Phase of the CELL CYCLE following G1 and preceding G2 when the entire DNA content of the nucleus is replicated. It is achieved by bidirectional replication at multiple sites along each chromosome.
The complex series of phenomena, occurring between the end of one CELL DIVISION and the end of the next, by which cellular material is duplicated and then divided between two daughter cells. The cell cycle includes INTERPHASE, which includes G0 PHASE; G1 PHASE; S PHASE; and G2 PHASE, and CELL DIVISION PHASE.
The period of the CELL CYCLE preceding DNA REPLICATION in S PHASE. Subphases of G1 include "competence" (to respond to growth factors), G1a (entry into G1), G1b (progression), and G1c (assembly). Progression through the G1 subphases is effected by limiting growth factors, nutrients, or inhibitors.
The process by which a DNA molecule is duplicated.
Proteins that control the CELL DIVISION CYCLE. This family of proteins includes a wide variety of classes, including CYCLIN-DEPENDENT KINASES, mitogen-activated kinases, CYCLINS, and PHOSPHOPROTEIN PHOSPHATASES as well as their putative substrates such as chromatin-associated proteins, CYTOSKELETAL PROTEINS, and TRANSCRIPTION FACTORS.
The interval between two successive CELL DIVISIONS during which the CHROMOSOMES are not individually distinguishable. It is composed of the G phases (G1 PHASE; G0 PHASE; G2 PHASE) and S PHASE (when DNA replication occurs).
A type of CELL NUCLEUS division by means of which the two daughter nuclei normally receive identical complements of the number of CHROMOSOMES of the somatic cells of the species.
A key regulator of CELL CYCLE progression. It partners with CYCLIN E to regulate entry into S PHASE and also interacts with CYCLIN A to phosphorylate RETINOBLASTOMA PROTEIN. Its activity is inhibited by CYCLIN-DEPENDENT KINASE INHIBITOR P27 and CYCLIN-DEPENDENT KINASE INHIBITOR P21.
Protein kinases that control cell cycle progression in all eukaryotes and require physical association with CYCLINS to achieve full enzymatic activity. Cyclin-dependent kinases are regulated by phosphorylation and dephosphorylation events.
A 50-kDa protein that complexes with CYCLIN-DEPENDENT KINASE 2 in the late G1 phase of the cell cycle.
A large family of regulatory proteins that function as accessory subunits to a variety of CYCLIN-DEPENDENT KINASES. They generally function as ENZYME ACTIVATORS that drive the CELL CYCLE through transitions between phases. A subset of cyclins may also function as transcriptional regulators.
A cyclin subtype that has specificity for CDC2 PROTEIN KINASE and CYCLIN-DEPENDENT KINASE 2. It plays a role in progression of the CELL CYCLE through G1/S and G2/M phase transitions.
The fission of a CELL. It includes CYTOKINESIS, when the CYTOPLASM of a cell is divided, and CELL NUCLEUS DIVISION.
A family of cell cycle-dependent kinases that are related in structure to CDC28 PROTEIN KINASE; S CEREVISIAE; and the CDC2 PROTEIN KINASE found in mammalian species.
The period of the CELL CYCLE following DNA synthesis (S PHASE) and preceding M PHASE (cell division phase). The CHROMOSOMES are tetraploid in this point.
A unique DNA sequence of a replicon at which DNA REPLICATION is initiated and proceeds bidirectionally or unidirectionally. It contains the sites where the first separation of the complementary strands occurs, a primer RNA is synthesized, and the switch from primer RNA to DNA synthesis takes place. (Rieger et al., Glossary of Genetics: Classical and Molecular, 5th ed)
A family of basic helix-loop-helix transcription factors that control expression of a variety of GENES involved in CELL CYCLE regulation. E2F transcription factors typically form heterodimeric complexes with TRANSCRIPTION FACTOR DP1 or transcription factor DP2, and they have N-terminal DNA binding and dimerization domains. E2F transcription factors can act as mediators of transcriptional repression or transcriptional activation.
A group of enzymes that catalyzes the phosphorylation of serine or threonine residues in proteins, with ATP or other nucleotides as phosphate donors.
Proteins which bind to DNA. The family includes proteins which bind to both double- and single-stranded DNA and also includes specific DNA binding proteins in serum which can be used as markers for malignant diseases.
Product of the retinoblastoma tumor suppressor gene. It is a nuclear phosphoprotein hypothesized to normally act as an inhibitor of cell proliferation. Rb protein is absent in retinoblastoma cell lines. It also has been shown to form complexes with the adenovirus E1A protein, the SV40 T antigen, and the human papilloma virus E7 protein.
Proteins found in the nucleus of a cell. Do not confuse with NUCLEOPROTEINS which are proteins conjugated with nucleic acids, that are not necessarily present in the nucleus.
An antiviral antibiotic produced by Cephalosporium aphidicola and other fungi. It inhibits the growth of eukaryotic cells and certain animal viruses by selectively inhibiting the cellular replication of DNA polymerase II or the viral-induced DNA polymerases. The drug may be useful for controlling excessive cell proliferation in patients with cancer, psoriasis or other dermatitis with little or no adverse effect upon non-multiplying cells.
A deoxyribonucleotide polymer that is the primary genetic material of all cells. Eukaryotic and prokaryotic organisms normally contain DNA in a double-stranded state, yet several important biological processes transiently involve single-stranded regions. DNA, which consists of a polysugar-phosphate backbone possessing projections of purines (adenine and guanine) and pyrimidines (thymine and cytosine), forms a double helix that is held together by hydrogen bonds between these purines and pyrimidines (adenine to thymine and guanine to cytosine).
Injuries to DNA that introduce deviations from its normal, intact structure and which may, if left unrepaired, result in a MUTATION or a block of DNA REPLICATION. These deviations may be caused by physical or chemical agents and occur by natural or unnatural, introduced circumstances. They include the introduction of illegitimate bases during replication or by deamination or other modification of bases; the loss of a base from the DNA backbone leaving an abasic site; single-strand breaks; double strand breaks; and intrastrand (PYRIMIDINE DIMERS) or interstrand crosslinking. Damage can often be repaired (DNA REPAIR). If the damage is extensive, it can induce APOPTOSIS.
An E2F transcription factor that interacts directly with RETINOBLASTOMA PROTEIN and CYCLIN A and activates GENETIC TRANSCRIPTION required for CELL CYCLE entry and DNA synthesis. E2F1 is involved in DNA REPAIR and APOPTOSIS.
A nucleoside that substitutes for thymidine in DNA and thus acts as an antimetabolite. It causes breaks in chromosomes and has been proposed as an antiviral and antineoplastic agent. It has been given orphan drug status for use in the treatment of primary brain tumors.
A quiescent state of cells during G1 PHASE.
Phosphoprotein with protein kinase activity that functions in the G2/M phase transition of the CELL CYCLE. It is the catalytic subunit of the MATURATION-PROMOTING FACTOR and complexes with both CYCLIN A and CYCLIN B in mammalian cells. The maximal activity of cyclin-dependent kinase 1 is achieved when it is fully dephosphorylated.
Nuclear antigen with a role in DNA synthesis, DNA repair, and cell cycle progression. PCNA is required for the coordinated synthesis of both leading and lagging strands at the replication fork during DNA replication. PCNA expression correlates with the proliferation activity of several malignant and non-malignant cell types.
Established cell cultures that have the potential to propagate indefinitely.
Within a eukaryotic cell, a membrane-limited body which contains chromosomes and one or more nucleoli (CELL NUCLEOLUS). The nuclear membrane consists of a double unit-type membrane which is perforated by a number of pores; the outermost membrane is continuous with the ENDOPLASMIC RETICULUM. A cell may contain more than one nucleus. (From Singleton & Sainsbury, Dictionary of Microbiology and Molecular Biology, 2d ed)
The first continuously cultured human malignant CELL LINE, derived from the cervical carcinoma of Henrietta Lacks. These cells are used for VIRUS CULTIVATION and antitumor drug screening assays.
Proteins obtained from the species SACCHAROMYCES CEREVISIAE. The function of specific proteins from this organism are the subject of intense scientific interest and have been used to derive basic understanding of the functioning similar proteins in higher eukaryotes.
A transcription factor that possesses DNA-binding and E2F-binding domains but lacks a transcriptional activation domain. It is a binding partner for E2F TRANSCRIPTION FACTORS and enhances the DNA binding and transactivation function of the DP-E2F complex.
A ubiquitously expressed regulatory protein that contains a retinoblastoma protein binding domain and an AT-rich interactive domain. The protein may play a role in recruiting HISTONE DEACETYLASES to the site of RETINOBLASTOMA PROTEIN-containing transcriptional repressor complexes.
A cyclin subtype that is transported into the CELL NUCLEUS at the end of the G2 PHASE. It stimulates the G2/M phase transition by activating CDC2 PROTEIN KINASE.
A cyclin-dependent kinase inhibitor that coordinates the activation of CYCLIN and CYCLIN-DEPENDENT KINASES during the CELL CYCLE. It interacts with active CYCLIN D complexed to CYCLIN-DEPENDENT KINASE 4 in proliferating cells, while in arrested cells it binds and inhibits CYCLIN E complexed to CYCLIN-DEPENDENT KINASE 2.
The material of CHROMOSOMES. It is a complex of DNA; HISTONES; and nonhistone proteins (CHROMOSOMAL PROTEINS, NON-HISTONE) found within the nucleus of a cell.
Technique using an instrument system for making, processing, and displaying one or more measurements on individual cells obtained from a cell suspension. Cells are usually stained with one or more fluorescent dyes specific to cell components of interest, e.g., DNA, and fluorescence of each cell is measured as it rapidly transverses the excitation beam (laser or mercury arc lamp). Fluorescence provides a quantitative measure of various biochemical and biophysical properties of the cell, as well as a basis for cell sorting. Other measurable optical parameters include light absorption and light scattering, the latter being applicable to the measurement of cell size, shape, density, granularity, and stain uptake.
The introduction of a phosphoryl group into a compound through the formation of an ester bond between the compound and a phosphorus moiety.
Enzyme activated in response to DNA DAMAGE involved in cell cycle arrest. The gene is located on the long (q) arm of chromosome 22 at position 12.1. In humans it is encoded by the CHEK2 gene.
A genus of ascomycetous fungi of the family Schizosaccharomycetaceae, order Schizosaccharomycetales.
Small chromosomal proteins (approx 12-20 kD) possessing an open, unfolded structure and attached to the DNA in cell nuclei by ionic linkages. Classification into the various types (designated histone I, histone II, etc.) is based on the relative amounts of arginine and lysine in each.
A species of the genus SACCHAROMYCES, family Saccharomycetaceae, order Saccharomycetales, known as "baker's" or "brewer's" yeast. The dried form is used as a dietary supplement.
Proteins obtained from the species Schizosaccharomyces pombe. The function of specific proteins from this organism are the subject of intense scientific interest and have been used to derive basic understanding of the functioning similar proteins in higher eukaryotes.
Genes that code for proteins that regulate the CELL DIVISION CYCLE. These genes form a regulatory network that culminates in the onset of MITOSIS by activating the p34cdc2 protein (PROTEIN P34CDC2).
Nucleoproteins, which in contrast to HISTONES, are acid insoluble. They are involved in chromosomal functions; e.g. they bind selectively to DNA, stimulate transcription resulting in tissue-specific RNA synthesis and undergo specific changes in response to various hormones or phytomitogens.
Protein encoded by the bcl-1 gene which plays a critical role in regulating the cell cycle. Overexpression of cyclin D1 is the result of bcl-1 rearrangement, a t(11;14) translocation, and is implicated in various neoplasms.
Compounds that inhibit cell production of DNA or RNA.
A cyclin-dependent kinase inhibitor that mediates TUMOR SUPPRESSOR PROTEIN P53-dependent CELL CYCLE arrest. p21 interacts with a range of CYCLIN-DEPENDENT KINASES and associates with PROLIFERATING CELL NUCLEAR ANTIGEN and CASPASE 3.
A group of cell cycle proteins that negatively regulate the activity of CYCLIN/CYCLIN-DEPENDENT KINASE complexes. They inhibit CELL CYCLE progression and help control CELL PROLIFERATION following GENOTOXIC STRESS as well as during CELL DIFFERENTIATION.
Proteins that are normally involved in holding cellular growth in check. Deficiencies or abnormalities in these proteins may lead to unregulated cell growth and tumor development.
Geminin inhibits DNA replication by preventing the incorporation of MCM complex into pre-replication complex. It is absent during G1 phase of the CELL CYCLE and accumulates through S, G2,and M phases. It is degraded at the metaphase-anaphase transition by the ANAPHASE-PROMOTING COMPLEX-CYCLOSOME.
A family of enzymes that catalyze the conversion of ATP and a protein to ADP and a phosphoprotein.
Connective tissue cells which secrete an extracellular matrix rich in collagen and other macromolecules.
Any detectable and heritable change in the genetic material that causes a change in the GENOTYPE and which is transmitted to daughter cells and to succeeding generations.
All of the processes involved in increasing CELL NUMBER including CELL DIVISION.
3-Hydroxy-4-oxo-1(4H)-pyridinealanine. An antineoplastic alanine-substituted pyridine derivative isolated from Leucena glauca.
Descriptions of specific amino acid, carbohydrate, or nucleotide sequences which have appeared in the published literature and/or are deposited in and maintained by databanks such as GENBANK, European Molecular Biology Laboratory (EMBL), National Biomedical Research Foundation (NBRF), or other sequence repositories.
Deoxyribonucleic acid that makes up the genetic material of fungi.
A family of structurally-related proteins that were originally identified by their ability to complex with cyclin proteins (CYCLINS). They share a common domain that binds specifically to F-BOX MOTIFS. They take part in SKP CULLIN F-BOX PROTEIN LIGASES, where they can bind to a variety of F-BOX PROTEINS.
Cyclin-dependent kinase 4 is a key regulator of G1 PHASE of the CELL CYCLE. It partners with CYCLIN D to phosphorylate RETINOBLASTOMA PROTEIN. CDK4 activity is inhibited by CYCLIN-DEPENDENT KINASE INHIBITOR P16.
The origin recognition complex is a multi-subunit DNA-binding protein that initiates DNA REPLICATION in eukaryotes.
Proteins found in any species of fungus.
A subclass of dual specificity phosphatases that play a role in the progression of the CELL CYCLE. They dephosphorylate and activate CYCLIN-DEPENDENT KINASES.
Cells propagated in vitro in special media conducive to their growth. Cultured cells are used to study developmental, morphologic, metabolic, physiologic, and genetic processes, among others.
A minichromosome maintenance protein that is a key component of the six member MCM protein complex. It is also found in tightly-bound trimeric complex with MINICHROMOSOME MAINTENANCE COMPLEX COMPONENT 6 and MINICHROMOSOME MAINTENANCE COMPLEX COMPONENT 7.
Endogenous substances, usually proteins, which are effective in the initiation, stimulation, or termination of the genetic transcription process.
A minichromosome maintenance protein that is a key component of the six member MCM protein complex. It is also found in tightly-bound trimeric complex with MINICHROMOSOME MAINTENANCE COMPLEX COMPONENT 4 and MINICHROMOSOME MAINTENANCE COMPLEX COMPONENT 6.
The temporal order in which the DNA of the GENOME is replicated.
Elements of limited time intervals, contributing to particular results or situations.
A cell line derived from cultured tumor cells.
A group of PROTEIN-SERINE-THREONINE KINASES which activate critical signaling cascades in double strand breaks, APOPTOSIS, and GENOTOXIC STRESS such as ionizing ultraviolet A light, thereby acting as a DNA damage sensor. These proteins play a role in a wide range of signaling mechanisms in cell cycle control.
Either of the two longitudinally adjacent threads formed when a eukaryotic chromosome replicates prior to mitosis. The chromatids are held together at the centromere. Sister chromatids are derived from the same chromosome. (Singleton & Sainsbury, Dictionary of Microbiology and Molecular Biology, 2d ed)
Cells grown in vitro from neoplastic tissue. If they can be established as a TUMOR CELL LINE, they can be propagated in cell culture indefinitely.
