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Wednesday, December 11, 2019

Death

From Wikipedia, the free encyclopedia
https://en.wikipedia.org/wiki/Death
 
The human skull is used universally as a symbol of death.
 
Statue of Death, personified as a human skeleton dressed in a shroud and clutching a scythe, from the Cathedral of Trier in Trier, Germany
 
Death tending to his flowers, in Kuoleman Puutarha, Hugo Simberg (1906)
 
Death is the permanent cessation of all biological functions that sustain a living organism. Phenomena which commonly bring about death include aging, predation, malnutrition, disease, suicide, homicide, starvation, dehydration, and accidents or major trauma resulting in terminal injury. In most cases, bodies of living organisms begin to decompose shortly after death.

Death – particularly the death of humans – has commonly been considered a sad or unpleasant occasion, due to the affection for the being that has died and the termination of social and familial bonds with the deceased. Other concerns include fear of death, necrophobia, anxiety, sorrow, grief, emotional pain, depression, sympathy, compassion, solitude, or saudade. Many cultures and religions have the idea of an afterlife, and also hold the idea of reward or judgement and punishment for past sin

Senescence

A dead magpie
 
Senescence refers to a scenario when a living being is able to survive all calamities, but eventually dies due to causes relating to old age. Animal and plant cells normally reproduce and function during the whole period of natural existence, but the aging process derives from deterioration of cellular activity and ruination of regular functioning. Aptitude of cells for gradual deterioration and mortality means that cells are naturally sentenced to stable and long-term loss of living capacities, even despite continuing metabolic reactions and viability. In the United Kingdom, for example, nine out of ten of all the deaths that occur on a daily basis relates to senescence, while around the world it accounts for two-thirds of 150,000 deaths that take place daily (Hayflick & Moody, 2003).

Almost all animals who survive external hazards to their biological functioning eventually die from biological aging, known in life sciences as "senescence". Some organisms experience negligible senescence, even exhibiting biological immortality. These include the jellyfish Turritopsis dohrnii, the hydra, and the planarian. Unnatural causes of death include suicide and predation. From all causes, roughly 150,000 people die around the world each day. Of these, two thirds die directly or indirectly due to senescence, but in industrialized countries – such as the United States, the United Kingdom, and Germany – the rate approaches 90% (i.e., nearly nine out of ten of all deaths are related to senescence).

Physiological death is now seen as a process, more than an event: conditions once considered indicative of death are now reversible. Where in the process a dividing line is drawn between life and death depends on factors beyond the presence or absence of vital signs. In general, clinical death is neither necessary nor sufficient for a determination of legal death. A patient with working heart and lungs determined to be brain dead can be pronounced legally dead without clinical death occurring. As scientific knowledge and medicine advance, formulating a precise medical definition of death becomes more difficult.

Diagnosis

World Health Organization estimated number of deaths per million persons in 2012
  1,054–4,598
  4,599–5,516
  5,517–6,289
  6,290–6,835
  6,836–7,916
  7,917–8,728
  8,729–9,404
  9,405–10,433
  10,434–12,233
  12,234–17,141

Signs

Signs of death or strong indications that a warm-blooded animal is no longer alive are:
  • Respiratory arrest (no breathing)
  • Cardiac arrest (no pulse)
  • Brain death (no neuronal activity)
  • Pallor mortis, paleness which happens in the 15–120 minutes after death
  • Algor mortis, the reduction in body temperature following death. This is generally a steady decline until matching ambient temperature
  • Rigor mortis, the limbs of the corpse become stiff (Latin rigor) and difficult to move or manipulate
  • Livor mortis, a settling of the blood in the lower (dependent) portion of the body
  • Putrefaction, the beginning signs of decomposition
  • Decomposition, the reduction into simpler forms of matter, accompanied by a strong, unpleasant odor.
  • Skeletonization, the end of decomposition, where all soft tissues have decomposed, leaving only the skeleton.
  • Fossilization, the natural preservation of the skeletal remains formed over a very long period

Problems of definition

Symbols of death in a painting: it shows a flower, a skull and an hourglass
A flower, a skull and an hourglass stand for life, death and time in this 17th-century painting by Philippe de Champaigne
 
Ivory pendant of a Monk's face. The left half of the pendant appears skeletal, while the right half appears living
French – 16th-/17th-century ivory pendant, Monk and Death, recalling mortality and the certainty of death (Walters Art Museum)
 
The concept of death is a key to human understanding of the phenomenon. There are many scientific approaches and various interpretations of the concept. Additionally, the advent of life-sustaining therapy and the numerous criteria for defining death from both a medical and legal standpoint, have made it difficult to create a single unifying definition.

One of the challenges in defining death is in distinguishing it from life. As a point in time, death would seem to refer to the moment at which life ends. Determining when death has occurred is difficult, as cessation of life functions is often not simultaneous across organ systems. Such determination therefore requires drawing precise conceptual boundaries between life and death. This is difficult, due to there being little consensus on how to define life. 

