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Diana Taurasi cannot come back from her sternum injury soon enough for Sandy Brondello’s team.
I dug my knees into the dirt, overlapped my hands, and placed the heel of my right hand on the monk’s sternum .
It goes from the back of your ear to the base of your sternum .
The bullet that hit me ricocheted off my sternum into my lung.
He lifted his t-shirt and showed us a long scar, running from sternum to waistband.
The point of the weapon was concealed by the sternum that it had penetrated with such surprising force.
Then you get a gander at the full monty, as it were, and he looks like someone inflated him from the sternum down.
He considers it the usual crazy talk until one night when his sternum is nearly crushed by a snarling, otherworldly apparition.
The indifferent pole is applied over the sternum or other convenient point.
This pouch, placed above the sternum , extends beneath the arm-holes, and communicates with the larynx.
A blister was then applied to the sternum , and six grains of calomel given in the evening.
On the 15th of November a blister was laid over the sternum , and ʒiss of oxymel scillitic.
But when we come to the determination of the sternum in fishes, difficulties abound, which Geoffroy solves in the following way.
German scientist Carl Vogt was first to describe the principle of apoptosis in 1842. In 1885, anatomist Walther Flemming delivered a more precise description of the process of programmed cell death. However, it was not until 1965 that the topic was resurrected. While studying tissues using electron microscopy, John Foxton Ross Kerr at the University of Queensland was able to distinguish apoptosis from traumatic cell death.  Following the publication of a paper describing the phenomenon, Kerr was invited to join Alastair R. Currie, as well as Andrew Wyllie, who was Currie's graduate student,  at University of Aberdeen. In 1972, the trio published a seminal article in the British Journal of Cancer.  Kerr had initially used the term programmed cell necrosis, but in the article, the process of natural cell death was called apoptosis. Kerr, Wyllie and Currie credited James Cormack, a professor of Greek language at University of Aberdeen, with suggesting the term apoptosis. Kerr received the Paul Ehrlich and Ludwig Darmstaedter Prize on March 14, 2000, for his description of apoptosis. He shared the prize with Boston biologist H. Robert Horvitz. 
For many years, neither "apoptosis" nor "programmed cell death" was a highly cited term. Two discoveries brought cell death from obscurity to a major field of research: identification of components of the cell death control and effector mechanisms, and linkage of abnormalities in cell death to human disease, in particular cancer.
The 2002 Nobel Prize in Medicine was awarded to Sydney Brenner, H. Robert Horvitz and John E. Sulston for their work identifying genes that control apoptosis. The genes were identified by studies in the nematode C. elegans and homologues of these genes function in humans to regulate apoptosis.
In Greek, apoptosis translates to the "falling off" of leaves from a tree.  Cormack, professor of Greek language, reintroduced the term for medical use as it had a medical meaning for the Greeks over two thousand years before. Hippocrates used the term to mean "the falling off of the bones". Galen extended its meaning to "the dropping of the scabs". Cormack was no doubt aware of this usage when he suggested the name. Debate continues over the correct pronunciation, with opinion divided between a pronunciation with the second p silent ( / æ p ə ˈ t oʊ s ɪ s / ap-ə- TOH -sis   ) and the second p pronounced ( / eɪ p ə p ˈ t oʊ s ɪ s / ),   as in the original Greek. [ citation needed ] In English, the p of the Greek -pt- consonant cluster is typically silent at the beginning of a word (e.g. pterodactyl, Ptolemy), but articulated when used in combining forms preceded by a vowel, as in helicopter or the orders of insects: diptera, lepidoptera, etc.
In the original Kerr, Wyllie & Currie paper,  there is a footnote regarding the pronunciation:
We are most grateful to Professor James Cormack of the Department of Greek, University of Aberdeen, for suggesting this term. The word "apoptosis" ( ἀπόπτωσις ) is used in Greek to describe the "dropping off" or "falling off" of petals from flowers, or leaves from trees. To show the derivation clearly, we propose that the stress should be on the penultimate syllable, the second half of the word being pronounced like "ptosis" (with the "p" silent), which comes from the same root "to fall", and is already used to describe the drooping of the upper eyelid.
The initiation of apoptosis is tightly regulated by activation mechanisms, because once apoptosis has begun, it inevitably leads to the death of the cell.   The two best-understood activation mechanisms are the intrinsic pathway (also called the mitochondrial pathway) and the extrinsic pathway.  The intrinsic pathway is activated by intracellular signals generated when cells are stressed and depends on the release of proteins from the intermembrane space of mitochondria.  The extrinsic pathway is activated by extracellular ligands binding to cell-surface death receptors, which leads to the formation of the death-inducing signaling complex (DISC). 
A cell initiates intracellular apoptotic signaling in response to a stress,  which may bring about cell suicide. The binding of nuclear receptors by glucocorticoids,  heat,  radiation,  nutrient deprivation,  viral infection,  hypoxia,  increased intracellular concentration of free fatty acids  and increased intracellular calcium concentration,   for example, by damage to the membrane, can all trigger the release of intracellular apoptotic signals by a damaged cell. A number of cellular components, such as poly ADP ribose polymerase, may also help regulate apoptosis.  Single cell fluctuations have been observed in experimental studies of stress induced apoptosis.  
Before the actual process of cell death is precipitated by enzymes, apoptotic signals must cause regulatory proteins to initiate the apoptosis pathway. This step allows those signals to cause cell death, or the process to be stopped, should the cell no longer need to die. Several proteins are involved, but two main methods of regulation have been identified: the targeting of mitochondria functionality,  or directly transducing the signal via adaptor proteins to the apoptotic mechanisms. An extrinsic pathway for initiation identified in several toxin studies is an increase in calcium concentration within a cell caused by drug activity, which also can cause apoptosis via a calcium binding protease calpain.
