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AW

A&W, AW, Aw, aW or aw may refer to:

Companies

 * A&W Restaurants
 * A&W Root Beer
 * A&W (Canada)
 * Addison-Wesley, publishers
 * Africa World Airlines, IATA code
 * Prefix for helicopters made by AgustaWestland
 * Alienware
 * Allied Waste Industries, Inc, stock symbol on NYSE
 * Armstrong Whitworth, a British manufacturing company

Media and entertainment

 * Accel World, a Japanese light novel series
 * Active Worlds, a 3D virtual reality platform
 * Another World (TV series), an American soap opera
 * Athletics Weekly, a monthly track and field magazine published in the United Kingdom
 * Aviation Week, magazine
 * Call of Duty: Advanced Warfare, an action video game

People

 * A. H. Weiler (1908 – 2002), The New York Times film critic whose early reviews were signed with his initials A. W.
 * A. W. (poet), anonymous 16th century poet
 * Abraham Washington (A. W.), American professional wrestler and wrestling commentator
 * Alan Walker (born 1997), English-Norwegian music producer and DJ
 * Aw (father), honorific title in the Harari and Somali languages
 * Aw (surname), a Cantonese surname
 * John-Allison Weiss, an American singer-songwriter formerly known as A. W.
 * Andy Warhol, a leading figure in the pop art movement.

Places

 * Ahrweiler (district), Germany, vehicle registration code
 * Aruba (ISO 3166-1 2-letter country code AW)

Science and technology

 * .aw, the internet top level domain country code for Aruba
 * Airwatt, a unit of the effectiveness of vacuum cleaners
 * Aw, categorization for tropical savanna climate in the Köppen classification system
 * AW, in German email subject line, equivalent to Re:
 * aw, or attowatt, an SI unit of power
 * aw, or water activity, the relative availability of water in a substance

Other uses

 * Agencja Wywiadu, the Polish foreign intelligence service
 * Ahnapee and Western Railway, A&W
 * Arctic Warfare, a sniper rifle
 * Anthony Wayne Local School District, an American school district in Ohio
 * Aviation Warfare Systems Operator, a rating in the United States Navy
 * Aw, a digraph in Latin-script
 * A US Navy hull classification symbol: Distilling ship (AW)

title: AW


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Talk:Apocalypse Now

Ride of the Valkyries and Military
The helicopter attack scene with the Ride of the Valkyries has its historical model in the Die Deutsche Wochenschau of June 4, 1941 (from minute 12:30), in which the air landing of the Germans on Crete was highlighted with the same piece. See and hear here: https://archive.org/details/1941-06-04-Die-Deutsche-Wochenschau-561 My English is too bad, so an English speaking author can put this in the article.--Mike Ax (talk) 13:06, 12 June 2023 (UTC)

 * Very interesting, thank you for sharing that.The problem we would face is in directly connecting that to Apocalypse Now as the work the inspiration derived from. The Ride of the Valkyries was used in film long before Die Deutsche Wochenschau - in The Birth of a Nation. So, absent a specific statement from Francis Ford Coppola that the former was the inspiration, rather than the latter, we'd be engaging in original research. The only reference I ran across that discussed this - https://flypaper.soundfly.com/discover/how-apocalypse-now-etched-wagners-ride-valkyries-into-our-brains/ - was regarding the efforts to use Sir Georg Solti's version, as  stated by editor Walter Murch. However, I did not intensely or deeply research beyond that. If you can find a source that confirms a direct connection, then it could be added.  cheers. anastrophe, an editor he is. 20:17, 12 June 2023 (UTC)
 * Hello Anastrophe, thanks for the information, this music was used so early in the film. Greetings Mike Ax Mike Ax (talk) 18:02, 13 June 2023 (UTC)
 * (This affords me one of the very rare opportunities to humble brag that I worked on Apocalypse Now, in the most trivial way - I sat and monitored the recording machines at Skywalker Sound while Mr. Murch was remixing AN for the laserdisc release - so long ago!) cheers. anastrophe, an editor he is. 20:22, 12 June 2023 (UTC)

Charlie
The phrase "Charlie don't surf" needs explanation. It's been almost 50 years since I saw the film, so I can't be 100% sure which group "charlie" refers to. (South) Vietnamese? Viet-Cong? North Vietnamese Army Regulars? I also note that the line is stereotyping and may be (mildly) offensive (today) - I really don't know. The line is notable enough to warrant explanation, I'd say. Since some American soldiers surfed during the Vietnam War, it is possible (or even likely) that both Vietnamese civilians and possibly even Viet Cong (of a certain age) did surf as well, just speculation but copy-catting is human nature.40.142.183.146 (talk) 22:09, 7 July 2023 (UTC)

Charlie refers to the Vietcong. Vietcong were known as VC, which is Victor Charlie in the NATO alphabet, hence Charlie. PatGallacher (talk) 21:24, 28 June 2024 (UTC)

Questions about Category.
In the categories section, the category "existentialist films" is selected, but I don't understand since there is nothing philosophical about the film aside from Kurtz's ramblings at the end of the film. If anyone can explain, that would be great. ONE RING (talk) 23:59, 26 January 2024 (UTC)

Golden Bough
Just one point I am bit surprised nobody has mentioned. At one point we see that Kurtz appears to have been reading The Golden Bough, about the ritual sacrifice of kings, not the sort of things directors would insert by accident. When Willard emerges from Kurtz's quarters at the end, people's reaction suggests that he who has killed the king has become the king himself. PatGallacher (talk) 21:30, 28 June 2024 (UTC)

license: Creative Commons - Attribution Share-Alike - https://creativecommons.org/licenses/by-sa/4.0/

title: Talk:Apocalypse Now


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Apoptosis

Apoptosis (from ἀπόπτωσις) is a form of programmed cell death that occurs in multicellular organisms and in some eukaryotic, single-celled microorganisms such as yeast. Biochemical events lead to characteristic cell changes (morphology) and death. These changes include blebbing, cell shrinkage, nuclear fragmentation, chromatin condensation, DNA fragmentation, and mRNA decay. The average adult human loses 50 to 70 billion cells each day due to apoptosis. For the average human child between 8 and 14 years old, each day the approximate loss is 20 to 30 billion cells.

In contrast to necrosis, which is a form of traumatic cell death that results from acute cellular injury, apoptosis is a highly regulated and controlled process that confers advantages during an organism's life cycle. For example, the separation of fingers and toes in a developing human embryo occurs because cells between the digits undergo apoptosis. Unlike necrosis, apoptosis produces cell fragments called apoptotic bodies that phagocytes are able to engulf and remove before the contents of the cell can spill out onto surrounding cells and cause damage to them.

Because apoptosis cannot stop once it has begun, it is a highly regulated process. Apoptosis can be initiated through one of two pathways. In the intrinsic pathway the cell kills itself because it senses cell stress, while in the extrinsic pathway the cell kills itself because of signals from other cells. Weak external signals may also activate the intrinsic pathway of apoptosis. Both pathways induce cell death by activating caspases, which are proteases, or enzymes that degrade proteins. The two pathways both activate initiator caspases, which then activate executioner caspases, which then kill the cell by degrading proteins indiscriminately.

In addition to its importance as a biological phenomenon, defective apoptotic processes have been implicated in a wide variety of diseases. Excessive apoptosis causes atrophy, whereas an insufficient amount results in uncontrolled cell proliferation, such as cancer. Some factors like Fas receptors and caspases promote apoptosis, while some members of the Bcl-2 family of proteins inhibit apoptosis.

Discovery and etymology
German scientist Carl Vogt was first to describe the principle of apoptosis in 1842. In 1885, anatomist Walther Flemming delivered a more precise description of the process of programmed cell death. However, it was not until 1965 that the topic was resurrected. While studying tissues using electron microscopy, John Kerr at the University of Queensland was able to distinguish apoptosis from traumatic cell death. Following the publication of a paper describing the phenomenon, Kerr was invited to join Alastair Currie, as well as Andrew Wyllie, who was Currie's graduate student, at the University of Aberdeen. In 1972, the trio published a seminal article in the British Journal of Cancer. Kerr had initially used the term programmed cell necrosis, but in the article, the process of natural cell death was called apoptosis. Kerr, Wyllie and Currie credited James Cormack, a professor of Greek language at University of Aberdeen, with suggesting the term apoptosis. Kerr received the Paul Ehrlich and Ludwig Darmstaedter Prize on March 14, 2000, for his description of apoptosis. He shared the prize with Boston biologist H. Robert Horvitz.

