document_title: Hills Like White Elephants

question_text: what is the operation in hills like white elephants

text: Hills Like White Elephants

text: Synopsis[edit]

text: The story focuses on a conversation between an American man and a woman at a Spanish train station while waiting for a train to Madrid. The woman compares the nearby hills to white elephants. The pair indirectly discuss an "operation" that the man apparently wants the woman to have, which is implied to be an abortion.[2]

text: Dialogue[edit]

text:
"They look like white elephants," she said.
"I've never seen one," the man drank his beer.
"No, you wouldn't have."
"I might have," the man said. "Just because you say I wouldn't have doesn't prove anything."
The girl looked at the bead curtain. "They've painted something on it," she said. "What does it say?"
"Anis del Toro. It's a drink."
"Could we try it?"

text: The reader must interpret their dialogue and body language to infer their backgrounds and their attitudes with respect to the situation at hand, and their attitudes toward one another. From the outset of the story, the contentious nature of the couple's conversation indicates resentment and unease. Some critics have written that the dialogue is a distillation of the contrasts between stereotypical male and female relationship roles: in the excerpt above, for instance, the woman draws the comparison with white elephants, but the hyper-rational male immediately denies it, dissolving the bit of poetry into objective realism with "I've never seen one." By saying, "No, you wouldn't have" she implies he hadn't had a child before, or hadn't allowed birth in the past. She also asks his permission to order a drink. Throughout the story, the woman is distant; the American is rational.[3] There may be more serious problems with the relationship than the purely circumstantial. While most critics have espoused relatively straightforward interpretations of the dialogue, a few have argued for alternate scenarios.[4]


document_title: The Delivery (The Office)

question_text: who plays the lactation consultant in the office

root

text: The Delivery (The Office)

text: Synopsis[edit]

text: Pam (Jenna Fischer) and Jim (John Krasinski) both acquire sales while making small talk about their baby's upcoming birth. Dwight (Rainn Wilson) wants to do the same and asks Angela (Angela Kinsey) to have a baby with him. Angela is initially excited, but gets annoyed with Dwight making a parenting contract with absurd demands he wants her to agree to.

tag: p

text: Michael (Steve Carell) anxiously waits for Pam and Jim's baby to be born; Jim urges Pam to let him take her to the hospital, but Pam would rather wait until midnight like she and Jim wanted to do initially (arriving after midnight means a longer hospital stay under the terms of their health insurance). She finds comfort in watching the rest of the office performing absurd activities to distract her from the pain. When Jim reaches his breaking point, Pam reveals that their baby is a girl, which calms Jim's nerves a bit, but then she tells him that her water broke.

text: Since Pam and Kevin (Brian Baumgartner) have gotten hungry at the same times, they have enjoyed regular meals together, and Kevin prepares her one final "Ultra Feast" before she gives birth. When the contractions appear to become too extreme, Jim, Michael, and Kevin all think it is time for her to go to the hospital. Pam still refuses, and finally breaks down admitting she is too scared to give birth. Jim initially assures her that everything will be all right, but goes into a panic when he's informed she is now at 2 minutes in between contractions (5–7 minutes is the suggested time to leave for the hospital). Pam finally acquiesces and Michael drives her and Jim to the hospital, with Dwight "escorting" them. Pam realizes she has forgotten her iPod with her desired birth music on it so they request that Dwight retrieve it from their house, asking that he not "touch anything". After 19 hours of labor Cecelia Marie Halpert is born at 8:31 pm, weighing in at 7 lbs 2oz.

text: Pam's breastfeeding does not go well, and though a male lactation consultant (Lee Kirk, Jenna Fischer's husband, and at that time Jenna's fiance) is summoned to provide apparently successful coaching, Cecelia still fails to "latch" properly. Against the advice of the nurse, Jim and Pam opt to have Cecelia spend the night with them instead of in the nursery, and they are kept up long hours tending to her. A sleep-deprived Pam accidentally nurses a baby that belongs to a new mom (Melissa Rauch) in the same hospital room. As Jim and Pam get ready to leave the hospital, Pam manages to breast feed Cecelia while Jim gets the car (which is littered with parking tickets, thanks to Michael parking the car in an ambulance only zone).

text: In the meantime, Michael sees the birth as proof that he is a successful office matchmaker. He sets up Kevin on a lunch date with Erin (Ellie Kemper), making Andy (Ed Helms) jealous and finally driving him to consider actually asking her out himself, to which she happily accepts as Michael looks on.

text: At the Halpert residence, Dwight embarks on a search for the iPod only to find mold under the sink and moves in for several days while he reconstructs the cabinets. Dwight and Angela make the final revisions to the parenting contract, but Dwight begins to have second thoughts after an encounter with Pam's friend Isabel (Kelen Coleman), with whom he had a one night stand at Jim and Pam's wedding. He signs the contract, but decides to hold it off.

text: Production[edit]

text: The first part of the episode was written by Daniel Chun his second writing credit for the series after "Murder" and directed by Seth Gordon his second directing credit for the series after "Double Date".[2] The second part was written by Charlie Grandy, his fourth writing credit of the series and directed by Harold Ramis, who also directed "A Benihana Christmas," "Safety Training" and "Beach Games."[3] The episode also guest stars Nelson Franklin playing Nick the IT Administrator who would appear in later episodes and Linda Purl who played Helene, Pam's mother who previously dated Michael.[4]

text: Reception[edit]

text: In its original American broadcast, part one of "The Delivery" was watched by 8.71 million viewers, with a 4.5 rating and a 12 share in the 18–49 demographic, with part two increasing in viewers to 9.35 million and a 4.9 rating and a 13 share winning its timeslot both times and helping NBC come third ahead of ABC and The CW.[5] The episode ranked 10th in the weekly 18–49 ratings and ranked 24th in total viewers weekly ratings.[6] It was the last episode of The Office to be viewed by over 9 million viewers.

text: Dan Phillips of IGN gave the episode a 6.6 saying that Pam's lactation problems and Kevin's lack of personality while dating Erin made consistently amusing plots, "But sadly everything that the episode's half-hour gets right doesn't make up for the painfully uncomfortable and largely unfunny first half." He particularly objected to the length that Pam's refusal to go to the hospital is stretched out, since the entire office supporting her irrational decision even after her water breaks was "uncomfortable and unbelievable".[7] Ken Tucker of Entertainment Weekly gave the episode a positive review saying "Last night managed to combine a thoroughly believable and funny central idea—that Pam would try to delay going to the hospital to get some extra time, gaming the office’s “stupid HMO”—with a batch of fine Michael scenes and a thoroughly didn’t-buy-it-for-a-second Dwight subplot."[8] Nathan Rabin of The A.V. Club gave the episode a B+ saying "It felt a little padded and implausible and lurched from one radically different tone to another but it was also very funny and intriguingly prickly and real when it wasn't being cartoonish and over the top. It wasn't a home run."[9]

text: Joel Keller of TV Squad gave the episode a mixed review saying "As usual with most one-hour 'Office' episodes, the first half was better than the second. But even the first half of this one had some problems".[10]


document_title: Mitochondrion

question_text: the job of mitochondria is to supply cells with

question_tokens: the job of mitochondria is to supply cells with

text: Mitochondrion

text: History

text: The first observations of intracellular structures that probably represented mitochondria were published in the 1840s.[19] Richard Altmann, in 1890, established them as cell organelles and called them "bioblasts".[19][20] The term "mitochondria" was coined by Carl Benda in 1898.[19][21] Leonor Michaelis discovered that Janus green can be used as a supravital stain for mitochondria in 1900. In 1904, Friedrich Meves, made the first recorded observation of mitochondria in plants in cells of the white waterlily, Nymphaea alba[19][22] and in 1908, along with Claudius Regaud, suggested that they contain proteins and lipids. Benjamin F. Kingsbury, in 1912, first related them with cell respiration, but almost exclusively based on morphological observations.[19] In 1913, particles from extracts of guinea-pig liver were linked to respiration by Otto Heinrich Warburg, which he called "grana". Warburg and Heinrich Otto Wieland, who had also postulated a similar particle mechanism, disagreed on the chemical nature of the respiration. It was not until 1925, when David Keilin discovered cytochromes, that the respiratory chain was described.[19]

text: In 1939, experiments using minced muscle cells demonstrated that cellular respiration using one oxygen atom can form two adenosine triphosphate (ATP) molecules, and, in 1941, the concept of the phosphate bonds of ATP being a form of energy in cellular metabolism was developed by Fritz Albert Lipmann. In the following years, the mechanism behind cellular respiration was further elaborated, although its link to the mitochondria was not known.[19] The introduction of tissue fractionation by Albert Claude allowed mitochondria to be isolated from other cell fractions and biochemical analysis to be conducted on them alone. In 1946, he concluded that cytochrome oxidase and other enzymes responsible for the respiratory chain were isolated to the mitchondria. Eugene Kennedy and Albert Lehninger discovered in 1948 that mitochondria are the site of oxidative phosphorylation in eukaryotes. Over time, the fractionation method was further developed, improving the quality of the mitochondria isolated, and other elements of cell respiration were determined to occur in the mitochondria.[19]

text: The first high-resolution electron micrographs appeared in 1952, replacing the Janus Green stains as the preferred way of visualising the mitochondria.[19] This led to a more detailed analysis of the structure of the mitochondria, including confirmation that they were surrounded by a membrane. It also showed a second membrane inside the mitochondria that folded up in ridges dividing up the inner chamber and that the size and shape of the mitochondria varied from cell to cell.