Intrinsic pathway Edit
The intrinsic pathway is also known as the mitochondrial pathway. Mitochondria are essential to multicellular life. Without them, a cell ceases to respire aerobically and quickly dies. This fact forms the basis for some apoptotic pathways. Apoptotic proteins that target mitochondria affect them in different ways. They may cause mitochondrial swelling through the formation of membrane pores, or they may increase the permeability of the mitochondrial membrane and cause apoptotic effectors to leak out.   They are very closely related to intrinsic pathway, and tumors arise more frequently through intrinsic pathway than the extrinsic pathway because of sensitivity.  There is also a growing body of evidence indicating that nitric oxide is able to induce apoptosis by helping to dissipate the membrane potential of mitochondria and therefore make it more permeable.  Nitric oxide has been implicated in initiating and inhibiting apoptosis through its possible action as a signal molecule of subsequent pathways that activate apoptosis. 
During apoptosis, cytochrome c is released from mitochondria through the actions of the proteins Bax and Bak. The mechanism of this release is enigmatic, but appears to stem from a multitude of Bax/Bak homo- and hetero-dimers of Bax/Bak inserted into the outer membrane.  Once cytochrome c is released it binds with Apoptotic protease activating factor – 1 (Apaf-1) and ATP, which then bind to pro-caspase-9 to create a protein complex known as an apoptosome. The apoptosome cleaves the pro-caspase to its active form of caspase-9, which in turn cleaves and activates pro-caspase into the effector caspase-3.
Mitochondria also release proteins known as SMACs (second mitochondria-derived activator of caspases) into the cell's cytosol following the increase in permeability of the mitochondria membranes. SMAC binds to proteins that inhibit apoptosis (IAPs) thereby deactivating them, and preventing the IAPs from arresting the process and therefore allowing apoptosis to proceed. IAP also normally suppresses the activity of a group of cysteine proteases called caspases,  which carry out the degradation of the cell. Therefore, the actual degradation enzymes can be seen to be indirectly regulated by mitochondrial permeability.
Extrinsic pathway Edit
Two theories of the direct initiation of apoptotic mechanisms in mammals have been suggested: the TNF-induced (tumor necrosis factor) model and the Fas-Fas ligand-mediated model, both involving receptors of the TNF receptor (TNFR) family  coupled to extrinsic signals.
TNF path Edit
TNF-alpha is a cytokine produced mainly by activated macrophages, and is the major extrinsic mediator of apoptosis. Most cells in the human body have two receptors for TNF-alpha: TNFR1 and TNFR2. The binding of TNF-alpha to TNFR1 has been shown to initiate the pathway that leads to caspase activation via the intermediate membrane proteins TNF receptor-associated death domain (TRADD) and Fas-associated death domain protein (FADD). cIAP1/2 can inhibit TNF-α signaling by binding to TRAF2. FLIP inhibits the activation of caspase-8.  Binding of this receptor can also indirectly lead to the activation of transcription factors involved in cell survival and inflammatory responses.  However, signalling through TNFR1 might also induce apoptosis in a caspase-independent manner.  The link between TNF-alpha and apoptosis shows why an abnormal production of TNF-alpha plays a fundamental role in several human diseases, especially in autoimmune diseases. The TNF-alpha receptor superfamily also includes death receptors (DRs), such as DR4 and DR5. These receptors bind to the proteinTRAIL and mediate apoptosis. Apoptosis is known to be one of the primary mechanisms of targeted cancer therapy.  Luminescent iridium complex-peptide hybrids (IPHs) have recently been designed, which mimic TRAIL and bind to death receptors on cancer cells, thereby inducing their apoptosis. 
The fas receptor (First apoptosis signal) – (also known as Apo-1 or CD95) is a transmembrane protein of the TNF family which binds the Fas ligand (FasL).  The interaction between Fas and FasL results in the formation of the death-inducing signaling complex (DISC), which contains the FADD, caspase-8 and caspase-10. In some types of cells (type I), processed caspase-8 directly activates other members of the caspase family, and triggers the execution of apoptosis of the cell. In other types of cells (type II), the Fas-DISC starts a feedback loop that spirals into increasing release of proapoptotic factors from mitochondria and the amplified activation of caspase-8. 
Following TNF-R1 and Fas activation in mammalian cells [ citation needed ] a balance between proapoptotic (BAX,  BID, BAK, or BAD) and anti-apoptotic (Bcl-Xl and Bcl-2) members of the Bcl-2 family are established. This balance is the proportion of proapoptotic homodimers that form in the outer-membrane of the mitochondrion. The proapoptotic homodimers are required to make the mitochondrial membrane permeable for the release of caspase activators such as cytochrome c and SMAC. Control of proapoptotic proteins under normal cell conditions of nonapoptotic cells is incompletely understood, but in general, Bax or Bak are activated by the activation of BH3-only proteins, part of the Bcl-2 family [ citation needed ] .
Caspases play the central role in the transduction of ER apoptotic signals. Caspases are proteins that are highly conserved, cysteine-dependent aspartate-specific proteases. There are two types of caspases: initiator caspases, caspase 2,8,9,10,11,12, and effector caspases, caspase 3,6,7. The activation of initiator caspases requires binding to specific oligomeric activator protein. Effector caspases are then activated by these active initiator caspases through proteolytic cleavage. The active effector caspases then proteolytically degrade a host of intracellular proteins to carry out the cell death program.