One of the mechanisms by which CELL DEATH occurs (compare with NECROSIS and AUTOPHAGOCYTOSIS). Apoptosis is the mechanism responsible for the physiological deletion of cells and appears to be intrinsically programmed. It is characterized by distinctive morphologic changes in the nucleus and cytoplasm, chromatin cleavage at regularly spaced sites, and the endonucleolytic cleavage of genomic DNA; (DNA FRAGMENTATION); at internucleosomal sites. This mode of cell death serves as a balance to mitosis in regulating the size of animal tissues and in mediating pathologic processes associated with tumor growth.
The biosynthesis of RNA carried out on a template of DNA. The biosynthesis of DNA from an RNA template is called REVERSE TRANSCRIPTION.
The sequence of PURINES and PYRIMIDINES in nucleic acids and polynucleotides. It is also called nucleotide sequence.
The reconstruction of a continuous two-stranded DNA molecule without mismatch from a molecule which contained damaged regions. The major repair mechanisms are excision repair, in which defective regions in one strand are excised and resynthesized using the complementary base pairing information in the intact strand; photoreactivation repair, in which the lethal and mutagenic effects of ultraviolet light are eliminated; and post-replication repair, in which the primary lesions are not repaired, but the gaps in one daughter duplex are filled in by incorporation of portions of the other (undamaged) daughter duplex. Excision repair and post-replication repair are sometimes referred to as "dark repair" because they do not require light.
Cell lines whose original growing procedure consisted being transferred (T) every 3 days and plated at 300,000 cells per plate (J Cell Biol 17:299-313, 1963). Lines have been developed using several different strains of mice. Tissues are usually fibroblasts derived from mouse embryos but other types and sources have been developed as well. The 3T3 lines are valuable in vitro host systems for oncogenic virus transformation studies, since 3T3 cells possess a high sensitivity to CONTACT INHIBITION.
Nuclear phosphoprotein encoded by the p53 gene (GENES, P53) whose normal function is to control CELL PROLIFERATION and APOPTOSIS. A mutant or absent p53 protein has been found in LEUKEMIA; OSTEOSARCOMA; LUNG CANCER; and COLORECTAL CANCER.
Structures within the nucleus of fungal cells consisting of or containing DNA, which carry genetic information essential to the cell.
A minichromosome maintenance protein that is a key component of the six member MCM protein complex. It contains a NUCLEAR LOCALIZATION SIGNAL, which provide targeting of the protein complex. In addition, acetylation of this protein may play a role in regulating of DNA replication and cell cycle progression.
The process in which substances, either endogenous or exogenous, bind to proteins, peptides, enzymes, protein precursors, or allied compounds. Specific protein-binding measures are often used as assays in diagnostic assessments.
A minichromosome maintenance protein that is a key component of the six member MCM protein complex. It contains a NUCLEAR LOCALIZATION SIGNAL which may provide targeting of the protein complex and an extended N-terminus which is rich in SERINE residues.
Transport proteins that carry specific substances in the blood or across cell membranes.
RNA sequences that serve as templates for protein synthesis. Bacterial mRNAs are generally primary transcripts in that they do not require post-transcriptional processing. Eukaryotic mRNA is synthesized in the nucleus and must be exported to the cytoplasm for translation. Most eukaryotic mRNAs have a sequence of polyadenylic acid at the 3' end, referred to as the poly(A) tail. The function of this tail is not known for certain, but it may play a role in the export of mature mRNA from the nucleus as well as in helping stabilize some mRNA molecules by retarding their degradation in the cytoplasm.
An E2F transcription factor that interacts directly with RETINOBLASTOMA PROTEIN and CYCLIN A. E2F2 activates GENETIC TRANSCRIPTION required for CELL CYCLE entry and DNA synthesis.
That portion of the electromagnetic spectrum immediately below the visible range and extending into the x-ray frequencies. The longer wavelengths (near-UV or biotic or vital rays) are necessary for the endogenous synthesis of vitamin D and are also called antirachitic rays; the shorter, ionizing wavelengths (far-UV or abiotic or extravital rays) are viricidal, bactericidal, mutagenic, and carcinogenic and are used as disinfectants.
An increased tendency of the GENOME to acquire MUTATIONS when various processes involved in maintaining and replicating the genome are dysfunctional.
Regulatory signaling systems that control the progression of the CELL CYCLE through the G1 PHASE and allow transition to S PHASE when the cells are ready to undergo DNA REPLICATION. DNA DAMAGE, or the deficiencies in specific cellular components or nutrients may cause the cells to halt before progressing through G1 phase.
A broadly expressed type D cyclin. Experiments using KNOCKOUT MICE suggest a role for cyclin D3 in LYMPHOCYTE development.
A cyclin D subtype which is regulated by GATA4 TRANSCRIPTION FACTOR. Experiments using KNOCKOUT MICE suggest a role for cyclin D2 in granulosa cell proliferation and gonadal development.
The order of amino acids as they occur in a polypeptide chain. This is referred to as the primary structure of proteins. It is of fundamental importance in determining PROTEIN CONFORMATION.
A widely-expressed cyclin A subtype that functions during the G1/S and G2/M transitions of the CELL CYCLE.
The rate dynamics in chemical or physical systems.
Complexes of enzymes that catalyze the covalent attachment of UBIQUITIN to other proteins by forming a peptide bond between the C-terminal GLYCINE of UBIQUITIN and the alpha-amino groups of LYSINE residues in the protein. The complexes play an important role in mediating the selective-degradation of short-lived and abnormal proteins. The complex of enzymes can be broken down into three components that involve activation of ubiquitin (UBIQUITIN-ACTIVATING ENZYMES), conjugation of ubiquitin to the ligase complex (UBIQUITIN-CONJUGATING ENZYMES), and ligation of ubiquitin to the substrate protein (UBIQUITIN-PROTEIN LIGASES).
Regulatory signaling systems that control the progression through the CELL CYCLE. They ensure that the cell has completed, in the correct order and without mistakes, all the processes required to replicate the GENOME and CYTOPLASM, and divide them equally between two daughter cells. If cells sense they have not completed these processes or that the environment does not have the nutrients and growth hormones in place to proceed, then the cells are restrained (or "arrested") until the processes are completed and growth conditions are suitable.
The span of viability of a cell characterized by the capacity to perform certain functions such as metabolism, growth, reproduction, some form of responsiveness, and adaptability.
In a prokaryotic cell or in the nucleus of a eukaryotic cell, a structure consisting of or containing DNA which carries the genetic information essential to the cell. (From Singleton & Sainsbury, Dictionary of Microbiology and Molecular Biology, 2d ed)
Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control (induction or repression) of gene action at the level of transcription or translation.
An E3 ubiquitin ligase primarily involved in regulation of the metaphase-to-anaphase transition during MITOSIS through ubiquitination of specific CELL CYCLE PROTEINS. Enzyme activity is tightly regulated through subunits and cofactors, which modulate activation, inhibition, and substrate specificity. The anaphase-promoting complex, or APC-C, is also involved in tissue differentiation in the PLACENTA, CRYSTALLINE LENS, and SKELETAL MUSCLE, and in regulation of postmitotic NEURONAL PLASTICITY and excitability.
A cyclin subtype that is specific for CYCLIN-DEPENDENT KINASE 4 and CYCLIN-DEPENDENT KINASE 6. Unlike most cyclins, cyclin D expression is not cyclical, but rather it is expressed in response to proliferative signals. Cyclin D may therefore play a role in cellular responses to mitogenic signals.
The uptake of naked or purified DNA by CELLS, usually meaning the process as it occurs in eukaryotic cells. It is analogous to bacterial transformation (TRANSFORMATION, BACTERIAL) and both are routinely employed in GENE TRANSFER TECHNIQUES.
An alkylating agent in cancer therapy that may also act as a mutagen by interfering with and causing damage to DNA.
A family of proteins that share the F-BOX MOTIF and are involved in protein-protein interactions. They play an important role in process of protein ubiquition by associating with a variety of substrates and then associating into SCF UBIQUITIN LIGASE complexes. They are held in the ubiquitin-ligase complex via binding to SKP DOMAIN PROTEINS.
An E2F transcription factor that represses GENETIC TRANSCRIPTION required for CELL CYCLE entry and DNA synthesis. E2F4 recruits chromatin remodeling factors indirectly to target gene PROMOTER REGIONS through RETINOBLASTOMA LIKE PROTEIN P130 and RETINOBLASTOMA LIKE PROTEIN P107.
Identification of proteins or peptides that have been electrophoretically separated by blot transferring from the electrophoresis gel to strips of nitrocellulose paper, followed by labeling with antibody probes.
A cyclin B subtype that colocalizes with MICROTUBULES during INTERPHASE and is transported into the CELL NUCLEUS at the end of the G2 PHASE.
DNA present in neoplastic tissue.
A family of structurally related proteins that were originally discovered for their role in cell-cycle regulation in CAENORHABDITIS ELEGANS. They play important roles in regulation of the CELL CYCLE and as components of UBIQUITIN-PROTEIN LIGASES.
A subfamily in the family MURIDAE, comprising the hamsters. Four of the more common genera are Cricetus, CRICETULUS; MESOCRICETUS; and PHODOPUS.
The portion of chromosome material that remains condensed and is transcriptionally inactive during INTERPHASE.
Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control of gene action in fungi.
A DNA-dependent DNA polymerase characterized in E. coli and other lower organisms. It may be present in higher organisms and has an intrinsic molecular activity only 5% of that of DNA Polymerase I. This polymerase has 3'-5' exonuclease activity, is effective only on duplex DNA with gaps or single-strand ends of less than 100 nucleotides as template, and is inhibited by sulfhydryl reagents. EC
The intracellular transfer of information (biological activation/inhibition) through a signal pathway. In each signal transduction system, an activation/inhibition signal from a biologically active molecule (hormone, neurotransmitter) is mediated via the coupling of a receptor/enzyme to a second messenger system or to an ion channel. Signal transduction plays an important role in activating cellular functions, cell differentiation, and cell proliferation. Examples of signal transduction systems are the GAMMA-AMINOBUTYRIC ACID-postsynaptic receptor-calcium ion channel system, the receptor-mediated T-cell activation pathway, and the receptor-mediated activation of phospholipases. Those coupled to membrane depolarization or intracellular release of calcium include the receptor-mediated activation of cytotoxic functions in granulocytes and the synaptic potentiation of protein kinase activation. Some signal transduction pathways may be part of larger signal transduction pathways; for example, protein kinase activation is part of the platelet activation signal pathway.
An E2F transcription factor that interacts directly with RETINOBLASTOMA PROTEIN and CYCLIN A. E2F3 regulates GENETIC TRANSCRIPTION required for CELL CYCLE entry and DNA synthesis.
Recombinant proteins produced by the GENETIC TRANSLATION of fused genes formed by the combination of NUCLEIC ACID REGULATORY SEQUENCES of one or more genes with the protein coding sequences of one or more genes.
Theoretical representations that simulate the behavior or activity of biological processes or diseases. For disease models in living animals, DISEASE MODELS, ANIMAL is available. Biological models include the use of mathematical equations, computers, and other electronic equipment.
Small double-stranded, non-protein coding RNAs (21-31 nucleotides) involved in GENE SILENCING functions, especially RNA INTERFERENCE (RNAi). Endogenously, siRNAs are generated from dsRNAs (RNA, DOUBLE-STRANDED) by the same ribonuclease, Dicer, that generates miRNAs (MICRORNAS). The perfect match of the siRNAs' antisense strand to their target RNAs mediates RNAi by siRNA-guided RNA cleavage. siRNAs fall into different classes including trans-acting siRNA (tasiRNA), repeat-associated RNA (rasiRNA), small-scan RNA (scnRNA), and Piwi protein-interacting RNA (piRNA) and have different specific gene silencing functions.
A diverse class of enzymes that interact with UBIQUITIN-CONJUGATING ENZYMES and ubiquitination-specific protein substrates. Each member of this enzyme group has its own distinct specificity for a substrate and ubiquitin-conjugating enzyme. Ubiquitin-protein ligases exist as both monomeric proteins multiprotein complexes.
A family of proteins that were originally identified in SACCHAROMYCES CEREVISIAE as being essential for maintaining the structure of minichromosomes00. They form into a protein complex that has helicase activity and is involved in a variety of DNA-related functions including replication elongation, RNA transcription, chromatin remodeling, and genome stability.
Cyclin-dependent kinase 6 associates with CYCLIN D and phosphorylates RETINOBLASTOMA PROTEIN during G1 PHASE of the CELL CYCLE. It helps regulate the transition to S PHASE and its kinase activity is inhibited by CYCLIN-DEPENDENT KINASE INHIBITOR P18.
The functional hereditary units of FUNGI.
Compounds or agents that combine with an enzyme in such a manner as to prevent the normal substrate-enzyme combination and the catalytic reaction.
Nocodazole is an antineoplastic agent which exerts its effect by depolymerizing microtubules.
The phase of cell nucleus division following METAPHASE, in which the CHROMATIDS separate and migrate to opposite poles of the spindle.
A single-stranded DNA-binding protein that is found in EUKARYOTIC CELLS. It is required for DNA REPLICATION; DNA REPAIR; and GENETIC RECOMBINATION.
DNA sequences which are recognized (directly or indirectly) and bound by a DNA-dependent RNA polymerase during the initiation of transcription. Highly conserved sequences within the promoter include the Pribnow box in bacteria and the TATA BOX in eukaryotes.
A negative regulatory effect on physiological processes at the molecular, cellular, or systemic level. At the molecular level, the major regulatory sites include membrane receptors, genes (GENE EXPRESSION REGULATION), mRNAs (RNA, MESSENGER), and proteins.
The clear constricted portion of the chromosome at which the chromatids are joined and by which the chromosome is attached to the spindle during cell division.
A gene silencing phenomenon whereby specific dsRNAs (RNA, DOUBLE-STRANDED) trigger the degradation of homologous mRNA (RNA, MESSENGER). The specific dsRNAs are processed into SMALL INTERFERING RNA (siRNA) which serves as a guide for cleavage of the homologous mRNA in the RNA-INDUCED SILENCING COMPLEX. DNA METHYLATION may also be triggered during this process.
Products of proto-oncogenes. Normally they do not have oncogenic or transforming properties, but are involved in the regulation or differentiation of cell growth. They often have protein kinase activity.
Any DNA sequence capable of independent replication or a molecule that possesses a REPLICATION ORIGIN and which is therefore potentially capable of being replicated in a suitable cell. (Singleton & Sainsbury, Dictionary of Microbiology and Molecular Biology, 2d ed)
The degree of replication of the chromosome set in the karyotype.
A negative regulator of the CELL CYCLE that undergoes PHOSPHORYLATION by CYCLIN-DEPENDENT KINASES. It contains a conserved pocket region that binds E2F4 TRANSCRIPTION FACTOR and interacts with viral ONCOPROTEINS such as POLYOMAVIRUS TUMOR ANTIGENS; ADENOVIRUS E1A PROTEINS; and PAPILLOMAVIRUS E7 PROTEINS.
A continuous cell line of high contact-inhibition established from NIH Swiss mouse embryo cultures. The cells are useful for DNA transfection and transformation studies. (From ATCC [Internet]. Virginia: American Type Culture Collection; c2002 [cited 2002 Sept 26]. Available from
High molecular weight proteins found in the MICROTUBULES of the cytoskeletal system. Under certain conditions they are required for TUBULIN assembly into the microtubules and stabilize the assembled microtubules.
Cellular DNA-binding proteins encoded by the c-myc genes. They are normally involved in nucleic acid metabolism and in mediating the cellular response to growth factors. Elevated and deregulated (constitutive) expression of c-myc proteins can cause tumorigenesis.

