Apoptosomes: Multimeric protein complexes formed in the CYTOSOL that play a role in the activation of APOPTOSIS. They can occur when MITOCHONDRIA become damaged due to cell stress and release CYTOCHROME C. Cytosolic cytochrome C associates with APOPTOTIC PROTEASE-ACTIVATING FACTOR 1 to form the apoptosomal protein complex. The apoptosome signals apoptosis by binding to and activating specific INITIATOR CASPASES such as CASPASE 9.Apoptotic Protease-Activating Factor 1: A CARD signaling adaptor protein that plays a role in the mitochondria-stimulated apoptosis (APOPTOSIS, INTRINSIC PATHWAY). It binds to CYTOCHROME C in the CYTOSOL to form an APOPTOSOMAL PROTEIN COMPLEX and activates INITIATOR CASPASES such as CASPASE 9.Apoptosis: 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.Caspases: A family of intracellular CYSTEINE ENDOPEPTIDASES that play a role in regulating INFLAMMATION and APOPTOSIS. They specifically cleave peptides at a CYSTEINE amino acid that follows an ASPARTIC ACID residue. Caspases are activated by proteolytic cleavage of a precursor form to yield large and small subunits that form the enzyme. Since the cleavage site within precursors matches the specificity of caspases, sequential activation of precursors by activated caspases can occur.Caspase 9: A long pro-domain caspase that contains a caspase recruitment domain in its pro-domain region. Caspase 9 is activated during cell stress by mitochondria-derived proapoptotic factors and by CARD SIGNALING ADAPTOR PROTEINS such as APOPTOTIC PROTEASE-ACTIVATING FACTOR 1. It activates APOPTOSIS by cleaving and activating EFFECTOR CASPASES.Caspase 3: A short pro-domain caspase that plays an effector role in APOPTOSIS. It is activated by INITIATOR CASPASES such as CASPASE 9. Isoforms of this protein exist due to multiple alternative splicing of its MESSENGER RNA.Amaryllidaceae Alkaloids: Alkaloids derived from TYRAMINE combined with 3,4-dihydroxybenzaldehyde via a norbelladine pathway, including GALANTAMINE, lycorine and crinine. They are found in the Amaryllidaceae (LILIACEAE) plant family.Physiological Phenomena: The functions and properties of living organisms, including both the physical and chemical factors and processes, supporting life in single- or multi-cell organisms from their origin through the progression of life.Metabolic Networks and Pathways: Complex sets of enzymatic reactions connected to each other via their product and substrate metabolites.Physiological Processes: The functions and activities of living organisms that support life in single- or multi-cellular organisms from their origin through the progression of life.Computational Biology: A field of biology concerned with the development of techniques for the collection and manipulation of biological data, and the use of such data to make biological discoveries or predictions. This field encompasses all computational methods and theories for solving biological problems including manipulation of models and datasets.Knowledge Bases: Collections of facts, assumptions, beliefs, and heuristics that are used in combination with databases to achieve desired results, such as a diagnosis, an interpretation, or a solution to a problem (From McGraw Hill Dictionary of Scientific and Technical Terms, 6th ed).Artemia: A genus of CRUSTACEA of the order ANOSTRACA, found in briny pools and lakes and often cultured for fish food. It has 168 chromosomes and differs from most crustaceans in that its blood contains hemoglobin.Biology: One of the BIOLOGICAL SCIENCE DISCIPLINES concerned with the origin, structure, development, growth, function, genetics, and reproduction of animals, plants, and microorganisms.Freeze Drying: Method of tissue preparation in which the tissue specimen is frozen and then dehydrated at low temperature in a high vacuum. This method is also used for dehydrating pharmaceutical and food products.Mitochondria: Semiautonomous, self-reproducing organelles that occur in the cytoplasm of all cells of most, but not all, eukaryotes. Each mitochondrion is surrounded by a double limiting membrane. The inner membrane is highly invaginated, and its projections are called cristae. Mitochondria are the sites of the reactions of oxidative phosphorylation, which result in the formation of ATP. They contain distinctive RIBOSOMES, transfer RNAs (RNA, TRANSFER); AMINO ACYL T RNA SYNTHETASES; and elongation and termination factors. Mitochondria depend upon genes within the nucleus of the cells in which they reside for many essential messenger RNAs (RNA, MESSENGER). Mitochondria are believed to have arisen from aerobic bacteria that established a symbiotic relationship with primitive protoeukaryotes. (King & Stansfield, A Dictionary of Genetics, 4th ed)Hermaphroditic Organisms: Animals and plants which have, as their normal mode of reproduction, both male and female sex organs in the same individual.Cyclophilins: A family of peptidyl-prolyl cis-trans isomerases that bind to CYCLOSPORINS and regulate the IMMUNE SYSTEM. EC 5.2.1.-Cell Death: The termination of the cell's ability to carry out vital functions such as metabolism, growth, reproduction, responsiveness, and adaptability.Peptidylprolyl Isomerase: An enzyme that catalyzes the isomerization of proline residues within proteins. EC 5.2.1.8.Amino Acid Isomerases: Enzymes that catalyze either the racemization or epimerization of chiral centers within amino acids or derivatives. EC 5.1.1.Mitochondrial ADP, ATP Translocases: A class of nucleotide translocases found abundantly in mitochondria that function as integral components of the inner mitochondrial membrane. They facilitate the exchange of ADP and ATP between the cytosol and the mitochondria, thereby linking the subcellular compartments of ATP production to those of ATP utilization.Ants: Insects of the family Formicidae, very common and widespread, probably the most successful of all the insect groups. All ants are social insects, and most colonies contain three castes, queens, males, and workers. Their habits are often very elaborate and a great many studies have been made of ant behavior. Ants produce a number of secretions that function in offense, defense, and communication. (From Borror, et al., An Introduction to the Study of Insects, 4th ed, p676)Encyclopedias as Topic: Works containing information articles on subjects in every field of knowledge, usually arranged in alphabetical order, or a similar work limited to a special field or subject. (From The ALA Glossary of Library and Information Science, 1983)Cysteine: A thiol-containing non-essential amino acid that is oxidized to form CYSTINE.Cysteine Proteases: A subclass of peptide hydrolases that depend on a CYSTEINE residue for their activity.Cysteine Endopeptidases: ENDOPEPTIDASES which have a cysteine involved in the catalytic process. This group of enzymes is inactivated by CYSTEINE PROTEINASE INHIBITORS such as CYSTATINS and SULFHYDRYL REAGENTS.Cysteine Proteinase Inhibitors: Exogenous and endogenous compounds which inhibit CYSTEINE ENDOPEPTIDASES.Cytochromes c: Cytochromes of the c type that are found in eukaryotic MITOCHONDRIA. They serve as redox intermediates that accept electrons from MITOCHONDRIAL ELECTRON TRANSPORT COMPLEX III and transfer them to MITOCHONDRIAL ELECTRON TRANSPORT COMPLEX IV.Cytochrome c Group: A group of cytochromes with covalent thioether linkages between either or both of the vinyl side chains of protoheme and the protein. (Enzyme Nomenclature, 1992, p539)Breast Neoplasms: Tumors or cancer of the human BREAST.Protein Processing, Post-Translational: Any of various enzymatically catalyzed post-translational modifications of PEPTIDES or PROTEINS in the cell of origin. These modifications include carboxylation; HYDROXYLATION; ACETYLATION; PHOSPHORYLATION; METHYLATION; GLYCOSYLATION; ubiquitination; oxidation; proteolysis; and crosslinking and result in changes in molecular weight and electrophoretic motility.Globins: A superfamily of proteins containing the globin fold which is composed of 6-8 alpha helices arranged in a characterstic HEME enclosing structure.New Zealand: A group of islands in the southwest Pacific. Its capital is Wellington. It was discovered by the Dutch explorer Abel Tasman in 1642 and circumnavigated by Cook in 1769. Colonized in 1840 by the New Zealand Company, it became a British crown colony in 1840 until 1907 when colonial status was terminated. New Zealand is a partly anglicized form of the original Dutch name Nieuw Zeeland, new sea land, possibly with reference to the Dutch province of Zeeland. (From Webster's New Geographical Dictionary, 1988, p842 & Room, Brewer's Dictionary of Names, 1992, p378)Alzheimer Disease: A degenerative disease of the BRAIN characterized by the insidious onset of DEMENTIA. Impairment of MEMORY, judgment, attention span, and problem solving skills are followed by severe APRAXIAS and a global loss of cognitive abilities. The condition primarily occurs after age 60, and is marked pathologically by severe cortical atrophy and the triad of SENILE PLAQUES; NEUROFIBRILLARY TANGLES; and NEUROPIL THREADS. (From Adams et al., Principles of Neurology, 6th ed, pp1049-57)Amyloid beta-Peptides: Peptides generated from AMYLOID BETA-PEPTIDES PRECURSOR. An amyloid fibrillar form of these peptides is the major component of amyloid plaques found in individuals with Alzheimer's disease and in aged individuals with trisomy 21 (DOWN SYNDROME). The peptide is found predominantly in the nervous system, but there have been reports of its presence in non-neural tissue.Neurons: The basic cellular units of nervous tissue. Each neuron consists of a body, an axon, and dendrites. Their purpose is to receive, conduct, and transmit impulses in the NERVOUS SYSTEM.Nerve Tissue ProteinsAmyloid: A fibrous protein complex that consists of proteins folded into a specific cross beta-pleated sheet structure. This fibrillar structure has been found as an alternative folding pattern for a variety of functional proteins. Deposits of amyloid in the form of AMYLOID PLAQUES are associated with a variety of degenerative diseases. The amyloid structure has also been found in a number of functional proteins that are unrelated to disease.NF-kappa B: Ubiquitous, inducible, nuclear transcriptional activator that binds to enhancer elements in many different cell types and is activated by pathogenic stimuli. The NF-kappa B complex is a heterodimer composed of two DNA-binding subunits: NF-kappa B1 and relA.Helix-Loop-Helix Motifs: Recurring supersecondary structures characterized by 20 amino acids folding into two alpha helices connected by a non-helical "loop" segment. They are found in many sequence-specific DNA-BINDING PROTEINS and in CALCIUM-BINDING PROTEINS.I-kappa B Kinase: A protein serine-threonine kinase that catalyzes the PHOSPHORYLATION of I KAPPA B PROTEINS. This enzyme also activates the transcription factor NF-KAPPA B and is composed of alpha and beta catalytic subunits, which are protein kinases and gamma, a regulatory subunit.Caspase Inhibitors: Endogenous and exogenous compounds and that either inhibit CASPASES or prevent their activation.Caspase 8: A long pro-domain caspase that contains a death effector domain in its pro-domain region. Caspase 8 plays a role in APOPTOSIS by cleaving and activating EFFECTOR CASPASES. Activation of this enzyme can occur via the interaction of its N-terminal death effector domain with DEATH DOMAIN RECEPTOR SIGNALING ADAPTOR PROTEINS.Exome: That part of the genome that corresponds to the complete complement of EXONS of an organism or cell.Point Mutation: A mutation caused by the substitution of one nucleotide for another. This results in the DNA molecule having a change in a single base pair.Melanoma: A malignant neoplasm derived from cells that are capable of forming melanin, which may occur in the skin of any part of the body, in the eye, or, rarely, in the mucous membranes of the genitalia, anus, oral cavity, or other sites. It occurs mostly in adults and may originate de novo or from a pigmented nevus or malignant lentigo. Melanomas frequently metastasize widely, and the regional lymph nodes, liver, lungs, and brain are likely to be involved. The incidence of malignant skin melanomas is rising rapidly in all parts of the world. (Stedman, 25th ed; from Rook et al., Textbook of Dermatology, 4th ed, p2445)gp100 Melanoma Antigen: A melanosome-associated protein that plays a role in the maturation of the MELANOSOME.Cancer Vaccines: Vaccines or candidate vaccines designed to prevent or treat cancer. Vaccines are produced using the patient's own whole tumor cells as the source of antigens, or using tumor-specific antigens, often recombinantly produced.MART-1 Antigen: A melanosome-specific protein that plays a role in the expression, stability, trafficking, and processing of GP100 MELANOMA ANTIGEN, which is critical to the formation of Stage II MELANOSOMES. The protein is used as an antigen marker for MELANOMA cells.Antigens, Neoplasm: Proteins, glycoprotein, or lipoprotein moieties on surfaces of tumor cells that are usually identified by monoclonal antibodies. Many of these are of either embryonic or viral origin.