text: The popular term "powerhouse of the cell" was coined by Philip Siekevitz in 1957.[23]

text: In 1967, it was discovered that mitochondria contained ribosomes.[24] In 1968, methods were developed for mapping the mitochondrial genes, with the genetic and physical map of yeast mitochondrial DNA being completed in 1976.[19]

text: Origin and evolution

text: There are two hypotheses about the origin of mitochondria: endosymbiotic and autogenous. The endosymbiotic hypothesis suggests that mitochondria were originally prokaryotic cells, capable of implementing oxidative mechanisms that were not possible for eukaryotic cells; they became endosymbionts living inside the eukaryote.[25] In the autogenous hypothesis, mitochondria were born by splitting off a portion of DNA from the nucleus of the eukaryotic cell at the time of divergence with the prokaryotes; this DNA portion would have been enclosed by membranes, which could not be crossed by proteins. Since mitochondria have many features in common with bacteria, the endosymbiotic hypothesis is more widely accepted.[25][26]

text: A mitochondrion contains DNA, which is organized as several copies of a single, circular chromosome. This mitochondrial chromosome contains genes for redox proteins, such as those of the respiratory chain. The CoRR hypothesis proposes that this co-location is required for redox regulation. The mitochondrial genome codes for some RNAs of ribosomes, and the 22 tRNAs necessary for the translation of messenger RNAs into protein. The circular structure is also found in prokaryotes. The proto-mitochondrion was probably closely related to the Rickettsia.[27][28] However, the exact relationship of the ancestor of mitochondria to the alphaproteobacteria and whether the mitochondrion was formed at the same time or after the nucleus, remains controversial.[29]

text: A recent study[30] by researchers of the University of Hawaii at Manoa and the Oregon State University indicates that the SAR11 clade of bacteria shares a relatively recent common ancestor with the mitochondria existing in most eukaryotic cells.

text:
Phylogeny of Rickettsiales

Magnetococcidae

Magnetococcales

Magnetococcaceae

Magnetococcus marinus

Caulobacteridae

Rhodospirillales, Sphingomonadales, Rhodobacteraceae, Rhizobiales, etc.

Holosporales

Rickettsidae

Pelagibacterales

Pelagibacteraceae

Pelagibacter

subgroups Ib, II, IIIa, IIIb, IV and V

Proto-mitochondria

Anaplasmataceae

Ehrlichia

Anaplasma

Wolbachia

Neorickettsia

Midichloriaceae

Midichloria

Rickettsiaceae

Rickettsia

Robust 16S + 23S phylogeny of Rickettsidae from Ferla et al. (2013)[31]

tag: table

text: The ribosomes coded for by the mitochondrial DNA are similar to those from bacteria in size and structure.[32] They closely resemble the bacterial 70S ribosome and not the 80S cytoplasmic ribosomes, which are coded for by nuclear DNA.

text: The endosymbiotic relationship of mitochondria with their host cells was popularized by Lynn Margulis.[33] The endosymbiotic hypothesis suggests that mitochondria descended from bacteria that somehow survived endocytosis by another cell, and became incorporated into the cytoplasm. The ability of these bacteria to conduct respiration in host cells that had relied on glycolysis and fermentation would have provided a considerable evolutionary advantage. This symbiotic relationship probably developed 1.7[34] to 2[35] billion years ago.

text: A few groups of unicellular eukaryotes have only vestigial mitochondria or derived structures: the microsporidians, metamonads, and archamoebae.[36] These groups appear as the most primitive eukaryotes on phylogenetic trees constructed using rRNA information, which once suggested that they appeared before the origin of mitochondria. However, this is now known to be an artifact of long-branch attraction—they are derived groups and retain genes or organelles derived from mitochondria (e.g., mitosomes and hydrogenosomes).[1]

text: Monocercomonoides appear to have lost their mitochondria completely and at least some of the mitochondrial functions seem to be carried out by cytoplasmic proteins now.[37]

text: Structure

text: A mitochondrion contains outer and inner membranes composed of phospholipid bilayers and proteins.[13] The two membranes have different properties. Because of this double-membraned organization, there are five distinct parts to a mitochondrion. They are:

text:
the outer mitochondrial membrane,
the intermembrane space (the space between the outer and inner membranes),
the inner mitochondrial membrane,
the cristae space (formed by infoldings of the inner membrane), and
the matrix (space within the inner membrane).

tag: ol

text: Mitochondria stripped of their outer membrane are called mitoplasts.

text: Outer membrane

text: The outer mitochondrial membrane, which encloses the entire organelle, is 60 to 75 angstroms (Å) thick. It has a protein-to-phospholipid ratio similar to that of the eukaryotic plasma membrane (about 1:1 by weight). It contains large numbers of integral membrane proteins called porins. These porins form channels that allow molecules of 5000 daltons or less in molecular weight to freely diffuse from one side of the membrane to the other.[13] Larger proteins can enter the mitochondrion if a signaling sequence at their N-terminus binds to a large multisubunit protein called translocase of the outer membrane, which then actively moves them across the membrane.[39] Mitochondrial pro-proteins are imported through specialised translocation complexes. The outer membrane also contains enzymes involved in such diverse activities as the elongation of fatty acids, oxidation of epinephrine, and the degradation of tryptophan. These enzymes include monoamine oxidase, rotenone-insensitive NADH-cytochrome c-reductase, kynurenine hydroxylase and fatty acid Co-A ligase. Disruption of the outer membrane permits proteins in the intermembrane space to leak into the cytosol, leading to certain cell death.[40] The mitochondrial outer membrane can associate with the endoplasmic reticulum (ER) membrane, in a structure called MAM (mitochondria-associated ER-membrane). This is important in the ER-mitochondria calcium signaling and is involved in the transfer of lipids between the ER and mitochondria. [41] Outside the outer membrane there are small (diameter: 60Å) particles named sub-units of Parson.

text: Intermembrane space

text: The intermembrane space is the space between the outer membrane and the inner membrane. It is also known as perimitochondrial space. Because the outer membrane is freely permeable to small molecules, the concentrations of small molecules, such as ions and sugars, in the intermembrane space is the same as in the cytosol.[13] However, large proteins must have a specific signaling sequence to be transported across the outer membrane, so the protein composition of this space is different from the protein composition of the cytosol. One protein that is localized to the intermembrane space in this way is cytochrome c.[40]

text: Inner membrane

text: The inner mitochondrial membrane contains proteins with five types of functions:[13]

text:
Those that perform the redox reactions of oxidative phosphorylation
ATP synthase, which generates ATP in the matrix
Specific transport proteins that regulate metabolite passage into and out of the matrix
Protein import machinery
Mitochondrial fusion and fission protein

text: It contains more than 151 different polypeptides, and has a very high protein-to-phospholipid ratio (more than 3:1 by weight, which is about 1 protein for 15 phospholipids). The inner membrane is home to around 1/5 of the total protein in a mitochondrion.[13] In addition, the inner membrane is rich in an unusual phospholipid, cardiolipin. This phospholipid was originally discovered in cow hearts in 1942, and is usually characteristic of mitochondrial and bacterial plasma membranes.[42] Cardiolipin contains four fatty acids rather than two, and may help to make the inner membrane impermeable.[13] Unlike the outer membrane, the inner membrane doesn't contain porins, and is highly impermeable to all molecules. Almost all ions and molecules require special membrane transporters to enter or exit the matrix. Proteins are ferried into the matrix via the translocase of the inner membrane (TIM) complex or via Oxa1.[39] In addition, there is a membrane potential across the inner membrane, formed by the action of the enzymes of the electron transport chain.

text: Cristae

text: The inner mitochondrial membrane is compartmentalized into numerous cristae, which expand the surface area of the inner mitochondrial membrane, enhancing its ability to produce ATP. For typical liver mitochondria, the area of the inner membrane is about five times as large as the outer membrane. This ratio is variable and mitochondria from cells that have a greater demand for ATP, such as muscle cells, contain even more cristae. These folds are studded with small round bodies known as F1 particles or oxysomes. These are not simple random folds but rather invaginations of the inner membrane, which can affect overall chemiosmotic function.[43]

text: One recent mathematical modeling study has suggested that the optical properties of the cristae in filamentous mitochondria may affect the generation and propagation of light within the tissue.[44]

text: Matrix

text: The matrix is the space enclosed by the inner membrane. It contains about 2/3 of the total protein in a mitochondrion.[13] The matrix is important in the production of ATP with the aid of the ATP synthase contained in the inner membrane. The matrix contains a highly concentrated mixture of hundreds of enzymes, special mitochondrial ribosomes, tRNA, and several copies of the mitochondrial DNA genome. Of the enzymes, the major functions include oxidation of pyruvate and fatty acids, and the citric acid cycle.[13]

text: Mitochondria have their own genetic material, and the machinery to manufacture their own RNAs and proteins (see: protein biosynthesis). A published human mitochondrial DNA sequence revealed 16,569 base pairs encoding 37 genes: 22 tRNA, 2 rRNA, and 13 peptide genes.[45] The 13 mitochondrial peptides in humans are integrated into the inner mitochondrial membrane, along with proteins encoded by genes that reside in the host cell's nucleus.

text: Mitochondria-associated ER membrane (MAM)

text: The mitochondria-associated ER membrane (MAM) is another structural element that is increasingly recognized for its critical role in cellular physiology and homeostasis. Once considered a technical snag in cell fractionation techniques, the alleged ER vesicle contaminants that invariably appeared in the mitochondrial fraction have been re-identified as membranous structures derived from the MAM—the interface between mitochondria and the ER.[46] Physical coupling between these two organelles had previously been observed in electron micrographs and has more recently been probed with fluorescence microscopy.[46] Such studies estimate that at the MAM, which may comprise up to 20% of the mitochondrial outer membrane, the ER and mitochondria are separated by a mere 10–25 nm and held together by protein tethering complexes.[46][47][48]

text: Purified MAM from subcellular fractionation has been shown to be enriched in enzymes involved in phospholipid exchange, in addition to channels associated with Ca2+ signaling.[46][48] These hints of a prominent role for the MAM in the regulation of cellular lipid stores and signal transduction have been borne out, with significant implications for mitochondrial-associated cellular phenomena, as discussed below. Not only has the MAM provided insight into the mechanistic basis underlying such physiological processes as intrinsic apoptosis and the propagation of calcium signaling, but it also favors a more refined view of the mitochondria. Though often seen as static, isolated 'powerhouses' hijacked for cellular metabolism through an ancient endosymbiotic event, the evolution of the MAM underscores the extent to which mitochondria have been integrated into overall cellular physiology, with intimate physical and functional coupling to the endomembrane system.