The yeast ser/thr phosphatases sit4 and ppz1 play opposite roles in regulation of the cell cycle. (1/4298)

Yeast cells overexpressing the Ser/Thr protein phosphatase Ppz1 display a slow-growth phenotype. These cells recover slowly from alpha-factor or nutrient depletion-induced G1 arrest, showing a considerable delay in bud emergence as well as in the expression of the G1 cyclins Cln2 and Clb5. Therefore, an excess of the Ppz1 phosphatase interferes with the normal transition from G1 to S phase. The growth defect is rescued by overexpression of the HAL3/SIS2 gene, encoding a negative regulator of Ppz1. High-copy-number expression of HAL3/SIS2 has been reported to improve cell growth and to increase expression of G1 cyclins in sit4 phosphatase mutants. We show here that the described effects of HAL3/SIS2 on sit4 mutants are fully mediated by the Ppz1 phosphatase. The growth defect caused by overexpression of PPZ1 is intensified in strains with low G1 cyclin levels (such as bck2Delta or cln3Delta mutants), whereas mutation of PPZ1 rescues the synthetic lethal phenotype of sit4 cln3 mutants. These results reveal a role for Ppz1 as a regulatory component of the yeast cell cycle, reinforce the notion that Hal3/Sis2 serves as a negative modulator of the biological functions of Ppz1, and indicate that the Sit4 and Ppz1 Ser/Thr phosphatases play opposite roles in control of the G1/S transition.  (+info)

p27 is involved in N-cadherin-mediated contact inhibition of cell growth and S-phase entry. (2/4298)

In this study the direct involvement of cadherins in adhesion-mediated growth inhibition was investigated. It is shown here that overexpression of N-cadherin in CHO cells significantly suppresses their growth rate. Interaction of these cells and two additional fibroblastic lines with synthetic beads coated with N-cadherin ligands (recombinant N-cadherin ectodomain or specific antibodies) leads to growth arrest at the G1 phase of the cell cycle. The cadherin-reactive beads inhibit the entry into S phase and the reduction in the levels of cyclin-dependent kinase (cdk) inhibitors p21 and p27, following serum-stimulation of starved cells. In exponentially growing cells these beads induce G1 arrest accompanied by elevation in p27 only. We propose that cadherin-mediated signaling is involved in contact inhibition of growth by inducing cell cycle arrest at the G1 phase and elevation of p27 levels.  (+info)

Leukemia translocation protein PLZF inhibits cell growth and expression of cyclin A. (3/4298)

The PLZF gene was identified by its fusion with the RARalpha locus in a therapy resistant form of acute promyelocytic leukemia (APL) associated with the t(11;17)(q23;q21) translocation. Here we describe PLZF as a negative regulator of cell cycle progression ultimately leading to growth suppression. PLZF can bind and repress the cyclin A2 promoter while expression of cyclin A2 reverts the growth suppressed phenotype of myeloid cells expressing PLZF. In contrast RARalpha-PLZF, a fusion protein generated in t(11;17)(q23;q21)-APL activates cyclin A2 transcription and allows expression of cyclin A in anchorage-deprived NIH3T3 cells. Therefore, cyclin A2 is a candidate target gene for PLZF and inhibition of cyclin A expression may contribute to the growth suppressive properties of PLZF. Deregulation of cyclin A2 by RARalpha-PLZF may represent an oncogenic mechanism of this chimeric protein and contribute to the aggressive clinical phenotype of t(11;17)(q23;q21)-associated APL.  (+info)

Interleukin-6 dependent induction of the cyclin dependent kinase inhibitor p21WAF1/CIP1 is lost during progression of human malignant melanoma. (4/4298)

Human melanoma cell lines derived from early stage primary tumors are particularly sensitive to growth arrest induced by interleukin-6 (IL-6). This response is lost in cell lines derived from advanced lesions, a phenomenon which may contribute to tumor aggressiveness. We sought to determine whether resistance to growth inhibition by IL-6 can be explained by oncogenic alterations in cell cycle regulators or relevant components of intracellular signaling. Our results show that IL-6 treatment of early stage melanoma cell lines caused G1 arrest, which could not be explained by changes in levels of G1 cyclins (D1, E), cdks (cdk4, cdk2) or by loss of cyclin/cdk complex formation. Instead, IL-6 caused a marked induction of the cdk inhibitor p21WAF1/CIP1 in three different IL-6 sensitive cell lines, two of which also showed a marked accumulation of the cdk inhibitor p27Kip1. In contrast, IL-6 failed to induce p21WAF1/CIP1 transcript and did not increase p21WAF1/CIP1 or p27kip1 proteins in any of the resistant lines. In fact, of five IL-6 resistant cell lines, only two expressed detectable levels of p21WAF1/CIP1 mRNA and protein, while in three other lines, p21WAF1/CIP1 was undetectable. IL-6 dependent upregulation of p21WAF1/CIP1 was associated with binding of both STAT3 and STAT1 to the p21WAF1/CIP1 promoter. Surprisingly, however, IL-6 stimulated STAT binding to this promoter in both sensitive and resistant cell lines (with one exception), suggesting that gross deregulation of this event is not the unifying cause of the defect in p21WAF1/CIP1 induction in IL-6 resistant cells. In somatic cell hybrids of IL-6 sensitive and resistant cell lines, the resistant phenotype was dominant and IL-6 failed to induce p21WAF1/CIP1. Thus, our results suggest that in early stage human melanoma cells, IL-6 induced growth inhibition involves induction of p21WAF1/CIP1 which is lost in the course of tumor progression presumably as a result of a dominant oncogenic event.  (+info)

Caffeine can override the S-M checkpoint in fission yeast. (5/4298)

The replication checkpoint (or 'S-M checkpoint') control prevents progression into mitosis when DNA replication is incomplete. Caffeine has been known for some time to have the capacity to override the S-M checkpoint in animal cells. We show here that caffeine also disrupts the S-M checkpoint in the fission yeast Schizosaccharomyces pombe. By contrast, no comparable effects of caffeine on the S. pombe DNA damage checkpoint were seen. S. pombe cells arrested in early S phase and then exposed to caffeine lost viability rapidly as they attempted to enter mitosis, which was accompanied by tyrosine dephosphorylation of Cdc2. Despite this, the caffeine-induced loss of viability was not blocked in a temperature-sensitive cdc2 mutant incubated at the restrictive temperature, although catastrophic mitosis was prevented under these conditions. This suggests that, in addition to S-M checkpoint control, a caffeine-sensitive function may be important for maintenance of cell viability during S phase arrest. The lethality of a combination of caffeine with the DNA replication inhibitor hydroxyurea was suppressed by overexpression of Cds1 or Chk1, protein kinases previously implicated in S-M checkpoint control and recovery from S phase arrest. In addition, the same combination of drugs was specifically tolerated in cells overexpressing either of two novel S. pombe genes isolated in a cDNA library screen. These findings should allow further molecular investigation of the regulation of S phase arrest, and may provide a useful system with which to identify novel drugs that specifically abrogate the checkpoint control.  (+info)

Regulation of the start of DNA replication in Schizosaccharomyces pombe. (6/4298)

Cells of Schizosaccharomyces pombe were grown in minimal medium with different nitrogen sources under steady-state conditions, with doubling times ranging from 2.5 to 14 hours. Flow cytometry and fluorescence microscopy confirmed earlier findings that at rapid growth rates, the G1 phase was short and cell separation occurred at the end of S phase. For some nitrogen sources, the growth rate was greatly decreased, the G1 phase occupied 30-50% of the cell cycle, and cell separation occurred in early G1. In contrast, other nitrogen sources supported low growth rates without any significant increase in G1 duration. The method described allows manipulation of the length of G1 and the relative cell cycle position of S phase in wild-type cells. Cell mass was measured by flow cytometry as scattered light and as protein-associated fluorescence. The extensions of G1 were not related to cell mass at entry into S phase. Our data do not support the hypothesis that the cells must reach a certain fixed, critical mass before entry into S. We suggest that cell mass at the G1/S transition point is variable and determined by a set of molecular parameters. In the present experiments, these parameters were influenced by the different nitrogen sources in a way that was independent of the actual growth rate.  (+info)

Immunologic proliferation marker Ki-S2 as prognostic indicator for lymph node-negative breast cancer. (7/4298)

BACKGROUND: Proper treatment of lymph node-negative breast cancer depends on an accurate prognosis. To improve prognostic models for this disease, we evaluated whether an immunohistochemical marker for proliferating cells, Ki-S2 (a monoclonal antibody that binds to a 100-kd nuclear protein expressed in S, G2, and M phases of the cell cycle), is an accurate indicator of prognosis. METHODS: We studied 371 Swedish women with lymph node-negative breast cancer; the median follow-up time was 95 months. The fraction of tumor cells in S phase was assessed by flow cytometry, and tumor cell proliferation was measured immunohistochemically with the monoclonal antibodies Ki-S2 and Ki-S5 (directed against the nuclear antigen Ki-67). A combined prognostic index was calculated on the basis of the S-phase fraction, progesterone receptor content, and tumor size. RESULTS: In multivariate analyses that did or did not (263 and 332 observations, respectively) include the S-phase fraction and the combined prognostic index, the Ki-S2 labeling index (percentage of antibody-stained tumor cell nuclei) emerged as the most statistically significant predictor of overall survival, disease-specific survival, and disease-free survival (all two-sided P<.0001). In the risk group defined by a Ki-S2 labeling index of 10% or less, life expectancy was not statistically significantly different from that of age-matched women without breast cancer, whereas the group with a high Ki-S2 labeling index had an increased risk of mortality of up to 20-fold. CONCLUSIONS: Cellular proliferation is a major determinant of the biologic behavior of breast cancer. Prognosis is apparently best indicated by the percentage of cells in S through M phases of the cell cycle. Measurement of the Ki-S2 labeling index of a tumor sample may improve a clinician's ability to make an accurate prognosis and to identify patients with a low risk of recurrence who may not need adjuvant therapy.  (+info)

Fus3p and Kss1p control G1 arrest in Saccharomyces cerevisiae through a balance of distinct arrest and proliferative functions that operate in parallel with Far1p. (8/4298)

In Saccharomyces cerevisiae, mating pheromones activate two MAP kinases (MAPKs), Fus3p and Kss1p, to induce G1 arrest prior to mating. Fus3p is known to promote G1 arrest by activating Far1p, which inhibits three Clnp/Cdc28p kinases. To analyze the contribution of Fus3p and Kss1p to G1 arrest that is independent of Far1p, we constructed far1 CLN strains that undergo G1 arrest from increased activation of the mating MAP kinase pathway. We find that Fus3p and Kss1p both control G1 arrest through multiple functions that operate in parallel with Far1p. Fus3p and Kss1p together promote G1 arrest by repressing transcription of G1/S cyclin genes (CLN1, CLN2, CLB5) by a mechanism that blocks their activation by Cln3p/Cdc28p kinase. In addition, Fus3p and Kss1p counteract G1 arrest through overlapping and distinct functions. Fus3p and Kss1p together increase the expression of CLN3 and PCL2 genes that promote budding, and Kss1p inhibits the MAP kinase cascade. Strikingly, Fus3p promotes proliferation by a novel function that is not linked to reduced Ste12p activity or increased levels of Cln2p/Cdc28p kinase. Genetic analysis suggests that Fus3p promotes proliferation through activation of Mcm1p transcription factor that upregulates numerous genes in G1 phase. Thus, Fus3p and Kss1p control G1 arrest through a balance of arrest functions that inhibit the Cdc28p machinery and proliferative functions that bypass this inhibition.  (+info)

