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https://www.readbyqxmd.com/read/29350722/chemical-decontamination-of-ips-cell-derived-neural-cell-mixtures
#1
Di Mao, Xie Khim Watson Chung, Tomoko Andoh-Noda, Ying Qin, Shin-Ichi Sato, Yasushi Takemoto, Wado Akamatsu, Hideyuki Okano, Motonari Uesugi
This report describes the design and evaluation of phosphorylated 7-ethyl-10-hydroxycamptothecin (SN38-P), which selectively eliminates tumor-forming proliferative stem cells, including human induced pluripotent stem cells (hiPSCs) and neural stem cells, from iPSC-derived neural cell mixtures. Results of the present study demonstrate that simple phosphorylation of an anticancer drug can provide a safe, cost-effective, and chemically-defined tool for decontaminating hiPSC-derived neuron.
January 19, 2018: Chemical Communications: Chem Comm
https://www.readbyqxmd.com/read/29349492/ganoderma-lucidum-phosphoglucomutase-is-required-for-hyphal-growth-polysaccharide-production-and-cell-wall-integrity
#2
Yanru Hu, Mengjiao Li, Shengli Wang, Sining Yue, Liang Shi, Ang Ren, Mingwen Zhao
Phosphoglucomutase (pgm) is an important enzyme in carbohydrate metabolism that is located at the branching point between glycolysis and the Leloir pathway. pgm catalyzes the reversible conversion reaction between glucose-6-phosphate (Glc-6-P) and glucose-1-phosphate (Glc-1-P). The glpgm gene was cloned in Escherichia coli, and the recombinant pgm protein from Ganoderma lucidum was purified in this study. The activity of native pgm was also detected to demonstrate that this predicted gene was functional in G...
January 18, 2018: Applied Microbiology and Biotechnology
https://www.readbyqxmd.com/read/29343702/analysis-of-mitochondrial-function-in-human-induced-pluripotent-stem-cells-from-patients-with-mitochondrial-diabetes-due-to-the-a3243g-mutation
#3
Masaki Matsubara, Hajime Kanda, Hiromi Imamura, Mayumi Inoue, Michio Noguchi, Kiminori Hosoda, Akira Kakizuka, Kazuwa Nakao
We previously established human induced pluripotent stem (iPS) cells in two diabetic patients from different families with the mitochondrial A3243G mutation and isolated isogenic iPS cell clones with either undetectable or high levels of the mutation in both patients. In the present study, we analyzed the mitochondrial functions of two mutation-undetectable and two mutation-high clones in each patient through four methods to assess complex I activity, mitochondrial membrane potential, mitochondrial respiration, and mitochondrial ATP production...
January 17, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29339073/the-human-gcom1-complex-gene-interacts-with-the-nmda-receptor-and-internexin-alpha
#4
Raymond S Roginski, Chi W Lau, Phillip P Santoiemma, Sara J Weaver, Peicheng Du, Patricia Soteropoulos, Jay Yang
The known functions of the human GCOM1 complex hub gene include transcription elongation and the intercalated disk of cardiac myocytes. However, in all likelihood, the gene's most interesting, and thus far least understood, roles will be found in the central nervous system. To investigate the functions of the GCOM1 gene in the CNS, we have cloned human and rat brain cDNAs encoding novel, 105 kDa GCOM1 combined (Gcom) proteins, designated Gcom15, and identified a new group of GCOM1 interacting genes, termed Gints, from yeast two-hybrid (Y2H) screens...
January 12, 2018: Gene
https://www.readbyqxmd.com/read/29338603/emerging-roles-of-inositol-pyrophosphates-as-key-modulators-of-fungal-pathogenicity
#5
Hyun Ah Kang
Inositol pyrophosphates (PP-IPs) are energy-rich small molecules that are omnipresent in eukaryotic cells, from yeast to mammals, playing central roles in overall cellular homeostasis as a diverse and multifaceted class of intracellular messengers. Recent studies of the metabolic pathways and physiological roles of PP-IPs in the human pathogenic fungus Cryptococcus neoformans have revealed that the PP-IP5 (IP7) is a key metabolite essential for fungal metabolic adaptation to the host environment, immune recognition, and pathogenicity...
January 17, 2018: Virulence
https://www.readbyqxmd.com/read/29334780/rules-governing-the-mechanism-of-epigenetic-reprogramming-memory
#6
Phuc-Loi Luu, Daniela Gerovska, Hans R Schöler, Marcos J Araúzo-Bravo
AIM: Disclosing the mechanisms that regulate reprogramming memory. MATERIALS & METHODS: We established computational procedure to find DNA methylation somatic memory sites (SMSs) at single CpGs and integrated them with genomics, epigenomics, transcriptomics and imprinting information. RESULTS & CONCLUSION: Reprogramming memory persists at late passages in low methylated regions. Contrarily to hypomethylated, hypermethylated SMSs occur at evolutionary conserved sites overlapping active transcription loci in dynamic chromatin regions...