Small molecule inhibitors of Apaf-1-related caspase- 3/-9 activation that control mitochondrial-dependent apoptosis. (1/62)

Apoptosis is a biological process relevant to human disease states that is strongly regulated through protein-protein complex formation. These complexes represent interesting points of chemical intervention for the development of molecules that could modulate cellular apoptosis. The apoptosome is a holoenzyme multiprotein complex formed by cytochrome c-activated Apaf-1 (apoptotic protease-activating factor), dATP and procaspase-9 that link mitochondria disfunction with activation of the effector caspases and in turn is of interest for the development of apoptotic modulators. In the present study we describe the identification of compounds that inhibit the apoptosome-mediated activation of procaspase-9 from the screening of a diversity-oriented chemical library. The active compounds rescued from the library were chemically optimised to obtain molecules that bind to both recombinant and human endogenous Apaf-1 in a cytochrome c-noncompetitive mechanism that inhibits the recruitment of procaspase-9 by the apoptosome. These newly identified Apaf-1 ligands decrease the apoptotic phenotype in mitochondrial-mediated models of cellular apoptosis.  (+info)

ARK, the Apaf-1 related killer in Drosophila, requires diverse domains for its apoptotic activity. (2/62)

In mammals and Drosophila, apoptotic caspases are under positive control of the CED-4-like proteins Apaf-1 and ARK, respectively. In an EMS-mutagenesis screen, we isolated 33 ark mutants as recessive suppressors of hid-induced apoptosis. The ark mutants are loss-of-function alleles characterized by reduced developmental apoptosis. Using the phenotypic series of these alleles, we identified helical domain I in the nucleotide oligomerization domain as critical for ARK's apoptotic activity. Interestingly, the WD40 region may also have an unanticipated positive requirement for the apoptotic activity of ARK. Considering structural information, we discuss the roles of these domains for assembly and activity of the ARK apoptosome, and propose that the WD40 region is anti-apoptotic in the absence of apoptotic signals, and pro-apoptotic in the presence of such signals. Furthermore, a defined null allele reveals that ark is required for most, but not all apoptosis suggesting the existence of an ARK-independent apoptotic pathway.  (+info)

Apoptosome dependent caspase-3 activation pathway is non-redundant and necessary for apoptosis in sympathetic neurons. (3/62)

Although sympathetic neurons are a well-studied model for neuronal apoptosis, the role of the apoptosome in activating caspases in these neurons remains debated. We find that the ability of sympathetic neurons to undergo apoptosis in response to nerve growth factor (NGF) deprivation is completely dependent on having an intact apoptosome pathway. Genetic deletion of Apaf-1, caspase-9, or caspase-3 prevents apoptosis after NGF deprivation, and importantly, allows these neurons to recover and survive long-term following readdition of NGF. The inability of caspase-3 deficient sympathetic neurons to undergo apoptosis is particularly striking, as apoptosis in dermal fibroblasts and cortical neurons proceeds even in the absence of caspase-3. Our results show that in contrast to dermal fibroblasts and cortical neurons, sympathetic neurons express no detectable levels of caspase-7. The strict requirement for an intact apoptosome, coupled with a lack of effector caspase redundancy, provides sympathetic neurons with a markedly increased control over their apoptotic pathway.  (+info)

The marine product cephalostatin 1 activates an endoplasmic reticulum stress-specific and apoptosome-independent apoptotic signaling pathway. (4/62)

