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https://www.readbyqxmd.com/read/29781950/report-of-the-key-opinion-leaders-meeting-on-stem-cell-derived-beta-cells
#1
Jon Odorico, James Markmann, Douglas Melton, Julia Greenstein, Albert Hwa, Cristina Nostro, Alireza Rezania, Jose Oberholzer, Daniel Pipeleers, Luhan Yang, Chad Cowan, Danwei Huangfu, Dieter Egli, Uri Ben-David, Ludovic Vallier, Shane T Grey, Qizhi Tang, Bart Roep, Camilo Ricordi, Ali Naji, Giuseppe Orlando, Daniel G Anderson, Mark Poznansky, Barbara Ludwig, Alice Tomei, Dale L Greiner, Melanie Graham, Melissa Carpenter, Giovanni Migliaccio, Kevin D'Amour, Bernhard Hering, Lorenzo Piemonti, Thierry Berney, Mike Rickels, Thomas Kay, Ann Adams
Beta cell replacement has the potential to restore euglycemia in patients with insulin dependent diabetes. While great progress has been made in establishing allogeneic islet transplantation from deceased donors as the standard of care for those with the most labile diabetes, it is also clear that the deceased donor organ supply cannot possibly treat all those who could benefit from restoration of a normal beta cell mass, especially if immunosuppression were not required. Against this background, the International Pancreas and Islet Transplant Association (IPITA) in collaboration with the Harvard Stem Cell Institute (HSCI), the Juvenile Diabetes Research Foundation (JDRF), and the Helmsley Foundation held a 2-day Key Opinion Leaders Meeting in Boston in 2016 to bring together experts in generating and transplanting beta cells derived from stem cells...
April 30, 2018: Transplantation
https://www.readbyqxmd.com/read/29730569/derivation-and-characterization-of-the-nih-registry-human-stem-cell-line-nyscf101-under-defined-feeder-free-conditions
#2
Ana Sevilla, Eliana Forero, Matthew Zimmer, Hector Martinez, Katie Reggio, Daniel Paull, Dieter Egli, Scott Noggle
The human embryonic stem cell line NYSCFe002-A was derived from a day 6 blastocyst in feeder-free and antibiotic free conditions. The blastocyst was voluntarily donated for research as surplus after in vitro fertilization treatment following informed consent. The NYSCFe002-A line expresses all the pluripotency markers and has the potential to differentiate into all three germ layers in vitro. The line presents normal karyotype and is mycoplasma free. This line is registered as NYSCF101 on the NIH Registry.
April 30, 2018: Stem Cell Research
https://www.readbyqxmd.com/read/29609718/reference-data-for-polysomnography-measured-and-subjective-sleep-in-healthy-adults
#3
Elisabeth Hertenstein, Agata Gabryelska, Kai Spiegelhalder, Christoph Nissen, Anna F Johann, Roza Umarova, Dieter Riemann, Chiara Baglioni, Bernd Feige
STUDY OBJECTIVES: Reference data for sleep are needed for the interpretation of clinical sleep parameters. This analysis aimed to provide polysomnography-measured, spectral analytic and subjective reference data based on a sample of healthy adults. In addition, effects of age and sex were investigated. METHODS: The sample was selected from the archival database of the Sleep Center at the University Medical Center Freiburg and consisted of 206 healthy adults aged 19 to 73 years...
March 30, 2018: Journal of Clinical Sleep Medicine: JCSM: Official Publication of the American Academy of Sleep Medicine
https://www.readbyqxmd.com/read/29241679/origins-and-predictors-of-friendships-in-6-to-8-year-old-children-born-at-neonatal-risk
#4
Katharina M Heuser, Julia Jaekel, Dieter Wolke
OBJECTIVE: To test effects of gestational age (GA), early social experiences, and child characteristics on children's friendships and perceived peer acceptance. STUDY DESIGN: As part of the prospective Bavarian Longitudinal Study (1147 children, 25-41 weeks GA), children's friendships (eg, number of friends, frequency of meeting friends) and perceived peer acceptance were assessed before school entry (6 years of age) and in second grade (8 years of age) using child and parent reports...
February 2018: Journal of Pediatrics
https://www.readbyqxmd.com/read/29161648/derivation-and-characterization-of-the-nyscfe003-a-human-embryonic-stem-cell-line
#5
Ana Sevilla, Eliana Forero, Matthew Zimmer, Hector Martinez, Katie Reggio, Daniel Paull, Dieter Egli, Scott Noggle
The human embryonic stem cell line NYSCFe003-A was derived from a day 5 to day 6 blastocyst in feeder-free and antibiotic free conditions. The blastocyst was voluntarily donated for research as surplus after in vitro fertilization treatment following informed consent. The NYSCFe003-A line expresses all the pluripotency markers and has the potential to differentiate into all three germ layers in vitro. The line presents normal karyotype and is mycoplasma free.