For many years, neither "apoptosis" nor "programmed cell death" was a highly cited term. Two discoveries brought cell death from obscurity to a major field of research: identification of the first component of the cell death control and effector mechanisms, and linkage of abnormalities in cell death to human disease, in particular cancer. This occurred in 1988 when it was shown that BCL2, the gene responsible for follicular lymphoma, encoded a protein that inhibited cell death.

The 2002 Nobel Prize in Medicine was awarded to Sydney Brenner, H. Robert Horvitz and John Sulston for their work identifying genes that control apoptosis. The genes were identified by studies in the nematode C. elegans and homologues of these genes function in humans to regulate apoptosis.

In Greek, apoptosis translates to the "falling off" of leaves from a tree. Cormack, professor of Greek language, reintroduced the term for medical use as it had a medical meaning for the Greeks over two thousand years before. Hippocrates used the term to mean "the falling off of the bones". Galen extended its meaning to "the dropping of the scabs". Cormack was no doubt aware of this usage when he suggested the name. Debate continues over the correct pronunciation, with opinion divided between a pronunciation with the second p silent and the second p pronounced. In English, the p of the Greek -pt- consonant cluster is typically silent at the beginning of a word (e.g. pterodactyl, Ptolemy), but articulated when used in combining forms preceded by a vowel, as in helicopter or the orders of insects: diptera, lepidoptera, etc.

In the original Kerr, Wyllie & Currie paper, there is a footnote regarding the pronunciation:

"We are most grateful to Professor James Cormack of the Department of Greek, University of Aberdeen, for suggesting this term. The word 'apoptosis' (ἀπόπτωσις) is used in Greek to describe the 'dropping off' or 'falling off' of petals from flowers, or leaves from trees. To show the derivation clearly, we propose that the stress should be on the penultimate syllable, the second half of the word being pronounced like 'ptosis' (with the 'p' silent), which comes from the same root 'to fall', and is already used to describe the drooping of the upper eyelid."

Activation mechanisms

The initiation of apoptosis is tightly regulated by activation mechanisms, because once apoptosis has begun, it inevitably leads to the death of the cell. The two best-understood activation mechanisms are the intrinsic pathway (also called the mitochondrial pathway) and the extrinsic pathway. The intrinsic pathway is activated by intracellular signals generated when cells are stressed and depends on the release of proteins from the intermembrane space of mitochondria. The extrinsic pathway is activated by extracellular ligands binding to cell-surface death receptors, which leads to the formation of the death-inducing signaling complex (DISC).

A cell initiates intracellular apoptotic signaling in response to a stress, which may bring about cell suicide. The binding of nuclear receptors by glucocorticoids, heat, radiation, nutrient deprivation, viral infection, hypoxia, increased intracellular concentration of free fatty acids and increased intracellular calcium concentration, for example, by damage to the membrane, can all trigger the release of intracellular apoptotic signals by a damaged cell. A number of cellular components, such as poly ADP ribose polymerase, may also help regulate apoptosis. Single cell fluctuations have been observed in experimental studies of stress induced apoptosis.

Before the actual process of cell death is precipitated by enzymes, apoptotic signals must cause regulatory proteins to initiate the apoptosis pathway. This step allows those signals to cause cell death, or the process to be stopped, should the cell no longer need to die. Several proteins are involved, but two main methods of regulation have been identified: the targeting of mitochondria functionality, or directly transducing the signal via adaptor proteins to the apoptotic mechanisms. An extrinsic pathway for initiation identified in several toxin studies is an increase in calcium concentration within a cell caused by drug activity, which also can cause apoptosis via a calcium binding protease calpain.

Intrinsic pathway
The intrinsic pathway is also known as the mitochondrial pathway. Mitochondria are essential to multicellular life. Without them, a cell ceases to respire aerobically and quickly dies. This fact forms the basis for some apoptotic pathways. Apoptotic proteins that target mitochondria affect them in different ways. They may cause mitochondrial swelling through the formation of membrane pores, or they may increase the permeability of the mitochondrial membrane and cause apoptotic effectors to leak out. There is also a growing body of evidence indicating that nitric oxide is able to induce apoptosis by helping to dissipate the membrane potential of mitochondria and therefore make it more permeable. Nitric oxide has been implicated in initiating and inhibiting apoptosis through its possible action as a signal molecule of subsequent pathways that activate apoptosis.

During apoptosis, cytochrome c is released from mitochondria through the actions of the proteins Bax and Bak. The mechanism of this release is enigmatic, but appears to stem from a multitude of Bax/Bak homo- and hetero-dimers of Bax/Bak inserted into the outer membrane. Once cytochrome c is released it binds with Apoptotic protease activating factor – 1 (Apaf-1) and ATP, which then bind to pro-caspase-9 to create a protein complex known as an apoptosome. The apoptosome cleaves the pro-caspase to its active form of caspase-9, which in turn cleaves and activates pro-caspase into the effector caspase-3.

Mitochondria also release proteins known as SMACs (second mitochondria-derived activator of caspases) into the cell's cytosol following the increase in permeability of the mitochondria membranes. SMAC binds to proteins that inhibit apoptosis (IAPs) thereby deactivating them, and preventing the IAPs from arresting the process and therefore allowing apoptosis to proceed. IAP also normally suppresses the activity of a group of cysteine proteases called caspases, which carry out the degradation of the cell. Therefore, the actual degradation enzymes can be seen to be indirectly regulated by mitochondrial permeability.

Extrinsic pathway

Two theories of the direct initiation of apoptotic mechanisms in mammals have been suggested: the TNF-induced (tumor necrosis factor) model and the Fas-Fas ligand-mediated model, both involving receptors of the TNF receptor (TNFR) family coupled to extrinsic signals.

TNF pathway
TNF-alpha is a cytokine produced mainly by activated macrophages, and is the major extrinsic mediator of apoptosis. Most cells in the human body have two receptors for TNF-alpha: TNFR1 and TNFR2. The binding of TNF-alpha to TNFR1 has been shown to initiate the pathway that leads to caspase activation via the intermediate membrane proteins TNF receptor-associated death domain (TRADD) and Fas-associated death domain protein (FADD). cIAP1/2 can inhibit TNF-α signaling by binding to TRAF2. FLIP inhibits the activation of caspase-8. Binding of this receptor can also indirectly lead to the activation of transcription factors involved in cell survival and inflammatory responses. However, signalling through TNFR1 might also induce apoptosis in a caspase-independent manner. The link between TNF-alpha and apoptosis shows why an abnormal production of TNF-alpha plays a fundamental role in several human diseases, especially in autoimmune diseases. The TNF-alpha receptor superfamily also includes death receptors (DRs), such as DR4 and DR5. These receptors bind to the protein TRAIL and mediate apoptosis. Apoptosis is known to be one of the primary mechanisms of targeted cancer therapy. Luminescent iridium complex-peptide hybrids (IPHs) have recently been designed, which mimic TRAIL and bind to death receptors on cancer cells, thereby inducing their apoptosis.

Fas pathway
The fas receptor (First apoptosis signal) – (also known as Apo-1 or CD95) is a transmembrane protein of the TNF family which binds the Fas ligand (FasL). The interaction between Fas and FasL results in the formation of the death-inducing signaling complex (DISC), which contains the FADD, caspase-8 and caspase-10. In some types of cells (type I), processed caspase-8 directly activates other members of the caspase family, and triggers the execution of apoptosis of the cell. In other types of cells (type II), the Fas-DISC starts a feedback loop that spirals into increasing release of proapoptotic factors from mitochondria and the amplified activation of caspase-8.

Common components
Following TNF-R1 and Fas activation in mammalian cells a balance between proapoptotic (BAX, BID, BAK, or BAD) and anti-apoptotic (Bcl-Xl and Bcl-2) members of the Bcl-2 family are established. This balance is the proportion of proapoptotic homodimers that form in the outer-membrane of the mitochondrion. The proapoptotic homodimers are required to make the mitochondrial membrane permeable for the release of caspase activators such as cytochrome c and SMAC. Control of proapoptotic proteins under normal cell conditions of nonapoptotic cells is incompletely understood, but in general, Bax or Bak are activated by the activation of BH3-only proteins, part of the Bcl-2 family.

