic tools can potentially be applied to cure or alleviate a variety of diseases, including genetic diseases that lack an efficient therapy...
May 17, 2017: Journal of Hepatology
https://www.readbyqxmd.com/read/28527664/a-new-hdv-mouse-model-identifies-mitochondrial-antiviral-signaling-protein-mavs-as-a-key-player-in-ifn-%C3%AE-induction
#20
Lester Suárez-Amarán, Carla Usai, Marianna Di Scala, Cristina Godoy, Yi Ni, Mirja Hommel, Laura Palomo, Víctor Segura, Cristina Olagüe, Africa Vales, Alicia Ruiz-Ripa, Maria Buti, Eduardo Salido, Jesús Prieto, Stephan Urban, Francisco Rodríguez-Frias, Rafael Aldabe, Gloria González-Aseguinolaza
BACKGROUND & AIMS: Studying hepatitis delta virus (HDV) and developing new treatments is hampered by the limited availability of small animal models. Here a description of a robust mouse model of HDV infection that mimics several important characteristics of the human disease is presented. METHODS: HDV- and HBV-replication competent genomes were delivered to the mouse liver using adeno-associated viruses (AAV) (AAV-HDV and AAV-HBV). Viral load, antigen expression and genomes were quantified at different time points after AAV injection...
May 17, 2017: Journal of Hepatology
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