January 16, 2018: Epigenomics
https://www.readbyqxmd.com/read/29327201/allele-specific-biased-expression-of-the-cntn6-gene-in-ips-cell-derived-neurons-from-a-patient-with-intellectual-disability-and-3p26-3-microduplication-involving-the-cntn6-gene
#7
Maria M Gridina, Natalia M Matveeva, Veniamin S Fishman, Aleksei G Menzorov, Helen A Kizilova, Nikolay A Beregovoy, Igor I Kovrigin, Inna E Pristyazhnyuk, Igor P Oscorbin, Maxim L Filipenko, Anna A Kashevarova, Nikolay A Skryabin, Tatyana V Nikitina, Elena A Sazhenova, Ludmila P Nazarenko, Igor N Lebedev, Oleg L Serov
Copy number variations (CNVs) of the human CNTN6 gene caused by megabase-scale microdeletions or microduplications in the 3p26.3 region are often the cause of neurodevelopmental disorders, including intellectual disability and developmental delay. Surprisingly, patients with different copy numbers of this gene display notable overlapping of neuropsychiatric symptoms. The complexity of the study of human neuropathologies is associated with the inaccessibility of brain material. This problem can be overcome through the use of reprogramming technologies that permit the generation of induced pluripotent stem (iPS) cells from fibroblasts and their subsequent in vitro differentiation into neurons...
January 11, 2018: Molecular Neurobiology
https://www.readbyqxmd.com/read/29324788/esrp1-is-a-marker-of-mouse-fetal-germ-cells-and-differentially-expressed-during-spermatogenesis
#8
Shaghayegh Saeidi, Farnaz Shapouri, Robb U de Iongh, Franca Casagranda, Jessie M Sutherland, Patrick S Western, Eileen A McLaughlin, Mary Familari, Gary R Hime
ESRP1 regulates alternative splicing, producing multiple transcripts from its target genes in epithelial tissues. It is upregulated during mesenchymal to epithelial transition associated with reprogramming of fibroblasts to iPS cells and has been linked to pluripotency. Mouse fetal germ cells are the founders of the adult gonadal lineages and we found that Esrp1 mRNA was expressed in both male and female germ cells but not in gonadal somatic cells at various stages of gonadal development (E12.5-E15.5). In the postnatal testis, Esrp1 mRNA was highly expressed in isolated cell preparations enriched for spermatogonia but expressed at lower levels in those enriched for pachytene spermatocytes and round spermatids...
2018: PloS One
https://www.readbyqxmd.com/read/29321585/site-specific-randomization-of-the-endogenous-genome-by-a-regulatable-crispr-cas9-piggybac-system-in-human-cells
#9
Kentaro Ishida, Huaigeng Xu, Noriko Sasakawa, Mandy Siu Yu Lung, Julia Alexandra Kudryashev, Peter Gee, Akitsu Hotta
Randomized mutagenesis at an endogenous chromosomal locus is a promising approach for protein engineering, functional assessment of regulatory elements, and modeling genetic variations. In mammalian cells, however, it is challenging to perform site-specific single-nucleotide substitution with single-stranded oligodeoxynucleotide (ssODN) donor templates due to insufficient homologous recombination and the infeasibility of positive selection. Here, we developed a DNA transposon based CRISPR-Cas9 regulated transcription and nuclear shuttling (CRONUS) system that enables the stable transduction of CRISPR-Cas9/sgRNA in broad cell types, but avoids undesired genome cleavage in the absence two chemical inducing molecules...
January 10, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29320737/genomic-circuitry-underlying-immunological-response-to-pediatric-acute-respiratory-infection
#10
Sarah E Henrickson, Sasikanth Manne, Douglas V Dolfi, Kathleen D Mansfield, Kaela Parkhouse, Rakesh D Mistry, Elizabeth R Alpern, Scott E Hensley, Kathleen E Sullivan, Susan E Coffin, E John Wherry
Acute respiratory tract viral infections (ARTIs) cause significant morbidity and mortality. CD8 T cells are fundamental to host responses, but transcriptional alterations underlying anti-viral mechanisms and links to clinical characteristics remain unclear. CD8 T cell transcriptional circuitry in acutely ill pediatric patients with influenza-like illness was distinct for different viral pathogens. Although changes included expected upregulation of interferon-stimulated genes (ISGs), transcriptional downregulation was prominent upon exposure to innate immune signals in early IFV infection...