text: Phospholipid transfer

text: The MAM is enriched in enzymes involved in lipid biosynthesis, such as phosphatidylserine synthase on the ER face and phosphatidylserine decarboxylase on the mitochondrial face.[49][50] Because mitochondria are dynamic organelles constantly undergoing fission and fusion events, they require a constant and well-regulated supply of phospholipids for membrane integrity.[51][52] But mitochondria are not only a destination for the phospholipids they finish synthesis of; rather, this organelle also plays a role in inter-organelle trafficking of the intermediates and products of phospholipid biosynthetic pathways, ceramide and cholesterol metabolism, and glycosphingolipid anabolism.[50][52]

text: Such trafficking capacity depends on the MAM, which has been shown to facilitate transfer of lipid intermediates between organelles.[49] In contrast to the standard vesicular mechanism of lipid transfer, evidence indicates that the physical proximity of the ER and mitochondrial membranes at the MAM allows for lipid flipping between opposed bilayers.[52] Despite this unusual and seemingly energetically unfavorable mechanism, such transport does not require ATP.[52] Instead, in yeast, it has been shown to be dependent on a multiprotein tethering structure termed the ER-mitochondria encounter structure, or ERMES, although it remains unclear whether this structure directly mediates lipid transfer or is required to keep the membranes in sufficiently close proximity to lower the energy barrier for lipid flipping.[52][53]

text: The MAM may also be part of the secretory pathway, in addition to its role in intracellular lipid trafficking. In particular, the MAM appears to be an intermediate destination between the rough ER and the Golgi in the pathway that leads to very-low-density lipoprotein, or VLDL, assembly and secretion.[50][54] The MAM thus serves as a critical metabolic and trafficking hub in lipid metabolism.

text: Calcium signaling

text: A critical role for the ER in calcium signaling was acknowledged before such a role for the mitochondria was widely accepted, in part because the low affinity of Ca2+ channels localized to the outer mitochondrial membrane seemed to fly in the face of this organelle's purported responsiveness to changes in intracellular Ca2+ flux.[46][55] But the presence of the MAM resolves this apparent contradiction: the close physical association between the two organelles results in Ca2+ microdomains at contact points that facilitate efficient Ca2+ transmission from the ER to the mitochondria.[46] Transmission occurs in response to so-called "Ca2+ puffs" generated by spontaneous clustering and activation of IP3R, a canonical ER membrane Ca2+ channel.[46][47]

text: The fate of these puffs—in particular, whether they remain restricted to isolated locales or integrated into Ca2+ waves for propagation throughout the cell—is determined in large part by MAM dynamics. Although reuptake of Ca2+ by the ER (concomitant with its release) modulates the intensity of the puffs, thus insulating mitochondria to a certain degree from high Ca2+ exposure, the MAM often serves as a firewall that essentially buffers Ca2+ puffs by acting as a sink into which free ions released into the cytosol can be funneled.[46][56][57] This Ca2+ tunneling occurs through the low-affinity Ca2+ receptor VDAC1, which recently has been shown to be physically tethered to the IP3R clusters on the ER membrane and enriched at the MAM.[46][47][58] The ability of mitochondria to serve as a Ca2+ sink is a result of the electrochemical gradient generated during oxidative phosphorylation, which makes tunneling of the cation an exergonic process.[58] Normally, mild calcium influx from cytosol into the mitochondrial matrix causes transient depolarization that is corrected by pumping out protons.

text: But transmission of Ca2+ is not unidirectional; rather, it is a two-way street.[55] The properties of the Ca2+ pump SERCA and the channel IP3R present on the ER membrane facilitate feedback regulation coordinated by MAM function. In particular, the clearance of Ca2+ by the MAM allows for spatio-temporal patterning of Ca2+ signaling because Ca2+ alters IP3R activity in a biphasic manner.[46] SERCA is likewise affected by mitochondrial feedback: uptake of Ca2+ by the MAM stimulates ATP production, thus providing energy that enables SERCA to reload the ER with Ca2+ for continued Ca2+ efflux at the MAM.[56][58] Thus, the MAM is not a passive buffer for Ca2+ puffs; rather it helps modulate further Ca2+ signaling through feedback loops that affect ER dynamics.

text: Regulating ER release of Ca2+ at the MAM is especially critical because only a certain window of Ca2+ uptake sustains the mitochondria, and consequently the cell, at homeostasis. Sufficient intraorganelle Ca2+ signaling is required to stimulate metabolism by activating dehydrogenase enzymes critical to flux through the citric acid cycle.[59] However, once Ca2+ signaling in the mitochondria passes a certain threshold, it stimulates the intrinsic pathway of apoptosis in part by collapsing the mitochondrial membrane potential required for metabolism.[46] Studies examining the role of pro- and anti-apoptotic factors support this model; for example, the anti-apoptotic factor Bcl-2 has been shown to interact with IP3Rs to reduce Ca2+ filling of the ER, leading to reduced efflux at the MAM and preventing collapse of the mitochondrial membrane potential post-apoptotic stimuli.[46] Given the need for such fine regulation of Ca2+ signaling, it is perhaps unsurprising that dysregulated mitochondrial Ca2+ has been implicated in several neurodegenerative diseases, while the catalogue of tumor suppressors includes a few that are enriched at the MAM.[58]

text: Molecular basis for tethering

text: Recent advances in the identification of the tethers between the mitochondrial and ER membranes suggest that the scaffolding function of the molecular elements involved is secondary to other, non-structural functions. In yeast, ERMES, a multiprotein complex of interacting ER- and mitochondrial-resident membrane proteins, is required for lipid transfer at the MAM and exemplifies this principle. One of its components, for example, is also a constituent of the protein complex required for insertion of transmembrane beta-barrel proteins into the lipid bilayer.[52] However, a homologue of the ERMES complex has not yet been identified in mammalian cells. Other proteins implicated in scaffolding likewise have functions independent of structural tethering at the MAM; for example, ER-resident and mitochondrial-resident mitofusins form heterocomplexes that regulate the number of inter-organelle contact sites, although mitofusins were first identified for their role in fission and fusion events between individual mitochondria.[46] Glucose-related protein 75 (grp75) is another dual-function protein. In addition to the matrix pool of grp75, a portion serves as a chaperone that physically links the mitochondrial and ER Ca2+ channels VDAC and IP3R for efficient Ca2+ transmission at the MAM.[46][47] Another potential tether is Sigma-1R, a non-opioid receptor whose stabilization of ER-resident IP3R may preserve communication at the MAM during the metabolic stress response.[60][61]

text: Perspective

text: The MAM is a critical signaling, metabolic, and trafficking hub in the cell that allows for the integration of ER and mitochondrial physiology. Coupling between these organelles is not simply structural but functional as well and critical for overall cellular physiology and homeostasis. The MAM thus offers a perspective on mitochondria that diverges from the traditional view of this organelle as a static, isolated unit appropriated for its metabolic capacity by the cell. Instead, this mitochondrial-ER interface emphasizes the integration of the mitochondria, the product of an endosymbiotic event, into diverse cellular processes.

text: Organization and distribution

text: Mitochondria (and related structures) are found in all eukaryotes (except one—the Oxymonad Monocercomonoides sp.).[2][62] Although commonly depicted as bean-like structures they form a highly dynamic network in the majority of cells where they constantly undergo fission and fusion. Mitochondria vary in number and location according to cell type. A single mitochondrion is often found in unicellular organisms. Conversely, numerous mitochondria are found in human liver cells, with about 1000–2000 mitochondria per cell, making up 1/5 of the cell volume.[13] The mitochondrial content of otherwise similar cells can vary substantially in size and membrane potential,[63] with differences arising from sources including uneven partitioning at cell divisions, leading to extrinsic differences in ATP levels and downstream cellular processes.[64] The mitochondria can be found nestled between myofibrils of muscle or wrapped around the sperm flagellum.[13] Often, they form a complex 3D branching network inside the cell with the cytoskeleton. The association with the cytoskeleton determines mitochondrial shape, which can affect the function as well:[65] different structures of the mitochondrial network may afford the population a variety of physical, chemical, and signalling advantages or disadvantages.[66] Mitochondria in cells are always distributed along microtubules and the distribution of these organelles is also correlated with the endoplasmic reticulum.[67] Recent evidence suggests that vimentin, one of the components of the cytoskeleton, is also critical to the association with the cytoskeleton.[68]

text: Function

text: The most prominent roles of mitochondria are to produce the energy currency of the cell, ATP (i.e., phosphorylation of ADP), through respiration, and to regulate cellular metabolism.[14] The central set of reactions involved in ATP production are collectively known as the citric acid cycle, or the Krebs cycle. However, the mitochondrion has many other functions in addition to the production of ATP.

text: Energy conversion

text: A dominant role for the mitochondria is the production of ATP, as reflected by the large number of proteins in the inner membrane for this task. This is done by oxidizing the major products of glucose: pyruvate, and NADH, which are produced in the cytosol.[14] This type of cellular respiration known as aerobic respiration, is dependent on the presence of oxygen. When oxygen is limited, the glycolytic products will be metabolized by anaerobic fermentation, a process that is independent of the mitochondria.[14] The production of ATP from glucose has an approximately 13-times higher yield during aerobic respiration compared to fermentation.[69] Recently it has been shown that plant mitochondria can produce a limited amount of ATP without oxygen by using the alternate substrate nitrite.[70] ATP crosses out through the inner membrane with the help of a specific protein, and across the outer membrane via porins. ADP returns via the same route.

