1.
Visual system
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The visual system is the part of the central nervous system which gives organisms the ability to process visual detail, as well as enabling the formation of several non-image photo response functions. It detects and interprets information from visible light to build a representation of the surrounding environment, the psychological process of visual information is known as visual perception, a lack of which is called blindness. Non-image forming visual functions, independent of perception, include the pupillary light reflex. This article mostly describes the system of mammals, humans in particular. Together the cornea and lens refract light into a small image, the retina transcribes this image into electrical pulses using rods and cones. The optic nerve then carries these pulses through the optic canal, upon reaching the optic chiasm the nerve fibers decussate. The fibers then branch and terminate in three places, most end in the lateral geniculate nucleus. Before the LGN forwards the pulses to V1 of the visual cortex it gauges the range of objects, the LGN also sends some fibers to V2 and V3. V1 performs edge-detection to understand spatial organization, V2 both forwards pulses to V1 and receives them. Pulvinar is responsible for saccade and visual attention, V2 serves much the same function as V1, however, it also handles illusory contours, determining depth by comparing left and right pulses, and foreground distinguishment. V3 helps process ‘global motion’ of objects, V3 connects to V1, V2, and the inferior temporal cortex. V4 recognizes simple shapes, gets input from V1, V2, V3, LGN, v5’s outputs include V4 and its surrounding area, and eye-movement motor cortices. V5’s functionality is similar to that of the other V’s, however, V6 works in conjunction with V5 on motion analysis. V5 analyzes self-motion, whereas V6 analyzes motion of objects relative to the background, v6’s primary input is V1, with V5 additions. V6 houses the topographical map for vision, V6 outputs to the region directly around it. V6A has direct connections to arm-moving cortices, including the premotor cortex, the inferior temporal gyrus recognizes complex shapes, objects, and faces or, in conjunction with the hippocampus, creates new memories. The pretectal area is seven unique nuclei, anterior, posterior and medial pretectal nuclei inhibit pain, aid in REM, and aid the accommodation reflex, respectively. The Edinger-Westphal nucleus moderates pupil dilation and aids in convergence of the eyes, nuclei of the optic tract are involved in smooth pursuit eye movement and the accommodation reflex, as well as REM
2.
Light
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Light is electromagnetic radiation within a certain portion of the electromagnetic spectrum. The word usually refers to light, which is visible to the human eye and is responsible for the sense of sight. Visible light is defined as having wavelengths in the range of 400–700 nanometres, or 4.00 × 10−7 to 7.00 × 10−7 m. This wavelength means a range of roughly 430–750 terahertz. The main source of light on Earth is the Sun, sunlight provides the energy that green plants use to create sugars mostly in the form of starches, which release energy into the living things that digest them. This process of photosynthesis provides virtually all the used by living things. Historically, another important source of light for humans has been fire, with the development of electric lights and power systems, electric lighting has effectively replaced firelight. Some species of animals generate their own light, a process called bioluminescence, for example, fireflies use light to locate mates, and vampire squids use it to hide themselves from prey. Visible light, as all types of electromagnetic radiation, is experimentally found to always move at this speed in a vacuum. In physics, the term sometimes refers to electromagnetic radiation of any wavelength. In this sense, gamma rays, X-rays, microwaves and radio waves are also light, like all types of light, visible light is emitted and absorbed in tiny packets called photons and exhibits properties of both waves and particles. This property is referred to as the wave–particle duality, the study of light, known as optics, is an important research area in modern physics. Generally, EM radiation, or EMR, is classified by wavelength into radio, microwave, infrared, the behavior of EMR depends on its wavelength. Higher frequencies have shorter wavelengths, and lower frequencies have longer wavelengths, when EMR interacts with single atoms and molecules, its behavior depends on the amount of energy per quantum it carries. There exist animals that are sensitive to various types of infrared, infrared sensing in snakes depends on a kind of natural thermal imaging, in which tiny packets of cellular water are raised in temperature by the infrared radiation. EMR in this range causes molecular vibration and heating effects, which is how these animals detect it, above the range of visible light, ultraviolet light becomes invisible to humans, mostly because it is absorbed by the cornea below 360 nanometers and the internal lens below 400. Furthermore, the rods and cones located in the retina of the eye cannot detect the very short ultraviolet wavelengths and are in fact damaged by ultraviolet. Many animals with eyes that do not require lenses are able to detect ultraviolet, by quantum photon-absorption mechanisms, various sources define visible light as narrowly as 420 to 680 to as broadly as 380 to 800 nm
3.
Signal
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A signal as referred to in communication systems, signal processing, and electrical engineering is a function that conveys information about the behavior or attributes of some phenomenon. The IEEE Transactions on Signal Processing states that the signal includes audio, video, speech, image, communication, geophysical, sonar, radar. Typically, signals are provided by a sensor, and often the form of a signal is converted to another form of energy using a transducer. For example, a microphone converts a signal to a voltage waveform. The formal study of the content of signals is the field of information theory. The information in a signal is accompanied by noise. The term noise usually means an undesirable random disturbance, but is extended to include unwanted signals conflicting with the desired signal. The prevention of noise is covered in part under the heading of signal integrity, the separation of desired signals from a background is the field of signal recovery, one branch of which is estimation theory, a probabilistic approach to suppressing random disturbances. Engineering disciplines such as electrical engineering have led the way in the design, study, and implementation of systems involving transmission, storage, definitions specific to sub-fields are common. For example, in theory, a signal is a codified message, that is. In the context of signal processing, arbitrary binary data streams are not considered as signals, in a communication system, a transmitter encodes a message to a signal, which is carried to a receiver by the communications channel. For example, the words Mary had a little lamb might be the message spoken into a telephone, the telephone transmitter converts the sounds into an electrical voltage signal. The signal is transmitted to the telephone by wires, at the receiver it is reconverted into sounds. In telephone networks, signalling, for example common-channel signaling, refers to number and other digital control information rather than the actual voice signal. Signals can be categorized in various ways, the most common distinction is between discrete and continuous spaces that the functions are defined over, for example discrete and continuous time domains. Discrete-time signals are often referred to as series in other fields. Continuous-time signals are often referred to as continuous signals even when the functions are not continuous. A second important distinction is between discrete-valued and continuous-valued, particularly in digital signal processing a digital signal is sometimes defined as a sequence of discrete values, that may or may not be derived from an underlying continuous-valued physical process
4.
Rod cell
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Rod cells are photoreceptor cells in the retina of the eye that can function in less intense light than the other type of visual photoreceptor, cone cells. Rods are usually concentrated at the outer edges of the retina and are used in peripheral vision. On average, there are approximately 90 million rod cells in the human retina, Rod cells are more sensitive than cone cells and are almost entirely responsible for night vision. However, rods have little role in vision, which is one of the main reasons why colors are much less apparent in darkness. Rods are a longer and leaner than cones but have the same structural basis. The opsin or pigment is on the side, lying on the Retinal pigment epithelium. This epithelium end contains many stacked disks, rods have a high area for visual pigment and thus substantial efficiency of light absorption. Rods are much more common than cones, with about 100 million rod cells compared to 7 million cone cells, like cones, rod cells have a synaptic terminal, an inner segment, and an outer segment. The synaptic terminal forms a synapse with another neuron, for example a septo cell, the inner and outer segments are connected by a cilium, which lines the distal segment. The inner segment contains organelles and the nucleus, while the rod outer segment. A human rod cell is about 2 microns in diameter and 100 microns long, rods are not all morphologically the same, in mice, rods close to the outer plexiform synaptic layer display a reduced length and due to short synaptic body. Those rods also have different synaptic organizations, in vertebrates, activation of a photoreceptor cell is a hyperpolarization of the cell. When they are not being stimulated, such as in the dark, rod cells and cone cells depolarize and this neurotransmitter hyperpolarizes the bipolar cell. Bipolar cells exist between photoreceptors and ganglion cells and act to transmit signals from the photoreceptors to the ganglion cells, as a result of the bipolar cell being hyperpolarized, it does not release its transmitter at the bipolar-ganglion synapse and the synapse is not excited. Depolarization of rod cells occurs because in the dark, cells have a high concentration of cyclic guanosine 3-5 monophosphate. Glutamate can depolarize some neurons and hyperpolarize others, allowing photoreceptors to interact in an antagonistic manner, when light hits photoreceptive pigments within the photoreceptor cell, the pigment changes shape. The pigment, called rhodopsin comprises a large protein called opsin, attached to which is a covalently bound prosthetic group, the retinal exists in the 11-cis-retinal form when in the dark, and stimulation by light causes its structure to change to all-trans-retinal. This structural change causes an increased affinity for the protein called transducin
5.
Cone cell
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Cone cells, or cones, are one of three types of photoreceptor cells in the retina of mammalian eyes. They are responsible for vision and function best in relatively bright light, as opposed to rod cells. Cone cells are packed in the fovea centralis, a 0.3 mm diameter rod-free area with very thin. There are about six to seven million cones in an eye and are most concentrated towards the macula. The commonly cited figure of six million cone cells in the eye was found by Osterberg in 1935. Oysters textbook cites work by Curcio et al. indicating a close to 4.5 million cone cells and 90 million rod cells in the human retina. Cones are less sensitive to light than the rod cells in the retina and they are also able to perceive finer detail and more rapid changes in images, because their response times to stimuli are faster than those of rods. Cones are normally one of the three types, each with different pigment, namely, S-cones, M-cones and L-cones, each cone is therefore sensitive to visible wavelengths of light that correspond to short-wavelength, medium-wavelength and long-wavelength light. Being colour blind can change this, and there have been some verified reports of people with four or more types of cones, destruction of the cone cells from disease would result in blindness. Humans normally have three types of cones, the first responds the most to light of long wavelengths, peaking at about 560 nm, this type is sometimes designated L for long. The second type responds the most to light of medium-wavelength, peaking at 530 nm, the third type responds the most to short-wavelength light, peaking at 420 nm, and is designated S for short. The three types have peak wavelengths near 564–580 nm, 534–545 nm, and 420–440 nm, respectively, the difference in the signals received from the three cone types allows the brain to perceive a continuous range of colours, through the opponent process of colour vision. All of the contain the protein photopsin, with variations in its conformation causing differences in the optimum wavelengths absorbed. Similarly, blue and violet hues are perceived when the S receptor is stimulated more, cones are most sensitive to light at wavelengths around 420 nm. People with aphakia, a condition where the eye lacks a lens, at lower light levels, where only the rod cells function, the sensitivity is greatest at a blueish-green wavelength. Separate connectivity is established in the inner plexiform layer so that each connection is parallel, while it has been discovered that there exists a mixed type of bipolar cells that bind to both rod and cone cells, bipolar cells still predominantly receive their input from cone cells. Cone cells are somewhat shorter than rods, but wider and tapered, and are less numerous than rods in most parts of the retina. Structurally, cone cells have a cone-like shape at one end where a pigment filters incoming light, giving them their different response curves
6.
