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https://www.readbyqxmd.com/read/29793131/tlr2-4-ligand-amplified-liver-inflammation-promotes-initiation-of-autoimmune-hepatitis-due-to-sustained-il-6-il-12-il-4-il-25-expression
#1
Gang Chi, Xin-Xia Feng, Ying-Xia Ru, Ting Xiong, Yuan Gao, Han Wang, Zhen-Long Luo, Ran Mo, Fang Guo, Yong-Pei He, Gui-Mei Zhang, De-An Tian, Zuo-Hua Feng
Autoimmune hepatitis (AIH), a serious autoimmune liver disease, can be a lifelong illness, leading to fibrosis, cirrhosis, and hepatocellular carcinoma (HCC). So far the mechanisms for disease initiation are largely unknown. Here we report that the amplified non-AIH liver inflammation could promote the initiation of AIH due to the sustained increase of IL-6, IL-12, IL-4, and IL-25 in the liver. The liver injury resulting from virus (adenovirus) or chemicals (CCl4 ) could induce an amplified (stronger/long-lasting) hepatic inflammation by releasing the ligands for TLR2/TLR4...
May 21, 2018: Molecular Immunology
https://www.readbyqxmd.com/read/29793020/epha2-stimulates-vcam-1-expression-through-calcium-dependent-nfat1-activity
#2
Steven Daniel Funk, Alexandra C Finney, Arif Yurdagul, Christopher B Pattillo, A Wayne Orr
Endothelial cell activation by proinflammatory stimuli drives leukocyte recruitment through enhanced expression of counter-receptors such as vascular cell adhesion molecule-1 (VCAM-1). We previously demonstrated that activation of the receptor tyrosine kinase EphA2 with its ligand ephrin-A1 induces VCAM-1 expression. Here, we sought to characterize the proinflammatory signaling pathways involved. Analysis of over-represented transcription factors in ephrin-A1-induced genes identified multiple potential transcriptional regulators, including the Rel family members nuclear factor-κB (NF-κB/p65) and nuclear factor of activated T-cells (NFAT)...
May 21, 2018: Cellular Signalling
https://www.readbyqxmd.com/read/29792271/dna-methylation-yields-epigenetic-clues-into-the-diabetic-nephropathy-of-pima-indians
#3
Karol Bomsztyk, Oleg Denisenko, Yuliang Wang
Environmental factors drive epigenetic programming. DNA methylation is the best studied modification transmitting epigenetic information. A study by Qiu et al. examined potential epigenetic roots for the decline of renal function in Pima Indians. A genomewide survey of blood leukocytes uncovered differentially methylated DNA sites in regulatory regions of genes associated with chronic kidney disease. This longitudinal study provides the first clues on epigenetic links between environmental factors and a high prevalence of diabetic kidney disease in Pima Indians...
June 2018: Kidney International
https://www.readbyqxmd.com/read/29792166/the-pdgfr%C3%AE-erk1-2-pathway-regulates-cdcp1-expression-in-triple-negative-breast-cancer
#4
Luca Forte, Federica Turdo, Cristina Ghirelli, Piera Aiello, Patrizia Casalini, Marilena Valeria Iorio, Elvira D'Ippolito, Patrizia Gasparini, Roberto Agresti, Beatrice Belmonte, Gabriella Sozzi, Lucia Sfondrini, Elda Tagliabue, Manuela Campiglio, Francesca Bianchi
BACKGROUND: CDCP1, a transmembrane protein with tumor pro-metastatic activity, was recently identified as a prognostic marker in TNBC, the most aggressive breast cancer subtype still lacking an effective molecular targeted therapy. The mechanisms driving CDCP1 over-expression are not fully understood, although several stimuli derived from tumor microenvironment, such as factors present in Wound Healing Fluids (WHFs), reportedly increase CDCP1 levels. METHODS: The expression of CDCP1, PDGFRβ and ERK1/2cell was tested by Western blot after stimulation of MDA-MB-231 cells with PDGF-BB and, similarly, in presence or not of ERK1/2 inhibitor in a panel of TNBC cell lines...
May 23, 2018: BMC Cancer
https://www.readbyqxmd.com/read/29791856/activation-of-the-arterial-program-drives-development-of-definitive-hemogenic-endothelium-with-lymphoid-potential
#5
Mi Ae Park, Akhilesh Kumar, Ho Sun Jung, Gene Uenishi, Oleg V Moskvin, James A Thomson, Igor I Slukvin
Understanding the pathways guiding the development of definitive hematopoiesis with lymphoid potential is essential for advancing human pluripotent stem cell (hPSC) technologies for the treatment of blood diseases and immunotherapies. In the embryo, lymphoid progenitors and hematopoietic stem cells (HSCs) arise from hemogenic endothelium (HE) lining arteries but not veins. Here, we show that activation of the arterial program through ETS1 overexpression or by modulating MAPK/ERK signaling pathways at the mesodermal stage of development dramatically enhanced the formation of arterial-type HE expressing DLL4 and CXCR4...
