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Crankshaft

A crankshaft is a mechanical component used in a piston engine to convert the reciprocating motion into rotational motion. The crankshaft is a rotating shaft containing one or more crankpins, that are driven by the pistons via the connecting rods.

The crankpins are also called rod bearing journals, and they rotate within the "big end" of the connecting rods.

Most modern crankshafts are located in the engine block. They are made from steel or cast iron, using either a forging, casting or machining process.

Design

The crankshaft is located within the engine block and held in place via main bearings which allow the crankshaft to rotate within the block. The up-down motion of each piston is transferred to the crankshaft via connecting rods. A flywheel is often attached to one end of the crankshaft, in order to smoothen the power delivery and reduce vibration.

A crankshaft is subjected to enormous stresses, in some cases more than 19000 lb per cylinder. Crankshafts for single-cylinder engines are usually a simpler design than for engines with multiple cylinders.

Bearings
The crankshaft is able to rotate in the engine block due to the 'main bearings'. Since the crankshaft is subject to large horizontal and torsional forces from each cylinder, these main bearings are located at various points along the crankshaft, rather than just one at each end. The number of main bearings is determined based on the overall load factor and the maximum engine speed. Crankshafts in diesel engines often use a main bearing between every cylinder and at both ends of the crankshaft, due to the high forces of combustion present.

Flexing of the crankshaft was a factor in V8 engines replacing straight-eight engines in the 1950s; the long crankshafts of the latter suffered from an unacceptable amount of flex when engine designers began using higher compression ratios and higher engine speeds (RPM).

Piston stroke
The distance between the axis of the crankpins and the axis of the crankshaft determines the stroke length of the engine.

Most modern car engines are classified as "over square" or short-stroke, wherein the stroke is less than the diameter of the cylinder bore. A common way to increase the low-RPM torque of an engine is to increase the stroke, sometimes known as "stroking" the engine. Historically, the trade-off for a long-stroke engine was a lower rev limit and increased vibration at high RPM, due to the increased piston velocity.

Cross-plane and flat-plane configurations
When designing an engine, the crankshaft configuration is closely related to the engine's firing order.

Most production V8 engines (such as the Ford Modular engine and the General Motors LS engine) use a cross-plane crank whereby the crank throws are spaced 90 degrees apart. However, some high-performance V8 engines (such as the Ferrari 488) instead use a flat-plane crank, whereby the throws are spaced 180° apart, which essentially results in two inline-four engines sharing a common crankcase. Flat-plane engines are usually able to operate at higher RPM, however they have higher second-order vibrations, so they are better suited to racing car engines.

Engine balance
For some engines it is necessary to provide counterweights for the reciprocating mass of the piston, conrods and crankshaft, in order to improve the engine balance. These counterweights are typically cast as part of the crankshaft but, occasionally, are bolt-on pieces.

Flying arms
In some engines, the crankshaft contains direct links between adjacent crank pins, without the usual intermediate main bearing. These links are called flying arms. This arrangement is sometimes used in V6 and V8 engines, in order to maintain an even firing interval while using different V angles, and to reduce the number of main bearings required. The downside of flying arms is that the rigidity of the crankshaft is reduced, which can cause problems at high RPM or high power outputs.

Counter-rotating crankshafts
In most engines, each connecting rod is attached a single crankshaft, which results in the angle of the connecting rod varying as the piston moves through its stroke. This variation in angle pushes the pistons against the cylinder wall, which causes friction between the piston and cylinder wall. To prevent this, some early engines – such as the 1900–1904 Lanchester Engine Company flat-twin engines – connected each piston to two crankshafts that are rotating in opposite directions. This arrangement cancels out the lateral forces and reduces the requirement for counterweights. This design is rarely used, however a similar principle applies to balance shafts, which are occasionally used.

Forged crankshafts

Crankshafts can be created from a steel bar using roll forging. Today, manufacturers tend to favour the use of forged crankshafts due to their lighter weight, more compact dimensions and better inherent damping. With forged crankshafts, vanadium micro-alloyed steels are mainly used as these steels can be air-cooled after reaching high strengths without additional heat treatment, except for the surface hardening of the bearing surfaces. The low alloy content also makes the material cheaper than high alloy steels. Carbon steels also require additional heat treatment to reach the desired properties.

Cast crankshafts
Another construction method is to cast the crankshaft from ductile. Cast iron crankshafts are today mostly found in cheaper production engines where the loads are lower.

Machined crankshafts
Crankshafts can also be machined from billet, often a bar of high quality vacuum remelted steel. Though the fiber flow (local inhomogeneities of the material's chemical composition generated during casting) does not follow the shape of the crankshaft (which is undesirable), this is usually not a problem since higher quality steels, which normally are difficult to forge, can be used. Per unit, these crankshafts tend to be very expensive due to the large amount of material that must be removed with lathes and milling machines, the high material cost, and the additional heat treatment required. However, since no expensive tooling is needed, this production method allows small production runs without high up-front costs.

China

The earliest hand-operated cranks appeared in China during the Han dynasty (202 BC – 220 AD). They were used for silk-reeling, hemp-spinning, for the agricultural winnowing fan, in the water-powered flour-sifter, for hydraulic-powered metallurgic bellows, and in the well windlass. The rotary winnowing fan greatly increased the efficiency of separating grain from husks and stalks. However, the potential of the crank of converting circular motion into reciprocal motion never seems to have been fully realized in China, and the crank was typically absent from such machines until the turn of the 20th century.

Europe

A crank in the form of an eccentrically-mounted handle of the rotary handmill appeared in 5th-century BC Celtiberian Spain and ultimately spread across the Roman Empire. A Roman iron crank dating to the 2nd century AD was excavated in Augusta Raurica, Switzerland. The crank-operated Roman mill is dated to the late 2nd century.

Evidence for the crank combined with a connecting rod appears in the Hierapolis mill, dating to the 3rd century; they are also found in stone sawmills in Roman Syria and Ephesus dating to the 6th century. The pediment of the Hierapolis mill shows a waterwheel fed by a mill race powering via a gear train two frame saws which cut blocks by the way of some kind of connecting rods and cranks. The crank and connecting rod mechanisms of the other two archaeologically-attested sawmills worked without a gear train. Water-powered marble saws in Germany were mentioned by the late 4th century poet Ausonius; about the same time, these mill types seem also to be indicated by Gregory of Nyssa from Anatolia.

A rotary grindstone operated by a crank handle is shown in the Carolingian manuscript Utrecht Psalter; the pen drawing of around 830 goes back to a late antique original. Cranks used to turn wheels are also depicted or described in various works dating from the tenth to thirteenth centuries.

The first depictions of the compound crank in the carpenter's brace appear between 1420 and 1430 in northern European artwork. The rapid adoption of the compound crank can be traced in the works of an unknown German engineer writing on the state of military technology during the Hussite Wars: first, the connecting-rod, applied to cranks, reappeared; second, double-compound cranks also began to be equipped with connecting-rods; and third, the flywheel was employed for these cranks to get them over the 'dead-spot'. The concept was much improved by the Italian engineer and writer Roberto Valturio in 1463, who devised a boat with five sets, where the parallel cranks are all joined to a single power source by one connecting-rod, an idea also taken up by his compatriot Italian painter Francesco di Giorgio.

The crank had become common in Europe by the early 15th century, as seen in the works of the military engineer Konrad Kyeser (1366–after 1405). Devices depicted in Kyeser's Bellifortis include cranked windlasses for spanning siege crossbows, cranked chain of buckets for water-lifting and cranks fitted to a wheel of bells. Kyeser also equipped the Archimedes' screws for water-raising with a crank handle, an innovation which subsequently replaced the ancient practice of working the pipe by treading.

Pisanello painted a piston-pump driven by a water-wheel and operated by two simple cranks and two connecting-rods.

The 15th century also saw the introduction of cranked rack-and-pinion devices, called cranequins, which were fitted to the crossbow's stock as a means of exerting even more force while spanning the missile weapon. In the textile industry, cranked reels for winding skeins of yarn were introduced.

The Italian physician Guido da Vigevano (c. 1280−1349), planning for a new crusade, made illustrations for a paddle boat and war carriages that were propelled by manually turned compound cranks and gear wheels, identified as an early crankshaft prototype by Lynn Townsend White. The Luttrell Psalter, dating to around 1340, describes a grindstone which was rotated by two cranks, one at each end of its axle; the geared hand-mill, operated either with one or two cranks, appeared later in the 15th century.

Around 1480, the early medieval rotary grindstone was improved with a treadle and crank mechanism. Cranks mounted on push-carts first appear in a German engraving of 1589. Crankshafts were also described by Leonardo da Vinci (1452–1519) and a Dutch farmer and windmill owner by the name Cornelis Corneliszoon van Uitgeest in 1592. His wind-powered sawmill used a crankshaft to convert a windmill's circular motion into a back-and-forward motion powering the saw. Corneliszoon was granted a patent for his crankshaft in 1597.

From the 16th century onwards, evidence of cranks and connecting rods integrated into machine design becomes abundant in the technological treatises of the period: Agostino Ramelli's The Diverse and Artifactitious Machines of 1588 depicts eighteen examples, a number that rises in the Theatrum Machinarum Novum by Georg Andreas Böckler to 45 different machines. Cranks were formerly common on some machines in the early 20th century; for example almost all phonographs before the 1930s were powered by clockwork motors wound with cranks. Reciprocating piston engines use cranks to convert the linear piston motion into rotational motion. Internal combustion engines of early 20th century automobiles were usually started with hand cranks, before electric starters came into general use.