Cephalostatin 1, a bis-steroidal marine natural product, has been reported to induce apoptosis without the requirement of an active caspase-8 or mitochondrial cytochrome c release and apoptosome formation. Here we show that despite the absence of these events, caspase-9 activation is essential for cephalostatin 1-induced apoptosis. Cephalostatin 1 initiates a rapid endoplasmic reticulum stress response characterized by phosphorylation of eukaryotic initiation factor-2 alpha-subunit and increased expression of the chaperone immunoglobulin heavy chain-binding protein GRP78 as well as the transcription factor C/EBP homologous protein (CHOP)/GADD153. Cephalostatin 1 activates apoptosis signal-regulating kinase 1 and c-Jun N-terminal kinase (JNK). However, this pathway does not play a major role in cephalostatin 1-induced apoptosis, as assessed by stable expression of a dominant negative apoptosis signal-regulating kinase 1. Importantly, the endoplasmic reticulum-associated caspase-4 is required and as shown by biochemical and genetic inhibition experiments, acts upstream of caspase-9 in cephalostatin-induced apoptosis.  (+info)

Apoptosome: a platform for the activation of initiator caspases. (5/62)

Apoptosome refers to the adaptor protein complex that mediates the activation of an initiator caspase at the onset of apoptosis. In mammalian cells, caspase-9, caspase-8, and caspase-2 rely on the apoptotic protease-activating factor 1 (Apaf-1)-apoptosome, death-inducing signaling complex (DISC), and PIDDosome, respectively, for activation. In Drosophila, activation of the caspase-9 homolog Dronc requires assembly of an apoptosome comprised of Dark/Hac-1/Dapaf-1. In Caenorhabditis elegans, activation of the caspase CED-3 is facilitated by the CED-4-apoptosome. Recent biochemical and structural investigation revealed significant insights into the assembly and function of the various apoptosomes. Nonetheless, conclusive mechanisms by which the initiator caspases are activated by the apoptosomes remain elusive. Several models have been proposed to explain the activation process. The induced proximity model summarizes the general process of initiator caspase activation. The proximity-driven dimerization model describes how initiator caspases respond to induced proximity and offers an explanation for their activation. Regardless of how initiator caspases are activated, enhanced activity must be correlated with altered active site conformation. The induced conformation model posits that the activated conformation for the active site of a given initiator caspase is attained through direct interaction with the apoptosome or through homo-oligomerization facilitated by the apoptosome.  (+info)

Bcl2L12 inhibits post-mitochondrial apoptosis signaling in glioblastoma. (6/62)

Glioblastoma (GBM) is an astrocytic brain tumor characterized by an aggressive clinical course and intense resistance to all therapeutic modalities. Here, we report the identification and functional characterization of Bcl2L12 (Bcl2-like-12) that is robustly expressed in nearly all human primary GBMs examined. Enforced Bcl2L12 expression confers marked apoptosis resistance in primary cortical astrocytes, and, conversely, its RNA interference (RNAi)-mediated knockdown sensitizes human glioma cell lines toward apoptosis in vitro and impairs tumor growth with increased intratumoral apoptosis in vivo. Mechanistically, Bcl2L12 expression does not affect cytochrome c release or apoptosome-driven caspase-9 activation, but instead inhibits post-mitochondrial apoptosis signaling at the level of effector caspase activation. One of Bcl2L12's mechanisms of action stems from its ability to interact with and neutralize caspase-7. Notably, while enforced Bcl2L12 expression inhibits apoptosis, it also engenders a pronecrotic state, which mirrors the cellular phenotype elicited by genetic or pharmacologic inhibition of post-mitochondrial apoptosis molecules. Thus, Bcl2L12 contributes to the classical tumor biological features of GBM such as intense apoptosis resistance and florid necrosis, and may provide a target for enhanced therapeutic responsiveness of this lethal cancer.  (+info)

Essential postmitochondrial function of p53 uncovered in DNA damage-induced apoptosis in neurons. (7/62)

In postmitotic sympathetic neurons, unlike most mitotic cells, death by apoptosis requires not only the release of cytochrome c from the mitochondria, but also an additional step to relieve X-linked inhibitor of apoptosis protein (XIAP)'s inhibition of caspases. Here, we examined the mechanism by which XIAP is inactivated following DNA damage and found that it is achieved by a mechanism completely different from that following apoptosis by nerve growth factor (NGF) deprivation. NGF deprivation relieves XIAP by selectively degrading it, whereas DNA damage overcomes XIAP via a p53-mediated induction of Apaf-1. Unlike wild-type neurons, p53-deficient neurons fail to overcome XIAP and remain resistant to cytochrome c after DNA damage. Restoring Apaf-1 induction in p53-deficient neurons is sufficient to overcome XIAP and sensitize cells to cytochrome c. Although a role for p53 in apoptosis upstream of cytochrome c release has been well established, this study uncovers an additional, essential role for p53 in regulating caspase activation downstream of mitochondria following DNA damage in neurons.  (+info)

Analysis of apoptosome dysregulation in pancreatic cancer and of its role in chemoresistance. (8/62)

The apoptosome is a multiprotein complex mediating the mitochondrial pathway of cell death. Its importance during development has been clearly demonstrated by knocking out key genes in mouse. APAF1 is the core protein of the apoptosome and its dosage is also critical in various cancer types, i.e., melanoma, germ line tumor, gastrointestinal cancer and B-type chronic lymphocytic leukemia. This is generally due to inactivation of the APAF1 locus by epigenetic phenomena or by activity of promoter regulators. We investigated the putative roles of the apoptosome in pancreatic ductal adenocarcinoma (PDAC). We found that both APAF1 mRNA and protein are dysregulated in human PDAC samples. Similarly, several PDAC cell lines exhibited variable levels of both APAF1 protein and mRNA. The response to cell death induction and its biochemical features were assessed by treatment of each line with commonly used chemotherapeutic agents. We found that the apoptosome pathway was not functional in most cell lines upon cytochrome c release from mitochondria. In addition, we restored APAF1 and Caspase-9 dosage in Panc-1 cells, where the apoptosome is downregulated, by overexpressing the murine cDNA of the two molecules, and we improved the death response to chemotherapeutic agents.  (+info)

