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https://www.readbyqxmd.com/read/28334154/ethical-issues-of-crispr-technology-and-gene-editing-through-the-lens-of-solidarity
#1
John J Mulvihill, Benjamin Capps, Yann Joly, Tamra Lysaght, Hub A E Zwart, Ruth Chadwick
Background: The avalanche of commentaries on CRISPR-Cas9 technology, a bacterial immune system modified to recognize any short DNA sequence, cut it out, and insert a new one, has rekindled hopes for gene therapy and other applications and raised criticisms of engineering genes in future generations. Sources of data: This discussion draws on articles that emphasize ethics, identified partly through PubMed and Google, 2014-2016. Areas of agreement: CRISPR-Cas9 has taken the pace and prospects for genetic discovery and applications to a high level, stoking anticipation for somatic gene engineering to help patients...
February 23, 2017: British Medical Bulletin
https://www.readbyqxmd.com/read/28300214/corrigendum-hipstr-and-thousands-of-lncrnas-are-heterogeneously-expressed-in-human-embryos-primordial-germ-cells-and-stable-cell-lines
#2
Dinar Yunusov, Leticia Anderson, Lucas Ferreira DaSilva, Joanna Wysocka, Toshihiko Ezashi, R Michael Roberts, Sergio Verjovski-Almeida
No abstract text is available yet for this article.
March 16, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28290517/sensitivity-to-oxazolone-induced-dermatitis-is-transferable-with-gut-microbiota-in-mice
#3
Line Fisker Zachariassen, Lukasz Krych, Kåre Engkilde, Dennis Sandris Nielsen, Witold Kot, Camilla Hartmann Friis Hansen, Axel Kornerup Hansen
Atopic Dermatitis (AD) has been associated with gut microbiota (GM) dysbiosis in humans, indicating a causative role of GM in AD etiology. Furthermore, the GM strongly correlates to essential disease parameters in the well-known oxazolone-induced mouse model of AD. Here, we demonstrate that it is possible to transfer both a high-responding and a low-responding AD phenotype with GM from conventional mice to germ-free mice. The mice inoculated with the high-responding GM had significantly higher clinical score, increased ear thickness, and increased levels of IL-1β, TNFα, IL-4, IL-5, and IL-6 compared to the mice inoculated with the low-responding GM...
March 14, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28287531/the-production-of-pluripotent-stem-cells-from-mouse-amniotic-fluid-cells-using-a-transposon-system
#4
Enrica Bertin, Martina Piccoli, Chiara Franzin, Andras Nagy, Maria Mileikovsky, Paolo De Coppi, Michela Pozzobon
Induced pluripotent stem (iPS) cells are generated from mouse and human somatic cells by forced expression of defined transcription factors using different methods. Here, we produced iPS cells from mouse amniotic fluid cells, using a non-viral-based transposon system. All obtained iPS cell lines exhibited characteristics of pluripotent cells, including the ability to differentiate toward derivatives of all three germ layers in vitro and in vivo. This strategy opens up the possibility of using cells from diseased fetuses to develop new therapies for birth defects...
February 28, 2017: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/28259963/comparison-of-the-early-response-of-human-embryonic-stem-cells-and-human-induced-pluripotent-stem-cells-to-ionizing-radiation
#5
Wiktoria Maria Suchorska, Ewelina Augustyniak, Magdalena Łukjanow
Despite the well-demonstrated efficacy of stem cell (SC) therapy, this approach has a number of key drawbacks. One important concern is the response of pluripotent SCs to treatment with ionizing radiation (IR), given that SCs used in regenerative medicine will eventually be exposed to IR for diagnostic or treatment‑associated purposes. Therefore, the aim of the present study was to examine and compare early IR‑induced responses of pluripotent SCs to assess their radioresistance and radiosensitivity. In the present study, 3 cell lines; human embryonic SCs (hESCs), human induced pluripotent SCs (hiPSCs) and primary human dermal fibroblasts (PHDFs); were exposed to IR at doses ranging from 0 to 15 gray (Gy)...
March 1, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28253983/micrornas-aging-cellular-senescence-and-alzheimer-s-disease
#6
P H Reddy, J Williams, F Smith, J S Bhatti, S Kumar, M Vijayan, R Kandimalla, C S Kuruva, R Wang, M Manczak, X Yin, A P Reddy
Aging is a normal process of living being. It has been reported that multiple cellular changes, including oxidative damage/mitochondrial dysfunction, telomere shortening, inflammation, may accelerate the aging process, leading to cellular senescence. These cellular changes induce age-related human diseases, including Alzheimer's, Parkinson's, multiple sclerosis, amyotrophic lateral sclerosis, cardiovascular, cancer, and skin diseases. Changes in somatic and germ-line DNA and epigenetics are reported to play large roles in accelerating the onset of human diseases...