Western Asia
The non-manual crank appears in several of the hydraulic devices described by the Banū Mūsā brothers in their 9th-century Book of Ingenious Devices. These automatically operated cranks appear in several devices, two of which contain an action which approximates to that of a crankshaft. The automatic crank described by the Banū Mūsā would not have allowed a full rotation, however, but only a small modification was required to convert it to a crankshaft.

title: Crankshaft


text:
CNS

CNS may refer to:

Science and medicine

 * Central nervous system
 * Clinical nurse specialist
 * Coagulase-negative staphylococcus
 * Connectedness to nature scale
 * Conserved non-coding sequence of DNA
 * Crigler–Najjar syndrome
 * Crystallography and NMR system, a software library
 * Color Naming System

Military

 * CNS (chemical weapon), a mixture of chloroacetophenone, chloropicrin and chloroform
 * Chief of the Naval Staff (disambiguation), in several countries
 * Former Taiwanese navy ship prefix

Education

 * Cicero-North Syracuse High School, New York, US
 * City of Norwich School, England
 * Computation and Neural Systems, a Caltech program

Organisations

 * Canadian Nuclear Society
 * Chinese Nuclear Society
 * Congress of Neurological Surgeons
 * Corporation for National Service, later the Corporation for National and Community Service, commonly known as AmeriCorps
 * Council for National Security, military junta of Thailand in 2006
 * Cuban National Series, baseball league
 * Szekler National Council (Consiliul Național Secuiesc), Romania

Media

 * Cartoon Network Studios
 * Catholic News Service
 * China News Service
 * CNSNews, formerly Cybercast News Service

Other

 * Cairns International Airport, IATA code
 * Chateau Neuf Spelemannslag, Norwegian folk music group
 * Chinese National Standards
 * Cooper Nuclear Station, a nuclear power plant in United States
 * Communication, navigation and surveillance, in air traffic management
 * Custody Notification Service, Australian advice service
 * "Cell, Nature, or Science" : a "CNS Paper" means a scientific publication in one of these high-evaluated scientific journals

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

title: CNS


text:
Central nervous system

The central nervous system (CNS) is the part of the nervous system consisting primarily of the brain and spinal cord. The CNS is so named because the brain integrates the received information and coordinates and influences the activity of all parts of the bodies of bilaterally symmetric and triploblastic animals—that is, all multicellular animals except sponges and diploblasts. It is a structure composed of nervous tissue positioned along the rostral (nose end) to caudal (tail end) axis of the body and may have an enlarged section at the rostral end which is a brain. Only arthropods, cephalopods and vertebrates have a true brain, though precursor structures exist in onychophorans, gastropods and lancelets.

The rest of this article exclusively discusses the vertebrate central nervous system, which is radically distinct from all other animals.

Overview
In vertebrates, the brain and spinal cord are both enclosed in the meninges. The meninges provide a barrier to chemicals dissolved in the blood, protecting the brain from most neurotoxins commonly found in food. Within the meninges the brain and spinal cord are bathed in cerebral spinal fluid which replaces the body fluid found outside the cells of all bilateral animals.

In vertebrates, the CNS is contained within the dorsal body cavity, while the brain is housed in the cranial cavity within the skull. The spinal cord is housed in the spinal canal within the vertebrae. Within the CNS, the interneuronal space is filled with a large amount of supporting non-nervous cells called neuroglia or glia from the Greek for "glue".

In vertebrates, the CNS also includes the retina and the optic nerve (cranial nerve II), as well as the olfactory nerves and olfactory epithelium. As parts of the CNS, they connect directly to brain neurons without intermediate ganglia. The olfactory epithelium is the only central nervous tissue outside the meninges in direct contact with the environment, which opens up a pathway for therapeutic agents which cannot otherwise cross the meninges barrier.

Structure
The CNS consists of two major structures: the brain and spinal cord. The brain is encased in the skull, and protected by the cranium. The spinal cord is continuous with the brain and lies caudally to the brain. It is protected by the vertebrae. The spinal cord reaches from the base of the skull, and continues through or starting below the foramen magnum, and terminates roughly level with the first or second lumbar vertebra, occupying the upper sections of the vertebral canal.

White and gray matter
Microscopically, there are differences between the neurons and tissue of the CNS and the peripheral nervous system (PNS). The CNS is composed of white and gray matter. This can also be seen macroscopically on brain tissue. The white matter consists of axons and oligodendrocytes, while the gray matter consists of neurons and unmyelinated fibers. Both tissues include a number of glial cells (although the white matter contains more), which are often referred to as supporting cells of the CNS. Different forms of glial cells have different functions, some acting almost as scaffolding for neuroblasts to climb during neurogenesis such as bergmann glia, while others such as microglia are a specialized form of macrophage, involved in the immune system of the brain as well as the clearance of various metabolites from the brain tissue. Astrocytes may be involved with both clearance of metabolites as well as transport of fuel and various beneficial substances to neurons from the capillaries of the brain. Upon CNS injury astrocytes will proliferate, causing gliosis, a form of neuronal scar tissue, lacking in functional neurons.

The brain (cerebrum as well as midbrain and hindbrain) consists of a cortex, composed of neuron-bodies constituting gray matter, while internally there is more white matter that form tracts and commissures. Apart from cortical gray matter there is also subcortical gray matter making up a large number of different nuclei.

Spinal cord

From and to the spinal cord are projections of the peripheral nervous system in the form of spinal nerves (sometimes segmental nerves ). The nerves connect the spinal cord to skin, joints, muscles etc. and allow for the transmission of efferent motor as well as afferent sensory signals and stimuli. This allows for voluntary and involuntary motions of muscles, as well as the perception of senses. All in all 31 spinal nerves project from the brain stem, some forming plexa as they branch out, such as the brachial plexa, sacral plexa etc. Each spinal nerve will carry both sensory and motor signals, but the nerves synapse at different regions of the spinal cord, either from the periphery to sensory relay neurons that relay the information to the CNS or from the CNS to motor neurons, which relay the information out.

The spinal cord relays information up to the brain through spinal tracts through the final common pathway to the thalamus and ultimately to the cortex.

Cranial nerves
Apart from the spinal cord, there are also peripheral nerves of the PNS that synapse through intermediaries or ganglia directly on the CNS. These 12 nerves exist in the head and neck region and are called cranial nerves. Cranial nerves bring information to the CNS to and from the face, as well as to certain muscles (such as the trapezius muscle, which is innervated by accessory nerves as well as certain cervical spinal nerves).

Two pairs of cranial nerves; the olfactory nerves and the optic nerves are often considered structures of the CNS. This is because they do not synapse first on peripheral ganglia, but directly on CNS neurons. The olfactory epithelium is significant in that it consists of CNS tissue expressed in direct contact to the environment, allowing for administration of certain pharmaceuticals and drugs.

Brain
At the anterior end of the spinal cord lies the brain. The brain makes up the largest portion of the CNS. It is often the main structure referred to when speaking of the nervous system in general. The brain is the major functional unit of the CNS. While the spinal cord has certain processing ability such as that of spinal locomotion and can process reflexes, the brain is the major processing unit of the nervous system.

Brainstem
The brainstem consists of the medulla, the pons and the midbrain. The medulla can be referred to as an extension of the spinal cord, which both have similar organization and functional properties. The tracts passing from the spinal cord to the brain pass through here.

Regulatory functions of the medulla nuclei include control of blood pressure and breathing. Other nuclei are involved in balance, taste, hearing, and control of muscles of the face and neck.

The next structure rostral to the medulla is the pons, which lies on the ventral anterior side of the brainstem. Nuclei in the pons include pontine nuclei which work with the cerebellum and transmit information between the cerebellum and the cerebral cortex. In the dorsal posterior pons lie nuclei that are involved in the functions of breathing, sleep, and taste.

The midbrain, or mesencephalon, is situated above and rostral to the pons. It includes nuclei linking distinct parts of the motor system, including the cerebellum, the basal ganglia and both cerebral hemispheres, among others. Additionally, parts of the visual and auditory systems are located in the midbrain, including control of automatic eye movements.

The brainstem at large provides entry and exit to the brain for a number of pathways for motor and autonomic control of the face and neck through cranial nerves, Autonomic control of the organs is mediated by the tenth cranial nerve. A large portion of the brainstem is involved in such autonomic control of the body. Such functions may engage the heart, blood vessels, and pupils, among others.

The brainstem also holds the reticular formation, a group of nuclei involved in both arousal and alertness.

Cerebellum
The cerebellum lies behind the pons. The cerebellum is composed of several dividing fissures and lobes. Its function includes the control of posture and the coordination of movements of parts of the body, including the eyes and head, as well as the limbs. Further, it is involved in motion that has been learned and perfected through practice, and it will adapt to new learned movements. Despite its previous classification as a motor structure, the cerebellum also displays connections to areas of the cerebral cortex involved in language and cognition. These connections have been shown by the use of medical imaging techniques, such as functional MRI and Positron emission tomography.

The body of the cerebellum holds more neurons than any other structure of the brain, including that of the larger cerebrum, but is also more extensively understood than other structures of the brain, as it includes fewer types of different neurons. It handles and processes sensory stimuli, motor information, as well as balance information from the vestibular organ.

