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Neuromuscular blocking drugs are often classified into two broad classes: *Pachycurares, which are bulky molecules with nondepolarizing activity *Leptocurares, which are thin and flexible molecules that tend to have depolarizing activity. It is also common to classify them based on their chemical structure. *Acetylcholine, suxamethonium, and decamethonium Suxamethonium was synthesised by connecting two acetylcholine molecules and has the same number of heavy atoms between methonium heads as decamethonium. Just like acetylcholine, succinylcholine, decamethonium and other polymethylene chains, of the appropriate length and with two methonium, heads have small trimethyl onium heads and flexible links. They all exhibit a depolarizing block. * Aminosteroids Pancuronium, vecuronium, rocuronium, rapacuronium, dacuronium, malouètine, dihydrochandonium, dipyrandium, pipecuronium, chandonium (HS-310), HS-342 and other HS- compounds are aminosteroidal agents. They have in common the steroid structural base, which provides a rigid and bulky body. Most of the agents in this category would also be classified as non-depolarizing. * Tetrahydroisoquinoline derivatives Compounds based on the tetrahydroisoquinoline moiety such as atracurium, mivacurium, and doxacurium would fall in this category. They have a long and flexible chain between the onium heads, except for the double bond of mivacurium. D-tubocurarine and dimethyltubocurarine are also in this category. Most of the agents in this category would be classified as non-depolarizing. * Gallamine and other chemical classes Gallamine is a trisquaternary ether with three ethonium heads attached to a phenyl ring through an ether linkage. Many other different structures have been used for their muscle relaxant effect such as alcuronium (alloferin), anatruxonium, diadonium, fazadinium (AH8165) and tropeinium. *Novel NMB agents In recent years much research has been devoted to new types of quaternary ammonium muscle relaxants. These are asymmetrical diester isoquinolinium compounds and bis-benzyltropinium compounds that are bistropinium salts of various diacids. These classes have been developed to create muscle relaxants that are faster and shorter acting. Both the asymmetric structure of diester isoquinolinium compounds and the acyloxylated benzyl groups on the bisbenzyltropiniums destabilizes them and can lead to spontaneous breakdown and therefore possibly a shorter duration of action.

Neurochemistry

Some ion channels are classified by the duration of their response to stimuli: *Transient receptor potential channels: This group of channels, normally referred to simply as TRP channels, is named after their role in Drosophila visual phototransduction. This family, containing at least 28 members, is diverse in its mechanisms of activation. Some TRP channels remain constitutively open, while others are gated by voltage, intracellular Ca, pH, redox state, osmolarity, and mechanical stretch. These channels also vary according to the ion(s) they pass, some being selective for Ca while others are less selective cation channels. This family is subdivided into 6 subfamilies based on homology: canonical TRP (TRPC), vanilloid receptors (TRPV), melastatin (TRPM), polycystins (TRPP), mucolipins (TRPML), and ankyrin transmembrane protein 1 (TRPA).

Neurochemistry

Coelenterazine can be crystallized into orange-yellow crystals. The molecule absorbs light in the ultraviolet and visible spectrum, with peak absorption at 435 nm in methanol, giving the molecule a yellow color. The molecule spontaneously oxidizes in aerobic conditions or in some organic solvents such as dimethylformamide and DMSO and is preferentially stored in methanol or with an inert gas.

Bioluminescence

* AM404 – an active metabolite of paracetamol. * AM1172 * LY-2183240 * O-2093 * OMDM-2 * UCM-707 * VDM-11 * Guineensine *WOBE437 and RX-055