It is possible to define life in terms of consciousness. When consciousness ceases, a living organism can be said to have died. One of the flaws in this approach is that there are many organisms which are alive but probably not conscious (for example, single-celled organisms). Another problem is in defining consciousness, which has many different definitions given by modern scientists, psychologists and philosophers. Additionally, many religious traditions, including Abrahamic and Dharmic traditions, hold that death does not (or may not) entail the end of consciousness. In certain cultures, death is more of a process than a single event. It implies a slow shift from one spiritual state to another.

Other definitions for death focus on the character of cessation of something. More specifically, death occurs when a living entity experiences irreversible cessation of all functioning. As it pertains to human life, death is an irreversible process where someone loses their existence as a person.

Historically, attempts to define the exact moment of a human's death have been subjective, or imprecise. Death was once defined as the cessation of heartbeat (cardiac arrest) and of breathing, but the development of CPR and prompt defibrillation have rendered that definition inadequate because breathing and heartbeat can sometimes be restarted. This type of death where circulatory and respiratory arrest happens is known as the circulatory definition of death (DCDD). Proponents of the DCDD believe that this definition is reasonable because a person with permanent loss of circulatory and respiratory function should be considered dead. Critics of this definition state that while cessation of these functions may be permanent, it does not mean the situation is not irreversible, because if CPR was applied, the person could be revived. Thus, the arguments for and against the DCDD boil down to a matter of defining the actual words "permanent" and "irreversible," which further complicates the challenge of defining death. Furthermore, events which were causally linked to death in the past no longer kill in all circumstances; without a functioning heart or lungs, life can sometimes be sustained with a combination of life support devices, organ transplants and artificial pacemakers

Today, where a definition of the moment of death is required, doctors and coroners usually turn to "brain death" or "biological death" to define a person as being dead; people are considered dead when the electrical activity in their brain ceases. It is presumed that an end of electrical activity indicates the end of consciousness. Suspension of consciousness must be permanent, and not transient, as occurs during certain sleep stages, and especially a coma. In the case of sleep, EEGs can easily tell the difference. 

The category of "brain death" is seen as problematic by some scholars. For instance, Dr. Franklin Miller, senior faculty member at the Department of Bioethics, National Institutes of Health, notes: "By the late 1990s... the equation of brain death with death of the human being was increasingly challenged by scholars, based on evidence regarding the array of biological functioning displayed by patients correctly diagnosed as having this condition who were maintained on mechanical ventilation for substantial periods of time. These patients maintained the ability to sustain circulation and respiration, control temperature, excrete wastes, heal wounds, fight infections and, most dramatically, to gestate fetuses (in the case of pregnant "brain-dead" women)."

While "brain death" is viewed as problematic by some scholars, there are certainly proponents of it that believe this definition of death is the most reasonable for distinguishing life from death. The reasoning behind the support for this definition is that brain death has a set of criteria that is reliable and reproducible. Also, the brain is crucial in determining our identity or who we are as human beings. The distinction should be made that "brain death" cannot be equated with one who is in a vegetative state or coma, in that the former situation describes a state that is beyond recovery.

Those people maintaining that only the neo-cortex of the brain is necessary for consciousness sometimes argue that only electrical activity should be considered when defining death. Eventually it is possible that the criterion for death will be the permanent and irreversible loss of cognitive function, as evidenced by the death of the cerebral cortex. All hope of recovering human thought and personality is then gone given current and foreseeable medical technology. At present, in most places the more conservative definition of death – irreversible cessation of electrical activity in the whole brain, as opposed to just in the neo-cortex – has been adopted (for example the Uniform Determination Of Death Act in the United States). In 2005, the Terri Schiavo case brought the question of brain death and artificial sustenance to the front of American politics.

Even by whole-brain criteria, the determination of brain death can be complicated. EEGs can detect spurious electrical impulses, while certain drugs, hypoglycemia, hypoxia, or hypothermia can suppress or even stop brain activity on a temporary basis. Because of this, hospitals have protocols for determining brain death involving EEGs at widely separated intervals under defined conditions. 

In the past, adoption of this whole-brain definition was a conclusion of the President's Commission for the Study of Ethical Problems in Medicine and Biomedical and Behavioral Research in 1980. They concluded that this approach to defining death sufficed in reaching a uniform definition nationwide. A multitude of reasons were presented to support this definition including: uniformity of standards in law for establishing death; consumption of a family's fiscal resources for artificial life support; and legal establishment for equating brain death with death in order to proceed with organ donation.

Aside from the issue of support of or dispute against brain death, there is another inherent problem in this categorical definition: the variability of its application in medical practice. In 1995, the American Academy of Neurology (AAN), established a set of criteria that became the medical standard for diagnosing neurologic death. At that time, three clinical features had to be satisfied in order to determine “irreversible cessation” of the total brain including: coma with clear etiology, cessation of breathing, and lack of brainstem reflexes. This set of criteria was then updated again most recently in 2010, but substantial discrepancies still remain across hospitals and medical specialties.

