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https://www.readbyqxmd.com/read/28626364/ex-vivo-generation-of-genetically-modified-macrophages-from-human-induced-pluripotent-stem-cells
#1
Mania Ackermann, Alexandra Kuhn, Jessica Kunkiel, Sylvia Merkert, Ulrich Martin, Thomas Moritz, Nico Lachmann
BACKGROUND: Pluripotent stem cells, including induced pluripotent stem cells (iPSCs), have the capacity to differentiate towards all three germ layers and have been highlighted as an attractive cell source for the field of regenerative medicine. Thus, stable expression of therapeutic transgenes in iPSCs, as well as thereof derived progeny of hematopoietic lineage, may lay the foundation for innovative cell replacement therapies. METHODS: We have utilized human iPSC lines genetically modified by lentiviral vector technology or targeted integration of reporter genes to evaluate transgene expression during hematopoietic specification and differentiation towards macrophages...
June 2017: Transfusion Medicine and Hemotherapy
https://www.readbyqxmd.com/read/28612512/the-germline-factor-ddx4-functions-in-blood-derived-cancer-cell-phenotypes
#2
Natalie Schudrowitz, Satoshi Takagi, Gary M Wessel, Mamiko Yajima
DDX4 (the human ortholog of Drosophila Vasa) is an RNA helicase and is present in the germ lines of all metazoans tested. It was historically thought to be expressed specifically in germline cells, but with additional organisms studied, it is now clear that in some animals DDX4/Vasa functions outside of the germline, in a variety of somatic cells in the embryo and adult. In this report, we document that DDX4 is widely expressed in soma-derived cancer cell lines, including myeloma (IM-9) and leukemia (THP-1) cells...
June 14, 2017: Cancer Science
https://www.readbyqxmd.com/read/28607084/systems-guided-forward-genetic-screen-reveals-a-critical-role-of-the-replication-stress-response-protein-etaa1-in-t-cell-clonal-expansion
#3
Lisa A Miosge, Yovina Sontani, Aaron Chuah, Keisuke Horikawa, Tiffany A Russell, Yan Mei, Mayura V Wagle, Debbie R Howard, Anselm Enders, David C Tscharke, Christopher C Goodnow, Ian A Parish
T-cell immunity requires extremely rapid clonal proliferation of rare, antigen-specific T lymphocytes to form effector cells. Here we identify a critical role for ETAA1 in this process by surveying random germ line mutations in mice using exome sequencing and bioinformatic annotation to prioritize mutations in genes of unknown function with potential effects on the immune system, followed by breeding to homozygosity and testing for immune system phenotypes. Effector CD8(+) and CD4(+) T-cell formation following immunization, lymphocytic choriomeningitis virus (LCMV) infection, or herpes simplex virus 1 (HSV1) infection was profoundly decreased despite normal immune cell development in adult mice homozygous for two different Etaa1 mutations: an exon 2 skipping allele that deletes Gly78-Leu119, and a Cys166Stop truncating allele that eliminates most of the 877-aa protein...
June 12, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28600283/inhibition-of-pcsk9-does-not-improve-lipopolysaccharide-induced-mortality-in-mice
#4
Jean-Mathieu Berger, Angel Loza Valdes, Jesper Gromada, Norma Anderson, Jay D Horton
PCSK9 is a secreted protein that targets LDL receptors (LDLR) for degradation in liver. Blocking the interaction of PCSK9 with the LDLR potently reduces plasma LDL-cholesterol levels and cardiovascular events. Recently, it has been suggested that inhibition of PCSK9 might also improve outcomes in mice and humans with sepsis, possibly by increasing LDL receptor (LDLR)-mediated clearance of endotoxins. Sepsis is a complication of a severe microbial infection that has shared pathways with lipid metabolism. Here, we tested whether anti-PCSK9 antibodies prevent death from lipopolysaccharide (LPS)-induced endotoxemia...