May 22, 2018: Cell Reports
https://www.readbyqxmd.com/read/29791254/a-genome-wide-mirna-screen-identifies-regulators-of-tetraploid-cell-proliferation
#6
Marc A Vittoria, Elizabeth M Shenk, Kevin P O'Rourke, Amanda F Bolgioni, Sanghee Lim, Victoria Kacprzak, Ryan J Quinton, Neil J Ganem
Tetraploid cells, which are most commonly generated by errors in cell division, are genomically unstable and have been shown to promote tumorigenesis. Recent genomic studies have estimated that ∼40% of all solid tumors have undergone a genome-doubling event during their evolution, suggesting a significant role for tetraploidy in driving the development of human cancers. To safeguard against the deleterious effects of tetraploidy, non transformed cells that fail mitosis and become tetraploid activate both the Hippo and p53 tumor suppressor pathways to restrain further proliferation...
May 23, 2018: Molecular Biology of the Cell
https://www.readbyqxmd.com/read/29791133/design-construction-and-validation-of-histone-binding-effectors-in-vitro-and-in-cells
#7
Stefan J Tekel, Cassandra M Barrett, Daniel A Vargas, Karmella A Haynes
Chromatin is a system of nuclear proteins and nucleic acids that plays a pivotal role in gene expression and cell behavior, and is therefore the subject of intense study for cell development and cancer research. Biochemistry, crystallography, and reverse genetics have elucidated the macromolecular interactions that drive chromatin regulation. One of the central mechanisms is the recognition of post translational modifications (PTMs) on histone proteins by a family of nuclear proteins known as "readers...
May 23, 2018: Biochemistry
https://www.readbyqxmd.com/read/29790924/typhoidal-salmonella-serovars-ecological-opportunity-and-the-evolution-of-a-new-pathovar
#8
Hirotaka Hiyoshi, Connor R Tiffany, Denise N Bronner, Andreas J Bäumler
Typhoid and paratyphoid fever are severe systemic infections caused by human-adapted typhoidal Salmonella serovars that are indistinguishable in their clinical presentation, but differ from human gastroenteritis caused by zoonotic non-typhoidal Salmonella serovars. Typhoidal Salmonella serovars evolved from ancestral gastrointestinal pathogens through genetic changes that supported a change in pathogen ecology. Typhoidal Salmonella serovars share virulence properties that were acquired through convergent evolution and therefore this group is not defined by the presence of shared virulence genes that are absent from non-typhoidal Salmonella serovars...
May 21, 2018: FEMS Microbiology Reviews
https://www.readbyqxmd.com/read/29789467/the-present-and-future-of-whole-genome-sequencing-wgs-and-whole-metagenome-sequencing-wms-for-surveillance-of-antimicrobial-resistant-microorganisms-and-antimicrobial-resistance-genes-across-the-food-chain
#9
REVIEW
Elena A Oniciuc, Eleni Likotrafiti, Adrián Alvarez-Molina, Miguel Prieto, Jesús A Santos, Avelino Alvarez-Ordóñez
Antimicrobial resistance (AMR) surveillance is a critical step within risk assessment schemes, as it is the basis for informing global strategies, monitoring the effectiveness of public health interventions, and detecting new trends and emerging threats linked to food. Surveillance of AMR is currently based on the isolation of indicator microorganisms and the phenotypic characterization of clinical, environmental and food strains isolated. However, this approach provides very limited information on the mechanisms driving AMR or on the presence or spread of AMR genes throughout the food chain...
May 22, 2018: Genes
https://www.readbyqxmd.com/read/29789379/correlated-gene-expression-and-anatomical-communication-support-synchronized-brain-activity-in-the-mouse-functional-connectome
#10
Brian D Mills, David S Grayson, Anandakumar Shunmugavel, Oscar Miranda-Dominguez, Eric Feczko, Eric Earl, Kim Neve, Damien A Fair
Cognition and behavior depend on synchronized intrinsic brain activity that is organized into functional networks across the brain. Research has investigated how anatomical connectivity both shapes and is shaped by these networks, but not how anatomical connectivity interacts with intra-areal molecular properties to drive functional connectivity. Here, we present a novel linear model to explain functional connectivity by integrating systematically obtained measurements of axonal connectivity, gene expression, and resting state functional connectivity MRI in the mouse brain...