The problem of defining death is especially imperative as it pertains to the Dead donor rule, which could be understood as one of the following interpretations of the rule: there must be an official declaration of death in a person before starting organ procurement or that organ procurement cannot result in death of the donor. A great deal of controversy has surrounded the definition of death and the dead donor rule. Advocates of the rule believe the rule is legitimate in protecting organ donors while also countering against any moral or legal objection to organ procurement. Critics, on the other hand, believe that the rule does not uphold the best interests of the donors and that the rule does not effectively promote organ donation.

Legal

The death of a person has legal consequences that may vary between different jurisdictions. A death certificate is issued in most jurisdictions, either by a doctor, or by an administrative office upon presentation of a doctor's declaration of death. 

Misdiagnosed

Antoine Wiertz's painting of a man buried alive
 
There are many anecdotal references to people being declared dead by physicians and then "coming back to life", sometimes days later in their own coffin, or when embalming procedures are about to begin. From the mid-18th century onwards, there was an upsurge in the public's fear of being mistakenly buried alive, and much debate about the uncertainty of the signs of death. Various suggestions were made to test for signs of life before burial, ranging from pouring vinegar and pepper into the corpse's mouth to applying red hot pokers to the feet or into the rectum. Writing in 1895, the physician J.C. Ouseley claimed that as many as 2,700 people were buried prematurely each year in England and Wales, although others estimated the figure to be closer to 800.

In cases of electric shock, cardiopulmonary resuscitation (CPR) for an hour or longer can allow stunned nerves to recover, allowing an apparently dead person to survive. People found unconscious under icy water may survive if their faces are kept continuously cold until they arrive at an emergency room. In science fiction scenarios where such technology is readily available, real death is distinguished from reversible death. 

Causes

The leading cause of human death in developing countries is infectious disease. The leading causes in developed countries are atherosclerosis (heart disease and stroke), cancer, and other diseases related to obesity and aging. By an extremely wide margin, the largest unifying cause of death in the developed world is biological aging, leading to various complications known as aging-associated diseases. These conditions cause loss of homeostasis, leading to cardiac arrest, causing loss of oxygen and nutrient supply, causing irreversible deterioration of the brain and other tissues. Of the roughly 150,000 people who die each day across the globe, about two thirds die of age-related causes. In industrialized nations, the proportion is much higher, approaching 90%. With improved medical capability, dying has become a condition to be managed. Home deaths, once commonplace, are now rare in the developed world. 

American children smoking in 1910. Tobacco smoking caused an estimated 100 million deaths in the 20th century.
 
In developing nations, inferior sanitary conditions and lack of access to modern medical technology makes death from infectious diseases more common than in developed countries. One such disease is tuberculosis, a bacterial disease which killed 1.8M people in 2015. Malaria causes about 400–900M cases of fever and 1–3M deaths annually. AIDS death toll in Africa may reach 90–100M by 2025.

According to Jean Ziegler (United Nations Special Reporter on the Right to Food, 2000 – Mar 2008), mortality due to malnutrition accounted for 58% of the total mortality rate in 2006. Ziegler says worldwide approximately 62M people died from all causes and of those deaths more than 36M died of hunger or diseases due to deficiencies in micronutrients.

Tobacco smoking killed 100 million people worldwide in the 20th century and could kill 1 billion people around the world in the 21st century, a World Health Organization report warned.

Many leading developed world causes of death can be postponed by diet and physical activity, but the accelerating incidence of disease with age still imposes limits on human longevity. The evolutionary cause of aging is, at best, only just beginning to be understood. It has been suggested that direct intervention in the aging process may now be the most effective intervention against major causes of death.

Selye proposed a unified non-specific approach to many causes of death. He demonstrated that stress decreases adaptability of an organism and proposed to describe the adaptability as a special resource, adaptation energy. The animal dies when this resource is exhausted. Selye assumed that the adaptability is a finite supply, presented at birth. Later on, Goldstone proposed the concept of a production or income of adaptation energy which may be stored (up to a limit), as a capital reserve of adaptation. In recent works, adaptation energy is considered as an internal coordinate on the "dominant path" in the model of adaptation. It is demonstrated that oscillations of well-being appear when the reserve of adaptability is almost exhausted.

In 2012, suicide overtook car crashes for leading causes of human injury deaths in the U.S., followed by poisoning, falls and murder. Causes of death are different in different parts of the world. In high-income and middle income countries nearly half up to more than two thirds of all people live beyond the age of 70 and predominantly die of chronic diseases. In low-income countries, where less than one in five of all people reach the age of 70, and more than a third of all deaths are among children under 15, people predominantly die of infectious diseases.

Autopsy

A painting of an autopsy, by Rembrandt, entitled "The Anatomy Lesson of Dr. Nicolaes Tulp"
An autopsy is portrayed in The Anatomy Lesson of Dr. Nicolaes Tulp, by Rembrandt
 
An autopsy, also known as a postmortem examination or an obduction, is a medical procedure that consists of a thorough examination of a human corpse to determine the cause and manner of a person's death and to evaluate any disease or injury that may be present. It is usually performed by a specialized medical doctor called a pathologist.