Caspase-independent apoptotic pathway
There also exists a caspase-independent apoptotic pathway that is mediated by AIF (apoptosis-inducing factor). 
Apoptosis model in amphibians Edit
Amphibian frog Xenopus laevis serves as an ideal model system for the study of the mechanisms of apoptosis. In fact, iodine and thyroxine also stimulate the spectacular apoptosis of the cells of the larval gills, tail and fins in amphibians metamorphosis, and stimulate the evolution of their nervous system transforming the aquatic, vegetarian tadpole into the terrestrial, carnivorous frog.    
Negative regulation of apoptosis inhibits cell death signaling pathways, helping tumors to evade cell death and developing drug resistance. The ratio between anti-apoptotic (Bcl-2) and pro-apoptotic (Bax) proteins determines whether a cell lives or dies.   Many families of proteins act as negative regulators categorized into either antiapoptotic factors, such as IAPs and Bcl-2 proteins or prosurvival factors like cFLIP, BNIP3, FADD, Akt, and NF-κB. 
Many pathways and signals lead to apoptosis, but these converge on a single mechanism that actually causes the death of the cell. After a cell receives stimulus, it undergoes organized degradation of cellular organelles by activated proteolytic caspases. In addition to the destruction of cellular organelles, mRNA is rapidly and globally degraded by a mechanism that is not yet fully characterized.  mRNA decay is triggered very early in apoptosis.
A cell undergoing apoptosis shows a series of characteristic morphological changes. Early alterations include:
- Cell shrinkage and rounding occur because of the retraction lamellipodia and the breakdown of the proteinaceous cytoskeleton by caspases. 
- The cytoplasm appears dense, and the organelles appear tightly packed.
- Chromatin undergoes condensation into compact patches against the nuclear envelope (also known as the perinuclear envelope) in a process known as pyknosis, a hallmark of apoptosis. 
- The nuclear envelope becomes discontinuous and the DNA inside it is fragmented in a process referred to as karyorrhexis. The nucleus breaks into several discrete chromatin bodies or nucleosomal units due to the degradation of DNA. 
Apoptosis progresses quickly and its products are quickly removed, making it difficult to detect or visualize on classical histology sections. During karyorrhexis, endonuclease activation leaves short DNA fragments, regularly spaced in size. These give a characteristic "laddered" appearance on agar gel after electrophoresis.  Tests for DNA laddering differentiate apoptosis from ischemic or toxic cell death. 
Apoptotic cell disassembly Edit
Before the apoptotic cell is disposed of, there is a process of disassembly. There are three recognized steps in apoptotic cell disassembly: 
- Membrane blebbing: The cell membrane shows irregular buds known as blebs. Initially these are smaller surface blebs. Later these can grow into larger so-called dynamic membrane blebs.  An important regulator of apoptotic cell membrane blebbing is ROCK1 (rho associated coiled-coil-containing protein kinase 1). 
- Formation of membrane protrusions: Some cell types, under specific conditions, may develop different types of long, thin extensions of the cell membrane called membrane protrusions. Three types have been described: microtubule spikes, apoptopodia (feet of death), and beaded apoptopodia (the latter having a beads-on-a-string appearance). Pannexin 1 is an important component of membrane channels involved in the formation of apoptopodia and beaded apoptopodia.  : The cell breaks apart into multiple vesicles called apoptotic bodies, which undergo phagocytosis. The plasma membrane protrusions may help bring apoptotic bodies closer to phagocytes.
Removal of dead cells Edit
The removal of dead cells by neighboring phagocytic cells has been termed efferocytosis.  Dying cells that undergo the final stages of apoptosis display phagocytotic molecules, such as phosphatidylserine, on their cell surface.  Phosphatidylserine is normally found on the inner leaflet surface of the plasma membrane, but is redistributed during apoptosis to the extracellular surface by a protein known as scramblase.  These molecules mark the cell for phagocytosis by cells possessing the appropriate receptors, such as macrophages.  The removal of dying cells by phagocytes occurs in an orderly manner without eliciting an inflammatory response.  During apoptosis cellular RNA and DNA are separated from each other and sorted to different apoptotic bodies separation of RNA is initiated as nucleolar segregation. 
Many knock-outs have been made in the apoptosis pathways to test the function of each of the proteins. Several caspases, in addition to APAF1 and FADD, have been mutated to determine the new phenotype. In order to create a tumor necrosis factor (TNF) knockout, an exon containing the nucleotides 3704–5364 was removed from the gene. This exon encodes a portion of the mature TNF domain, as well as the leader sequence, which is a highly conserved region necessary for proper intracellular processing. TNF-/- mice develop normally and have no gross structural or morphological abnormalities. However, upon immunization with SRBC (sheep red blood cells), these mice demonstrated a deficiency in the maturation of an antibody response they were able to generate normal levels of IgM, but could not develop specific IgG levels. Apaf-1 is the protein that turns on caspase 9 by cleavage to begin the caspase cascade that leads to apoptosis. Since a -/- mutation in the APAF-1 gene is embryonic lethal, a gene trap strategy was used in order to generate an APAF-1 -/- mouse. This assay is used to disrupt gene function by creating an intragenic gene fusion. When an APAF-1 gene trap is introduced into cells, many morphological changes occur, such as spina bifida, the persistence of interdigital webs, and open brain. In addition, after embryonic day 12.5, the brain of the embryos showed several structural changes. APAF-1 cells are protected from apoptosis stimuli such as irradiation. A BAX-1 knock-out mouse exhibits normal forebrain formation and a decreased programmed cell death in some neuronal populations and in the spinal cord, leading to an increase in motor neurons.
