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Embryonic lethal

René P Andrié, Thomas Beiert, Vincent Knappe, Markus Linhart, Florian Stöckigt, Alexandra M Klein, Alexander Ghanem, Indra Lübkemeier, Wilhelm Röll, Georg Nickenig, Bernd K Fleischmann, Jan W Schrickel
BACKGROUND: Clinical and experimental data give evidence that transplantation of stem and progenitor cells in myocardial infarction could be beneficial, although the underlying mechanism has remained elusive. Ventricular tachyarrhythmia is the most frequent and potentially lethal complication of myocardial infarction, but the impact of mono nuclear cells on the incidence of ventricular arrhythmia is still not clear. OBJECTIVE: We aimed to characterize the influence of splenic mononuclear cell populations on ventricular arrhythmia after myocardial infarction...
2019: PloS One
Nara Shin, Luciann Cuenca, Rajendiran Karthikraj, Kurunthachalam Kannan, Monica P Colaiácovo
Chemicals that are highly prevalent in our environment, such as phthalates and pesticides, have been linked to problems associated with reproductive health. However, rapid assessment of their impact on reproductive health and understanding how they cause such deleterious effects, remain challenging due to their fast-growing numbers and the limitations of various current toxicity assessment model systems. Here, we performed a high-throughput screen in C. elegans to identify chemicals inducing aneuploidy as a result of impaired germline function...
February 2019: PLoS Genetics
Sungwook Choi, Victor Ambros
C. elegans heterochronic genes determine the timing of expression of specific cell fates in particular stages of developing larva. However, their broader roles in coordinating developmental events across diverse tissues have been less well investigated. Here, we show that loss of lin-28 , a central heterochronic regulator of hypodermal development, causes reduced fertility associated with abnormal somatic gonadal morphology. In particular, the abnormal spermatheca-uterine valve morphology of lin-28(lf) hermaphrodites traps embryos in the spermatheca, which disrupts ovulation and causes embryonic lethality...
February 11, 2019: Development
Marlenne Luja-Mondragón, Leobardo Manuel Gómez-Oliván, Nely SanJuan-Reyes, Hariz Islas-Flores, José Manuel Orozco-Hernández, Gerardo Heredia-García, Marcela Galar-Martínez, Octavio Dublán-García
Hospital functioning generates a great quantity of contaminants, among which organic materials, heavy metals, and diverse pharmaceuticals are noteworthy that can affect organisms if they are not properly removed from the effluents. The hospital effluent evaluated in the present study came from IMSS (Instituto Mexicano del Seguro Social) Clinic 221 in downtown Toluca, State of Mexico, a secondary care facility. The contaminants identified in hospitals have been associated with deleterious effects on aquatic organisms; however, it is necessary to continue with more studies in order to be able to regulate the production of said contaminants which are generally dumped into the city sewage system...
April 10, 2019: Science of the Total Environment
A C Hepburn, R E Steele, R Veeratterapillay, L Wilson, E E Kounatidou, A Barnard, P Berry, J R Cassidy, M Moad, A El-Sherif, L Gaughan, I G Mills, C N Robson, R Heer
Stem cell characteristics have been associated with treatment resistance and poor prognosis across many cancer types. The ability to induce and regulate the pathways that sustain these characteristic hallmarks of lethal cancers in a novel in vitro model would greatly enhance our understanding of cancer progression and treatment resistance. In this work, we present such a model, based simply on applying standard pluripotency/embryonic stem cell media alone. Core pluripotency stem cell master regulators (OCT4, SOX2 and NANOG) along with epithelial-mesenchymal transition (EMT) markers (Snail, Slug, vimentin and N-cadherin) were induced in human prostate, breast, lung, bladder, colorectal, and renal cancer cells...