2017: Progress in Molecular Biology and Translational Science
https://www.readbyqxmd.com/read/28244148/detection-of-inherited-chromosomally-integrated-hhv-6-cihhv-6-in-a-marker-chromosome
#7
Diana Campioni, Valentina Gentili, Francesco Cavazzini, Daria Bortolotti, Elisabeth P Nacheva, Antonio Cuneo, Dario Di Luca, Roberta Rizzo
OBJECTIVES: Inherited chromosomally integrated human herpesvirus 6 (ciHHV-6) is characterized by the complete HHV-6 genome integration into the host germ line genome and is vertically transmitted with a Mendelian inheritance. By now, the only relationship between ciHHV-6 and diseases seems to be with angina pectoris. METHODS: We report a case of an 82 years old male diagnosed with Diffuse Large B-cell Lymphoma (DLBCL) on October 2014. To substantiate the suspicion of ciHHV-6, we analysed peripheral blood mononuclear cells, bone marrow biopsy and pleural effusion derived mesothelial cells with PCR, RT-PCR and FISH...
February 28, 2017: European Journal of Haematology
https://www.readbyqxmd.com/read/28240438/feeder-independent-canine-induced-pluripotent-stem-cells-maintained-under-serum-free-conditions
#8
Toshiya Nishimura, Shingo Hatoya, Ryoji Kanegi, Daluthgamage Pasty Himali Wijesekera, Kousuke Sanno, Erina Tanaka, Kikuya Sugiura, Noritoshi Kawate, Hiromitsu Tamada, Hiroshi Imai, Toshio Inaba
Canine induced pluripotent stem cells (ciPSCs) are an attractive source for regenerative veterinary medicine, and may also serve as a disease model for human regenerative medicine. Extending the application of ciPSCs from bench to bedside, however, requires the resolution of many issues. We generated ciPSCs expressing doxycycline-inducible murine Oct3/4 (Pou5f1), Sox2, Klf4, and c-Myc, which were introduced using lentiviral vectors. The resultant ciPSCs required doxycycline to proliferate in the undifferentiated state...
February 27, 2017: Molecular Reproduction and Development
https://www.readbyqxmd.com/read/28224202/germline-specific-dgcr8-knockout-in-zebrafish-using-a-back-approach
#9
Yun Liu, Zeyao Zhu, Idy H T Ho, Yujian Shi, Yuxin Xie, Jianzhen Li, Yong Zhang, Matthew T V Chan, Christopher H K Cheng
Zebrafish is an important model to study developmental biology and human diseases. However, an effective approach to achieve spatial and temporal gene knockout in zebrafish has not been well established. In this study, we have developed a new approach, namely bacterial artificial chromosome-rescue-based knockout (BACK), to achieve conditional gene knockout in zebrafish using the Cre/loxP system. We have successfully deleted the DiGeorge syndrome critical region gene 8 (dgcr8) in zebrafish germ line and demonstrated that the maternal-zygotic dgcr8 (MZdgcr8) embryos exhibit MZdicer-like phenotypes with morphological defects which could be rescued by miR-430, indicating that canonical microRNAs play critical role in early development...
February 21, 2017: Cellular and Molecular Life Sciences: CMLS
https://www.readbyqxmd.com/read/28222195/autoantibodies-against-mono-and-tri-methylated-lysine-display-similar-but-also-distinctive-characteristics
#10
Zhiqiang Wang, Younan Ma, Fan Liu, Linjie Chen, Ruitong Gao, Wei Zhang
Autoantibodies can be either harmful or beneficial to the body. The beneficial autoantibodies play important roles in immunosurveillance, clearance of body waste and maintenance of immune homeostasis. Despite their importance, however, people's knowledge on the protective autoantibodies is still very limited. In the current study, we examined two autoantibodies that recognized epitopes with only one amino acid. One was against mono-methylated lysine (Kme) and the other was against tri-methylated lysine (Kme3)...