Diencephalon
The two structures of the diencephalon worth noting are the thalamus and the hypothalamus. The thalamus acts as a linkage between incoming pathways from the peripheral nervous system as well as the optical nerve (though it does not receive input from the olfactory nerve) to the cerebral hemispheres. Previously it was considered only a "relay station", but it is engaged in the sorting of information that will reach cerebral hemispheres (neocortex).

Apart from its function of sorting information from the periphery, the thalamus also connects the cerebellum and basal ganglia with the cerebrum. In common with the aforementioned reticular system the thalamus is involved in wakefulness and consciousness, such as though the SCN.

The hypothalamus engages in functions of a number of primitive emotions or feelings such as hunger, thirst and maternal bonding. This is regulated partly through control of secretion of hormones from the pituitary gland. Additionally the hypothalamus plays a role in motivation and many other behaviors of the individual.

Cerebrum
The cerebrum of cerebral hemispheres make up the largest visual portion of the human brain. Various structures combine to form the cerebral hemispheres, among others: the cortex, basal ganglia, amygdala and hippocampus. The hemispheres together control a large portion of the functions of the human brain such as emotion, memory, perception and motor functions. Apart from this the cerebral hemispheres stand for the cognitive capabilities of the brain.

Connecting each of the hemispheres is the corpus callosum as well as several additional commissures. One of the most important parts of the cerebral hemispheres is the cortex, made up of gray matter covering the surface of the brain. Functionally, the cerebral cortex is involved in planning and carrying out of everyday tasks.

The hippocampus is involved in storage of memories, the amygdala plays a role in perception and communication of emotion, while the basal ganglia play a major role in the coordination of voluntary movement.

Difference from the peripheral nervous system

This differentiates the CNS from the PNS, which consists of neurons, axons, and Schwann cells. Oligodendrocytes and Schwann cells have similar functions in the CNS and PNS, respectively. Both act to add myelin sheaths to the axons, which acts as a form of insulation allowing for better and faster proliferation of electrical signals along the nerves. Axons in the CNS are often very short, barely a few millimeters, and do not need the same degree of isolation as peripheral nerves. Some peripheral nerves can be over 1 meter in length, such as the nerves to the big toe. To ensure signals move at sufficient speed, myelination is needed.

The way in which the Schwann cells and oligodendrocytes myelinate nerves differ. A Schwann cell usually myelinates a single axon, completely surrounding it. Sometimes, they may myelinate many axons, especially when in areas of short axons. Oligodendrocytes usually myelinate several axons. They do this by sending out thin projections of their cell membrane, which envelop and enclose the axon.

Development
During early development of the vertebrate embryo, a longitudinal groove on the neural plate gradually deepens and the ridges on either side of the groove (the neural folds) become elevated, and ultimately meet, transforming the groove into a closed tube called the neural tube. The formation of the neural tube is called neurulation. At this stage, the walls of the neural tube contain proliferating neural stem cells in a region called the ventricular zone. The neural stem cells, principally radial glial cells, multiply and generate neurons through the process of neurogenesis, forming the rudiment of the CNS.

The neural tube gives rise to both brain and spinal cord. The anterior (or 'rostral') portion of the neural tube initially differentiates into three brain vesicles (pockets): the prosencephalon at the front, the mesencephalon, and, between the mesencephalon and the spinal cord, the rhombencephalon. (By six weeks in the human embryo) the prosencephalon then divides further into the telencephalon and diencephalon; and the rhombencephalon divides into the metencephalon and myelencephalon. The spinal cord is derived from the posterior or 'caudal' portion of the neural tube.

As a vertebrate grows, these vesicles differentiate further still. The telencephalon differentiates into, among other things, the striatum, the hippocampus and the neocortex, and its cavity becomes the first and second ventricles. Diencephalon elaborations include the subthalamus, hypothalamus, thalamus and epithalamus, and its cavity forms the third ventricle. The tectum, pretectum, cerebral peduncle and other structures develop out of the mesencephalon, and its cavity grows into the mesencephalic duct (cerebral aqueduct). The metencephalon becomes, among other things, the pons and the cerebellum, the myelencephalon forms the medulla oblongata, and their cavities develop into the fourth ventricle.

Planaria
Planarians, members of the phylum Platyhelminthes (flatworms), have the simplest, clearly defined delineation of a nervous system into a CNS and a PNS. Their primitive brains, consisting of two fused anterior ganglia, and longitudinal nerve cords form the CNS. Like vertebrates, have a distinct CNS and PNS. The nerves projecting laterally from the CNS form their PNS.

A molecular study found that more than 95% of the 116 genes involved in the nervous system of planarians, which includes genes related to the CNS, also exist in humans.

Arthropoda
In arthropods, the ventral nerve cord, the subesophageal ganglia and the supraesophageal ganglia are usually seen as making up the CNS. Arthropoda, unlike vertebrates, have inhibitory motor neurons due to their small size.

Chordata
The CNS of chordates differs from that of other animals in being placed dorsally in the body, above the gut and notochord/spine. The basic pattern of the CNS is highly conserved throughout the different species of vertebrates and during evolution. The major trend that can be observed is towards a progressive telencephalisation: the telencephalon of reptiles is only an appendix to the large olfactory bulb, while in mammals it makes up most of the volume of the CNS. In the human brain, the telencephalon covers most of the diencephalon and the entire mesencephalon. Indeed, the allometric study of brain size among different species shows a striking continuity from rats to whales, and allows us to complete the knowledge about the evolution of the CNS obtained through cranial endocasts.

Mammals
Mammals – which appear in the fossil record after the first fishes, amphibians, and reptiles – are the only vertebrates to possess the evolutionarily recent, outermost part of the cerebral cortex (main part of the telencephalon excluding olfactory bulb) known as the neocortex. This part of the brain is, in mammals, involved in higher thinking and further processing of all senses in the sensory cortices (processing for smell was previously only done by its bulb while those for non-smell senses were only done by the tectum). The neocortex of monotremes (the duck-billed platypus and several species of spiny anteaters) and of marsupials (such as kangaroos, koalas, opossums, wombats, and Tasmanian devils) lack the convolutions – gyri and sulci – found in the neocortex of most placental mammals (eutherians). Within placental mammals, the size and complexity of the neocortex increased over time. The area of the neocortex of mice is only about 1/100 that of monkeys, and that of monkeys is only about 1/10 that of humans. In addition, rats lack convolutions in their neocortex (possibly also because rats are small mammals), whereas cats have a moderate degree of convolutions, and humans have quite extensive convolutions. Extreme convolution of the neocortex is found in dolphins, possibly related to their complex echolocation.

Diseases
There are many CNS diseases and conditions, including infections such as encephalitis and poliomyelitis, early-onset neurological disorders including ADHD and autism, seizure disorders such as epilepsy, headache disorders such as migraine, late-onset neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease, and essential tremor, autoimmune and inflammatory diseases such as multiple sclerosis and acute disseminated encephalomyelitis, genetic disorders such as Krabbe's disease and Huntington's disease, as well as amyotrophic lateral sclerosis and adrenoleukodystrophy. Lastly, cancers of the central nervous system can cause severe illness and, when malignant, can have very high mortality rates. Symptoms depend on the size, growth rate, location and malignancy of tumors and can include alterations in motor control, hearing loss, headaches and changes in cognitive ability and autonomic functioning.

Specialty professional organizations recommend that neurological imaging of the brain be done only to answer a specific clinical question and not as routine screening.

title: Central nervous system


text:
Cell cycle

The cell cycle, or cell-division cycle, is the sequential series of events that take place in a cell that causes it to divide into two daughter cells. These events include the growth of the cell, duplication of its DNA (DNA replication) and some of its organelles, and subsequently the partitioning of its cytoplasm, chromosomes and other components into two daughter cells in a process called cell division.

In eukaryotic cells (having a cell nucleus) including animal, plant, fungal, and protist cells, the cell cycle is divided into two main stages: interphase, and the M phase that includes mitosis and cytokinesis. During interphase, the cell grows, accumulating nutrients needed for mitosis, and replicates its DNA and some of its organelles. During the M phase, the replicated chromosomes, organelles, and cytoplasm separate into two new daughter cells. To ensure the proper replication of cellular components and division, there are control mechanisms known as cell cycle checkpoints after each of the key steps of the cycle that determine if the cell can progress to the next phase.

In cells without nuclei the prokaryotes, bacteria and archaea, the cell cycle is divided into the B, C, and D periods. The B period extends from the end of cell division to the beginning of DNA replication. DNA replication occurs during the C period. The D period refers to the stage between the end of DNA replication and the splitting of the bacterial cell into two daughter cells.

In single-celled organisms, a single cell-division cycle is how the organism reproduces to ensure it's survival. In multicellular organisms such as plants and animals, a series of cell-division cycles is how the organism develops from a single-celled fertilized egg into a mature organism, and is also the process by which hair, skin, blood cells, and some internal organs are regenerated and healed (with possible exception of nerves; see nerve damage). After cell division, each of the daughter cells begin the interphase of a new cell cycle. Although the various stages of interphase are not usually morphologically distinguishable, each phase of the cell cycle has a distinct set of specialized biochemical processes that prepare the cell for initiation of the cell division.