February 11, 2019: Oncogene
John P Dowling, Mohamed Alsabbagh, Christina Del Casale, Zheng-Gang Liu, Jianke Zhang
TRADD is an adaptor for TNFR1-induced apoptosis and NFκB activation. However, TRADD-deficient mice undergo normal development and contain normal lymphoid populations, which contrasts with an embryonic defect in mice lacking FADD, the shared adaptor mediating apoptosis. Recent studies indicate FADD suppresses embryonic necroptosis mediated by RIPK1. TRADD was suggested to also mediate necroptosis. Here we report that targeting TRADD fails to rescue Fadd-/- embryos from necroptosis, and ablation of TRADD rescues Ripk1-/- mice from perinatal lethality when RIPK3-mediated necroptosis is disabled...
February 11, 2019: Nature Communications
Hanne M Hoffmann, Rachel Larder, Jessica Lee, Rachael Hu, Crystal Trang, Brooke Devries, Daniel Clark, Pamela L Mellon
<br>Increasingly, studies utilize cell-specific deletion of genes through conditional gene deletion by CRE recombination. Despite numerous advantages, this strategy also has limits such as ectopic CRE-expression and germline recombination. Two commonly used gonadotropin-releasing hormone (Gnrh)-driven CRE-expressing mice both target GnRH neurons. However, a direct comparison of the cells targeted, and their phenotypic outcome has not yet been presented. To compare where recombination takes place, we crossed the Gnrh-cre and Lhrh-cre lines with the Rosa26-LacZ reporter mouse...
February 10, 2019: Neuroendocrinology
Triveni Menon, Sreelaja Nair
Metazoan animals are typically diploid, possessing two sets of a chromosome in the somatic cells of an organism. In naturally diploid species, alteration from the endogenous diploid state is usually embryonic lethal. However, the ability to experimentally manipulate ploidy of animal embryos has fundamental as well as applied biology advantages. In this chapter we describe experimental procedures to convert normally diploid zebrafish embryos into haploid or tetraploid states. We also describe methodologies to verify the ploidy of embryos and the utility of ploidy manipulation in expediting the isolation of mutations using both forward and reverse genetic strategies in zebrafish...
2019: Methods in Molecular Biology
Markus Horsthemke, Lauryl M J Nutter, Anne C Bachg, Boris V Skryabin, Ulrike Honnert, Thomas Zobel, Sven Bogdan, Monika Stoll, Matthias D Seidl, Frank U Mueller, Ursula Ravens, Andreas Unger, Wolfgang A Linke, Pim R R van Gorp, Antoine A F de Vries, Martin Bähler, Peter J Hanley
Whereas myosin 18B (Myo18B) is known to be a critical sarcomeric protein, the function of myosin 18A (Myo18A) is unclear, although it has been implicated in cell motility and Golgi shape. Here we show that homozygous deletion (homozygous tm1a, tm1b or tm1d alleles) of Myo18a in mouse is embryonic lethal. Reminiscent of Myo18b, Myo18a was highly expressed in the embryo heart, and cardiac-restricted Myo18a deletion in mice was embryonic lethal. Surprisingly, using Western blot analysis, we were unable to detect the known isoforms of Myo18A, Myo18Aα and Myo18Aβ, in mouse heart using a custom C-terminal antibody...
February 8, 2019: Journal of Biological Chemistry
Evangelia Koutelou, Li Wang, Andria Schibler, Hsueh-Ping Chao, Xianghong Kuang, Kevin Lin, Yue Lu, Jianjun Shen, Collene R Jeter, Andrew Salinger, Marenda Wilson, Yi Chun Chen, Boyko S Atanassov, Dean G Tang, Sharon Yr Dent
Usp22, a component of the SAGA complex, is over expressed in highly aggressive cancers, but the normal functions of this deubiquitinase are not well defined. We determined that loss of Usp22 in mice results in embryonic lethality due to defects in extra-embryonic placental tissues and failure to establish proper vascular interactions with the maternal circulatory system. These phenotypes arise from abnormal gene expression patterns that reflect defective kinase signaling, including TGFβ and several receptor tyrosine kinase (RTK) pathways...
