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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
#1
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
#2
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
#3
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
#4
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
#5
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
#6
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
#7
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
#8
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...
January 30, 2017: Nature Genetics
https://www.readbyqxmd.com/read/28134624/dosage-dependent-copy-number-gains-in-e2f1-and-e2f3-drive-hepatocellular-carcinoma
#9
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)...
January 30, 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
#10
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
https://www.readbyqxmd.com/read/28107194/transdifferentiation-of-human-male-germline-stem-cells-to-hepatocytes-in-vivo-via-the-transplantation-under-renal-capsules
#11
Zheng Chen, Minghui Niu, Min Sun, Qingqing Yuan, Chencheng Yao, Jingmei Hou, Hong Wang, Liping Wen, Hongyong Fu, Fan Zhou, Zheng Li, Zuping He
Here we proposed a new concept that human spermatogonial stem cells (SSCs) can transdifferentiate into hepatocytes in vivo. We first established liver injury model of mice by carbon tetrachloride to provide proper environment for human SSC transplantation. Liver mesenchymal cells were isolated from mice and identified phenotypically. Human SSC line was recombined with liver mesenchymal cells, and they were transplanted under renal capsules of nude mice with liver injury. The grafts expressed hepatocyte hallmarks, including ALB, AAT, CK18, and CYP1A2, whereas germ cell and SSC markers VASA and GPR125 were undetected in these cells, implicating that human SSCs were converted to hepatocytes...
January 18, 2017: Oncotarget
https://www.readbyqxmd.com/read/28106558/validation-of-suspected-somatic-single-nucleotide-variations-in-the-brain-of-alzheimer-s-disease-patients
#12
Alberto Gomez-Ramos, Angel J Picher, Esther García, Patricia Garrido, Felix Hernandez, Eduardo Soriano, Jesús Avila
Next-generation sequencing techniques and genome-wide association study analyses have provided a huge amount of data, thereby enabling the identification of DNA variations and mutations related to disease pathogenesis. New techniques and software tools have been developed to improve the accuracy and reliability of this identification. Most of these tools have been designed to discover and validate single nucleotide variants (SNVs). However, in addition to germ-line mutations, human tissues bear genomic mosaicism, which implies that somatic events are present only in low percentages of cells within a given tissue, thereby hindering the validation of these variations using standard genetic tools...
January 19, 2017: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/28073973/human-foetal-ovary-shares-meiotic-preventing-factors-with-the-developing-testis
#13
Nelly Frydman, Marine Poulain, Brahim Arkoun, Clotilde Duquenne, Sophie Tourpin, Sébastien Messiaen, René Habert, Virginie Rouiller-Fabre, Alexandra Benachi, Gabriel Livera
STUDY QUESTION: How can pre-meiotic germ cells persist in the human foetal ovary? SUMMARY ANSWER: Numerous oogonia escaping meiotic entry were retrieved throughout human ovarian development simultaneously with the expression of signalling pathways preventing meiosis, typically described in the rodent embryonic testis. WHAT IS KNOWN ALREADY: The transition from mitosis to meiosis is a key event in female germ cells that remains poorly documented in research on the human ovary...
January 9, 2017: Human Reproduction
https://www.readbyqxmd.com/read/28053071/mouse-models-for-drug-discovery-can-new-tools-and-technology-improve-translational-power
#14
Aamir Zuberi, Cathleen Lutz
The use of mouse models in biomedical research and preclinical drug evaluation is on the rise. The advent of new molecular genome-altering technologies such as CRISPR/Cas9 allows for genetic mutations to be introduced into the germ line of a mouse faster and less expensively than previous methods. In addition, the rapid progress in the development and use of somatic transgenesis using viral vectors, as well as manipulations of gene expression with siRNAs and antisense oligonucleotides, allow for even greater exploration into genomics and systems biology...
December 2016: ILAR Journal
https://www.readbyqxmd.com/read/28049852/in-vivo-severity-ranking-of-ras-pathway-mutations-associated-with-developmental-disorders
#15
Granton A Jindal, Yogesh Goyal, Kei Yamaya, Alan S Futran, Iason Kountouridis, Courtney A Balgobin, Trudi Schüpbach, Rebecca D Burdine, Stanislav Y Shvartsman
Germ-line mutations in components of the Ras/MAPK pathway result in developmental disorders called RASopathies, affecting about 1/1,000 human births. Rapid advances in genome sequencing make it possible to identify multiple disease-related mutations, but there is currently no systematic framework for translating this information into patient-specific predictions of disease progression. As a first step toward addressing this issue, we developed a quantitative, inexpensive, and rapid framework that relies on the early zebrafish embryo to assess mutational effects on a common scale...