Phases
The eukaryotic cell cycle consists of four distinct phases: G1 phase, S phase (synthesis), G2 phase (collectively known as interphase) and M phase (mitosis and cytokinesis). M phase is itself composed of two tightly coupled processes: mitosis, in which the cell's nucleus divides, and cytokinesis, in which the cell's cytoplasm and cell membrane divides forming two daughter cells. Activation of each phase is dependent on the proper progression and completion of the previous one. Cells that have temporarily or reversibly stopped dividing are said to have entered a state of quiescence called G0 phase or the resting phase.

G0 phase (quiescence)

G0 is a resting phase where the cell has left the cycle and has stopped dividing. The cell cycle starts with this phase. Non-proliferative (non-dividing) cells in multicellular eukaryotes generally enter the quiescent G0 state from G1 and may remain quiescent for long periods of time, possibly indefinitely (as is often the case for neurons). This is very common for cells that are fully differentiated. Some cells enter the G0 phase semi-permanently and are considered post-mitotic, e.g., some liver, kidney, and stomach cells. Many cells do not enter G0 and continue to divide throughout an organism's life, e.g., epithelial cells.

The word "post-mitotic" is sometimes used to refer to both quiescent and senescent cells. Cellular senescence occurs in response to DNA damage and external stress and usually constitutes an arrest in G1. Cellular senescence may make a cell's progeny nonviable; it is often a biochemical alternative to the self-destruction of such a damaged cell by apoptosis.

Interphase
Interphase represents the phase between two successive M phases. Interphase is a series of changes that takes place in a newly formed cell and its nucleus before it becomes capable of division again. It is also called preparatory phase or intermitosis. Typically interphase lasts for at least 91% of the total time required for the cell cycle.

Interphase proceeds in three stages, G1, S, and G2, followed by the cycle of mitosis and cytokinesis. The cell's nuclear DNA contents are duplicated during S phase.

G1 phase (First growth phase or Post mitotic gap phase)

The first phase within interphase, from the end of the previous M phase until the beginning of DNA synthesis, is called G1 (G indicating gap). It is also called the growth phase. During this phase, the biosynthetic activities of the cell, which are considerably slowed down during M phase, resume at a high rate. The duration of G1 is highly variable, even among different cells of the same species. In this phase, the cell increases its supply of proteins, increases the number of organelles (such as mitochondria, ribosomes), and grows in size. In G1 phase, a cell has three options. The deciding point is called check point (Restriction point). This check point is called the restriction point or START and is regulated by G1/S cyclins, which cause transition from G1 to S phase. Passage through the G1 check point commits the cell to division.
 * To continue cell cycle and enter S phase
 * Stop cell cycle and enter G0 phase for undergoing differentiation.
 * Become arrested in G1 phase hence it may enter G0 phase or re-enter cell cycle.

S phase (DNA replication)
The ensuing S phase starts when DNA synthesis commences; when it is complete, all of the chromosomes have been replicated, i.e., each chromosome consists of two sister chromatids. Thus, during this phase, the amount of DNA in the cell has doubled, though the ploidy and number of chromosomes are unchanged. Rates of RNA transcription and protein synthesis are very low during this phase. An exception to this is histone production, most of which occurs during the S phase.

G2 phase (growth)
G2 phase occurs after DNA replication and is a period of protein synthesis and rapid cell growth to prepare the cell for mitosis. During this phase microtubules begin to reorganize to form a spindle (preprophase). Before proceeding to mitotic phase, cells must be checked at the G2 checkpoint for any DNA damage within the chromosomes. The G2 checkpoint is mainly regulated by the tumor protein p53. If the DNA is damaged, p53 will either repair the DNA or trigger the apoptosis of the cell. If p53 is dysfunctional or mutated, cells with damaged DNA may continue through the cell cycle, leading to the development of cancer.

Mitotic phase (chromosome separation)
The relatively brief M phase consists of nuclear division (karyokinesis) and division of cytoplasm (cytokinesis). It is a relatively short period of the cell cycle. M phase is complex and highly regulated. The sequence of events is divided into phases, corresponding to the completion of one set of activities and the start of the next. These phases are sequentially known as:
 * prophase
 * prometaphase
 * metaphase
 * anaphase
 * telophase

Mitosis is the process by which a eukaryotic cell separates the chromosomes in its cell nucleus into two identical sets in two nuclei. During the process of mitosis the pairs of chromosomes condense and attach to microtubules that pull the sister chromatids to opposite sides of the cell.

Mitosis occurs exclusively in eukaryotic cells, but occurs in different ways in different species. For example, animal cells undergo an "open" mitosis, where the nuclear envelope breaks down before the chromosomes separate, while fungi such as Aspergillus nidulans and Saccharomyces cerevisiae (yeast) undergo a "closed" mitosis, where chromosomes divide within an intact cell nucleus.

Cytokinesis phase (separation of all cell components)
Mitosis is immediately followed by cytokinesis, which divides the nuclei, cytoplasm, organelles and cell membrane into two cells containing roughly equal shares of these cellular components. Cytokinesis occurs differently in plant and animal cells. While the cell membrane forms a groove that gradually deepens to separate the cytoplasm in animal cells, a cell plate is formed to separate it in plant cells. The position of the cell plate is determined by the position of a preprophase band of microtubules and actin filaments. Mitosis and cytokinesis together define the division of the parent cell into two daughter cells, genetically identical to each other and to their parent cell. This accounts for approximately 10% of the cell cycle.

Because cytokinesis usually occurs in conjunction with mitosis, "mitosis" is often used interchangeably with "M phase". However, there are many cells where mitosis and cytokinesis occur separately, forming single cells with multiple nuclei in a process called endoreplication. This occurs most notably among the fungi and slime molds, but is found in various groups. Even in animals, cytokinesis and mitosis may occur independently, for instance during certain stages of fruit fly embryonic development. Errors in mitosis can result in cell death through apoptosis or cause mutations that may lead to cancer.

Regulation of eukaryotic cell cycle

Regulation of the cell cycle involves processes crucial to the survival of a cell, including the detection and repair of genetic damage as well as the prevention of uncontrolled cell division. The molecular events that control the cell cycle are ordered and directional; that is, each process occurs in a sequential fashion and it is impossible to "reverse" the cycle.

Role of cyclins and CDKs
Two key classes of regulatory molecules, cyclins and cyclin-dependent kinases (CDKs), determine a cell's progress through the cell cycle. Leland H. Hartwell, R. Timothy Hunt, and Paul M. Nurse won the 2001 Nobel Prize in Physiology or Medicine for their discovery of these central molecules. Many of the genes encoding cyclins and CDKs are conserved among all eukaryotes, but in general, more complex organisms have more elaborate cell cycle control systems that incorporate more individual components. Many of the relevant genes were first identified by studying yeast, especially Saccharomyces cerevisiae; genetic nomenclature in yeast dubs many of these genes cdc (for "cell division cycle") followed by an identifying number, e.g. cdc25 or cdc20.

Cyclins form the regulatory subunits and CDKs the catalytic subunits of an activated heterodimer; cyclins have no catalytic activity and CDKs are inactive in the absence of a partner cyclin. When activated by a bound cyclin, CDKs perform a common biochemical reaction called phosphorylation that activates or inactivates target proteins to orchestrate coordinated entry into the next phase of the cell cycle. Different cyclin-CDK combinations determine the downstream proteins targeted. CDKs are constitutively expressed in cells whereas cyclins are synthesised at specific stages of the cell cycle, in response to various molecular signals.

General mechanism of cyclin-CDK interaction
Upon receiving a pro-mitotic extracellular signal, G1 cyclin-CDK complexes become active to prepare the cell for S phase, promoting the expression of transcription factors that in turn promote the expression of S cyclins and of enzymes required for DNA replication. The G1 cyclin-CDK complexes also promote the degradation of molecules that function as S phase inhibitors by targeting them for ubiquitination. Once a protein has been ubiquitinated, it is targeted for proteolytic degradation by the proteasome. However, results from a recent study of E2F transcriptional dynamics at the single-cell level argue that the role of G1 cyclin-CDK activities, in particular cyclin D-CDK4/6, is to tune the timing rather than the commitment of cell cycle entry.

Active S cyclin-CDK complexes phosphorylate proteins that make up the pre-replication complexes assembled during G1 phase on DNA replication origins. The phosphorylation serves two purposes: to activate each already-assembled pre-replication complex, and to prevent new complexes from forming. This ensures that every portion of the cell's genome will be replicated once and only once. The reason for prevention of gaps in replication is fairly clear, because daughter cells that are missing all or part of crucial genes will die. However, for reasons related to gene copy number effects, possession of extra copies of certain genes is also deleterious to the daughter cells.

Mitotic cyclin-CDK complexes, which are synthesized but inactivated during S and G2 phases, promote the initiation of mitosis by stimulating downstream proteins involved in chromosome condensation and mitotic spindle assembly. A critical complex activated during this process is a ubiquitin ligase known as the anaphase-promoting complex (APC), which promotes degradation of structural proteins associated with the chromosomal kinetochore. APC also targets the mitotic cyclins for degradation, ensuring that telophase and cytokinesis can proceed.

Specific action of cyclin-CDK complexes
Cyclin D is the first cyclin produced in the cells that enter the cell cycle, in response to extracellular signals (e.g. growth factors). Cyclin D levels stay low in resting cells that are not proliferating. Additionally, CDK4/6 and CDK2 are also inactive because CDK4/6 are bound by INK4 family members (e.g., p16), limiting kinase activity. Meanwhile, CDK2 complexes are inhibited by the CIP/KIP proteins such as p21 and p27, When it is time for a cell to enter the cell cycle, which is triggered by a mitogenic stimuli, levels of cyclin D increase. In response to this trigger, cyclin D binds to existing CDK4/6, forming the active cyclin D-CDK4/6 complex. Cyclin D-CDK4/6 complexes in turn mono-phosphorylates the retinoblastoma susceptibility protein (Rb) to pRb. The un-phosphorylated Rb tumour suppressor functions in inducing cell cycle exit and maintaining G0 arrest (senescence).