text: Pyruvate and the citric acid cycle

text: Pyruvate molecules produced by glycolysis are actively transported across the inner mitochondrial membrane, and into the matrix where they can either be oxidized and combined with coenzyme A to form CO2, acetyl-CoA, and NADH,[14] or they can be carboxylated (by pyruvate carboxylase) to form oxaloacetate. This latter reaction ”fills up” the amount of oxaloacetate in the citric acid cycle, and is therefore an anaplerotic reaction, increasing the cycle’s capacity to metabolize acetyl-CoA when the tissue's energy needs (e.g. in muscle) are suddenly increased by activity.[71]

text: In the citric acid cycle, all the intermediates (e.g. citrate, iso-citrate, alpha-ketoglutarate, succinate, fumarate, malate and oxaloacetate) are regenerated during each turn of the cycle. Adding more of any of these intermediates to the mitochondrion therefore means that the additional amount is retained within the cycle, increasing all the other intermediates as one is converted into the other. Hence, the addition of any one of them to the cycle has an anaplerotic effect, and its removal has a cataplerotic effect. These anaplerotic and cataplerotic reactions will, during the course of the cycle, increase or decrease the amount of oxaloacetate available to combine with acetyl-CoA to form citric acid. This in turn increases or decreases the rate of ATP production by the mitochondrion, and thus the availability of ATP to the cell.[71]

text: Acetyl-CoA, on the other hand, derived from pyruvate oxidation, or from the beta-oxidation of fatty acids, is the only fuel to enter the citric acid cycle. With each turn of the cycle one molecule of acetyl-CoA is consumed for every molecule of oxaloacetate present in the mitochondrial matrix, and is never regenerated. It is the oxidation of the acetate portion of acetyl-CoA that produces CO2 and water, with the energy thus released captured in the form of ATP.[71]

text: In the liver, the carboxylation of cytosolic pyruvate into intra-mitochondrial oxaloacetate is an early step in the gluconeogenic pathway, which converts lactate and de-aminated alanine into glucose,[14][71] under the influence of high levels of glucagon and/or epinephrine in the blood.[71] Here, the addition of oxaloacetate to the mitochondrion does not have a net anaplerotic effect, as another citric acid cycle intermediate (malate) is immediately removed from the mitochondrion to be converted into cytosolic oxaloacetate, which is ultimately converted into glucose, in a process that is almost the reverse of glycolysis.[71]

text: The enzymes of the citric acid cycle are located in the mitochondrial matrix, with the exception of succinate dehydrogenase, which is bound to the inner mitochondrial membrane as part of Complex II.[72] The citric acid cycle oxidizes the acetyl-CoA to carbon dioxide, and, in the process, produces reduced cofactors (three molecules of NADH and one molecule of FADH2) that are a source of electrons for the electron transport chain, and a molecule of GTP (that is readily converted to an ATP).[14]

text: NADH and FADH2: the electron transport chain

text: The redox energy from NADH and FADH2 is transferred to oxygen (O2) in several steps via the electron transport chain. These energy-rich molecules are produced within the matrix via the citric acid cycle but are also produced in the cytoplasm by glycolysis. Reducing equivalents from the cytoplasm can be imported via the malate-aspartate shuttle system of antiporter proteins or feed into the electron transport chain using a glycerol phosphate shuttle.[14] Protein complexes in the inner membrane (NADH dehydrogenase (ubiquinone), cytochrome c reductase, and cytochrome c oxidase) perform the transfer and the incremental release of energy is used to pump protons (H+) into the intermembrane space. This process is efficient, but a small percentage of electrons may prematurely reduce oxygen, forming reactive oxygen species such as superoxide.[14] This can cause oxidative stress in the mitochondria and may contribute to the decline in mitochondrial function associated with the aging process.[73]

text: As the proton concentration increases in the intermembrane space, a strong electrochemical gradient is established across the inner membrane. The protons can return to the matrix through the ATP synthase complex, and their potential energy is used to synthesize ATP from ADP and inorganic phosphate (Pi).[14] This process is called chemiosmosis, and was first described by Peter Mitchell[74][75] who was awarded the 1978 Nobel Prize in Chemistry for his work. Later, part of the 1997 Nobel Prize in Chemistry was awarded to Paul D. Boyer and John E. Walker for their clarification of the working mechanism of ATP synthase.[76]

text: Heat production

text: Under certain conditions, protons can re-enter the mitochondrial matrix without contributing to ATP synthesis. This process is known as proton leak or mitochondrial uncoupling and is due to the facilitated diffusion of protons into the matrix. The process results in the unharnessed potential energy of the proton electrochemical gradient being released as heat.[14] The process is mediated by a proton channel called thermogenin, or UCP1.[77] Thermogenin is a 33 kDa protein first discovered in 1973.[78] Thermogenin is primarily found in brown adipose tissue, or brown fat, and is responsible for non-shivering thermogenesis. Brown adipose tissue is found in mammals, and is at its highest levels in early life and in hibernating animals. In humans, brown adipose tissue is present at birth and decreases with age.[77]

text: Storage of calcium ions

text: The concentrations of free calcium in the cell can regulate an array of reactions and is important for signal transduction in the cell. Mitochondria can transiently store calcium, a contributing process for the cell's homeostasis of calcium.[79] [80] In fact, their ability to rapidly take in calcium for later release makes them very good "cytosolic buffers" for calcium.[81][82][83] The endoplasmic reticulum (ER) is the most significant storage site of calcium,[55] and there is a significant interplay between the mitochondrion and ER with regard to calcium.[84] The calcium is taken up into the matrix by the mitochondrial calcium uniporter on the inner mitochondrial membrane.[85] It is primarily driven by the mitochondrial membrane potential.[80] Release of this calcium back into the cell's interior can occur via a sodium-calcium exchange protein or via "calcium-induced-calcium-release" pathways.[85] This can initiate calcium spikes or calcium waves with large changes in the membrane potential. These can activate a series of second messenger system proteins that can coordinate processes such as neurotransmitter release in nerve cells and release of hormones in endocrine cells.[86]

text: Ca2+ influx to the mitochondrial matrix has recently been implicated as a mechanism to regulate respiratory bioenergetics by allowing the electrochemical potential across the membrane to transiently "pulse" from ΔΨ-dominated to pH-dominated, facilitating a reduction of oxidative stress.[87] In neurons, concomitant increases in cytosolic and mitochondrial calcium act to synchronize neuronal activity with mitochondrial energy metabolism. Mitochondrial matrix calcium levels can reach the tens of micromolar levels, which is necessary for the activation of isocitrate dehydrogenase, one of the key regulatory enzymes of the Kreb's cycle.[88]

text: Additional functions

text: Mitochondria play a central role in many other metabolic tasks, such as:

text:
Signaling through mitochondrial reactive oxygen species[89]
Regulation of the membrane potential[14]
Apoptosis-programmed cell death[90]
Calcium signaling (including calcium-evoked apoptosis)[91]
Regulation of cellular metabolism[92]
Certain heme synthesis reactions[93] (see also: porphyrin)
Steroid synthesis.[81]
Hormonal signaling [94] Mitochondria are sensitive and responsive to hormones, in part by the action of mitochondrial estrogen receptors (mtERs). These receptors have been found in various tissues and cell types, including brain [95] and heart [96]

tag: ul

text: Some mitochondrial functions are performed only in specific types of cells. For example, mitochondria in liver cells contain enzymes that allow them to detoxify ammonia, a waste product of protein metabolism. A mutation in the genes regulating any of these functions can result in mitochondrial diseases.

text: Cellular proliferation regulation

text: The relationship between cellular proliferation and mitochondria has been investigated using cervical cancer HeLa cells. Tumor cells require an ample amount of ATP (Adenosine triphosphate) in order to synthesize bioactive compounds such as lipids, proteins, and nucleotides for rapid cell proliferation.[97] The majority of ATP in tumor cells is generated via the oxidative phosphorylation pathway (OxPhos).[98] Interference with OxPhos have shown to cause cell cycle arrest suggesting that mitochondria play a role in cell proliferation.[98] Mitochondrial ATP production is also vital for cell division in addition to other basic functions in the cell including the regulation of cell volume, solute concentration, and cellular architecture.[99][100][101] ATP levels differ at various stages of the cell cycle suggesting that there is a relationship between the abundance of ATP and the cell's ability to enter a new cell cycle.[102] ATP's role in the basic functions of the cell make the cell cycle sensitive to changes in the availability of mitochondrial derived ATP.[102] The variation in ATP levels at different stages of the cell cycle support the hypothesis that mitochondria play an important role in cell cycle regulation.[102] Although the specific mechanisms between mitochondria and the cell cycle regulation is not well understood, studies have shown that low energy cell cycle checkpoints monitor the energy capability before committing to another round of cell division.[103]

text: Genome

text: Mitochondria contain their own genome, an indication that they are derived from bacteria through endosymbiosis (see Origin and evolution above). However, the ancestral endosymbiont genome has lost most of its genes so that the mitochondrial genome is one of the most reduced genomes across organisms.

text: The human mitochondrial genome is a circular DNA molecule of about 16 kilobases.[104] It encodes 37 genes: 13 for subunits of respiratory complexes I, III, IV and V, 22 for mitochondrial tRNA (for the 20 standard amino acids, plus an extra gene for leucine and serine), and 2 for rRNA.[104] One mitochondrion can contain two to ten copies of its DNA.[105]

text: As in prokaryotes, there is a very high proportion of coding DNA and an absence of repeats. Mitochondrial genes are transcribed as multigenic transcripts, which are cleaved and polyadenylated to yield mature mRNAs. Not all proteins necessary for mitochondrial function are encoded by the mitochondrial genome; most are coded by genes in the cell nucleus and the corresponding proteins are imported into the mitochondrion.[45] The exact number of genes encoded by the nucleus and the mitochondrial genome differs between species. Most mitochondrial genomes are circular, although exceptions have been reported.[106] In general, mitochondrial DNA lacks introns, as is the case in the human mitochondrial genome;[45] however, introns have been observed in some eukaryotic mitochondrial DNA,[107] such as that of yeast[108] and protists,[109] including Dictyostelium discoideum.[110] Between protein-coding regions, tRNAs are present. During transcription, the tRNAs acquire their characteristic L-shape that gets recognized and cleaved by specific enzymes. Mitochondrial tRNA genes have different sequences from the nuclear tRNAs but lookalikes of mitochondrial tRNAs have been found in the nuclear chromosomes with high sequence similarity.[111]

text: In animals, the mitochondrial genome is typically a single circular chromosome that is approximately 16 kb long and has 37 genes. The genes, while highly conserved, may vary in location. Curiously, this pattern is not found in the human body louse (Pediculus humanus). Instead, this mitochondrial genome is arranged in 18 minicircular chromosomes, each of which is 3–4 kb long and has one to three genes.[112] This pattern is also found in other sucking lice, but not in chewing lice. Recombination has been shown to occur between the minichromosomes. The reason for this difference is not known.