February 4, 2019: Development
Khouloud Boukadida, Jérôme Cachot, Bénédicte Morin, Christelle Clerandeau, Mohamed Banni
The present study aims to evaluate the effects of copper and silver alone or along with a moderate temperature increase on embryonic development, DNA integrity and target gene expression levels in early life stages of Mytilus galloprovincialis. For this purpose, upon fertilized embryos were exposed to a sub-lethal concentration of Cu (9.54 μg/L), Ag (2.55 μg/L) and to the mixture of the two metals (Cu (6.67 μg/L) + Ag (1.47 μg/L)) along with a temperature gradient (18, 20 and 22 °C). In all experiments, larvae were exposed to stressors for 48 h except for those designed to DNA damage analysis exposed only for 24 h (before shell formation)...
January 19, 2019: Science of the Total Environment
Baolu Shi, Jiangyang Xue, Hao Yin, Rui Guo, Mengcheng Luo, Lan Ye, Qinghua Shi, Xiaoyan Huang, Mingxi Liu, Jiahao Sha, P Jeremy Wang
Meiotic recombination permits exchange of genetic material between homologous chromosomes. The replication protein A (RPA) complex, the predominant ssDNA-binding complex, is required for nearly all aspects of DNA metabolism, but its role in mammalian meiotic recombination remains unknown due to the embryonic lethality of RPA mutant mice. RPA is a heterotrimer of RPA1, RPA2, and RPA3. We find that loss of RPA1, the largest subunit, leads to disappearance of RPA2 and RPA3, resulting in the absence of the RPA complex...
February 4, 2019: PLoS Genetics
Nobuhiko Harada, Atsushi Hasegawa, Ikuo Hirano, Masayuki Yamamoto, Ritsuko Shimizu
The transcription factor GATA2 regulates normal hematopoiesis, particularly in stem cell maintenance and myeloid differentiation. Various heteroallelic GATA2 gene mutations are associated with a variety of hematological neoplasms, including myelodysplastic syndromes and leukemias. Here, we report that impaired GATA2 expression induces myelodysplastic and myeloproliferative neoplasm development in elderly animals, and this neoplasm resembles chronic myelomonocytic leukemia in humans. GATA2 hypomorphic mutant (G2f GN / fGN ) mice that were generated by the germline insertion of a neo-cassette into the Gata2 gene locus avoided the early embryonic lethality observed in Gata2-null mice...
February 2, 2019: Cancer Science
Lilia Magomedova, Jens Tiefenbach, Emma Zilberman, Florian Le Billan, Veronique Voisin, Michael Saikali, Vincent Boivin, Melanie Robitaille, Serge Gueroussov, Manuel Irimia, Debashish Ray, Rucha Patel, ChangJiang Xu, Pancharatnam Jeyasuria, Gary D Bader, Timothy R Hughes, Quaid D Morris, Michelle S Scott, Henry Krause, Stephane Angers, Benjamin J Blencowe, Carolyn L Cummins
Stress hormones bind and activate the glucocorticoid receptor (GR) in many tissues including the brain. We identified arginine and glutamate rich 1 (ARGLU1) in a screen for new modulators of glucocorticoid signaling in the CNS. Biochemical studies show that the glutamate rich C-terminus of ARGLU1 coactivates multiple nuclear receptors including the glucocorticoid receptor (GR) and the arginine rich N-terminus interacts with splicing factors and binds to RNA. RNA-seq of neural cells depleted of ARGLU1 revealed significant changes in the expression and alternative splicing of distinct genes involved in neurogenesis...
January 30, 2019: Nucleic Acids Research
Jyoti Gautam, Jeffrey H Miner, Yao Yao
Endothelial cells make laminin-411 and laminin-511. Although laminin-411 is well studied, the role of laminin-511 remains largely unknown due to the embryonic lethality of lama5-/- mutants. In this study, we generated endothelium-specific lama5 conditional knockout (α5-TKO) mice and investigated the biological functions of endothelial lama5 in blood-brain barrier (BBB) maintenance under homeostatic conditions and the pathogenesis of intracerebral hemorrhage (ICH). First, the BBB integrity of α5-TKO mice was measured under homeostatic conditions...