December 2017: Stem Cell Research
https://www.readbyqxmd.com/read/29142306/an-exome-sequencing-based-approach-for-genome-wide-association-studies-in-the-dog
#6
Bart J G Broeckx, Thomas Derrien, Stéphanie Mottier, Valentin Wucher, Edouard Cadieu, Benoît Hédan, Céline Le Béguec, Nadine Botherel, Kerstin Lindblad-Toh, Jimmy H Saunders, Dieter Deforce, Catherine André, Luc Peelman, Christophe Hitte
Genome-wide association studies (GWAS) are widely used to identify loci associated with phenotypic traits in the domestic dog that has emerged as a model for Mendelian and complex traits. However, a disadvantage of GWAS is that it always requires subsequent fine-mapping or sequencing to pinpoint causal mutations. Here, we performed whole exome sequencing (WES) and canine high-density (cHD) SNP genotyping of 28 dogs from 3 breeds to compare the SNP and linkage disequilibrium characteristics together with the power and mapping precision of exome-guided GWAS (EG-GWAS) versus cHD-based GWAS...
November 15, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28931519/%C3%AE-cell-replacement-in-mice-using-human-type-1-diabetes-nuclear-transfer-embryonic-stem-cells
#7
Lina Sui, Nichole Danzl, Sean R Campbell, Ryan Viola, Damian Williams, Yuan Xing, Yong Wang, Neil Phillips, Greg Poffenberger, Bjarki Johannesson, Jose Oberholzer, Alvin C Powers, Rudolph L Leibel, Xiaojuan Chen, Megan Sykes, Dieter Egli
β-Cells derived from stem cells hold great promise for cell replacement therapy for diabetes. Here we examine the ability of nuclear transfer embryonic stem cells (NT-ESs) derived from a patient with type 1 diabetes to differentiate into β-cells and provide a source of autologous islets for cell replacement. NT-ESs differentiate in vitro with an average efficiency of 55% into C-peptide-positive cells, expressing markers of mature β-cells, including MAFA and NKX6.1. Upon transplantation in immunodeficient mice, grafted cells form vascularized islet-like structures containing MAFA/C-peptide-positive cells...
January 2018: Diabetes
https://www.readbyqxmd.com/read/28548589/tying-genetic-stability-to-cell-identity
#8
Daniela Georgieva, Dieter Egli
No abstract text is available yet for this article.
June 18, 2017: Cell Cycle
https://www.readbyqxmd.com/read/28263958/genomic-instability-during-reprogramming-by-nuclear-transfer-is-dna-replication-dependent
#9
Gloryn Chia, Judith Agudo, Nathan Treff, Mark V Sauer, David Billing, Brian D Brown, Richard Baer, Dieter Egli
Somatic cells can be reprogrammed to a pluripotent state by nuclear transfer into oocytes, yet developmental arrest often occurs. While incomplete transcriptional reprogramming is known to cause developmental failure, reprogramming also involves concurrent changes in cell cycle progression and nuclear structure. Here we study cellular reprogramming events in human and mouse nuclear transfer embryos prior to embryonic genome activation. We show that genetic instability marked by frequent chromosome segregation errors and DNA damage arise prior to, and independent of, transcriptional activity...
April 2017: Nature Cell Biology
https://www.readbyqxmd.com/read/28242217/genome-transfer-prevents-fragmentation-and-restores-developmental-potential-of-developmentally-compromised-postovulatory-aged-mouse-oocytes
#10
Mitsutoshi Yamada, Dieter Egli
Changes in oocyte quality can have great impact on the developmental potential of early embryos. Here we test whether nuclear genome transfer from a developmentally incompetent to a developmentally competent oocyte can restore developmental potential. Using in vitro oocyte aging as a model system we performed nuclear transfer in mouse oocytes at metaphase II or at the first interphase, and observed that development to the blastocyst stage and to term was as efficient as in control embryos. The increased developmental potential is explained primarily by correction of abnormal cytokinesis at anaphase of meiosis and mitosis, by a reduction in chromosome segregation errors, and by normalization of the localization of chromosome passenger complex components survivin and cyclin B1...