The caspase proteins are integral parts of the apoptosis pathway, so it follows that knock-outs made have varying damaging results. A caspase 9 knock-out leads to a severe brain malformation. A caspase 8 knock-out leads to cardiac failure and thus embryonic lethality. However, with the use of cre-lox technology, a caspase 8 knock-out has been created that exhibits an increase in peripheral T cells, an impaired T cell response, and a defect in neural tube closure. These mice were found to be resistant to apoptosis mediated by CD95, TNFR, etc. but not resistant to apoptosis caused by UV irradiation, chemotherapeutic drugs, and other stimuli. Finally, a caspase 3 knock-out was characterized by ectopic cell masses in the brain and abnormal apoptotic features such as membrane blebbing or nuclear fragmentation. A remarkable feature of these KO mice is that they have a very restricted phenotype: Casp3, 9, APAF-1 KO mice have deformations of neural tissue and FADD and Casp 8 KO showed defective heart development, however, in both types of KO other organs developed normally and some cell types were still sensitive to apoptotic stimuli suggesting that unknown proapoptotic pathways exist.
In order to perform analysis of apoptotic versus necrotic (necroptotic) cells, one can do analysis of morphology by label-free live cell imaging, time-lapse microscopy, flow fluorocytometry, and transmission electron microscopy. There are also various biochemical techniques for analysis of cell surface markers (phosphatidylserine exposure versus cell permeability by flow cytometry), cellular markers such as DNA fragmentation  (flow cytometry),  caspase activation, Bid cleavage, and cytochrome c release (Western blotting). It is important to know how primary and secondary necrotic cells can be distinguished by analysis of supernatant for caspases, HMGB1, and release of cytokeratin 18. However, no distinct surface or biochemical markers of necrotic cell death have been identified yet, and only negative markers are available. These include absence of apoptotic markers (caspase activation, cytochrome c release, and oligonucleosomal DNA fragmentation) and differential kinetics of cell death markers (phosphatidylserine exposure and cell membrane permeabilization). A selection of techniques that can be used to distinguish apoptosis from necroptotic cells could be found in these references.    
Defective pathways Edit
The many different types of apoptotic pathways contain a multitude of different biochemical components, many of them not yet understood.  As a pathway is more or less sequential in nature, removing or modifying one component leads to an effect in another. In a living organism, this can have disastrous effects, often in the form of disease or disorder. A discussion of every disease caused by modification of the various apoptotic pathways would be impractical, but the concept overlying each one is the same: The normal functioning of the pathway has been disrupted in such a way as to impair the ability of the cell to undergo normal apoptosis. This results in a cell that lives past its "use-by date" and is able to replicate and pass on any faulty machinery to its progeny, increasing the likelihood of the cell's becoming cancerous or diseased.
A recently described example of this concept in action can be seen in the development of a lung cancer called NCI-H460.  The X-linked inhibitor of apoptosis protein (XIAP) is overexpressed in cells of the H460 cell line. XIAPs bind to the processed form of caspase-9, and suppress the activity of apoptotic activator cytochrome c, therefore overexpression leads to a decrease in the amount of proapoptotic agonists. As a consequence, the balance of anti-apoptotic and proapoptotic effectors is upset in favour of the former, and the damaged cells continue to replicate despite being directed to die. Defects in regulation of apoptosis in cancer cells occur often at the level of control of transcription factors. As a particular example, defects in molecules that control transcription factor NF-κB in cancer change the mode of transcriptional regulation and the response to apoptotic signals, to curtail dependence on the tissue that the cell belongs. This degree of independence from external survival signals, can enable cancer metastasis. 
Dysregulation of p53 Edit
The tumor-suppressor protein p53 accumulates when DNA is damaged due to a chain of biochemical factors. Part of this pathway includes alpha-interferon and beta-interferon, which induce transcription of the p53 gene, resulting in the increase of p53 protein level and enhancement of cancer cell-apoptosis.  p53 prevents the cell from replicating by stopping the cell cycle at G1, or interphase, to give the cell time to repair, however it will induce apoptosis if damage is extensive and repair efforts fail.  Any disruption to the regulation of the p53 or interferon genes will result in impaired apoptosis and the possible formation of tumors.
Inhibition of apoptosis can result in a number of cancers, inflammatory diseases, and viral infections. It was originally believed that the associated accumulation of cells was due to an increase in cellular proliferation, but it is now known that it is also due to a decrease in cell death. The most common of these diseases is cancer, the disease of excessive cellular proliferation, which is often characterized by an overexpression of IAP family members. As a result, the malignant cells experience an abnormal response to apoptosis induction: Cycle-regulating genes (such as p53, ras or c-myc) are mutated or inactivated in diseased cells, and further genes (such as bcl-2) also modify their expression in tumors. Some apoptotic factors are vital during mitochondrial respiration e.g. cytochrome C.  Pathological inactivation of apoptosis in cancer cells is correlated with frequent respiratory metabolic shifts toward glycolysis (an observation known as the “Warburg hypothesis”. 