Caspases
Caspases play the central role in the transduction of ER apoptotic signals. Caspases are proteins that are highly conserved, cysteine-dependent aspartate-specific proteases. There are two types of caspases: initiator caspases (caspases 2, 8, 9, 10, 11, and 12) and effector caspases (caspases 3, 6, and 7). The activation of initiator caspases requires binding to specific oligomeric activator protein. Effector caspases are then activated by these active initiator caspases through proteolytic cleavage. The active effector caspases then proteolytically degrade a host of intracellular proteins to carry out the cell death program.

Caspase-independent apoptotic pathway
There also exists a caspase-independent apoptotic pathway that is mediated by AIF (apoptosis-inducing factor).

Apoptosis model in amphibians
The frog Xenopus laevis serves as an ideal model system for the study of the mechanisms of apoptosis. In fact, iodine and thyroxine also stimulate the spectacular apoptosis of the cells of the larval gills, tail and fins in amphibian's metamorphosis, and stimulate the evolution of their nervous system transforming the aquatic, vegetarian tadpole into the terrestrial, carnivorous frog.

Negative regulators of apoptosis
Negative regulation of apoptosis inhibits cell death signaling pathways, helping tumors to evade cell death and developing drug resistance. The ratio between anti-apoptotic (Bcl-2) and pro-apoptotic (Bax) proteins determines whether a cell lives or dies. Many families of proteins act as negative regulators categorized into either antiapoptotic factors, such as IAPs and Bcl-2 proteins or prosurvival factors like cFLIP, BNIP3, FADD, Akt, and NF-κB.

Proteolytic caspase cascade: Killing the cell
Many pathways and signals lead to apoptosis, but these converge on a single mechanism that actually causes the death of the cell. After a cell receives stimulus, it undergoes organized degradation of cellular organelles by activated proteolytic caspases. In addition to the destruction of cellular organelles, mRNA is rapidly and globally degraded by a mechanism that is not yet fully characterized. mRNA decay is triggered very early in apoptosis.

A cell undergoing apoptosis shows a series of characteristic morphological changes. Early alterations include:
 * 1) Cell shrinkage and rounding occur because of the retraction of lamellipodia and the breakdown of the proteinaceous cytoskeleton by caspases.
 * 2) The cytoplasm appears dense, and the organelles appear tightly packed.
 * 3) Chromatin undergoes condensation into compact patches against the nuclear envelope (also known as the perinuclear envelope) in a process known as pyknosis, a hallmark of apoptosis.
 * 4) The nuclear envelope becomes discontinuous and the DNA inside it is fragmented in a process referred to as karyorrhexis. The nucleus breaks into several discrete chromatin bodies or nucleosomal units due to the degradation of DNA.

Apoptosis progresses quickly and its products are quickly removed, making it difficult to detect or visualize on classical histology sections. During karyorrhexis, endonuclease activation leaves short DNA fragments, regularly spaced in size. These give a characteristic "laddered" appearance on agar gel after electrophoresis. Tests for DNA laddering differentiate apoptosis from ischemic or toxic cell death.

Apoptotic cell disassembly
Before the apoptotic cell is disposed of, there is a process of disassembly. There are three recognized steps in apoptotic cell disassembly:
 * 1) Membrane blebbing: The cell membrane shows irregular buds known as blebs. Initially these are smaller surface blebs. Later these can grow into larger so-called dynamic membrane blebs. An important regulator of apoptotic cell membrane blebbing is ROCK1 (rho associated coiled-coil-containing protein kinase 1).
 * 2) Formation of membrane protrusions: Some cell types, under specific conditions, may develop different types of long, thin extensions of the cell membrane called membrane protrusions. Three types have been described: microtubule spikes, apoptopodia (feet of death), and beaded apoptopodia (the latter having a beads-on-a-string appearance).   Pannexin 1 is an important component of membrane channels involved in the formation of apoptopodia and beaded apoptopodia.
 * 3) Fragmentation: The cell breaks apart into multiple vesicles called apoptotic bodies, which undergo phagocytosis. The plasma membrane protrusions may help bring apoptotic bodies closer to phagocytes.

Removal of dead cells
The removal of dead cells by neighboring phagocytic cells has been termed efferocytosis. Dying cells that undergo the final stages of apoptosis display phagocytotic molecules, such as phosphatidylserine, on their cell surface. Phosphatidylserine is normally found on the inner leaflet surface of the plasma membrane, but is redistributed during apoptosis to the extracellular surface by a protein known as scramblase. These molecules mark the cell for phagocytosis by cells possessing the appropriate receptors, such as macrophages. The removal of dying cells by phagocytes occurs in an orderly manner without eliciting an inflammatory response. During apoptosis cellular RNA and DNA are separated from each other and sorted to different apoptotic bodies; separation of RNA is initiated as nucleolar segregation.

Pathway knock-outs
Many knock-outs have been made in the apoptosis pathways to test the function of each of the proteins. Several caspases, in addition to APAF1 and FADD, have been mutated to determine the new phenotype. In order to create a tumor necrosis factor (TNF) knockout, an exon containing the nucleotides 3704–5364 was removed from the gene. This exon encodes a portion of the mature TNF domain, as well as the leader sequence, which is a highly conserved region necessary for proper intracellular processing. TNF-/- mice develop normally and have no gross structural or morphological abnormalities. However, upon immunization with SRBC (sheep red blood cells), these mice demonstrated a deficiency in the maturation of an antibody response; they were able to generate normal levels of IgM, but could not develop specific IgG levels. Apaf-1 is the protein that turns on caspase 9 by cleavage to begin the caspase cascade that leads to apoptosis. Since a -/- mutation in the APAF-1 gene is embryonic lethal, a gene trap strategy was used in order to generate an APAF-1 -/- mouse. This assay is used to disrupt gene function by creating an intragenic gene fusion. When an APAF-1 gene trap is introduced into cells, many morphological changes occur, such as spina bifida, the persistence of interdigital webs, and open brain. In addition, after embryonic day 12.5, the brain of the embryos showed several structural changes. APAF-1 cells are protected from apoptosis stimuli such as irradiation. A BAX-1 knock-out mouse exhibits normal forebrain formation and a decreased programmed cell death in some neuronal populations and in the spinal cord, leading to an increase in motor neurons.

The caspase proteins are integral parts of the apoptosis pathway, so it follows that knock-outs made have varying damaging results. A caspase 9 knock-out leads to a severe brain malformation. A caspase 8 knock-out leads to cardiac failure and thus embryonic lethality. However, with the use of cre-lox technology, a caspase 8 knock-out has been created that exhibits an increase in peripheral T cells, an impaired T cell response, and a defect in neural tube closure. These mice were found to be resistant to apoptosis mediated by CD95, TNFR, etc. but not resistant to apoptosis caused by UV irradiation, chemotherapeutic drugs, and other stimuli. Finally, a caspase 3 knock-out was characterized by ectopic cell masses in the brain and abnormal apoptotic features such as membrane blebbing or nuclear fragmentation. A remarkable feature of these KO mice is that they have a very restricted phenotype: Casp3, 9, APAF-1 KO mice have deformations of neural tissue and FADD and Casp 8 KO showed defective heart development, however, in both types of KO other organs developed normally and some cell types were still sensitive to apoptotic stimuli suggesting that unknown proapoptotic pathways exist.

Methods for distinguishing apoptotic from necrotic cells
Label-free live cell imaging, time-lapse microscopy, flow fluorocytometry, and transmission electron microscopy can be used to compare apoptotic and necrotic cells. There are also various biochemical techniques for analysis of cell surface markers (phosphatidylserine exposure versus cell permeability by flow cytometry), cellular markers such as DNA fragmentation (flow cytometry), caspase activation, Bid cleavage, and cytochrome c release (Western blotting). Supernatant screening for caspases, HMGB1, and cytokeratin 18 release can identify primary from secondary necrotic cells. However, no distinct surface or biochemical markers of necrotic cell death have been identified yet, and only negative markers are available. These include absence of apoptotic markers (caspase activation, cytochrome c release, and oligonucleosomal DNA fragmentation) and differential kinetics of cell death markers (phosphatidylserine exposure and cell membrane permeabilization). A selection of techniques that can be used to distinguish apoptosis from necroptotic cells could be found in these references.

