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  • 1
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    Centrosomes. Regulated assembly of a supramolecular centrosome scaffold in vitro (2015)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2015-05-16
    Description: The centrosome organizes microtubule arrays within animal cells and comprises two centrioles surrounded by an amorphous protein mass called the pericentriolar material (PCM). Despite the importance of centrosomes as microtubule-organizing centers, the mechanism and regulation of PCM assembly are not well understood. In Caenorhabditis elegans, PCM assembly requires the coiled-coil protein SPD-5. We found that recombinant SPD-5 could polymerize to form micrometer-sized porous networks in vitro. Network assembly was accelerated by two conserved regulators that control PCM assembly in vivo, Polo-like kinase-1 and SPD-2/Cep192. Only the assembled SPD-5 networks, and not unassembled SPD-5 protein, functioned as a scaffold for other PCM proteins. Thus, PCM size and binding capacity emerge from the regulated polymerization of one coiled-coil protein to form a porous network.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Woodruff, Jeffrey B -- Wueseke, Oliver -- Viscardi, Valeria -- Mahamid, Julia -- Ochoa, Stacy D -- Bunkenborg, Jakob -- Widlund, Per O -- Pozniakovsky, Andrei -- Zanin, Esther -- Bahmanyar, Shirin -- Zinke, Andrea -- Hong, Sun Hae -- Decker, Marcus -- Baumeister, Wolfgang -- Andersen, Jens S -- Oegema, Karen -- Hyman, Anthony A -- R01-GM074207/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 2015 May 15;348(6236):808-12. doi: 10.1126/science.aaa3923.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Max Planck Institute of Molecular Cell Biology and Genetics, Pfotenhauerstrasse 108, 01307 Dresden, Germany. ; Department of Cellular and Molecular Medicine, Ludwig Institute for Cancer Research, University of California, San Diego, La Jolla, CA 92093, USA. ; Department of Molecular Structural Biology, Max Planck Institute of Biochemistry, Martinsried 82152, Germany. ; Department of Clinical Biochemistry, Copenhagen University Hospital, Hvidovre 2650, Denmark. Department of Biochemistry and Molecular Biology, University of Southern Denmark, Odense, Denmark. ; Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA 94720, USA. ; Department of Biochemistry and Molecular Biology, University of Southern Denmark, Odense, Denmark. ; Department of Cellular and Molecular Medicine, Ludwig Institute for Cancer Research, University of California, San Diego, La Jolla, CA 92093, USA. hyman@mpi-cbg.de koegema@ucsd.edu. ; Max Planck Institute of Molecular Cell Biology and Genetics, Pfotenhauerstrasse 108, 01307 Dresden, Germany. hyman@mpi-cbg.de koegema@ucsd.edu.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25977552" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Caenorhabditis elegans/*genetics/*metabolism ; Caenorhabditis elegans Proteins/chemistry/genetics/*metabolism ; Cell Cycle Proteins/chemistry/genetics/*metabolism ; Centrosome/*metabolism/ultrasonography ; Metabolic Networks and Pathways ; Phosphorylation ; Polymerization ; Protein Binding ; Protein Structure, Tertiary ; Protein-Serine-Threonine Kinases/*metabolism ; Proto-Oncogene Proteins/*metabolism
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
    Published by American Association for the Advancement of Science (AAAS)
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  • 2
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    Breast Cancer Risk in Opposite-Sexed Twins: Influence of Birth Weight and Co-Twin Birth Weight (2013)
    Oxford University Press
    Details
    Publication Date: 2013-12-04
    Description: Most, but not all, studies report a positive association between birth weight, as an indirect marker of prenatal hormone exposure, and offspring breast cancer risk, particularly premenopausal breast cancer. Females from opposite-sexed twin pairs may also be prenatally exposed to androgens from their twin brothers. A Swedish study of opposite-sexed twins with a small sample size found a very strong positive association between female birth weight and breast cancer risk. In this case–control study, nested within a cohort of female opposite-sexed twins, we included 543 breast cancer case subjects diagnosed in the period from 1972 to 2008 and 2715 matched control subjects. Conditional logistic regression estimated the breast cancer risk associated with birth weight and other birth characteristics, including gestational age and co-twin birth weight. All statistical tests were two-sided. There was no association between birth weight (odds ratio = 1.01; 95% confidence interval = 0.70 to 1.46) or twin brother’s birth weight and risk of breast cancer, which suggests the previously reported strong positive association may have been a chance finding.