George Wald
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George David Wald was an American scientist who was best known for his work with pigments in the retina. He won a share of the 1967 Nobel Prize in Physiology or Medicine with Haldan Keffer Hartline, as a postdoctoral researcher, Wald discovered that vitamin A was a component of the retina. His further experiments showed that when the pigment rhodopsin was exposed to light, it yielded the protein opsin and this suggested that vitamin A was essential in retinal function. In the 1950s, Wald and his colleagues used chemical methods to extract pigments from the retina, then, using a spectrophotometer, they were able to measure the light absorbance of the pigments. Since the absorbance of light by retina pigments corresponds to the wavelengths that best activate photoreceptor cells, however, since rod cells make up most of the retina, what Wald and his colleagues were specifically measuring was the absorbance of rhodopsin, the main photopigment in rods. Later, with a technique called microspectrophotometry, he was able to measure the absorbance directly from cells and this allowed Wald to determine the absorbance of pigments in the cone cells. George Wald was born in New York City, the son of Ernestine and Isaac Wald and he was a member of the first graduating class of the Brooklyn Technical High School in New York in 1922. He received his Bachelor of Science degree from New York University in 1927, after graduating, he received a travel grant from the US National Research Council. Wald used this grant to work in Germany with Otto Heinrich Warburg where he identified vitamin A in the retina, Wald then went on to work in Zurich, Switzerland with the discoverer of vitamin A, Paul Karrer. In 1934, Wald went to Harvard University where he became an instructor and he was elected to the National Academy of Sciences in 1950 and in 1967 was awarded the Nobel Prize for Physiology or Medicine for his discoveries in vision. In 1966 he was awarded the Frederic Ives Medal by the OSA, Wald spoke out on many political and social issues and his fame as a Nobel laureate brought national and international attention to his views. He was an opponent of the Vietnam War and the nuclear arms race. Speaking at MIT in 1969 Wald bemoaned that Our government has become preoccupied with death, with the business of killing and being killed, in 1980, Wald served as part of Ramsey Clarks delegation to Iran during the Iran hostage crisis. With a small number of other Nobel laureates, he was invited in 1986 to fly to Moscow to advise Mikhail Gorbachev on a number of environmental questions. While there, he questioned Gorbachev about the arrest, detention and exile to Gorki of Yelena Bonner and her husband, Wald reported that Gorbachev said he knew nothing about it. Bonner and Sakharov were released thereafter, in December,1986. He was married twice, in 1931 to Frances Kingsley and in 1958 to the biochemist Ruth Hubbard and he had two sons with Kingsley—Michael and David, he and Hubbard had a son—the award-winning musicologist and musician Elijah Wald—and a daughter, Deborah, a prominent family law attorney. List of Jewish Nobel laureates Retinal Nobel Prize Biography John E. Dowling, George Wald, 1906–1997, A Biographical Memoir in Biographical Memoirs, Washington, the National Academy Press, Volume 78,298,317
7.
Photon
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A photon is an elementary particle, the quantum of the electromagnetic field including electromagnetic radiation such as light, and the force carrier for the electromagnetic force. The photon has zero rest mass and is moving at the speed of light. Like all elementary particles, photons are currently best explained by quantum mechanics and exhibit wave–particle duality, exhibiting properties of both waves and particles. For example, a photon may be refracted by a lens and exhibit wave interference with itself. The quanta in a light wave cannot be spatially localized, some defined physical parameters of a photon are listed. The modern concept of the photon was developed gradually by Albert Einstein in the early 20th century to explain experimental observations that did not fit the classical model of light. The benefit of the model was that it accounted for the frequency dependence of lights energy. The photon model accounted for observations, including the properties of black-body radiation. In that model, light was described by Maxwells equations, in 1926 the optical physicist Frithiof Wolfers and the chemist Gilbert N. Lewis coined the name photon for these particles. After Arthur H. Compton won the Nobel Prize in 1927 for his studies, most scientists accepted that light quanta have an independent existence. In the Standard Model of particle physics, photons and other particles are described as a necessary consequence of physical laws having a certain symmetry at every point in spacetime. The intrinsic properties of particles, such as charge, mass and it has been applied to photochemistry, high-resolution microscopy, and measurements of molecular distances. Recently, photons have been studied as elements of quantum computers, in 1900, the German physicist Max Planck was studying black-body radiation and suggested that the energy carried by electromagnetic waves could only be released in packets of energy. In his 1901 article in Annalen der Physik he called these packets energy elements, the word quanta was used before 1900 to mean particles or amounts of different quantities, including electricity. In 1905, Albert Einstein suggested that waves could only exist as discrete wave-packets. He called such a wave-packet the light quantum, the name photon derives from the Greek word for light, φῶς. Arthur Compton used photon in 1928, referring to Gilbert N. Lewis, the name was suggested initially as a unit related to the illumination of the eye and the resulting sensation of light and was used later in a physiological context. Although Wolferss and Lewiss theories were contradicted by many experiments and never accepted, in physics, a photon is usually denoted by the symbol γ
8.
Opsin
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Opsins are a group of light-sensitive proteins found in photoreceptor cells of the retina. Five classical groups of opsins are involved in vision, mediating the conversion of a photon of light into an electrochemical signal, another opsin found in the mammalian retina, melanopsin, is involved in circadian rhythms and pupillary reflex but not in image-forming. Opsins can be classified several ways, including function, type of chromophore, molecular structure, signal output, there are two groups of protein termed opsins. Type I opsins are employed by prokaryotes and by algae and fungi. No opsins have been found outside these groups, at one time it was thought that type I and type II were related because of structural and functional similarities. With the advent of genetic sequencing it became apparent that sequence identity was no greater than could be accounted for by random chance, however, in recent years new methods have been developed specific to deep phylogeny. Like type II opsins, type I opsins have a seven transmembrane domain structure similar to found in eukaryotic G-protein coupled receptors. Type I opsins are found in all three domains of life, Archaea, Bacteria, and Eukaryota, in Eukaryota, type I opsins are found mainly in unicellular organisms such as green algae, and in fungi. In most complex multicellular eukaryotes, type I opsins have been replaced with other molecules such as cryptochrome and phytochrome in plants. Microbial opsins are often known by the form of the molecule. Several type I opsins, such as proteo- and bacteriorhodopsin, are used by various groups to harvest energy from light to carry out metabolic processes using a non-chlorophyll-based pathway. Beside that, halorhodopsins of Halobacteria and channelrhodopsins of some algae, e. g. Volvox, serve them as light-gated ion channels, sensory rhodopsins exist in Halobacteria that induce a phototactic response by interacting with transducer membrane-embedded proteins that have no relation to G proteins. Type I opsins are used in optogenetics to switch on or off neuronal activity, type I opsins are preferred if the neuronal activity should be modulated at higher frequency, because they respond faster than type II opsins. Type II opsins are seven-transmembrane proteins belonging to the G protein-coupled receptor superfamily, type II opsins fall phylogenetically into four groups, C-opsins, Cnidops, R-opsins, and Go/RGR opsins. The Go/RGR opsins are divided into four sub-clades, Go-opsins, RGR, Peropsins, C-opsins, R-opsins, and the Go/RGR opsins are found only in Bilateria. Type II visual opsins are traditionally classified as either ciliary or rhabdomeric, ciliary opsins, found in vertebrates and cnidarians, attach to ciliary structures such as rods and cones. Rhabdomeric opsins are attached to light-gathering organelles called rhabdomeres and this classification cuts across phylogenetic categories so that both the terms ciliary and rhabdomeric can be ambiguous. Here, C-opsins refers to a clade found exclusively in Bilateria, similarly, R-opsin includes melanopsin even though it does not occur on rhabdomeres in vertebrates
9.
Chromophore
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A chromophore is the part of a molecule responsible for its color. The color that is seen by our eyes is the one not absorbed within a certain spectrum of visible light. The chromophore is a region in the molecule where the difference between two separate molecular orbitals falls within the range of the visible spectrum. Visible light that hits the chromophore can thus be absorbed by exciting an electron from its state into an excited state. In biological molecules that serve to capture or detect light energy, in the conjugated chromophores, the electrons jump between energy levels that are extended pi orbitals, created by a series of alternating single and double bonds, often in aromatic systems. Common examples include retinal, various food colorings, fabric dyes, pH indicators, lycopene, β-carotene, various factors in a chromophores structure go into determining at what wavelength region in a spectrum the chromophore will absorb. Lengthening or extending a conjugated system with more unsaturated bonds in a molecule will tend to shift absorption to longer wavelengths, woodward-Fieser rules can be used to approximate ultraviolet-visible maximum absorption wavelength in organic compounds with conjugated pi-bond systems. Some of these are metal complex chromophores, which contain a metal in a complex with ligands. Examples are chlorophyll, which is used by plants for photosynthesis and hemoglobin, the highly conjugated pi-bonding system of the macrocycle ring absorbs visible light. The nature of the metal can also influence the absorption spectrum of the metal-macrocycle complex or properties such as excited state lifetime. The tetrapyrrole moiety in organic compounds which is not macrocyclic but still has a conjugated pi-bond system still acts as a chromophore, examples of such compounds include bilirubin and urobilin, which exhibit a yellow color. An auxochrome is a group of atoms attached to the chromophore which modifies the ability of the chromophore to absorb light. Halochromism occurs when a substance changes color as the pH changes and this is a property of pH indicators, whose molecular structure changes upon certain changes in the surrounding pH. This change in structure affects a chromophore in the pH indicator molecule, because of their limited extent, the aromatic rings only absorb light in the ultraviolet region, and so the compound appears colorless in the 0-8 pH range. However, as the pH increases beyond 8.2, that central carbon becomes part of a double bond becoming sp2 hybridized and this makes the three rings conjugate together to form an extended chromophore absorbing longer wavelength visible light to show a fuchsia color. At pH ranges outside 0-12, other molecular structure changes result in other color changes, visual phototransduction Woodwards rules Chromatophore Pigment Photophore Fluorophore Litmus Biological pigment Causes of Color, physical mechanisms by which color is generated. High Speed Nano-Sized Electronics May be Possible with Chromophores - Azonano. com
10.