Defective pathways
The many different types of apoptotic pathways contain a multitude of different biochemical components, many of them not yet understood. As a pathway is more or less sequential in nature, removing or modifying one component leads to an effect in another. In a living organism, this can have disastrous effects, often in the form of disease or disorder. A discussion of every disease caused by modification of the various apoptotic pathways would be impractical, but the concept overlying each one is the same: The normal functioning of the pathway has been disrupted in such a way as to impair the ability of the cell to undergo normal apoptosis. This results in a cell that lives past its "use-by date" and is able to replicate and pass on any faulty machinery to its progeny, increasing the likelihood of the cell's becoming cancerous or diseased.

A recently described example of this concept in action can be seen in the development of a lung cancer called NCI-H460. The X-linked inhibitor of apoptosis protein (XIAP) is overexpressed in cells of the H460 cell line. XIAPs bind to the processed form of caspase-9 and suppress the activity of apoptotic activator cytochrome c, therefore overexpression leads to a decrease in the number of proapoptotic agonists. As a consequence, the balance of anti-apoptotic and proapoptotic effectors is upset in favour of the former, and the damaged cells continue to replicate despite being directed to die. Defects in regulation of apoptosis in cancer cells occur often at the level of control of transcription factors. As a particular example, defects in molecules that control transcription factor NF-κB in cancer change the mode of transcriptional regulation and the response to apoptotic signals, to curtail dependence on the tissue that the cell belongs. This degree of independence from external survival signals, can enable cancer metastasis.

Dysregulation of p53
The tumor-suppressor protein p53 accumulates when DNA is damaged due to a chain of biochemical factors. Part of this pathway includes alpha-interferon and beta-interferon, which induce transcription of the p53 gene, resulting in the increase of p53 protein level and enhancement of cancer cell-apoptosis. p53 prevents the cell from replicating by stopping the cell cycle at G1, or interphase, to give the cell time to repair; however, it will induce apoptosis if damage is extensive and repair efforts fail. Any disruption to the regulation of the p53 or interferon genes will result in impaired apoptosis and the possible formation of tumors.

Inhibition
Inhibition of apoptosis can result in a number of cancers, inflammatory diseases, and viral infections. It was originally believed that the associated accumulation of cells was due to an increase in cellular proliferation, but it is now known that it is also due to a decrease in cell death. The most common of these diseases is cancer, the disease of excessive cellular proliferation, which is often characterized by an overexpression of IAP family members. As a result, the malignant cells experience an abnormal response to apoptosis induction: Cycle-regulating genes (such as p53, ras or c-myc) are mutated or inactivated in diseased cells, and further genes (such as bcl-2) also modify their expression in tumors. Some apoptotic factors are vital during mitochondrial respiration e.g. cytochrome C. Pathological inactivation of apoptosis in cancer cells is correlated with frequent respiratory metabolic shifts toward glycolysis (an observation known as the "Warburg hypothesis".

HeLa cell
Apoptosis in HeLa cells is inhibited by proteins produced by the cell; these inhibitory proteins target retinoblastoma tumor-suppressing proteins. These tumor-suppressing proteins regulate the cell cycle, but are rendered inactive when bound to an inhibitory protein. HPV E6 and E7 are inhibitory proteins expressed by the human papillomavirus, HPV being responsible for the formation of the cervical tumor from which HeLa cells are derived. HPV E6 causes p53, which regulates the cell cycle, to become inactive. HPV E7 binds to retinoblastoma tumor suppressing proteins and limits its ability to control cell division. These two inhibitory proteins are partially responsible for HeLa cells' immortality by inhibiting apoptosis to occur.

Treatments
The main method of treatment for potential death from signaling-related diseases involves either increasing or decreasing the susceptibility of apoptosis in diseased cells, depending on whether the disease is caused by either the inhibition of or excess apoptosis. For instance, treatments aim to restore apoptosis to treat diseases with deficient cell death and to increase the apoptotic threshold to treat diseases involved with excessive cell death. To stimulate apoptosis, one can increase the number of death receptor ligands (such as TNF or TRAIL), antagonize the anti-apoptotic Bcl-2 pathway, or introduce Smac mimetics to inhibit the inhibitor (IAPs). The addition of agents such as Herceptin, Iressa, or Gleevec works to stop cells from cycling and causes apoptosis activation by blocking growth and survival signaling further upstream. Finally, adding p53-MDM2 complexes displaces p53 and activates the p53 pathway, leading to cell cycle arrest and apoptosis. Many different methods can be used either to stimulate or to inhibit apoptosis in various places along the death signaling pathway.

Apoptosis is a multi-step, multi-pathway cell-death programme that is inherent in every cell of the body. In cancer, the apoptosis cell-division ratio is altered. Cancer treatment by chemotherapy and irradiation kills target cells primarily by inducing apoptosis.

Hyperactive apoptosis
On the other hand, loss of control of cell death (resulting in excess apoptosis) can lead to neurodegenerative diseases, hematologic diseases, and tissue damage. Neurons that rely on mitochondrial respiration undergo apoptosis in neurodegenerative diseases such as Alzheimer's and Parkinson's. (an observation known as the "Inverse Warburg hypothesis" ). Moreover, there is an inverse epidemiological comorbidity between neurodegenerative diseases and cancer. The progression of HIV is directly linked to excess, unregulated apoptosis. In a healthy individual, the number of CD4+ lymphocytes is in balance with the cells generated by the bone marrow; however, in HIV-positive patients, this balance is lost due to an inability of the bone marrow to regenerate CD4+ cells. In the case of HIV, CD4+ lymphocytes die at an accelerated rate through uncontrolled apoptosis, when stimulated. At the molecular level, hyperactive apoptosis can be caused by defects in signaling pathways that regulate the Bcl-2 family proteins. Increased expression of apoptotic proteins such as BIM, or their decreased proteolysis, leads to cell death and can cause a number of pathologies, depending on the cells where excessive activity of BIM occurs. Cancer cells can escape apoptosis through mechanisms that suppress BIM expression or by increased proteolysis of BIM.

Treatments
Treatments aiming to inhibit works to block specific caspases. Finally, the Akt protein kinase promotes cell survival through two pathways. Akt phosphorylates and inhibits Bad (a Bcl-2 family member), causing Bad to interact with the 14-3-3 scaffold, resulting in Bcl dissociation and thus cell survival. Akt also activates IKKα, which leads to NF-κB activation and cell survival. Active NF-κB induces the expression of anti-apoptotic genes such as Bcl-2, resulting in inhibition of apoptosis. NF-κB has been found to play both an antiapoptotic role and a proapoptotic role depending on the stimuli utilized and the cell type.

HIV progression
The progression of the human immunodeficiency virus infection into AIDS is due primarily to the depletion of CD4+ T-helper lymphocytes in a manner that is too rapid for the body's bone marrow to replenish the cells, leading to a compromised immune system. One of the mechanisms by which T-helper cells are depleted is apoptosis, which results from a series of biochemical pathways:
 * 1) HIV enzymes deactivate anti-apoptotic Bcl-2. This does not directly cause cell death but primes the cell for apoptosis should the appropriate signal be received.  In parallel, these enzymes activate proapoptotic procaspase-8, which does directly activate the mitochondrial events of apoptosis.
 * 2) HIV may increase the level of cellular proteins that prompt Fas-mediated apoptosis.
 * 3) HIV proteins decrease the amount of CD4 glycoprotein marker present on the cell membrane.
 * 4) Released viral particles and proteins present in extracellular fluid are able to induce apoptosis in nearby "bystander" T helper cells.
 * 5) HIV decreases the production of molecules involved in marking the cell for apoptosis, giving the virus time to replicate and continue releasing apoptotic agents and virions into the surrounding tissue.
 * 6) The infected CD4+ cell may also receive the death signal from a cytotoxic T cell.

Cells may also die as direct consequences of viral infections. HIV-1 expression induces tubular cell G2/M arrest and apoptosis. The progression from HIV to AIDS is not immediate or even necessarily rapid; HIV's cytotoxic activity toward CD4+ lymphocytes is classified as AIDS once a given patient's CD4+ cell count falls below 200.