2017: PloS One
https://www.readbyqxmd.com/read/28207785/dna-methylation-of-the-fthl17-5-upstream-region-regulates-differential-fthl17-expression-in-lung-cancer-cells-and-germline-stem-cells
#11
Nana Aoki, Kentaro Mochizuki, Yasuhisa Matsui
The Ferritin heavy polypeptide-like 17 (Fthl17) gene is a member of the cancer/testis antigen gene family, and is preferentially expressed in cancer cells and in testis. Although DNA methylation has been linked to the regulation of human FTHL17 gene expression, detailed epigenetic regulation of its expression has not been investigated. To address this, we assessed the epigenetic regulation of murine Fthl17 gene expression in cancer cells and germ cells. Fthl17 was more highly expressed in testis, a murine lung cancer cell line, KLN205, and in germline stem cells (GSCs) than in normal lung tissues...
2017: PloS One
https://www.readbyqxmd.com/read/28202061/in-vitro-generation-of-sertoli-like-and-haploid-spermatid-like-cells-from-human-umbilical-cord-perivascular-cells
#12
Ekaterina Shlush, Leila Maghen, Sonja Swanson, Shlomit Kenigsberg, Sergey Moskovtsev, Tanya Barretto, Andrée Gauthier-Fisher, Clifford L Librach
BACKGROUND: First trimester (FTM) and term human umbilical cord-derived perivascular cells (HUCPVCs), which are rich sources of mesenchymal stem cells (MSCs), can give rise to Sertoli cell (SC)-like as well as haploid germ cell (GC)-like cells in vitro using culture conditions that recapitulate the testicular niche. Gamete-like cells have been produced ex vivo using pluripotent stem cells as well as MSCs. However, the production of functional gametes from human stem cells has yet to be achieved...
February 15, 2017: Stem Cell Research & Therapy
https://www.readbyqxmd.com/read/28186187/factors-associated-with-aberrant-imprint-methylation-and-oligozoospermia
#13
Norio Kobayashi, Naoko Miyauchi, Nozomi Tatsuta, Akane Kitamura, Hiroaki Okae, Hitoshi Hiura, Akiko Sato, Takafumi Utsunomiya, Nobuo Yaegashi, Kunihiko Nakai, Takahiro Arima
Disturbingly, the number of patients with oligozoospermia (low sperm count) has been gradually increasing in industrialized countries. Epigenetic alterations are believed to be involved in this condition. Recent studies have clarified that intrinsic and extrinsic factors can induce epigenetic transgenerational phenotypes through apparent reprogramming of the male germ line. Here we examined DNA methylation levels of 22 human imprinted loci in a total of 221 purified sperm samples from infertile couples and found methylation alterations in 24...
February 10, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28159550/characterization-of-the-diversity-of-t-cell-receptor-%C3%AE-%C3%AE-complementary-determinant-region-3-in-human-peripheral-blood-by-immune-repertoire-sequencing
#14
Hui Chen, Mingjin Zou, Da Teng, Jianmin Zhang, Wei He
γδ T cells function as sentinels in early host response to infections and malignancies. Although γδ T cells are regarded as innate immune cells and recognize antigens in a non-MHC restricted manner, they possess a huge diversity of complementary determinant region 3 (CDR3) of T cell receptor (TCR) generated by the rearrangement of germ-line gene V- (D) -J-C fragments. However, the detailed characteristics of the TCRγδ CDR3 repertoire remain unclear. A comprehensive analysis would answer fundamental questions about the diversity of the TCRγδ CDR3 repertoire and elucidate the mechanism underlying γδ T cell recognition of pathogens and tumor antigens...
January 31, 2017: Journal of Immunological Methods
https://www.readbyqxmd.com/read/28146567/differential-dna-methylation-regions-in-adult-human-sperm-following-adolescent-chemotherapy-potential-for-epigenetic-inheritance
#15
Margarett Shnorhavorian, Stephen M Schwartz, Barbara Stansfeld, Ingrid Sadler-Riggleman, Daniel Beck, Michael K Skinner
BACKGROUND: The potential that adolescent chemotherapy can impact the epigenetic programming of the germ line to influence later life adult fertility and promote epigenetic inheritance was investigated. Previous studies have demonstrated a number of environmental exposures such as abnormal nutrition and toxicants can promote sperm epigenetic changes that impact offspring. METHODS: Adult males approximately ten years after pubertal exposure to chemotherapy were compared to adult males with no previous exposure...