January 17, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28038682/comparison-of-a-teratogenic-transcriptome-based-predictive-test-based-on-human-embryonic-versus-inducible-pluripotent-stem-cells
#16
Vaibhav Shinde, Sureshkumar Perumal Srinivasan, Margit Henry, Tamara Rotshteyn, Jürgen Hescheler, Jörg Rahnenführer, Marianna Grinberg, Johannes Meisig, Nils Blüthgen, Tanja Waldmann, Marcel Leist, Jan Georg Hengstler, Agapios Sachinidis
BACKGROUND: Human embryonic stem cells (hESCs) partially recapitulate early embryonic three germ layer development, allowing testing of potential teratogenic hazards. Because use of hESCs is ethically debated, we investigated the potential for human induced pluripotent stem cells (hiPSCs) to replace hESCs in such tests. METHODS: Three cell lines, comprising hiPSCs (foreskin and IMR90) and hESCs (H9) were differentiated for 14 days. Their transcriptome profiles were obtained on day 0 and day 14 and analyzed by comprehensive bioinformatics tools...
December 30, 2016: Stem Cell Research & Therapy
https://www.readbyqxmd.com/read/28025795/possible-role-of-hiwi2-in-modulating-tight-junction-proteins-in-retinal-pigment-epithelial-cells-through-akt-signaling-pathway
#17
Suganya Sivagurunathan, Karthikka Palanisamy, Jayamuruga Pandian Arunachalam, Subbulakshmi Chidambaram
PIWI subfamily of proteins is shown to be primarily expressed in germline cells. They maintain the genomic integrity by silencing the transposable elements. Although the role of PIWI proteins in germ cells has been documented, their presence and function in somatic cells remains unclear. Intriguingly, we detected all four members of PIWI-like proteins in human ocular tissues and somatic cell lines. When HIWI2 was knocked down in retinal pigment epithelial cells, the typical honeycomb morphology was affected...
March 2017: Molecular and Cellular Biochemistry
https://www.readbyqxmd.com/read/28018848/mitochondrial-transfer-implications-for-assisted-reproductive-technologies
#18
REVIEW
A S Reznichenko, C Huyser, M S Pepper
The use of mitochondrial transfer as a clinic procedure is drawing closer to reality. Here we provide a detailed overview of mitochondrial transfer techniques - both established and recent - including pronuclear, spindle, ooplasmic and blastomere transfer. Reasons as to why some techniques are more suitable for the prevention of mitochondrial DNA disease than others, as well as the advantages and disadvantages of each methodology, are discussed. The possible clinical introduction of these techniques has raised concerns about the adverse effects they may have on resultant embryos and offspring...
December 2016: Applied & Translational Genomics
https://www.readbyqxmd.com/read/28000896/mir%C3%A2-223%C3%A2-3p-regulates-cell-growth-and-apoptosis-via-fbxw7-suggesting-an-oncogenic-role-in-human-testicular-germ-cell-tumors
#19
Jikai Liu, Hao Shi, Xidan Li, Gang Chen, Catharina Larsson, Weng-Onn Lui
miR‑223‑3p is deregulated in several tumor types and plays an important role in tumorigenesis and progression. However, its role in the pathogenesis of testicular germ cell tumor (TGCT) remains uncharacterized. We previously demonstrated that miR‑223‑3p expression was increased in TGCTs compared with normal testes (NT), suggesting that miR‑223‑3p may have an oncogenic role in TGCT. Using published dataset and The Cancer Genome Atlas database, we validated higher miR‑223‑3p expression in TGCTs than NT, and found a negative correlation between miR-223-3p and FBXW7 mRNA expression levels...
February 2017: International Journal of Oncology
https://www.readbyqxmd.com/read/27992447/heat-sensing-receptor-trpv1-is-a-mediator-of-thermotaxis-in-human-spermatozoa
#20
Luca De Toni, Andrea Garolla, Massimo Menegazzo, Sabina Magagna, Andrea Di Nisio, Iva Šabović, Maria Santa Rocca, Valentina Scattolini, Andrea Filippi, Carlo Foresta
The molecular bases of sperm thermotaxis, the temperature-oriented cell motility, are currently under investigation. Thermal perception relies on a subclass of the transient receptor potential [TRP] channels, whose member TRPV1 is acknowledged as the heat sensing receptor. Here we investigated the involvement of TRPV1 in human sperm thermotaxis. We obtained semen samples from 16 normozoospermic subjects attending an infertility survey programme, testis biopsies from 6 patients with testicular germ cell cancer and testis fine needle aspirates from 6 patients with obstructive azoospermia undergoing assisted reproductive technologies...
2016: PloS One
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