Researchers from Kumamoto University in Japan have developed a new method to eradicate HIV in viral reservoir cells, named "Lock-in and apoptosis." Using the synthesized compound Heptanoylphosphatidyl L-Inositol Pentakisphophate (or L-Hippo) to bind strongly to the HIV protein PR55Gag, they were able to suppress viral budding. By suppressing viral budding, the researchers were able to trap the HIV virus in the cell and allow for the cell to undergo apoptosis (natural cell death). Associate Professor Mikako Fujita has stated that the approach is not yet available to HIV patients because the research team has to conduct further research on combining the drug therapy that currently exists with this "Lock-in and apoptosis" approach to lead to complete recovery from HIV.

Viral infection
Viral induction of apoptosis occurs when one or several cells of a living organism are infected with a virus, leading to cell death. Cell death in organisms is necessary for the normal development of cells and the cell cycle maturation. It is also important in maintaining the regular functions and activities of cells.

Viruses can trigger apoptosis of infected cells via a range of mechanisms including: Canine distemper virus (CDV) is known to cause apoptosis in central nervous system and lymphoid tissue of infected dogs in vivo and in vitro. Apoptosis caused by CDV is typically induced via the extrinsic pathway, which activates caspases that disrupt cellular function and eventually leads to the cells death. In normal cells, CDV activates caspase-8 first, which works as the initiator protein followed by the executioner protein caspase-3. However, apoptosis induced by CDV in HeLa cells does not involve the initiator protein caspase-8. HeLa cell apoptosis caused by CDV follows a different mechanism than that in vero cell lines. This change in the caspase cascade suggests CDV induces apoptosis via the intrinsic pathway, excluding the need for the initiator caspase-8. The executioner protein is instead activated by the internal stimuli caused by viral infection not a caspase cascade.
 * Receptor binding
 * Activation of protein kinase R (PKR)
 * Interaction with p53
 * Expression of viral proteins coupled to MHC proteins on the surface of the infected cell, allowing recognition by cells of the immune system (such as natural killer and cytotoxic T cells) that then induce the infected cell to undergo apoptosis.

The Oropouche virus (OROV) is found in the family Bunyaviridae. The study of apoptosis brought on by Bunyaviridae was initiated in 1996, when it was observed that apoptosis was induced by the La Crosse virus into the kidney cells of baby hamsters and into the brains of baby mice.

OROV is a disease that is transmitted between humans by the biting midge (Culicoides paraensis). It is referred to as a zoonotic arbovirus and causes febrile illness, characterized by the onset of a sudden fever known as Oropouche fever.

The Oropouche virus also causes disruption in cultured cells – cells that are cultivated in distinct and specific conditions. An example of this can be seen in HeLa cells, whereby the cells begin to degenerate shortly after they are infected.

With the use of gel electrophoresis, it can be observed that OROV causes DNA fragmentation in HeLa cells. It can be interpreted by counting, measuring, and analyzing the cells of the Sub/G1 cell population. When HeLA cells are infected with OROV, the cytochrome C is released from the membrane of the mitochondria, into the cytosol of the cells. This type of interaction shows that apoptosis is activated via an intrinsic pathway.

In order for apoptosis to occur within OROV, viral uncoating, viral internalization, along with the replication of cells is necessary. Apoptosis in some viruses is activated by extracellular stimuli. However, studies have demonstrated that the OROV infection causes apoptosis to be activated through intracellular stimuli and involves the mitochondria.

Many viruses encode proteins that can inhibit apoptosis. Several viruses encode viral homologs of Bcl-2. These homologs can inhibit proapoptotic proteins such as BAX and BAK, which are essential for the activation of apoptosis. Examples of viral Bcl-2 proteins include the Epstein-Barr virus BHRF1 protein and the adenovirus E1B 19K protein. Some viruses express caspase inhibitors that inhibit caspase activity and an example is the CrmA protein of cowpox viruses. Whilst a number of viruses can block the effects of TNF and Fas. For example, the M-T2 protein of myxoma viruses can bind TNF preventing it from binding the TNF receptor and inducing a response. Furthermore, many viruses express p53 inhibitors that can bind p53 and inhibit its transcriptional transactivation activity. As a consequence, p53 cannot induce apoptosis, since it cannot induce the expression of proapoptotic proteins. The adenovirus E1B-55K protein and the hepatitis B virus HBx protein are examples of viral proteins that can perform such a function.

Viruses can remain intact from apoptosis in particular in the latter stages of infection. They can be exported in the apoptotic bodies that pinch off from the surface of the dying cell, and the fact that they are engulfed by phagocytes prevents the initiation of a host response. This favours the spread of the virus. Prions can cause apoptosis in neurons.

Plants
Programmed cell death in plants has a number of molecular similarities to that of animal apoptosis, but it also has differences, notable ones being the presence of a cell wall and the lack of an immune system that removes the pieces of the dead cell. Instead of an immune response, the dying cell synthesizes substances to break itself down and places them in a vacuole that ruptures as the cell dies. Additionally, plants do not contain phagocytic cells, which are essential in the process of breaking down and removing apoptotic bodies. Whether this whole process resembles animal apoptosis closely enough to warrant using the name apoptosis (as opposed to the more general programmed cell death) is unclear.

Caspase-independent apoptosis
The characterization of the caspases allowed the development of caspase inhibitors, which can be used to determine whether a cellular process involves active caspases. Using these inhibitors it was discovered that cells can die while displaying a morphology similar to apoptosis without caspase activation. Later studies linked this phenomenon to the release of AIF (apoptosis-inducing factor) from the mitochondria and its translocation into the nucleus mediated by its NLS (nuclear localization signal). Inside the mitochondria, AIF is anchored to the inner membrane. In order to be released, the protein is cleaved by a calcium-dependent calpain protease.

title: Apoptosis


text:
Talk:Apoptosis

Frog apoptosis
Is it me? Or does this section appear to fail to provide much additional information in terms of types of apoptosis? I feel like it needs to either qualify how it is different from the intrinsic and extrinsic pathways or should be moved somewhere else Sawerchessread (talk) 01:17, 9 April 2017 (UTC)

Herceptin, Iressa or Gleevec
Could this article please ellaborate on Herceptin, Iressa and Gleevec. What are they? Are they registered trademarks or known pharmaceutical drugs? I want to know more. — Preceding unsigned comment added by 197.64.17.242 (talk) 03:31, 26 January 2013 (UTC)

First sentence
"Deliberate life relinquishment" is an awkward wording.
 * I thought it was quite elegant actually... but any suggestions are always welcomed. "Cell suicide" has too many connotations to be used. --  Serephine   ♠   talk   - 00:13, 8 May 2007 (UTC)
 * I also thought it was a little awkward. How about "Apoptosis is the main type of programmed cell death in a multicellular organism, and involves an orchestrated series of biochemical events leading to a characteristic cell morphology and death." 128.111.209.143 19:37, 10 May 2007 (UTC)Mike

Nine syllables across 3 words is always going to be awkward. — Preceding unsigned comment added by 194.176.105.147 (talk) 15:57, 26 February 2013 (UTC)
 * The current first sentence is "Apoptosis is the process of programmed cell death (PCD) that may occur in multicellular organisms". The "may" is a bit vague here. Is this saying that that apoptosis is the multi-cellular organism form of PCD? This would not be correct as there are other forms of PCD that may occur in the cells of a multi-cellular organism. Is it saying that apoptosis only occurs in multi-cellular organisms? There is strong evidence for apoptosis in yeast (e.g. http://jcb.rupress.org/content/166/7/938.1, http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2555920/). The Gene Ontology differentiates apoptosis from PCD in general via characteristics such as "...lead to rounding-up of the cell, retraction of pseudopodes, reduction of cellular volume (pyknosis), chromatin condensation, nuclear fragmentation (karyorrhexis), plasma membrane blebbing and fragmentation of the cell into apoptotic bodies." (citations: GO:0006915, ISBN:0198506732, PMID:18846107, PMID:21494263). I'm not sure how best to condense this. I prefer Mike's suggestion from 2007 above to the current wording. Cmungall (talk) 00:13, 10 June 2013 (UTC)