Schiff base
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A Schiff base is a compound with the general structure R2C=NR. They can be considered a sub-class of imines, being either secondary ketimines or secondary depending on their structure. The term is synonymous with azomethine which refers specifically to secondary aldimines. A number of naming systems exist for these compounds. For instance a Schiff base derived from an aniline, where R3 is a phenyl or a substituted phenyl, can be called an anil, the term Schiff base is normally applied to these compounds when they are being used as ligands to form coordination complexes with metal ions. Such complexes do occur naturally, for instance in Corrin, but the majority of Schiff bases are artificial and are used to form many important catalysts, such as Jacobsens catalyst. Schiff bases can be synthesized from an aliphatic or aromatic amine, the common enzyme cofactor PLP forms a Schiff base with a lysine residue and is transaldiminated to the substrate. Similarly, the cofactor retinal forms a Schiff base in rhodopsins, including human rhodopsin, an example where the substrate forms a Schiff base to the enzyme is in the fructose 1, 6-bisphosphate aldolase catalyzed reaction during glycolysis and in the metabolism of amino acids. Schiff bases are common ligands in coordination chemistry, the imine nitrogen is basic and exhibits pi-acceptor properties. The ligands are derived from alkyl diamines and aromatic aldehydes. Chiral Schiff bases were one of the first ligands used for asymmetric catalysis, in 1968 Ryōji Noyori developed a copper-Schiff base complex for the metal-carbenoid cyclopropanation of styrene. For this work he was awarded a share of the 2001 Nobel Prize in Chemistry. Their simple and clean chemistry make them a candidate as a low cost alternative to currently used conjugated materials. Schiff base chemistry is used to prepare covalent organic framework
11.
Photoisomerization
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In chemistry, photoisomerization is molecular behavior in which structural change between isomers is caused by photoexcitation. Both reversible and irreversible isomerization reactions exist, however, the word photoisomerization usually indicates a reversible process. Photoisomerizable molecules are already put to use, for instance, in pigments for rewritable CDs, DVDs. In fact, photoisomerization of the retinal in the eye is the mechanism that allows for vision. In addition, recent interest in photoisomerizable molecules has been aimed at molecular devices, such as switches, molecular motors. Photoisomerization behavior can be categorized into several classes. Two major classes are trans-cis conversion, and open-closed ring transition, examples of the former include stilbene and azobenzene. This type of compounds has a bond, and rotation or inversion around the double bond affords isomerization between the two states. Examples of the latter include fulgide and diarylethene and this type of compounds undergoes bond cleavage and bond creation upon irradiation with particular wavelengths of light. Still another class is the di-pi-methane rearrangement
12.
Retinal
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Retinal is also known as retinaldehyde. It was originally called retinene, and renamed after it was discovered to be vitamin A aldehyde, retinal is one of the many forms of vitamin A. Retinal is a chromophore, bound to proteins called opsins. Retinal allows certain microorganisms to convert light into metabolic energy, vertebrate animals ingest retinal directly from meat, or they produce retinal from carotenoids, either from one of two carotenes or from β-cryptoxanthin, a type of xanthophyll. These carotenoids must be obtained from plants or other photosynthetic organisms, no other carotenoids can be converted by animals to retinal, and some carnivores cannot convert any carotenoids at all. The other main forms of vitamin A, retinol, and an active form, retinoic acid. Invertebrates such as insects and squid use hydroxylated forms of retinal in their visual systems, living organisms produce retinal by irreversible oxidative cleavage of carotenoids. For example, beta-carotene + O2 →2 retinal catalyzed by a beta-carotene 15, 15-monooxygenase or a beta-carotene 15, vision begins with the photoisomerization of retinal. When the 11-cis-retinal chromophore absorbs a photon it isomerizes from the 11-cis state to the all-trans state, the absorbance spectrum of the chromophore depends on its interactions with the opsin protein to which it is bound, different opsins produce different absorbance spectra. Opsins are proteins and the visual pigments found in the photoreceptor cells in the retinas of eyes. An opsin is arranged into a bundle of seven transmembrane alpha-helices connected by six loops, in rod cells the opsin molecules are embedded in the membranes of the disks which are entirely inside of the cell. The N-terminus head of the molecule extends into the interior of the disk, in cone cells the disks are defined by the cells plasma membrane so that the N-terminus head extends outside of the cell. Retinal binds covalently to a lysine on the transmembrane helix nearest the C-terminus of the protein through a Schiff base linkage, formation of the Schiff base linkage involves removing the oxygen atom from retinal and two hydrogen atoms from the free amino group of lysine, giving H2O. Retinylidene is the divalent group formed by removing the oxygen atom from retinal, opsins are prototypical G protein-coupled receptors. Bovine rhodopsin, the opsin of the rod cells of cattle, was the first GPCR to have its X-ray structure determined, bovine rhodopsin contains 348 amino acid residues. The retinal chromophore binds at Lys296, although mammals use retinal exclusively as the opsin chromophore, other groups of animals additionally use four chromophores closely related to retinal. These are 3, 4-didehydroretinal, -3-hydroxyretinal, -3-hydroxyretinal, and -4-hydroxyretinal, many fish and amphibians use 3, 4-didehydroretinal, also called dehydroretinal. With the exception of the dipteran suborder Cyclorrhapha, the higher flies
13.
Signal transduction
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Proteins responsible for detecting stimuli are generally termed receptors, although in some cases the term sensor is used. The changes elicited by ligand binding in a receptor give rise to a cascade of events along a signalling pathway. When signalling pathways interact with one another they form networks, which allow cellular responses to be coordinated and these molecular events are the basic mechanisms controlling cell growth, proliferation, metabolism and many other processes. In multicellular organisms, signal transduction pathways have evolved to regulate cell communication in a variety of ways. Each component of a pathway is classified according to the role it plays with respect to the initial stimulus. Ligands are termed first messengers, while receptors are the signal transducers, such effectors are often linked to second messengers, which can activate secondary effectors, and so on. Depending on the efficiency of the nodes, a signal can be amplified, as with other signals, the transduction of biological signals is characterised by delay, noise and interference, which can range from negligible to pathological. With the advent of computational biology, the analysis of signalling pathways and networks has become a tool to understand cellular functions. The basis for signal transduction is the transformation of a certain stimulus into a biochemical signal, traditionally, signals that reach the central nervous system are classified as senses. These are transmitted from neuron to neuron in a process called synaptic transmission, many other intercellular signal relay mechanisms exist in multicellular organisms, such as those that govern embryonic development. The majority of signal transduction pathways involve the binding of signalling molecules, known as ligands, the combination of a signaling molecule with a receptor causes a change in the conformation of the receptor, known as receptor activation. Most ligands are soluble molecules from the medium which bind to cell surface receptors. These include growth factors, cytokines and neurotransmitters, components of the extracellular matrix such as fibronectin and hyaluronan can also bind to such receptors. In addition, some such as steroid hormones are lipid-soluble. In the case of hormone receptors, their stimulation leads to binding to the promoter region of steroid-responsive genes. Not all classifications of signalling molecules take into account the nature of each class member. For example, odorants belong to a range of molecular classes, as do neurotransmitters. Moreover, some molecules may fit more than one class, e. g. epinephrine is a neurotransmitter when secreted by the central nervous system
14.
Protein
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Proteins are large biomolecules, or macromolecules, consisting of one or more long chains of amino acid residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, responding to stimuli, a linear chain of amino acid residues is called a polypeptide. A protein contains at least one long polypeptide, short polypeptides, containing less than 20–30 residues, are rarely considered to be proteins and are commonly called peptides, or sometimes oligopeptides. The individual amino acid residues are bonded together by peptide bonds, the sequence of amino acid residues in a protein is defined by the sequence of a gene, which is encoded in the genetic code. In general, the code specifies 20 standard amino acids, however. Sometimes proteins have non-peptide groups attached, which can be called prosthetic groups or cofactors, proteins can also work together to achieve a particular function, and they often associate to form stable protein complexes. Once formed, proteins only exist for a period of time and are then degraded and recycled by the cells machinery through the process of protein turnover. A proteins lifespan is measured in terms of its half-life and covers a wide range and they can exist for minutes or years with an average lifespan of 1–2 days in mammalian cells. Abnormal and or misfolded proteins are degraded more rapidly due to being targeted for destruction or due to being unstable. Like other biological macromolecules such as polysaccharides and nucleic acids, proteins are essential parts of organisms, many proteins are enzymes that catalyse biochemical reactions and are vital to metabolism. Proteins also have structural or mechanical functions, such as actin and myosin in muscle and the proteins in the cytoskeleton, other proteins are important in cell signaling, immune responses, cell adhesion, and the cell cycle. In animals, proteins are needed in the diet to provide the essential amino acids that cannot be synthesized, digestion breaks the proteins down for use in the metabolism. Methods commonly used to study structure and function include immunohistochemistry, site-directed mutagenesis, X-ray crystallography, nuclear magnetic resonance. Most proteins consist of linear polymers built from series of up to 20 different L-α-amino acids, all proteinogenic amino acids possess common structural features, including an α-carbon to which an amino group, a carboxyl group, and a variable side chain are bonded. Only proline differs from this structure as it contains an unusual ring to the N-end amine group. The amino acids in a chain are linked by peptide bonds. Once linked in the chain, an individual amino acid is called a residue, and the linked series of carbon, nitrogen. The peptide bond has two forms that contribute some double-bond character and inhibit rotation around its axis, so that the alpha carbons are roughly coplanar
15.