In the last few decades, a model has been widely accepted whereby pRB proteins are inactivated by cyclin D-Cdk4/6-mediated phosphorylation. Rb has 14+ potential phosphorylation sites. Cyclin D-Cdk 4/6 progressively phosphorylates Rb to hyperphosphorylated state, which triggers dissociation of pRB–E2F complexes, thereby inducing G1/S cell cycle gene expression and progression into S phase.

However, scientific observations from a recent study show that Rb is present in three types of isoforms: (1) un-phosphorylated Rb in G0 state; (2) mono-phosphorylated Rb, also referred to as "hypo-phosphorylated' or 'partially' phosphorylated Rb in early G1 state; and (3) inactive hyper-phosphorylated Rb in late G1 state. In early G1 cells, mono-phosphorylated Rb exists as 14 different isoforms, one of each has distinct E2F binding affinity. Rb has been found to associate with hundreds of different proteins and the idea that different mono-phosphorylated Rb isoforms have different protein partners was very appealing. A recent report confirmed that mono-phosphorylation controls Rb's association with other proteins and generates functional distinct forms of Rb. All different mono-phosphorylated Rb isoforms inhibit E2F transcriptional program and are able to arrest cells in G1-phase. Importantly, different mono-phosphorylated forms of Rb have distinct transcriptional outputs that are extended beyond E2F regulation.

In general, the binding of pRb to E2F inhibits the E2F target gene expression of certain G1/S and S transition genes including E-type cyclins. The partial phosphorylation of Rb de-represses the Rb-mediated suppression of E2F target gene expression, begins the expression of cyclin E. The molecular mechanism that causes the cell switched to cyclin E activation is currently not known, but as cyclin E levels rise, the active cyclin E-CDK2 complex is formed, bringing Rb to be inactivated by hyper-phosphorylation. Hyperphosphorylated Rb is completely dissociated from E2F, enabling further expression of a wide range of E2F target genes are required for driving cells to proceed into S phase [1]. Recently, it has been identified that cyclin D-Cdk4/6 binds to a C-terminal alpha-helix region of Rb that is only distinguishable to cyclin D rather than other cyclins, cyclin E, A and B. This observation based on the structural analysis of Rb phosphorylation supports that Rb is phosphorylated in a different level through multiple Cyclin-Cdk complexes. This also makes feasible the current model of a simultaneous switch-like inactivation of all mono-phosphorylated Rb isoforms through one type of Rb hyper-phosphorylation mechanism. In addition, mutational analysis of the cyclin D- Cdk 4/6 specific Rb C-terminal helix shows that disruptions of cyclin D-Cdk 4/6 binding to Rb prevents Rb phosphorylation, arrests cells in G1, and bolsters Rb's functions in tumor suppressor. This cyclin-Cdk driven cell cycle transitional mechanism governs a cell committed to the cell cycle that allows cell proliferation. A cancerous cell growth often accompanies with deregulation of Cyclin D-Cdk 4/6 activity.

The hyperphosphorylated Rb dissociates from the E2F/DP1/Rb complex (which was bound to the E2F responsive genes, effectively "blocking" them from transcription), activating E2F. Activation of E2F results in transcription of various genes like cyclin E, cyclin A, DNA polymerase, thymidine kinase, etc. Cyclin E thus produced binds to CDK2, forming the cyclin E-CDK2 complex, which pushes the cell from G1 to S phase (G1/S, which initiates the G2/M transition). Cyclin B-cdk1 complex activation causes breakdown of nuclear envelope and initiation of prophase, and subsequently, its deactivation causes the cell to exit mitosis. A quantitative study of E2F transcriptional dynamics at the single-cell level by using engineered fluorescent reporter cells provided a quantitative framework for understanding the control logic of cell cycle entry, challenging the canonical textbook model. Genes that regulate the amplitude of E2F accumulation, such as Myc, determine the commitment in cell cycle and S phase entry. G1 cyclin-CDK activities are not the driver of cell cycle entry. Instead, they primarily tune the timing of E2F increase, thereby modulating the pace of cell cycle progression.

Endogenous
Two families of genes, the cip/kip (CDK interacting protein/Kinase inhibitory protein) family and the INK4a/ARF (Inhibitor of Kinase 4/Alternative Reading Frame) family, prevent the progression of the cell cycle. Because these genes are instrumental in prevention of tumor formation, they are known as tumor suppressors.

The cip/kip family includes the genes p21, p27 and p57. They halt the cell cycle in G1 phase by binding to and inactivating cyclin-CDK complexes. p21 is activated by p53 (which, in turn, is triggered by DNA damage e.g. due to radiation). p27 is activated by Transforming Growth Factor β (TGF β), a growth inhibitor.

The INK4a/ARF family includes p16INK4a, which binds to CDK4 and arrests the cell cycle in G1 phase, and p14ARF which prevents p53 degradation.

Synthetic
Synthetic inhibitors of Cdc25 could also be useful for the arrest of cell cycle and therefore be useful as antineoplastic and anticancer agents.

Many human cancers possess the hyper-activated Cdk 4/6 activities. Given the observations of cyclin D-Cdk 4/6 functions, inhibition of Cdk 4/6 should result in preventing a malignant tumor from proliferating. Consequently, scientists have tried to invent the synthetic Cdk4/6 inhibitor as Cdk4/6 has been characterized to be a therapeutic target for anti-tumor effectiveness. Three Cdk4/6 inhibitors – palbociclib, ribociclib, and abemaciclib – currently received FDA approval for clinical use to treat advanced-stage or metastatic, hormone-receptor-positive (HR-positive, HR+), HER2-negative (HER2-) breast cancer. For example, palbociclib is an orally active CDK4/6 inhibitor which has demonstrated improved outcomes for ER-positive/HER2-negative advanced breast cancer. The main side effect is neutropenia which can be managed by dose reduction.

Cdk4/6 targeted therapy will only treat cancer types where Rb is expressed. Cancer cells with loss of Rb have primary resistance to Cdk4/6 inhibitors.

Transcriptional regulatory network
Current evidence suggests that a semi-autonomous transcriptional network acts in concert with the CDK-cyclin machinery to regulate the cell cycle. Several gene expression studies in Saccharomyces cerevisiae have identified 800–1200 genes that change expression over the course of the cell cycle. They are transcribed at high levels at specific points in the cell cycle, and remain at lower levels throughout the rest of the cycle. While the set of identified genes differs between studies due to the computational methods and criteria used to identify them, each study indicates that a large portion of yeast genes are temporally regulated.

Many periodically expressed genes are driven by transcription factors that are also periodically expressed. One screen of single-gene knockouts identified 48 transcription factors (about 20% of all non-essential transcription factors) that show cell cycle progression defects. Genome-wide studies using high throughput technologies have identified the transcription factors that bind to the promoters of yeast genes, and correlating these findings with temporal expression patterns have allowed the identification of transcription factors that drive phase-specific gene expression. The expression profiles of these transcription factors are driven by the transcription factors that peak in the prior phase, and computational models have shown that a CDK-autonomous network of these transcription factors is sufficient to produce steady-state oscillations in gene expression).

Experimental evidence also suggests that gene expression can oscillate with the period seen in dividing wild-type cells independently of the CDK machinery. Orlando et al. used microarrays to measure the expression of a set of 1,271 genes that they identified as periodic in both wild type cells and cells lacking all S-phase and mitotic cyclins (clb1,2,3,4,5,6). Of the 1,271 genes assayed, 882 continued to be expressed in the cyclin-deficient cells at the same time as in the wild type cells, despite the fact that the cyclin-deficient cells arrest at the border between G1 and S phase. However, 833 of the genes assayed changed behavior between the wild type and mutant cells, indicating that these genes are likely directly or indirectly regulated by the CDK-cyclin machinery. Some genes that continued to be expressed on time in the mutant cells were also expressed at different levels in the mutant and wild type cells. These findings suggest that while the transcriptional network may oscillate independently of the CDK-cyclin oscillator, they are coupled in a manner that requires both to ensure the proper timing of cell cycle events. Other work indicates that phosphorylation, a post-translational modification, of cell cycle transcription factors by Cdk1 may alter the localization or activity of the transcription factors in order to tightly control timing of target genes.

While oscillatory transcription plays a key role in the progression of the yeast cell cycle, the CDK-cyclin machinery operates independently in the early embryonic cell cycle. Before the midblastula transition, zygotic transcription does not occur and all needed proteins, such as the B-type cyclins, are translated from maternally loaded mRNA.

DNA replication and DNA replication origin activity
Analyses of synchronized cultures of Saccharomyces cerevisiae under conditions that prevent DNA replication initiation without delaying cell cycle progression showed that origin licensing decreases the expression of genes with origins near their 3' ends, revealing that downstream origins can regulate the expression of upstream genes. This confirms previous predictions from mathematical modeling of a global causal coordination between DNA replication origin activity and mRNA expression,  and shows that mathematical modeling of DNA microarray data can be used to correctly predict previously unknown biological modes of regulation.