TY - JOUR. T1 - Suppression of replication fork progression in low-dose-specific p53-dependent S-phase DNA damage checkpoint. AU - Shimura, T.. AU - Toyoshima, M.. AU - Adiga, S. K.. AU - Kunoh, T.. AU - Nagai, H.. AU - Shimizu, N.. AU - Inoue, M.. AU - Niwa, O.. PY - 2006/9/28. Y1 - 2006/9/28. N2 - The S-phase DNA damage checkpoint is activated by DNA damage to delay DNA synthesis allowing time to resolve the replication block. We previously discovered the p53-dependent S-phase DNA damage checkpoint in mouse zygotes fertilized with irradiated sperm. Here, we report that the same p53 dependency holds in mouse embryonic fibroblasts (MEFs) at low doses of irradiation. DNA synthesis in p53 wild-type (WT) MEFs was suppressed in a biphasic manner in which a sharp decrease below 2.5 Gy was followed by a more moderate decrease up to 10 Gy. In contrast, p53-/- MEFs exhibited radioresistant DNA synthesis below 2.5 Gy whereas the cells retained the moderate suppression above 5 Gy. DNA fiber analysis ...
The Mre11-Rad50-Nbs1 (MRN) complex has many biological functions: processing of double-strand breaks in meiosis, homologous recombination, telomere maintenance, S-phase checkpoint, and genome stability during replication. In the S-phase DNA damage checkpoint, MRN acts both in activation of checkpoint signaling and downstream of the checkpoint kinases to slow DNA replication. Mechanistically, MRN, along with its cofactor Ctp1, is involved in 5 resection to create single-stranded DNA that is required for both signaling and homologous recombination. However, it is unclear whether resection is essential for all of the cellular functions of MRN. To dissect the various roles of MRN, we performed a structure-function analysis of nuclease dead alleles and potential separation-of-function alleles analogous to those found in the human disease ataxia telangiectasia-like disorder, which is caused by mutations in Mre11. We find that several alleles of rad32 (the fission yeast homologue of mre11), along with
Cells were treated with either UVA or TMP/UVA. a Sequential IP demonstrates association of early-replicating Alu sequences with DONSON and late-replicating Satellite 3 sequences with FANCM. LINE-1 elements replicate throughout the S phase and are found in all fractions. Representative blot (n = 3). b DONSON interaction with the H3K4me3 euchromatin mark is more frequent in early S phase cells than in late S phase, while there is little interaction with the H3K9me3 heterochromatin mark in either stage. Sorted early and late S phase cells were examined by PLA. Scored nuclei: PLA between GFP-D: H3K4me3 of early S phase = 67, late S phase = 64, PLA between GFP-D: H3K9me3 of early S phase = 70, late S phase = 85, from three biological replicates. Data are mean ± s.e.m. c FANCM interaction with H3K9me3 heterochromatin mark is biased toward late S phase, while there is low interaction frequency with H3K4me3 in either stage. Scored nuclei: PLA between FANCM: H3K4me3 of early S phase = 64, late S phase = ...
CDC25A plays a role in the unperturbed cell cycle (Ben-Yehoyada et al., 2007); to address the concern that the CDC25A siRNA was slowing down replication, which would affect the result, we pulsed cells with BrdU after 48 h of CDC25A siRNA transfection and chased the cells for 8 h. Flow cytometric analysis revealed that the progression through S phase at these time points was largely unaffected by the lower cellular concentration of CDC25A (Fig. S3 E). Thus, repression of DNA damage after CDC25A depletion is not caused by markedly slowed progression through S phase or G1-phase arrest.. Finally, we asked whether CDC25A accumulation could be an important determinant of the proliferative capability of cells depleted for CHK1 because coknockdown of CDC25A with CHK1 abolished the majority of DNA damage. Importantly, TIG-3-tert cells depleted for CHK1 proliferated very poorly, whereas this phenotype was partly rescued by codepletion of CDC25A. In fact, cells depleted for both CDC25A and CHK1 ...
BioAssay record AID 609847 submitted by ChEMBL: Cell cycle arrest in human HeLaS3 cells assessed as accumulation at S phase at 150 uM after 48 hrs using propidium iodide staining by flow cytometry (Rvb = 19.62%).
PR-Set7/SET8 is a histone H4-lysine 20 methyltransferase required for normal cell proliferation. However, the exact functions of this enzyme remain to be determined. In this study, we show that human PR-Set7 functions during S phase to regulate cellular proliferation. PR-Set7 associates with replication foci and maintains the bulk of H4-K20 mono- and trimethylation. Consistent with a function in chromosome dynamics during S phase, inhibition of PR-Set7 methyltransferase activity by small hairpin RNA causes a replicative stress characterized by alterations in replication fork velocity and origin firing. This stress is accompanied by massive induction of DNA strand breaks followed by a robust DNA damage response. The DNA damage response includes the activation of ataxia telangiectasia mutated and ataxia telangiectasia related kinase-mediated pathways, which, in turn, leads to p53-mediated growth arrest to avoid aberrant chromosome behavior after improper DNA replication. Collectively, these data ...
To achieve faithful replication of the genome once in each cell cycle, reinitiation of S phase is prevented in G(2) and origins are restricted from refiring within S phase. We have investigated the block to rereplication during G(2) in fission yeast. The DNA synthesis that occurs when G(2)/M cyclin-dependent kinase (CDK) activity is depleted has been assumed to be repeated rounds of S phase without mitosis, but this has not been demonstrated to be the case. We show here that on G(2)/M CDK depletion in G(2), repeated S phases are induced, which are correlated with normal G(1)/S transcription and attainment of doublings in cell size. Mostly normal mitotic S-phase origins are utilized, although at different efficiencies, and replication is essentially equal across the genome. We conclude that CDK inhibits reinitiation of S phase during G(2), and if G(2)/M CDK is depleted, replication results from induction of a largely normal S-phase program with only small differences in origin usage and efficiency ...
In Saccharomyces cerevisiae, a single cyclin-dependent kinase, Cdc28, regulates both G1/S and G2/M phase transitions by associating with stage-specific cyclins. During progression through S phase and G2/M, Cdc28 is activated by the B-type cyclins Clb1-6. Because of functional redundancy, specific roles for individual Clbs have been difficult to assign. To help genetically define such roles, strains carrying a cdc28(ts) allele, combined with single CLB deletions were studied. It is assumed that by limiting the activity of the kinase, these strains would be rendered more sensitive to loss of individual Clbs. By this approach, a novel phenotype associated with CLB5 mutation was observed. Homozygous cdc28-4(ts) clb5 diploids are not viable at room temperature. Cells are defective in spindle positioning, leading to migration of undivided nuclei into the bud. Occasionally, misplaced spindles are observed in cdc28-4 clb5 haploids; additional deletion of CLB6 causes full penetrance. Thus, CLB5 brings ...
numerous post-translational modifications lead to stabil- In contrast to the key role of p53 in maintenance of the isation of the p53 protein and activation of its DNA-induced G1 arrest, no specific roles for p53 or p21 sequence-specific DNA binding [9,30]. Only then can p53 have been implicated in the control of the intra-S-phase efficiently stimulate transcription of cell-cycle inhibitors checkpoint. This is perhaps not so surprising as the such as p21 (Figure 2). Furthermore, the p21 protein has to S-phase checkpoint, manifested by a decreased rate of accumulate to levels sufficiently high to inhibit the CDK- DNA synthesis after generation of DSBs, is by definition a containing complexes, before cell-cycle progression transient phenomenon [5]. The absence of the mainte- becomes efficiently blocked. Although p53 has recently nance component during S phase, contrary to the G1 and been described binding to 5′ untranslated region of CDK4 G2 checkpoints, might be beneficial for the cells by ...
ABSTRACTAims:Breast cancer is the major diagnosed cancer and the leading reason of cancer related death among women, and the tumor size is one of the risk factors. Therefore, it is significant to reveal the principle of breaking the subtle homeostasis of cell cycle and sustaining chronic proliferati
Duplication of a cells genetic material is of paramount importance. This task must be completed accurately, efficiently and occur once and only once within any given cell cycle. Origin firing, which occurs according to a temporal program, results in the establishment of bidirectional replication forks. As replication forks traverse the chromosomal landscape, their stability is threatened by endogenous obstacles such as heavily transcribed tRNAs, protein-DNA complexes and replication slow zones. In addition, fork stability can also be threatened by genotoxic agents. During S phase, in response to genotoxin-induced stress, the cell activates the intra-S phase checkpoint. The intra-S phase checkpoint is comprised of three major groups of proteins: sensors, adaptors and effectors. Sensor proteins detect problems at the replication fork and elicit a phosphorylation cascade that is mediated by adaptor proteins and results in the activation of effector kinases. Together, these proteins act to ...
Faithful duplication and segregation of undamaged DNA is critical to the survival of all organisms and prevention of oncogenesis in multicellular organisms. To ensure inheritance of intact DNA, cells rely on checkpoints. Checkpoints alter cellular processes in the presence of DNA damage preventing cell cycle transitions until replication is completed or DNA damage is repaired. Several checkpoints are specific to S-phase. The S-M replication checkpoint prevents mitosis in the presence of unreplicated DNA. Rather than outright halting replication, the S-phase DNA damage checkpoint slows replication in response to DNA damage. This checkpoint utilizes two general mechanisms to slow replication. First, this checkpoint prevents origin firing thus limiting the number of replication forks traversing the genome in the presence of damaged DNA. Second, this checkpoint slows the progression of the replication forks. Inhibition of origin firing in response to DNA damage is well established, however when this thesis
To maintain genome stability, DNA replication occurs only once in each cell cycle. This is achieved by the cell cycle-dependent licensing control that permits assembly of prereplication complexes (pre-RCs) at replication origins only once per cell cycle (Mendez and Stillman, 2003; Diffley, 2004; Nishitani and Lygerou, 2004; Blow and Dutta, 2005; Arias and Walter, 2007). On exit from metaphase, the minichromosome maintenance (MCM) 2-7 complex is recruited to replication origins to establish pre-RCs. Once replication is activated by the Cdks and Cdc7/Dbf4 kinase, pre-RCs are disassembled and the reassociation of MCM proteins with origins is not permitted until the completion of mitosis.. Regulation of Cdt1 activity during the cell cycle is critical for the prevention of reassembly of pre-RCs within a single cell cycle (Blow and Dutta, 2005; Arias and Walter, 2007). When cells enter S phase, Cdt1 is ubiquitinated and degraded (Nishitani et al., 2001; Li et al., 2003; Zhong et al., 2003; Arias and ...
Mechanisms for the initiation signal that delays the MI division.We address three possible mechanisms for the earlier start of the MI division in initiation mutants. The first hypothesis is that WT cells have a longer S phase because of the presence of recombination initiation proteins and that this results in a normal delay of the MI division. Cha et al. (4) showed that premeiotic S phase is shorter in spo11 mutants than in WT cells (4). This is consistent with the view that the shorter S phase results in the earlier timing of the MI division observed in spo11 mutants. The same authors, however, also showed that rec102 mutants had normal timing of premeiotic S phase (4). This is something of a paradox, since rec102 mutants clearly begin the MI division earlier than WT cells. We observe no significant differences in the timing of S phase (measured in three different ways) between WT cells and rec102, rec104, rec114, and spo11 mutants (Table 1). We note that the exact time at which 50% of cells ...
In the absence of Rif1, this mid‐S‐phase architecture is not formed, allowing Cdc7 kinase to gain access in early‐S‐phase to the origins that would normally not be activated until mid‐S‐phase. This would explain the increased Cdc7‐dependent phosphorylation of the target proteins and hyper‐loading of Cdc45 and PCNA onto chromatin in Rif1‐depleted cells at early‐S‐phase (Figure 1). As a result of loss of mid‐S replication domains, replication timing domain structures may undergo genome‐wide alteration. It should be noted that replication timing is generally more centred to mid‐S in the absence of Rif1, although mid‐S replication foci pattern is lost and all the replication foci appear to adopt the early‐S‐like pattern (Supplementary Figure S9). This effect of Rif1 on replication timing is similar to what we observed in fission yeast rif1Δ mutant, where some early‐firing origins are delayed and late‐firing/dormant origins are fired earlier (Hayano et al, ...
Clinical experience has shown that mammary carcinomas can be classified according to their type of progression into slow-growing and fast-growing ones, where the terms
A stochastic model for interpreting BrdUrd DNA FCM-derived data is proposed. The model is based on branching processes and describes the progression of the DNA distribution of BrdUrd-labelled cells through the cell cycle. With the main focus on estimating the S phase duration and its variation, the DNA replication rate is modelled by a piecewise linear function, while assuming a gamma distribution for the S phase duration. Estimation of model parameters was carried out using maximum likelihood for data from two different cell lines. The results provided quite a good fit to the data, suggesting that stochastic models may be a valuable tool for analysing this kind of data.
Single-stranded DNA origin-binding and annealing protein; required for the initiation of DNA replication; phosphorylated in S phase by cyclin-dependent kinases (Cdks), promoting origin binding, DNA replication and Dpb11p complex formation; component of the preloading complex; unphosphorylated or CDK-phosphorylated Sld2p binds to the MCM2-7 complex;required for the S phase checkpoint; relative distribution to the nucleus increases upon DNA replication stress ...
Cyclin-dependent Kinase Inhibitor (CKI); Inhibitor Of Cdc28-Clb Kinase Complexes That Controls G1/S Phase Transition, Preventing Premature S Phase And Ensuring Genomic Integrity; Phosphorylated By Clb5/6-Cdk1 And Cln1/2-Cdk1 Kinase Which Regulate Timing Of Sic1p Degradation; Phosphorylation Targets Sic1p For SCF(CDC4)-dependent Turnover; Functional Homolog Of Mammalian Kip1
The precise replication of the genome and the continuous surveillance of its integrity are essential for survival and the avoidance of various diseases. Cells respond to DNA damage by activating a complex network of the so-called checkpoint pathways to delay their cell-cycle progression and repair t …
In this study we show that CPS and nordihydrocapsiate (CPT) inhibit early and late events in T cell activation, including CD69, CD25 and ICAM-1 cell surface expression, progression to the S phase of the cell cycle and proliferation in response to TCR and CD28 co-engagement ...
Eucerin Dermatoclean Refreshing Cleansing Gel is a gentle cleansing gel that cleanses the skin and removes make-up, especially suitable for cleaning normal s...
TY - JOUR. T1 - p107 inhibits G1 to S phase progression by down-regulating expression of the F-box protein Skp2. AU - Rodier, Geneviève. AU - Makris, Constantin. AU - Coulombe, Philippe. AU - Scime, Anthony. AU - Nakayama, Keiko. AU - Nakayama, Keiichi I.. AU - Meloche, Sylvain. PY - 2005/1/3. Y1 - 2005/1/3. N2 - Cell cycle progression is negatively regulated by the pocket proteins pRb, p107, and p130. However, the mechanisms responsible for this inhibition are not fully understood. Here, we show that overexpression of p107 in fibroblasts inhibits Cdk2 activation and delays S phase entry. The inhibition of Cdk2 activity is correlated with the accumulation of p27, consequent to a decreased degradation of the protein, with no change of Thr187 phosphorylation. Instead, we observed a marked decrease in the abundance of the F-box receptor Skp2 in p107-overexpressing cells. Reciprocally, Skp2 accumulates to higher levels in p107-/- embryonic fibroblasts. Ectopic expression of Skp2 restores p27 ...