March 14, 2017: Stem Cell Reports
https://www.readbyqxmd.com/read/28132887/pc1-3-deficiency-impacts-pro-opiomelanocortin-processing-in-human-embryonic-stem-cell-derived-hypothalamic-neurons
#11
Liheng Wang, Lina Sui, Sunil K Panigrahi, Kana Meece, Yurong Xin, Jinrang Kim, Jesper Gromada, Claudia A Doege, Sharon L Wardlaw, Dieter Egli, Rudolph L Leibel
We recently developed a technique for generating hypothalamic neurons from human pluripotent stem cells. Here, as proof of principle, we examine the use of these cells in modeling of a monogenic form of severe obesity: PCSK1 deficiency. The cognate enzyme, PC1/3, processes many prohormones in neuroendocrine and other tissues. We generated PCSK1 (PC1/3)-deficient human embryonic stem cell (hESC) lines using both short hairpin RNA and CRISPR-Cas9, and investigated pro-opiomelanocortin (POMC) processing using hESC-differentiated hypothalamic neurons...
February 14, 2017: Stem Cell Reports
https://www.readbyqxmd.com/read/28094769/ipsc-derived-%C3%AE-cells-model-diabetes-due-to-glucokinase-deficiency
#12
Haiqing Hua, Linshan Shang, Hector Martinez, Matthew Freeby, Mary Pat Gallagher, Thomas Ludwig, Liyong Deng, Ellen Greenberg, Charles LeDuc, Wendy K Chung, Robin Goland, Rudolph L Leibel, Dieter Egli
No abstract text is available yet for this article.
March 1, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/27941249/deficiency-in-prohormone-convertase-pc1-impairs-prohormone-processing-in-prader-willi-syndrome
#13
Lisa C Burnett, Charles A LeDuc, Carlos R Sulsona, Daniel Paull, Richard Rausch, Sanaa Eddiry, Jayne F Martin Carli, Michael V Morabito, Alicja A Skowronski, Gabriela Hubner, Matthew Zimmer, Liheng Wang, Robert Day, Brynn Levy, Ilene Fennoy, Beatrice Dubern, Christine Poitou, Karine Clement, Merlin G Butler, Michael Rosenbaum, Jean Pierre Salles, Maithe Tauber, Daniel J Driscoll, Dieter Egli, Rudolph L Leibel
Prader-Willi syndrome (PWS) is caused by a loss of paternally expressed genes in an imprinted region of chromosome 15q. Among the canonical PWS phenotypes are hyperphagic obesity, central hypogonadism, and low growth hormone (GH). Rare microdeletions in PWS patients define a 91-kb minimum critical deletion region encompassing 3 genes, including the noncoding RNA gene SNORD116. Here, we found that protein and transcript levels of nescient helix loop helix 2 (NHLH2) and the prohormone convertase PC1 (encoded by PCSK1) were reduced in PWS patient induced pluripotent stem cell-derived (iPSC-derived) neurons...
January 3, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/27789403/induced-pluripotent-stem-cells-ipsc-created-from-skin-fibroblasts-of-patients-with-prader-willi-syndrome-pws-retain-the-molecular-signature-of-pws
#14
Lisa C Burnett, Charles A LeDuc, Carlos R Sulsona, Daniel Paull, Sanaa Eddiry, Brynn Levy, Jean Pierre Salles, Maithe Tauber, Daniel J Driscoll, Dieter Egli, Rudolph L Leibel
Prader-Willi syndrome (PWS) is a syndromic obesity caused by loss of paternal gene expression in an imprinted interval on 15q11.2-q13. Induced pluripotent stem cells were generated from skin cells of three large deletion PWS patients and one unique microdeletion PWS patient. We found that genes within the PWS region, including SNRPN and NDN, showed persistence of DNA methylation after iPSC reprogramming and differentiation to neurons. Genes within the PWS minimum critical deletion region remain silenced in both PWS large deletion and microdeletion iPSC following reprogramming...
November 2016: Stem Cell Research
https://www.readbyqxmd.com/read/27763625/identification-and-propagation-of-haploid-human-pluripotent-stem-cells
#15
Ido Sagi, Dieter Egli, Nissim Benvenisty
Haploid human pluripotent stem cells (PSCs) integrate haploidy and pluripotency, providing a novel system for functional genomics and developmental research in humans. We have recently derived haploid human embryonic stem cells (ESCs) by parthenogenesis and demonstrated their wide differentiation potential and applicability for genetic screening. Because haploid cells can spontaneously become diploid, their enrichment at an early passage is key for successful derivation. In this protocol, we describe two methodologies, namely metaphase spread analysis and cell sorting, for the identification of haploid human cells within parthenogenetic ESC lines...