HeLa cell Edit
Apoptosis in HeLa [b] cells is inhibited by proteins produced by the cell these inhibitory proteins target retinoblastoma tumor-suppressing proteins.  These tumor-suppressing proteins regulate the cell cycle, but are rendered inactive when bound to an inhibitory protein.  HPV E6 and E7 are inhibitory proteins expressed by the human papillomavirus, HPV being responsible for the formation of the cervical tumor from which HeLa cells are derived.  HPV E6 causes p53, which regulates the cell cycle, to become inactive.  HPV E7 binds to retinoblastoma tumor suppressing proteins and limits its ability to control cell division.  These two inhibitory proteins are partially responsible for HeLa cells' immortality by inhibiting apoptosis to occur.  Canine distemper virus (CDV) is able to induce apoptosis despite the presence of these inhibitory proteins. This is an important oncolytic property of CDV: this virus is capable of killing canine lymphoma cells. Oncoproteins E6 and E7 still leave p53 inactive, but they are not able to avoid the activation of caspases induced from the stress of viral infection. These oncolytic properties provided a promising link between CDV and lymphoma apoptosis, which can lead to development of alternative treatment methods for both canine lymphoma and human non-Hodgkin lymphoma. Defects in the cell cycle are thought to be responsible for the resistance to chemotherapy or radiation by certain tumor cells, so a virus that can induce apoptosis despite defects in the cell cycle is useful for cancer treatment. 
The main method of treatment for potential death from signaling-related diseases involves either increasing or decreasing the susceptibility of apoptosis in diseased cells, depending on whether the disease is caused by either the inhibition of or excess apoptosis. For instance, treatments aim to restore apoptosis to treat diseases with deficient cell death, and to increase the apoptotic threshold to treat diseases involved with excessive cell death. To stimulate apoptosis, one can increase the number of death receptor ligands (such as TNF or TRAIL), antagonize the anti-apoptotic Bcl-2 pathway, or introduce Smac mimetics to inhibit the inhibitor (IAPs).  The addition of agents such as Herceptin, Iressa, or Gleevec works to stop cells from cycling and causes apoptosis activation by blocking growth and survival signaling further upstream. Finally, adding p53-MDM2 complexes displaces p53 and activates the p53 pathway, leading to cell cycle arrest and apoptosis. Many different methods can be used either to stimulate or to inhibit apoptosis in various places along the death signaling pathway. 
Apoptosis is a multi-step, multi-pathway cell-death programme that is inherent in every cell of the body. In cancer, the apoptosis cell-division ratio is altered. Cancer treatment by chemotherapy and irradiation kills target cells primarily by inducing apoptosis.
Hyperactive apoptosis Edit
On the other hand, loss of control of cell death (resulting in excess apoptosis) can lead to neurodegenerative diseases, hematologic diseases, and tissue damage. It is of interest to note that neurons that rely on mitochondrial respiration undergo apoptosis in neurodegenerative diseases such as Alzheimer's  and Parkinson's.  (an observation known as the “Inverse Warburg hypothesis”   ). Moreover, there is an inverse epidemiological comorbidity between neurodegenerative diseases and cancer.  The progression of HIV is directly linked to excess, unregulated apoptosis. In a healthy individual, the number of CD4+ lymphocytes is in balance with the cells generated by the bone marrow however, in HIV-positive patients, this balance is lost due to an inability of the bone marrow to regenerate CD4+ cells. In the case of HIV, CD4+ lymphocytes die at an accelerated rate through uncontrolled apoptosis, when stimulated. At the molecular level, hyperactive apoptosis can be caused by defects in signaling pathways that regulate the Bcl-2 family proteins. Increased expression of apoptotic proteins such as BIM, or their decreased proteolysis, leads to cell death, and can cause a number of pathologies, depending on the cells where excessive activity of BIM occurs. Cancer cells can escape apoptosis through mechanisms that suppress BIM expression or by increased proteolysis of BIM. [ citation needed ]
Treatments aiming to inhibit works to block specific caspases. Finally, the Akt protein kinase promotes cell survival through two pathways. Akt phosphorylates and inhibits Bad (a Bcl-2 family member), causing Bad to interact with the 14-3-3 scaffold, resulting in Bcl dissociation and thus cell survival. Akt also activates IKKα, which leads to NF-κB activation and cell survival. Active NF-κB induces the expression of anti-apoptotic genes such as Bcl-2, resulting in inhibition of apoptosis. NF-κB has been found to play both an antiapoptotic role and a proapoptotic role depending on the stimuli utilized and the cell type. 
HIV progression Edit
The progression of the human immunodeficiency virus infection into AIDS is due primarily to the depletion of CD4+ T-helper lymphocytes in a manner that is too rapid for the body's bone marrow to replenish the cells, leading to a compromised immune system. One of the mechanisms by which T-helper cells are depleted is apoptosis, which results from a series of biochemical pathways: 
- HIV enzymes deactivate anti-apoptotic Bcl-2. This does not directly cause cell death but primes the cell for apoptosis should the appropriate signal be received. In parallel, these enzymes activate proapoptotic procaspase-8, which does directly activate the mitochondrial events of apoptosis.
- HIV may increase the level of cellular proteins that prompt Fas-mediated apoptosis.
- HIV proteins decrease the amount of CD4 glycoprotein marker present on the cell membrane.
- Released viral particles and proteins present in extracellular fluid are able to induce apoptosis in nearby "bystander" T helper cells.
- HIV decreases the production of molecules involved in marking the cell for apoptosis, giving the virus time to replicate and continue releasing apoptotic agents and virions into the surrounding tissue.
- The infected CD4+ cell may also receive the death signal from a cytotoxic T cell.
Cells may also die as direct consequences of viral infections. HIV-1 expression induces tubular cell G2/M arrest and apoptosis.  The progression from HIV to AIDS is not immediate or even necessarily rapid HIV's cytotoxic activity toward CD4+ lymphocytes is classified as AIDS once a given patient's CD4+ cell count falls below 200. 