Neurochemistry

Traumatic brain injury is defined as a “direct physical impact or trauma to the head followed by a dynamic series of injury and repair events”. Recently, neuroproteomics have been applied to studying the disability that over 5.4 million Americans live with. In addition to physically injuring the brain tissue, traumatic brain injury induces the release of glutamate that interacts with ionotropic glutamate receptors (iGluRs). These glutamate receptors acidify the surrounding intracranial fluid, causing further injury on the molecular level to nearby neurons. The death of the surrounding neurons is induced through normal apoptosis mechanisms, and it is this cycle that is being studied with neuroproteomics. Three different cysteine protease derivatives are involved in the apoptotic pathway induced by the acidic environment triggered by glutamate. These cysteine proteases include calpain, caspase, and cathepsin. These three proteins are examples of detectable signs of traumatic brain injury that are much more specific than temperature, oxygen level, or intracranial pressure. Proteomics thus also offers a tracking mechanism by which researchers can monitor the progression of traumatic brain injury, or a chronic disease such as Alzheimer’s or Parkinson’s. Especially in Parkinson’s, in which neurotransmitters play a large role, recent proteomic research has involved the study of synaptotagmin. Synaptotagmin is involved in the calcium-induced budding of vesicle containing neurotransmitters from the presynaptic membrane. By studying the intracellular mechanisms involved in neural apoptosis after traumatic brain injury, researchers can create a map that genetic changes can follow later on.

Neurochemistry

The first type of photocyte granule has been found to contain between two and twelve microtubules. In addition, the matrix of the type I granule lacks a uniform shape or structure with ferritin distributed throughout.

Bioluminescence

Bioluminescence is produced by the dinoflagellate Pyrodinium bahamense, which glows blue when agitated. Although the phytoplankton responsible for the phenomenon of bioluminescence is found throughout the Antilles, Puerto Mosquito is one of the seven year-round bioluminescent bays in the Caribbean. The bioluminescence is the product of a number of factors: the water conditions and ecosystem created by the surrounding mangrove forest (mostly Rhizophora mangle), the complete lack of modern development in the lagoon, the temperature of the water and the depth of the bay.

Bioluminescence

Fish generally use bioluminescence for camouflage to hide from predators. Endogenous photocytes are more commonly used for bioluminescence than other means like bacteria. Some fish may use the bioluminescence produced by their photocytes as a means of communication.

Bioluminescence

*Chloride channels: This superfamily of channels consists of approximately 13 members. They include ClCs, CLICs, Bestrophins and CFTRs. These channels are non-selective for small anions; however chloride is the most abundant anion, and hence they are known as chloride channels. *Potassium channels **Voltage-gated potassium channels e.g., Kvs, Kirs etc. **Calcium-activated potassium channels e.g., BKCa or MaxiK, SK, etc. **Inward-rectifier potassium channels **Two-pore-domain potassium channels: This family of 15 members form what is known as leak channels, and they display Goldman-Hodgkin-Katz (open) rectification. *Sodium channels ** Voltage-gated sodium channels (NaVs) ** Epithelial sodium channels (ENaCs) *Calcium channels (CaVs) *Proton channels **Voltage-gated proton channels *Non-selective cation channels: These non-selectively allow many types of cations, mainly Na, K and Ca, through the channel. **Most transient receptor potential channels