Autopsies are either performed for legal or medical purposes. A forensic autopsy is carried out when the cause of death may be a criminal matter, while a clinical or academic autopsy is performed to find the medical cause of death and is used in cases of unknown or uncertain death, or for research purposes. Autopsies can be further classified into cases where external examination suffices, and those where the body is dissected and an internal examination is conducted. Permission from next of kin may be required for internal autopsy in some cases. Once an internal autopsy is complete the body is generally reconstituted by sewing it back together. Autopsy is important in a medical environment and may shed light on mistakes and help improve practices.

A necropsy, which is not always a medical procedure, was a term previously used to describe an unregulated postmortem examination . In modern times, this term is more commonly associated with the corpses of animals.

Cryonics

Technicians prepare a body for cryopreservation in 1985.

Cryonics (from Greek κρύος 'kryos-' meaning 'icy cold') is the low-temperature preservation of animals and humans who cannot be sustained by contemporary medicine, with the hope that healing and resuscitation may be possible in the future.

Cryopreservation of people or large animals is not reversible with current technology. The stated rationale for cryonics is that people who are considered dead by current legal or medical definitions may not necessarily be dead according to the more stringent information-theoretic definition of death.
Some scientific literature is claimed to support the feasibility of cryonics. Medical science and cryobiologists generally regards cryonics with skepticism.

Life extension

Life extension refers to an increase in maximum or average lifespan, especially in humans, by slowing down or reversing the processes of aging. Average lifespan is determined by vulnerability to accidents and age or lifestyle-related afflictions such as cancer, or cardiovascular disease. Extension of average lifespan can be achieved by good diet, exercise and avoidance of hazards such as smoking. Maximum lifespan is also determined by the rate of aging for a species inherent in its genes. Currently, the only widely recognized method of extending maximum lifespan is calorie restriction. Theoretically, extension of maximum lifespan can be achieved by reducing the rate of aging damage, by periodic replacement of damaged tissues, or by molecular repair or rejuvenation of deteriorated cells and tissues. 

A United States poll found that religious people and irreligious people, as well as men and women and people of different economic classes have similar rates of support for life extension, while Africans and Hispanics have higher rates of support than white people. 38 percent of the polled said they would desire to have their aging process cured. 

Researchers of life extension are a subclass of biogerontologists known as "biomedical gerontologists". They try to understand the nature of aging and they develop treatments to reverse aging processes or to at least slow them down, for the improvement of health and the maintenance of youthful vigor at every stage of life. Those who take advantage of life extension findings and seek to apply them upon themselves are called "life extensionists" or "longevists". The primary life extension strategy currently is to apply available anti-aging methods in the hope of living long enough to benefit from a complete cure to aging once it is developed. 

Reperfusion

"One of medicine's new frontiers: treating the dead", recognizes that cells that have been without oxygen for more than five minutes die, not from lack of oxygen, but rather when their oxygen supply is resumed. Therefore, practitioners of this approach, e.g., at the Resuscitation Science institute at the University of Pennsylvania, "aim to reduce oxygen uptake, slow metabolism and adjust the blood chemistry for gradual and safe reperfusion."

Location

Before about 1930, most people in Western countries died in their own homes, surrounded by family, and comforted by clergy, neighbors, and doctors making house calls. By the mid-20th century, half of all Americans died in a hospital. By the start of the 21st century, only about 20-25% of people in developed countries died outside of a medical institution. The shift away from dying at home, towards dying in a professional medical environment, has been termed the "Invisible Death". This shift occurred gradually over the years, until most deaths now occur outside the home.

Emotional response

Many people are afraid of dying. Talking about it, thinking about it, or planning for their own deaths causes them discomfort. This fear may cause them to put off financial planning, preparing a will and testament, or requesting help from a hospice organization.

Different people have different responses to the idea of their own deaths.

Philosopher Galen Strawson writes that the death that many people wish for is an instant, painless, unexperienced annihilation. In this unlikely scenario, the person dies without realizing it and without being able fear it. One moment the person is walking, eating, or sleeping, and the next moment, the person is dead. Strawson reasons that this type of death would not take anything away from the person, as he believes that a person cannot have a legitimate claim to ownership in the future.

Society and culture

A duke insulting the corpse of Klaus Fleming
The regent duke Charles (later king Charles IX of Sweden) insulting the corpse of Klaus Fleming. Albert Edelfelt, 1878.
 
Dead bodies can be mummified either naturally, as this one from Guanajuato, or by intention, as those in ancient Egypt.
 
In society, the nature of death and humanity's awareness of its own mortality has for millennia been a concern of the world's religious traditions and of philosophical inquiry. This includes belief in resurrection or an afterlife (associated with Abrahamic religions), reincarnation or rebirth (associated with Dharmic religions), or that consciousness permanently ceases to exist, known as eternal oblivion (associated with atheism).

Commemoration ceremonies after death may include various mourning, funeral practices and ceremonies of honouring the deceased. The physical remains of a person, commonly known as a corpse or body, are usually interred whole or cremated, though among the world's cultures there are a variety of other methods of mortuary disposal. In the English language, blessings directed towards a dead person include rest in peace, or its initialism RIP.