June 9, 2017: Journal of Lipid Research
https://www.readbyqxmd.com/read/28588016/commensal-microbes-provide-first-line-defense-against-listeria-monocytogenes-infection
#5
Simone Becattini, Eric R Littmann, Rebecca A Carter, Sohn G Kim, Sejal M Morjaria, Lilan Ling, Yangtsho Gyaltshen, Emily Fontana, Ying Taur, Ingrid M Leiner, Eric G Pamer
Listeria monocytogenes is a foodborne pathogen that causes septicemia, meningitis and chorioamnionitis and is associated with high mortality. Immunocompetent humans and animals, however, can tolerate high doses of L. monocytogenes without developing systemic disease. The intestinal microbiota provides colonization resistance against many orally acquired pathogens, and antibiotic-mediated depletion of the microbiota reduces host resistance to infection. Here we show that a diverse microbiota markedly reduces Listeria monocytogenes colonization of the gut lumen and prevents systemic dissemination...
June 6, 2017: Journal of Experimental Medicine
https://www.readbyqxmd.com/read/28582519/x-chromosome-inactivation-in-human-pluripotent-stem-cells-as-a-model-for-human-development-back-to-the-drawing-board
#6
Mieke Geens, Susana M Chuva De Sousa Lopes
BACKGROUND: Human pluripotent stem cells (hPSC), both embryonic and induced (hESC and hiPSC), are regarded as a valuable in vitro model for early human development. In order to fulfil this promise, it is important that these cells mimic as closely as possible the in vivo molecular events, both at the genetic and epigenetic level. One of the most important epigenetic events during early human development is X chromosome inactivation (XCI), the transcriptional silencing of one of the two X chromosomes in female cells...
June 5, 2017: Human Reproduction Update
https://www.readbyqxmd.com/read/28574707/new-ustilaginoidins-from-rice-false-smut-balls-caused-by-villosiclava-virens-and-their-phytotoxic-and-cytotoxic-activities
#7
Weibo Sun, Ali Wang, Dan Xu, Weixuan Wang, Jiajia Meng, Jungui Dai, Yang Liu, Daowan Lai, Ligang Zhou
Ustilaginoidins are a class of bis-naphtho-γ-pyrones, typically produced by Villosiclava virens, the pathogen of the rice false smut (RFS) which has been one of the most destructive rice fungal diseases. Previously, we found that the ustilaginoidins identified from the culture of V. virens on rice medium were less polar than those reported from the RFS balls in general. In this study, we re-investigated the HPLC-DAD-HRMS profile of the EtOAc extract of the RFS balls, and found several interesting peaks that corresponding to new ustilaginoidins...
June 2, 2017: Journal of Agricultural and Food Chemistry
https://www.readbyqxmd.com/read/28569402/lrwd1-regulates-microtubule-nucleation-and-proper-cell-cycle-progression-in-the-human-testicular-embryonic-carcinoma-cells
#8
Chia-Yih Wang, Yu-Han Hong, Jhih-Siang Syu, Yung-Chieh Tsai, Xiu-Ying Liu, Ting-Yu Chen, Yin-Mei Su, Pao-Lin Kuo, Yung-Ming Lin, Yen-Ni Teng
Leucine-rich repeats and WD repeat domain containing protein 1 (LRWD1) is a testis-specific protein that mainly expressed in the sperm neck where centrosome is located. By using microarray analysis, LRWD1 is identified as a putative gene that involved in spermatogenesis. However, its role in human male germ cell development has not been extensively studied. When checking in the semen of patients with asthenozoospermia, teratozoospermia, and asthenoteratozoospermia, the level of LRWD1 in the sperm neck was significantly reduced with a defective neck or tail...
June 1, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/28544640/an-in%C3%A2-vitro-model-demonstrates-the-potential-of-neoplastic-human-germ-cells-to-influence-the-tumour-microenvironment
#9
B Klein, H-C Schuppe, M Bergmann, M P Hedger, B E Loveland, K L Loveland
Testicular germ cell tumours (TGCT) typically contain high numbers of infiltrating immune cells, yet the functional nature and consequences of interactions between GCNIS (germ cell neoplasia in situ) or seminoma cells and immune cells remain unknown. A co-culture model using the seminoma-derived TCam-2 cell line and peripheral blood mononuclear cells (PBMC, n = 7 healthy donors) was established to investigate how tumour and immune cells each contribute to the cytokine microenvironment associated with TGCT...