TY - JOUR. T1 - Caspase-mediated cleavage of HuR in the cytoplasm contributes to pp32/PHAP-I regulation of apoptosis. AU - Mazroui, Rachid. AU - Di Marco, Sergio. AU - Clair, Eveline. AU - Von Roretz, Christopher. AU - Tenenbaum, Scott A.. AU - Keene, Jack D.. AU - Saleh, Maya. AU - Gallouzi, Imed Eddine. PY - 2008/1/14. Y1 - 2008/1/14. N2 - The RNA-binding protein HuR affects cell fate by regulating the stability and/or the translation of messenger RNAs that encode cell stress response proteins. In this study, we delineate a novel regulatory mechanism by which HuR contributes to stress-induced cell death. Upon lethal stress, HuR translocates into the cytoplasm by a mechanism involving its association with the apoptosome activator pp32/PHAP-I. Depleting the expression of pp32/PHAP-I by RNA interference reduces both HuR cytoplasmic accumulation and the efficiency of caspase activation. In the cytoplasm, HuR undergoes caspase-mediated cleavage at aspartate 226. This cleavage activity is ...
Apoptosis is a controlled form of cellular demolition, catalyzed by a family of cysteine proteases called caspases. In response to diverse proapoptotic stimuli, caspase-9 is recruited and activated within an oligomeric complex called the apoptosome. The apoptosome drives autocatalytic processing of caspase-9, triggering a proteolytic caspase cascade that results in the biochemical and morphological changes characteristic of cell death. It is unclear why caspase-9 undergoes autocatalytic processing following apoptosome recruitment, because interdomain processing is dispensable for caspase-9 activity. A study has shed light on this issue by demonstrating that caspase-9 processing within the apoptosome promotes its displacement from the complex, leading to inactivation of this protease. Thus, autoprocessing of caspase-9 within the apoptosome serves as a "molecular timer" that limits the proteolytic activity of this complex through displacement of bound caspase-9 molecules. This timer mechanism may ...
Apoptotic signaling is altered at many loci in cancer cells. Although many tumors develop resistance to cytochrome c-induced apoptosis, we have discovered that breast cancer cells exhibit a unique hypersensitivity to cytochrome c-induced apoptosis. Interestingly, this sensitivity is not due to changes in core apoptosomal proteins ( 44) but is due to a PHAPI-mediated posttranslational event that enhances the recruitment of caspase-9 to the Apaf-1 CARD. These findings have the potential to affect breast cancer chemotherapy through the development of apoptosome activators or cytochrome c mimetics as shown, in principle, by the fact that malignant mammary epithelial cells could be more easily killed by cytosolic cytochrome c than their normal counterparts.. PHAPI-mediated increase in caspase activation in breast cancer. Whereas many inhibitory signaling pathways converge on the apoptosome, there are very few physiologic/pathologic examples of enhanced apoptosome activation. Our data suggest that ...
Common Atom functions. module Language.Atom.Common ( -- * Timers Timer , timer , startTimer , startTimerIf , timerDone -- * One Shots , oneShotRise , oneShotFall -- * Debouncing , debounce -- * Lookup Tables , lookupTable -- * Hysteresis , hysteresis ) where import Data.Word import Language.Atom.Language -- , A Timer. data Timer = Timer (V Word64) -- , Creates a new timer. timer :: Name -, Atom Timer timer name = do timer ,- word64 name 0 return $ Timer timer -- , Starts a Timer. A timer can be restarted at any time. startTimer :: Timer -, E Word64 -, Atom () startTimer t = startTimerIf t true -- , Conditionally start a Timer. startTimerIf :: Timer -, E Bool -, E Word64 -, Atom () startTimerIf (Timer t) a time = t ,== mux a (clock + time) (value t) -- , True when a timer has completed. timerDone :: Timer -, E Bool timerDone (Timer t) = value t ,=. clock -- , One-shot on a rising transition. oneShotRise :: E Bool -, Atom (E Bool) oneShotRise a = do last ,- bool "last" False last ,== a return $ ...
Reactome is pathway database which provides intuitive bioinformatics tools for the visualisation, interpretation and analysis of pathway knowledge.
Hi all [smile] Im learning loads from the Maybies discussions, but wanted to ask a few dim questions without taking hijacking their thread! Im 16
:babydust1:Why does it take 50 million sperm to fertilize one egg?:babydust1: Because they wont ask for directions either! August 1st - AnnieJ 2nd - page 76
Bcl-xL is an antiapoptotic Bcl-2 family member that is required for embryonic development and can contribute to cancer cell survival (Letai, 2008; Hardwick and Youle, 2009). The traditional viewpoint is that anti- and proapoptotic Bcl-2 family proteins actively engage each other to determine cell fate after a death stimulus (Galonek and Hardwick, 2006; Youle and Strasser, 2008). The best-characterized cell survival activity of Bcl-xL is its ability to inhibit Bax-induced pores in the outer mitochondrial membrane (Billen et al., 2008). In this manner, Bcl-xL prevents release of mitochondrial cytochrome c into the cytoplasm, where cytochrome c induces apoptosome formation to trigger caspase-dependent death of mammalian cells. Attention has been focused on the functional interactions and the binding specificities between anti- and proapoptotic Bcl-2-related proteins, leading to new therapeutic strategies (Oltersdorf et al., 2005).. The evolutionary conservation of Bcl-2-like proteins cannot be ...
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I am not sure if this is even a valid bug; my brother killed another player in Stendhal 1.05 (private server) some time ago and he was waiting for the 2-week-expiration. He told me that apparently the timer has been reset to 2 weeks whenever he bought an outfit ( http://stendhalgame.org/wiki/Stendhal_Games#Hiring_special_outfits ) and that outfit expired. It might also have been a server restart which resetted the timer. Whatever it was: if he is right and didnt attack anyone, there seems to be a bug which resets the timer.. I know that bug reports like this one are not as helpful as others, but if this is a valid bug, the report might help anyway. ;-). ToBeFree ...
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APAF1兔多克隆抗体(ab2001)可与小鼠, 大鼠, 人样本反应并经WB, IHC, ICC/IF实验严格验证,被7篇文献引用。所有产品均提供质保服务,中国75%以上现货。
The apoptosome is the cellular structure that facilitates programmed cell death. A new 3D map of it lays groundwork for future drug development.
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While it may be an old timer in the tuner world, the Dodge Challenger is still getting plenty of 2009 SEMA show limelight. The Challenger package as a whole works well and as you can see, a few notable SEMA tuners tend to agree.
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After a dozen years of use, our washing machine no longer works during what should be the spin cycle. The timer will need replacement, but can be given a...
Oralt Voksne. 1 strøget doseringsmål (ca. 15 g) 3-4 gange dgl. Ved P-kalium > 6 mmol/l gentages dosis med 1-2 timers mellemrum, indtil P-kalium er < 5 mmol/l. Rektalt 30 g opblandet i 150 ml laktulose eller methylcellulose. Opløsningen skal forblive i tarmen i minimum 30-45 min. - hvis muligt op til 9 timer. ...
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Hotels near Tango Bar, Fira on TripAdvisor: Find 37,189 traveler reviews, 15,030 candid photos, and prices for 165 hotels near Tango Bar in Fira, Greece.
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ON ANOTHER note!!! I want to congratulate ALL of you guys on this blog! I think that you ALL worked GREAT with one another!!! I think that you all stuck with the problem and tried to really solve this ongoing delima for some T drivers. It was good to hear your problems and trials and errors. This is how you solve problems that can drive a fella crazy trying to solve a driving problem. Part of the problems I had and never did try to tour any of my cars as I was tired of having problems and not fun when I tried to travel 50 to 100 miles in one of my Ts! I am reading a lot of what you guys say and maybe Ill try to dive one of mine further than 30 miles this time around. ???? Timer problems were one of my pet peeves. I have used all of the timers except the electronic one that costs 400.00. I also have a couple of distributors in my stock piles but I just cant put one of them on a real restored T. Nor OHV heads,or down draft carbs either. WHY? I don/t know as I have real hot rod and muscle cars ...
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|p|The Model CST-440 Capillary Suction Timer (CST) consists of a digital timer, sample cell, and a specially selected filter paper composed of unidirectional fibers|/p|
Rosewood: TV Tango is your complete reference guide for Rosewood. Episode listings, photos, DVDs, videos, downloads, show information, links and much more.