text: Alternative genetic code

text: While slight variations on the standard genetic code had been predicted earlier,[113] none was discovered until 1979, when researchers studying human mitochondrial genes determined that they used an alternative code.[114] However, the mitochondria of many other eukaryotes, including most plants, use the standard code.[115] Many slight variants have been discovered since,[116] including various alternative mitochondrial codes.[117] Further, the AUA, AUC, and AUU codons are all allowable start codons.

text:
Exceptions to the standard genetic code in mitochondria[13]

Organism
Codon
Standard
Mitochondria

Mammals
AGA, AGG
Arginine
Stop codon

Invertebrates
AGA, AGG
Arginine
Serine

Fungi
CUA
Leucine
Threonine

All of the above
AUA
Isoleucine
Methionine

UGA
Stop codon
Tryptophan

text: Some of these differences should be regarded as pseudo-changes in the genetic code due to the phenomenon of RNA editing, which is common in mitochondria. In higher plants, it was thought that CGG encoded for tryptophan and not arginine; however, the codon in the processed RNA was discovered to be the UGG codon, consistent with the standard genetic code for tryptophan.[118] Of note, the arthropod mitochondrial genetic code has undergone parallel evolution within a phylum, with some organisms uniquely translating AGG to lysine.[119]

text: Evolution and diversity

text: Mitochondrial genomes have far fewer genes than the bacteria from which they are thought to be descended. Although some have been lost altogether, many have been transferred to the nucleus, such as the respiratory complex II protein subunits.[104] This is thought to be relatively common over evolutionary time. A few organisms, such as the Cryptosporidium, actually have mitochondria that lack any DNA, presumably because all their genes have been lost or transferred.[120] In Cryptosporidium, the mitochondria have an altered ATP generation system that renders the parasite resistant to many classical mitochondrial inhibitors such as cyanide, azide, and atovaquone.[120]

text: Replication and inheritance

text: Mitochondria divide by binary fission, similar to bacterial cell division.[121] The regulation of this division differs between eukaryotes. In many single-celled eukaryotes, their growth and division is linked to the cell cycle. For example, a single mitochondrion may divide synchronously with the nucleus. This division and segregation process must be tightly controlled so that each daughter cell receives at least one mitochondrion. In other eukaryotes (in mammals for example), mitochondria may replicate their DNA and divide mainly in response to the energy needs of the cell, rather than in phase with the cell cycle. When the energy needs of a cell are high, mitochondria grow and divide. When the energy use is low, mitochondria are destroyed or become inactive. In such examples, and in contrast to the situation in many single celled eukaryotes, mitochondria are apparently randomly distributed to the daughter cells during the division of the cytoplasm. Understanding of mitochondrial dynamics, which is described as the balance between mitochondrial fusion and fission, has revealed that functional and structural alterations in mitochondrial morphology are important factors in pathologies associated with several disease conditions.[122]

text: The hypothesis of mitochondrial binary fission has relied on the visualization by fluorescence microscopy and conventional transmission electron microscopy (TEM). The resolution of fluorescence microscopy(~200 nm) is insufficient to distinguish structural details, such as double mitochondrial membrane in mitochondrial division or even to distinguish individual mitochondria when several are close together. Conventional TEM has also some technical limitations[which?] in verifying mitochondrial division. Cryo-electron tomography was recently used to visualize mitochondrial division in frozen hydrated intact cells. It revealed that mitochondria divide by budding.[123]

text: An individual's mitochondrial genes are not inherited by the same mechanism as nuclear genes. Typically, the mitochondria are inherited from one parent only. In humans, when an egg cell is fertilized by a sperm, the egg nucleus and sperm nucleus each contribute equally to the genetic makeup of the zygote nucleus. In contrast, the mitochondria, and therefore the mitochondrial DNA, usually come from the egg only. The sperm's mitochondria enter the egg, but do not contribute genetic information to the embryo.[124] Instead, paternal mitochondria are marked with ubiquitin to select them for later destruction inside the embryo.[125] The egg cell contains relatively few mitochondria, but it is these mitochondria that survive and divide to populate the cells of the adult organism. Mitochondria are, therefore, in most cases inherited only from mothers, a pattern known as maternal inheritance. This mode is seen in most organisms, including the majority of animals. However, mitochondria in some species can sometimes be inherited paternally. This is the norm among certain coniferous plants, although not in pine trees and yews.[126] For Mytilids, paternal inheritance only occurs within males of the species.[127][128][129] It has been suggested that it occurs at a very low level in humans.[130] There is a recent suggestion that mitochondria that shorten male lifespan stay in the system because they are inherited only through the mother. By contrast, natural selection weeds out mitochondria that reduce female survival as such mitochondria are less likely to be passed on to the next generation. Therefore, it is suggested that human females and female animals tend to live longer than males. The authors claim that this is a partial explanation.[131]

text: Uniparental inheritance leads to little opportunity for genetic recombination between different lineages of mitochondria, although a single mitochondrion can contain 2–10 copies of its DNA.[105] For this reason, mitochondrial DNA is usually thought to reproduce by binary fission. What recombination does take place maintains genetic integrity rather than maintaining diversity. However, there are studies showing evidence of recombination in mitochondrial DNA. It is clear that the enzymes necessary for recombination are present in mammalian cells.[132] Further, evidence suggests that animal mitochondria can undergo recombination.[133] The data are a bit more controversial in humans, although indirect evidence of recombination exists.[134][135] If recombination does not occur, the whole mitochondrial DNA sequence represents a single haplotype, which makes it useful for studying the evolutionary history of populations.

text: Entities undergoing uniparental inheritance and with little to no recombination may be expected to be subject to Muller's ratchet, the inexorable accumulation of deleterious mutations until functionality is lost. Animal populations of mitochondria avoid this buildup through a developmental process known as the mtDNA bottleneck. The bottleneck exploits stochastic processes in the cell to increase in the cell-to-cell variability in mutant load as an organism develops: a single egg cell with some proportion of mutant mtDNA thus produces an embryo where different cells have different mutant loads. Cell-level selection may then act to remove those cells with more mutant mtDNA, leading to a stabilisation or reduction in mutant load between generations. The mechanism underlying the bottleneck is debated,[136][137][138] with a recent mathematical and experimental metastudy providing evidence for a combination of random partitioning of mtDNAs at cell divisions and random turnover of mtDNA molecules within the cell.[139]

text: Population genetic studies

text: The near-absence of genetic recombination in mitochondrial DNA makes it a useful source of information for scientists involved in population genetics and evolutionary biology.[140] Because all the mitochondrial DNA is inherited as a single unit, or haplotype, the relationships between mitochondrial DNA from different individuals can be represented as a gene tree. Patterns in these gene trees can be used to infer the evolutionary history of populations. The classic example of this is in human evolutionary genetics, where the molecular clock can be used to provide a recent date for mitochondrial Eve.[141][142] This is often interpreted as strong support for a recent modern human expansion out of Africa.[143] Another human example is the sequencing of mitochondrial DNA from Neanderthal bones. The relatively large evolutionary distance between the mitochondrial DNA sequences of Neanderthals and living humans has been interpreted as evidence for the lack of interbreeding between Neanderthals and anatomically modern humans.[144]

text: However, mitochondrial DNA reflects only the history of the females in a population and so may not represent the history of the population as a whole. This can be partially overcome by the use of paternal genetic sequences, such as the non-recombining region of the Y-chromosome.[143] In a broader sense, only studies that also include nuclear DNA can provide a comprehensive evolutionary history of a population.[145]

text: Recent measurements of the molecular clock for mitochondrial DNA[146] reported a value of 1 mutation every 7884 years dating back to the most recent common ancestor of humans and apes, which is consistent with estimates of mutation rates of autosomal DNA (10−8 per base per generation[147]).

text: Dysfunction and disease

text: Mitochondrial diseases

text: Damage and subsequent dysfunction in mitochondria is an important factor in a range of human diseases due to their influence in cell metabolism. Mitochondrial disorders often present themselves as neurological disorders, including autism.[12] They can also manifest as myopathy, diabetes, multiple endocrinopathy, and a variety of other systemic disorders.[148] Diseases caused by mutation in the mtDNA include Kearns-Sayre syndrome, MELAS syndrome and Leber's hereditary optic neuropathy.[149] In the vast majority of cases, these diseases are transmitted by a female to her children, as the zygote derives its mitochondria and hence its mtDNA from the ovum. Diseases such as Kearns-Sayre syndrome, Pearson syndrome, and progressive external ophthalmoplegia are thought to be due to large-scale mtDNA rearrangements, whereas other diseases such as MELAS syndrome, Leber's hereditary optic neuropathy, myoclonic epilepsy with ragged red fibers (MERRF), and others are due to point mutations in mtDNA.[148]

text: In other diseases, defects in nuclear genes lead to dysfunction of mitochondrial proteins. This is the case in Friedreich's ataxia, hereditary spastic paraplegia, and Wilson's disease.[150] These diseases are inherited in a dominance relationship, as applies to most other genetic diseases. A variety of disorders can be caused by nuclear mutations of oxidative phosphorylation enzymes, such as coenzyme Q10 deficiency and Barth syndrome.[148] Environmental influences may interact with hereditary predispositions and cause mitochondrial disease. For example, there may be a link between pesticide exposure and the later onset of Parkinson's disease.[151][152] Other pathologies with etiology involving mitochondrial dysfunction include schizophrenia, bipolar disorder, dementia, Alzheimer's disease,[153] Parkinson's disease, epilepsy, stroke, cardiovascular disease, chronic fatigue syndrome, retinitis pigmentosa, and diabetes mellitus.[154][155]

