Publish in OALib Journal

ISSN: 2333-9721

APC: Only $99


Search Results: 1 - 10 of 3852 matches for " Tim Stearns "
All listed articles are free for downloading (OA Articles)
Page 1 /3852
Display every page Item
Mammalian cells lack checkpoints for tetraploidy, aberrant centrosome number, and cytokinesis failure
Connie Wong, Tim Stearns
BMC Cell Biology , 2005, DOI: 10.1186/1471-2121-6-6
Abstract: Primary human diploid fibroblasts with intact cell cycle checkpoints were used in all experiments. Synchronized cells exhibited G1 arrest in response to division failure caused by treatment with either cytochalasin or the myosin II inhibitor blebbistatin. The role of tetraploidy, aberrant centrosome number, and increased cell size were tested by cell/cell and cell/cytoplast fusion experiments; none of these conditions resulted in G1 arrest. Instead we found that various drug treatments of the cells resulted in cellular damage, which was the likely cause of the arrest. When cytokinesis was blocked in the absence of damage-inducing drug treatments no G1 arrest was observed.We show that neither tetraploidy, aberrant centrosome number, cell size, nor failure of cytokinesis lead to G1 arrest, suggesting that there is no tetraploidy checkpoint. Rather, certain standard synchronization treatments cause damage that is the likely cause of G1 arrest. Since tetraploid cells can cycle when created with minimal manipulation, previous reports of a tetraploidy checkpoint can probably be explained by side effects of the drug treatments used to observe them.Cell cycle checkpoints preserve genome integrity by monitoring the fidelity of DNA replication and segregation. In mammalian somatic cells, the best-characterized checkpoints are the DNA damage/replication checkpoints and the mitotic spindle checkpoint. The DNA damage/replication checkpoints result in cell cycle arrest if DNA is not fully replicated, or is damaged [1]. The mitotic spindle checkpoint results in cell cycle arrest prior to anaphase if the spindle is not properly assembled [2].There is also evidence that defects in events relating to cell division itself can result in cell cycle arrest. Lanni and Jacks [3] and Casenghi et al.[4] found that mammalian cells that had adapted to microtubule depolymerization and exited mitosis without undergoing cytokinesis arrested in G1 of the subsequent cell cycle. Kurimura and Hirano
FOP Is a Centriolar Satellite Protein Involved in Ciliogenesis
Joanna Y. Lee, Tim Stearns
PLOS ONE , 2013, DOI: 10.1371/journal.pone.0058589
Abstract: Centriolar satellites are proteinaceous granules that are often clustered around the centrosome. Although centriolar satellites have been implicated in protein trafficking in relation to the centrosome and cilium, the details of their function and composition remain unknown. FOP (FGFR1 Oncogene Partner) is a known centrosome protein with homology to the centriolar satellite proteins FOR20 and OFD1. We find that FOP partially co-localizes with the satellite component PCM1 in a cell cycle-dependent manner, similarly to the satellite and cilium component BBS4. As for BBS4, FOP localization to satellites is cell cycle dependent, with few satellites labeled in G1, when FOP protein levels are lowest, and most labeled in G2. FOP-FGFR1, an oncogenic fusion that causes a form of leukemia called myeloproliferative neoplasm, also localizes to centriolar satellites where it increases tyrosine phosphorylation. Depletion of FOP strongly inhibits primary cilium formation in human RPE-1 cells. These results suggest that FOP is a centriolar satellite cargo protein and, as for several other satellite-associated proteins, is involved in ciliogenesis. Localization of the FOP-FGFR1 fusion kinase to centriolar satellites may be relevant to myeloproliferative neoplasm disease progression.
Plk1-Dependent Recruitment of γ-Tubulin Complexes to Mitotic Centrosomes Involves Multiple PCM Components
Laurence Haren, Tim Stearns, Jens Lüders
PLOS ONE , 2009, DOI: 10.1371/journal.pone.0005976
Abstract: The nucleation of microtubules requires protein complexes containing γ-tubulin, which are present in the cytoplasm and associate with the centrosome and with the mitotic spindle. We have previously shown that these interactions require the γ-tubulin targeting factor GCP-WD/NEDD1, which has an essential role in spindle formation. The recruitment of additional γ-tubulin to the centrosomes occurs during centrosome maturation at the G2/M transition and is regulated by the mitotic kinase Plk1. However, the molecular details of this important pathway are unknown and a Plk1 substrate that controls γ-tubulin recruitment has not been identified. Here we show that Plk1 associates with GCP-WD in mitosis and Plk1 activity contributes to phosphorylation of GCP-WD. Plk1 depletion or inhibition prevents accumulation of GCP-WD at mitotic centrosomes, but GCP-WD mutants that are defective in Plk1-binding and -phosphorylation still accumulate at mitotic centrosomes and recruit γ-tubulin. Moreover, Plk1 also controls the recruitment of other PCM proteins implicated in centrosomal γ-tubulin attachment (Cep192/hSPD2, pericentrin, Cep215/Cdk5Rap2). Our results support a model in which Plk1-dependent recruitment of γ-tubulin to mitotic centrosomes is regulated upstream of GCP-WD, involves multiple PCM proteins and therefore potentially multiple Plk1 substrates.