    Electronic ISSN: 1460-2105
    Topics: Medicine
    Published by Oxford University Press
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  • 3
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    Pregnancy history and risk of premenopausal breast cancer--a nested case-control study (2016)
    Oxford University Press
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    Publication Date: 2016-09-01
    Description: Background: Reproductive factors are well-known risk factors for premenopausal breast cancer (PBC). It is unknown whether these associations are modified by familial factors, including genetic and early environment factors. Methods: Using Swedish health registries, we performed a nested case-control study with two control groups: sister controls and population controls. The study population included women with live singleton births between 1973 and 2010, who also had a full sister who gave birth during this period. All women subsequently diagnosed with PBC were selected as cases ( n = 8327). Sisters with the least age difference and without PBC at the time of her sister’s diagnosis were selected as sister controls. For each incident case, one population control without previous PBC was selected.The population controls were individually matched with the sister controls on year of birth. Conditional logistic regression was used to estimate associations between reproductive factors and PBC. Results: Increasing parity was inversely associated with PBC using population controls, and multiparity was a risk factor using sister controls. Very preterm delivery (≤ 31 weeks) was associated with a slightly higher PBC risk using sister controls. Preeclampsia was associated with a slightly protective effect using population controls. With respect to other factors, there were no substantial differences in risks of PBC by choice of control group. Conclusions: The divergent results with regard to parity and PBC risk when using sister and population controls suggest that the influence of childbearing may be modified by genotype. Selection bias when using different control groups must also be considered.
    Print ISSN: 0300-5771
    Electronic ISSN: 1464-3685
    Topics: Medicine
    Published by Oxford University Press
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  • 4
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    Pioglitazone use and risk of bladder cancer in patients with type 2 diabetes: retrospective cohort study using datasets from four European countries (2016)
    BMJ Publishing Group
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    Publication Date: 2016-08-17
    Description: Objective To evaluate the association between pioglitazone use and bladder cancer risk in patients with type 2 diabetes.Design Retrospective cohort study using propensity score matched...
    Topics: Medicine
    Published by BMJ Publishing Group
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  • 5
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    A novel small molecule that disrupts a key event during the oocyte-to-embryo transition in C. elegans [RESEARCH ARTICLE] (2016)
    The Company of Biologists
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    Publication Date: 2016-10-08
    Description: Steven E. Weicksel, Assaf Mahadav, Mark Moyle, Patricia G. Cipriani, Michelle Kudron, Zachary Pincus, Shirin Bahmanyar, Laura Abriola, Janie Merkel, Michelle Gutwein, Anita G. Fernandez, Fabio Piano, Kristin C. Gunsalus, and Valerie Reinke The complex cellular events that occur in response to fertilization are essential for mediating the oocyte-to-embryo transition. Here, we describe a comprehensive small-molecule screen focused on identifying compounds that affect early embryonic events in Caenorhabditis elegans . We identify a single novel compound that disrupts early embryogenesis with remarkable stage and species specificity. The compound, named C22, primarily impairs eggshell integrity, leading to osmotic sensitivity and embryonic lethality. The C22-induced phenotype is dependent upon the upregulation of the LET-607/CREBH transcription factor and its candidate target genes, which primarily encode factors involved in diverse aspects of protein trafficking. Together, our data suggest that in the presence of C22, one or more key components of the eggshell are inappropriately processed, leading to permeable, inviable embryos. The remarkable specificity and reversibility of this compound will facilitate further investigation into the role and regulation of protein trafficking in the early embryo, as well as serve as a tool for manipulating the life cycle for other studies such as those involving aging.
    Print ISSN: 0950-1991
    Electronic ISSN: 1477-9129
    Topics: Biology
    Published by The Company of Biologists
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  • 6
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    Spatial control of phospholipid flux restricts endoplasmic reticulum sheet formation to allow nuclear envelope breakdown [Research Communications] (2014)
    Cold Spring Harbor Laboratory Press
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    Publication Date: 2014-01-22
    Description: The nuclear envelope is a subdomain of the endoplasmic reticulum (ER). Here we characterize CNEP-1 (CTD [C-terminal domain] nuclear envelope phosphatase-1), a nuclear envelope-enriched activator of the ER-associated phosphatidic acid phosphatase lipin that promotes synthesis of major membrane phospholipids over phosphatidylinositol (PI). CNEP-1 inhibition led to ectopic ER sheets in the vicinity of the nucleus that encased the nuclear envelope and interfered with nuclear envelope breakdown (NEBD) during cell division. Reducing PI synthesis suppressed these phenotypes, indicating that CNEP-1 spatially regulates phospholipid flux, biasing it away from PI production in the vicinity of the nuclear envelope to prevent excess ER sheet formation and NEBD defects.
    Print ISSN: 0890-9369
    Topics: Biology
    Published by Cold Spring Harbor Laboratory Press
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