November 2016: Nature Protocols
https://www.readbyqxmd.com/read/27500271/a-proposal-for-early-dosing-regimens-in-heart-transplant-patients-receiving-thymoglobulin-and-calcineurin-inhibition
#16
REVIEW
Markus J Barten, Uwe Schulz, Andres Beiras-Fernandez, Michael Berchtold-Herz, Udo Boeken, Jens Garbade, Stephan Hirt, Manfred Richter, Arjang Ruhpawar, Jan Dieter Schmitto, Felix Schönrath, Rene Schramm, Martin Schweiger, Markus Wilhelm, Andreas Zuckermann
There is currently no consensus regarding the dose or duration of rabbit antithymocyte globulin (rATG) induction in different types of heart transplant patients, or the timing and intensity of initial calcineurin inhibitor (CNI) therapy in rATG-treated individuals. Based on limited data and personal experience, the authors propose an approach to rATG dosing and initial CNI administration. Usually rATG is initiated immediately after exclusion of primary graft failure, although intraoperative initiation may be appropriate in specific cases...
June 2016: Transplantation Direct
https://www.readbyqxmd.com/read/27385103/analysis-of-chromosomal-aberrations-and-recombination-by-allelic-bias-in-rna-seq
#17
Uri Weissbein, Maya Schachter, Dieter Egli, Nissim Benvenisty
Genomic instability has profound effects on cellular phenotypes. Studies have shown that pluripotent cells with abnormal karyotypes may grow faster, differentiate less and become more resistance to apoptosis. Previously, we showed that microarray gene expression profiles can be utilized for the analysis of chromosomal aberrations by comparing gene expression levels between normal and aneuploid samples. Here we adopted this method for RNA-Seq data and present eSNP-Karyotyping for the detection of chromosomal aberrations, based on measuring the ratio of expression between the two alleles...
July 7, 2016: Nature Communications
https://www.readbyqxmd.com/read/27367166/efficient-generation-of-hypothalamic-neurons-from-human-pluripotent-stem-cells
#18
Liheng Wang, Dieter Egli, Rudolph L Leibel
The hypothalamus comprises neuronal clusters that are essential for body weight regulation and other physiological functions. Insights into the complex cellular physiology of this region of the brain are critical to understanding the pathogenesis of obesity, but human hypothalamic cells are largely inaccessible for direct study. Here we describe a technique for generation of arcuate-like hypothalamic neurons from human pluripotent stem (hPS) cells. Early activation of SHH signaling and inhibition of BMP and TGFβ signaling, followed by timed inhibition of NOTCH, can efficiently differentiate hPS cells into NKX2...
July 1, 2016: Current Protocols in Human Genetics
https://www.readbyqxmd.com/read/27212703/genetic-drift-can-compromise-mitochondrial-replacement-by-nuclear-transfer-in-human-oocytes
#19
Mitsutoshi Yamada, Valentina Emmanuele, Maria J Sanchez-Quintero, Bruce Sun, Gregory Lallos, Daniel Paull, Matthew Zimmer, Shardonay Pagett, Robert W Prosser, Mark V Sauer, Michio Hirano, Dieter Egli
Replacement of mitochondria through nuclear transfer between oocytes of two different women has emerged recently as a strategy for preventing inheritance of mtDNA diseases. Although experiments in human oocytes have shown effective replacement, the consequences of small amounts of mtDNA carryover have not been studied sufficiently. Using human mitochondrial replacement stem cell lines, we show that, even though the low levels of heteroplasmy introduced into human oocytes by mitochondrial carryover during nuclear transfer often vanish, they can sometimes instead result in mtDNA genotypic drift and reversion to the original genotype...
June 2, 2016: Cell Stem Cell
https://www.readbyqxmd.com/read/27064284/hypomorphism-of-fto-and-rpgrip1l-causes-obesity-in-mice
#20
George Stratigopoulos, Lisa Cole Burnett, Richard Rausch, Richard Gill, David Barth Penn, Alicja A Skowronski, Charles A LeDuc, Anthony J Lanzano, Pumin Zhang, Daniel R Storm, Dieter Egli, Rudolph L Leibel
Noncoding polymorphisms in the fat mass and obesity-associated (FTO) gene represent common alleles that are strongly associated with effects on food intake and adiposity in humans. Previous studies have suggested that the obesity-risk allele rs8050136 in the first intron of FTO alters a regulatory element recognized by the transcription factor CUX1, thereby leading to decreased expression of FTO and retinitis pigmentosa GTPase regulator-interacting protein-1 like (RPGRIP1L). Here, we evaluated the effects of rs8050136 and another potential CUX1 element in rs1421085 on expression of nearby genes in human induced pluripotent stem cell-derived (iPSC-derived) neurons...
May 2, 2016: Journal of Clinical Investigation
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