May 22, 2018: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/29786967/developmental-chromatin-restriction-of-pro-growth-gene-networks-acts-as-an-epigenetic-barrier-to-axon-regeneration-in-cortical-neurons
#11
Ishwariya Venkatesh, Vatsal Mehra, Zimei Wang, Ben Califf, Murray G Blackmore
Axon regeneration in the central nervous system is prevented in part by a developmental decline in the intrinsic regenerative ability of maturing neurons. This loss of axon growth ability likely reflects widespread changes in gene expression, but the mechanisms that drive this shift remain unclear. Chromatin accessibility has emerged as a key regulatory mechanism in other cellular contexts, raising the possibility that chromatin structure may contribute to the age-dependent loss of regenerative potential. Here we establish an integrated bioinformatic pipeline that combines analysis of developmentally dynamic gene networks with transcription factor regulation and genome-wide maps of chromatin accessibility...
May 22, 2018: Developmental Neurobiology
https://www.readbyqxmd.com/read/29786779/dnmt3a-controls-mir-200b-in-cardiac-fibroblast-autophagy-and-cardiac-fibrosis
#12
Xu-Dong Zhao, Run-He Qin, Jing-Jing Yang, Sheng-Song Xu, Hui Tao, Xuan-Sheng Ding, Kai-Hu Shi
AIM AND OBJECTIVE: Regulation of microRNA gene expression by DNA methylation may represent a key mechanism to drive cardiac fibrosis progression. Cardiac fibroblast autophagy is the primary source of cardiac fibrosis, but the mechanisms underlying this process are incompletely understood. Here we found that DNMT3A suppression of the microRNA-200b (miR-200b) through pathway leads to cardiac fibroblast autophagy in cardiac fibrosis. METHODS: To understand the impact of DNMT3A on miR-200b at cardiac fibrosis, the rat cardiac fibrosis model was established via the abdominal aortic coarctation...
May 21, 2018: Inflammation Research: Official Journal of the European Histamine Research Society ... [et Al.]
https://www.readbyqxmd.com/read/29785946/-crispr-cas-systems-in-genome-engineering-of-bacteriophages
#13
Cai Jiao Liang, Fan Mei Meng, Yun Can Ai
Researches on CRISPR/Cas (clustered regularly interspaced short palindromic repeats/CRISPR-associated genes) systems, that are adaptive immunity systems encoded by prokaryotes, have promoted the development of new genome-editing tools. Bacteriophages are not only the driving elements for the evolution of prokaryotes' CRISPR arrays, but also the targets of the CRISPR/Cas systems. Studies on functional genomics of bacteriophages have been lagging behind the discovery of new phage strains and the sequencing of their genomes...
May 20, 2018: Yi Chuan, Hereditas
https://www.readbyqxmd.com/read/29785587/a-study-on-the-use-of-strain-specific-and-homologous-promoters-for-heterologous-expression-in-industrial-saccharomyces-cerevisiae-strains
#14
Daniel Pereira de Paiva, Tiago Benoliel Rocha, Marciano Regis Rubini, André Moraes Nicola, Viviane Castelo Branco Reis, Fernando Araripe Gonçalves Torres, Lidia Maria Pepe de Moraes
Polymorphism is well known in Saccharomyces cerevisiae strains used for different industrial applications, however little is known about its effects on promoter efficiency. In order to test this, five different promoters derived from an industrial and a laboratory (S288c) strain were used to drive the expression of eGFP reporter gene in both cells. The ADH1 promoter (P ADH1 ) in particular, which showed more polymorphism among the promoters analyzed, also exhibited the highest differences in intracellular fluorescence production...
May 21, 2018: AMB Express
https://www.readbyqxmd.com/read/29785489/trpc6-inactivation-confers-protection-in-a-model-of-severe-nephrosis-in-rats
#15
Eun Young Kim, Parisa Yazdizadeh Shotorbani, Stuart E Dryer
Mutations in canonical transient receptor potential-6 (TRPC6) channels give rise to rare familial forms of focal and segmental glomerulosclerosis (FSGS). Here we examined a possible role for TRPC6 in the progression of chronic puromycin aminonucleoside (PAN) nephrosis in Sprague-Dawley rats, a classic model of acquired nephrotic syndromes. We used CRISPR/Cas9 technology to delete a 239-bp region within exon 2 of the Trpc6 gene (Trpc6del allele). Trpc6del/del rats expressed detectable Trpc6 transcripts missing exon 2, and TRPC6 proteins could be detected by immunoblot of renal cortex...