January 9, 2018: Cell Reports
https://www.readbyqxmd.com/read/29316596/van-neck-odelberg-disease-a-3-5-year-follow-up-case-report-and-systematic-review
#11
Patrick J Mixa, Frank A Segreto, Hiram Luigi-Martinez, Bassel G Diebo, Qais Naziri, Srinivas Kolla, Aditya V Maheshwari
V an Neck-Odelberg disease (VND) is a benign skeletal overgrowth of the ischiopubic synchondrosis (IPS) in prepubescent patients. There is a paucity of long-term follow-up data and reviews on management decision-making. We report on a 15-year-old female, with a history of sickle-cell disease (HbSS), presenting with unilateral groin pain. Patient's physical examination, radiographs, and a literature-review determined a diagnosis of VND. Conservative treatment was issued. Clinical symptoms resolved at three months, followed by complete lesion resolution at three years...
December 12, 2017: Surgical Technology International
https://www.readbyqxmd.com/read/29315221/introduction-of-exogenous-hsv-tk-suicide-gene-increases-safety-of-keratinocyte-derived-induced-pluripotent-stem-cells-by-providing-genetic-emergency-exit-switch
#12
Maciej Sułkowski, Paweł Konieczny, Paula Chlebanowska, Marcin Majka
Since their invention in 2006, induced Pluripotent Stem (iPS) cells remain a great promise for regenerative medicine circumventing the ethical issues linked to Embryonic Stem (ES) cell research. iPS cells can be generated in a patient-specific manner as an unlimited source of various cell types for in vitro drug screening, developmental biology studies and regenerative use. Having the capacity of differentiating into the cells of all three primary germ layers, iPS cells have high potential to form teratoma tumors...
January 9, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29312817/murine-pluripotent-stem-cells-that-escape-differentiation-inside-teratomas-maintain-pluripotency
#13
Yangli Pei, Liang Yue, Wei Zhang, Jinzhu Xiang, Zhu Ma, Jianyong Han
Background: Pluripotent stem cells (PSCs) offer immense potential as a source for regenerative therapies. The teratoma assay is widely used in the field of stem cells and regenerative medicine, but the cell composition of teratoma is still elusive. Methods: We utilized PSCs expressing enhanced green fluorescent protein (EGFP) under the control of the Pou5f1 promoter to study the persistence of potential pluripotent cells during teratoma formation in vivo. OCT4-MES (mouse embryonic stem cells) were isolated from the blastocysts of 3...
2018: PeerJ
https://www.readbyqxmd.com/read/29311471/metabolism-of-fentanyl-and-acetylfentanyl-in-human-induced-pluripotent-stem-cell-derived-hepatocytes
#14
Tatsuyuki Kanamori, Yuko Togawa Iwata, Hiroki Segawa, Tadashi Yamamuro, Kenji Kuwayama, Kenji Tsujikawa, Hiroyuki Inoue
To evaluate the capability of human-induced pluripotent stem cell-derived hepatocytes (h-iPS-HEP) in drug metabolism, the profiles of the metabolites of fentanyl, a powerful synthetic opioid, and acetylfentanyl, an N-acetyl analog of fentanyl, in the cells were determined and analyzed. Commercially available h-iPS-HEP were incubated with fentanyl or acetylfentanyl for 24 or 48 h. After enzymatic hydrolysis, the medium was deproteinized with acetonitrile, then analyzed by LC/MS. Desphenethylated metabolites and some hydroxylated metabolites, including 4'-hydroxy-fentanyl and β-hydroxy-fentanyl, were detected as metabolites of fentanyl and acetylfentanyl in the medium...
2018: Biological & Pharmaceutical Bulletin
https://www.readbyqxmd.com/read/29305325/modeling-trastuzumab-related-cardiotoxicity-in-vitro-using-human-stem-cell-derived-cardiomyocytes
#15
Yosuke K Kurokawa, Michael R Shang, Rose T Yin, Steven C George
Trastuzumab (Herceptin®), a monoclonal antibody against the ErbB2 (HER2) receptor, has significantly improved clinical outcomes for HER2+ breast cancer patients. However, the drug also has known cardiotoxic side effects through mechanisms that are not fully understood. Here we utilized human induced pluripotent stem cell-derived cardiomyocytes (iPS-CMs) to model trastuzumab-related cardiotoxicity in vitro. We demonstrate that cardiotoxic effects of ErbB2 inhibition by trastuzumab can be recapitulated only when the cardioprotective effects of ErbB2/4 signaling is observed...