text: Mitochondria-mediated oxidative stress plays a role in cardiomyopathy in Type 2 diabetics. Increased fatty acid delivery to the heart increases fatty acid uptake by cardiomyocytes, resulting in increased fatty acid oxidation in these cells. This process increases the reducing equivalents available to the electron transport chain of the mitochondria, ultimately increasing reactive oxygen species (ROS) production. ROS increases uncoupling proteins (UCPs) and potentiate proton leakage through the adenine nucleotide translocator (ANT), the combination of which uncouples the mitochondria. Uncoupling then increases oxygen consumption by the mitochondria, compounding the increase in fatty acid oxidation. This creates a vicious cycle of uncoupling; furthermore, even though oxygen consumption increases, ATP synthesis does not increase proportionally because the mitochondria is uncoupled. Less ATP availability ultimately results in an energy deficit presenting as reduced cardiac efficiency and contractile dysfunction. To compound the problem, impaired sarcoplasmic reticulum calcium release and reduced mitochondrial reuptake limits peak cytosolic levels of the important signaling ion during muscle contraction. The decreased intra-mitochondrial calcium concentration increases dehydrogenase activation and ATP synthesis. So in addition to lower ATP synthesis due to fatty acid oxidation, ATP synthesis is impaired by poor calcium signaling as well, causing cardiac problems for diabetics.[156]

text: Possible relationships to aging

text: Given the role of mitochondria as the cell's powerhouse, there may be some leakage of the high-energy electrons in the respiratory chain to form reactive oxygen species. This was thought to result in significant oxidative stress in the mitochondria with high mutation rates of mitochondrial DNA (mtDNA).[157] Hypothesized links between aging and oxidative stress are not new and were proposed in 1956,[158] which was later refined into the mitochondrial free radical theory of aging.[159] A vicious cycle was thought to occur, as oxidative stress leads to mitochondrial DNA mutations, which can lead to enzymatic abnormalities and further oxidative stress.

text: A number of changes can occur to mitochondria during the aging process.[160] Tissues from elderly patients show a decrease in enzymatic activity of the proteins of the respiratory chain.[161] However, mutated mtDNA can only be found in about 0.2% of very old cells.[162] Large deletions in the mitochondrial genome have been hypothesized to lead to high levels of oxidative stress and neuronal death in Parkinson's disease.[163]

text: In popular culture

text: Madeleine L'Engle's 1973 science fantasy novel A Wind in the Door prominently features the mitochondria of main character Charles Wallace Murry, as being inhabited by creatures known as the farandolae. The novel also features other characters travelling inside one of Murry's mitochondria.

text: The 1995 horror fiction novel Parasite Eve by Hideaki Sena depicts mitochondria as having some consciousness and mind control abilities, attempting to use these to overtake eukaryotes as the dominant life form. This text was adapted into an eponymous film, video game, and video game sequel all involving a similar premise.

text: In the Star Wars franchise, microorganisms referred to as "midi-chlorians" give some characters the ability to sense and use the Force. George Lucas, director of the 1999 film Star Wars: Episode I – The Phantom Menace, in which midi-chlorians were introduced, described them as "a loose depiction of mitochondria".[164] The non-fictional Midichloria genus of bacteria was later named after the midi-chlorians of Star Wars.

text: As a result of the mitochondrion's prominence in modern science education, the phrase "mitochondria is [sic] the powerhouse of the cell" became a popular Internet meme.[165] The meme is used to imply that secondary education places an insufficient focus on life skills, compared to academic knowledge such as the role of the mitochondrion, which has been considered comparatively impractical.[166]


document_title: Selection and Training in the British Army

question_text: where do you go for phase 1 training

question_tokens: where do you go for phase 1 training

text: Selection[edit]

text: Candidates for all three of the British Armed Forces are first handled through Armed Forces Career Offices, which are located in major conurbations around the United Kingdom supporting the respective recruitment functions. The selection process involves a number of suitability interviews, an aptitude test to identify training potential, medical and fitness assessments and a residential selection board. For potential soldiers, this will include an opportunity to select a Regiment or Corps, as well as a trade to join. Later training is oriented around this choice. Officer candidates will, during the selection process, become sponsored by a Regiment or Corps to undertake training. This sponsor does not undertake to accept the candidate on completion of officer training.

text: Regular Army[edit]

text: Training[edit]

text: Candidates for the Army undergo common training to bring all personnel to a similar standard in basic military skills, and further specialist training is delivered according to the Regiment or Corps for which the individual has been identified as a candidate. Completion of Phase 2 training brings the individual onto the trained strength; however, each of the British Armed Forces will continue to deliver specialist and generalist training throughout the individual career.

text: Much training in the British Armed Forces has been accredited by various awarding bodies, resulting in the opportunity to gain civilian qualifications through service training activities.

text: Phase 1[edit]

text: Phase 1 training features basic training for all new recruits. For other ranks, this is the Common Military Syllabus (Recruits) (CMSR). CMSR covers the skills and fitness needed to survive and operate in a field environment, and seeks to imbue the ethos and principles of the British Army. The trainee is required to demonstrate competence in thirteen training objectives over the fourteen-week course. Officers undertake the Commissioning Course, which covers the basic aspects of soldiering as well as command, leadership and management. The standard course for new Direct Entry Officers lasts 44 weeks. Professionally qualified officers (those that have joined the army having already gained a professional qualification, such as doctors, lawyers or chaplains) undergo a shorter, ten-week course.[1] The Late Entry Officers Course is a four-week course for already serving soldiers that have been chosen for commissioning as officers.[2]

text: There are five training establishments for Phase 1 training in the Regular Army:

text:
Title
Name
Course length
Attendees

Officers

Royal Military Academy Sandhurst
Sandhurst
44 wk
All Arms Direct Entry Officers

10 wk
Professionally Qualified Officers

4 wk
Late Entry Officers

Other Ranks

Army Foundation College
Harrogate
49 wk
All Arms Junior Soldier (ages 16–17½)

Army Training Regiment
Pirbright
14 wk

Corps of Royal Electrical and Mechanical Engineers
Army Air Corps
Royal Regiment of Artillery
Royal Corps of Signals
Royal Logistic Corps
Adjutant General's Corps
Royal Army Medical Corps
Intelligence Corps

Army Training Regiment
Winchester
14 wk

Royal Armoured Corps
Army Air Corps
Royal Regiment of Artillery
Corps of Royal Engineers
Royal Corps of Signals
Royal Logistic Corps
Adjutant General's Corps
Royal Army Medical Corps
Intelligence Corps

Infantry Training Centre
Catterick
26 wk
Infantry Regiments

text: Phase 1 training is intended to bring all recruits to a base level of military competency, capable of operating in the field, providing force protection, operational security and displaying the other characteristics of a member of the British Army. For officers this also includes the professional competencies required for command. During this period, recruits pass in and receive their regimental berets; they then pass out and continue to phase 2 to undergo job training. The training embeds the core values:

text:
Courage
Discipline
Respect for others
Integrity
Loyalty
Selfless commitment

text: Phase 2[edit]

text: The second phase involves the new officer or soldier training for the branch of the service they wish to specialise in, and then undergoing the specific training. This is with one of the specialist schools located around the country:

text:
Name
Location
Arm
Comments

Infantry Training Centre
Catterick
Infantry
Combined Phase 1 and 2

Armour Centre
Bovington Camp
Royal Armoured Corps
Household Cavalry

Royal School of Artillery
Larkhill
Royal Artillery

Army Aviation Centre
Middle Wallop
Army Air Corps

Royal School of Military Engineering
Chatham
Royal Engineers

Royal School of Signals
Blandford Camp
Royal Corps of Signals

Defence School of Electronic and Mechanical Engineering
Lyneham
Royal Electrical and Mechanical Engineers

Defence College of Logistics
Various
Royal Logistic Corps

Defence Medical Services Training Centre
Whittington Barracks
Royal Army Medical Corps

Defence School of Personnel Administration
Worthy Down Barracks
Adjutant General's Corps

Defence College of Policing and Guarding
Southwick Park
Royal Military Police

Royal Military School of Music
Kneller Hall
Corps of Army Music

Joint Intelligence Training Group
Chicksands
Intelligence Corps

text: Infantry Training Centre[edit]

text: As of 2001, infantry training for other ranks is undertaken as a single 26-week course (28 weeks for the parachute regiment, or any of the five guards regiments) at the Infantry Training Centre at Catterick Garrison, as opposed to being divided into Phase 1 and Phase 2 training. The ITC is divided into four separate battalions; these are divided into companies, each of which are responsible for one of the infantry's administrative divisions:

text:
1st Infantry Training Battalion is responsible for training soldiers destined to join the regiments of the Queen's Division, Prince of Wales' Division, the Royal Irish Regiment and The Rifles, King's Division and the Royal Regiment of Scotland. The 1st Battalion has five training companies:[3]

Queen's Division Company
Prince of Wales's Division Company
Rifles Training Company
King's Division Company
Royal Regiment of Scotland Training Company

2nd Infantry Training Battalion has responsibility for training recruits who will join one of the regiments of the Guards Division, the Parachute Regiment and the Brigade of Gurkhas. 2 ITB is also responsible for the Phase 2 training for junior entry recruits from the Army Foundation College, as well as training for the infantry elements of the Army Reserve.[4]

Guards Training Company
Parachute Regiment Training Company
Gurkha Training Company
Anzio Company

The ITC Support Battalion is the ITC's primary support unit, dealing with logistic and medical support. The battalion is structured to provide maximum support throughout the ITC and consists of the following departments:[5]

Headquarter (HQ) Company
Hook VC Company (discharged soldiers)
Gym
Army School of Ceremonial
Army School of Bagpipe Music and Highland Drumming
Quartermaster's (QMs) Department
G7 Training
400 Troop, Royal Logistic Corps

text: Further infantry training, as well as Phase 2 training for new infantry officers, is undertaken at the Infantry Battle School and the Specialist Weapons School.