The Dimplex 400W low wattage panel heater is an ideal background heating solution for rooms where there is the need to keep a chill off, such as hallways or small bedrooms. Slimline and simple to use, this low output freestanding panel heater has a 24 hour timer with single heat setting operated by a side switch and comes complete with fitted plug. Comes with a 3 year guarantee.. This product is only suitable for well insulated spaces or occasional use. ...
Mitochondria are involved either directly or indirectly in oncogenesis and the alteration of metabolism in cancer cells. Cancer cells contain large numbers of abnormal mitochondria and produce large amounts of reactive oxygen species (ROS). Oxidative stress is caused by an imbalance between the production of ROS and the antioxidant capacity of the cell. Several cancer therapies, such as chemotherapeutic drugs and radiation, disrupt mitochondrial homeostasis and release cytochrome c, leading to apoptosome formation, which activates the intrinsic pathway. This is modulated by the extent of mitochondrial oxidative stress. The peroxiredoxin (Prx) system is a cellular defense system against oxidative stress, and mitochondria in cancer cells are known to contain high levels of Prx III. Here, we review accumulating evidence suggesting that mitochondrial oxidative stress is involved in cancer, and discuss the role of the mitochondrial Prx III antioxidant system as a potential target for cancer therapy. We hope
playlists (72) Tango history (50) cortinology (14) tango festivals (10) DJ resources (9) pearls of wisdom (8) Francisco Canaro (7) Russian tango (6) folk music history (6) tango statistics (6) Carlos di Sarli (5) Donato Racciatti (5) Miguel Calo (5) Pedro Laurenz (5) alternative music (5) tango foxtrot (5) tango orchestras (5) Argentine food (4) Dia del Tango (4) Enrique Rodriguez (4) Ojos negros que fascinan (4) empanadas (4) Adolfo Carabelli (3) Edgardo Donato (3) Federico Scorticati (3) Juan DArienzo (3) Lucio Demare (3) Maruja Pacheco (3) Mountain Milonga Retreat 2015 (3) Osvaldo Pugliese (3) Sebastian Piana (3) chacarera (3) tango musicality (3) Alberto Besprosvan (2) Alberto Podesta (2) Baile del Internado (2) Ben Molar (2) Daniel Diaz (2) Eddie Rosner (2) Erskine Maytorena (2) Lita Morales (2) Mountain Milonga Retreat 2014 (2) Osvalso Fresedo (2) Palais de Glace (2) Pedro Maffia (2) Piotr Leschenko (2) Poema (2) QTANGO (2) Raúl Kaplún (2) Roberto Firpo (2) Rodolfo Biagi (2) Romeo ...
This gene encodes a member of the cysteine-aspartic acid protease (caspase) family. Sequential activation of caspases plays a central role in the execution-phase of cell apoptosis. Caspases exist as inactive proenzymes which undergo proteolytic processing at conserved aspartic residues to produce two subunits, large and small, that dimerize to form the active enzyme. This protein can undergo autoproteolytic processing and activation by the apoptosome, a protein complex of cytochrome c and the apoptotic peptidase activating factor 1; this step is thought to be one of the earliest in the caspase activation cascade. This protein is thought to play a central role in apoptosis and to be a tumor suppressor. Alternative splicing results in multiple transcript variants. [provided by RefSeq, May 2013 ...
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I remember my first tango festival like it was yesterday. I was attending the Denver Labor Day festival with my friend Richard and had no idea what to expect. He prepared me the best he could but I still felt like I was in another world once I walked in. So many classes. I took them all! Every single class. So many hours of milongas! I danced every single moment possible. The only break I had was the evening break scheduled in the event meant for eating. I slept very little. When I returned I needed 2 full days to recover from sleep deprivation and another week to readjust my body to normal activity. Many of you may have already perfected your action plan for long tango weekends, but for those of you who may be new or rusty, here are some tips that I follow. 1. Get plenty of exercise, rest properly, and eat healthy meals in the week leading up to the event. Now this one is a general life tip, but its especially pertinent when you need to be at the top of your game during a tango weekend. Being ...
The classical tango is a dance characterized by a 2/4 or 4/4 rhythm in which the partners dance in a coordinated way, allowing dynamic contact. There is a surprising similarity between the tango and how KCNE β-subunits
The UTL882 kitchen clock and timer with magnet, pocket clip and stand has a countdown capacity of 24 Hours. The memory timer allows you to store a p
The Medicines Company (NASDAQ:MDCO) today announced that new data from its TANGO II study of VABOMERE (meropenem and vaborbactam) will be presented th
Book now at Tango Bistro in Bryn Mawr, PA. Explore menu, see photos and read 1171 reviews: Very tasty and great service. The place is very warm and inviting
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This serie description Ar Florascent Tu esi princese, kura rotaļājas plaukstošu rožu ziedu okeānā. Vai arī karaliene jasmīns - eleganta un cienīga! Vai bagāta kā austrumu šeihs, vai vieda kā indiešu guru. Baudi svaigu vēja brīzi uz baltas jahtas klāja Vidusjūras saulē, pastaigas Ķīnas imperatora ziedošajā dārzā vai dejo kaislīgu tango tveicīgā Spānijas piepilsētā. Ceļo, pārvērties un parādi savas personības dižciltību! Parfimērijas māksla un tradicionālas metodes, ko, gatavojot parfīmus aristokrātiem izmantoja 17.gs. Francijā, šodien atdzīvojušās vācu meistaru radītajos daudzveidīgajos un valdzinošajos Florascent aromātos. Florascent tualetes ūdeņi: • izgatavoti tikai no dabīgām izejvielām - izsmalcinātām augtākās kvalitātes augu esencēm un ēteriskajām eļļām; • nesatur ftalātus, naftas ķīmiju, sintētiskas vielas, dzīvnieku izcelsmes vielas; nav testēti uz dzīvniekiem; • teicama noturība panākta tikai ar ...
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In the previous two parts (1)(2), I described the directed evolution of fast folding fluorescent proteins. But why is it important? Why do we need fast folding GFP? Why do we need to know the maturation time? For most applications, it usually doesnt matter. If we express these proteins constitutively, then we should already have…
Vurdering av hudens fuktighet med et Corneometer som hovedparameter, vurdering av barriere-funksjon med et Vapometer som sekundært parameter. Deltakerne vasket sine underarmer med såpe 2 timer før målingene ble utført. Utgangsmålinger ble gjort med intrumentene. Bio-Oil og en referanseolje ble deretter applisert på ulike steder på undersiden av underarmen hos alle deltakere. Det ble gjort nye målinger igjen umiddelbart etter applisering av produktet samt 2 timer senere, både før og etter at produktene ble tørket av. Et ubehandlet kontrollområde ble også målt samtidig ...
Vurdering av hudens fuktighet med et Corneometer som hovedparameter, vurdering av barriere-funksjon med et Vapometer som sekundært parameter. Deltakerne vasket sine underarmer med såpe 2 timer før målingene ble utført. Utgangsmålinger ble gjort med intrumentene. Bio-Oil og en referanseolje ble deretter applisert på ulike steder på undersiden av underarmen hos alle deltakere. Det ble gjort nye målinger igjen umiddelbart etter applisering av produktet samt 2 timer senere, både før og etter at produktene ble tørket av. Et ubehandlet kontrollområde ble også målt samtidig ...
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Download bloom, bud, flower, herb, leaves, magic, plant icon in .PNG or .ICO format. Icon designed by Yury Velikanov found in the icon set Magic flowers
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TABLE-US-00001 CODE APPENDIX ;; Assembly code for PillSafe ;; list p=12f675 include "p12f675.inc" timer_cnt equ 0x20 isr_w_save equ 0x21 isr_status_save equ 0x22 WAIT_H equ 0x23 WAIT_L equ 0x24 CNT1 equ 0x25 CNT0 equ 0x26 GP_SOLENOID equ 0x0 GP_BUTTON_USER equ 0x1 GP_LED equ 0x2 GP_BUTTON_DONE equ 0x3 _CONFIG _CPD_OFF & _CP_OFF & _BODEN_OFF & _MCLRE_OFF & _PWRTE_OFF & _WDT_OFF & _INTRC_OSC_NOCLKOUT goto main org 0x004 dispatch_interrupt: ;; save W, STATUS movwf isr_w_save swapf STATUS, W ; swapf does not affect status reg. movwf isr_status_save btfsc PIR1, TMR1IF ; did we get here because of a timer1 overflow? call timer1_isr btfsc INTCON, GPIF ; interrupt on GPIO pin? call gpio_change_isr ;; restore W, Status swapf isr_status_save, W movwf STATUS swapf isr_w_save, F ; swapf does not affect STATUS swapf isr_w_save, W retfie timer1_isr: ;; clear timer interrupt flag, and set timer_cnt flag bcf PIR1, TMR1IF ; bsf timer_cnt, 0 return gpio_change_isr: ;; read from GPIO to prevent GPIF getting set ...
3050 - Tango. Deeply lobed and frilly, similar to endive with a light pale-green color, oak leaf shape and lofty texture. Makes a small, compact head. Harvest e
