Página 21 dos resultados de 45945 itens digitais encontrados em 0.043 segundos

‣ Cell Biology of Mating in Candida albicans

Lockhart, Shawn R.; Daniels, Karla J.; Zhao, Rui; Wessels, Deborah; Soll, David R.
Fonte: American Society for Microbiology Publicador: American Society for Microbiology
Tipo: Artigo de Revista Científica
Publicado em /02/2003 Português
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It was recently demonstrated that strains homozygous for either of the mating type-like loci MTLa and MTLα of Candida albicans undergo white-opaque switching and that expression of the opaque-phase phenotype greatly enhances mating between strains. Exploiting the latter property to obtain high-frequency mating, we have characterized the cell biology of the mating process of C. albicans. Employing continuous videomicroscopy, computer-assisted three-dimensional reconstruction of living cells, and fluorescence microscopy, we have monitored the mating-associated processes of conjugation, tube formation, fusion, budding, septum formation, and daughter cell development and the spatial and temporal dynamics of nuclear migration and division. From these observations, a model for the stages in C. albicans mating is formulated. The stages include shmooing, chemotropism of conjugation tubes, fusion of tubes and nuclear association, vacuole expansion and nuclear separation in the conjugation bridge, asynchronous nuclear division in the zygote, bud growth, nuclear migration into the daughter cell, septation, and daughter cell budding. Since there was no cytological indication of karyogamy, genetic experiments were performed to assess marker segregation. Recombination was not observed...

‣ FM19G11, a New Hypoxia-inducible Factor (HIF) Modulator, Affects Stem Cell Differentiation Status*

Moreno-Manzano, Victoria; Rodríguez-Jiménez, Francisco J.; Aceña-Bonilla, Jose L.; Fustero-Lardíes, Santos; Erceg, Slaven; Dopazo, Joaquin; Montaner, David; Stojkovic, Miodrag; Sánchez-Puelles, Jose M.
Fonte: American Society for Biochemistry and Molecular Biology Publicador: American Society for Biochemistry and Molecular Biology
Tipo: Artigo de Revista Científica
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The biology of the α subunits of hypoxia-inducible factors (HIFα) has expanded from their role in angiogenesis to their current position in the self-renewal and differentiation of stem cells. The results reported in this article show the discovery of FM19G11, a novel chemical entity that inhibits HIFα proteins that repress target genes of the two α subunits, in various tumor cell lines as well as in adult and embryonic stem cell models from rodents and humans, respectively. FM19G11 inhibits at nanomolar range the transcriptional and protein expression of Oct4, Sox2, Nanog, and Tgf-α undifferentiating factors, in adult rat and human embryonic stem cells, FM19G11 activity occurs in ependymal progenitor stem cells from rats (epSPC), a cell model reported for spinal cord regeneration, which allows the progression of oligodendrocyte cell differentiation in a hypoxic environment, has created interest in its characterization for pharmacological research. Experiments using small interfering RNA showed a significant depletion in Sox2 protein only in the case of HIF2α silencing, but not in HIF1α-mediated ablation. Moreover, chromatin immunoprecipitation data, together with the significant presence of functional hypoxia response element consensus sequences in the promoter region of Sox2...

‣ Intracellular Shuttling and Mitochondrial Function of Thioredoxin-interacting Protein*