Retinol
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Retinol, also known as Vitamin A1, is a vitamin found in food and used as a dietary supplement. As a supplement it is used to treat and prevent vitamin A deficiency, in areas where deficiency is common a single large dose is recommended to those at high risk a couple of times a year. It is also used to prevent further issues in those who have measles and it is used by mouth or injection into a muscle. Retinol at normal doses is well tolerated, high doses may result in an enlarged liver, dry skin, or hypervitaminosis A. High doses during pregnancy may result in harm to the baby, Retinol is in the vitamin A family. It or other forms of vitamin A are needed for eye sight, maintenance of the skin and it is converted in the body to retinal and retinoic acid through which it acts. Dietary sources include fish, dairy products, and meat, Retinol was discovered in 1909, isolated in 1931, and first made in 1947. It is on the World Health Organizations List of Essential Medicines, Retinol is available as a generic medication and over the counter. The wholesale cost in the world is about 0.02 to 0.30 USD per 50,000 units. In the United States it is not very expensive, Retinol is used to treat vitamin A deficiency. The Tolerable Upper Intake Level for vitamin A, for a 25-year-old male, is 3,000 micrograms/day, too much vitamin A in retinoid form can be harmful or fatal, resulting in what is known as hypervitaminosis A. The body converts the dimerized form, carotene, into vitamin A as it is needed, the livers of certain animals, especially those adapted to polar environments, often contain amounts of vitamin A that would be toxic to humans. Thus, vitamin A toxicity is typically reported in Arctic explorers, Vitamin A acute toxicity occurs when an individual ingests vitamin A in large amounts more than the daily recommended value in the threshold of 25,000 IU/kg or more. Often, the individual consumes about 3–4 times the RDAs specification, the former occurs few hours or days after ingestion of large amounts of vitamin A accidentally or via inappropriate therapy. The later toxicity takes place when about 4,000 IU/kg or more of vitamin A is consumed for a period of time. Symptoms associated with both toxicities include nausea, blurred vision, fatigue, weight-loss, menstrual abnormalities etc, excess vitamin A has also been suspected to be a contributor to osteoporosis. This seems to happen at lower doses than those required to induce acute intoxication. Only preformed vitamin A can cause problems, because the conversion of carotenoids into vitamin A is downregulated when physiological requirements are met
16.
Retinal pigment epithelium
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The RPE is composed of a single layer of hexagonal cells that are densely packed with pigment granules. At the ora serrata, the RPE continues as a membrane passing over the ciliary body and this generates the fibers of the dilator. Directly beneath this epithelium is the neuroepithelium passes jointly with the RPE, both, combined, are understood to be the ciliary epithelium of the embryo. The front end continuation of the retina is the posterior iris epithelium, when viewed from the outer surface, these cells are smooth and hexagonal in shape. The RPE has several functions, namely, light absorption, epithelial transport, spatial ion buffering, visual cycle, phagocytosis, secretion, light absorption, RPE are responsible for absorbing scattered light. Melanosomes absorb the light and thus diminish the photo-oxidative stress. The high perfusion of retina brings a high oxygen tension environment, the combination of light and oxygen brings oxidative stress, and RPEs have many mechanism to cope with it. This is important for the privilege of eyes, a highly selective transport of substances for a tightly controlled environment. RPE supply nutrients to photoreceptors, control ion homeostasis and eliminate water, visual cycle, The visual cycle fulfills an essential task of maintaining visual function and needs therefore to be adapted to different visual needs such as vision in darkness or lightness. For this, functional aspects come into play, the storage of retinal, basically vision at low light intensities requires a lower turn-over rate of the visual cycle whereas during light the turn-over rate is much higher. In the transition from darkness to light suddenly, large amount of 11-cis retinal is required, phagocytosis of photoreceptor outer segment membranes, POS are exposed to constant photo-oxidative stress, and they go through constant destruction by it. They are constantly renew, by shedding the ends and then RPE phagocytose, in order to communicate with the neighboring tissues the RPE is able to secrete a large variety of factors and signaling molecules. Many of these molecules have important physiopathologic roles. Immune privilege of the eye, The inner eye represents an immune privileged space which is disconnected from the system of the blood stream. The immune privilege is supported by the RPE in two ways, first, it represents a mechanical and tight barrier which separates the inner space of the eye from the blood stream. Second, the RPE is able to communicate with the system in order to silence immune reaction in the healthy eye or, on the other hand. In the eyes of albinos, the cells of this layer contain no pigment, dysfunction of the RPE is found in age-related macular degeneration and retinitis pigmentosa. RPE are also involved in diabetic retinopathy
17.
Ester
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In chemistry, esters are chemical compounds derived from an acid in which at least one –OH group is replaced by an –O–alkyl group. Usually, esters are derived from an acid and an alcohol. Glycerides, which are fatty acid esters of glycerol, are important esters in biology, being one of the classes of lipids. Esters with low weight are commonly used as fragrances and found in essential oils. Phosphoesters form the backbone of DNA molecules, nitrate esters, such as nitroglycerin, are known for their explosive properties, while polyesters are important plastics, with monomers linked by ester moieties. The word ester was coined in 1848 by German chemist Leopold Gmelin, probably as a contraction of the German Essigäther, ester names are derived from the parent alcohol and the parent acid, where the latter may be organic or inorganic. Esters derived from more complex carboxylic acids are, on the hand, more frequently named using the systematic IUPAC name. For example, the ester hexyl octanoate, also known under the trivial name hexyl caprylate, has the formula CH36CO25CH3, the chemical formulas of organic esters usually take the form RCO2R′, where R and R′ are the hydrocarbon parts of the carboxylic acid and the alcohol, respectively. For example, butyl acetate, derived from butanol and acetic acid would be written CH3CO2C4H9, alternative presentations are common including BuOAc and CH3COOC4H9. Cyclic esters are called lactones, regardless of whether they are derived from an organic or an inorganic acid, one example of a lactone is γ-valerolactone. An uncommon class of organic esters are the orthoesters, which have the formula RC3, triethylorthoformate is derived, in terms of its name from orthoformic acid and ethanol. Esters can also be derived from an acid and an alcohol. For example, triphenyl phosphate is the derived from phosphoric acid. Organic carbonates are derived from acid, for example, ethylene carbonate is derived from carbonic acid. So far an alcohol and inorganic acid are linked via oxygen atoms, in corollary, boron features borinic esters, boronic esters, and borates. As oxygen is a group 16 chemical element, sulfur atoms can replace some oxygen atoms in carbon–oxygen–central inorganic atom covalent bonds of an ester, esters contain a carbonyl center, which gives rise to 120 ° C–C–O and O–C–O angles. Unlike amides, esters are structurally flexible functional groups because rotation about the C–O–C bonds has a low barrier and their flexibility and low polarity is manifested in their physical properties, they tend to be less rigid and more volatile than the corresponding amides. The pKa of the alpha-hydrogens on esters is around 25, the preference for the Z conformation is influenced by the nature of the substituents and solvent, if present
18.
Lecithin retinol acyltransferase
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Lecithin retinol acyltransferase is an enzyme that in humans is encoded by the LRAT gene. Mutations in this gene have been associated with early-onset severe retinal dystrophy, LRAT was overexpressed in colorectal cancer cells compared to normal colonic epithelium. Strong LRAT expression was associated with a poor prognosis in patients with colorectal cancer, the Visual Cycle GeneReviews/NCBI/NIH/UW entry on Retinitis Pigmentosa Overview
19.
RPE65
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Retinal pigment epithelium-specific 65 kDa protein, also known as retinoid isomerohydrolase, is an enzyme of the vertebrate visual cycle that is encoded in humans by the RPE65 gene. RPE65 is located in the pigment epithelium and is responsible for the conversion of all-trans-retinyl esters to 11-cis-retinol during phototransduction. 11-cis-retinol is then used in visual pigment regeneration in photoreceptor cells, RPE65 belongs to the carotenoid oxygenase family of enzymes. RPE65 is an enzyme in the vertebrate visual cycle found in both rods and cones. The photoisomerization of 11-cis-retinal to all-trans-retinal initiates the phototransduction pathway through which the brain detects light, all-trans-retinol is not photoactive and therefore must be reconverted to 11-cis-retinal before it can recombine with opsin to form an active visual pigment. RPE65 reverses the photoisomerization by converting an all-trans-retinyl ester to 11-cis-retinol, most commonly, the ester substrate is retinyl palmitate. The other enzymes of the visual cycle complete the necessary to oxidize and esterify all-trans-retinol to a retinyl ester. RPE65 is also referred to as retinol isomerase or retinoid isomerase, owing to past debates about the enzymes substrate, RPE65 is a dimer of two identical, enzymatically independent subunits. The active site of each subunit has a seven-bladed beta-propeller structure with four histidines that hold an iron cofactor and this structural motif is common across the studied members of the carotenoid oxygenase family of enzymes. RPE65 is strongly associated with the membrane of the endoplasmic reticulum in RPE cells. The active site of each RPE65 active site contains an Fe cofactor bound by four histidines, three of the four histidines are coordinated to nearby glutamic acid residues, which are thought to help position the histidines to bind the iron cofactor in an octahedral geometry. Phe103, Thr147, and Glu148 surround the site where they help stabilize the carbocation intermediate. Reactants and products likely enter and leave the site through a hydrophobic tunnel which is thought to open into the lipid membrane for direct lipid substrate absorption. A second, smaller tunnel also reaches the site and may serve as a pathway for water. RPE65 is strongly associated with the membrane of the sER. sER is abnormally abundant in RPE cells due to their role in processing lipidic retinoids. Structural studies indicate that RPE65 is partially imbedded in the sER membrane via interactions between its hydrophobic face and the interior of the lipid membrane and this is supported by the need for detergent to solubilize RPE65. A major portion of RPE65’s hydrophobic face, residues 109-126, forms an alpha helix that likely contributes to the protein’s membrane affinity. Additionally, Cys112 is palmitoylated in native RPE65, further supporting the theory that the face of RPE65 is imbedded in the membrane
20.