After checking on Falls of Clyde this morning, I walked down the street to Pier 13. Tango II is still there, tied to a barge. A previous post about the vessel: High and Dry
I have a Rival deep fryer Model CZF630-CN,the timer plastic button is broken can you tell me where i can find one - Rival CZF630 Deep Fryer question
C.A.P. Custom Automated Products: REPLACEMENT PROBE, 3 CABLE [MTR-RP3] - pH, EC, PPM & TDS Testers - Meters, Timers & Instruments - Gardening & Hydroponics Store -
Okay so Im a first timer as far as incubating chicken eggs so I filled my incubator a lg still air that I installed a PC fan in and Im hand turning...
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Our policies on the use of a remote rating form on your web site are very strict. If we find a web site in violation of the acceptable terms, we have the right to ...
4. To automatically collect results set a script trigger by Tools -, Script Editor then Triggers -, Current scripts triggers... -, No trigger set up. Click here to add one now. Then select collectTweets for Run and Time-driven for Events and choose Day timer for dailly updates or Week timer for weekly ...
I was quite daunted when I went to make my first order, so I figured id post up for people who dont know where to start: I like these guys. If...
My RNY was 7 yrs. ago. I originally lost 113 (18 lbs. short of my goal weight) then gained 40 lbs. in the last 2 years. On July 7th this year I had a stomaphyx...
Well, for me the timer is a week ahead of me actually finishing the game. Someone slow time down for e the next week. I need 36 hours in each of the next two days ...
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Michelle Williams has revealed that she is open to a Dawsons Creek reunion.. The actress, who was nominated for an Oscar this year for her portrayal of Marilyn Monroe in My Week With Marilyn, played Jen Lindley in the smash hit 90s teen drama. And responding to co-star James Van Der Beeks interest in reuniting the cast, Williams has now said she is "totally up" for the idea.. ...
Finnish tango, or FINtango,[1] music is an established variation of the Argentine tango but whose rhythm follows the Ballroom tango. It was one of the most popular music forms for decades in Finland. Brought to Europe in the 1910s, and to Finland itself in 1913,[1] by travelling musicians, Finns began to take up the form and write their own tangos in the 1930s.[2] The first Finnish tango was written by Emil Kauppi in 1914 for a film called Salainen perintömääräys (meaning The Secret Testament). It features a typical Finnish rhythm pattern with habanera. In the 1920s the tango was danced exclusively by Helsinkis bohemians.[1] By the 1940s about half of the entries on the popular music charts were occupied by tangos, and the post war period saw tangos spread from a popular urban phenomenon to their enthusiastic adoption by the countryside as well.[3] Finnish tango peaked in the late 1950s and early 1960s.[1] Special characteristics of Finnish tango include the change of rhythm to beguine ...
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Dance your way to ecstasy with luxurious glide and slippery smooth sensations. Passionately pink Tango Jazzy Power Vibe is made of special skin-safe gelatin rubber to provide stretch and resilience and will deliver new exciting erotic experience.
In the United States education in this field is not as universally organized - some universities have solid programs in dance medicine, but most do not. The people that I know in the field, in the US and in other countries, have forged their own path and sought education from a variety of sources - which is now what I find myself doing. Im working with my tango teacher, Daniela Arcuri, to get a picture of what is really needed in my own community, and with other teachers and mentors around the world to get an idea of what education is available and appropriate to the program I am trying to create ...
Im using OpenGL timers to benchmark some of the render stages in my program. Each render stage has its own query object and is rendered independently of the other stages. My code looks something like this: GLuint queryObjectFirst; GLuint queryObjectSecond; glGenQueries(1, &queryObjectFirst); glGenQueries(1, &queryObjectSecond);
Im using OpenGL timers to benchmark some of the render stages in my program. Each render stage has its own query object and is rendered independently of the other stages. My code looks something like this: GLuint queryObjectFirst; GLuint queryObjectSecond; glGenQueries(1, &queryObjectFirst); glGenQueries(1, &queryObjectSecond);
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Svarer til de enkelte indholdsstoffer: Tamsulosin: Biotilgængelighed ca. 70-79%. Absorptionsgrad og -hastighed øges ved samtidig fedtholdig fødeindtagelse. Maksimal plasmakoncentration nås i løbet af 4-6 timer. Fordelingsvolumen ca. 0,23 l/kgl . Metaboliseres i leveren. Plasmahalveringstid ca. 10 timer. Solifenacin: Biotilgængelighed ca. 90%. Maksimal plasmakoncentration nås efter 3-8 timer. Fordelingsvolumen ca. 8,58 l/kg. Metaboliseres i leveren via CYP3A4 til delvis aktive metabolitter. Udskilles gennem nyrerne. ...
Flylady.net is a great website founded by Marla Cilley. I actually have followed the site for years, but not down to the tee. But I do several things Marla suggests. One thing that really helps is setting a timer for 15 minutes. Sometimes I will look at a mess and get so overwhelmed, I dont even want to start. She says, just tell yourself you will work on it for 15 minutes. It is amazing what you can get done in 15 minutes! Sometimes the task you have been procrastinating doesnt even take 15 minutes but you have thought about it for days instead of just doing it! Also, once the timer goes off, you may be really getting into it, so it is ok to keep setting it for another 15 minutes! And you can take breaks! I still do this today-even did it to start writing this blog entry. Set my timer to make myself get started! And now I cant seem to stop.. Another Flylady technique is having an evening and morning routine. Flylady is big on having a clean kitchen sink. So every night I get the dishes ...
Svarer til de enkelte indholdsstoffer: Tamsulosin: Biotilgængelighed ca. 70-79%. Absorptionsgrad og -hastighed øges ved samtidig fedtholdig fødeindtagelse. Maksimal plasmakoncentration nås i løbet af 4-6 timer. Fordelingsvolumen ca. 0,23 l/kgl . Metaboliseres i leveren. Plasmahalveringstid ca. 10 timer. Solifenacin: Biotilgængelighed ca. 90%. Maksimal plasmakoncentration nås efter 3-8 timer. Fordelingsvolumen ca. 8,58 l/kg. Metaboliseres i leveren via CYP3A4 til delvis aktive metabolitter. Udskilles gennem nyrerne. ...
(Intro - Kanobby & A$AP Ferg) Making money for the long term Off these words Yeah, yeah give me one more, one more Were getting more and getting more
Not too long ago, one of my favorite Chattanooga writers was taking a timeout from putting an article together. During that break, he Tweeted an article hed found titled: Why Writers Are the Worst Procrastinators. The link flashed across my iPhone screen while I was, conveniently, taking my own pause from work. Of course, I clicked the link, thus procrastinating the project I was supposed to be completing a little longer.
A syringe apparatus for use with balloon-tipped catheters is disclosed having a pressure gauge and timer assembly. In one mode, the timer assembly displays the duration of a current event of inflation or deflation, and the duration of the most recent past event of inflation or deflation. In another mode, the timer assembly displays historical information showing the event number and duration of past events of inflation and deflation. The pressure gauge display and the timer assembly display are situated conveniently on the syringe assembly and in proximity to one another so as to enable a syringe operator to substantially simultaneously monitor durations of inflation and deflation without the need for an assistant, yet without requiring purchase or use of computerized monitors. In another mode, the timer assembly can be detached from the syringe assembly at the completion of an inflation procedure and then reused with another syringe assembly. In this mode, the pressure gauge is permanently mounted to
0088] FIG. 20 illustrates a flow diagram of an embodiment for detecting pulses using the pace detection circuitry illustrated in FIG. 19. State 1, represented at 2001, is a state in which the circuit waits for the first pulse. If the first pulse is positive, three timers are started and the circuit enters State 2P, represented at 2002. These timers include a first timer identified as a really short timer (RST), a second timer identified as a short timer (ST), and a third timer identified as a long timer (LT). The names given to these timers represent a manner of degree, and are not intended to be limiting. State 2P is a state in which the circuit waits for the first timer (RST) to expire. The end of the time represented by RST represents a beginning of a time frame for an expected negative pulse to occur after the positive pulse sensed at 2001. Once the first timer expires, the circuit enters State 3P, represented at 2003, which is a state in which the circuit waits for the expected negative ...