Transcriptional Program of Ciliated Epithelial Cells Reveals New Cilium and Centrosome Components and Links to Human Disease
Ramona A. Hoh, Timothy R. Stowe, Erin Turk, Tim Stearns
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0052166
Abstract: Defects in the centrosome and cilium are associated with a set of human diseases having diverse phenotypes. To further characterize the components that define the function of these organelles we determined the transcriptional profile of multiciliated tracheal epithelial cells. Cultures of mouse tracheal epithelial cells undergoing differentiation in vitro were derived from mice expressing GFP from the ciliated-cell specific FOXJ1 promoter (FOXJ1:GFP). The transcriptional profile of ciliating GFP+ cells from these cultures was defined at an early and a late time point during differentiation and was refined by subtraction of the profile of the non-ciliated GFP- cells. We identified 649 genes upregulated early, when most cells were forming basal bodies, and 73 genes genes upregulated late, when most cells were fully ciliated. Most, but not all, of known centrosome proteins are transcriptionally upregulated early, particularly Plk4, a master regulator of centriole formation. We found that three genes associated with human disease states, Mdm1, Mlf1, and Dyx1c1, are upregulated during ciliogenesis and localize to centrioles and cilia. This transcriptome for mammalian multiciliated epithelial cells identifies new candidate centrosome and cilia proteins, highlights similarities between components of motile and primary cilia, and identifies new links between cilia proteins and human disease.
Centrosome-Kinase Fusions Promote Oncogenic Signaling and Disrupt Centrosome Function in Myeloproliferative Neoplasms
Joanna Y. Lee, Wan-Jen Hong, Ravindra Majeti, Tim Stearns
PLOS ONE , 2014, DOI: 10.1371/journal.pone.0092641
Abstract: Chromosomal translocations observed in myeloproliferative neoplasms (MPNs) frequently fuse genes that encode centrosome proteins and tyrosine kinases. This causes constitutive activation of the kinase resulting in aberrant, proliferative signaling. The function of centrosome proteins in these fusions is not well understood. Among others, kinase centrosome localization and constitutive kinase dimerization are possible consequences of centrosome protein-kinase fusions. To test the relative contributions of localization and dimerization on kinase signaling, we targeted inducibly dimerizable FGFR1 to the centrosome and other subcellular locations and generated a mutant of the FOP-FGFR1 MPN fusion defective in centrosome localization. Expression in mammalian cells followed by western blot analysis revealed a significant decrease in kinase signaling upon loss of FOP-FGFR1 centrosome localization. Kinase dimerization alone resulted in phosphorylation of the FGFR1 signaling target PLCγ, however levels comparable to FOP-FGFR1 required subcellular targeting in addition to kinase dimerization. Expression of MPN fusion proteins also resulted in centrosome disruption in epithelial cells and transformed patient cells. Primary human MPN cells showed masses of modified tubulin that colocalized with centrin, Smoothened (Smo), IFT88, and Arl13b. This is distinct from acute myeloid leukemia (AML) cells, which are not associated with centrosome-kinase fusions and had normal centrosomes. Our results suggest that effective proliferative MPN signaling requires both subcellular localization and dimerization of MPN kinases, both of which may be provided by centrosome protein fusion partners. Furthermore, centrosome disruption may contribute to the MPN transformation phenotype.
Two passages in Ibn al-Kha īb's account of the kings of Christian Iberia
Stearns, Justin
Al-Qantara : Revista de Estudios Arabes , 2004,
Abstract: Not available No disponible
DCP Series
Philip Stearns
continent. , 2011,
Abstract: Photo essay. A collection of Images produced by intentionally corrupting the circuitry of a Kodak DC280 2 MP digitalcamera. By rewiring the electronics of a digital camera, glitched images are produced in a manner that parallels chemically processing unexposed film or photographic paper to produce photographic images without exposure to light. The DCP Series of Digital Images are direct visualizations of data generated by a digital camera as it takes a picture. Electronic processes associated with the normal operations of the camera, which are usually taken for granted, are revealed through an act of intervention. The camera is turned inside-out through complexes of short-circuits, selected by the artist, transforming the camera from a picture taking device to a data capturing device that renders raw data (electronic signals) as images. In essence, these images are snap-shots of electronic signals dancing through the camera's circuits, manually rerouted, written directly to the on-board memory device. Rather than seeing images of the world through a lens, we catch a glimpse of what the camera sees when it is forced to peer inside its own mind.