Death is the center of many traditions and organizations; customs relating to death are a feature of every culture around the world. Much of this revolves around the care of the dead, as well as the afterlife and the disposal of bodies upon the onset of death. The disposal of human corpses does, in general, begin with the last offices before significant time has passed, and ritualistic ceremonies often occur, most commonly interment or cremation. This is not a unified practice; in Tibet, for instance, the body is given a sky burial and left on a mountain top. Proper preparation for death and techniques and ceremonies for producing the ability to transfer one's spiritual attainments into another body (reincarnation) are subjects of detailed study in Tibet. Mummification or embalming is also prevalent in some cultures, to retard the rate of decay

Legal aspects of death are also part of many cultures, particularly the settlement of the deceased estate and the issues of inheritance and in some countries, inheritance taxation

Gravestones in Japan
Gravestones in Kyoto, Japan
 
Capital punishment is also a culturally divisive aspect of death. In most jurisdictions where capital punishment is carried out today, the death penalty is reserved for premeditated murder, espionage, treason, or as part of military justice. In some countries, sexual crimes, such as adultery and sodomy, carry the death penalty, as do religious crimes such as apostasy, the formal renunciation of one's religion. In many retentionist countries, drug trafficking is also a capital offense. In China, human trafficking and serious cases of corruption are also punished by the death penalty. In militaries around the world courts-martial have imposed death sentences for offenses such as cowardice, desertion, insubordination, and mutiny.

Death in warfare and in suicide attack also have cultural links, and the ideas of dulce et decorum est pro patria mori, mutiny punishable by death, grieving relatives of dead soldiers and death notification are embedded in many cultures. Recently in the western world, with the increase in terrorism following the September 11 attacks, but also further back in time with suicide bombings, kamikaze missions in World War II and suicide missions in a host of other conflicts in history, death for a cause by way of suicide attack, and martyrdom have had significant cultural impacts.

Suicide is also present in some subcultures. In recent times for example in the emo subculture. The qualitative research has shown emo respondents reported “attitudes including high acceptance for suicidal behavior and self-injury”. And concluded: “The identification with the emo youth subculture is considered to be a factor strengthening vulnerability towards risky behaviors.”

Suicide in general, and particularly euthanasia, are also points of cultural debate. Both acts are understood very differently in different cultures. In Japan, for example, ending a life with honor by seppuku was considered a desirable death, whereas according to traditional Christian and Islamic cultures, suicide is viewed as a sin. Death is personified in many cultures, with such symbolic representations as the Grim Reaper, Azrael, the Hindu God Yama and Father Time.

In Brazil, a human death is counted officially when it is registered by existing family members at a cartório, a government-authorized registry. Before being able to file for an official death, the deceased must have been registered for an official birth at the cartório. Though a Public Registry Law guarantees all Brazilian citizens the right to register deaths, regardless of their financial means, of their family members (often children), the Brazilian government has not taken away the burden, the hidden costs and fees, of filing for a death. For many impoverished families, the indirect costs and burden of filing for a death lead to a more appealing, unofficial, local, cultural burial, which in turn raises the debate about inaccurate mortality rates.

Talking about death and witnessing it is a difficult issue with most cultures. Western societies may like to treat the dead with the utmost material respect, with an official embalmer and associated rites. Eastern societies (like India) may be more open to accepting it as a fait accompli, with a funeral procession of the dead body ending in an open air burning-to-ashes of the same. 

Consciousness

Much interest and debate surround the question of what happens to one's consciousness as one's body dies. The belief in the permanent loss of consciousness after death is often called eternal oblivion. Belief that the stream of consciousness is preserved after physical death is described by the term afterlife. Neither are likely to ever be confirmed without the ponderer having to actually die. 

In biology

Earthworms are a good example of soil-dwelling detritivores.
 
After death, the remains of an organism become part of the biogeochemical cycle, during which animals may be consumed by a predator or a scavenger. Organic material may then be further decomposed by detritivores, organisms which recycle detritus, returning it to the environment for reuse in the food chain, where these chemicals may eventually end up being consumed and assimilated into the cells of a living organism. Examples of detritivores include earthworms, woodlice and dung beetles.

Microorganisms also play a vital role, raising the temperature of the decomposing matter as they break it down into yet simpler molecules. Not all materials need to be fully decomposed. Coal, a fossil fuel formed over vast tracts of time in swamp ecosystems, is one example.

Natural selection

Contemporary evolutionary theory sees death as an important part of the process of natural selection. It is considered that organisms less adapted to their environment are more likely to die having produced fewer offspring, thereby reducing their contribution to the gene pool. Their genes are thus eventually bred out of a population, leading at worst to extinction and, more positively, making the process possible, referred to as speciation. Frequency of reproduction plays an equally important role in determining species survival: an organism that dies young but leaves numerous offspring displays, according to Darwinian criteria, much greater fitness than a long-lived organism leaving only one.