Research Dancing the Argentine tango could have potential benefits for people at certain stages in the development of Parkinsons disease, according to findings in a new study by researchers at McGill, the Montreal Neurological Institute and Hospital, and and the Research Institute of the McGill University Health Centre. The study looked at changes in patients motor abilities following a 12-week tango course, and is also the first study to assess the effect that tango has on non-motor symptoms.. ...
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Watch this video to learn about wide variety uses for the Bruker Optics TANGO System for Instant FT-NIR Identification and Quantification of Constituents in Food, Feed, Polymer, Chemical and Pharma Applications.
at MJM Magic O-Korto Box Set by Tango - Trick - Your O-Korto Box set consists of (1) Okito Coin Box, (1) German Coin Box, and a Small Box.
At the top of the Tango music scene, the orchestra founded in Italy in 2008 by Mariano Speranza leads an international career with over 500...
|p|The Adorne SensaSwitch 60 Minute Timer Sensor Switch 15A is proof that simple doesnt have to mean boring. With a Manual-ON/Timed-OFF function, the Adorne ASTM2M2 allows you to turn lights on when you enter a room and automatically turns them off at a
I hit the tango scene last night too as I was feeling better. Also tonight after the rawk jim. Weve been doing this group thing that has morphed into me teaching which Im not that into. So I think well do a couple more Thursdays and be done with it. Its been a pretty sweet last six months or so with that whole scene. Theres this famous teacher who came up here to live for a few months and I have this whole bromance thing going on with him and rock it now with the tango ladies as a result ...
I hit the tango scene last night too as I was feeling better. Also tonight after the rawk jim. Weve been doing this group thing that has morphed into me teaching which Im not that into. So I think well do a couple more Thursdays and be done with it. Its been a pretty sweet last six months or so with that whole scene. Theres this famous teacher who came up here to live for a few months and I have this whole bromance thing going on with him and rock it now with the tango ladies as a result ...
Here I go again lol!! I FINALLY found the specs for the lighting I have on my Current Ramp Timer Pro. Please tell me what you guys think. · 48-60
Wenger gets some relief as Chilean striker scores an opening goal with his hand before completing his brace from the penalty spot against Tigers
This leads to the formation of a Caspase activating multiprotein complex called the Apoptosome. Once activated, initiator ...
2006) The apoptosome activates caspase-9 by dimerization. Mol Cell 22: 269-275 Eckelman BP, Salvesen GS. (2006) The human anti- ... Biochem J 409, 461-469 Riedl, S. J. and Salvesen, G. S. (2007) The apoptosome: signalling platform of cell death. Nat Rev Mol ...
Using energy from the ATPs in the mitochondrion, the Apaf-1 and cytochrome C bind together to form apoptosomes. The apoptosomes ...
Saleh A, Srinivasula SM, Balkir L, Robbins PD, Alnemri ES (Aug 2000). "Negative regulation of the Apaf-1 apoptosome by Hsp70". ...
Upon binding cytochrome c and dATP, this protein forms an oligomeric apoptosome. The apoptosome binds and cleaves Procaspase 9 ... Zou H, Li Y, Liu X, Wang X (Apr 1999). "An APAF-1.cytochrome c multimeric complex is a functional apoptosome that activates ... Saleh A, Srinivasula SM, Balkir L, Robbins PD, Alnemri ES (Aug 2000). "Negative regulation of the Apaf-1 apoptosome by Hsp70". ... The precise mechanism for this reaction is still debated though work published by Guy Salvesen suggests that the apoptosome may ...
Apoptosis is contingent upon ATP levels to form the energy dependent apoptosome. A distinct biochemical event only seen in ...
... inhibits this process by blocking the recruitment of procaspase-9 to the Apaf-1/dATP/cytochrome c apoptosome complex. It ... "Heat-shock protein 70 inhibits apoptosis by preventing recruitment of procaspase-9 to the Apaf-1 apoptosome". Nature Cell ... which then recruits Apaf-1 and dATP/ATP into an apoptosome complex. This complex then cleaves procaspase-9, activating caspase- ...
Histone H1.2 also forms a complex with the apoptosome, possibly regulating its formation. GRCh38: Ensembl release 89: ...
Hu Q, Wu D, Chen W, Yan Z, Shi Y (May 2013). "Proteolytic processing of the caspase-9 zymogen is required for apoptosome- ... Processing occurs when the apoptosome binds to pro-caspase-9 as apaf-1 assists in the autoproteolytic processing of the zymogen ... Acehan D, Jiang X, Morgan DG, Heuser JE, Wang X, Akey CW (2002). "Three-dimensional structure of the apoptosome: implications ... Apoptotic signals cause the release of cytochrome c from mitochondria and activation of apaf-1 (apoptosome), which then cleaves ...
Analogous to the apoptosome, which activates apoptotic cascades, the inflammasome activates an inflammatory cascade. Once ...
... forming a complex called apoptosome. The activation of caspase 3 and 9 by the apoptosome starts a proteolitic cascade that ...
Chu ZL, Pio F, Xie Z, Welsh K, Krajewska M, Krajewski S, Godzik A, Reed JC (2001). "A novel enhancer of the Apaf1 apoptosome ... "A novel enhancer of the Apaf1 apoptosome involved in cytochrome c-dependent caspase activation and apoptosis". J. Biol. Chem. ...
2001). "A novel enhancer of the Apaf1 apoptosome involved in cytochrome c-dependent caspase activation and apoptosis". J. Biol ...
"Apoptosis initiated by Bcl-2-regulated caspase activation independently of the cytochrome c/Apaf-1/caspase-9 apoptosome". ...
... which then bind to pro-caspase-9 to create a protein complex known as an apoptosome. The apoptosome cleaves the pro-caspase to ... "Predominant suppression of apoptosome by inhibitor of apoptosis protein in non-small cell lung cancer H460 cells: therapeutic ...
This implies that DCC regulates a novel pathway for caspase activation, and that it is one that is apoptosome-independent. To ... This causes the activation of caspase-3 through caspase-9, and initiates apoptosis without the formation of an apoptosome or ...
... which then bind to pro-caspase-9 to create a protein complex known as an apoptosome. The apoptosome cleaves the pro-caspase to ... Yang L, Mashima T, Sato S (February 2003). "Predominant suppression of apoptosome by inhibitor of apoptosis protein in non- ...
Cytochrome c then forms a multi-protein complex known as the "apoptosome" and initiates activation of the caspase cascade ...
These components are essential for forming a ternary complex called the apoptosome that activates Caspase-3 downstream of the ...
Anoikis Apoptosis-inducing factor Apoptosis versus Pseudoapoptosis Apoptosome Apoptotic DNA fragmentation Autolysis (biology) ...
... may be activated by proteolysis through its association with a protein complex that forms apoptosome, or by granzyme B, or via ...
Apoptosis Apoptosome Bcl-2 Bcl-2-associated X protein (BAX) BH3 interacting domain death agonist (BID) Caspases Cytochrome c ...
Apoptosis Apoptosome Bcl-2 Bcl-2-associated X protein (BAX) BH3 interacting domain death agonist (BID) Caspases Cytochrome c ...
Apoptosis Apoptosome Bcl-2 homologous antagonist killer (BAK) Bcl-2-associated X protein (BAX) Bcl-xL BH3 interacting domain ...
... that precedes the release of the cytochrome c complex from the mitochondria and the formation of the apoptosome. The presence ... and Bcl-xL and up-regulates the pro-apoptotic proteins Bax and Bad that ultimately lead to the formation of the apoptosome. PD1 ...
The mammalian apoptosome had never been crystallized, but a human APAF-1/cytochrome-c apoptosome has been imaged at lower (2 nm ... The stable APAF-1 and cytochrome mutimeric complex fit this description, and is now called the apoptosome. The apoptosome was ... Recent structural studies of apoptosome prove that Apaf-1-ALT cannot form apoptosome as it misses key structural components for ... Because the resolution of the apoptosome structure was relatively low, two controversial models for apoptosome assembly were ...
... caspase-9 is recruited and activated within an oligomeric complex called the apoptosome. The apoptosome drives autocatalytic ... A study has shed light on this issue by demonstrating that caspase-9 processing within the apoptosome promotes its displacement ... This timer mechanism may enable cells to prevent low amounts of apoptosome activation from spiraling out of control unless ... Thus, autoprocessing of caspase-9 within the apoptosome serves as a "molecular timer" that limits the proteolytic activity of ...