Saxena, Geetu; Chen, Junqin; Shalev, Anath
Fonte: American Society for Biochemistry and Molecular Biology Publicador: American Society for Biochemistry and Molecular Biology
Tipo: Artigo de Revista Científica
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The thioredoxin-interacting protein TXNIP is a ubiquitously expressed redox protein that promotes apoptosis. Recently, we found that TXNIP deficiency protects against type 1 and 2 diabetes by inhibiting beta cell apoptosis and maintaining pancreatic beta cell mass, indicating that TXNIP plays a key role in beta cell biology. However, very little is known about the intracellular localization and function of TXNIP, and although TXNIP has been thought to be a cytoplasmic protein, our immunohistochemistry studies in beta cells surprisingly revealed a nuclear TXNIP localization, suggesting that TXNIP may shuttle within the cell. Using immunohistochemistry/confocal imaging and cell fractionation/co-immunoprecipitation, we found that, under physiological conditions, TXNIP is localized primarily in the nucleus of pancreatic beta cells, whereas oxidative stress leads to TXNIP shuttling into the mitochondria. In mitochondria, TXNIP binds to and oxidizes Trx2, thereby reducing Trx2 binding to ASK1 and allowing for ASK1 phosphorylation/activation, resulting in induction of the mitochondrial pathway of apoptosis with cytochrome c release and caspase-3 cleavage. TXNIP overexpression and Trx2 (but not cytosolic Trx1) silencing mimic these effects. Thus...

‣ An Undergraduate Course to Bridge the Gap between Textbooks and Scientific Research

Wiegant, Fred; Scager, Karin; Boonstra, Johannes
Fonte: American Society for Cell Biology Publicador: American Society for Cell Biology
Tipo: Artigo de Revista Científica
Publicado em 01/03/2011 Português
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This article reports on a one-semester Advanced Cell Biology course that endeavors to bridge the gap between gaining basic textbook knowledge about cell biology and learning to think and work as a researcher. The key elements of this course are 1) learning to work with primary articles in order to get acquainted with the field of choice, to learn scientific reasoning, and to identify gaps in our current knowledge that represent opportunities for further research; 2) formulating a research project with fellow students; 3) gaining thorough knowledge of relevant methodology and technologies used within the field of cell biology; 4) developing cooperation and leadership skills; and 5) presenting and defending research projects before a jury of experts. The course activities were student centered and focused on designing a genuine research program. Our 5-yr experience with this course demonstrates that 1) undergraduate students are capable of delivering high-quality research designs that meet professional standards, and 2) the authenticity of the learning environment in this course strongly engages students to become self-directed and critical thinkers. We hope to provide colleagues with an example of a course that encourages and stimulates students to develop essential research thinking skills.

‣ Micro/nano-fabrication technologies for cell biology

Qian, Tongcheng; Wang, Yingxiao
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
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Micro/nano-fabrication techniques, such as soft lithography and electrospinning, have been well-developed and widely applied in many research fields in the past decade. Due to the low costs and simple procedures, these techniques have become important and popular for biological studies. In this review, we focus on the studies integrating micro/nano-fabrication work to elucidate the molecular mechanism of signaling transduction in cell biology. We first describe different micro/nano-fabrication technologies, including techniques generating three-dimensional scaffolds for tissue engineering. We then introduce the application of these technologies in manipulating the physical or chemical micro/nano-environment to regulate the cellular behavior and response, such as cell life and death, differentiation, proliferation, and cell migration. Recent advancement in integrating the micro/nano-technologies and live cell imaging are also discussed. Finally, potential schemes in cell biology involving micro/nano-fabrication technologies are proposed to provide perspectives on the future research activities.

‣ Cell biology: At the center of modern biomedicine

Budde, Priya Prakash; Williams, Elizabeth H.; Misteli, Tom
Fonte: The Rockefeller University Press Publicador: The Rockefeller University Press
Tipo: Artigo de Revista Científica
Publicado em 01/10/2012 Português
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How does basic cell biology contribute to biomedicine? A new series of Features in JCB provides a cross section of compelling examples of how basic cell biology findings can lead to therapeutics. These articles highlight the fruitful, essential, and increasingly prominent bridge that exists between cell biology and the clinic.