Researchers from Kumamoto University in Japan have developed a new method to eradicate HIV in viral reservoir cells, named "Lock-in and apoptosis." Using the synthesized compound Heptanoylphosphatidyl L-Inositol Pentakisphophate (or L-Hippo) to bind strongly to the HIV protein PR55Gag, they were able to suppress viral budding. By suppressing viral budding, the researchers were able to trap the HIV virus in the cell and allow for the cell to undergo apoptosis (natural cell death). Associate Professor Mikako Fujita has stated that the approach is not yet available to HIV patients because the research team has to conduct further research on combining the drug therapy that currently exists with this "Lock-in and apoptosis" approach to lead to complete recovery from HIV. 
Viral infection Edit
Viral induction of apoptosis occurs when one or several cells of a living organism are infected with a virus, leading to cell death. Cell death in organisms is necessary for the normal development of cells and the cell cycle maturation.  It is also important in maintaining the regular functions and activities of cells.
Viruses can trigger apoptosis of infected cells via a range of mechanisms including:
- Receptor binding
- Activation of protein kinase R (PKR)
- Interaction with p53
- Expression of viral proteins coupled to MHC proteins on the surface of the infected cell, allowing recognition by cells of the immune system (such as Natural Killer and cytotoxic T cells) that then induce the infected cell to undergo apoptosis. 
Canine distemper virus (CDV) is known to cause apoptosis in central nervous system and lymphoid tissue of infected dogs in vivo and in vitro.  Apoptosis caused by CDV is typically induced via the extrinsic pathway, which activates caspases that disrupt cellular function and eventually leads to the cells death.  In normal cells, CDV activates caspase-8 first, which works as the initiator protein followed by the executioner protein caspase-3.  However, apoptosis induced by CDV in HeLa cells does not involve the initiator protein caspase-8. HeLa cell apoptosis caused by CDV follows a different mechanism than that in vero cell lines.  This change in the caspase cascade suggests CDV induces apoptosis via the intrinsic pathway, excluding the need for the initiator caspase-8. The executioner protein is instead activated by the internal stimuli caused by viral infection not a caspase cascade. 
The Oropouche virus (OROV) is found in the family Bunyaviridae. The study of apoptosis brought on by Bunyaviridae was initiated in 1996, when it was observed that apoptosis was induced by the La Crosse virus into the kidney cells of baby hamsters and into the brains of baby mice. 
OROV is a disease that is transmitted between humans by the biting midge (Culicoides paraensis).  It is referred to as a zoonotic arbovirus and causes febrile illness, characterized by the onset of a sudden fever known as Oropouche fever. 
The Oropouche virus also causes disruption in cultured cells – cells that are cultivated in distinct and specific conditions. An example of this can be seen in HeLa cells, whereby the cells begin to degenerate shortly after they are infected. 
With the use of gel electrophoresis, it can be observed that OROV causes DNA fragmentation in HeLa cells. It can be interpreted by counting, measuring, and analyzing the cells of the Sub/G1 cell population.  When HeLA cells are infected with OROV, the cytochrome C is released from the membrane of the mitochondria, into the cytosol of the cells. This type of interaction shows that apoptosis is activated via an intrinsic pathway. 
In order for apoptosis to occur within OROV, viral uncoating, viral internalization, along with the replication of cells is necessary. Apoptosis in some viruses is activated by extracellular stimuli. However, studies have demonstrated that the OROV infection causes apoptosis to be activated through intracellular stimuli and involves the mitochondria. 
Many viruses encode proteins that can inhibit apoptosis.  Several viruses encode viral homologs of Bcl-2. These homologs can inhibit proapoptotic proteins such as BAX and BAK, which are essential for the activation of apoptosis. Examples of viral Bcl-2 proteins include the Epstein-Barr virus BHRF1 protein and the adenovirus E1B 19K protein.  Some viruses express caspase inhibitors that inhibit caspase activity and an example is the CrmA protein of cowpox viruses. Whilst a number of viruses can block the effects of TNF and Fas. For example, the M-T2 protein of myxoma viruses can bind TNF preventing it from binding the TNF receptor and inducing a response.  Furthermore, many viruses express p53 inhibitors that can bind p53 and inhibit its transcriptional transactivation activity. As a consequence, p53 cannot induce apoptosis, since it cannot induce the expression of proapoptotic proteins. The adenovirus E1B-55K protein and the hepatitis B virus HBx protein are examples of viral proteins that can perform such a function. 
Viruses can remain intact from apoptosis in particular in the latter stages of infection. They can be exported in the apoptotic bodies that pinch off from the surface of the dying cell, and the fact that they are engulfed by phagocytes prevents the initiation of a host response. This favours the spread of the virus. 
Programmed cell death in plants has a number of molecular similarities to that of animal apoptosis, but it also has differences, notable ones being the presence of a cell wall and the lack of an immune system that removes the pieces of the dead cell. Instead of an immune response, the dying cell synthesizes substances to break itself down and places them in a vacuole that ruptures as the cell dies. Whether this whole process resembles animal apoptosis closely enough to warrant using the name apoptosis (as opposed to the more general programmed cell death) is unclear.  
The characterization of the caspases allowed the development of caspase inhibitors, which can be used to determine whether a cellular process involves active caspases. Using these inhibitors it was discovered that cells can die while displaying a morphology similar to apoptosis without caspase activation.  Later studies linked this phenomenon to the release of AIF (apoptosis-inducing factor) from the mitochondria and its translocation into the nucleus mediated by its NLS (nuclear localization signal). Inside the mitochondria, AIF is anchored to the inner membrane. In order to be released, the protein is cleaved by a calcium-dependent calpain protease.