About the mitochondrial apoptosis signalling pathway
The VDAC interacts with Bak to inhibit its own mitochondrial outermembrane permeablisation (MOMP) activity? I thought Bak or Bax can interact with VDAC to directly induce permeablisation (when they multimerise), and it's the binding of these pro-apoptotic proteins to the anti-apoptotic Bcl-2/Bcl-Xl that inhibits MOMP? Can someone clarify? -Unsigned
 * Actually the role of VDAC, if any, might be to assist Bax on membrane permeabilization. I think the issue is not sufficiently clear among scientists, so I would remove all mentions to VDAC until it is clarified. We should cite recent articles, not reviews from the nineties, which are obsolete - --85.50.70.8 (talk) 06:25, 28 April 2010 (UTC)Cristina Muñoz-Pinedo
 * Moreover, there is no evidence that Bcl-2 proteins control death downstream of mitochondrial permeabilization. I will remove this sentence and its reference, really old. --85.50.70.8 (talk) 06:27, 28 April 2010 (UTC)Muñoz-Pinedo

Statistics on cells developing into cancerous cells
I know I read somewhere that (statistically) each day, every human has two cells developing into cancer cells, but are stopped by the immune system via apoptosis. If someone can back this up, it should be included in the article. --Magnus Manske
 * The statistics mentioned by Magnus are quite relevant: I will add mention to this as soon as I find corroboration in a trusted publication. Of course, if someone corroborates this before I do, please add it. -- jaimeglz

Philosophical implications
What the article doesn't seem to discuss much is the philosophical implication of having a cell programmed to kill itself on purpose. Which is all fine and well, since its mostly a scientific article, but I have read many many articles in magazines that discuss apoptosis and cite it as the fact that being a kamikaze or a suicide bomber, or suicide itself isn't as "unnatural" as everyone makes it out to be, whether this is true/NPOV or not. But would there be a place for this in the article?

And on a different note, I think this article can make it for WP:FAC if there were some neat diagrams and images - I have already emailed a webmaster for permission to use one (which happens to be 300 KB large), but of course to be an FA you have to have more images. -- Natalinasmpf 06:33, 30 Apr 2005 (UTC)

 * Response: Sorry for taking so long to answer. There is no doubt on the importance of the implications of this topic for the philosophy of science. As Lowe et al. mention in their 18 Nov. 2004 Nature article, "Intrinsic tumour suppression": "Cell proliferation and cell death are such diametrically opposed cellular fates that the discovery that the two are linked and interdependent processes was a great surprise." However, the only way I foresee to legitimately introduce wider philosophical questions into a Wikipedia article like "apoptosis" would be to quote or paraphrase highly recognized authors' opinions. And there is an additional difficulty involved, because it has already been suggested that the article is too long (see discussion above). Suggestions are welcome, but probably the best solution will be to place material on the wider implications (when found) into articles dealing with the philosophy of science.
 * jaimeglz, 5 Mar. 2006.

Intercellular signals for apoptosis
This article doesn't appear to elaborate on this too much, especially, how do immune cells recognise cells that have been infected by viruses? Do their cell membranes change, or something? Do they withdraw signals? And of other things, for example, a lack of a cell stimuli as much as presence of stimuli can also cause apoptosis (I have read) - ie. if there's a cell without an "anchor" tying it to other cells at a cer Would the article explain more on this programming? Can more be elaborated on this? If we don't know (we probably don't know a lot), can the article clarify? -- Natalinasmpf 19:22, 24 Jun 2005 (UTC)
 * Response: There is abundant reference material on cell signalling at the end of the article. Follow the links and take a look: many of the papers are quite readable for the non-specialist. Would you really like to dig into the subject? Alberts et al. monumental Molecular Biology of the Cell (with its step-by-step explanation) can be read for free on the web. jaimeglz 5 Mar. 2006

Apoptosis pronunciation
The article only mentions one pronunciation, and the reference link provided says that it's controversial. I've heard the word said by professionals in any of 4 different ways, and don't like the idea that the article only mentions one. While I pronounce it with a silent second-p, I don't accept that as standard because I also don't pronounce "helicopter" as "helicotter," nor do I use Greek and Latin plurals when an English one is acceptable. To me, the pronunciation as indicated is derived from pretentiousness rather than accuracy, because if accuracy was the issue, ptosis wouldn't be the most accurate Greek suffix.--Trypsin 15:31, 2 May 2006 (UTC)
 * I have always pronounced it as A-POP-TOW-SIS, I have only ever heard this pronounciation. I would like to see some mention in the article that the pronounciation is disputed (just like the linked to article). Adenosine | Talk 17:56, 27 June 2006 (UTC)
 * I do the same, mainly because I read the word before I heard it and the phonetic pronunciation stuck. --  Serephine   ♠   talk   - 03:36, 18 December 2006 (UTC)
 * I got yelled at by an old boss for doing that... so it's been ingrained in me to silence the 'p' (as in "pterosaur"). – ClockworkSoul 18:51, 18 December 2006 (UTC)
 * Well from one of my lectures with Professor Wyllie, he himself said that the correct pronunciation is with A-POP-TOW-SIS (pronouncing the "p"). He explained that, in Greek, when the "pt" is in the middle of the word, the "p" should be pronounced. 128.232.249.94 14:07, 25 February 2007 (UTC)

Having lived in Greece, and speaking fluent Demotic Greek, I can say that the Greeks do pronounce both the 'p' and the 't'.

but it is commonly pronounced exactly as written despite the fact that in Greek it would be pronounced with a silent second p: The linked reference did not say which pronunciation was more common and in fact leaned on the silent-p side. So I changed this to with opinion divided between a pronunciation with a silent p (a-PO-tosis), and the p spelt out (a-POP-tosis). - Two  Oars  19:04, 11 August 2007 (UTC)

It is clearly spelled out phonetically in Taber's Cyclopedic Medical Dictionary as being pronounced as both ă-pŏp-tŏ’sĭs and apo tō' sis. I find it to be regional on which pronunciation is used. —Preceding unsigned comment added by 76.90.57.194 (talk) 20:25, 12 October 2007 (UTC)

What about "apo-PTO-sis"? This would be etymologically the most "correct;" that is, most in line with classical Greek as it is pronounced by modern English-speaking Classicists. I'm not sure that's totally relevant- perhaps the pronunciation of modern English-speaking bilogists is more important; but if there are going to be claims of historical correctness, this is the one that should take it. Just a suggestion. Helikophis (talk) 19:26, 26 December 2007 (UTC)

There has never been a "silent p" in Greek; the p is always articulated regardless of its position in the word. It is only silent in English, and only word-initially. I have tweaked the text to reflect that. ·ΚΕΚΡΩΨ· (talk) 12:32, 16 May 2008 (UTC)

 The following should put the debate to rest.

Has anyone ever tried finding the original source of the word? If you did, you would have found the original article (here is a pubmed link without the text: http://www.ncbi.nlm.nih.gov/pubmed/4561027).

In the article, it clearly states in a footnote how the original authors wanted the word pronounced. The following is a direct quotation of this footnote:

'We are most grateful to Professor James Cormack of the Department of Greek, University of Aberdeen, for suggesting this term. The word "apoptosis" (Greek spelling of apoptosis) is used in Greek to describe the "dropping off" or "falling off" of petals from flowers, or leaves from trees. To show the derivation clearly, we propose that the stress should be on the penultimate syllable, the second half of the word being pronounced like "ptosis" (with the "p" silent), which comes from the same root "to fall", and is already used to describe the drooping of the upper eyelid. '

There is still a problem with the IPA form, there's no such thing as a 'soft p' in English. Either the 'p' is pronounced, and then it is /ptosis/, or it is not pronounced, and then it is /tosis/. The whole point of the IPA is to reflect what is actually pronounced... Besides isn't it awkward to give one pronouciation and refer to a dictionary which recommends another ? I'd say that the word doesn't belong to the person who introduces it. The pronounciation without 'p' seems contrary to English usage.

Prof. James Cormack is correct. The p is silent. And it is wrong and misleading to say "A-poptosis" as one so often hears. Doctors are used to words like apraxia, aphasia etc, which indicates a negative condition. But there is no such thing as a "Poptosis", so you cannot have a lack of it. The correct pronounciation is "Apo-(p)tosis", withg equal stress on both syllables and a silent "P" Historygypsy (talk) 14:20, 7 June 2009 (UTC)

Role of NO
Hi, I am a little puzzled that the role of nitric oxide in regulating apoptosis has not been given due importance in this article. I would be enlightened if someone could include the significance of NO given that this topic of research is being pursued greatly in scientific circles. Thanks. Sriram sh 07:39, 6 December 2006 (UTC)
 * Thankyou for pointing this out, I've included a small reference to this in the text. --  Serephine   ♠   talk   - 03:36, 18 December 2006 (UTC)
 * Hi, thanks Serephine for that little bit of information. I really appreciate that very much especially since I have been scouring all over the place for relevant and useful info. Sriram sh 08:59, 24 December 2006 (UTC)

Much was lost in the rewriting of the article
Citation and recognition of articles by women and young researchers is gone. Citations and recognition of articles by both a variety of US, European and other nationality researchers is gone. The history of how apoptosis was researched, discovered and brought to the forefront of international science by both collaboration and competition by many different people has been removed from the article and placed somewhere else, despite that it was explicitly asked in this discussion section not to do so.