‣ Newly Identified Roles of PML in Stem Cell Biology

Ito, Kyoko; Ito, Keisuke
Fonte: Frontiers Media S.A. Publicador: Frontiers Media S.A.
Tipo: Artigo de Revista Científica
Publicado em 14/03/2013 Português
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It has long been believed that the tumor suppressor promyelocytic leukemia (PML), the core component of the nuclear substructures known as the PML-nuclear bodies, plays a key part in acute PML (APL), as it is first cloned at the breakpoint of the t(15;17) translocation typical of that disease. Research over the past decade, however, has radically changed our view of how this tumor suppressor is regulated, how it can be therapeutically targeted, and how it functions in a number of tissue systems. One noteworthy recent study, for instance, revealed that PML regulates the activation of fatty acid metabolism, and that this metabolic reprograming plays an essential role in cancer biology and stem cell biology through the control it exerts over stem cell fate decisions. These findings sparked exciting new investigations of PML as a critical “rheostat” responsible for fine-tuning tissue homeostasis, and thus created at the intersection of cancer and stem cell biology a new field of study with important therapeutic implications.

‣ Onward from the cradle

Satir, Peter
Fonte: The American Society for Cell Biology Publicador: The American Society for Cell Biology
Tipo: Artigo de Revista Científica
Publicado em 01/11/2014 Português
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This essay records a voyage of discovery from the “cradle of cell biology” to the present, focused on the biology of the oldest known cell organelle, the cilium. In the “romper room” of cilia and microtubule (MT) biology, the sliding MT hypothesis of ciliary motility was born. From the “summer of love,” students and colleagues joined the journey to test switch-point mechanisms of motility. In the new century, interest in nonmotile (primary) cilia, never lost from the cradle, was rekindled, leading to discoveries relating ciliogenesis to autophagy and hypotheses of how molecules cross ciliary necklace barriers for cell signaling.

‣ Histone H2A Mono-Ubiquitination Is a Crucial Step to Mediate PRC1-Dependent Repression of Developmental Genes to Maintain ES Cell Identity

Endoh, Mitsuhiro; Endo, Takaho A.; Endoh, Tamie; Isono, Kyo-ichi; Sharif, Jafar; Ohara, Osamu; Toyoda, Tetsuro; Ito, Takashi; Eskeland, Ragnhild; Bickmore, Wendy A.; Koseki, Haruhiko; Vidal, Miguel; Bernstein, Bradley E.
Fonte: Public Library of Science Publicador: Public Library of Science
Tipo: Artigo de Revista Científica
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Two distinct Polycomb complexes, PRC1 and PRC2, collaborate to maintain epigenetic repression of key developmental loci in embryonic stem cells (ESCs). PRC1 and PRC2 have histone modifying activities, catalyzing mono-ubiquitination of histone H2A (H2AK119u1) and trimethylation of H3 lysine 27 (H3K27me3), respectively. Compared to H3K27me3, localization and the role of H2AK119u1 are not fully understood in ESCs. Here we present genome-wide H2AK119u1 maps in ESCs and identify a group of genes at which H2AK119u1 is deposited in a Ring1-dependent manner. These genes are a distinctive subset of genes with H3K27me3 enrichment and are the central targets of Polycomb silencing that are required to maintain ESC identity. We further show that the H2A ubiquitination activity of PRC1 is dispensable for its target binding and its activity to compact chromatin at Hox loci, but is indispensable for efficient repression of target genes and thereby ESC maintenance. These data demonstrate that multiple effector mechanisms including H2A ubiquitination and chromatin compaction combine to mediate PRC1-dependent repression of genes that are crucial for the maintenance of ESC identity. Utilization of these diverse effector mechanisms might provide a means to maintain a repressive state that is robust yet highly responsive to developmental cues during ES cell self-renewal and differentiation.

‣ Folliculin, the Product of the Birt-Hogg-Dube Tumor Suppressor Gene, Interacts with the Adherens Junction Protein p0071 to Regulate Cell-Cell Adhesion