January 2, 2018: Toxicology Letters
https://www.readbyqxmd.com/read/29296963/novel-tpo-receptor-agonist-ta-316-contributes-to-platelet-biogenesis-from-human-ips-cells
#16
Ayako Aihara, Tomo Koike, Natsuki Abe, Sou Nakamura, Akira Sawaguchi, Takanori Nakamura, Naoshi Sugimoto, Hiromitsu Nakauchi, Taito Nishino, Koji Eto
Signaling by thrombopoietin (TPO) in complex with its receptor, c-MPL, is critical for hematopoietic stem cell (HSC) homeostasis and platelet generation. Here we show that TA-316, a novel chemically synthesized c-MPL agonist (CMA), is useful for ex vivo platelet generation from human-induced pluripotent stem (iPS) cell-derived immortalized megakaryocyte progenitor cell lines (imMKCLs). Moreover, the generation is clinically applicable, because self-renewal expansion and platelet release is tightly controllable...
February 28, 2017: Blood Advances
https://www.readbyqxmd.com/read/29290585/a-human-ips-model-implicates-embryonic-b-myeloid-fate-restriction-as-developmental-susceptibility-to-b%C3%A2-acute-lymphoblastic-leukemia-associated-etv6-runx1
#17
Charlotta Böiers, Simon E Richardson, Emma Laycock, Alya Zriwil, Virginia A Turati, John Brown, Jason P Wray, Dapeng Wang, Chela James, Javier Herrero, Ewa Sitnicka, Stefan Karlsson, Andrew J H Smith, Sten Erik W Jacobsen, Tariq Enver
ETV6-RUNX1 is associated with childhood acute B-lymphoblastic leukemia (cALL) functioning as a first-hit mutation that initiates a clinically silent pre-leukemia in utero. Because lineage commitment hierarchies differ between embryo and adult, and the impact of oncogenes is cell-context dependent, we hypothesized that the childhood affiliation of ETV6-RUNX1 cALL reflects its origins in a progenitor unique to embryonic life. We characterize the first emerging B cells in first-trimester human embryos, identifying a developmentally restricted CD19-IL-7R+ progenitor compartment, which transitions from a myeloid to lymphoid program during ontogeny...
December 27, 2017: Developmental Cell
https://www.readbyqxmd.com/read/29288969/generation-of-an-induced-pluripotent-stem-cell-ipsc-line-from-a-40-year-old-patient-with-the-a8344g-mutation-of-mitochondrial-dna-and-merrf-myoclonic-epilepsy-with-ragged-red-fibers-syndrome
#18
Yu-Ting Wu, Yu-Hung Hsu, Ching-Ying Huang, Ming-Ching Ho, Yu-Che Cheng, Cheng-Hao Wen, Hui-Wen Ko, Huai-En Lu, Yen-Chun Chen, Chia-Ling Tsai, Yi-Chao Hsu, Yau-Huei Wei, Patrick C H Hsieh
Mitochondrial defects are associated with clinical manifestations from common diseases to rare genetic disorders. Myoclonus epilepsy associated with ragged-red fibers (MERRF) syndrome results from an A to G transition at nucleotide position 8344 in the tRNALys gene of mitochondrial DNA (mtDNA) and is characterized by myoclonus, myopathy and severe neurological symptoms. In this study, Sendai reprogramming method was used to generate an iPS cell line carrying the A8344G mutation of mtDNA from a MERRF patient...
December 19, 2017: Stem Cell Research
https://www.readbyqxmd.com/read/29285521/enhanced-differentiation-of-human-preosteoblasts-on-electrospun-blend-fiber-mats-of-polydioxanone-and-anionic-sulfated-polysaccharides
#19
Nowsheen Goonoo, Archana Bhaw-Luximon, Ulrich Jonas, Dhanjay Jhurry, Holger Schönherr
The viability and differentiation of SaOS-2 preosteoblasts on fiber mats of blends comprising of the biodegradable poly(ester-ether) polydioxanone (PDX) and the sulfate-containing anionic polysaccharides kappa-carrageenan (KCG) and fucoidan (FUC) were investigated for a range of different blend compositions. The detailed analysis of the blend nanofiber properties revealed a different degree of miscibility of PDX and the polysaccharide leading to a different enrichment at the surface of the blend nanofibers, which were observed to be stable in phosphate buffer solution (PBS) for up to 5 weeks...
December 11, 2017: ACS Biomaterials Science & Engineering
https://www.readbyqxmd.com/read/29282838/the-inositol-pyrophosphate-pathway-in-health-and-diseases
#20
Anutosh Chakraborty
Inositol pyrophosphates (IPPs) are present in organisms ranging from plants, slime moulds and fungi to mammals. Distinct classes of kinases generate different forms of energetic diphosphate-containing IPPs from inositol phosphates (IPs). Conversely, polyphosphate phosphohydrolase enzymes dephosphorylate IPPs to regenerate the respective IPs. IPPs and/or their metabolizing enzymes regulate various cell biological processes by modulating many proteins via diverse mechanisms. In the last decade, extensive research has been conducted in mammalian systems, particularly in knockout mouse models of relevant enzymes...
December 27, 2017: Biological Reviews of the Cambridge Philosophical Society
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