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Rib cage, in vertebrate anatomy, basketlike skeletal structure that forms the chest, or thorax, and is made up of the ribs and their corresponding attachments to the sternum (breastbone) and the vertebral column. The rib cage surrounds the lungs and the heart, serving as an important means of bony protection for these vital organs.In total, the rib cage consists of the 12 thoracic vertebrae and the 24 ribs, in addition to the sternum. With each succeeding rib, from the first, or uppermost, the curvature of the rib cage becomes more open. The rib cage is semirigid but expansile, able to increase in size. The small joints between the ribs and the vertebrae permit a gliding motion of the ribs on the vertebrae during breathing and other activities.
The first seven ribs in the rib cage are attached to the sternum by pliable cartilages called costal cartilages these ribs are called true ribs. Of the remaining five ribs, which are called false, the first three have their costal cartilages connected to the cartilage above them. The last two, the floating ribs, have their cartilages ending in the muscle in the abdominal wall. The configuration of the lower five ribs gives freedom for the expansion of the lower part of the rib cage and for the movements of the diaphragm, which has an extensive origin from the rib cage and the vertebral column. The motion is limited by the ligamentous attachments between ribs and vertebrae.
The Editors of Encyclopaedia Britannica This article was most recently revised and updated by Kara Rogers, Senior Editor.
The rib cage (also called thoracic cage) is aptly named, because it forms a sort of cage that holds within it the organs of the upper part of the trunk, including the heart and lungs . It is shown in Figures 11.3.6–11.3.8. The rib cage includes the 12 thoracic vertebrae and the sternum, as well as 12 pairs of ribs, which are attached at joints to the vertebrae. The ribs are divided into three groups, called true ribs, false ribs, and floating ribs. The top seven pairs of ribs are true ribs. They are attached by cartilage directly to the sternum. The next three pairs of ribs are false ribs. They are attached by cartilage to the ribs above them, rather than directly to the sternum. The lowest two pairs of ribs are floating ribs. They are attached by cartilage to muscles in the abdominal wall. The attachments of false and floating ribs let the lower part of the rib cage expand to accommodate the internal movements of breathing.
|Figure 11.3.6 True ribs are attached to both the vertebrae and the sternum. In this image, true ribs are highlighted in red.||Figure 11.3.7 False ribs are attached to the vertebrae and to the ribs above them by cartilage. In this image, false ribs and floating ribs are highlighted in red.||Figure 11.3.8 Floating ribs are attached to vertebrae and the the muscles in the abdominal wall. In this image floating ribs are highlighted in red.|
The appendicular skeleton , shown in red (Figure 11.3.9), consists of a total of 126 bones. It includes all the bones of the limbs (arms, legs, hands, and feet,) as well as the bones of the shoulder (shoulder girdle) and pelvis (pelvic girdle).
Figure 11.3.9 The appendicular skeleton includes the upper and lower appendages and girdles.
Ivan K. H. Poon and Christopher D. Lucas: These authors contributed equally to this work.
Center for Cell Clearance and the Department of Microbiology, Immunology, and Cancer Biology, University of Virginia, Charlottesville, 22908, Virginia, USA
Ivan K. H. Poon & Kodi S. Ravichandran
Department of Biochemistry, La Trobe Institute for Molecular Science, La Trobe University, 3086, Victoria, Australia
MRC Centre for Inflammation Research, The Queen's Medical Research Institute, University of Edinburgh, Edinburgh, EH16 4TJ, UK
Christopher D. Lucas & Adriano G. Rossi
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Machine Learning for Automatic Paraspinous Muscle Area and Attenuation Measures on Low-Dose Chest CT Scans
Rationale and objectives: To develop and evaluate an automated machine learning (ML) algorithm for segmenting the paraspinous muscles on chest computed tomography (CT) scans to evaluate for presence of sarcopenia.
Materials and methods: A convolutional neural network based on the U-Net architecture was trained to perform muscle segmentation on a dataset of 1875 single slice CT images and was tested on 209 CT images of participants in the National Lung Screening Trial. Low-dose, noncontrast CT examinations were obtained at 33 clinical sites, using scanners from four manufacturers. The study participants had a mean age of 71.6 years (range, 70-74 years). Ground truth was obtained by manually segmenting the left paraspinous muscle at the level of the T12 vertebra. Muscle cross-sectional area (CSA) and muscle attenuation (MA) were recorded. Comparison between the ML algorithm and ground truth measures of muscle CSA and MA were obtained using Dice similarity coefficients and Pearson correlations.
Results: Compared to ground truth segmentation, the ML algorithm achieved median (standard deviation) Dice scores of 0.94 (0.04) in the test set. Mean (SD) muscle CSA was 14.3 (3.6) cm 2 for ground truth and 13.7 (3.5) cm 2 for ML segmentation. Mean (SD) MA was 41.6 (7.6) Hounsfield units (HU) for ground truth and 43.5 (7.9) HU for ML segmentation. There was high correlation between ML algorithm and ground truth for muscle CSA (r 2 = 0.86 p < 0.0001) and MA (r 2 = 0.95 p < 0.0001).
Conclusion: The ML algorithm for measurement of paraspinous muscles compared favorably to manual ground truth measurements in the NLST. The algorithm generalized well to a heterogeneous set of low-dose CT images and may be capable of automated quantification of muscle metrics to screen for sarcopenia on routine chest CT examinations.
Keywords: Chest CT Machine learning Muscle Myosteatosis Sarcopenia.
Copyright © 2019 The Association of University Radiologists. Published by Elsevier Inc. All rights reserved.