Cells divide with remarkable fidelity, allowing complex organisms to develop and possess longevity. Checkpoint controls contribute by ensuring that genome duplication and segregation occur without error so that genomic instability, associated with developmental abnormalities and a hallmark of most human cancers, is avoided. S-phase checkpoints prevent cell division while DNA is replicating. Budding yeast Mec1p and Rad53p, homologues of human checkpoint kinases ATM/ATR and Chk2, are needed for this control system. How Mec1p and Rad53p prevent mitosis in S phase is not known. Here we provide evidence that budding yeasts avoid mitosis during S phase by regulating the anaphase-promoting complex (APC) specificity factor Cdc20p: Mec1p and Rad53p repress the accumulation of Cdc20p in S phase. Because precocious Cdc20p accumulation causes anaphase onset and aneuploidy, Cdc20p concentrations must be precisely regulated during each and every cell cycle. Catastrophic mitosis induced by Cdc20p in S phase ...
1. Kotsantis P, Petermann E, Boulton SJ. Mechanisms of Oncogene-Induced Replication Stress: Jigsaw Falling into Place. Cancer Discov. 2018;8(5):537-55. doi: 10.1158/2159-8290.CD-17-1461 29653955. 2. Gaillard H, García-Muse T, Aguilera A. Replication stress and cancer. Nat Rev Cancer. 2015;15(5):276-89. doi: 10.1038/nrc3916 25907220. 3. Heller R, C., Kang S, Lam W, M., Chen S, Chan C, S., Bell S, P. Eukaryotic origin-dependent DNA replication in vitro reveals sequential action of DDK and S-CDK kinases. Cell. 2011;146(1):80-91. doi: 10.1016/j.cell.2011.06.012 21729781. 4. Sheu YJ, Stillman B. Cdc7-Dbf4 phosphorylates MCM proteins via a docking site-mediated mechanism to promote S phase progression. Mol Cell. 2006;24(1):101-13. doi: 10.1016/j.molcel.2006.07.033 17018296. 5. Tanaka S, Nakato R, Katou Y, Shirahige K, Araki H. Origin association of Sld3, Sld7, and Cdc45 proteins is a key step for determination of origin-firing timing. Curr Biol. 2011;21(24):2055-63. doi: 10.1016/j.cub.2011.11.038 ...
Molecular cloning and characterisation of a human nuclear protein designated BM28 is reported. On the amino acid level this 892 amino acid protein, migrating on SDS-gels as a 125 kDa polypeptide, shares areas of significant similarity with a recently defined family of early S phase proteins. The members of this family, the Saccharomyces cerevisiae Mcm2p, Mcm3p, Cdc46p/Mcm5p, the Schizosaccharomyces pombe Cdc21p and the mouse protein P1 are considered to be involved in the onset of DNA replication. The highest similarity was found with Mcm2p (42% identity over the whole length and higher than 75% over a conservative region of 215 amino acid residues), suggesting that BM28 could represent the human homologue of the S. cerevisiae MCM2. Using antibodies raised against the recombinant BM28 the corresponding antigen was found to be localised in the nuclei of various mammalian cells. Microinjection of anti-BM28 antibody into synchronised mouse NIH3T3 or human HeLa cells presents evidence for the ...
TY - JOUR. T1 - SU9516, a cyclin-dependent kinase 2 inhibitor, promotes accumulation of high molecular weight E2F complexes in human colon carcinoma cells. AU - Yu, Bo. AU - Lane, Maureen E.. AU - Wadler, Scott. PY - 2002/10/1. Y1 - 2002/10/1. N2 - The E2F family plays a critical role in the expression of genes required for entry into and progression through S phase. E2F-mediated transcription is repressed by the tumor suppressor retinoblastoma protein (pRb), which results in sequestration of E2F in a multiprotein complex that includes pRb. Derepression of E2F results from a series of complex phosphorylation events mediated by cyclin D/cdk4 and cyclin E/cdk2. We have employed a novel 3-substituted indolinone compound, 3-[1-(3H-imidazol-4-yl)-meth-(Z)-ylidene]-5-methoxy-1,3-dihydro-indol-2-one (SU9516), which selectively inhibits cdk2 activity (Lane et al., Cancer Res 2001;61:6170-7) to investigate these events. Electrophoretic mobility gel shift assays were performed on SU9516-treated and ...
Progression through S phase of the eukaryotic cell cycle is regulated by the action of the cyclin dependent protein kinase 2 (CDK2) in association with cyclin A. CDK2/cyclin A phosphorylates numerous substrates. Substrate specificity often employs a dual recognition strategy in which the sequence flanking the phospho-acceptor site (Ser.Pro.X.Arg/Lys) is recognized by CDK2, while the cyclin A component of the complex contains a hydrophobic site that binds Arg/Lys.X.Leu (RXL or KXL) substrate recruitment motifs. To determine additional sequence specificity motifs around the RXL sequence, we have performed X-ray crystallographic studies at 2.3 A resolution and isothermal calorimetry measurements on complexes of phospho-CDK2/cyclin A with a recruitment peptide derived from E2F1 and with shorter 11-mer peptides from p53, pRb, p27, E2F1, and p107. The results show that the cyclin recruitment site accommodates a second hydrophobic residue either immediately C-terminal or next adjacent to the ...
Progression through S phase of the eukaryotic cell cycle is regulated by the action of the cyclin dependent protein kinase 2 (CDK2) in association with cyclin A. CDK2/cyclin A phosphorylates numerous substrates. Substrate specificity often employs a dual recognition strategy in which the sequence flanking the phospho-acceptor site (Ser.Pro.X.Arg/Lys) is recognized by CDK2, while the cyclin A component of the complex contains a hydrophobic site that binds Arg/Lys.X.Leu (RXL or KXL) substrate recruitment motifs. To determine additional sequence specificity motifs around the RXL sequence, we have performed X-ray crystallographic studies at 2.3 A resolution and isothermal calorimetry measurements on complexes of phospho-CDK2/cyclin A with a recruitment peptide derived from E2F1 and with shorter 11-mer peptides from p53, pRb, p27, E2F1, and p107. The results show that the cyclin recruitment site accommodates a second hydrophobic residue either immediately C-terminal or next adjacent to the ...
Muktadir S. Hossain completed his Ph.D. at the University of Tokyo, Japan in 2004 where he showed that quiescent (G0) phase cells of multicellular eukaryotes like mammals and insects require DNA topoisomeras II enzyme for the re-entry into the cell cycle, whereas the unicellular eukaryotes like yeast do not. The title of his Ph.D. dissertation is Requirement for DNA topoisomerase II during the G0-to-S phase transition in mammalian and insect cells. In the University of Tokyo as a Ph.D. student, he participated in the isolation of temperature-sensitive mutants of the pathogenic bacterium, Staphylococcus aureus. In the University of Tokyo as a Ph.D. student, he also showed that the DNA double-strand break-inducing drugs that are used to treat cancner can induce myogenic differentiation in cultured cells of the fruit fly, Drosophila melanogaster. In the University of Tokyo as a Research Assistant, he established the larvae of the silk moth, Bombyx mori as animal model to study purified toxins ...
Traversing the cell-division cycle may require more than a single exposure to growth factor. Jones and Kazlauskas suggest that the G0 to S interval may be divided into two phases, each requiring stimulation of distinct signaling events by growth factor. Serum-arrested fibroblast cells could be driven into S phase either by continuous long exposure to platelet-derived growth factor (PDGF) or by two shorter pulses of PDGF at distinct times. The first segment of the G1 phase required activation of the Erk pathway and c-Myc; the latter part of G1 required phosphatidylinositol-3-kinase activity. An analysis of growth factors that stimulate either receptor tyrosine kinases or G protein-coupled receptors revealed that exposure to different combinations of these agents in the first and second phases of the interval could also promote progression to S phase. The authors propose that the earlier biochemical events may cause accumulation of proteins that are required by the later signaling events to ...
The p53 oncosuppressor protein is a critical mediator of the response to injury in mammalian cells and is mutationally inactivated in the majority of lung malignancies. In this analysis, the effects of p53-deficiency were investigated in short-term primary cultures of murine bronchiolar Clara cells. Clara cells, isolated from gene-targeted p53-deficient mice, were compared to cells derived from wild type littermates. p53 null cultures displayed abnormal morphology; specifically, a high incidence of multinucleation, which increased with time in culture. Multinucleated cells were proficient in S phase DNA synthesis, as determined by BrdU incorporation. However, multinucleation did not reflect altered rates of S phase synthesis, which were similar between wild type and p53-/- cultures. Nucleation defects in p53-/- Clara cells associated with increased centrosome number, as determined by confocal microscopy of pericentrin-stained cultures, and may highlight a novel role of p53 in preserving genomic
Synchronized VSMCs were obtained by the method of double-thymidine block,colchicine treatment and serum starvation . Synchronized growth was monitored by flow cytometry. All the synchronized VSMCs distribution ration were 89.22% (±3.54%) at G0 phase, (66.74±7.16%) at G1/S phase, (63.24±4.06)% at S phase and (51.64±11.18)% at G2/M phase. The expression of ORC1 mRNA and CyclinA in a quiescent stage of VSMC was not significantly found, After synchronized, peaked(50.4%) at G2/M of CyclinA, and decreased(1.03%) at G2/M of ORC1, CyclinA in preventing the ORC1 from bind during G2/Mphase. The expression of ORC1 protein and CyclinA had a same change as ORC1 mRNA and CyclinA in different cell cycles of VSMC by flow cytometry (P,0.001). ...
Fingerprint Dive into the research topics of Staphylococcus aureus gyrase-quinolone-DNA ternary complexes fail to arrest replication fork progression in vitro: Effects of salt on the DNA binding mode and the catalytic activity of S. aureus gyrase. Together they form a unique fingerprint. ...
Chromosome replication is a key event in the eukaryotic cell division cycle. During S phase the entire genome must be faithfully duplicated with the minimum of errors. The many thousands of replication forks involved in this process must be co-ordinated to ensure that despite the very large quantities of DNA involved, no section of DNA is left unreplicated and no section of DNA is replicated more than once. Cells achieve this by having a distinct stage that occurs prior to S phase when replication origins are licensed for replication. At the onset of S phase, replication forks are initiated only at these licensed replication origins. As initiation occurs at each origin, the licence is removed, thereby ensuring that it fires only once in each cell cycle. Mistakes made in this process may cause irreversible genetic modifications that could ultimately lead to the cells becoming cancerous. Many early stage cancer cells have lost the ability to correctly down-regulate the licensing system, ...
p21CDKN1A does not interfere with loading of PCNA at DNA replication sites, but inhibits subsequent binding of DNA polymerase delta at the G1/S phase transition.
The p110α and p110β catalytic subunits of phosphoinositide 3-kinase (PI3K) regulate cell cycle events. Marqués et al. found that NIH 3T3 cells overexpressing p110β, but not p110α, divided more rapidly than control cells, whereas cells expressing a catalytically inactive p110β point mutant (Lys805→Arg; K805R) divided more slowly than control cells or cells expressing a catalytically inactive p110α mutant. Specifically, S phase progression was accelerated in cells overexpressing p110β and slowed in cells expressing the K805R mutant, suggesting a role for p110β in DNA elongation. Individual DNA fibers were isolated from synchronously dividing NIH 3T3 cells treated with inhibitors specific for p110α (PIK75) or for p110β (TGX221) and subsequently incubated with bromodeoxyuridine (BrdU). In DNA fibers from TGX221-treated cells, the BrdU-labeled sections were shorter in length and closer together compared with those from PIK75-treated cells, implying that replication fork progression was ...
Plays a role in viral genome replication by driving entry of quiescent cells into the cell cycle. Stimulation of progression from G1 to S phase allows the virus to efficiently use the cellular DNA replicating machinery to achieve viral genome replication. E7 protein has both transforming and trans-activating activities. Induces the disassembly of the E2F1 transcription factor from RB1, with subsequent transcriptional activation of E2F1-regulated S-phase genes. Interferes with host histone deacetylation mediated by HDAC1 and HDAC2, leading to transcription activation. Plays also a role in the inhibition of both antiviral and antiproliferative functions of host interferon alpha. Interaction with host TMEM173/STING impairs the ability of TMEM173/STING to sense cytosolic DNA and promote the production of type I interferon (IFN-alpha and IFN-beta ...
BioAssay record AID 461873 submitted by ChEMBL: Cell cycle arrest in human HeLa cells assessed as increase in S phase accumulation at 10 uM after 24 hrs by FACS analysis.
E, CAL120 cells were either untreated or pretreated with gemcitabine for 24 hours followed by treatment with AZD7762 and /or MK-1775 for an additional 2 hours (top) or 8 hours (bottom), before lysis. Western blot analysis of Cyclin B1, CDK1 (phospho-Y15 and total) expression, and β-tubulin as loading control. F, induction of the intra-S-phase checkpoint was not affected by WEE1 inhibition. CAL120 cells were pulse-labeled with 10 μmol/L BrdU for 30 minutes, washed (W), and then treated with 1 μmol/L camptothecin (CPT) for 30 minutes. After CPT removal (0 hours), BrdU-labeled S-phase cells (BrdU+ , indicated by boxed area) were monitored at the indicated time points in the absence (iii) or presence of MK-1775 (iv) or AZD7762 as a positive control (v). Control cells (ctr) were not exposed to CPT and cultured in the absence (i) or presence of MK-1775 (ii). Arrowheads indicate delayed S-phase progression.. ...
Fidelity of histone gene regulation, and ultimately of histone protein biosynthesis, is obligatory for packaging of newly replicated DNA into chromatin. Control of histone gene expression within the 3‐dimensional context of nuclear organization is reflected by two well documented observations....
The end of the S phase of the cell cycle leads to G2 phase, which in turns leads to the M phase or mitosis. During G2 phase, there must be an increasing amount of molecules needed for M phase. G2 phase has been traditionally regarded as a transitional phase between S and M phases. However, during G2 phase, it is checked if any error occurred during DNA replication and if the DNA has been completely replicated. If something went wrong during S phase, M phase does not start until the errors are repaired. It is of great importance the detection of errors before M phase starts, otherwise they will be inherited by the daughter cells. During G2 phase, cell increases the size, and centrosomes of animal cells, duplicated during S phase too, are positioned at opposite locations of the cytoplasm for starting the polymerization of the mitotic spindle during M phase. ...
TY - JOUR. T1 - Rapid cell cycle analysis. II. Phase durations and dispersions from computer analysis of RC curves.. AU - Gray, J. W.. AU - Bogart, E.. AU - Gavel, D. T.. AU - George, Y. S.. AU - Moore, D. H.. PY - 1983/9. Y1 - 1983/9. N2 - In this paper, we present a procedure for the rapid, quantitative estimation of the G1, S, and G2 + M phase durations and dispersions and the growth fraction for asynchronously growing cell populations. In this procedure, the cell population is pulse-labelled with a radioactive DNA precursor at the beginning of the analysis and then sampled periodically. The samples are dispersed, stained with a DNA specific dye, and processed through a cell sorter where cells from mid-S phase and G1 phase are sorted. The radioactivity per cell (RC) is determined for each sorted sample. In addition, the variation in the rate of incorporation of the radioactive DNA precursor across S phase is determined and the fractions of cells in the G1, S, and G2 + M phase are estimated ...
Replication times for all important chromosome bands, of both types R and Q (277 structures) are analysed. - The R-bands form a group of structures whose DNA replicates during the early S-phase, while