I perfectly understand that any article can be subjected to changes by any contributor, and that the order or the wording could have benefited a lot from good editing. However, great care had been taken to make the article acurate and founded on the best scientific literature available.
 * Sorry for the tone of the note I left yesterday. I take it back, and recognize it was totally inapproprite. Although it is not a justification, I did get irked at the fact that I had explicitly requested the article not to be broken into several pieces, and I still don't understand why there has been so much insistence. -jaimeglz

 * OK, well I'm assuming that this is directed at me as I rewrote this article a few weeks ago. I'd like to address a couple of issues you raised here:

 * 1) I'm Australian and have no interest in promoting a US-centric point of view. If anything, the Americanisation of Wikipedia irks me. I maintain the British English spelling of the Golgi apparatus article in silent protest against this fact, so please don't accuse me of something so unfounded. I moved all citations, at great trouble (every one was checked against the sentence I included it in), to the in-line style of referencing, as you noticed. I even added a few new ones. I removed any reference not contributing to the article after I edited it, these were references dealing with extremely complicated topics which, in all honesty, would interest no-one but an expert in the field. Said expert doesn't need the help of an online encyclopaedia to find these articles, hence my justification in removing all of 3 articles.
 * 2) The history of apoptosis has been removed to its own page, and linked from the main article. This, I believe, was a good move on my behalf to centre the article more on the process and function of apoptosis, which the majority of the visitors would want from the page. Should you wish to include an outline of the major points along with the link, please feel free, indeed this would only improve the article.
 * Your passive-aggressive tone in denouncing my changes comes as somewhat of a disappointment considering that part of your spiel was directed at how I've degraded the article, somewhat ironic since you have broken a Wikipedian tenet and haven't assumed good faith. I think that the elucidation of the article, the inclusion of diagrams, cleaned up references, improved readability and the promotion of the article from a "B" to an "A" class article would actually contradict your entire basis for your attack. I would hope that you would consider simply listing your grievances in the future rather than launching into a sarcastic attack on both my personal inclinations and the tenets of Wikipedia. Quite frankly, I'm offended and insulted. --  Serephine   ♠   talk   - 00:51, 1 January 2007 (UTC)

Justification
Your note had all the hallmarks of being written more with passion than calculated thoughtfulness, so it's ok :) It's natural to feel very protective of something you've worked very hard upon - as I saw with the level of references included in the article. I was very impressed with this, and this was in part the reason I initiated my large clean-up. Plus you re-worded the tone of your note and effectively apologised, for that I can easily forgive you - although I hope you mean that it was inappropriate because it was unprofessional rather than because I am not American ;) To address your points and hopefully reach a conclusion: Should you have any concerns over my justifications and still do not agree with the direction the article has taken, please let me know and we can get a couple of people from Wikiproject MCB to arbitrate and input into any issues. I realise that you've said "much was lost in the rewriting of this article", but look at how much has been gained: readability, context, diagrams, easy references, appropriate headings, and of course it scraped up an "A" and paved the way for further contribution. Thanks for your understanding --  Serephine   ♠   talk   - 02:00, 2 January 2007 (UTC)
 * 1) When removing references, I did not remove them on the basis of whether they were by PhD students or women. I removed them because they no longer had any relevance to the text. There is no need to "fill-up" references to make sure all demographics are equally represented, therefore your point, to me, makes no sense. I myself am female and not a researcher, therefore I can't be accused of bias.
 * 2) On the topic of removing references, my justification for removing them stemmed from the fact that referencing was not in-line: i.e. not linked from the end of the sentence/paragraph it supports. Therefore, when placing the references I had to check each (both the abstract and full text thanks to a university proxy) to see what exactly they supported. Hence when cleaning up the article from reading like a journal review to reading like an encyclopaedia ("Thibert et al. showed that..." -> "It has been shown that  ") there were inevitably references which had to be removed, as they had no relevance in the text.
 * 3) On the topic of cleaning up: when I first came to this article I recoiled in horror at the unfriendly and unreadable layout; big, unbroken paragraphs, a review-like format, needlessly detailed explanations, sections referring back to previous sections, a big clunky list of references at the end (though I noticed the effort on the discussion page to neaten these up, most impressive). I re-did the headings and systematically rewrote the article to be readable by at least a university student (which I am). The problem at hand was prose: there was no flow in idea progression or sentence - hence when reading a paragraph you would need to recheck it a couple of times to understand what was being said, and even then you might come across the dastardly "See also above ...". There were sections also that made no sense as context was not provided.
 * 4) I tried not to eliminate detail where possible, and rewrote much of it to be relevant to the article. I apologise for removing it, I know the feeling of having a large chunk of work removed, but I was being brutal to mould the page into a useful one for anyone who came across it. I shouldn't have to say that Wikipedia isn't a scientific encyclopaedia - it's open to anyone and therefore the information should be written for anyone interested in that topic. Detail like what I removed would be better used in an article more specific for the processes, where the hardcore enthusiasts and scientifically literate would be more inclined to go for that calibre of information.
 * 5) Finally, the history move. Another aplology on my behalf - I didn't not see the discussion on this page. I was being a bold editor, though I think it was for the better. I do not think the article in it's entirety should be moved back to this page - it is big enough as a separate entity to exist on its own. However, as I mentioned above, a short summary of the main points would flesh out the heading in the main article and encourage people to visit the history article.

Mispronounciation
Letters that appear in words derived from Latin roots that are not pronounced (such as the p in pneumonia or pteradactyl are in fact pronounced when the letter from the same root appears within the middle of a word, as in the case of the second p in the word apoptosis (the second Latin root being ptosis, in which the p is not pronounced when it begins the word) or the c in the word gastrocnemius. Thus there is no legitimate pronunciation of this word without the second letter p.  DRosenbach  ( Talk 13:43, 15 January 2008 (UTC)
 * You mean Greek and pterodactyl. ·ΚΕΚΡΩΨ· (talk) 11:58, 16 May 2008 (UTC)
 * It appears that the pronunciation guide and the explanation of the guide are contradictory. I'm not up on my IPA, but isn't the second "p" supposed to be absent from the guide if it's silent? -Bobsagat 21:19 CST, Feb 13 2009  —Preceding undated comment was added at 03:19, 14 February 2009 (UTC).

Reply
Apoptosis is not a common word, but a fusion, a word made up by medical people to explain a phenomenon. The word was (clumsily) constructed to describe programmed cell death, where defective or damaged or aged cells literally "close up and fall away" of their own accord, a sort of cell suicide due to innate cell programming which quietly does away with unwanted cells. Apo refers to from, away from, off, asunder or separate. Ptosis originally referred to autumn leaves which shrivel up and fall away, hence "apo-tosis". The word should be pronounced "Apo-tosis", never "apop-tosis" nor "a-poptosis, since cells do not "poptose" nor to they "tose" (even without a "p"). One consequence of failure of the apoptosis mechanism allows cancer cells to survive and multiply instead of performing "seppuku" (The correct term for harakiri, the later is vulgar "Cut Belly") Historygypsy (talk) 18:12, 17 May 2011 (UTC)

Caspases
In Execution it talks about the process happening in finality through proteolytic caspases. I am wondering if this is being excessively descriptive? When I looked up what a caspase was, it says they are a family of proteases. Since all proteases engage in proteolysis, it leads me to presume there is no such thing as a non-proteolytic caspase, and as such, the adjective is unnecessary? Sort of like saying a mammally dolphin or something (I apologize for my lack of ability to compose a good analogy). Tyciol (talk) 18:14, 29 November 2008 (UTC)
 * a fair point but English frequently uses mild repetition/redundancy for emphasis. "very unique" for example or "proteolytic degradation" or even to quote your own comment, "process happening". They aren't purely redundant. I think people find them reassuring or maybe they just save you the mental effort of extracting the meaning of a statement that is overly concise. Wikipedia usually is not written in the tight style of a journal article since the audience is broader. Oh, another favorite of these phrases is "radiating outward" or even (I actually heard this in a lecture) "radiating radially outward". 71.237.182.219 (talk)jawshoeaw —Preceding undated comment added 13:01, 2 March 2009 (UTC).