Extinction

Painting of a dodo
A dodo, the bird that became a byword in the English language for the extinction of a species
 
Extinction is the cessation of existence of a species or group of taxa, reducing biodiversity. The moment of extinction is generally considered to be the death of the last individual of that species (although the capacity to breed and recover may have been lost before this point). Because a species' potential range may be very large, determining this moment is difficult, and is usually done retrospectively. This difficulty leads to phenomena such as Lazarus taxa, where species presumed extinct abruptly "reappear" (typically in the fossil record) after a period of apparent absence. New species arise through the process of speciation, an aspect of evolution. New varieties of organisms arise and thrive when they are able to find and exploit an ecological niche – and species become extinct when they are no longer able to survive in changing conditions or against superior competition. 

Evolution of aging and mortality

Inquiry into the evolution of aging aims to explain why so many living things and the vast majority of animals weaken and die with age (exceptions include Hydra and the already cited jellyfish Turritopsis dohrnii, which research shows to be biologically immortal). The evolutionary origin of senescence remains one of the fundamental puzzles of biology. Gerontology specializes in the science of human aging processes.

Organisms showing only asexual reproduction (e.g. bacteria, some protists, like the euglenoids and many amoebozoans) and unicellular organisms with sexual reproduction (colonial or not, like the volvocine algae Pandorina and Chlamydomonas) are "immortal" at some extent, dying only due to external hazards, like being eaten or meeting with a fatal accident. In multicellular organisms (and also in multinucleate ciliates), with a Weismannist development, that is, with a division of labor between mortal somatic (body) cells and "immortal" germ (reproductive) cells, death becomes an essential part of life, at least for the somatic line.

The Volvox algae are among the simplest organisms to exhibit that division of labor between two completely different cell types, and as a consequence include death of somatic line as a regular, genetically regulated part of its life history.

Religious views

Death is an important subject of religious doctrine.

Buddhism

In Buddhist doctrine and practice, death plays an important role. Awareness of death was what motivated Prince Siddhartha to strive to find the "deathless" and finally to attain enlightenment. In Buddhist doctrine, death functions as a reminder of the value of having been born as a human being. Being reborn as a human being is considered the only state in which one can attain enlightenment. Therefore, death helps remind oneself that one should not take life for granted. The belief in rebirth among Buddhists does not necessarily remove death anxiety, since all existence in the cycle of rebirth is considered filled with suffering, and being reborn many times does not necessarily mean that one progresses.

Death is part of several key Buddhist tenets, such as the Four Noble Truths and dependent origination.

Christianity

Islam

Judaism

A yahrtzeit candle lit in memory of a loved one on the anniversary of the death

Death is seen in Judaism as tragic and intimidating. Persons who come into contact with corpses are ritually impure. There are a variety of beliefs about the afterlife within Judaism, but none of them contradict the preference of life over death. This is partially because death puts a cessation to the possibility of fulfilling any commandments.

Language around death

Study of Skeletons, c. 1510, by Leonardo da Vinci
 
The word death comes from Old English dēaþ, which in turn comes from Proto-Germanic *dauþuz (reconstructed by etymological analysis). This comes from the Proto-Indo-European stem *dheu- meaning the "process, act, condition of dying".

The concept and symptoms of death, and varying degrees of delicacy used in discussion in public forums, have generated numerous scientific, legal, and socially acceptable terms or euphemisms for death. When a person has died, it is also said they have passed away, passed on, expired, or are gone, among numerous other socially accepted, religiously specific, slang, and irreverent terms.

As a formal reference to a dead person, it has become common practice to use the participle form of "decease", as in the deceased; another noun form is decedent.

Bereft of life, the dead person is then a corpse, cadaver, a body, a set of remains, and when all flesh has rotted away, a skeleton. The terms carrion and carcass can also be used, though these more often connote the remains of non-human animals. The ashes left after a cremation are sometimes referred to by the neologism cremains, a portmanteau of "cremation" and "remains".

Tau protein

From Wikipedia, the free encyclopedia
 
MAPT
PDB 1i8h EBI.jpg
Available structures
PDBOrtholog search: PDBe RCSB
Identifiers
AliasesMAPT, DDPAC, FTDP-17, MAPTL, MSTD, MTBT1, MTBT2, PPND, PPP1R103, TAU, microtubule associated protein tau, Tau proteins
External IDsOMIM: 157140 MGI: 97180 HomoloGene: 74962 GeneCards: MAPT
Gene location (Human)
Chromosome 17 (human)
Chr.Chromosome 17 (human)
Chromosome 17 (human)
Genomic location for MAPT
Genomic location for MAPT
Band17q21.31Start45,894,382 bp
End46,028,334 bp
RNA expression pattern
PBB GE MAPT 203928 x at fs.png

PBB GE MAPT 203929 s at fs.png

PBB GE MAPT 203930 s at fs.png
More reference expression data
Orthologs
SpeciesHumanMouse
Entrez


Ensembl


UniProt


RefSeq (mRNA)
NM_001038609
NM_010838
NM_001285454
NM_001285455
NM_001285456
RefSeq (protein)
NP_001033698
NP_001272383
NP_001272384
NP_001272385
NP_034968
Location (UCSC)Chr 17: 45.89 – 46.03 MbChr 11: 104.23 – 104.33 Mb

Tau proteins (or τ proteins, after the Greek letter with that name) are proteins that stabilize microtubules. They are abundant in neurons of the central nervous system and are less common elsewhere, but are also expressed at very low levels in CNS astrocytes and oligodendrocytes. Pathologies and dementias of the nervous system such as Alzheimer's disease and Parkinson's disease are associated with tau proteins that have become defective and no longer stabilize microtubules properly.