Medvetz, Douglas A; Khabibullin, Damir; Hariharan, Venkatesh; Ongusaha, Pat P.; Goncharova, Elena A.; Schlechter, Tanja; Darling, Thomas N.; Hofmann, Ilse; Krymskaya, Vera P.; Liao, James K.; Huang, Hayden; Henske, Elizabeth Petri
Fonte: Public Library of Science Publicador: Public Library of Science
Tipo: Artigo de Revista Científica
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Birt-Hogg-Dube (BHD) is a tumor suppressor gene syndrome associated with fibrofolliculomas, cystic lung disease, and chromophobe renal cell carcinoma. In seeking to elucidate the pathogenesis of BHD, we discovered a physical interaction between folliculin (FLCN), the protein product of the BHD gene, and p0071, an armadillo repeat containing protein that localizes to the cytoplasm and to adherens junctions. Adherens junctions are one of the three cell-cell junctions that are essential to the establishment and maintenance of the cellular architecture of all epithelial tissues. Surprisingly, we found that downregulation of FLCN leads to increased cell-cell adhesion in functional cell-based assays and disruption of cell polarity in a three-dimensional lumen-forming assay, both of which are phenocopied by downregulation of p0071. These data indicate that the FLCN-p0071 protein complex is a negative regulator of cell-cell adhesion. We also found that FLCN positively regulates RhoA activity and Rho-associated kinase activity, consistent with the only known function of p0071. Finally, to examine the role of Flcn loss on cell-cell adhesion in vivo, we utilized keratin-14 cre-recombinase (K14-cre) to inactivate Flcn in the mouse epidermis. The K14-Cre-Bhdflox/flox mice have striking delays in eyelid opening...

‣ Dimethyl Sulfoxide (DMSO) Exacerbates Cisplatin-induced Sensory Hair Cell Death in Zebrafish (Danio rerio)

Uribe, Phillip M.; Mueller, Melissa; Gleichman, Julia S.; Kramer, Matthew; Wang, Qi; Sibrian-Vazquez, Martha; Strongin, Robert M.; Steyger, Peter S.; Cotanche, Douglas; Matsui, Jonathan I.
Fonte: Public Library of Science Publicador: Public Library of Science
Tipo: Artigo de Revista Científica
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Inner ear sensory hair cells die following exposure to aminoglycoside antibiotics or chemotherapeutics like cisplatin, leading to permanent auditory and/or balance deficits in humans. Zebrafish (Danio rerio) are used to study drug-induced sensory hair cell death since their hair cells are similar in structure and function to those found in humans. We developed a cisplatin dose-response curve using a transgenic line of zebrafish that expresses membrane-targeted green fluorescent protein under the control of the Brn3c promoter/enhancer. Recently, several small molecule screens have been conducted using zebrafish to identify potential pharmacological agents that could be used to protect sensory hair cells in the presence of ototoxic drugs. Dimethyl sulfoxide (DMSO) is typically used as a solvent for many pharmacological agents in sensory hair cell cytotoxicity assays. Serendipitously, we found that DMSO potentiated the effects of cisplatin and killed more sensory hair cells than treatment with cisplatin alone. Yet, DMSO alone did not kill hair cells. We did not observe the synergistic effects of DMSO with the ototoxic aminoglycoside antibiotic neomycin. Cisplatin treatment with other commonly used organic solvents (i.e. ethanol, methanol...

‣ Structural Correlates of Rotavirus Cell Entry

Abdelhakim, Aliaa H.; Salgado, Eric N.; Fu, Xiaofeng; Pasham, Mithun; Nicastro, Daniela; Kirchhausen, Tomas; Harrison, Stephen C.
Fonte: Public Library of Science Publicador: Public Library of Science
Tipo: Artigo de Revista Científica
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Cell entry by non-enveloped viruses requires translocation into the cytosol of a macromolecular complex—for double-strand RNA viruses, a complete subviral particle. We have used live-cell fluorescence imaging to follow rotavirus entry and penetration into the cytosol of its ∼700 Å inner capsid particle (“double-layered particle”, DLP). We label with distinct fluorescent tags the DLP and each of the two outer-layer proteins and track the fates of each species as the particles bind and enter BSC-1 cells. Virions attach to their glycolipid receptors in the host cell membrane and rapidly become inaccessible to externally added agents; most particles that release their DLP into the cytosol have done so by ∼10 minutes, as detected by rapid diffusional motion of the DLP away from residual outer-layer proteins. Electron microscopy shows images of particles at various stages of engulfment into tightly fitting membrane invaginations, consistent with the interpretation that rotavirus particles drive their own uptake. Electron cryotomography of membrane-bound virions also shows closely wrapped membrane. Combined with high resolution structural information about the viral components, these observations suggest a molecular model for membrane disruption and DLP penetration.