Checkpoints
Cell cycle checkpoints are used by the cell to monitor and regulate the progress of the cell cycle. Checkpoints prevent cell cycle progression at specific points, allowing verification of necessary phase processes and repair of DNA damage. The cell cannot proceed to the next phase until checkpoint requirements have been met. Checkpoints typically consist of a network of regulatory proteins that monitor and dictate the progression of the cell through the different stages of the cell cycle.

It is estimated that in normal human cells about 1% of single-strand DNA damages are converted to about 50 endogenous DNA double-strand breaks per cell per cell cycle. Although such double-strand breaks are usually repaired with high fidelity, errors in their repair are considered to contribute significantly to the rate of cancer in humans.

There are several checkpoints to ensure that damaged or incomplete DNA is not passed on to daughter cells. Three main checkpoints exist: the G1/S checkpoint, the G2/M checkpoint and the metaphase (mitotic) checkpoint. Another checkpoint is the Go checkpoint, in which the cells are checked for maturity. If the cells fail to pass this checkpoint by not being ready yet, they will be discarded from dividing.

G1/S transition is a rate-limiting step in the cell cycle and is also known as restriction point. This is where the cell checks whether it has enough raw materials to fully replicate its DNA (nucleotide bases, DNA synthase, chromatin, etc.). An unhealthy or malnourished cell will get stuck at this checkpoint.

The G2/M checkpoint is where the cell ensures that it has enough cytoplasm and phospholipids for two daughter cells. But sometimes more importantly, it checks to see if it is the right time to replicate. There are some situations where many cells need to all replicate simultaneously (for example, a growing embryo should have a symmetric cell distribution until it reaches the mid-blastula transition). This is done by controlling the G2/M checkpoint.

The metaphase checkpoint is a fairly minor checkpoint, in that once a cell is in metaphase, it has committed to undergoing mitosis. However that's not to say it isn't important. In this checkpoint, the cell checks to ensure that the spindle has formed and that all of the chromosomes are aligned at the spindle equator before anaphase begins.

While these are the three "main" checkpoints, not all cells have to pass through each of these checkpoints in this order to replicate. Many types of cancer are caused by mutations that allow the cells to speed through the various checkpoints or even skip them altogether. Going from S to M to S phase almost consecutively. Because these cells have lost their checkpoints, any DNA mutations that may have occurred are disregarded and passed on to the daughter cells. This is one reason why cancer cells have a tendency to exponentially acquire mutations. Aside from cancer cells, many fully differentiated cell types no longer replicate so they leave the cell cycle and stay in G0 until their death. Thus removing the need for cellular checkpoints. An alternative model of the cell cycle response to DNA damage has also been proposed, known as the postreplication checkpoint.

Checkpoint regulation plays an important role in an organism's development. In sexual reproduction, when egg fertilization occurs, when the sperm binds to the egg, it releases signalling factors that notify the egg that it has been fertilized. Among other things, this induces the now fertilized oocyte to return from its previously dormant, G0, state back into the cell cycle and on to mitotic replication and division.

p53 plays an important role in triggering the control mechanisms at both G1/S and G2/M checkpoints. In addition to p53, checkpoint regulators are being heavily researched for their roles in cancer growth and proliferation.

Fluorescence imaging of the cell cycle
Pioneering work by Atsushi Miyawaki and coworkers developed the fluorescent ubiquitination-based cell cycle indicator (FUCCI), which enables fluorescence imaging of the cell cycle. Originally, a green fluorescent protein, mAG, was fused to hGem(1/110) and an orange fluorescent protein (mKO2) was fused to hCdt1(30/120). Note, these fusions are fragments that contain a nuclear localization signal and ubiquitination sites for degradation, but are not functional proteins. The green fluorescent protein is made during the S, G2, or M phase and degraded during the G0 or G1 phase, while the orange fluorescent protein is made during the G0 or G1 phase and destroyed during the S, G2, or M phase. A far-red and near-infrared FUCCI was developed using a cyanobacteria-derived fluorescent protein (smURFP) and a bacteriophytochrome-derived fluorescent protein (movie found at this link).

Role in tumor formation
A disregulation of the cell cycle components may lead to tumor formation. As mentioned above, when some genes like the cell cycle inhibitors, RB, p53 etc. mutate, they may cause the cell to multiply uncontrollably, forming a tumor. Although the duration of cell cycle in tumor cells is equal to or longer than that of normal cell cycle, the proportion of cells that are in active cell division (versus quiescent cells in G0 phase) in tumors is much higher than that in normal tissue. Thus there is a net increase in cell number as the number of cells that die by apoptosis or senescence remains the same.

The cells which are actively undergoing cell cycle are targeted in cancer therapy as the DNA is relatively exposed during cell division and hence susceptible to damage by drugs or radiation. This fact is made use of in cancer treatment; by a process known as debulking, a significant mass of the tumor is removed which pushes a significant number of the remaining tumor cells from G0 to G1 phase (due to increased availability of nutrients, oxygen, growth factors etc.). Radiation or chemotherapy following the debulking procedure kills these cells which have newly entered the cell cycle.

The fastest cycling mammalian cells in culture, crypt cells in the intestinal epithelium, have a cycle time as short as 9 to 10 hours. Stem cells in resting mouse skin may have a cycle time of more than 200 hours. Most of this difference is due to the varying length of G1, the most variable phase of the cycle. M and S do not vary much.

In general, cells are most radiosensitive in late M and G2 phases and most resistant in late S phase. For cells with a longer cell cycle time and a significantly long G1 phase, there is a second peak of resistance late in G1. The pattern of resistance and sensitivity correlates with the level of sulfhydryl compounds in the cell. Sulfhydryls are natural substances that protect cells from radiation damage and tend to be at their highest levels in S and at their lowest near mitosis.

Homologous recombination (HR) is an accurate process for repairing DNA double-strand breaks. HR is nearly absent in G1 phase, is most active in S phase, and declines in G2/M. Non-homologous end joining, a less accurate and more mutagenic process for repairing double strand breaks, is active throughout the cell cycle.

Evolution of the genome
The cell cycle must duplicate all cellular constituents and equally partition them into two daughter cells. Many constituents, such as proteins and ribosomes, are produced continuously throughout the cell cycle (except during M-phase). However, the chromosomes and other associated elements like MTOCs, are duplicated just once during the cell cycle. A central component of the cell cycle is its ability to coordinate the continuous and periodic duplications of different cellular elements, which evolved with the formation of the genome.

The pre-cellular environment contained functional and self-replicating RNAs. All RNA concentrations depended on the concentrations of other RNAs that might be helping or hindering the gathering of resources. In this environment, growth was simply the continuous production of RNAs. These pre-cellular structures would have had to contend with parasitic RNAs, issues of inheritance, and copy-number control of specific RNAs.

Partitioning "genomic" RNA from "functional" RNA helped solve these problems. The fusion of multiple RNAs into a genome gave a template from which functional RNAs were cleaved. Now, parasitic RNAs would have to incorporate themselves into the genome, a much greater barrier, in order to survive. Controlling the copy number of genomic RNA also allowed RNA concentration to be determined through synthesis rates and RNA half-lives, instead of competition. Separating the duplication of genomic RNAs from the generation of functional RNAs allowed for much greater duplication fidelity of genomic RNAs without compromising the production of functional RNAs. Finally, the replacement of genomic RNA with DNA, which is a more stable molecule, allowed for larger genomes. The transition from self-catalysis enzyme synthesis to genome-directed enzyme synthesis was a critical step in cell evolution, and had lasting implications on the cell cycle, which must regulate functional synthesis and genomic duplication in very different ways.

Cyclin-dependent kinase and cyclin evolution
Cell-cycle progression is controlled by the oscillating concentrations of different cyclins and the resulting molecular interactions from the various cyclin-dependent kinases (CDKs). In yeast, just one CDK (Cdc28 in S. cerevisiae and Cdc2 in S. pombe) controls the cell cycle. However, in animals, whole families of CDKs have evolved. Cdk1 controls entry to mitosis and Cdk2, Cdk4, and Cdk6 regulate entry into S phase. Despite the evolution of the CDK family in animals, these proteins have related or redundant functions. For example, cdk2 cdk4 cdk6 triple knockout mice cells can still progress through the basic cell cycle. cdk1 knockouts are lethal, which suggests an ancestral CDK1-type kinase ultimately controlling the cell cycle.

Arabidopsis thaliana has a Cdk1 homolog called CDKA;1, however cdka;1 A. thaliana mutants are still viable, running counter to the opisthokont pattern of CDK1-type kinases as essential regulators controlling the cell cycle. Plants also have a unique group of B-type CDKs, whose functions may range from development-specific functions to major players in mitotic regulation.

G1/S checkpoint evolution
The G1/S checkpoint is the point at which the cell commits to division through the cell cycle. Complex regulatory networks lead to the G1/S transition decision. Across opisthokonts, there are both highly diverged protein sequences as well as strikingly similar network topologies.

Entry into S-phase in both yeast and animals is controlled by the levels of two opposing regulators. The networks regulating these transcription factors are double-negative feedback loops and positive feedback loops in both yeast and animals. Additional regulation of the regulatory network for the G1/S checkpoint in yeast and animals includes the phosphorylation/de-phosphorylation of CDK-cyclin complexes. The sum of these regulatory networks creates a hysteretic and bistable scheme, despite the specific proteins being highly diverged. For yeast, Whi5 must be suppressed by Cln3 phosphorylation for SBF to be expressed, while in animals Rb must be suppressed by the Cdk4/6-cyclin D complex for E2F to be expressed. Both Rb and Whi5 inhibit transcript through the recruitment of histone deacetylase proteins to promoters. Both proteins additionally have multiple CDK phosphorylation sites through which they are inhibited. However, these proteins share no sequence similarity.