Rhodopsin
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Rhodopsin is a light-sensitive receptor protein involved in visual phototransduction. It is named after ancient Greek ῥόδον for “rose”, due to its pinkish color, Rhodopsin is a biological pigment found in the rods of the retina and is a G-protein-coupled receptor. Rhodopsin is extremely sensitive to light, and thus enables vision in low-light conditions, when rhodopsin is exposed to light, it immediately photobleaches. In humans, it is regenerated fully in about 30 minutes, Rhodopsin was discovered by Franz Christian Boll in 1876. Rhodopsin consists of a protein moiety also called scotopsin, which binds covalently a cofactor called retinal, opsins are G protein coupled receptors and have seven transmembrane domains. The seven transmembrane domains form a pocket, where the retinal binds to a residue in the seventh transmembrane domain. The retinal lies horizontally to the cell membrane, and the cell membrane lipid bilayer embeds half of the rhodopsin. Thousands of rhodopsin molecules are found in outer segment disc of the host rod cell. Retinol is produced in the retina from Vitamin A, from dietary beta-carotene, Rhodopsin of the rods most strongly absorbs green-blue light and, therefore, appears reddish-purple, which is why it is also called visual purple. It is responsible for vision in the dark. Several closely related opsins exist that only in a few amino acids. Humans have eight different other opsins besides rhodopsin, as well as cryptochrome, the photopsins are found in the different types of the cone cells of the retina and are the basis of color vision. They have absorption maxima for yellowish-green, green, and bluish-violet light, the remaining opsin is found in photosensitive ganglion cells and absorbs blue light most strongly. In rhodopsin, the group of retinal is covalently linked to the amino group of a lysine residue on the protein in a protonated Schiff base. The intermediates formed during this process were first investigated in the laboratory of George Wald, the photoisomerization dynamics has been subsequently investigated with time-resolved IR spectroscopy and UV/Vis spectroscopy. A first photoproduct called photorhodopsin forms within 200 femtoseconds after irradiation and this intermediate can be trapped and studied at cryogenic temperatures, and was initially referred to as prelumirhodopsin. In subsequent intermediates lumirhodopsin and metarhodopsin I, the Schiffs base linkage to all-trans retinal remains protonated, the structure of rhodopsin has been studied in detail via x-ray crystallography on rhodopsin crystals. Several models attempt to explain how the group can change its conformation without clashing with the enveloping rhodopsin protein pocket
21.
Photoreceptor cell
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A photoreceptor cell is a specialized type of cell found in the retina that is capable of phototransduction. The great biological importance of photoreceptors is that they convert light signals that can stimulate biological processes. To be more specific, photoreceptor proteins in the cell absorb photons, there are currently three known types of photoreceptor cells in mammalian eyes, rods, cones, and photosensitive retinal ganglion cells. The two classic photoreceptor cells are rods and cones, each contributing information used by the system to form a representation of the visual world. The rods are narrower than the cones and distributed differently across the retina, a third class of mammalian photoreceptor cell was discovered during the 1990s, the photosensitive ganglion cells. These cells do not contribute to sight directly, but are thought to support circadian rhythms, there are major functional differences between the rods and cones. Rods are extremely sensitive, and can be triggered by a single photon, at very low light levels, visual experience is based solely on the rod signal. This explains why colors cannot be seen at low light levels, cones require significantly brighter light in order to produce a signal. In humans, there are three different types of cell, distinguished by their pattern of response to different wavelengths of light. Color experience is calculated from three distinct signals, perhaps via an opponent process. The three types of cone cell respond to light of short, medium, and long wavelengths, note that, due to the principle of univariance, the firing of the cell depends upon only the number of photons absorbed. The different responses of the three types of cells are determined by the likelihoods that their respective photoreceptor proteins will absorb photons of different wavelengths. So, for example, an L cone cell contains a protein that more readily absorbs long wavelengths of light. Light of a wavelength can also produce the same response. The human retina contains about 120 million rod cells, and 6 million cone cells, the number and ratio of rods to cones varies among species, dependent on whether an animal is primarily diurnal or nocturnal. Certain owls, such as the owl, have a tremendous number of rods in their retinae. In addition, there are about 2.4 million to 3 million ganglion cells in the visual system,1 to 2% of them photosensitive. The axons of cells form the two optic nerves
22.
Aldehyde
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The group—without R—is the aldehyde group, also known as the formyl group. Aldehydes are common in organic chemistry, Aldehydes feature an sp2-hybridized, planar carbon center that is connected by a double bond to oxygen and a single bond to hydrogen. The C–H bond is not ordinarily acidic, because of resonance stabilization of the conjugate base, an α-hydrogen in an aldehyde is far more acidic, with a pKa near 15, compared to the acidity of a typical alkane. This acidification is attributed to the quality of the formyl center and the fact that the conjugate base. Related to, the group is somewhat polar. Aldehydes can exist in either the keto or the enol tautomer, keto-enol tautomerism is catalyzed by either acid or base. Usually the enol is the minority tautomer, but it is more reactive, the common names for aldehydes do not strictly follow official guidelines, such as those recommended by IUPAC, but these rules are useful. IUPAC prescribes the following nomenclature for aldehydes, Acyclic aliphatic aldehydes are named as derivatives of the longest carbon chain containing the aldehyde group, thus, HCHO is named as a derivative of methane, and CH3CH2CH2CHO is named as a derivative of butane. The name is formed by changing the suffix -e of the parent alkane to -al, so that HCHO is named methanal, in other cases, such as when a -CHO group is attached to a ring, the suffix -carbaldehyde may be used. Thus, C6H11CHO is known as cyclohexanecarbaldehyde, if the presence of another functional group demands the use of a suffix, the aldehyde group is named with the prefix formyl-. This prefix is preferred to methanoyl-, the word aldehyde was coined by Justus von Liebig as a contraction of the Latin alcohol dehydrogenatus. In the past, aldehydes were sometimes named after the corresponding alcohols, for example, the term formyl group is derived from the Latin word formica ant. This word can be recognized in the simplest aldehyde, formaldehyde, Aldehydes have properties that are diverse and that depend on the remainder of the molecule. Smaller aldehydes are more soluble in water, formaldehyde and acetaldehyde completely so, the volatile aldehydes have pungent odors. Aldehydes degrade in air via the process of autoxidation, the two aldehydes of greatest importance in industry, formaldehyde and acetaldehyde, have complicated behavior because of their tendency to oligomerize or polymerize. They also tend to hydrate, forming the geminal diol, the oligomers/polymers and the hydrates exist in equilibrium with the parent aldehyde. Aldehydes are readily identified by spectroscopic methods, using IR spectroscopy, they display a strong νCO band near 1700 cm−1. In their 1H NMR spectra, the formyl hydrogen center absorbs near δH =9 and this signal shows the characteristic coupling to any protons on the alpha carbon
23.
Wavelength
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In physics, the wavelength of a sinusoidal wave is the spatial period of the wave—the distance over which the waves shape repeats, and thus the inverse of the spatial frequency. Wavelength is commonly designated by the Greek letter lambda, the concept can also be applied to periodic waves of non-sinusoidal shape. The term wavelength is also applied to modulated waves. Wavelength depends on the medium that a wave travels through, examples of wave-like phenomena are sound waves, light, water waves and periodic electrical signals in a conductor. A sound wave is a variation in air pressure, while in light and other electromagnetic radiation the strength of the electric, water waves are variations in the height of a body of water. In a crystal lattice vibration, atomic positions vary, wavelength is a measure of the distance between repetitions of a shape feature such as peaks, valleys, or zero-crossings, not a measure of how far any given particle moves. For example, in waves over deep water a particle near the waters surface moves in a circle of the same diameter as the wave height. The range of wavelengths or frequencies for wave phenomena is called a spectrum, the name originated with the visible light spectrum but now can be applied to the entire electromagnetic spectrum as well as to a sound spectrum or vibration spectrum. In linear media, any pattern can be described in terms of the independent propagation of sinusoidal components. The wavelength λ of a sinusoidal waveform traveling at constant speed v is given by λ = v f, in a dispersive medium, the phase speed itself depends upon the frequency of the wave, making the relationship between wavelength and frequency nonlinear. In the case of electromagnetic radiation—such as light—in free space, the speed is the speed of light. Thus the wavelength of a 100 MHz electromagnetic wave is about, the wavelength of visible light ranges from deep red, roughly 700 nm, to violet, roughly 400 nm. For sound waves in air, the speed of sound is 343 m/s, the wavelengths of sound frequencies audible to the human ear are thus between approximately 17 m and 17 mm, respectively. Note that the wavelengths in audible sound are much longer than those in visible light, a standing wave is an undulatory motion that stays in one place. A sinusoidal standing wave includes stationary points of no motion, called nodes, the upper figure shows three standing waves in a box. The walls of the box are considered to require the wave to have nodes at the walls of the box determining which wavelengths are allowed, the stationary wave can be viewed as the sum of two traveling sinusoidal waves of oppositely directed velocities. Consequently, wavelength, period, and wave velocity are related just as for a traveling wave, for example, the speed of light can be determined from observation of standing waves in a metal box containing an ideal vacuum. In that case, the k, the magnitude of k, is still in the same relationship with wavelength as shown above
24.
Potassium
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Potassium is a chemical element with symbol K and atomic number 19. It was first isolated from potash, the ashes of plants, in the periodic table, potassium is one of the alkali metals. Potassium in nature only in ionic salts. It is found dissolved in sea water, and is part of many minerals, naturally occurring potassium is composed of three isotopes, of which 40K is radioactive. Traces of 40K are found in all potassium, and it is the most common radioisotope in the human body, Potassium is chemically very similar to sodium, the previous element in Group 1 of the periodic table. They have a similar energy, which allows for each atom to give up its sole outer electron. That they are different elements combine with the same anions to make similar salts was suspected in 1702. Most industrial applications of potassium exploit the high solubility in water of potassium compounds, heavy crop production rapidly depletes the soil of potassium, and this can be remedied with agricultural fertilizers containing potassium, accounting for 95% of global potassium chemical production. Potassium ions are necessary for the function of all living cells, fresh fruits and vegetables are good dietary sources of potassium. Potassium is the second least dense metal after lithium and it is a soft solid with a low melting point, and can be easily cut with a knife. Freshly cut potassium is silvery in appearance, but it begins to tarnish toward gray immediately on exposure to air, in a flame test, potassium and its compounds emit a lilac color with a peak emission wavelength of 766.5 nanometers. Neutral potassium atoms have 19 electrons, one more than the stable configuration of the noble gas argon. This process requires so little energy that potassium is readily oxidized by atmospheric oxygen, in contrast, the second ionization energy is very high, because removal of two electrons breaks the stable noble gas electronic configuration. Potassium therefore does not readily form compounds with the state of +2 or higher. Potassium is an active metal that reacts violently with oxygen in water. With oxygen it forms potassium peroxide, and with water potassium forms potassium hydroxide, the reaction of potassium with water is dangerous because of its violent exothermic character and the production of hydrogen gas. Hydrogen reacts again with atmospheric oxygen, producing water, which reacts with the remaining potassium and this reaction requires only traces of water, because of this, potassium and the liquid sodium-potassium — NaK — are potent desiccants that can be used to dry solvents prior to distillation. Because of the sensitivity of potassium to water and air, reactions with other elements are only in an inert atmosphere such as argon gas using air-free techniques
25.