The tau proteins are the product of alternative splicing from a single gene that in humans is designated MAPT (microtubule-associated protein tau) and is located on chromosome 17.

The tau proteins were identified in 1975 as heat-stable proteins essential for microtubule assembly  and since then, they have been characterized as intrinsically disordered proteins.

Neurons were grown in tissue culture and stained with antibody to MAP2 protein in green and MAP tau in red using the immunofluorescence technique. MAP2 is found only in dendrites and perikarya, while tau is found not only in the dendrites and perikarya but also in axons. As a result, axons appear red while the dendrites and perikarya appear yellow, due to superimposition of the red and green signals. DNA is shown in blue using the DAPI stain which highlights the nuclei.

Function

Tau protein is a highly soluble microtubule-associated protein tau (MAPT). In humans, these proteins are found mostly in neurons compared to non-neuronal cells. One of tau's main functions is to modulate the stability of axonal microtubules. Other nervous system MAPs may perform similar functions, as suggested by tau knock out mice that did not show abnormalities in brain development - possibly because of compensation in tau deficiency by other MAPs. Tau is not present in dendrites and is active primarily in the distal portions of axons where it provides microtubule stabilization but also flexibility as needed. This contrasts with MAP6 (STOP) proteins in the proximal portions of axons, which, in essence, lock down the microtubules and MAP2 that stabilizes microtubules in dendrites. In addition to their microtubule stabilizing functions, MAPTs have also been found to recruit signaling proteins and regulation of microtubule-mediated transport.

Tau proteins interact with tubulin to stabilize microtubules and promote tubulin assembly into microtubules. Tau has two ways of controlling microtubule stability: isoforms and phosphorylation.

Tau regulates cytoskeletal stability and translation (negatively) in Drosophila as well, but also facilitates habituation (a form of non-associative learning) and negatively regulates long-term memory, two higher and more integrated neural functions.

Genetics

In humans, the MAPT gene for encoding tau protein is located on chromosome 17q21, containing 16 exons. The major tau protein in the human brain is encoded by 11 exons. Exons 2, 3 and 10 are alternatively spliced that lead to formation of six tau isoforms. In human brain, tau proteins constitute a family of six isoforms with a range of 352-441 amino acids. Tau isoforms are different in either zero, one, or two inserts of 29 amino acids at the N-terminal part (exon 2 and 3), and three or four repeat-regions at the C-terminal part (exon 10). Thus, the longest isoform in the CNS has four repeats (R1, R2, R3 and R4) and two inserts (441 amino acids total), while the shortest isoform has three repeats (R1, R3 and R4) and no insert (352 amino acids total). 

The MAPT gene has two haplogroups, H1 and H2, in which the gene appears in inverted orientations. Haplogroup H2 is common only in Europe and in people with European ancestry. Haplogroup H1 appears to be associated with increased probability of certain dementias, such as Alzheimer's disease. The presence of both haplogroups in Europe means that recombination between inverted haplotypes can result in the lack of one of the functioning copies of the gene, resulting in congenital defects.

Structure

Six tau isoforms exist in human brain tissue, and they are distinguished by their number of binding domains. Three isoforms have three binding domains and the other three have four binding domains. The binding domains are located in the carboxy-terminus of the protein and are positively charged (allowing it to bind to the negatively charged microtubule). The isoforms with four binding domains are better at stabilizing microtubules than those with three binding domains. The isoforms are a result of alternative splicing in exons 2, 3, and 10 of the tau gene. Tau is a phosphoprotein with 79 potential Serine (Ser) and Threonine (Thr) phosphorylation sites on the longest tau isoform. Phosphorylation has been reported on approximately 30 of these sites in normal tau proteins.

Phosphorylation of tau is regulated by a host of kinases, including PKN, a serine/threonine kinase. When PKN is activated, it phosphorylates tau, resulting in disruption of microtubule organization. Phosphorylation of tau is also developmentally regulated. For example, fetal tau is more highly phosphorylated in the embryonic CNS than adult tau. The degree of phosphorylation in all six isoforms decreases with age due to the activation of phosphatases. Like kinases, phosphatases too play a role in regulating the phosphorylation of tau. For example, PP2A and PP2B are both present in human brain tissue and have the ability to dephosphorylate Ser396. The binding of these phosphatases to tau affects tau's association with MTs. 

Mechanism

The accumulation of hyperphosphorylated tau in neurons leads to the neurofibrillary degeneration. The actual mechanism of how tau propagates from one cell to another is not well identified. Also, other mechanisms, including tau release and toxicity, are unclear. As tau aggregates, it replaces tubulin, which in turn enhances fibrilization of tau. Several propagation methods have been proposed which occur by synaptic contact such as synaptic cell adhesion proteins and neuronal activity and other synaptic and non-synaptic mechanisms. The mechanism of tau aggregation is still not completely elucidated, but several factors favor this process, including tau phosphorylation and zinc ions.