Studies in A. thaliana extend our knowledge of the G1/S transition across eukaryotes as a whole. Plants also share a number of conserved network features with opisthokonts, and many plant regulators have direct animal homologs. For example, plants also need to suppress Rb for E2F translation in the network. These conserved elements of the plant and animal cell cycles may be ancestral in eukaryotes. While yeast share a conserved network topology with plants and animals, the highly diverged nature of yeast regulators suggests possible rapid evolution along the yeast lineage.

title: Cell cycle


text:
Cartesian

Cartesian means of or relating to the French philosopher René Descartes—from his Latinized name Cartesius. It may refer to:

Mathematics

 * Cartesian closed category, a closed category in category theory
 * Cartesian coordinate system, modern rectangular coordinate system
 * Cartesian diagram, a construction in category theory
 * Cartesian geometry, now more commonly called analytic geometry
 * Cartesian morphism, formalisation of pull-back operation in category theory
 * Cartesian oval, a curve
 * Cartesian product, a direct product of two sets
 * Cartesian product of graphs, a binary operation on graphs
 * Cartesian tree, a binary tree in computer science

Philosophy

 * Cartesian anxiety, a hope that studying the world will give us unchangeable knowledge of ourselves and the world
 * Cartesian circle, a potential mistake in reasoning
 * Cartesian doubt, a form of methodical skepticism as a basis for philosophical rigor
 * Cartesian dualism, the philosophy of the distinction between mind and body
 * Cartesianism, the philosophy of René Descartes
 * Cartesianists, followers of Cartesianism
 * Cartesian Meditations, a work by Edmund Husserl
 * Cartesian linguistics, a work by Noam Chomsky
 * Cartesian theatre, a derisive view of Cartesian dualism coined by Daniel Dennett

Science

 * Cartesian diver, a science experiment demonstrating buoyancy and the ideal gas law
 * Cartesian physics, attempts to explain gravity without a need for action at distance

title: Cartesian


text:
Talk:Central nervous system

clean-up tag
there was this clean-up tag since december 2006, but I wasn't able to find the reason why it was there in the first place... there's nothing about central nervous system in december 2006 in the clean-up page... Rto 13:13, 11 April 2007 (UTC)

Moved from page: this is the brain Insert non-formatted text here

Headline text
Cranial nerves: are they part of the CNS? -- The cranial nerves III-XII are a part of the PNS, Peripheral nervous system.

The articles nervous system and centeral nervous system should be merged with re-directs for both of these names. I might do it later...or someone else can sooner. Hi, i'm stuck with my science homework.....so could anybody tell me what the 4 main parts of the nervous system are. I know the brain and the spinal cord are 2, but i just don't know the other 2. I'd be very grateful if anybody could tell me. Thank you!

Please sign your posts. Thank you. 71.248.149.216 03:01, 16 February 2007 (UTC)

Folic acid
I erased this phrase: "In the development phase, folic acid is a critical dietary supplement for proper nural tube development." The article is just meant to be an introduction to the other CNS articles. The diet that goverment suggests to mothers during pregnancy are beyond its scope... Rto 11:09, 5 August 2006 (UTC)

Deleted*

Introduction
Is it just me, or is the introductory paragraph a little hard to understand? Someone should clarify and define 'behavior' in the second sentence. --Gabycs 23:59, 17 March 2007 (UTC) CELIA WAZ HERE 5-21-2007

I find the diagram in the introduction almost useless. "Schematic diagram showing the central nervous system in yellow, peripheral in orange" On my screen I can barely see any difference between 'orange' and 'yellow'. It's a lovely diagram. But use of two more contrasting colours would be appreciated. — Preceding unsigned comment added by 31.185.62.166 (talk) 16:35, 11 February 2022 (UTC)

Human orientation
This article is clearly geared solely toward the CNS of humans. Can we possibly expand the article so that it explains what Central Nervous Systems are rather than what the CNS in humans is? Animals have CNS too. -- Noetic  Sage  04:27, 27 September 2007 (UTC)

 * I agree! The article should perhaps be renamed: Central nervous system of humans -- or of primates -- or of vertebrates.  Do we have an article about the CNS in various (other) animals, which maybe I just haven't found??

 * Just as the article Sleep was 'taken over' by humans, such that we later got Sleep (non-human), some such work needs to be done here. --Hordaland (talk) 15:02, 27 April 2008 (UTC)

Parts of the CNS
In the text book of surgery by Bailey and Love the 1st and 2nd cranial nerves are also included as a part of the CNS. Please discuss and add to the parts of the CNSsarindam7 (talk) 07:56, 21 June 2008 (UTC)

EVOLUTION: Planarians
I added a paragrah about the CNS of planarians. In one of the sentences, I state, "A molecular study found that >95% of the 116 genes involved in the nervous system of planarians, which includes those related to the planarian CNS, also exist in humans." I do not know how to create a reference for the article. Below is the information on that article. If anyone else can setup the reference for me, please do so.

Katsuhiko Mineta, Masumi Nakazawa, Francesc Cebrià, Kazuho Ikeo, Kiyokazu Agata, and Takashi Gojobori, Origin and evolutionary process of the CNS elucidated by comparative genomics analysis of planarian ESTs, PNAS June 24, 2003 vol. 100 no. 13 7666-7671 —Preceding unsigned comment added by 24.94.233.30 (talk) 19:50, 27 September 2008 (UTC)
 * This article needs a huge rewrite, but that information is definitely going to be relevant, so thanks for adding it. You might look at another article, for example Alzheimer's disease, to see how to cite journal articles:  basically it should look like .  If you don't get around to it, I'll fix it at some point. Looie496 (talk) 00:58, 28 September 2008 (UTC)

Neuroanatomy section
First, can the section be called "anatomy"? I think this is clearer.

Second, the section uses the words "becomes" and "gives rise to", which are unclear or ambiguous in this context. Do they refer to evolution or perhaps to development of an individual? In either case, why? The section is about anatomy, which means the different parts of the CNS and their functions, not about their development or evolution. -Pgan002 (talk) 19:49, 29 July 2009 (UTC)
 * I'm OK with calling it neuroanatomy, although I don't feel strongly about it. I agree with you very much about "becomes" and "gives rise to." I think that it's clear from context that it does not mean evolution, but it sort of sounds like development, and I've made a possibly-temporary edit to try to make that clearer. However, the text and chart can also be construed to mean that the various specific structures are parts within the larger structures (unrelated to changes over time). I hope other editors will also look at that, because I find it unclear. --Tryptofish (talk) 20:34, 29 July 2009 (UTC)

Deceptive first sentence
The implication seems to be that ALL organisms have a CNS. Should this be changed to refer specifically to animals? Let me know if you find a plant with a brain... 67.184.127.168 (talk) 02:35, 21 September 2009 (UTC)
 * Done. (Although I've met people who... never mind!) --Tryptofish (talk) 17:16, 21 September 2009 (UTC)
 * Needed a bit more qualification -- sponges and radiates are multicellular animals but lack a CNS. Looie496 (talk) 01:29, 22 September 2009 (UTC)
 * Right, thanks for catching that, which I should have done myself. (Should I say thanks for sponging that up?) --Tryptofish (talk) 16:37, 22 September 2009 (UTC)

"Function" section
An IP just removed the Function section from the article, without edit summary. Normally I would revert something that like automatically, but in this case I'm letting it stand, because the section was unsourced and really pretty much useless -- a proper CNS Function section ought to discuss the advantages of a centralized nervous system over a distributed nervous system such as a jellyfish has. Looie496 (talk) 16:18, 9 October 2009 (UTC)
 * Hmm, before seeing your comment here, I reverted (cf: herding cats). Given that there was no edit summary for the deletion, I felt the material should be restored pending discussion. But that doesn't mean I'd oppose any action. --Tryptofish (talk) 17:36, 9 October 2009 (UTC)

The retina is part of the CNS
This line: "In vertebrates, the central nervous system is enclosed in the meninges," is not entirely correct. Technically, the retina is part of the CNS, but it is not enclosed in the meninges. In fact the retina isn't mentioned as part of the CNS in the entire article and ought to be, as it is a somewhat exceptional part of the CNS. Pdavis68 (talk) 17:04, 19 March 2010 (UTC)
 * Yes, per retina, you are correct. I have fixed the lead. --Tryptofish (talk) 19:33, 19 March 2010 (UTC)

CNS & PNS are controversial definitions
"The meninges enclose the central nervous system (CNS) and separate it from the peripheral nervous system (PNS)." from "Concise Text of Neuroscience (2nd ed.)" (2000), R. E. Kingsley, Lippincott Williams & Wilkins, p. 1.

This definition is coming from a neuroscientist and is fairly inclusive. However, the succinctness of the definition hides the reasons for defining CNS this way. Consider cranial nerves, for example. Inside the meninges, cranial nerves are myelinated by oligodendrocytes, the CNS myelinating cell, with astrocytes as glial support cells. Outside the meninges, they are myelinated by Schwann cells, the peripheral myelinating cell, with satellite cells as glial support cells. It is at this junction where the cranial nerves perforate the meninges that Schwann cell cancers (Schwannomas) frequently arise. Hence, cranial nerves belong to both the CNS and PNS, depending upon the position along the nerve.