text: Army Reserve[edit]

text: Soldiers[edit]

text: For Army Reserve soldiers, recruit training is structured into two phases: Phase 1, also known as the Common Military Syllabus (Reserve) (CMS(R)) Course, and Phase 2, special-to-arm training.[6]

text: Phase 1

text: In Phase 1, recruits cover the Common Military Syllabus 14 (CMS14) Part 'a' is a series of 4 training weekends at Army Training Units (ATUs), formerly known as Regional Training Centres (RTCs). At some ATUs the Phase 1a is also run as a consolidated course. For all Army Reserve soldiers Phase 1 concludes with a two-week training course (Phase 1b) normally held at an Army Training Regiment,[7] Infantry recruits then do their Phase 2 Training at Catterick.[8] Recruits to the 4th Battalion, The Parachute Regiment[9] and the Honourable Artillery Company[10] complete their equivalent of CMS(R) within their own units.

text: Phase 2

text: Phase 1 is followed by Phase 2, a further period of special-to-arm training specific to the type of unit the recruit is joining. This is normally conducted by the Arm or Service that the recruit is joining, for example for infantry units, Phase 2 consists of the two-week Combat Infantryman's Course (Reserve) (CIC (Res)) held at the Infantry Training Centre, Catterick.[8]

text: Officers[edit]

text: To gain a commission, Potential Officers have to pass through four modules of training, which together form the Army Reserve Commissioning Course.

text: Module A consists of basic field training and elementary military skills. This can be completed at either a UOTC over a number of weekends, or over 2 weeks at the Royal Military Academy Sandhurst (RMAS)

text: Module B covers training in Tactics, Leadership, Doctrine and Navigation, both in theory and in practice, with a focus on the section battle drills and the platoon combat estimate. This training can either be spread over 10 weekends at a UOTC, or 2 weeks at the RMAS.

text: Module C builds on the Tactics, Leadership, Doctrine and Navigation taught in Module B, with a greater focus on the theory behind these constructs. CBRN training is also added at this point, and Officer Cadets undergo a number of field exercises to test their military and leadership skills. Module C can only be undertaken at the RMAS.

text: Module D Once the Officer Cadet has completed their Army Officer Selection Board, they can complete this final module, after which they will become commissioned officers in the British Army. Based at the RMAS, this module consists primarily of a prolonged field exercise, followed by drill training in preparation for the passing out parade.

text: On successful completion of Module D, the Officer Cadets receive their Commission and become Second Lieutenants. Further training that is required prior to them being considered for operational deployment and promotion to Lieutenant includes:

text: Post Commissioning Training (formerly known as Module 5), again run at an OTC, over 3 weekends.

text: Special To Arm training is specific to the type of unit the Subaltern is joining, and covers a 2-week period. This is increasingly integrated with the tactics phase of a Regular training course. For example, the Platoon Commander's Battle Course held at the Infantry Battle School in Brecon, which is integrated with Regular training, or the Yeomanry Tactics Course held at the Land Warfare Centre in Warminster, which is not.


document_title: Pelagic zone

question_text: what two components make up the epipelagic zone at the surface

text: Pelagic zone

text: Depth and layers[edit]

text: Depending on how deep the sea is, the pelagic zone can extend over up to five horizontal regions in the ocean. From the top down, these are:

text: Epipelagic (sunlight)[edit]

text: From the surface (MSL) down to around 200 m (660 ft)

text: This is the illuminated zone at the surface of the sea where enough light is available for photosynthesis. Nearly all primary production in the ocean occurs here. Consequently, plants and animals are largely concentrated in this zone. Examples of organisms living in this zone are plankton, floating seaweed, jellyfish, tuna, many sharks and dolphins.

text: Mesopelagic (twilight)[edit]

text: From 200 m (660 ft) down to around 1,000 m (3,300 ft)

text: The most abundant organisms thriving into the mesopelagic zone are heterotrophic bacteria.[4] Examples of animals that live here are swordfish, squid, Anarhichadidae or "wolffish" and some species of cuttlefish. Many organisms that live in this zone are bioluminescent.[5] Some creatures living in the mesopelagic zone rise to the epipelagic zone at night to feed.[5]

text: Bathypelagic (midnight)[edit]

text: From 1,000 m (3,300 ft) down to around 4,000 m (13,000 ft)

text: The name stems from Greek βαθύς, meaning 'deep'. At this depth, the ocean is pitch black, apart from occasional bioluminescent organisms, such as anglerfish. No living plant exists here. Most animals living here survive by consuming the detritus falling from the zones above, which is known as "marine snow", or, like the marine hatchetfish, by preying on other inhabitants of this zone. Other examples of this zone's inhabitants are giant squid, smaller squids and the grimpoteuthis or "dumbo octopus". The giant squid is hunted here by deep-diving sperm whales.

text: Abyssopelagic (lower midnight)[edit]

text: From around 4,000 m (13,000 ft) down to above the ocean floor

text: The name is derived from Greek ἄβυσσος, meaning 'bottomless' (a holdover from the times when the deep ocean, or abyss, was believed to be bottomless). Very few creatures live in the cold temperatures, high pressures and complete darkness of this depth.[5] Among the species found in this zone are several species of squid; echinoderms including the basket star, swimming cucumber, and the sea pig; and marine arthropods including the sea spider.[5] Many of the species living at these depths are transparent and eyeless because of the total lack of light in this zone.[5]

text: Hadopelagic[edit]

text: The deep water in ocean trenches

text: The name is derived from the realm of Hades, the Greek underworld. However, many organisms live in hydrothermal vents in this and other zones. Some define the hadopelagic as waters below 6,000 m (20,000 ft), whether in a trench or not.

text: Pelagic ecosystem[edit]

text: The pelagic ecosystem is based on phytoplankton. Phytoplankton manufacture their own food using a process of photosynthesis. Because they need sunlight, they inhabit the upper, sunlit epipelagic zone, which includes the coastal or neritic zone. Biodiversity diminishes markedly in the deeper zones below the epipelagic zone as dissolved oxygen diminishes, water pressure increases, temperatures become colder, food sources become scarce, and light diminishes and finally disappears.[7]

text: Pelagic birds[edit]

text: Pelagic birds, also called oceanic birds, live on the open sea, rather than around waters adjacent to land or around inland waters. Pelagic birds feed on planktonic crustaceans, squid and forage fish. Examples are the Atlantic puffin, macaroni penguins, sooty terns, shearwaters, and Procellariiformes such as the albatross, Procellariidae and petrels.

text: The term seabird includes birds which live around the sea adjacent to land, as well as pelagic birds.

text: Pelagic fish[edit]

text: Pelagic fish live in the water column of coastal, ocean, and lake waters, but not on or near the bottom of the sea or the lake. They can be contrasted with demersal fish, which live on or near the bottom, and coral reef fish.[8]

text: These fish are often migratory forage fish, which feed on plankton, and the larger fish that follow and feed on the forage fish. Examples of migratory forage fish are herring, anchovies, capelin, and menhaden. Examples of larger pelagic fish which prey on the forage fish are billfish, tuna, and oceanic sharks.

text: Pelagic invertebrates[edit]

text: Some examples of pelagic invertebrates include krill, copepods, jellyfish, decapod larvae, hyperiid amphipods, rotifers and cladocerans.

text: Thorson's rule states that benthic marine invertebrates at low latitudes tend to produce large numbers of eggs developing to widely dispersing pelagic larvae, whereas at high latitudes such organisms tend to produce fewer and larger lecithotrophic (yolk-feeding) eggs and larger offspring.[9][10]

text: Pelagic reptiles[edit]

text: Pelamis platura, the pelagic sea snake, is the only one of the 65 species of marine snakes to spend its entire life in the pelagic zone. It bears live young at sea and is helpless on land. The species sometimes forms aggregations of thousands along slicks in surface waters. The pelagic sea snake is the world’s most widely distributed snake species.

text: Many species of sea turtles spend the first years of their lives in the pelagic zone, moving closer to shore as they reach maturity.


document_title: Will Jackson (Wentworth)

question_text: who killed will jackson's wife on wentworth

question_tokens: who killed will jackson 's wife on wentworth

text: Will Jackson (Wentworth)

text: Development[edit]

text: Magasiva talked about getting the role. He said "It was an interesting time. It was a learning curve for me. If the whole idea was to get into a room with a casting director and make an impression I did what I came for. They've seen my work and have me in mind, so I've achieved that. I came back thinking it was the most impossible thing to do, there's no chance of me ever kind of making it there. But I came back and thought if I put in the hard work and keep on doing what I'm doing it is doable."[1]

text: Storylines[edit]

text: Backstory[edit]

text: Before his wife's death, Will seemed to be a very easy going officer. He was quite relaxed around the prisoners. Like his colleague, Vera Bennett, he cared about the women, and got involved in prison life, but unlike Vera, he didn't get too concerned with the prisoners problems.