14.3: Video- The Sternum - Biology
GOA-ON is a collaborative international network to detect and understand the drivers of ocean acidification in estuarine-coastal-open ocean environments, the resulting impacts on marine ecosystems, and to make the information available to optimize modelling studies. The network is fundamental to providing early warning of the impacts of ocean acidification on natural ecosystems, wild and aquaculture fisheries, coastal protection, tourism and local economies. The network provides key input to communities, industry and governments seeking to develop action plans, best practices, and mitigation or adaptation strategies to address ocean acidification impacts.
The GOA-ON data portal provides easy access to data and visualizations
Regional Changes in Southern Ocean Biogeochemistry Due to Projected Carbon Uptake
Please join us for the next GOA-ON Webinar, which will feature Dr. Eric Mortenson, a postdoctoral researcher with CSIRO. He will discuss his biogeochemical modeling research, which has identified regions of pronounced change and forecasts increased carbon uptake in the Southern Ocean. The webinar will take place on Wednesday, 14 July 2021 at 10:00 Australian Eastern Standard Time (UTC +10). Click the registration link for more information.
14.3: Video- The Sternum - Biology
Journal of Cell Science publishes cutting-edge science, encompassing all aspects of cell biology.
The journal is led by Editor-in-Chief Michael Way and a prestigious team of Editors who are research-active academics and leaders in their respective fields they are supported by an outstanding Editorial Advisory Board that reflects all relevant areas in cell biology, including recently emerging fields. Rigorous peer review and fair decisions form the bedrock of the journal and maintain Journal of Cell Science as a solid forum for communicating the best research.
Our latest special issue, Cell Biology of Lipids, is now open. Articles will be added to the issue over the coming months. To view the latest articles, click here.
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This middle school physical science course is specifically designed to be the second course taken during junior high. It is created to give middle school students an understanding of the basic world that surrounds them each day of their lives and the forces in creation, so that they can appreciate the real-world relevance of scientific inquiry and the beauty of creation. We believe that students’ educations should prepare them for life, not just an academic year.
Our award-winning, homeschool, junior high physical science course covers:
- The basics of science including the scientific process, scientific theories and laws, inferences and models, and measurement and units
- Chemistry including properties and states of matter, atomic structure and the periodic table, chemical bonds and reactions and energy
- Physics including motion, forces, energy, waves and sound, light and electricity and magnetism
- Earth Science including the Earth’s structure and processes and our atmosphere and beyond
- Chemistry and Physics in the life sciences
- Physical Science research
If all we ever offer our students is a textbook version of science, they will never get to “own” a discovery that they make during an experiment. Our world is not a world of chaos, and once students begin to see that they can observe a phenomenon, ask questions, and set up a methodical test to answer questions, science will no longer be a class but rather a means to discover their world.
Throughout their academic school year, your students will conduct controlled experiments where they observe a problem, ask a question, formulate a testable hypothesis, and then conduct the experiment and analyze the data to see if their results support their hypothesis. It involves quantitative data that require measurements. The lab portion of Apologia guides students through this process.
Additionally, students will conduct descriptive experiments to use their 5 senses to make qualitative observations and describe what they learn. Again, our homeschool curriculum was designed with your student’s success in mind, and we guide students through this process with detailed descriptions and photographs.
Yahoo Answers is shutting down - here are 10 of the best questions ever asked
For more than a decade the site was a magnet for trolls and pure comic genius, but Yahoo Answers is set to be shut down.
Tuesday 6 April 2021 12:11, UK
Yahoo Answers is going to be shut down after more than 15 years of providing the web with hilarious content.
The website is first slipping into read-only mode from 20 April, before being shut down entirely on 4 May - redirecting visitors to the Yahoo homepage instead.
When the site disappears then all of its many brilliant questions - with their innovative grammatical and spelling errors, and the amazing credulity of the askers - will be lost, like tears in rain.
While "how is babby formed? How girl get pragnent?" will forever be the site's greatest contribution to web culture, there are many more to find - at least, for the next month or so.
While we can, here are 10 more of the best questions and answers the site has ever featured.
1) do you think humans will ever walk on the sun?
It is actually hypothetically possible to walk on the sun - as long as we defined what the surface was - but it would be a brief walk.
2) HOW DO I TURN OFF CAPLOCK?
3) Is throwing your hair in the garbage safe?
The user continued: "I wanted to be sure because in biology we learned that it had DNA and stuff so is it safe?"
4) What if the girl that thinks i'm the dad isn't the mom?
This is frightening on a number of levels.
5) Is there a spell to become a mermaid that actually works?
User bmx4life only ever asked three questions, including the above.
They also asked: "My sister walks around with out socks on all the time and her feet ar starting to stink really bad, why?" and the classic: "runescape please answer?"
6) If i eat myself would i become twice as big or disappear completely?
Although official accounts claim that French philosopher Gilles Deleuze died in 1995, but this question contributes to a body of evidence he was active online up until quite recently, posting metaphysical provocations on Yahoo Answers.
7) Why does my cat "vibrate"?
This purrplexed user wrote: "Her chest always vibrates like she was worms or something in her. Is it normal? When she vibrated she makes a tiny vibrate noise and its scaring me it doesn't seem normal!"
8) Can I tell by the smell of my husbands gas if he has been cheating?
"I know this sounds crazy. BUT," begins this anonymous post. Sadly, three years later, we can only imagine what the status of this marriage is as the question was never updated.
9) Will my laptop get heavier if I put more files on it?
10) how many calories are in a booger?
The answer to this potential troll is even better than the remarkably poignant description: "it sometimes wet and color yellow".