The controversy arises when you consider the medical definition: "The central nervous system (CNS) consists of the brain and spinal cord .... It is covered by three "membranes" -- the meninges." written by Bruce Ransom in "Medical Physiology" (2005), Boron & Boulpaep, Elsevier & Saunders, p. 257. Here, you have two conflicting definitions in one sentence. You have the simplified statement "brain and spinal cord" which is commonly used for the medical students along with the more sophisticated definition involving the meninges. Bruce Ransom works with the optic nerve and routinely calls the optic nerve a CNS tract (see the introduction of http://www.ncbi.nlm.nih.gov/pubmed/21179073 for an example of Dr. Ransom's work in optic nerve). Therefore, he is simplifying the definition, probably to make things easier for med. students to memorize.

I think the controversy comes from the use of a simplified definition for medical students and a more sophisticated definition for neuroscientists. Some mention should be made in the article that this is not a real controversy for neuroscientists.

The criteria I prefer for CNS are: 1) CNS tissue communicates with cerebrospinal fluid (i.e., is contained within the meninges) 2) The CNS does not typically contain the cell bodies of PNS-resident cells (i.e., no satellite cells or Schwann cells, such as are found in the PNS) 3) The CNS is protected by the blood brain barrier (BBB). Thus, capillaries of CNS tissue must include tight junctions.  This excludes the adenohypophysis and neurohypophysis of the pituitary from the CNS but would allow retinal ganglion cells.

These criteria reduce to functionality. The CNS has a shared intracellular environment, a unique set of resident cell types, and is protected from many compounds & proteins in the blood. All other tissues differ from this. — Preceding unsigned comment added by Neuro taxa (talk • contribs) 23:50, 22 May 2012 (UTC)

 * Sorry, I find that a bit difficult to understand. Would your revised definition result in the CNS including anything different, or is this just a matter of how the definition is worded? Looie496 (talk) 04:29, 23 May 2012 (UTC)
 * Perhaps you could propose a specific change (presenting before and after versions here on the talk page)? --Anthonyhcole (talk) 05:21, 23 May 2012 (UTC)
 * The definition I cited from Kingsley's book is the definition commonly used in neuroscience, in contrast to the definition "CNS is composed of the brain and spinal cord" found in introductory texts. There is also a third definition based on "integrative function" that I see you have also included in the wikipedia article.  It looks like the current article has all three definitions but doesn't really enunciate them as competing definitions, which they are.  I think the article needs to reflect the fact that these definitions are an attempt to categorize living things and that defitions change with understanding.  In other words, we should be clear that these definitions come from different perspectives and aim at different goals, sometimes leading to conflict.

The main change that should be made is to mention all the definitions as clearly distinct but having significant overlap. In particular, quote and cite Kingsley's definition or Ransom's definition.

I want to point out that people who use the "integrative" definition of CNS frequently end up including the retina or various ganglia because they have integrating functions. Cephalopods (think octopus) have distributed integrating functions to their nervous system that might lie outside their brain capsule (see http://www.biolbull.org/content/210/3/308.full).

The wikipedia article should mention that using the meninges as a landmark to define the CNS is a convenient coincidence. The CNS and PNS are technically connected together in an undivided nervous system. The division CNS/PNS is artificial but enriches our discussion of the nervous system.

The question the wikipedia authors need to answer is how technical they want the discussion to get. If you want me to put up a sandboxed page, I can't really dedicate the time right now. I was hoping one of the current authors could use the citations I was providing. comment added by Neuro taxa (talk •contribs) 23:50, 22 May 2012 (UTC)
 * Get me a review and I will add the controversy to the article. We can not use primary sources so the pubmed links are unfortunately not viable for Wikipedia. My library does not carry "Concise Text of Neuroscience (2nd ed.)" (2000), R. E. Kingsley, Lippincott Williams & Wilkins so if you'd want to add that you'll have to do so yourself.
 * Additionally my bible: Principles of neural science, Kandel, 2013 which you probably know is by no means an introductory text-book says "The nervous system has two anatomically distinct components. The central nervous system consists of the brain and the spinal cord, while the peripheral nervous system is composed of specialized clusters of neurons (ganglia) and peripheral nerves." CFCF (talk) 10:45, 22 December 2013 (UTC)
 * The Human Central Nervous System (Rudolf Nieuwenhuys M.D., Ph.D., Jan Voogd M.D., Ph.D., Christiaan van Huijzen F.M.A.A, 2008) - page 3: "The human central nervous system or neuraxis consists of the brain (encephalon) and the spinal cord (medulla spinalis)." CFCF (talk) 10:53, 22 December 2013 (UTC)

It should be called the Central Nerve System
The Human race should not be defined by the word nervous (frightened/anxious) for untold decades into the future. I suggest renaming it the 'Central Nerve System' - sounds better and had no implications of fear. --Dr zoidberg590 (talk) 13:58, 30 June 2020 (UTC)
 * Titles should use the most commonly recognized name. Pubmed hits: "central nerve system" 421, "central nervous system" 251,624. The preponderance is unambiguous. BiologicalMe (talk) 17:58, 30 June 2020 (UTC)

Infobox caption incorrect
The infobox caption for image of CNS is now incorrect, it says "Schematic diagram showing the central nervous system in yellow, peripheral in orange" -- There is now no difference in color, that image was replaced with one where it is all the same color. In my opinion the former image was easier to understand, but probably there was some reason that motivated the change back to having peripheral and central mingled together in color again (some nerves are technically part of the CNS like some cranial nerves, optic nerve etc, maybe that was it). FrozenDino (talk) 02:07, 24 October 2021 (UTC)

title: Talk:Central nervous system


text:
Connection (dance)

In partner dancing, connection is physical, non-verbal communication between dancers to facilitate synchronized or coordinated dance movements. Some forms of connection involve "lead/follow" in which one dancer (the "lead") directs the movements of the other dancer (the "follower") by means of non-verbal directions conveyed through a physical connection between the dancers. In other forms, connection involves multiple dancers (more than two) without a distinct leader or follower (e.g. contact improvisation). Connection refers to a host of different techniques in many types of partner dancing, especially (but not exclusively) those that feature significant physical contact between the dancers, including the Argentine Tango, Lindy Hop, Balboa, East Coast Swing, West Coast Swing, Salsa, and other ballroom dances.

Other forms of communication, such as visual cues or spoken cues, sometimes aid in connecting with one's partner, but are often used in specific circumstances (e.g., practicing figures, or figures which are purposely danced without physical connection). Connection can be used to transmit power and energy as well as information and signals; some dance forms (and some dancers) primarily emphasize power or signaling, but most are probably a mixture of both. Philosopher of dance Ilya Vidrin argues that connection between partners involves norm-based communication that include “a physical exchange of information on the basis of ethically-bound conditions” (proximity, orientation, and points of contact) which constrain agency and predictability.

Lead/Follow
Following and leading in a partner dance is accomplished by maintaining a physical connection called the frame that allows the leader to transmit body movement to the follower, and for the follower to suggest ideas to the leader. A frame is a stable structural combination of both bodies maintained through the dancers' arms and/or legs.

Connection occurs in both open and closed dance positions (also called "open frame" and "closed frame").

In closed position with body contact, connection is achieved by maintaining the frame. The follower moves to match the leader, maintaining the pressure between the two bodies as well as the position.

When creating frame, tension is the primary means of establishing communication. Changes in tension are made to create rhythmic variations in moves and movements, and are communicated through points of contact. In an open position or a closed position without body contact, the hands and arms alone provide the connection, which may be one of three forms: tension, compression or neutral.

 * During tension or leverage connection, the dancers are pulling away from each other with an equal and opposite force. The arms do not originate this force alone: they are often assisted by tension in trunk musculature, through body weight or by momentum.
 * During compression connection, the dancers are pushing towards each other.
 * In a neutral position, the hands do not impart any force other than the touch of the follower's hands in the leader's.

In swing dances, tension and compression may be maintained for a significant period of time. In other dances, such as Latin, tension and compression may be used as indications of upcoming movement. However, in both styles, tension and compression do not signal immediate movement: the follow must be careful not to move prior to actual movement by the lead. Until then, the dancers must match pressures without moving their hands. In some styles of Lindy Hop, the tension may become quite high without initiating movement.

The general rule for open connections is that moves of the leader's hands back, forth, left or right are originated through moves of the entire body. Accordingly, for the follower, a move of the connected hand is immediately transformed into the corresponding move of the body. Tensing the muscles and locking the arm achieves this effect but is neither comfortable nor correct. Such tension eliminates the subtler communication in the connection, and eliminates free movement up and down, such as is required to initiate many turns.

Instead of just tensing the arms, connection is achieved by engaging the shoulder, upper body and torso muscles. Movement originates in the body's core. A leader leads by moving himself and maintaining frame and connection. Different forms of dance and different movements within each dance may call for differences in the connection. In some dances the separation distance between the partners remains pretty constant. In others e.g. Modern Jive moving closer together and further apart are fundamental to the dance, requiring flexion and extension of the arms, alternating compression and tension.

The connection between two partners has a different feel in every dance and with every partner. Good social dancers adapt to the conventions of the dance and the responses of their partners.

title: Connection (dance)