May 22, 2018: Journal of Molecular Medicine: Official Organ of the "Gesellschaft Deutscher Naturforscher und Ärzte"
https://www.readbyqxmd.com/read/29784935/a-causal-mechanism-for-childhood-acute-lymphoblastic-leukaemia
#16
REVIEW
Mel Greaves
In this Review, I present evidence supporting a multifactorial causation of childhood acute lymphoblastic leukaemia (ALL), a major subtype of paediatric cancer. ALL evolves in two discrete steps. First, in utero initiation by fusion gene formation or hyperdiploidy generates a covert, pre-leukaemic clone. Second, in a small fraction of these cases, the postnatal acquisition of secondary genetic changes (primarily V(D)J recombination-activating protein (RAG) and activation-induced cytidine deaminase (AID)-driven copy number alterations in the case of ETS translocation variant 6 (ETV6)-runt-related transcription factor 1 (RUNX1)+ ALL) drives conversion to overt leukaemia...
May 21, 2018: Nature Reviews. Cancer
https://www.readbyqxmd.com/read/29782499/tgf%C3%AE-signaling-limits-lineage-plasticity-in-prostate-cancer
#17
Yi Hao, Glen A Bjerke, Karolina Pietrzak, Tiffany A Melhuish, Yu Han, Stephen D Turner, Henry F Frierson, David Wotton
Although treatment options for localized prostate cancer (CaP) are initially effective, the five-year survival for metastatic CaP is below 30%. Mutation or deletion of the PTEN tumor suppressor is a frequent event in metastatic CaP, and inactivation of the transforming growth factor (TGF) ß signaling pathway is associated with more advanced disease. We previously demonstrated that mouse models of CaP based on inactivation of Pten and the TGFß type II receptor (Tgfbr2) rapidly become invasive and metastatic...
May 21, 2018: PLoS Genetics
https://www.readbyqxmd.com/read/29781813/the-notch1-cd44-axis-drives-pathogenesis-in-a-t-cell-acute-lymphoblastic-leukemia-model
#18
Marina García-Peydró, Patricia Fuentes, Marta Mosquera, María J García-León, Juan Alcain, Antonio Rodríguez, Purificación García de Miguel, Pablo Menéndez, Kees Weijer, Hergen Spits, David T Scadden, Carlos Cuesta-Mateos, Cecilia Muñoz-Calleja, Francisco Sánchez-Madrid, María L Toribio
NOTCH1 is a prevalent signaling pathway in T cell acute lymphoblastic leukemia (T-ALL), but crucial NOTCH1 downstream signals and target genes contributing to T-ALL pathogenesis cannot be retrospectively analyzed in patients and thus remain ill defined. This information is clinically relevant, as initiating lesions that lead to cell transformation and leukemia-initiating cell (LIC) activity are promising therapeutic targets against the major hurdle of T-ALL relapse. Here, we describe the generation in vivo of a human T cell leukemia that recapitulates T-ALL in patients, which arises de novo in immunodeficient mice reconstituted with human hematopoietic progenitors ectopically expressing active NOTCH1...
May 21, 2018: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/29781541/the-two-rules-of-speciation-in-species-with-young-sex-chromosomes
#19
Dmitry A Filatov
The two "rules of speciation", Haldane's rule (HR) and the large-X effect (LXE), are thought to be caused by recessive species incompatibilities exposed in the phenotype due to the hemizygosity of X-linked genes in the heterogametic sex. Thus, the reports of HR and the LXE in species with recently evolved non- or partially-degenerate Y-chromosomes, such as Silene latifolia and its relatives, were surprising. Here I argue that rapid species-specific degeneration of Y-linked genes and associated adjustment of expression of X-linked gametologs (dosage compensation) may lead to rapid evolution of sex-linked species incompatibilities...
May 21, 2018: Molecular Ecology
https://www.readbyqxmd.com/read/29780443/separase-inhibitor-sepin-1-inhibits-foxm1-expression-and-breast-cancer-cell-growth
#20
Nenggang Zhang, Debananda Pati
Sepin-1, a potent non-competitive inhibitor of separase, inhibits cancer cell growth, but the mechanisms of Sepin-1-mediated growth inhibition are not fully understood. Here we report that Sepin-1 hinders growth of breast cancer cells, cell migration, and wound healing. Inhibition of cell growth induced by Sepin-1 in vitro doesn't appear to be through apoptosis but rather due to growth inhibition. Following Sepin-1 treatment caspases 3 and 7 are not activated and Poly (ADP-ribose) polymerase (Parp) is not cleaved...
2018: Journal of Cancer Science & Therapy
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