Sodium channel
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Sodium channels are integral membrane proteins that form ion channels, conducting sodium ions through a cells plasma membrane. They are classified according to the trigger that opens the channel for such ions, in excitable cells such as neurons, myocytes, and certain types of glia, sodium channels are responsible for the rising phase of action potentials. These channels go through 3 different states called as resting, active and inactive states, even though the resting and inactive states wouldnt allow the ions to flow through the channels the difference exists with respect to their structural conformation. Sodium channels are selective for the transport of sodium ions across cell membranes. The high selectivity with respect to the ion is achieved in many different ways. All involve encapsulation of the ion in a cavity of specific size within a larger molecule. Sodium channels consist of large α subunits that associate with proteins, an α subunit forms the core of the channel and is functional on its own. When the α subunit protein is expressed by a cell, it is able to form channels that conduct Na+ in a voltage-gated way, when accessory proteins assemble with α subunits, the resulting complex can display altered voltage dependence and cellular localization. The α-subunit has four domains, labeled I through IV, each containing six membrane-spanning segments. The highly conserved S4 segment acts as the voltage sensor. The voltage sensitivity of this channel is due to amino acids located at every third position. When stimulated by a change in voltage, this segment moves toward the extracellular side of the cell membrane. The ions are conducted through a pore, which can be broken into two regions, the more external portion of the pore is formed by the P-loops of the four domains. This region is the most narrow part of the pore and is responsible for its ion selectivity, the inner portion of the pore is formed by the combined S5 and S6 segments of the four domains. The region linking domains III and IV is also important for channel function and this region plugs the channel after prolonged activation, inactivating it. Voltage-gated Na+ channels have three main states, closed, open and inactivated. Forward/back transitions between states are correspondingly referred to as activation/deactivation, inactivation/reactivation, and recovery from inactivation/closed-state inactivation. Closed and inactivated states are ion impermeable, because the voltage across the membrane is initially negative, as its voltage increases to and past zero, it is said to depolarize
26.
Na+/K+-ATPase
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Na+/K+-ATPase is an enzyme found in the plasma membrane of all animal cells. The Na+/K+-ATPase enzyme is a pump that pumps sodium out of cells while pumping potassium into cells. This pumping is active and is important for cell physiology, an example application is nerve conduction. Active transport is responsible for the fact that cells contain a high concentration of potassium ions. The mechanism responsible for this is the pump, which moves these two ions in opposite directions across the plasma membrane. This was investigated by following the passage of radioactively labeled ions across the membrane of certain cells. It was found that the concentrations of sodium and potassium ions on the two sides of the membrane are interdependent, suggesting that the same carrier transports both ions. It is now known that the carrier is an ATP-ase and that it pumps three sodium ions out of the cell for every two potassium ions pumped in. The sodium-potassium pump was discovered in the 1950s by a Danish scientist, Jens Christian Skou, the Na+/K+-ATPase helps maintain resting potential, effect transport, and regulate cellular volume. It also functions as a signal transducer/integrator to regulate MAPK pathway, ROS, in most animal cells, the Na+/K+-ATPase is responsible for about 1/5 of the cells energy expenditure. For neurons, the Na+/K+-ATPase can be responsible for up to 2/3 of the energy expenditure. In order to maintain the membrane potential, cells keep a low concentration of sodium ions. The sodium-potassium pump mechanism moves 3 sodium ions out and moves 2 potassium ions in, thus, in total, the action of the sodium-potassium pump is not the only mechanism responsible for the generation of the resting membrane potential. Also, the permeability of the cells plasma membrane for the different ions plays an important role. All mechanisms involved are explained in the article on generation of the resting membrane potential. Another important task of the Na+-K+ pump is to provide a Na+ gradient that is used by certain carrier processes, similar processes are located in the renal tubular system. Failure of the Na+-K+ pumps can result in swelling of the cell, a cells osmolarity is the sum of the concentrations of the various ion species and many proteins and other organic compounds inside the cell. When this is higher than the osmolarity outside of the cell and this can cause the cell to swell up and lyse
27.
Glutamic acid
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Glutamic acid is an α-amino acid with formula C 5H 9O 4N. It is usually abbreviated as Glu or E in biochemistry and its molecular structure could be idealized as HOOC-CH-2-COOH, with two carboxyl groups -COOH and one amino group -NH2. However, in the state and mildly acid water solutions. Glutamic acid is used by almost all living beings in the biosynthesis of proteins and it is non-essential in humans, meaning the body can synthesize it. The acid can lose one proton from second carboxyl group to form the conjugate base and this form of the compound is prevalent in neutral solutions. The glutamate neurotransmitter plays the role in neural activation. This anion is also responsible for the flavor of certain foods. In highly alkaline solutions the doubly negative anion −OOC-CH-2-COO− prevails, the radical corresponding to glutamate is called glutamyl. When glutamic acid is dissolved in water, the group may gain a proton, and/or the carboxyl groups may lose protons. In sufficiently acid environments, the group gains a proton. At pH values between about 2.5 and 4.1, the carboxylic acid closer to the amine generally loses a proton, and the acid becomes the neutral zwitterion −OOC-CH-2-COOH. This is also the form of the compound in the solid state. The switchover is gradual, the two forms are in equal concentrations at pH2.10, at even higher pH, the other carboxyl loses its proton and the acid exists almost entirely as the glutamate anion −OOC-CH-2-COO−, with a single negative charge. The switchover occurs at pH4.07, the latter is the case, in particular, in the physiological pH range. At even higher pH, the group loses the extra proton. The switchover occurs at pH9.47, the carbon atom adjacent to the amino group is chiral, so glutamic acid can exist in two optical isomers, D and L. The L form is the one most widely occurring in nature, but the D form occurs in special contexts, such as the cell walls of the bacterium Escherichia coli. Although they occur naturally in foods, the flavor contributions made by glutamic acid
28.
Scotopic vision
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Scotopic vision is the vision of the eye under low light conditions. The term comes from Greek skotos meaning darkness and -opia meaning a condition of sight, scotopic vision is dominated by retina amacrine cells, specifically all-amacrine cells. AII-amacrine cells capture rod bipolar cell input and redistribute it to cone bipolar cells since rod-driven bipolar cells do not synapse on ganglion cells, scotopic vision occurs at luminance levels of 10−3 to 10−6 cd/m². Other species are not universally color blind in low-light conditions, the Elephant Hawk-moth displays advanced color discrimination even in dim starlight. Mesopic vision occurs in intermediate lighting conditions and is effectively a combination of scotopic and photopic vision and this however gives inaccurate visual acuity and color discrimination. In normal light, the vision of cone cells dominates and is photopic vision, there is good visual acuity and color discrimination. In scientific literature, one encounters the term scotopic lux which corresponds to photopic lux. The normal human observer’s relative wavelength sensitivity will not change due to background illumination change under scotopic vision, the wavelength sensitivity is determined by the rhodopsin photopigment. This is a red pigment and can be seen at the back of eye of animals that have a background to their eye called Tapetum lucidum. The pigment is not noticeable under photopic and mesopic conditions, the principle that the wavelength sensitivity does not change during scotopic vision led to the ability to detect two functional cone classes in individuals. If two cone classes are present, then their relative sensitivity will change the wavelength sensitivity. ”For adaption to occur at very low levels. This leads to the eye being unable to resolve high spatial frequencies in low light since the observer is spatially averaging the light signal. The behavior of the rhodopsin photopigment explains why the human eye cannot resolve lights with different spectral power distributions under low light, the reaction of this single photopigment will give the same quanta for 400 nm light and 700 nm light. Therefore, this photopigment only maps the rate of absorption and does not encode information about the spectral composition of the light. Another reason that vision is poor under scotopic vision is that rods and this many-to-one ratio leads to poor spatial frequency sensitivity. Photopic vision Mesopic vision Adaptation Averted vision Night vision Purkinje effect Rod cell Spatial frequency Marc, R. E. Anderson, J. R. Jones, B. W. Sigulinsky, C. L. Lauritzen, the AII amacrine cell connectome, A dense network hub
29.
Synaptic vesicle
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In a neuron, synaptic vesicles store various neurotransmitters that are released at the synapse. The release is regulated by a voltage-dependent calcium channel, Vesicles are essential for propagating nerve impulses between neurons and are constantly recreated by the cell. The area in the axon that holds groups of vesicles is a terminal or bouton. Up to 130 vesicles can be released per bouton over a period of stimulation at 0.2 Hz. In the human brain region V1 synaptic vesicles have a diameter of 39.5 nanometers with a standard deviation of 5.1 nanometers. With the advent of modern electron microscopic techniques in the early 1950s, the term synaptic vesicle was first introduced by De Robertis and Bennett in 1954. It was thus reasonable to hypothesize that the substance was contained in such vesicles. The missing link was the demonstration that the acetylcholine is actually contained in synaptic vesicles. Two competing laboratories were involved in work, that of Victor P. Both groups released synaptic vesicles from isolated synaptosomes by osmotic shock, the content of acetylcholine in a vesicle was originally estimated to be 1000–2000 molecules. Subsequent work identified the vesicular localization of other neurotransmitters, such as acids, catecholamines, serotonin. Later, synaptic vesicles could also be isolated from tissues such as the superior cervical ganglion. The isolation of highly purified fractions of cholinergic synaptic vesicles from the ray Torpedo electric organ was an important step forward in the study of vesicle biochemistry, Synaptic vesicles are relatively simple because only a limited number of proteins fit into a sphere of 40 nm diameter. The necessary proton gradient is created by V-ATPase, which breaks down ATP for energy, vesicular transporters move neurotransmitters from the cells cytoplasm into the synaptic vesicles. Vesicular glutamate transporters, for example, sequester glutamate into vesicles by this process and they include intrinsic membrane proteins, peripherally bound proteins, and proteins such as SNAREs. Many but not all of the synaptic vesicle proteins interact with non-vesicular proteins and are linked to specific functions. The stoichiometry for the movement of different neurotransmitters into a vesicle is given in the following table, recently, it has been discovered that synaptic vesicles also contain small RNA molecules, including transfer RNA fragments, Y RNA fragments and mirRNAs. This discovery is believed to have impact on studying chemical synapses
30.