Over the following 36 h, we quantified by movement cytometry the charge of EdU nucleotide analogue incor poration from the cells and their total DNA content material, which allowed us to assign cells to G0G1, S, and G2M phases with the cell cycle. When compared to cells transfected using a management non targeting microRNA, cells transfected with miR 29 contained fewer cells in G0G1 and much more cells in S phase at twenty and 24 h submit transfec tion. At 28 and 32 h right after trans fection, cells transfected with miR 29 contained fewer cells in S phase and much more cells in G2M phase than these transfected with the handle. miR 29 overexpression thus hastens re entry into the cell cycle from a quiescent state. To more discover the results of miR 29 expression around the cell cycle, we transfected miR 29 or perhaps a detrimental manage microRNA into asynchronously cycling fibroblasts.. Forty eight hrs publish transfection, miR 29 transfection led to extra cells in G2M. As anticipated ...
Flow-cytometric analysis was used to examine the cell cycle characteristics of BMKs from each of the three genotypes ( Fig. 4A), and the data shown are representative of three independently derived cultures from each genotype. LSL-K-rasG12D BMKs infected with Ad-Cre displayed a higher percentage of cells in G1 and S phases (40.8% and 15.2%, respectively) than control cells (33.4% and 11.5%, respectively). We believe that this is indicative of an increased rate of exit from G2-M and increased cellular proliferation, as supported by data obtained from daily cell counts in LSL-K-rasG12D BMKs (see Fig. 4C and below). Importantly, Ad-Cre-infected Rac1flox/flox BMKs displayed similar growth kinetics to LSL-K-rasG12D BMKs (39.6% of cells in the G1 phase and 13.5% in the S phase compared with controls at 34.9% in the G1 phase and 11.6% in the S phase). Thus, in BMK cells, loss of Rac1 function alone is not lethal and is compatible with proliferation. In contrast, following Ad-Cre infection, ...
No, mitosis cannot occur without DNA replication in S phase. For the formation of new cells additional DNA is required and it is very necessary to maintain the chromosomal number in the dayughter cells. thus, mitosis cannot occue without the duplication of DNA in the S phase
When does DNA replication happen? A. During the G1 phase of the cell cycle B. During the S phase of the cell cycle C. During the G2 phase of the cell...
Components and dynamics of DNA replication complexes in S. cerevisiae: Redistribution of MCM proteins and Cdc45p during S phase ...
Doç. Dr. Enes Murat Atasoyu, genel sağlığımız açısından son derece önem taşıyan, böbrek sağlığını koruyabilmek için altın kurallar olarak belirttiği önerileri sıralıyor:. 1.)Hareket edin; Düzenli olarak yürüyüş, hafif koşu, bisiklete binmek gibi egzersizler yapın ki dinç bir bedene sahip olun ve fazla kilolarınızdan da kurtulun. Böylece diyabet, hipertansiyon gibi hastalıkların böbreklerde yol açabileceği hasarı önleyebilir veya azaltabilirsiniz.. 2. )Kan şekerinizi düzenli kontrol edin; Diyabet, kronik böbrek rahatsızlığına neden olan hastalıklar içinde ilk sırada yer alıyor. Uygun ilaç tedavisi, diyet ve egzersiz programı ile kan şekeri düzeyi ve kan basıncı normal sınırlarda tutularak, böbrekler diyabetin olumsuz etkilerinden korunabilir. Diyabet gelişimi riskine sahipseniz (kilo fazlalığı olan, az hareket eden, ailesinde diyabet bulunan vb.) yılda bir kez kan şekeri ölçümü yaptırın.. 3.) Kan basıncınıza dikkat ...
Look up Phase, phase, or phases in Wiktionary, the free dictionary. Phase or phases may refer to: State of matter, or phase, ... Phase 2 (disambiguation) Phase 3 (disambiguation) Phase 4 (disambiguation) Phase 5 (disambiguation) Phase space (disambiguation ... Phase space formulation, a formulation of quantum mechanics in phase space Phase (waves), the position of a point in time (an ... Phase (band), a Greek alternative rock band Phases (band), an indie pop American band, formerly known as JJAMZ Phase (album), a ...
The G1 phase, gap 1 phase, or growth 1 phase, is the first of four phases of the cell cycle that takes place in eukaryotic cell ... Around 30 to 40 percent of cell cycle time is spent in the G1 phase. G1 phase together with the S phase and G2 phase comprise ... The G1/S checkpoint is the point between G1 phase and the S phase in which the cell is cleared for progression into the S phase ... the G1 phase is barely existent and is defined as the gap, if one exists, between the end of mitosis and the S phase. G1 phase ...
... is a health science and pop culture podcast that aims to debunk health and wellness-industry myths and ... "Maintenance Phase Twitter Status". Twitter. Retrieved June 1, 2022. Dibdin, Emma (January 27, 2022). "For an Antidote to Diet ...
... is a 1986 American made-for-television thriller drama film directed by Tony Richardson and starring Peter Strauss ... Penalty Phase at IMDb v t e (Articles with short description, Short description matches Wikidata, Short description is ... Penalty Phase' looks at problems of a judge". The New York Times. Retrieved 26 November 2015. Allan Jalon (November 20, 1986 ...
This permits the expression of the pupil-plane phase aberrations φ {\displaystyle \varphi } to the image plane Fourier phase as ... New Brown Dwarf Binaries from Kernel Phase Interferometry [2] Ireland 2013 : Phase errors in diffraction-limited imaging: ... This equation can be used for model-fitting as it represents the interpretation of a sub-space of the Fourier phase that is ... In order to extract kernel-phases from an image, some requirements must be met: Images are nyquist-sampled (at least 2 pixels ...
Multiplying the equation of a plane wave Aei(k·r − ωt) by a phase factor shifts the phase of the wave by θ: e i θ A e i ( k ⋅ r ... In optics, the phase factor is an important quantity in the treatment of interference. Berry phase Bra-ket notation Euler's ... However, differences in phase factors between two interacting quantum states can sometimes be measurable (such as in the Berry ... For any complex number written in polar form (such as r eiθ), the phase factor is the complex exponential factor (eiθ). As such ...
... is the creation of two distinct phases from a single homogeneous mixture. The most common type of phase ... Colloids are formed by phase separation, though not all phase separations forms colloids - for example oil and water can form ... Phase separation also exists in ultracold gas systems. It has been shown experimentally in a two-component ultracold Fermi gas ... The phase separation can compete with other phenomena as vortex lattice formation or an exotic Fulde-Ferrell-Larkin-Ovchinnikov ...
... may refer to: Phase reversal Phase inversion (chemistry) This disambiguation page lists articles associated ... with the title Phase inversion. If an internal link led you here, you may wish to change the link to point directly to the ...
750~150 BCE Pigeon Phase, ca. 200 BCE-100 CE Connestee Phase, 150-1000 CE Pisgah phase, 1000-1500 CE Qualla Phase, ca. 1500 CE- ... 7500-4300 BCE Morrow Mountain Phase, ca. 4300-2500 BCE Savannah River Phase, ca. 2500-750 BCE Swannanoa Phase, ca. ... The Qualla Phase pottery that followed is thought to have resulted from be the result of the merging of Lamar and Pisgah phases ... The Pisgah phase (1000 to 1450/1500 CE) is an archaeological phase of the South Appalachian Mississippian culture (a regional ...
Official website Phase 7 at IMDb Phase 7 at Rotten Tomatoes The director talks about the film (in Spanish) (Articles with short ... "Phase 7". Retrieved 2014-03-15. Miska, Brad (2011-06-20). "Bloody Disgusting Selects: 'Phase 7' Hits Theaters ... "Phase 7 (2011)". Rotten Tomatoes. Retrieved 2014-03-15. Nelson, Rob (2011-07-06). "Review: 'Phase 7'". Variety. Retrieved 2014- ... Keough, Peter (2011-07-12). "Review: Phase 7". The Phoenix. Retrieved 2014-03-15. Hewitt, Chris (2011-07-13). "'Phase 7' review ...
... (RP) refer to : Reversed-phase chromatography, any chromatographic method that uses a non-polar stationary phase ... Reverse phase protein lysate microarray, a micro-cell lysate dot-blot that allows measurement of protein expression levels This ... disambiguation page lists articles associated with the title Reverse phase. If an internal link led you here, you may wish to ...
It is now widely accepted that the anti-phase cell firing that results from phase precession is an important component of ... O'Keefe and Recce termed this advancement relative to the wave phase "phase precession". Subsequent studies showed that each ... Bose A, Recce M (19 June 2001). "Phase precession and phase-locking of hippocampal pyramidal cells". Hippocampus. 11 (3): 204- ... or whether phase precession was a peculiar property of hippocampal tissue. The finding that theta wave phase precession is also ...
Phase lineup on Wikimedia Commons has media related to Phase (band). Official website Phase discography at ... Phase (26 April 2015). "Phase Back on Track #2 ~ Perdition". Phaseship - The Phase Archives. Retrieved 12 October 2016. " ... Phase". Billboard magazine. 124 (21): 36. ISSN 0006-2510. OCLC 732913734. Retrieved 23 June 2012. "Phase - New Songs, Playlists ... Phase /feɪz/ is a UK-based rock band formed in Larissa, Greece in 2003. It was founded by Thanos Grigoriou, who was performing ...
... is Maria Mena's debut album, which was released by Sony Music Norway. It reached #6 on the Norwegian charts. Her ... Album information from cdon Maria Mena's Official Website v t e "Norwegian album certifications - Maria Mena - Another Phase" ( ...
Phase line, 1-dimensional case Phase space, n-dimensional case Phase portrait D.W. Jordan; P. Smith (2007). Non-Linear Ordinary ... any pair of variables). It is a two-dimensional case of the general n-dimensional phase space. The phase plane method refers to ... The entire field is the phase portrait, a particular path taken along a flow line (i.e. a path always tangent to the vectors) ... In this way, phase planes are useful in visualizing the behaviour of physical systems; in particular, of oscillatory systems ...
In signal processing, linear phase is a property of a filter where the phase response of the filter is a linear function of ... Some examples of linear and non-linear phase are shown below. A discrete-time filter with linear phase may be achieved by an ... Therefore, both magnitude and phase graphs (Bode plots) are customarily used to examine a filter's linearity. A "linear" phase ... has a maximally flat group delay approximation function a phase equalizer A filter is called a linear phase filter if the phase ...
... methods exist in two main domains: Acoustic phase conjugation Optical phase conjugation A. P. Brysev et al., ... As in time reversal, the wave re-emitted by a phase conjugation mirror will auto-compensate the phase distortion and auto-focus ... Propagation of a time reversal replica demonstrates a remarkable property of phase-conjugated wave fields. Phase conjugation of ... Wave phase conjugation of ultrasonic beams, Physics-Uspekhi (1998) Okulov, A Yu (2008). "Angular momentum of photons and phase ...
Look up phase angle in Wiktionary, the free dictionary. Phase angle may refer to: Phase (waves), the angular displacement of a ... instantaneous phase of an analytic signal representation Phase angle (astronomy), the angle between the incident light and ... angular component of the complex number representation of a sinusoid Analytic representation phase, ... reflected light Angle Polar coordinate system This disambiguation page lists articles associated with the title Phase angle. If ...
From early Angel 2 phase to late Angel 3 phase, the percentage of decorated sherds relative to all sherds declined from 3% to ... The proposed Angel 1 phase (Stephan-Steinkamp phase, 1100 to 1200?), is represented only by pottery sherds in the vicinity of, ... Angel phase archaeological sites date from c. 1050 - 1350 CE and are located on the northern and southern sides of the Ohio ... During this phase at Angel, pottery design indicates that this was the same time period as when Middle Wickliffe transitioned ...
... (Synthesis Phase) is the phase of the cell cycle in which DNA is replicated, occurring between G1 phase and G2 phase. ... S phase index (SPI) S-fraction or S-phase fraction (oncology/pathology prognosis) Restriction point David M (2007). The cell ... Throughout M phase and G1 phase, cells assemble inactive pre-replication complexes (pre-RC) on replication origins distributed ... This process depends on the kinase activity of Cdc7 and various S-phase CDKs, both of which are upregulated upon S-phase entry ...
The track "Pure Phase" was the basis for a limited edition release called "Pure Phase Tones For DJs", which consisted of 16 ... "Pure Phase - Spiritualized". AllMusic. Retrieved 4 January 2016. Kot, Greg (30 March 1995). "Spiritualized: Pure Phase ( ... Mulvey, John (July 2021). "Spiritualized: Pure Phase". Mojo. No. 332. p. 99. "Spiritualized: Pure Phase". Q. No. 102. March ... Pure Phase is the second studio album by Spiritualized, released on 28 March 1995. The album was recorded in the Moles Studio ...
... (Quarta Fase, QF) is a faction within the Democratic Party (PD), a political party in Italy. The name of the ... This phase, according to the faction's website, started with the foundation of Democracy is Freedom - The Daisy (DL), that put ... Fourth Phase (All articles with dead external links, Articles with dead external links from February 2022, CS1 maint: archived ... The failure of The Populars to be a united faction led Fioroni, Franceschini and Soro, backed by Marini, to set Fourth Phase. ...
... "Boss Burger N' Chips (Remix) - From Exclusives for Others by Inverse Phase". Inverse Phase (via Bandcamp). ... Inverse Phase - Shuttle Scuttle OST released Inverse Phase. "Pretty Eight Machine". Inverse Phase (via (Bandcamp). Retrieved ... Inverse Phase. "Nine Inch Nintendos? 8-Bit Nails? Something like that!". Inverse Phase (via Kickstarter). Retrieved March 9, ... Inverse Phase - VGMdb "Music , Inverse Phase". Bandcamp. Retrieved August 9, 2022. Stinson, Elizabeth (September 28, 2010). " ...
The phase detector needs to compute the phase difference of its two input signals. Let α be the phase of the first input and β ... The phase detector is an essential element of the phase-locked loop (PLL). Detecting phase difference is important in other ... A phase detector for a bang-bang charge pump must always have a dead band where the phases of inputs are close enough that the ... Phase detectors for phase-locked loop circuits may be classified in two types. A Type I detector is designed to be driven by ...
The imperial phase is the period in which a musical artist is regarded to be at their commercial and creative peak ... While its original usage implied that an imperial phase was a one-time occurrence for a single artist, artists have been ... Finally, "self-definition" is the concept that the imperial phase defines the rest of the artist's career; future works will be ... Macpherson, Alex (10 January 2019). "Ariana Grande's Imperial Phase As A Pop Star Began In Earnest With 'Thank U, Next'". ...
The difference between a minimum phase and a general transfer function is that a minimum phase system has all of the poles and ... only for a minimum-phase system, the phase response of H(s) is related to the gain by arg ⁡ [ H ( j ω ) ] = − H { log ⁡ ( , H ... only the class of minimum phase systems is closed under inversion. Intuitively, the minimum phase part of a general causal ... A minimum-phase system, whether discrete-time or continuous-time, has an additional useful property that the natural logarithm ...
... refers to a period in the late 11th and early 12th centuries, when drastic changes in ceramics and masonry ... and the masonry and layout of great houses built during the McElmo phase, which was the last major construction era in the ... which overlaps with the McElmo Phase. Archeologists initially suggested that the McElmo influence was brought to Chaco Canyon ... canyon, differ significantly from those built during the early parts of the Bonito Phase (850 to 1140), ...
... is a brief transitional phase between the Ġgantija and Tarxien phases, the two main phases during which the principal ... The Saflieni phase is one of the eleven phases of Maltese prehistory, the fourth of five in the middle or Temple period. It is ... 21 Saflieni-phase ceramics may provide a useful indication of separation between the two long phases.: 45 They have been ... The Saflieni phase, from approximately 3300-3000 BC,[citation needed] ...