‣ In Vitro Studies of Amyotrophic Lateral Sclerosis Using Human Pluripotent Stem Cell-Derived Motor Neurons

Williams Gonzalez, Luis A.
Fonte: Harvard University Publicador: Harvard University
Tipo: Thesis or Dissertation; text Formato: application/pdf
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Among the disciplines of medicine, the study of neurological disorders such as amyotrophic lateral sclerosis (ALS) is particularly challenging. In ALS, both cortical and spinal motor neurons progressively degenerate, leading to paralysis and death. The fundamental inaccessibility and the postmitotic state of these cells prevent their isolation and culture for studies of degenerative mechanisms or for drug screening efforts. The studies presented here support the premise that human motor neurons (MNs) generated by directed differentiation of induced pluripotent (iPS) or embryonic stem cells (ES) represent a great research tool to address this challenge. We show that MNs derived from patient-specific iPS cells with known ALS-linked mutations can recapitulate molecular and functional phenotypes associated with the disease. The phenotypes observed included transcriptional and morphological changes in mitochondria, protein solubility, membrane hyperexcitability, and defects in cell survival and axonal transport. By utilizing gene-targeting technology we further validated the requirement, and in some cases the sufficiency, of the SOD1A4V mutant allele to drive some of these phenotypes. Additionally, by means of a human ES cell line with a stable MN-specific green fluorescence protein (GFP) reporter...

‣ The roles of Cabin1 and Left1 in T cell development; Roles of Cabin one and Left one in T-cell development

Esau, Christine C. (Christine Carol), 1972-
Fonte: Massachusetts Institute of Technology Publicador: Massachusetts Institute of Technology
Tipo: Tese de Doutorado Formato: 148 leaves; 12313909 bytes; 12313665 bytes; application/pdf; application/pdf
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Cabinl binds calcineurin and myocyte enhancer factor 2 (MEF2) through the C-terminal region. In cell lines, these interactions inhibit calcineurin activity following TCR signaling and transcriptional activation of Nur77 by MEF2. The role of these interactions in vivo was investigated using a mutant mouse strain that expresses a truncated Cabin 1 lacking the C-terminal calcineurin and MEF2 binding domains. Although mutant mice exhibited normal lymphocyte development and thymocyte apoptosis, they had elevated levels of serum IgG 1, IgG2b and IgE and produced more IgG1 and IgG2b in response to a T-dependent antigen. The increased antibody production is apparently not due to changes in immunoglobulin class switching as B cells from mutant mice switched to IgG 1 at the same frequency as wildtype B cells in vitro in the presence of IL-4. However, in response to anti-CD3 stimulation, mutant T cells expressed significantly higher levels of IL-2, IL-4, IL-9, IL-13, and IFN-y. Thus, the calcineurin and MEF2 binding domain of Cabin 1 is dispensable for thymocyte development and apoptosis, but is required for proper regulation of T cell cytokine expression and Th2 antibody responses. In our analysis of gene expression in memory CD8+ T cells, we identified a member of the membrane spanning 4A gene family...

‣ The rhinoceros gene of drosophila restricts cell fate specification in the developing eye