Neurotransmitter
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Neurotransmitters, also known as chemical messengers, are endogenous chemicals that enable neurotransmission. They transmit signals across a synapse, such as a neuromuscular junction, from one neuron to another target neuron, muscle cell. Neurotransmitters are released from synaptic vesicles in synapses into the synaptic cleft, neurotransmitters play a major role in shaping everyday life and functions. Their exact numbers are unknown, but more than 100 chemical messengers have been uniquely identified, neurotransmitters are stored in a synapse in synaptic vesicles, clustered beneath the membrane in the axon terminal located at the presynaptic side of the synapse. Neurotransmitters are released into and diffused across the cleft, where they bind to specific receptors in the membrane on the postsynaptic side of the synapse. Most neurotransmitters are about the size of an amino acid, however. Nevertheless, short-term exposure of the receptor to a neurotransmitter is typically sufficient for causing a postsynaptic response by way of synaptic transmission, in response to a threshold action potential or graded electrical potential, a neurotransmitter is released at the presynaptic terminal. Low level baseline release also occurs without electrical stimulation, the released neurotransmitter may then move across the synapse to be detected by and bind with receptors in the postsynaptic neuron. Binding of neurotransmitters may influence the postsynaptic neuron in either an inhibitory or excitatory way and this neuron may be connected to many more neurons, and if the total of excitatory influences are greater than those of inhibitory influences, the neuron will also fire. Ultimately it will create a new action potential at its axon hillock to release neurotransmitters, until the early 20th century, scientists assumed that the majority of synaptic communication in the brain was electrical. However, through the careful histological examinations by Ramón y Cajal, upon completion of this experiment, Loewi asserted that sympathetic regulation of cardiac function can be mediated through changes in chemical concentrations. Furthermore, Otto Loewi is credited with discovering acetylcholine —the first known neurotransmitter, some neurons do, however, communicate via electrical synapses through the use of gap junctions, which allow specific ions to pass directly from one cell to another. There are four criteria for identifying neurotransmitters, The chemical must be synthesized in the neuron or otherwise be present in it. When the neuron is active, the chemical must be released, the same response must be obtained when the chemical is experimentally placed on the target. A mechanism must exist for removing the chemical from its site of activation after its work is done, have little or no effect on membrane voltage, but have a common carrying function such as changing the structure of the synapse. Communicate by sending messages that affect the release or reuptake of transmitters. Various techniques and experiments such as staining, stimulating, and collecting can be used to identify throughout the central nervous system. There are many different ways to classify neurotransmitters, dividing them into amino acids, peptides, and monoamines is sufficient for some classification purposes
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Chemical synapse
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Chemical synapses are biological junctions through which neurons signals can be exchanged to each other and to non-neuronal cells such as those in muscles or glands. Chemical synapses allow neurons to form circuits within the nervous system. They are crucial to the computations that underlie perception and thought. They allow the system to connect to and control other systems of the body. At a chemical synapse, one neuron releases neurotransmitter molecules into a space that is adjacent to another neuron. The neurotransmitters are kept within small sacs called vesicles, and are released into the synaptic cleft by exocytosis and these molecules then bind to receptors on the postsynaptic cells side of the synaptic cleft. The adult human brain is estimated to contain from 1014 to 5 ×1014 synapses, every cubic millimeter of cerebral cortex contains roughly a billion of them. The word synapse comes from synaptein, which Sir Charles Scott Sherrington and colleagues coined from the Greek syn-, chemical synapses are not the only type of biological synapse, electrical and immunological synapses also exist. Without a qualifier, however, synapse commonly means chemical synapse, synapses are functional connections between neurons, or between neurons and other types of cells. A typical neuron gives rise to several thousand synapses, although there are types that make far fewer. Most synapses connect axons to dendrites, but there are other types of connections, including axon-to-cell-body, axon-to-axon. Chemical synapses pass information directionally from a cell to a postsynaptic cell and are therefore asymmetric in structure. Synaptic vesicles are docked at the plasma membrane at regions called active zones. Immediately opposite is a region of the cell containing neurotransmitter receptors. Immediately behind the postsynaptic membrane is a complex of interlinked proteins called the postsynaptic density. Proteins in the PSD are involved in anchoring and trafficking neurotransmitter receptors, the receptors and PSDs are often found in specialized protrusions from the main dendritic shaft called dendritic spines. Synapses may be described as symmetric or asymmetric, when examined under an electron microscope, asymmetric synapses are characterized by rounded vesicles in the presynaptic cell, and a prominent postsynaptic density. Symmetric synapses in contrast have flattened or elongated vesicles, and do not contain a prominent postsynaptic density, the synaptic cleft is a gap between the pre- and postsynaptic cells that is about 20 nm wide
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Retina bipolar cell
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As a part of the retina, bipolar cells exist between photoreceptors and ganglion cells. They act, directly or indirectly, to transmit signals from the photoreceptors to the ganglion cells, Bipolar cells are so-named as they have a central body from which two sets of processes arise. They can synapse with either rods or cones, and they also accept synapses from horizontal cells, the bipolar cells then transmit the signals from the photoreceptors or the horizontal cells, and pass it on to the ganglion cells directly or indirectly. Unlike most neurons, bipolar cells communicate via graded potentials, rather than action potentials, Bipolar cells receive synaptic input from either rods or cones, or both rods and cones, though they are generally designated rod bipolar or cone bipolar cells. There are roughly 10 distinct forms of cone cells, however, only one rod bipolar cell. In the dark, a cell will release glutamate, which inhibits the ON bipolar cells. This causes the ON bipolar cell to lose its inhibition and become active, while the OFF bipolar cell loses its excitation, rod bipolar cells do not synapse directly on to ganglion cells. OFF bipolar cells synapse in the layer of the inner plexiform layer of the retina. Bipolar cells effectively transfer information from rods and cones to ganglion cells, the horizontal cells and the amacrine cells complicate matters somewhat. The horizontal cells introduce lateral inhibition and give rise to the center-surround inhibition which is apparent in retinal receptive fields, the amacrine cells also introduce lateral inhibition, however, its role is not yet well understood. The mechanism for producing the center of a bipolar cells receptive field is known, direct innervation of the photoreceptor cell above it. However, the mechanism for producing the monochromatic surround of the receptive field is under investigation. While it is known that an important cell in the process is the horizontal cell, amacrine cell Retinal ganglion cell Nicholls, John G. A. Robert Martin, Bruce G. Wallace, Paul A. Fuchs. The fundamental plan of the retina, Retinal bipolar cells at the US National Library of Medicine Medical Subject Headings Diagram at mcgill. ca NIF Search - Retinal Bipolar Cell via the Neuroscience Information Framework
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Metabotropic glutamate receptor 6
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Glutamate receptor, metabotropic 6, also known as GRM6, is a protein which in humans is encoded by the GRM6 gene. L-glutamate is the major excitatory neurotransmitter in the nervous system. Glutamatergic neurotransmission is involved in most aspects of brain function. Group I includes GRM1 and GRM5 and these receptors have shown to activate phospholipase C. Group II includes GRM2 and GRM3, while Group III includes GRM4, GRM6, GRM7, Group II and III receptors are linked to the inhibition of the cyclic AMP cascade but differ in their agonist selectivities. Metabotropic glutamate receptor This article incorporates text from the United States National Library of Medicine, which is in the public domain
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Visual phototransduction
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Visual phototransduction is the sensory transduction of the visual system. It is a process by which light is converted into signals in the rod cells, cone cells. This cycle was elucidated by George Wald for which he received the Nobel Prize in 1967. It is so called Walds Visual Cycle after him, the visual cycle is the biological conversion of a photon into an electrical signal in the retina. This process occurs via G-protein coupled receptors called opsins which contain the chromophore 11-cis retinal, 11-cis retinal is covalently linked to the opsin receptor via Schiff base forming retinylidene protein. Following isomerization and release from the protein, all-trans retinal is reduced to all-trans retinol. It is first esterified by lecithin retinol acyltransferase and then converted to 11-cis retinol by the isomerohydrolase RPE65, the isomerase activity of RPE65 has been shown, it is still uncertain whether it also acts as hydrolase. Finally, it is oxidized to 11-cis retinal before traveling back to the rod outer segment where it is conjugated to an opsin to form new. The photoreceptor cells involved in vision are the rods and cones and these cells contain a chromophore bound to cell membrane protein, opsin. Rods deal with low level and do not mediate color vision. Cones, on the hand, can code the color of an image through comparison of the outputs of the three different types of cones. Each cone type responds best to certain wavelengths, or colors, the three types of cones are L-cones, M-cones and S-cones that respond optimally to long wavelengths, medium wavelengths, and short wavelengths respectively. Humans have a visual system consisting of three unique systems, rods, mid and long-wavelength sensitive cones and short wavelength sensitive cones. To understand the behaviour to light intensities, it is necessary to understand the roles of different currents. There is an ongoing outward potassium current through nongated K+-selective channels and this outward current tends to hyperpolarize the photoreceptor at around -70 mV. There is also an inward sodium current carried by cGMP-gated sodium channels and this so-called dark current depolarizes the cell to around -40 mV. Note that this is significantly more depolarized than most other neurons, in photopic conditions, photoreceptors hyperpolarize to a potential of -60mV. It is this switching off that activates the cell and sends an excitatory signal down the neural pathway. In the dark, cGMP levels are high and keep cGMP-gated sodium channels open allowing a steady inward current and this dark current keeps the cell depolarized at about -40 mV
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Isomerization
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In chemistry isomerization is the process by which one molecule is transformed into another molecule which has exactly the same atoms, but the atoms have a different arrangement e. g. A-B-C → B-A-C. In some molecules and under conditions, isomerization occurs spontaneously. When the isomerization occurs intramolecularly it is considered a rearrangement reaction, an example of an organometallic isomerization is the production of decaphenylferrocene, from its linkage isomer. Isomerization in hydrocarbon cracking is usually employed in chemistry, where fuels, such as diesel or pentane. The straight- and branched-chain isomers in the mixture then have to be separated. Another industrial process is the isomerisation of n-butane into isobutane, trans-cis isomerism is where, in certain compounds, an interconversion of cis and trans isomers can be observed. For instance, with acid and with azobenzene, often by photoisomerization. g. Bullvalene, and valence isomerization, the isomerization of molecules which involve structural changes resulting only from a relocation of single and double bonds, if a dynamic equilibrium is established between the two isomers it is also referred to as valence tautomerism. In a cycloisomerization a cyclic compound is formed, isomerization reactions can also be found with specific aromatic hydrocarbons. The energy difference between two isomers is called isomerization energy