May 23, 2017: Andrology
https://www.readbyqxmd.com/read/28543417/toward-public-bioethics
#10
EDITORIAL
Gregory E Kaebnick
This issue of the Hastings Center Report (May-June 2017) features a couple of interesting takes on the governance challenges of emerging technologies. In an essay on the National Academies of Science, Engineering, and Medicine report published this February on human germ-line gene editing, Eric Juengst, a philosopher at the University of North Carolina, argues that the NASEM committee did not manage to rethink the rules. Juengst reaches what he calls an "eccentric conclusion": "The committee's 2017 consensus report has been widely interpreted as 'opening the door' to inheritable human genetic modification and holding a line against enhancement interventions...
May 2017: Hastings Center Report
https://www.readbyqxmd.com/read/28543411/crowdsourcing-the-moral-limits-of-human-gene-editing
#11
Eric T Juengst
In 2015, a flourish of "alarums and excursions" by the scientific community propelled CRISPR/Cas9 and other new gene-editing techniques into public attention. At issue were two kinds of potential gene-editing experiments in humans: those making inheritable germ-line modifications and those designed to enhance human traits beyond what is necessary for health and healing. The scientific consensus seemed to be that while research to develop safe and effective human gene editing should continue, society's moral uncertainties about these two kinds of experiments needed to be better resolved before clinical trials of either type should be attempted...
May 2017: Hastings Center Report
https://www.readbyqxmd.com/read/28539189/the-individual-and-population-genetics-of-antibody-immunity
#12
REVIEW
Corey T Watson, Jacob Glanville, Wayne A Marasco
Antibodies (Abs) produced by immunoglobulin (IG) genes are the most diverse proteins expressed in humans. While part of this diversity is generated by recombination during B-cell development and mutations during affinity maturation, the germ-line IG loci are also diverse across human populations and ethnicities. Recently, proof-of-concept studies have demonstrated genotype-phenotype correlations between specific IG germ-line variants and the quality of Ab responses during vaccination and disease. However, the functional consequences of IG genetic variation in Ab function and immunological outcomes remain underexplored...
May 20, 2017: Trends in Immunology
https://www.readbyqxmd.com/read/28536242/mutation-in-tdrd9-causes-non-obstructive-azoospermia-in-infertile-men
#13
Maram Arafat, Iris Har-Vardi, Avi Harlev, Eliahu Levitas, Atif Zeadna, Maram Abofoul-Azab, Victor Dyomin, Val C Sheffield, Eitan Lunenfeld, Mahmoud Huleihel, Ruti Parvari
BACKGROUND: Azoospermia is diagnosed when sperm cells are completely absent in the ejaculate even after centrifugation. It is identified in approximately 1% of all men and in 10%-20% of infertile males. Non-obstructive azoospermia (NOA) is characterised by the absence of sperm due to either a Sertoli cell-only pattern, maturation arrest, hypospermatogenesis or mixed patterns. NOA is a severe form of male infertility, with limited treatment options and low fertility success rates. In the majority of patients, the cause for NOA is not known and mutations in only a few genes were shown to be causative...
May 23, 2017: Journal of Medical Genetics
https://www.readbyqxmd.com/read/28533935/a-review-of-the-emerging-potential-therapy-for-neurological-disorders-human-embryonic-stem-cell-therapy
#14
REVIEW
Geeta Shroff, Jyoti Dhanda Titus, Rhea Shroff
The first human embryonic stem cell (hESC) line was developed in the late nineties. hESCs are capable of proliferating indefinitely and differentiate into all the three embryonic germ layers. Further, the differentiation of hESC lines into neural precursor cells and neurons, astrocytes and oligodendrocytes showed their potential in treating several incurable neurological disorders such as spinal cord injury (SCI), cerebral palsy (CP), Parkinson's disease (PD). In this review, we will discuss the global scenario of research and therapeutic use of hESCs in the treatment of neurological disorders...
2017: American Journal of Stem Cells
https://www.readbyqxmd.com/read/28533810/tc003132-is-essential-for-the-follicle-stem-cell-lineage-in-telotrophic-tribolium-oogenesis
#15
Matthias Teuscher, Nadi Ströhlein, Markus Birkenbach, Dorothea Schultheis, Michael Schoppmeier
BACKGROUND: Stem cells are undifferentiated cells with a potential for self-renewal, which are essential to support normal development and homeostasis. To gain insight into the molecular mechanisms underlying adult stem cell biology and organ evolution, we use the telotrophic ovary of the beetle Tribolium. To this end, we participated in a large-scale RNAi screen in the red flour beetle Tribolium, which identified functions in embryonic and postembryonic development for more than half of the Tribolium genes...