Early contrasting views either considered non-proliferating cells to simply be in an extended G1 phase or in a cell cycle phase ... Stem cell quiescence has been recently suggested to be composed of two distinct functional phases, G0 and an 'alert' phase ... The G0 phase describes a cellular state outside of the replicative cell cycle. Classically, cells were thought to enter G0 ... Thus it was thought of as a resting phase. G0 is now known to take different forms and occur for multiple reasons. For example ...
A phase splitter is a device that separates a signal[clarification needed] into multiple phases (or polarities). The term is ... Phase Splitters - Transistors Tutorial Part 2: "Bipolar Transistors" "A high performance phase splitter". EXPERIMENTO COM UM ... but opposite phase, voltages on the outputs. This technique was first described by O.H. Schmitt. if the shared emitter (or ... 180 degrees phase difference), but sometimes is used to refer to the generation of quadrature signals (i.e. differing by 90 ...
Supercrystal: A hidden phase of matter created by a burst of light Peer-Reviewed Publication Penn State ... image: A 3D image of a supercrystal from phase-field simulations using the software μ-PRO. view more ... This put the whole system into a delicate but "frustrated" state with multiple phases randomly distributed in the volume. At ... Supercrystal: A hidden phase of matter created by a burst of light. Penn State ...
Los Angeles Times:. And Obamas recent moves regarding a lawsuit by detainees have left some liberal groups and Bush critics, including the American Civil Liberties Union, feeling betrayed, given that Obama was a harsh critic of Bushs detainee policies when running for office last year.. The anxiety is also being felt in the labor movement, one of Obamas most important support bases. Some union officials and their allies are frustrated that at a crucial point in negotiations over his massive stimulus package, Obama seemed to call for limits on "Buy American" provisions in the bill aimed at making sure stimulus money would be spent on U.S.-made materials.. Obama has been president for less than a month, and his liberal critics concede that the economic crisis has understandably taken the focus off their issues. But some of the issues in play were crucial to building excitement on the left and mobilizing grass-roots support for Obamas candidacy.. Read more ...
... in the mould of the venerable MXR Phase 100. However, where the MXR sets the intensity with a four-way rotary switch, ... Wed have liked the top speed of the phasing to be faster but this is still very usable phasing for effect with the four ... However, where the MXR sets the intensity with a four-way rotary switch, the Phase Shifter offers a pair of two-way switches ... This is a 10-stage phaser with variable speed and four preset levels of intensity, in the mould of the venerable MXR Phase 100 ...
... EasyChair Preprint no. 3791. 10 pages•Date: July 8, 2020 ... Evaluating Smart PSS Solutions with Context-Awareness in Usage Phase}, howpublished = {EasyChair Preprint no. 3791}, year = { ... a context-aware approach to evaluate the smart PSS performance before launching to the market and even during the usage phase. ... the smart PSS performance and whether it is worth to reallocate the resources of product-service bundles during the usage phase ...
"We look forward to exploring the findings from our Phase 1b trial further in the ongoing randomized Phase 2 PINNACLE clinical ... Tarextumab in Small Cell Lung Cancer Phase 1b Results. The Phase 1b open-label study enrolled a total of 27 patients with ... OncoMed Presents Phase 1b Clinical Trial Data for Tarextumab in Small Cell Lung Cancer at the 2015 ASCO Annual Meeting. Dose- ... Data from the Phase 1b study of tarextumab were presented today by Dr. M. Catherine Pietanza, M.D., of Memorial Sloan-Kettering ...
The following checklist may be useful for identifying missing or incorrect elements in your Phase II Science Program. Please ... Have you included a Phase II filling note to the top of the program.The title of the notes should be Phase II filling - ... Phase II was overfilled, of the N science observations execute only M of them (this option is used when the PI overfills the ... The Phase II was filled to only N hours, as the PI wants to assess data from the first observations before defining ...
... Head Coach Frank Reich meets with the media following the conclusion of Colts ...
User Data Phase. During the user data phase, character replacement at the end of frame and end of multiframe is ... User Data Phase Character replacement for non-scrambled data Character replacement for scrambled data ...
Thank you for being here! We are so glad to be back for Phase Seven: Emergence, September 30 - October 2, 2022 at Stable ...
said Tuesday it ended a Phase III study for an experimental lung-cancer drug called figitumumab that had been associated with ...
Konami of Europe has announced the second phase of its phenomenally successful Yu-Gi-Oh! ONLINE campaign, with a new DU… ... Yu-Gi-Oh!™ ONLINE enters Phase 2 Konami of Europe unveils DUELPASS Phase 2 as Yu-Gi-Oh!s online presence continues to expand ... Phase 2 of the game has been designed to add further variety to the online action, with the new cards adding more traps, ... Yu-Gi-Oh! ONLINE Phase 2 will be launched for PC in November. For more information, please contact Steve Merrett at Voltage PR ...
In the acute phase, the patient should apply ice to the nose and elevate the head to aid in reduction of any swelling present. ... Acute Phase. Medical Issues/Complications. High-force midfacial injuries may involve structures other than the nose itself. ...
... important growth phase with a reversal of the firms recent production decline in Ukraine and had continued to grow its new ...
Phase Diagrams BIBLIOGRAPHY Source for information on Phase Diagrams: International Encyclopedia of the Social Sciences ... They can be one-dimensional (called a phase line ) or two-dimensional, involving a two-dimensional phase space. Phase diagrams ... Phase Diagrams. BIBLIOGRAPHY. Phase diagrams display the characteristics of dynamical systems. They include fixed points ( ... Economic Dynamics: Phase Diagrams and Their Economic Application. 2nd ed. Cambridge, U.K.: Cambridge University Press. ...
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... noting that phase two will not commence until at least two weeks after phase one. ... New Yorks second phase of reopening will require individual businesses input.. "This is not a one-sided equation here," Cuomo ... Governor Andrew Cuomo Discusses Phases of Reopening New York. By Emily Czachor On 4/26/20 at 1:33 PM EDT. ... The first phase will allow construction and manufacturing companies to resume operations, though determining which entities can ...
High quality Moon Phases-inspired gifts and merchandise. T-shirts, posters, stickers, home decor, and more, designed and sold ... moon phases, moon phases, moon phases, moon phases, moon phases, moon phases, moon phases housewares, moon phases coffee cup, ... lunar, phases, moon, moon phases, moon phase, phase, lunar phases, lunar phase, tumblr, style, fashion, glam, glamour, love, ... moon phases, moon, luna, lune, moon phases, moon phases, moon toaster, moon, moon art, black, phases of the moon, la lune, la ...
The fundamental component of this project is to implement the Phase II of the Banks 2010 loan as originally envisaged, i.e. ... Based on the findings, the ESAP for Phase I has been revised. ... consultants included review of the existing reports for Phase I ...
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... dainty details and eye-catching prints in the Phase Eight collection. Find casual styles and elevated pieces at M&S ... Phase Eight. PHASE EIGHT. In the Phase Eight collection, flattering cuts are key for both everyday designs and occasionwear. ...
Season Two MVP Thandie Newton Shines in Westworlds Scattered "Phase Space". (Episode 2.06). By Jacob Oller , May 28, 2018 , 10 ... "Phase Space" starts off with an error. Dolores, after bumping Teddy (James Marsden) up to maximum badassitude, is getting a ...
This page provides a step-by-step process of the fourth phase of building a training cadre - Evaluation. ...
... and Moon phase in Ghatshila - Jharkhand - India for December 2022. When and where does the Moon rise and set? ... Moon Phases*Night Sky*Meteor Showers*Day and Night Map*Moon Light World Map*Eclipses*Live Streams*Seasons ... Sun & Moon Today Sunrise & Sunset Moonrise & Moonset Moon Phases Eclipses Night Sky ...
This example shows how to control and initialize a Synchronous Machine (SM).
The Syrian army has successfully concluded the first phase of its operation in the strategic western city of Qusayr. ...
Phase 3: Based on Phase 1 and Phase 2, develop a screening method which accurately predicts the standard test performance, and ... 1] The project is in the 2nd year of phase 1. The long term vision is to enable the development of new gas phase fire ... Phase 1: Understand mechanism of phosphorus FR systems.. *Phase 2: Understand the mechanism of and antimony/bromine FR systems ... Some progress has been made in understanding the gas-phase inhibition mechanism of some species of interest as gas-phase FRs, ...
Time for next phase of Yankees season By Ken Davidoff Social Links for Ken Davidoff * View Author Archive ... But its time for the next phase, the one in which they have talent that can actually match their toughest competitors. That ... Could Joe Girardis group be receiving a starker signal that theyre entering a new phase of 2013? ...
U.S. Manufacturings Next Phase. Richard M. Daley and Bruce Katz Wednesday, May 9, 2012. ...
  • CHICAGO, June 1, 2015 (GLOBE NEWSWIRE) -- OncoMed Pharmaceuticals Inc. (Nasdaq:OMED) presented new survival and biomarker data and updated clinical response and safety results from its Phase 1b clinical trial of tarextumab (anti-Notch2/3, OMP-59R5) in patients with first-line extensive-stage small cell lung cancer at the 2015 ASCO Annual Meeting. (
  • We look forward to exploring the findings from our Phase 1b trial further in the ongoing randomized Phase 2 PINNACLE clinical trial of tarextumab plus platinum-based therapy in patients with extensive-stage small cell lung cancer. (
  • A new study by researchers from the International Agency for Research on Cancer (IARC), the Daffodil Centre (a joint venture between the University of Sydney and Cancer Council NSW, Australia), and partners assesses changes in tobacco smoking behaviours during the early pre-vaccination phases of the COVID-19 pandemic in 2020. (
  • The findings, published in the journal eClinicalMedicine , suggest that there was a relative reduction of 13% in overall smoking prevalence - the proportion of the population who smoke - during the early phase of the pandemic in 2020 compared with the years before the pandemic. (
  • We are so glad to be back for Phase Seven: Emergence, September 30 - October 2, 2022 at Stable Studios. (
  • Phase 1 reviews assess the quality of a jurisdiction's legal and regulatory framework for the exchange of information, while Phase 2 reviews look at the practical implementation of that framework. (
  • and WHEREAS: The approved DWFMP recommended parallel tracks for phasing and implementation of elementary and high school projects. (
  • Following the successful implementation of the first phase, the AWHC initiative continues its mission of placing young African women professionals aged between 22 and 35 years as UN Volunteer health champions across WHO Country Offices in Africa. (
  • Serum progesterone levels have been studied as a means to diagnose luteal phase deficiency (LPD). (
  • [ 6 ] Ultrasound measurement of endometrial thickness has not been shown to be effective in the prediction of luteal phase deficiency. (
  • In 1950, Noyes, Hertig, and Rock established that the diagnosis of luteal phase deficiency (LPD) is centered on histologic dating of the endometrium. (
  • Boutzios G, Karalaki M, Zapanti E. Common pathophysiological mechanisms involved in luteal phase deficiency and polycystic ovary syndrome. (
  • Diagnosis and treatment of luteal phase deficiency: a committee opinion. (
  • The goals of pharmacotherapy in luteal phase deficiency are to restore ovarian function, reduce morbidity, and prevent complications. (
  • Current clinical irrelevance of luteal phase deficiency: a committee opinion. (
  • Figure one shows the World Health Organization's "Continuum of Pandemic Phases," displayed as a distribution curve of the hypothetical global average of pandemic cases over time based on a continued pandemic risk assessment. (
  • From left to right, the curve shows the increase and decrease of the global average of pandemic cases across four phases of the pandemic continuum. (
  • The phases in the continuum also overlap with the stages of the pandemic risk assessment. (
  • The global average of cases greatly increase through the "alert" and "pandemic" phases, with the greatest global average of cases occurring in the "pandemic" phase. (
  • The figure shows a slight increase of the global average of cases during the "transition" phase, indicating a possible second wave of pandemic cases. (
  • India should implement phased reduction in tariffs for the alcoholic beverages (alcobev) sector and create transparent policies, according to Indian Council for Research on International Economic Relations (Icrier). (
  • The fundamental component of this project is to implement the Phase II of the Bank's 2010 loan as originally envisaged, i.e. restructure the financing into a limited recourse structure. (
  • Phase 2 of the game has been designed to add further variety to the online action, with the new cards adding more traps, monsters and spells for the player to implement in their Yu-Gi-Oh! (
  • Now that Central Bucks officially began to implement Phase 2 of Distance Learning, it is expected that students will learn new material as well as maintain the skills they received during Distance Learning in order to make a smoother transition once school is back in session. (
  • These events involved offsite power circuits with one open phase. (
  • Phase diagrams display the characteristics of dynamical systems. (
  • Phase diagrams have been employed in a number of areas in the social sciences. (
  • Phase diagrams can also be used to display discrete systems of difference equations or continuous systems of differential equations - although the latter is the most common. (
  • This course will explore higher-level details about phase diagrams, including the Fe-Fe3C phase diagram. (
  • The use of principles of the Fe-Fe3C phase diagrams to predict microstructures and properties of carbon steel alloys. (
  • In this module, we will examine phase diagrams and the Fe-Fe3C model system. (
  • The Moon takes 27.3 days to orbit Earth, but the lunar phase cycle (from new Moon to new Moon) is 29.5 days. (
  • Herein, the therapeutic potential and safety of early Elabela intervention treatment in treating phase 1 ROP and the possible underlying mechanisms were investigated using an oxygen -induced retinopathy (OIR) mouse model. (
  • baseline audit (phase 1), educational intervention (phase 2) and post-intervention audit (phase 3). (
  • For more research news, visit or follow @OsakaMetUniv_en and #OMUScience . (
  • Osaka Metropolitan University scientists have discovered an unprecedented phase transition during which crystals achieve amorphous characteristics while retaining their crystalline properties. (
  • This research aimed at describing the characteristics of the acquisition phase, the first phase of the family life cycle, marked by the union of the couple and the living with small children. (
  • In the acute phase, the patient should apply ice to the nose and elevate the head to aid in reduction of any swelling present. (
  • The primary focus for Phase Two, which will be rolled out in early 2019, will be to develop EV fast charger stations along I-295, I-95 through Bangor, and along coastal Route 1 to fill out a network of EV fast chargers as far as Bar Harbor. (
  • The school plans to begin renovation work on its second phase in 2019. (
  • Illinois Gov. J.B. Pritzker announces the start of Phase 1B of coronavirus vaccinations in the state. (
  • The first phase will allow construction and manufacturing companies to resume operations, though determining which entities can reopen and when depends on their location-in addition to their ability to uphold safety measures to protect against the coronavirus' further spread. (
  • Per the White House's national reopening plan, a region cannot initiate phase one until it reports a 14-day decline in new coronavirus cases. (
  • Construction on the phase-one project began in December of 2017 and was completed in August 2018. (