text: Will was a social worker before becoming a prison officer, during his time as a social worker, he removed a baby from a prisoner, who was later murdered because of her inappropriate relationship with an officer.[2]

text: Will is first seen processing Bea (Danielle Cormack) when she is brought into Wentworth Prison. Will then is seen flirting with Meg and is caught by Matthew Fletcher (Aaron Jeffery). Will then takes Bea out for a smoke when she is in the slots. The episode ends with Will finding Meg dead and Bea covered in her blood.[3]

text: Following Meg’s death, Will was seen watching the interviews of the prisoners on his laptop. When Doreen and Kaiya make a picture for Will, he rips it up in front of them.[4]

text: Will continues to investigate the death of his wife Meg, he the discovers how his friend Fletch and Meg had a peculiar relationship.[5] Will later discovers that his wife Meg had an abortion sometime before she died, Fletch had to help him come to his senses after he got so high on cocaine and nearly overdosed.[6] Soon after, Will is blackmailed by Jacs Holt when he confronts her about catching Brayden and Debbie doing drugs.[7]

text: Will supports Bea during the death of her daughter Debbie. When Bea isn’t allowed to see the body, Will visits Debbie and spends some time with her and passes on that Bea loves her.[8]

text: In the season one finale, Will listens to a recording of Jacs convincing Brayden to kill Debbie. When Will confronts Jacs, she manipulates him to delete the recording in return for information about Meg’s murder. When Will and Fletch do a cell toss, Will finds Meg’s bracelet in Jacs’ cell but unknown to him Liz Birdsworth planted it there to protect Franky.[9]

text: A calmer Will returned for season two as he believed Meg’s killer, Jac’s Holt, had paid the ultimate price with her own life and moves on with prison nurse, Rose Atkins.[10]

text: Will gets quizzed by Joan Ferguson about his past as a social worker. Joan then tells him that the addiction programs would cease from that moment on.[11]

text: In Twist The Knife, Will learns that Fletch was having an affair with his wife Meg, Will brutually attacks Fletch in the boiler room during a prison lockdown.[12]

text: When Maxine Conway tries to escape prison, she is caught by Will.[13]

text: Will refuses to let Harry Smith see Bea, Harry then accuses Will of having an affair with Bea. Will and Rose later go on a date where a mysterious van runs them off the road. Will goes to Harry’s to confront him and smashes his van up. Will is then arrested for criminal damage. Ferguson gets Will off the charges but it is revealed in a flashback that Ferguson is trying to get revenge against Will.[2]

text: In the Season Two lead up to the finale, Bea has a battle with Franky where she slashes her wrists to avoid cuffing, Will leaves Bea unattended and Bea then escapes.[14] Will then goes searching for Bea and speaks to Liz Birdsworth. Joan leads the police to believe that Bea and Will were working together. Will is later arrested.[15]

text: In Season Three it is revealed that Will received four months suspension for “aiding” Bea. Will holds a grudge against Bea for a while. Ferguson then has Will framed for murdering Harry Smith. Will continues to date Rose.

text: In Failing Upwards, Will visits Fletch and finds it in himself to move on from his negative history with him. Will is also accused of murdering Harry.[16] During the time trying to prove his innocence, Joan Ferguson plans the murder weapon in his garage and then presumably tips off the police.

text: On the day of Franky’s parole, Ferguson sends Will a confession from Franky admitting that she killed Meg. Will then confronts Franky but ends up forgiving her which displeased Ferguson.[17]

text: Will is arrested again on suspicion of Harry’s murder but Bea manages to get him a name that she received from a vigilante. Will then helps Bea and Franky rescue Joshua and Ferguson from a fire in the prison that was started to cover up Jess Warner’s death.[18]

text: In Season 4 Will has been promoted to Deputy Governor and becomes a target for Kaz Proctor and The Red Right Hand as the one sided rivalry with Ferguson continues.[19]

text: Ferguson, having found protection in Kaz's crew, cunningly blames Will for her brutal ganging, a move which only strengthens Kaz's support for her. When Bea defends Will, it backfires dramatically.[20]

text: In the season finale Will is suspended. Bea forces Ferguson into stabbing her 13 times, providing the evidence needed to keep her incarcerated. The situation is witnessed by both Will and Vera. Will tries to keep her alive but shortly after Bea dies in his arms.

text: Season 5 begins with the aftermath of the death of Bea Smith. Still shocked and saddened Will informs the women Bea is dead. Vera thanks Will at Bea's funeral for organizing it and offers him to return to work despite his recent suspension, Will accepts with Franky keeping his faith in justice. Later Franky is framed for murder but Will believes she's innocent.

text: Will is determined to end the drug issue at Wentworth reinforcing security and is supported by Vera, he is successful. But soon former Governor Ferguson makes sure the drugs return to Wentworth with help of now Deputy Governor, Jake Stewart.

text: Kaz is confident an officer is involved and blames Will, first to Vera and then informs the women why he had been suspended. Kaz is on her way to her sentence appeal with Will and another prison guard, taking fellow officer Linda Miles' place so he could have a chance to confront Kaz. Moments later the van suddenly crashes into a river due to the tyre bolts being loosened by Franky, as she thought her trial hearing was that day so she would be in the van and therefore end up in hospital in an attempt to free herself from Wentworth and prove her innocence. Will risks his own life and almost drowns while saving Kaz from the back of the van. The two finally reach safety and go to hospital. On their arrival back at Wentworth, she thanks Will for saving her life and tells him things could possibly be different between the two of them from there on, Ferguson sees it, unknown to them.

text: Will and Kaz, now friendly, find out Jake is the corrupt officer bringing drugs to the prison, Will asks Kaz to tell Allie Novak to speak to Vera, but Kaz refuses believing Vera would listen to Will. Kaz convinces Allie to talk but is blackmailed by Ferguson through Jake, threatening Franky's sister, Will argues with a naive Vera and is informed of her relationship with Jake. After she doesn't believe him Will calls general manager, Derek Channing, to expose Jake. Kaz shares with Will she doesn't have his same faith in the system.

text: Channing discovers the truth but supports Jake for his own gain and offers Will a transfer, Will, tired of all the injustice informs him he will resign. Privately, Will talks to Kaz and confesses his complete loss of faith in the system and tells her he's leaving Wentworth. Kaz tries to convince him to stay saying the women need him more than ever but he says they can find someone else, until Kaz tearfully asks him to stay by telling him she needs him and also needs to know there's at least one good man.

text: Vera briefly holds a grudge against Will for her permant demotion from governorship by Channing, still unaware Will was right. After Ferguson confirms Will's accusations were correct, she apologizes acknowledging he was the only one to see through Jake.

text: Will concerned about Vera asks her if she's okay, Vera informs him her relationship with Jake not only was false but orchestrated by Ferguson herself to get revenge on her. Will reflects on how both, despite all she's done saved her life.

text: After that conversation and a brief chat with Linda, Will makes a research and realizes Jake killed Nils Jespers for Ferguson, Will confronts Jake again, first he denies it then admits it, Will is upset Jake won't tell the police and leaves him crying on the floor.

text: Later, in medical Ferguson begins to taunt him about the death of his wife, Meg, and how he did nothing to avenge her, thus revealing she was the one that sent him the recording of Franky's confession. A very angry Will leaves Ferguson, then saddened, Will chats with Kaz and takes the blame of all of Ferguson's victims since he saved her from the fire and fears Kaz will be next. Kaz admits maybe both were wrong for trying to save her, Will says Ferguson won't stop until she's dead and Kaz agrees by saying sometimes to get justice you have to cross the line.

text: Will, still angry with Jake ignores him when he tries to talk to him but Jake insists and informs him of Allie's and Franky's escape plan. In the final scene, it is revealed Will has teamed up with Jake and Allie and is burying Ferguson alive to end her reign of terror and avenge Bea.

text: Reception[edit]

text: In both 2014 and 2015, Robbie Magasiva was nominated for Most Outstanding Male Performance in the ASTRA Awards for his role as Will Jackson.[21][22]


document_title: We All Die Young

question_text: who sings the song we all die young in the movie rockstar

text: We All Die Young

text: This article does not cite any sources. Please help improve this article by adding citations to reliable sources. Unsourced material may be challenged and removed. (December 2009) (Learn how and when to remove this template message)

text:
"We All Die Young"

Song by Steelheart

from the album Wait

Released
October 25, 1996

Recorded
1996

Genre
Hard rock

Length
5:06

Label
Dream Train/Z Records

Songwriter(s)
Miljenko Matijevic, Kenny Kanowski

Producer(s)
Miljenko Matijevic, Kit Woolven

Wait track listing

"We All Die Young"
(1)
"Live to Die"
(2)

text: "We All Die Young" is a song by Michael Matijevic of Steelheart, and Kenny Kanowski formerly of Steelheart. It is the first song from the 1996 album Wait. The song was covered by the fictional band Steel Dragon in the 2001 film Rock Star, with Miljenko Matijevic on vocals, Zakk Wylde on guitar, Jeff Pilson on bass and Jason Bonham on drums. For the movie, Matijevic performed the vocals for Mark Wahlberg's character, Chris "Izzy" Cole.

text: In 2007, the song was covered by melodic metal band Eden's Curse for their self-titled debut album.

text:
This 1990s rock song-related article is a stub. You can help Wikipedia by expanding it.

v
t
e

text:
[hide]

v
t
e

Steelheart

Miljenko Matijevic
Uros Raskovski
Rev Jones
Mike Humbert

Chris Risola
Frank DiCostanzo
James Ward
John Fowler
Kenny Kanowski
Vincent Mele
Alex Makarovich
Bill Lonero
Jack Wilkenson

Studio albums

Steelheart
Tangled in Reins
Wait
Just a Taste
Good 2B Alive

Songs

"She's Gone"
"We All Die Young"

text: 1996 songsSteelheart songs1990s rock song stubs

text: Articles lacking sources from December 2009All articles lacking sourcesArticles with hAudio microformatsAll stub articles


question_text: who wrote the theme song for sanford and son

text:
"Sanford and Son Theme (The Streetbeater)"

1973 7" vinyl single (US)

Single by Quincy Jones

from the album 'You've Got It Bad, Girl'

Released
1973

Recorded
1972

Genre
Electric blues, funk

Length
3:06
0:51 (Theme version)

Label
A&M

Producer(s)
Quincy Jones

text: "Sanford and Son Theme (The Streetbeater)" is the theme to the 1970s situation comedy Sanford and Son. It was composed by Quincy Jones.

text: Overview[edit]

text: "The Streetbeater" was first released by A&M Records on Jones' 1973 album You've Got It Bad Girl and as a single from that album.[1][2] It is also featured on his Greatest Hits album.

text: Although the piece itself only reached #294 and did not reach Billboard status for that year, it has maintained mainstream popularity, ranking 9th in a Rolling Stone Reader Poll of Television Themes Songs [3]

text: Other recordings[edit]

text: Harry James recorded a version in 1979 on his album Still Harry After All These Years (Sheffield Lab LAB 11).