Voas, Matthew G. (Matthew Gary), 1973-
Fonte: Massachusetts Institute of Technology Publicador: Massachusetts Institute of Technology
Tipo: Tese de Doutorado Formato: 270, [2] p.; 10924636 bytes; 10924435 bytes; application/pdf; application/pdf
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Inductive signaling between cells in the developing eye of Drosophila is very important for establishing the correct number and identity of cell fates. Among the signaling pathways that regulate cell fate determination in the developing eye, RTK/Ras/MAPK is among the most important. One effect of RTK/Ras/MAPK signaling is to downregulate the transcription factor Yan, thus allowing differentiation. A previous genetic screen identified modifiers of YanACT, a constitutively active isoform of Yan. From this screen, two alleles of Enhancer of YanAC, 3-5 (EY3-5) were identified as enhancers. A genetic screen was conducted to isolate new EY3-5 alleles for genetic and molecular characterization. The conclusion is reached that the defining phenotype of EY3-5 is a multigenic effect caused by large deletions present in the two founding alleles of EY3-5. These studies led to the investigation of the roles of three genes in signal transduction. The strongest enhancer of YanACT among these three genes, called hidden clones, appears to be necessary for growth and is involved in early cell fate decisions in the eye. Also described here is the role of the rhinoceros (rno) gene in regulating eye cell fates. Mutation of mo causes the overproduction of eye cell fates and inhibits apoptosis. These phenotypes are similar to those seen when EGFR is hyperactivated in argos mutants. Tests between argos and rno alleles show a strong genetic interaction. Furthermore...

‣ Chromosome dynamics of the early meiotic cell cycle in S. cerevisiae

Blitzblau, Hannah G
Fonte: Massachusetts Institute of Technology Publicador: Massachusetts Institute of Technology
Tipo: Tese de Doutorado Formato: 186 p.
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In every cell cycle the genetic material must be duplicated and transmitted to the daughter cells. Meiosis is a developmental program that allows a diploid cell to produce haploid progeny. The reduction in chromosome number obtained during meiosis requires specialized mechanisms that are absent during the canonical mitotic cell cycle. Although previous studies found strong similarities between pre-mitotic and pre-meiotic DNA replication, pre-meiotic S phase is longer than pre-mitotic S phase, suggesting that meiosis-specific events regulate the rate of DNA replication. Additionally, after DNA replication, homologous recombination is initiated by the introduction of hundreds DNA double-strand breaks (DSBs) into the genome to produce physical DNA exchanges, or crossovers, between homologous chromosomes. To investigate the chromosome dynamics of the early meiotic cell cycle, I performed comprehensive analysis of pre-meiotic DNA replication and DSB formation in budding yeast. Genome-wide studies of pre-meiotic DNA replication confirmed that the same replication origins are selected and activated in pre-meiotic and pre-mitotic cells, although replication was delayed at a large number of origins. These results indicate that the regulation of DNA replication is similar in the meiotic and mitotic cell cycles...

‣ Critical reviews in oral biology & medicine: Mesenchymal stem cells derived from dental tissues vs. those from other sources: their biology and role in regenerative medicine

Huang, G.J.; Gronthos, S.; Shi, S.
Fonte: Inter Amer Assoc Dental Research Publicador: Inter Amer Assoc Dental Research
Tipo: Artigo de Revista Científica
Publicado em //2009 Português
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To date, 5 different human dental stem/progenitor cells have been isolated and characterized: dental pulp stem cells (DPSCs), stem cells from exfoliated deciduous teeth (SHED), periodontal ligament stem cells (PDLSCs), stem cells from apical papilla (SCAP), and dental follicle progenitor cells (DFPCs). These postnatal populations have mesenchymal-stem-cell-like (MSC) qualities, including the capacity for self-renewal and multilineage differentiation potential. MSCs derived from bone marrow (BMMSCs) are capable of giving rise to various lineages of cells, such as osteogenic, chondrogenic, adipogenic, myogenic, and neurogenic cells. The dental-tissue-derived stem cells are isolated from specialized tissue with potent capacities to differentiate into odontogenic cells. However, they also have the ability to give rise to other cell lineages similar to, but different in potency from, that of BMMSCs. This article will review the isolation and characterization of the properties of different dental MSC-like populations in comparison with those of other MSCs, such as BMMSCs. Important issues in stem cell biology, such as stem cell niche, homing, and immunoregulation, will also be discussed.; G.T.-J. Huang, S. Gronthos and S. Shi; Copyright © 2009 by International & American Associations for Dental Research