January 29, 2019: Translational Stroke Research
Cinzia Milesi, Paola Alberici, Benedetta Pozzi, Amanda Oldani, Galina V Beznoussenko, Andrea Raimondi, Blanche Ekalle Soppo, Stefania Amodio, Giusi Caldieri, Maria Grazia Malabarba, Giovanni Bertalot, Stefano Confalonieri, Dario Parazzoli, Alexander A Mironov, Carlo Tacchetti, Pier Paolo Di Fiore, Sara Sigismund, Nina Offenhäuser
EPS15 and its homologous EPS15L1 are endocytic accessory proteins. Studies in mammalian cell lines suggested that EPS15 and EPS15L1 regulate endocytosis in a redundant manner. However, at the organismal level, it is not known to which extent the functions of the two proteins overlap. Here, by exploiting various constitutive and conditional null mice, we report redundant and nonredundant functions of the two proteins. EPS15L1 displays a unique nonredundant role in the nervous system, whereas both proteins are fundamental during embryo development as shown by the embryonic lethality of - Eps15/Eps15L1 -double KO mice...
February 2019: Life science alliance
Manon Jaud, Céline Philippe, Loic Van Den Berghe, Christèle Ségura, Laurent Mazzolini, Stéphane Pyronnet, Henrik Laurell, Christian Touriol
Delta-like 4 (DLL4) is a pivotal endothelium specific Notch ligand that has been shown to function as a regulating factor during physiological and pathological angiogenesis. DLL4 functions as a negative regulator of angiogenic branching and sprouting. Interestingly, Dll4 is with Vegf-a one of the few examples of haplo-insufficiency, resulting in obvious vascular abnormalities and in embryonic lethality. These striking phenotypes are a proof of concept of the crucial role played by the bioavailability of VEGF and DLL4 during vessel patterning and that there must be a very fine-tuning of DLL4 expression level...
January 25, 2019: Cancers
Lars Kristian Benner, Katherine Perkins Prothro, Katherine McJunkin
The germline sex determination pathway in C. elegans determines whether germ cells develop as oocytes or sperm, with no previously known effect on viability. The mir-35 family of microRNAs are expressed in the C. elegans germline and embryo and are essential for both viability and normal hermaphroditic sex determination, preventing aberrant male gene expression in XX hermaphrodite embryos. Here we show that combining feminizing mutations with partial loss of function of the mir-35 family results in enhanced penetrance embryonic lethality that preferentially kills XO animals...
January 24, 2019: G3: Genes—Genomes—Genetics
Weiran Shan, Jun Li, Wenhao Xu, Hong Li, Zhiyi Zuo
Ubiquinol cytochrome c reductase core protein I (UQCRC1) is a component of the complex III in the respiratory chain. Its biological functions are unknown. Here, we showed that knockout of UQCRC1 led to embryonic lethality. Disrupting one UQCRC1 allele in mice (heterozygous mice) of both sexes did not affect their growth but reduced UQCRC1 mRNA and protein in the brain. These mice had decreased complex III formation, complex III activity and ATP content in the brain at baseline. They developed worsened neurological outcome after brain ischemia/hypoxia or focal brain ischemia compared with wild-type mice...
January 21, 2019: Cellular and Molecular Life Sciences: CMLS
Z Hu, K I Lavik, Y Liu, A H Vo, C E Richter, J Di Paola, J A Shavit
BACKGROUND: Mutations in the alpha chain of fibrinogen (FGA), like deficiencies in other fibrinogen subunits, lead to rare inherited autosomal recessive hemostatic disorders. These range from asymptomatic to catastrophic life-threatening bleeds, and the molecular basis of inherited fibrinogen deficiencies is only partially understood. Zinc finger nucleases have been used to produce mutations in zebrafish fga, resulting in overt adult onset hemorrhage and reduced survival. OBJECTIVES: To determine the age of onset of hemostatic defects in afibrinogenemic zebrafish, and model human fibrinogen deficiencies...
January 21, 2019: Journal of Thrombosis and Haemostasis: JTH
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