2017: Frontiers in Zoology
https://www.readbyqxmd.com/read/28528424/trps1-gene-alterations-in-human-subependymoma
#16
Sascha B Fischer, Michelle Attenhofer, Sakir H Gultekin, Donald A Ross, Karl Heinimann
Subependymoma is a rare primary brain tumor, constituting 0.07-0.51% of brain tumors. Genetic alterations in subependymoma are largely unknown, but familial occurrences have been reported. Trichorhinophalangeal syndrome type 1 (TRPS1) is a rare hereditary malformation complex caused by mutations in a gene identified in the year 2000 on 8q24.12. We report two patients with TRPS I and surgically treated subependymomas, one of whom has a first degree relative, now deceased, who was affected and also had a subependymoma...
May 20, 2017: Journal of Neuro-oncology
https://www.readbyqxmd.com/read/28502982/why-are-hematopoietic-stem-cells-so-sexy-on-a-search-for-developmental-explanation
#17
REVIEW
Mariusz Z Ratajczak
Evidence has accumulated that normal human and murine hematopoietic stem cells express several functional pituitary and gonadal sex hormones and that, in fact, some sex hormones, such as androgens, have been employed for many years to stimulate hematopoiesis in patients with bone marrow aplasia. Interestingly, sex hormone receptors are also expressed by leukemic cell lines and blasts. In this review I will discuss the emerging question of why hematopoietic cells express these receptors. A tempting hypothetical explanation for this phenomenon is that hematopoietic stem cells are related to subpopulation of migrating primordial germ cells...
May 15, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/28446200/human-germ-stem-cell-specific-gene-tex19-influences-cancer-cell-proliferation-and-cancer-prognosis
#18
Vicente Planells-Palop, Ali Hazazi, Julia Feichtinger, Jana Jezkova, Gerhard Thallinger, Naif O Alsiwiehri, Mikhlid Almutairi, Lee Parry, Jane A Wakeman, Ramsay J McFarlane
BACKGROUND: Cancer/testis (CT) genes have expression normally restricted to the testis, but become activated during oncogenesis, so they have excellent potential as cancer-specific biomarkers. Evidence is starting to emerge to indicate that they also provide function(s) in the oncogenic programme. Human TEX19 is a recently identified CT gene, but a functional role for TEX19 in cancer has not yet been defined. METHODS: siRNA was used to deplete TEX19 levels in various cancer cell lines...
April 26, 2017: Molecular Cancer
https://www.readbyqxmd.com/read/28439515/endogenous-retroviruses-with-us-and-against-us
#19
REVIEW
Thomas J Meyer, Jimi L Rosenkrantz, Lucia Carbone, Shawn L Chavez
Mammalian genomes are scattered with thousands of copies of endogenous retroviruses (ERVs), mobile genetic elements that are relics of ancient retroviral infections. After inserting copies into the germ line of a host, most ERVs accumulate mutations that prevent the normal assembly of infectious viral particles, becoming trapped in host genomes and unable to leave to infect other cells. While most copies of ERVs are inactive, some are transcribed and encode the proteins needed to generate new insertions at novel loci...
2017: Frontiers in Chemistry
https://www.readbyqxmd.com/read/28417059/susceptibility-of-human-oral-squamous-cell-carcinoma-oscc-h103-and-h376-cell-lines-to-retroviral-oskm-mediated-reprogramming
#20
Nalini Devi Verusingam, Swee Keong Yeap, Huynh Ky, Ian C Paterson, Suan Phaik Khoo, Soon Keng Cheong, Alan H K Ong, Tunku Kamarul
Although numbers of cancer cell lines have been shown to be successfully reprogrammed into induced pluripotent stem cells (iPSCs), reprogramming Oral Squamous Cell Carcinoma (OSCC) to pluripotency in relation to its cancer cell type and the expression pattern of pluripotent genes under later passage remain unexplored. In our study, we reprogrammed and characterised H103 and H376 oral squamous carcinoma cells using retroviral OSKM mediated method. Reprogrammed cells were characterized for their embryonic stem cells (ESCs) like morphology, pluripotent gene expression via quantitative real-time polymerase chain reaction (RT-qPCR), immunofluorescence staining, embryoid bodies (EB) formation and directed differentiation capacity...
2017: PeerJ
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