Production and Financial Analyses of the Rotating Living Wall, an Urban Agricultural System  [PDF]
Jonathan Gumble, Robert Berghage, Dan Stearns
Journal of Environmental Protection (JEP) , 2015, DOI: 10.4236/jep.2015.69091
Abstract: Experiments were performed from June 2014 to May 2015 at Penn State University’s greenhouse facilities in order to understand the production capacities and financial viability of an innovative growing system referred to as the Rotating Living Wall produced by GreenTowers, a student innovation/entrepreneurship team. The system is a six-foot vertical conveyor that rotates troughs of microgreen plants to achieve even distribution of sunlight as well as relatively low maintenance within a minimal square foot area. Experiments were performed to understand differences in seasonal yields, differences in yields based on variety of microgreen, yield comparison to a traditionally grown microgreen control group; both on a yields per/trough method as well as a yields per/ft.2 method, rotational timing, moving versus stationary growth, differences in growth based on media depth, and differences in production yields from supplemental lighting. Performance criteria were based on measuring fresh weight, dry weight, height, and SPAD-meter readings (soil plant analysis development). Differences in yields throughout seasons were significant as well as differences between the Rotating Living Wall systems compared to a control group of traditional static greenhouse benches. The use of LED supplemental lighting provided significant differences in yields throughout winter season growing. Rotational timing, media depth, and physical movement of plants showed minimal or no significant influence on yields. By establishing the potential revenues and costs that were part of growing with the Rotating Living Wall system, financial viability was analyzed showing that these systems could be profitable when utilized in State College, PA, within certain operating parameters. The research completed throughout these studies has not only provided a baseline of operation for the systems but has also shown potential for the development of urban agricultural systems capable of aiding in the elimination of “food deserts” or urban neighborhoods and rural towns with limited food access.
Mechanosensing by the Primary Cilium: Deletion of Kif3A Reduces Bone Formation Due to Loading
Sara Temiyasathit,W. Joyce Tang,Philipp Leucht,Charles T. Anderson,Stefanie D. Monica,Alesha B. Castillo,Jill A. Helms,Tim Stearns,Christopher R. Jacobs
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0033368
Abstract: Primary cilia, solitary microtubule-based structures that grow from the centriole and extend into the extracellular space, have increasingly been implicated as sensors of a variety of biochemical and biophysical signals. Mutations in primary cilium-related genes have been linked to a number of rare developmental disorders as well as dysregulation of cell proliferation. We propose that primary cilia are also important in mechanically regulated bone formation in adults and that their malfunction could play a role in complex multi-factorial bone diseases, such as osteoporosis. In this study, we generated mice with an osteoblast- and osteocyte-specific knockout of Kif3a, a subunit of the kinesin II intraflagellar transport (IFT) protein; IFT is required for primary cilia formation, maintenance, and function. These Colα1(I) 2.3-Cre;Kif3afl/fl mice exhibited no obvious morphological skeletal abnormalities. Skeletally mature Colα1(I) 2.3-Cre;Kif3afl/fl and control mice were exposed to 3 consecutive days of cyclic axial ulna loading, which resulted in a significant increase in bone formation in both the conditional knockouts and controls. However, Colα1(I) 2.3-Cre;Kif3afl/fl mice did exhibit decreased formation of new bone in response to mechanical ulnar loading compared to control mice. These results suggest that primary cilia act as cellular mechanosensors in bone and that their function may be critical for the regulation of bone physiology due to mechanical loading in adults.
Aromatase inhibitor-associated bone and musculoskeletal effects: new evidence defining etiology and strategies for management
Stéphanie Gaillard, Vered Stearns
Breast Cancer Research , 2011, DOI: 10.1186/bcr2818
Abstract: In 2010, it is estimated that more than 200,000 women will be newly diagnosed with invasive breast cancer in the United States [1], making it the most commonly diagnosed cancer in women. The majority of women are post-menopausal at the time of diagnosis. Adjuvant endocrine manipulations reduce the risk of breast cancer-related recurrence and death in women with hormone receptor-positive disease. The introduction of aromatase inhibitors (AIs) to the adjuvant treatment of postmenopausal women with hormone receptor-positive breast cancer has significantly changed the management of the disease. These agents are commonly used instead of or in sequence with tamoxifen because of the demonstrated improvement in disease-free survival compared to tamoxifen alone [2]. Since long-term survival rates are high in patients with early-stage breast cancer who receive AIs and treatment may continue for many years, the complications arising from therapy in this patient population can have long-term effects and may greatly impact patient quality of life.The three third-generation AIs in routine clinical use - anastrozole (Arimidex), letrozole (Femara), and exemestane (Aromasin) - have similar efficacy and toxicity profiles when evaluated in cross-study comparisons. The primary adverse effects include menopausal symptoms, vaginal dryness, sexual dysfunction, and musculoskeletal symptoms, including bone demineralization with risk of osteoporosis and fracture, arthralgias, and myalgias. This review will focus on AI-associated bone and musculo-skeletal toxicities, including prevalence, typical symptoms, potential etiologies, and strategies for management of these side effects.Estrogen is primarily produced in the ovary prior to menopause. After menopause, estrogen production occurs in peripheral tissues (skin, muscle, fat, and benign and malignant breast tissue) through the conversion of androgens to estrogens by the P450 cytochrome enzyme aromatase (CYP19) [3-6]. There are two primary app
Page 1 /3852
Display every page Item

Copyright © 2008-2017 Open Access Library. All rights reserved.