Release

Tau involves in uptake and release process, which is known as seeding. Uptake of tau protein mechanism requires the presence of heparan sulfate proteoglycans at the cell surface, which happen by macropinocytosis. On the other hand, tau release depends on neuronal activity. Many factors influence tau release, for example, type of isoforms or MAPT mutations that change the extracellular level of tau. According to Asai and his colleagues, spreading of tau protein occurs from entorhinal cortex to the hippocampal region in the early stages of the disease. They also suggested that microglia were also involved in the transport process and their actual role is still unknown.

Toxicity

Tau causes toxic effects through its accumulation inside cells. Many enzymes are involved in toxicity mechanism such as PAR-1 kinase. This enzyme stimulates phosphorylation of serine 262 and 356, which in turn leads to activate other kinases (GSK-3 and Cdk5) that cause disease-associated phosphoepitopes. The degree of toxicity is affected by different factors, such as the degree of microtubule binding. Toxicity could also happen by neurofibrillary tangles (NFTs), which leads to cell death and cognitive decline.

Clinical significance

Hyperphosphorylation of the tau protein (tau inclusions, pTau) can result in the self-assembly of tangles of paired helical filaments and straight filaments, which are involved in the pathogenesis of Alzheimer's disease, frontotemporal dementia, and other tauopathies.

All of the six tau isoforms are present in an often hyperphosphorylated state in paired helical filaments from Alzheimer's disease brain. In other neurodegenerative diseases, the deposition of aggregates enriched in certain tau isoforms has been reported. When misfolded, this otherwise very soluble protein can form extremely insoluble aggregates that contribute to a number of neurodegenerative diseases. 

Tau protein has a direct effect on the breakdown of a living cell caused by tangles that form and block nerve synapses. Tangles are clumps of tau protein that stick together and block essential nutrients that need to be distributed to cells in the brain, causing the cells to die.

Gender-specific tau gene expression across different regions of the human brain has recently been implicated in gender differences in the manifestations and risk for tauopathies.

Some aspects of how the disease functions also suggest that it has some similarities to prion proteins.

Traumatic brain injury

Repetitive mild traumatic brain injury (TBI) is now recognized as a central component of brain injury in contact sports, especially American football, and the concussive force of military blasts. It can lead to chronic traumatic encephalopathy (CTE) that is characterized by fibrillar tangles of hyperphosphorylated tau.

High levels of tau protein in fluid bathing the brain are linked to poor recovery after head trauma.

Tau hypothesis of Alzheimer's disease

The tau hypothesis states that excessive or abnormal phosphorylation of tau results in the transformation of normal adult tau into paired helical filament (PHF) tau and neurofibrillary tangles (NFTs). The stage of the disease determines NFTs' phosphorylation. In AD, at least 19 amino acids are phosphorylated, such as pre-NFT phosphorylation occurs at serine 119, 202, and 409. While intra-NFT phosphorylation happens at serine 396 and threonine 231. Tau protein is a highly soluble microtubule-associated protein tau (MAPT). Through its isoforms and phosphorylation, tau protein interacts with tubulin to stabilize microtubule assembly. All of the six tau isoforms are present in an often hyperphosphorylated state in paired helical filaments (PHFs) from AD.

Tau mutations have many consequences such as changing the expression level of tau isoforms or lead to MTs dysfunction. Mutations that alter function and isoform expression of tau lead to hyperphosphorylation. The process of tau aggregation in the absence of mutations is not known, but might result from increased phosphorylation, protease action, or exposure to polyanions, such as glycosaminoglycans. Hyperphosphorylated tau disassembles microtubules and sequesters normal tau, MAPT 1 (microtubule associated protein tau 1), MAPT 2, and ubiquitin into tangles of PHFs. This insoluble structure damages cytoplasmic functions and interferes with axonal transport, which can lead to cell death. Hyperphosphorylated forms of tau protein are the main component of PHFs of NFTs in the brain of AD patients. It has been well demonstrated that regions of tau six-residue segments, namely PHF6 (VQIVYK) and PHF6 (VQIINK), can form tau PHF aggregation in AD. Apart from the PHF6, some other residue sites like Ser285, Ser289, Ser293, Ser305, and Tyr310, located near the C-terminal of the PHF6 sequences, play key roles in the phosphorylation of tau.

A68 Protein

The A68 protein is a hyperphosphorylated Tau protein differing in its sensitivity and its Kinase as well as Alkaline phosphatase and is along with beta-amyloid a component of pathologic lesions in Alzheimer disease, and is found in the brains of individuals with Alzheimer's disease.

Interactions

Tau protein has been shown to interact with proto-oncogene tyrosine-protein kinase:

Lie group

From Wikipedia, the free encyclopedia https://en.wikipedia.org/wiki/Lie_group In mathematics , a Lie gro...