‣ An Intermittent Live Cell Imaging Screen for siRNA Enhancers and Suppressors of a Kinesin-5 Inhibitor

Tsui, Melody; Carpenter, Anne E.; Xie, Tiao; Orth, James Daniel; Rudnicki, Stewart; Kim, Suejong; Shamu, Caroline Elizabeth; Mitchison, Timothy J.
Fonte: Public Library of Science Publicador: Public Library of Science
Tipo: Artigo de Revista Científica
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Kinesin-5 (also known as Eg5, KSP and Kif11) is required for assembly of a bipolar mitotic spindle. Small molecule inhibitors of Kinesin-5, developed as potential anti-cancer drugs, arrest cell in mitosis and promote apoptosis of cancer cells. We performed a genome-wide siRNA screen for enhancers and suppressors of a Kinesin-5 inhibitor in human cells to elucidate cellular responses, and thus identify factors that might predict drug sensitivity in cancers. Because the drug's actions play out over several days, we developed an intermittent imaging screen. Live HeLa cells expressing GFP-tagged histone H2B were imaged at 0, 24 and 48 hours after drug addition, and images were analyzed using open-source software that incorporates machine learning. This screen effectively identified siRNAs that caused increased mitotic arrest at low drug concentrations (enhancers), and vice versa (suppressors), and we report siRNAs that caused both effects. We then classified the effect of siRNAs for 15 genes where 3 or 4 out of 4 siRNA oligos tested were suppressors as assessed by time lapse imaging, and by testing for suppression of mitotic arrest in taxol and nocodazole. This identified 4 phenotypic classes of drug suppressors, which included known and novel genes. Our methodology should be applicable to other screens...

‣ The changing world of modern cell biology

Misteli, Tom
Fonte: The Rockefeller University Press Publicador: The Rockefeller University Press
Tipo: Artigo de Revista Científica
Publicado em 12/01/2009 Português
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Change is always ambiguous. There is the enticing prospect of novelty and better times ahead, but at the same time the concern of losing the good of the past. It is with these sentiments that I take over as the Editor-in-Chief from Ira Mellman who for a decade has cleverly and effectively lead the JCB. During this time he directed and oversaw an extensive modernization of the journal and guided it through dramatic changes in the publishing world. Ira lead the journal with unyielding dedication and enthusiasm and we in the cell biology community must thank him profoundly for his service. It is his work, together with the invaluable contribution of the best editorial board and the most dedicated professional editorial staff in the scientific publishing business, that allows me to now take over the stewardship of the JCB with a tremendous sense of excitement and determination to continue and expand the JCB's role as the leading journal in the cell biology community and as a trendsetter in the rapidly changing world of modern cell biology.

‣ Complex Systems Analysis of Cell Cycling Models in Carcinogenesis

I. C. Baianu
Fonte: Nature Preceedings Publicador: Nature Preceedings
Tipo: Manuscript
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A new approach to the modular, complex systems analysis of nonlinear dynamics in cell cycling network transformations involved in carcinogenesis is proposed. Carcinogenesis is a complex process that involves dynamically inter-connected biomolecules in the intercellular, membrane, cytosolic, nuclear and nucleolar compartments that form numerous inter-related pathways referred to as networks. The variable biotopology of such dynamic networks is highly complex, and has a number of interesting properties that can be formally characterized at one level of organization by mathematical structures called 'biogroupoids'. One such family of pathways contains the cell cyclins. Cyclins are proteins that link several critical pro-apoptotic and other cell cycling/ division components, including the tumor suppressor gene TP53 and its product, the Thomsen-Friedenreich antigen (T antigen), Rb, mdm2, c-Myc, p21, p27, Bax, Bad and Bcl-2, which all play major roles in carcinogenesis of many cancers. A novel theoretical analysis is thus possible based on recently published studies of cyclin signaling, with special emphasis placed on the roles of cyclins D1 and E, suggests novel clinical trials and rational therapies of cancer through reestablishment of cell cycling inhibition in metastatic cancer cells.