  • Facing to the problems of disequilibrium of service investment and the expected values, it is critical to determine when to evaluate the smart PSS performance and whether it is worth to reallocate the resources of product-service bundles during the usage phase. (
  • In this article, we treat the smart PSS evaluation process as a complex and multi-criterion decision-making (MCDM) problem, and propose a context-aware approach to evaluate the smart PSS performance before launching to the market and even during the usage phase. (
  • LPTN ), the industry leader in bioactive lipid-targeted therapeutics, announced today completion of its Phase 1 double-blind, placebo-controlled, single ascending dose study to evaluate the safety, tolerability, immunogenicity and pharmacokinetics of Lpathomab™ in healthy volunteers. (
  • This event, and others similar to it, led the NRC and the nuclear power industry to evaluate open phase conditions. (
  • Either way, CPM can help your team plan your project work during the pre-construction phase, track deliverables during the construction phase, evaluate project delivery, and close out at the end of the initiative. (
  • SOLO3 is a Phase 3 randomized, open-label, controlled, multi-center trial to evaluate the efficacy and safety of LYNPARZA tablets following two or more prior lines of chemotherapy. (
  • KENILWORTH, N.J.-( BUSINESS WIRE )-AstraZeneca and Merck (NYSE:MRK), known as MSD outside the United States and Canada), today presented full results from the Phase 3 SOLO3 trial which evaluated LYNPARZA, compared to chemotherapy, for the treatment of platinum-sensitive relapsed patients with germline BRCA1/2 -mutated (g BRCA m) advanced ovarian cancer, who have received two more prior lines of chemotherapy. (
  • Cite this: Late-Phase Reaction in Ocular Allergy - Medscape - Oct 01, 2008. (
  • State and local health departments should include mental health management in each phase of a disaster (pre-event, response, recovery, and evaluation). (
  • Hajishaiha M, Ghasemi-Rad M, Karimpour N, Mladkova N, Boromand F. Transvaginal sonographic evaluation at different menstrual cycle phases in diagnosis of uterine lesions. (
  • The Phase II was filled to only N hours, as the PI wants to assess data from the first observations before defining observations for the remainder of the allocation. (
  • erratic temps during follicular phase? (
  • Does anyone know if erratic BBT temps during the follicular phase mean anything? (
  • Dh and I are about to start cycle 4 of TTC and I am wondering if I should be taking something/doing something during the follicular phase. (
  • I don't know what follicular phase means. (
  • If follicular phase means before O, then it is fine for temps to bounce around. (
  • If follicular phase means after O, then as long as they are above the cover line, it is okay. (
  • Yep, follicular phase is before O. I read somewhere that temps on a 'normal' chart, shouldn't bounce around more than .5 degrees before O. (
  • Based on the findings, the ESAP for Phase I has been revised. (
  • Abnormal uterine findings were de Recherche et d'Application en identified in 95.8% of patients attending hysteroscopy at GESHRTH. (
  • Osaka, Japan - If you have ever watched water freeze to ice, you have witnessed what physicists call a 'phase transition. (
  • A typical phase transition exhibited by crystalline solids involves a change in the crystal structure. (
  • In the dielectric compound Ba 1- x Sr x Al 2 O 4 , the structural phase transition is driven by an acoustic soft mode, the atomic vibration pattern of which is similar to that of sound waves. (
  • The global average of cases greatly decreases moving into the "transition" phase, which overlaps with the "recovery" stage of the risk assessment. (
  • Some authors believe that mid-luteal phase biopsy is the best for accurate diagnosis of LPD. (
  • Sonntag B, Ludwig M. An integrated view on the luteal phase: diagnosis and treatment in subfertility. (
  • Diagnosis and appropriate correction of intrauterine anomalies are considered et d'Application en Chirurgie essential in order to increase chances of conception. (
  • Brangwynne, a biophysicist specializing in soft matter physics, is a founder of the field of biomolecular condensates, having discovered and elucidated the biophysical principles underlying how liquid-liquid phase separation drives the organization, material properties, function, and dysfunction of the membraneless organelles. (
  • Given these elements, the trajectory of the system is defined and can be plotted in a phase diagram . (
  • This figure also shows a typical phase diagram in two-dimensional space. (
  • We will use the Fe-Fe3C phase diagram to predict the possible phases and microstructures of a steel alloy based on its composition. (
  • Nereid says its drug discovery efforts will focus initially on forms of cancer and neurodegenerative diseases where pathological protein behaviors appear to be governed or influenced by phase transitions. (
  • Such structural phase transitions usually occur at finite temperatures. (
  • Najmuddin said with the completion of Phase Two - which stretches for another 19 stations to Kajang - operations would begin to serve the estimated 1.2 million people living along that that corridor. (
  • The Construction Administrator must remain involved throughout the design phases to monitor and work towards the successful completion of design of the construction documents. (
  • Losing one or two phases, with or without ground, on the primary (high voltage) side of a transformer connected to the transmission system can cause unbalanced voltage on the secondary (low voltage) side of the transformer, connected to plant safety equipment. (
  • Again, take the results of phase one and phase two of history and layer on top this new contradiction, and the defensiveness is easier to see. (
  • Russia and Ukraine-focused JKX Oil & Gas used its results for 2012 to confirm that it has embarked on an 'important growth phase' with a reversal of the firm's recent production decline in Ukraine and had continued to grow its new Russian production. (
  • If LPD is caused by hypothyroidism, correction of endocrine disease results in normal luteal phase. (
  • This is the fourth positive Phase 2 or Phase 3 trial in advanced ovarian cancer for LYNPARZA across multiple lines of therapy. (
  • Nereid Therapeutics says its drug discovery platform is based on proprietary technologies aimed at precisely measuring, interrogating, and controlling phase separation in mammalian cells. (
  • While it is known that phase separation and biomolecular condensate formation in mammalian cells play roles in disease processes, it has been difficult to measure the impact of therapeutics on those processes until now. (
  • We can use these approaches as fingerprints of the underlying biomolecular driving forces at play in cells, and then ask how those driving forces are modulated when subjected to therapeutics," Brangwynne told GEN. "We think that it's a really completely new way of understanding how to modulate the phase behavior within a living cell. (
  • At the new Moon phase, the Moon is so close to the Sun in the sky that none of the side facing Earth is illuminated (position 1 in illustration). (
  • But if a certain moon phase gives me even a slight advantage, I'll take it. (
  • The rut guide I provide on my site ( ) season was spot on based on these moon phase observations last year. (
  • The Phase 1b open-label study enrolled a total of 27 patients with extensive-stage small cell lung cancer who had not received prior treatment for extensive stage disease. (
  • Pfizer Inc. said Tuesday it ended a Phase III study for an experimental lung-cancer drug called figitumumab that had been associated with an unexpected number of deaths in testing among patients. (
  • The U-Mass Lowell PHASE in healthcare research project has been a five-year NIOSH-funded study of health disparities among healthcare workers. (
  • While using the conjunctival provocation test (CPT), which was initially employed to study the early-phase response (EPR), researchers discovered that the conjunctiva also exhibited a dose-dependent LPR. (
  • The study was carried through with 50 middle-class families, in the acquisition phase of the Family Life Cycle, from the city of Vitória, ES. (
  • The primary objective of this study was to conduct a mixed-method qualitative assessment by using nominal group technique (NGT) (phase 1) and traditional focus group technique (phase 2) to determine what features should be included in an Internet-based tool to promote PA in overweight and obese young adult AA women. (
  • The FR additives, principally the bromine compounds and antimony oxide (almost always added with bromine, and also under regulatory pressure) both are believed to work in the gas phase by interfering with the combustion chemistry. (
  • Industrial chemists, while very good at understanding the condensed-phase chemistry related to forming stable FR additives and their interaction with the base polymer, have little insight into what they are aiming to achieve in the gas phase: i.e., what compounds actually need to make it to the gas phase, and what they need to do once they are there. (
  • The phase chemistry selection allows users to screen for the retention and selectivity required to achieve sample preparation objectives. (
  • Illinois and Chicago have both entered the next phase of their vaccination rollout, called Phase 1b, increasing the eligibility to millions of residents. (
  • Participating in Phase III of SCOAP 3 demonstrates APS's ongoing commitment to this community and to our mission to support the research community and advance and diffuse the knowledge of physics' he said. (
  • The existing literature demonstrates that an ocular late-phase reaction also exists and has implications in the development severity of disease, change of reactivity and progression of the atopic disease state from a localized target organ, such as the nose or eye, to a more systemic atopic disorder. (
  • Phase 2 settings include settings for a security association (SA), which defines how data packets are secured when they are passed between two endpoints. (
  • The Phase 2 Settings also include a setting for Perfect Forward Secrecy (PFS). (
  • Today we're going to start with Phase One - the Commitment phase. (
  • Phase One with us today, which is the Commitment phase. (
  • Before we dive into the Commitment phase, I'd love for you to start by telling us more about your specific job- title and the role of the Ohio Disability and Health program, and also how you are uniquely integrated at the state health department. (
  • So, before we dive into our first phase of really talking about the commitment aspect of the work and the project partners, I'd really - David - I'd love to hear from you. (
  • The Obama administration and Congress now face many difficult choices if they choose to comply with the G20 commitment to phase-out fossil fuel subsidies," the API said. (
  • Medical treatment centers on hormonal support of the patient's luteal phase. (
  • Standard treatment usually helps in this phase. (
  • In this phase, people often have symptoms and standard treatment may not be as effective as in the chronic phase. (
  • The goal of the work is to understand how the properties of the flames over burning polymers interacts with the gas-phase inhibition, so that proper screening methods can be employed by industry, and appropriate standard test methods can be used that represent the relevant full-scale behavior. (
  • To effectively develop new fire retardants, industry needs an understanding of how the existing and most promising new gas phase FRs work, and how the properties of the fire (or standard test method) influence the gas-phase chemical inhibition mechanism of the FR. (
  • The liquid and glass states of metal-organic frameworks (MOFs) have recently become of interest due to the potential for liquid-phase separations and ion transport, alongside the fundamental nature of the latter as a new, fourth category of melt-quenched glass. (
  • PDU output current consumption in amps per-phase or per-receptacle can be displayed locally via visual meter or remotely via web/network interface to warn of potential overloads before critical IT mains or branch breakers trip. (
  • Previous studies have established that the severity of vaso-obliteration in phase 1 largely influences subsequent stages, suggesting that prevention of vessels loss may be a potential therapeutic target for ROP. (
  • Phase II was filled to the allocated time, execute all science observations. (
  • Find Moon Phases-inspired gifts and merchandise printed on quality products one at a time in socially responsible ways. (
  • NHIS-D Phase I: The Phase I Disability questionnaire was administered at the same time as the NHIS Core, and collected information about all members of the NHIS households. (
  • This time frame allows for the current Phase I elementary projects to be completed, providing insight for future projects. (
  • As effects of the state's outbreak become less severe, he explained that New York will collaborate with local officials as well as neighboring governors to "reopen in phases, based on regional analysis. (
  • The ribbon-cutting ceremony for the first phase of the trail takes place the following day, Friday, April 26, at Grant Playground (73 E. McMicken Ave.). This event is free and begins at 3 p.m. with Brewery District representatives, city officials and donors present. (
  • This first phase of the Maine Electric Vehicle Charging Initiative will install Level 3 "fast charge" stations at the Maine Turnpike Authority service plazas in Kennebunk (North and South) and West Gardiner, on Rt. (
  • In Phase One of the Initiative, ChargePoint will provide private investment to cover a share of the equipment and operating costs for the seven sites where the fourteen charging stations will be deployed. (
  • In Phase Two of the Initiative, Efficiency Maine will solicit bids for installation and operation of EV fast chargers located in sites that will complement the locations where fast chargers have previously been installed or are being installed through Phase One. (
  • A third phase of the Initiative is expected to further complement the network of fast charger stations with strategically located Level 2 chargers. (
  • Social media accounts were created in phase III ( Twitter has 304 followers, Facebook group has 7,000 members and Facebook page has 1095 members, Flickr has 370 photos uploaded, Youtube has 600 views). (
  • For official phase times and dates for this month, check our Stargazing [2] page. (
  • From the Branch Office VPN page for a tunnel or the BOVPN Virtual Interface page, select the Phase 2 Settings tab. (
  • Welcome to Mrs. Tomolonis' Distance Learning Phase 2 Page! (
  • The first phase of the trail opens this weekend with a celebration featuring three events: a Toast to the Trail dinner on April 25, a ribbon cutting on April 26 and a free immersive tour on April 27. (
  • Studies regarding cell adhesion molecules or integrins, growth factors, and cytokines are all in the experimental phase. (
  • estudio de intervención casi experimental, tipo antes y después, conducido en maternidad pública, Amapá. (
  • This project really builds upon a previous Healthy Communities model used by NACDD and was modified to consist of six phases that really are a crucial part of the inclusive healthy community change processes that are focused on improving the health and well-being of people with disabilities. (
  • says Republicans are in a pre-negotiating phase when it comes to health care. (
  • DSN: CC37.NHIS95.DISABIL.CONDITON 1995 NATIONAL HEALTH INTERVIEW SURVEY Disability Phase I Public Use Data File Background In the United States there are an estimated 35-43 million people with physical and mental disabilities. (
  • As with the NHIS Core, the NHIS-D Phase I questions were answered by any available adult in the household who was knowledgeable about the health of other household members. (
  • In order to examine these issues in detail, the Phase I questionnaire had 3 sections exclusively for children: a section on special health needs of children, a section on special education services for children, and a section on early childhood development for children under 5 years of age. (
  • Health planning--a new phase. (
  • Beginning Monday, several Walgreens and Jewel-Osco locations began vaccinations or opened up appointments for Illinois residents eligible under Phase 1B of the state's vaccine rollout. (