Apoptosome dependent caspase-3 activation pathway is non-redundant and necessary for apoptosis in sympathetic neurons.. Wright ... Although sympathetic neurons are a well-studied model for neuronal apoptosis, the role of the apoptosome in activating caspases ... deprivation is completely dependent on having an intact apoptosome pathway. Genetic deletion of Apaf-1, caspase-9, or caspase-3 ... The strict requirement for an intact apoptosome, coupled with a lack of effector caspase redundancy, provides sympathetic ...
A cryo-electron microscopy model of the active human apoptosome illuminates how this wheel of death binds the protease ... 5) The authors structure of the platform of the pc-9 bound apoptosome and the unbound apoptosome recently reported by Zhou et ... The apoptosome and pc-9 activation. We have presented a structure for the central hub and extended arms of an active apoptosome ... Model of the active apoptosome.. (A, C) Top views are shown of the heptameric platform from the apoptosome model, with and ...
Autoprocessing of procaspase-9 reduces its affinity for the apoptosome. (A) Apoptosome complexes were assembled with decreasing ... E, F) Apoptosome-bound T7-tagged C9-p35/p12 or ProC9-TM were incubated with T7-tagged ProC9*-R56A and either T7-tagged ProC3* ... Each bar represents the mean of four separate experiments±s.e.m. (B) KM values for apoptosome-bound C9-p35/p12 (25 nM) and ... B) The initial velocities (V0) of apoptosome-bound C9-p35/p12, ProC9-TM, and C9-p35/p12-R56A on the substrate ProC3 were ...
This dysfunctional apoptosome activity was not correlated with any decrease of apoptosome component factors, but it was linked ... Here, we show that the apoptosome deficiency was observed in chemoresistant NSCLC NCI-H460 cells. No deficient apoptosome ... on the apoptosome activity of H460 cells and saw the low apoptosome activity dramatically reversed (Fig. 2C) ⇓ . Surprisingly, ... This apoptosome recruits and activates caspase-9, which in turn activates the executioner caspases, caspase-3 and caspase-7 (7 ...
Cytochrome c-mediated activation of the apoptosome was very efficient in naïve cell extracts as the apoptosome-processed, p35- ... Apoptosome-mediated cleavage of caspase-9 generates a 35-kD and a 12-kD fragment (Liu et al., 1996; Cain et al., 2002). ... Efficiency of apoptosome sets the threshold for IAPs to inhibit apoptosis in cells. If the differential ability of endogenous ... To reduce apoptosome function in naïve cells, we simply decreased the amount of exogenous cytochrome c, thereby limiting the ...
hccs downregulation induces apoptosome-independent caspase-9 activation in mitochondriaA-C. TUNEL assays on st30 embryos co- ... Mentions: Non-canonical apoptosome-independent caspase-9 activation has been observed in few specific conditions (Hao et al, ... Mentions: Non-canonical apoptosome-independent caspase-9 activation has been observed in few specific conditions (Hao et al, ... fig05: hccs downregulation induces apoptosome-independent caspase-9 activation in mitochondriaA-C. TUNEL assays on st30 embryos ...
Formation of apoptosome (Homo sapiens) * Regulation of the apoptosome activity (Homo sapiens) * UACA binds apoptosome (Homo ... Mouse Uaca, showing both cytoplasmic and perinuclear/nuclear localization, was suggested to translocate Apaf1-apoptosome to the ... thereby acting as a stabilizer for the apoptosome (Sakai T et al. 2004). Uaca was shown to induce apoptosis in mammalian cells ...
apoptosome. id: GO:0043293. name: apoptosome. namespace: cellular_component. type: go. obsolete: False. ...
Apoptosome Formation - Duration: 2 minutes, 21 seconds.. *9,932 views. *5 years ago ...
Work on the assembly and function of DARK, the apoptosome of D. melanogaster, has indicated that cyt-c is not required for its ... Cyt-c and apoptosome assembly. A classic downstream effect of the mitochondrial release of pro-apoptotic factors is the cyt-c ... Yu, X., Wang, L., Acehan, D., Wang, X. and Akey, C. W. (2006). Three-dimensional structure of a double apoptosome formed by the ... Chereau, D., Zou, H., Spada, A. P. and Wu, J. C. (2005). A nucleotide binding site in caspase-9 regulates apoptosome activation ...
Kuwano Y, Gallouzi I, Gorospe M. Role of the RNA-binding protein HuR in apoptosis and apoptosome function. In Apoptosome: An Up ... Role of the RNA-binding protein HuR in apoptosis and apoptosome function. Apoptosome: An Up-and-coming Therapeutical Tool. ... Kuwano, Y., Gallouzi, I., & Gorospe, M. (2010). Role of the RNA-binding protein HuR in apoptosis and apoptosome function. In ... Apoptosome: An Up-and-coming Therapeutical Tool. Springer Netherlands, 2010. p. 203-220.. Research output: Chapter in Book/ ...
Apoptosome Formation. Once cytochrome c is released into the cytoplasm, it binds WD40 repeats in the C-terminus of the adaptor ... Zou H, Li Y, Liu X, Wang X. An APAF-1.cytochrome c multimeric complex is a functional apoptosome that activates procaspase-9. J ... Recruitment, activation and retention of caspases-9 and -3 by Apaf-1 apoptosome and associated XIAP complexes. Embo J. 2001; 20 ... Heat-shock protein 70 inhibits apoptosis by preventing recruitment of procaspase-9 to the Apaf-1 apoptosome. Nat Cell Biol. ...
This leads to the formation of a Caspase activating multiprotein complex called the Apoptosome. Once activated, initiator ...
... apoptosome-procaspase-9 CARD complex (). All images were created using OpenAstexViewer as implemented on the EMDB atlas pages ...
The binding of cytochrome c to Apaf-1 forms apoptosomes.. *Apoptosomes bind to caspase-9 and activates it. Caspase-9 is a ...
... these complexes aggregate to form apoptosomes. The apoptosomes bind to and activate caspase-9. Caspase-9 is one of a family of ...
Oligomeric Apaf-1 mediates the cytochrome c-dependent autocatalytic activation of pro-caspase-9 (Apaf-3), leading to the activation of caspase-3 and apoptosis. This activation requires ATP.
R-RNO-111458. Formation of apoptosome. R-RNO-111459. Activation of caspases through apoptosome-mediated cleavage. R-RNO-2151201 ... R-RNO-111458. Formation of apoptosome. R-RNO-111459. Activation of caspases through apoptosome-mediated cleavage. R-RNO-2151201 ...
mitochondria, apoptosomes and associated proteins mediate this route; involves damage or stress transmitted to mitochondria ... mitochondria, apoptosomes and associated proteins mediate this route; involves damage or stress transmitted to mitochondria ... membrane pore opening in outer mitochondrial membrane due to stress, releases cytochrome C for participation in apoptosome ... membrane pore opening in outer mitochondrial membrane due to stress, releases cytochrome C for participation in apoptosome is ...
Although PHAPI seems to regulate apoptosome formation, it does not interact physically with the apoptosome ( 28). There are a ... Apoptosome formation assays. To assess Apaf-1 binding to cytochrome c, cell extracts (500 μg total protein at 10 μg/μL) were ... To immunoprecipitate the apoptosome, 10 μg of caspase-9 antibody (Upstate) were pre-coupled to 25 μL of protein G-Sepharose. ... Predominant suppression of apoptosome by inhibitor of apoptosis protein in non-small cell lung cancer H460 cells: therapeutic ...
Ho AT, Zacksenhaus E (2004) Splitting the apoptosome. Cell Cycle 3:446-448PubMedCrossRefGoogle Scholar ...
Rat Apoptosome Rat Apoptosome: Monoclonal Antibody - Caspase-9 (C9) Mouse mAb - Western Blotting, UniProt ID P55211, Entrez ID ...
The apoptosome activates caspase-9 by dimerization. Mol Cell. 2006;22:269-75.PubMedGoogle Scholar ... A structure of the human apoptosome at 12.8 A resolution provides insights into this cell death platform. Structure. 2005;13: ... Three-dimensional structure of the apoptosome: implications for assembly, procaspase-9 binding, and activation. Mol Cell. 2002; ... A new model for the transition of APAF-1 from inactive monomer to caspase-activating apoptosome. J Biol Chem. 2009;284:32717-24 ...
  • Mouse Uaca, showing both cytoplasmic and perinuclear/nuclear localization, was suggested to translocate Apaf1-apoptosome to the nucleus after proapoptotic stress (Sakai T et al. (reactome.org)
  • Our results indicate that IAP-dependent suppression of apoptosome predominantly occurs in IAP-overexpressing tumor, and the IAP-targeting Smac peptide is an effective molecule to increase tumor cell death induced by chemotherapy in vitro and in vivo . (aacrjournals.org)
  • We show herein that apoptosome-mediated cleavage of procaspase-9 occurs exclusively through a CARD-displacement mechanism, so that unlike the effector procaspase-3, procaspase-9 cannot be processed by the apoptosome as a typical substrate. (nih.gov)
  • Neuronal differentiation was also accompanied with a marked reduction in Apaf-1, resulting in a significant decrease in apoptosome activity. (rupress.org)