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Transducin
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Transducin is a protein naturally expressed in vertebrate retina rods and cones and it is very important in vertebrate phototransduction. It is a type of heterotrimeric G-protein with different α subunits in rod, light leads to conformational changes in rhodopsin, which in turn leads to the activation of transducin. Transducin activates phosphodiesterase, which results in the breakdown of cGMP, the intensity of the flash response is directly proportional to the number of transducin activated. Transducin is activated by metarhodopsin II, a change in rhodopsin caused by the absorption of a photon by the rhodopsin moiety retinal. The light causes isomerization of retinal from 11-cis to all-trans, isomerization causes a change in the opsin to become metarhodopsin II. When metarhodopsin activates transducin, the guanosine diphosphate bound to the α subunit is exchanged for guanosine triphosphate from the cytoplasm, decrease in cGMP concentration leads to decreased opening of cation channels and subsequently, hyperpolarization of the membrane potential. Transducin is deactivated when the α-subunit-bound GTP is hydrolyzed to GDP and this process is accelerated by a complex containing an RGS -protein and the gamma-subunit of the effector, cyclic GMP Phosphodiesterase. The Tα subunit of transducin contains three domains, one for rhodopsin/Tβγ interaction, one for GTP binding, and the last for activation of cGMP phosphodiesterase. Although the focus for phototransduction is on Tα, Tβγ is crucial for rhodopsin to bind to transducin, the rhodopsin/Tβγ binding domain contains the amino and carboxyl terminal of the Tα. The amino terminal is the site of interaction for rhodopsin while the terminal is that for Tβγ binding. The amino terminal might be anchored or in proximity to the carboxyl terminal for activation of the transducin molecule by rhodopsin. Interaction with photolyzed rhodopsin opens up the GTP-binding site to allow for exchange of GDP for GTP. The binding site is in the conformation in the absence of photolyzed rhodopsin. Normally in the conformation, an α-helix located near the binding site is in a position which hinders the GTP/GDP exchange. A conformational change of the Tα by photolyzed rhodopsin causes the tilting of the helix, the conformational changes initiated in the transducin by binding of GTP are transmitted to the PDE binding site and cause it to be exposed for binding to PDE. The GTP-induced conformational changes could also disrupt the binding site. An underlying assumption for G-proteins is that α, β, and γ subunits are present in the same concentration, however, there is evidence that there are more Tβ and Tγ than Tα in rod outer segments. The excess Tβ and Tγ have been concluded to be floating freely around in the ROS, one possible explanation for the excess Tβγ is increased availability for Tα to rebind
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Phosphodiesterase
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A phosphodiesterase is an enzyme that breaks a phosphodiester bond. Usually, phosphodiesterase refers to cyclic nucleotide phosphodiesterases, which have great significance and are described below. The cyclic nucleotide phosphodiesterases comprise a group of enzymes that degrade the bond in the second messenger molecules cAMP and cGMP. They regulate the localization, duration, and amplitude of cyclic nucleotide signaling within subcellular domains, pDEs are therefore important regulators of signal transduction mediated by these second messenger molecules. The potential for selective phosphodiesterase inhibitors to be used as agents was predicted in the 1970s. This prediction has now come to pass in a variety of fields, the superfamily of PDE enzymes is classified into 12 families, namely PDE1-PDE12, in mammals. Some are cAMP-selective hydrolases, others are cGMP-selective, others can hydrolyse both cAMP and cGMP. PDE3 is sometimes referred to as cGMP-inhibited phosphodiesterase, although PDE2 can hydrolyze both cyclic nucleotides, binding of cGMP to the regulatory GAF-B domain will increase cAMP affinity and hydrolysis to the detriment of cGMP. This mechanism, as well as others, allows for cross-regulation of the cAMP and cGMP pathways, phosphodiesterase enzymes are often targets for pharmacological inhibition due to their unique tissue distribution, structural properties, and functional properties. Inhibitors of PDE can prolong or enhance the effects of physiological processes mediated by cAMP or cGMP by inhibition of their degradation by PDE. Sildenafil is an inhibitor of cGMP-specific phosphodiesterase type 5, which enhances the effects of cGMP in the corpus cavernosum and is used to treat erectile dysfunction. PDE also are important in seizure incidence, for example, PDE compromised the antiepileptic activity of adenosine. This inhibition allows red blood cells to be able to bend. This is useful in such as intermittent claudication, as the cells can maneuver through constricted veins. Xanthines such as caffeine and theobromine are cAMP-phosphodiesterase inhibitors, however, the inhibitory effect of xanthines on phosphodiesterases are only seen at dosages higher than what people normally consume. Phosphoric Diester Hydrolases at the US National Library of Medicine Medical Subject Headings
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Adaptation (eye)
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In ocular physiology, adaptation is the ability of the eye to adjust to various levels of darkness and light. The human eye can function from very dark to very bright levels of light and this means that the brightest and the darkest light signal that the eye can sense are a factor of roughly 1,000,000,000 apart. However, in any moment of time, the eye can only sense a contrast ratio of 1,000. What enables the wider reach is that the eye adapts its definition of what is black, the eye takes approximately 20–30 minutes to fully adapt from bright sunlight to complete darkness and become 10,000 to 1,000,000 times more sensitive than at full daylight. In this process, the perception of color changes as well. However, it approximately five minutes for the eye to adapt from darkness to bright sunlight. This is due to obtaining more sensitivity when first entering the dark for the first five minutes. Dark adaptation is far quicker and deeper in young people than the elderly, a minor mechanism of adaptation is the pupillary light reflex, adjusting the amount of light that reaches the retina. In response to varying ambient light levels, rods and cones of eye function both in isolation and in tandem to adjust the visual system, changes in the sensitivity of rods and cones in the eye are the major contributors to dark adaptation. Above a certain level, the cone mechanism is involved in mediating vision. Below this level, the rod mechanism comes into play providing scotopic vision, the range where two mechanisms are working together is called the mesopic range, as there is not an abrupt transition between the two mechanism. This adaptation forms the basis of the Duplicity Theory, Rhodopsin, a biological pigment in the photoreceptors of the retina, immediately photobleaches in response to light. Rods are more sensitive to light and so take longer to adapt to the change in light. Rods, whose photopigments regenerate more slowly, do not reach their maximum sensitivity for about half an hour, cones take approximately 9–10 minutes to adapt to the dark. Sensitivity to light is modulated by changes in intracellular calcium ions, the sensitivity of the rod pathway improves considerably within 5–10 minutes in the dark. Color testing has been used to determine the time at which rod mechanism takes over, in addition the absolute threshold takes longer to reach. The opposite is true for decreasing the levels of pre-adapting luminances, size and location on the retina The location of the test spot affects the dark adaptation curve because of the distribution of the rods and cones in the retina. Wavelength of the threshold light Varying the wavelengths of stimuli also affect the dark adaptation curve, long wavelengths, such as extreme red, create the absence of a distinct rod/cone break as the rod and cone cells have similar sensitivities to light of long wavelengths
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Recoverin
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Recoverin is a 23 kilodalton neuronal calcium-binding protein that is primarily detected in the photoreceptor cells of the eye. It plays a key role in the inhibition of rhodopsin kinase, recoverin is involved in the recovery phase of visual excitation and in adaptation to background light. It controls the life span of photoexcited rhodopsin by helping to inhibit rhodopsin kinase, an image of bovine recoverin with 3.00 Å resolution is shown. This three-dimensional structure was determined by X-ray diffraction, covalently attached at the amino-terminal of recoverin is a myristoyl group. When recoverin is not bound to calcium, it stays in cytosol, when recoverin binds calcium, it migrates to the disc membrane and is embedded into the membrane using the myristoyl group to anchor itself. This calcium-bound form of recoverin slows the activity of rhodopsin kinase, recent publications point out additional functions for recoverin. For instance, it goes through a light-dependent intracellular translocation to rod synaptic terminals, in humans, the recoverin protein is encoded by the RCVRN gene. Recoverin at the US National Library of Medicine Medical Subject Headings
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Arrestin
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Arrestins are a small family of proteins important for regulating signal transduction at G protein-coupled receptors. In response to a stimulus, GPCRs activate heterotrimeric G proteins, in order to turn off this response, or adapt to a persistent stimulus, active receptors need to be desensitized. The first step is phosphorylation by a class of serine/threonine kinases called G protein coupled receptor kinases, GRK phosphorylation specifically prepares the activated receptor for arrestin binding. In addition to GPCRs, arrestins bind to other classes of surface receptors. Mammals express four arrestin subtypes and each arrestin subtype is known by multiple aliases and it was later renamed visual arrestin, but when another cone-specific visual subtype was cloned the term rod arrestin was coined. This also turned out to be a misnomer, arrestin-1 expresses at comparable very high levels in both rod and cone photoreceptor cells, arrestin-2 was the first non-visual arrestin cloned. It was first named β-arrestin simply because between two GPCRs available in purified form at the time, rhodopsin and β2-adrenergic receptor, it showed preference for the latter, systematic names, arrestin-2 and arrestin-3, respectively, were proposed soon after that. Arrestin-4 was cloned by two groups and termed cone arrestin, after photoreceptor type that expresses it, and X-arrestin, in the HUGO database its gene is called arrestin-3. Fish and other vertebrates appear to have only three arrestins, no equivalent of arrestin-2, which is the most abundant non-visual subtype in mammals, was cloned so far. The proto-chordate C. intestinalis has only one arrestin, which serves as visual in its mobile larva with highly developed eyes, conserved positions of multiple introns in its gene and those of our arrestin subtypes suggest that they all evolved from this ancestral arrestin. Lower invertebrates, such as roundworm C. elegans, also have only one arrestin, insects have arr1 and arr2, originally termed “visual arrestins” because they are expressed in photoreceptors, and one non-visual subtype. Later arr1 and arr2 were found to play an important role in olfactory neurons, fungi have distant arrestin relatives involved in pH sensing. One or more arrestin is expressed in every eukaryotic cell. In mammals, arrestin-1 and arrestin-4 are largely confined to photoreceptors, whereas arrestin-2, neurons have the highest expression level of both non-visual subtypes. In neuronal precursors both are expressed at levels, whereas in mature neurons arrestin-2 is present at 10-20 fold higher levels than arrestin-3. Arrestins block GPCR coupling to G proteins in two ways, first, arrestin binding to the cytoplasmic face of the receptor occludes the binding site for heterotrimeric G-protein, preventing its activation. Subsequently, the receptor could be directed to degradation compartments or recycled back to the plasma membrane where it can again signal. Arrestins are elongated molecules, in which several intra-molecular interactions hold the relative orientation of the two domains, in unstimulated cell arrestins are localized in the cytoplasm in this basal “inactive” conformation