2017: PloS One
https://www.readbyqxmd.com/read/28143957/insights-into-the-pathological-mechanisms-of-p85%C3%AE-mutations-using-a-yeast-based-phosphatydilinositol-3-kinase-model
#16
María D Oliver, Teresa Fernández-Acero, Sandra Luna, Isabel Rodríguez-Escudero, María Molina, Rafael Pulido, Victor J Cid
In higher eukaryotes, cell proliferation is regulated by class I phosphatidylinositol 3-kinase (PI3K), which transduces stimuli received from neighboring receptors by local generation of PtdIns(3,4,5)P3 in cellular membranes. PI3K is a heterodimeric protein consisting of a regulatory and a catalytic subunit (p85 and p110, respectively). Heterologous expression of p110a in S. cerevisiae leads to toxicity by conversion of essential PtdIns(4,5)P2 into futile PtdIns(3,4,5)P3, providing a humanized yeast model for functional studies on this pathway...
January 31, 2017: Bioscience Reports
https://www.readbyqxmd.com/read/28137366/somatic-mutations-in-cancer-stochastic-versus-predictable
#17
Barry Gold
The origins of human cancers remain unclear except for a limited number of potent environmental mutagens, such as tobacco and UV light, and in rare cases, familial germ line mutations that affect tumor suppressor genes or oncogenes. A significant component of cancer etiology has been deemed stochastic and correlated with the number of stem cells in a tissue, the number of times the stem cells divide and a low incidence of random DNA polymerase errors that occur during each cell division. While somatic mutations occur during each round of DNA replication, mutations in cancer driver genes are not stochastic...
February 2017: Mutation Research
https://www.readbyqxmd.com/read/28135246/avian-w-and-mammalian-y-chromosomes-convergently-retained-dosage-sensitive-regulators
#18
Daniel W Bellott, Helen Skaletsky, Ting-Jan Cho, Laura Brown, Devin Locke, Nancy Chen, Svetlana Galkina, Tatyana Pyntikova, Natalia Koutseva, Tina Graves, Colin Kremitzki, Wesley C Warren, Andrew G Clark, Elena Gaginskaya, Richard K Wilson, David C Page
After birds diverged from mammals, different ancestral autosomes evolved into sex chromosomes in each lineage. In birds, females are ZW and males are ZZ, but in mammals females are XX and males are XY. We sequenced the chicken W chromosome, compared its gene content with our reconstruction of the ancestral autosomes, and followed the evolutionary trajectory of ancestral W-linked genes across birds. Avian W chromosomes evolved in parallel with mammalian Y chromosomes, preserving ancestral genes through selection to maintain the dosage of broadly expressed regulators of key cellular processes...
March 2017: Nature Genetics
https://www.readbyqxmd.com/read/28134624/dosage-dependent-copy-number-gains-in-e2f1-and-e2f3-drive-hepatocellular-carcinoma
#19
Lindsey N Kent, Sooin Bae, Shih-Yin Tsai, Xing Tang, Arunima Srivastava, Christopher Koivisto, Chelsea K Martin, Elisa Ridolfi, Grace C Miller, Sarah M Zorko, Emilia Plevris, Yannis Hadjiyannis, Miguel Perez, Eric Nolan, Raleigh Kladney, Bart Westendorp, Alain de Bruin, Soledad Fernandez, Thomas J Rosol, Kamal S Pohar, James M Pipas, Gustavo Leone
Disruption of the retinoblastoma (RB) tumor suppressor pathway, either through genetic mutation of upstream regulatory components or mutation of RB1 itself, is believed to be a required event in cancer. However, genetic alterations in the RB-regulated E2F family of transcription factors are infrequent, casting doubt on a direct role for E2Fs in driving cancer. In this work, a mutation analysis of human cancer revealed subtle but impactful copy number gains in E2F1 and E2F3 in hepatocellular carcinoma (HCC)...
March 1, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28117672/reprogramming-methods-do-not-affect-gene-expression-profile-of-human-induced-pluripotent-stem-cells
#20
Marta Trevisan, Giovanna Desole, Giulia Costanzi, Enrico Lavezzo, Giorgio Palù, Luisa Barzon
Induced pluripotent stem cells (iPSCs) are pluripotent cells derived from adult somatic cells. After the pioneering work by Yamanaka, who first generated iPSCs by retroviral transduction of four reprogramming factors, several alternative methods to obtain iPSCs have been developed in order to increase the yield and safety of the process. However, the question remains open on whether the different reprogramming methods can influence the pluripotency features of the derived lines. In this study, three different strategies, based on retroviral vectors, episomal vectors, and Sendai virus vectors, were applied to derive iPSCs from human fibroblasts...
January 20, 2017: International Journal of Molecular Sciences
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