mouse foot picture
That picture is not very clear - a skeptic (no, I've never heard of apoptosis doubters but good little scientist larvae rightfully ask these questions) might say for example that the digits just grow longer - a second photo would be nice, or arrows demonstrating unambiguously that apoptosis is necessary for interdigital separation. The second photo of the mature rat or mouse foot was too funny. Too many pictures on wikipedia are like this - essentially just stock photos that do not support the articles or support them weakly. There was a science journal parody years ago with an article about the flexibility of stock photos to meet the needs of many scientific disciplines - only the captions needed to be changed. —Preceding unsigned comment added by 71.237.182.219 (talk) 12:52, 2 March 2009 (UTC)

The last sentence of the mouse foot picture caption reads "(Compare this image with image of leg of mouse.)". Where is the picture of the mouse leg to compare with? SpencerCollins (talk) 09:04, 10 June 2010 (UTC)

 * I was wondering that, too. David Spector (talk) 15:02, 21 December 2011 (UTC)

Mitochondria?
Does it all mean if mitochondria are destroyed in a cell it will self destruct due to released factors? —Preceding unsigned comment added by 91.99.166.36 (talk) 12:17, 30 January 2010 (UTC)

doesn't add up

 * For an average child between the ages of 8 and 14, approximately 20 billion to 30 billion cells die a day. In a year, this amounts to the proliferation and subsequent destruction of a mass of cells equal to an individual's body weight. []

The cell article claims we have about 10^14 cells, so something's wrong somewhere, probably the sentence with the challenge tag, which I removed. Please undo/correct/whatever if you know better. --99.245.206.188 (talk) 03:19, 3 July 2010 (UTC)

yeah by my upper limit estimates this would be around 5kg assuming average cell volume of 450fl and approx density of water 147.252.112.85 (talk) 18:23, 21 February 2011 (UTC)

Evolution?
I can't find any mention in the article of how apoptotic processes might have evolved. This is, I think, rather important information and it could be of interest to other readers.24.245.92.178 (talk) 23:17, 23 August 2010 (UTC)

Image showing ossification should be replaced
Hi! I am new to editing Wikipedia, but I have relevant expertise for this article. The image now accompanying the article shows bone formation from cartilage. Although cartilage cells are said to degenerate in this process, their morphology is quite far from that which is typical for apoptosis. In my opinion, the image should be removed until a more suitable new image can be located. A suggestion for a new image is figure 2 from the following scientific article: http://arthritis-research.com/content/10/4/R86. This image may be freely used provided a proper reference to the original work is made, according to the journal's copyright policy. As I am so new to this I don't really dare to make these changes myself. /GN 130.229.40.79 (talk) 07:41, 15 August 2011 (UTC)

Control Of The Apoptotic Mechanisms picture
Does anyone know how to contact the author of picture to get him to correct the misspelling "mecanism"? Thanks /Carl.moxey (talk) 16:00, 18 August 2011 (UTC)

Merger proposal
Induce apoptosis in cancer cell lines is based entirely on primary sources (see WP:MEDRS). If there is any content that can be sourced to secondary reviews, it can be added here. I propose that article be merged and redirected to here. Sandy Georgia (Talk) 14:33, 3 April 2012 (UTC)
 * And another one, created same day; although this one is sourced mostly to a secondary review compliant with WP:MEDRS, it doesn't seem to cover any territory that doesn't belong here? Viral induction of apoptosis.  Sandy Georgia  (Talk) 14:54, 3 April 2012 (UTC)

 * Support Jesse V. (talk) 15:19, 3 April 2012 (UTC)

 * The article by Acrani has been cited in three other articles. I found these citations in Google scholar. I am new to this program so any information on the next step which I should take is very helpful to me. Below is a link of one of the articles where Acrani has been cited.

 * http://www.jbc.org/content/286/5/3227.full#xref-ref-9-1 — Preceding unsigned comment added by Nmcca (talk • contribs) 18:22, 3 April 2012 (UTC)

 * Support – the new articles are very specialized and can easily fit within the scope of the parent article. In addition, I agree that secondary sources are preferable.  However WP:MEDRS applies to articles that are "sources of health information".  These articles concern more basic science that may eventually have health implications, but the subject matter is currently restricted to the lab and not the clinic. Please also note that according to Secondary_source "A survey of previous work in the field in a primary peer-reviewed source is secondary".  So we will make a good faith effort to find relevant secondary sources, but I think it is going overboard to insist that all of the sources are secondary. Boghog (talk) 19:20, 3 April 2012 (UTC)

I have no problem with merging the article to the parent article. Do I do this myself or do you slot it in where you find it most appropriate? — Preceding unsigned comment added by Nmcca (talk • contribs) 22:12, 3 April 2012 (UTC)

I have merged my content with the apoptosis page as you recommended. I have also added my info to the HeLa cell page, however when I click on the link "induce apoptosis in cancer cell lines " it takes me to the page I created. I would like to know if you can assist me in changing this so that the link goes to the apoptosis page instead. Thank you. — Preceding unsigned comment added by Eottergonzalez (talk • contribs) 02:40, 6 April 2012 (UTC)

 * The links in the merge proposal explained how to do a merge in a way that respects Wikipedia licensing ... that wasn't done, so I redid it all. I believe everything is done now, but most of the article Induce apoptosis in cancer cell lines relied on primary sources, so that text here should be reviewed with the aim of either upgrading it to secondary reviews or deleting that text if necessary.  Sandy Georgia  (Talk) 21:01, 13 April 2012 (UTC)

Misleading acronym: File:TFN-signalling.png
Hi, just wanted to note a small error but an error non the less. The text speaks about tumor necrosis factor TNF but the image at "Process->TNF path" speaks of TFN or tumor factor necrosis. — Preceding unsigned comment added by 80.217.108.22 (talk) 16:05, 26 November 2012 (UTC)

Blebbishield emergency program, etc
I'm moving the content of this edit from the lead to the talk page, per WP:UNDUE (I think). Although the information appears interesting and might fit somewhere deeper into the page I think it is inappropriately weighted in the lead (as a search term, "blebbishield" currently gets just 8 hits on Google Scholar).

"For example, cancer stem cells can resurrect after apoptosis using recently discovered blebbishield emergency program."

Figure: Overview of TNF (left) signalling in apoptosis
The abbreviation of tumor necrosis factor is TNF as stated in the description of the figure. Why does the author use TFN instead of TNF two times within the figure? First for the receptor (upper left corner) and also for the ligand (green triangle)? Giseler146 (talk) 16:46, 14 March 2015 (UTC)

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title: Talk:Apoptosis


text:
Appomattox

Appomattox, shorthand for the surrender of Robert E. Lee to Ulysses S. Grant in the American Civil War, may refer to:

 * Battle of Appomattox Court House, a battle of the American Civil War that was a culmination of the Appomattox Campaign and resulted in the surrender of Robert E. Lee
 * Appomattox Court House National Historical Park, a National Historical Park in Virginia at the site of the surrender

Appomattox may also refer to:
 * Appomattox County, Virginia, in the United States
 * Appomattox, Virginia, a town and the seat of that county
 * Appomattox Court House (disambiguation), several courthouses in Appomattox, Virginia
 * Appomattox River, a tributary of the James River in Virginia
 * Appomattox Basin, a name for the Tri-Cities, Virginia region
 * Appomattox Manor, a manor in City Point, Hopewell, Virginia
 * Battle of Appomattox Station, a battle of the American Civil War in Appomattox, Virginia, a day before the Battle of Appomattox Court House
 * SS Appomattox, a large American wooden steamship operated mainly on the Great Lakes
 * SS Appomattox (1893), a British steamship of the early 20th century
 * Appomattox (opera), a 2007 opera in based on the American Civil War, composed by Philip Glass
 * Appomattox (statue), a bronze Confederate soldier memorial in Alexandria, Virginia

title: Appomattox