Neurochemistry

The dysfunction of potassium channels, including SK channels, is thought to play a role in the pathogenesis of Parkinson's disease (PD), a progressive neurodegenerative disorder. SK channel blockers control the firing rate (the number of action potentials produced by a neuron in a given time) and the firing pattern (the way action potentials are allocated throughout time) through their production of m-AHP. SK channel activators decrease the firing rate, neuron sensitivity to excitatory stimuli, mediating neuroprotection, whereas SK channel blockers increase the firing rate and sensitivity to excitatory stimuli. This has important implications as to the function of dopaminergic neurons. For example, the amount of dopamine released by midbrain dopaminergic neurons is much higher when the frequency of firing increases than when they fire at a constant rate. SK channels are widely expressed in midbrain dopaminergic neurons. Multiple pharmacological techniques have been used to adjust SK affinity for calcium ions, thereby modulating the excitability of substantia nigra dopaminergic neurons. Blockage of SK channels in vivo increases the firing rate of substantia nigra cells, which increases the amount of dopamine released from the synaptic terminals. When a large amount of dopamine accumulates in the cytosol, cell damage is induced due to the build-up of free radicals and damage to mitochondria. In addition, techniques have been used to modulate SK channels in order to alter the dopamine phenotype of neurons. After the loss of TH+ (tyrosine hydroxylase-positive) substantia nigra compacta (SNc) neurons due to Parkinson’s-induced neurodegeneration, the number of these neurons can partially recover via a cell phenotype "shift" from TH- (tyrosine hydroxylase-negative) to TH+. The number of TH+ neurons can be altered by SK channel modulation; to be specific, the infusion of SK agonists into substantia nigra increases the number of TH+ neurons, whereas the infusion of SK antagonist decreases the number of TH+ neurons. The reason for this relationship between SK channels and TH expression may be due to neuroprotection against dopamine toxicity. Two contradictory methods have been suggested as therapeutic options for the improvement of PD symptoms: Inhibition of SK channels *Inhibition of SK channels, to be specific the blockage of SK3 channels, increases the frequency of firing in dopaminergic neurons, thereby increasing the release of dopamine. It is, therefore, thought that the application of SK3 channels blockers in PD patients may alleviate short-term motor symptoms. *However, inhibition also results in a decreased number of TH+ substantia nigra compacta (SNc) neurons in the cell, which results in a decrease in dopamine synthesis over the long term. Facilitation of SK channels *Enhancing the function of SK channels increases the number of TH+ substantia nigra compacta (SNc) neurons in the cell, thereby maintaining dopamine synthesis over the long term. *However, the facilitation of SK channels decreases the firing frequency in dopaminergic neurons over the short term.

Neurochemistry

Patients receiving chronic treatment are relatively resistance to nondepolarising NMBAs due to the accelerated clearance.

Neurochemistry

K2.3 is found in the central nervous system (CNS), muscle, liver, pituitary, prostate, kidney, pancreas and vascular endothelium tissues. K2.3 is most abundant in regions of the brain, but has also been found to be expressed in significant levels in many other peripheral tissues, particularly those rich in smooth muscle, including the rectum, corpus cavernosum, colon, small intestine and myometrium. The expression level of KCNN3 is dependent on hormonal regulation, particularly by the sex hormone estrogen. Estrogen not only enhances transcription of the KCNN3 gene, but also affects the activity of K2.3 channels on the cell membrane. In GABAergic preoptic area neurons, estrogen enhanced the ability of α1 adrenergic receptors to inhibit K2.3 activity, increasing cell excitability. Links between hormonal regulation of sex organ function and K2.3 expression have been established. The expression of K2.3 in the corpus cavernosum in patients undergoing estrogen treatment as part of gender reassignment surgery was found to be increased up to 5-fold. The influence of estrogen on K2.3 has also been established in the hypothalamus, uterine and skeletal muscle.

Neurochemistry

The phenomenon is known as mareel in Shetland. This term is derived from the Norn word *mareld, which is itself derived from the Old Norse word mǫrueldr, which is a compound of marr (mere, sea) and eldr (fire). In the Somali language it is called “Kaluunka Iftiima”. The term translates to glowing sea creatures or glowing fish as the word Kaluun refers to any bio organism that lives in the sea. It is most commonly used to refer to fish.

Bioluminescence

Apoaequorin is an ingredient in "Prevagen", which is marketed by Quincy Bioscience as a memory supplement. In 2017, the US Federal Trade Commission (FTC) charged the maker with falsely advertising that the product improves memory, provides cognitive benefits, and is "clinically shown" to work. According to the FTC, "the marketers of Prevagen preyed on the fears of older consumers experiencing age-related memory loss". Quincy said that it would fight the charges. Prior to the suit, a clinical trial run by researchers employed by Quincy Bioscience "found no overall benefit compared to a placebo for its primary endpoints involving memory and cognition", while the company's advertising misleadingly cited a few contested subgroup analyses that showed slight improvements. The suit (Spath, et al. v. Quincy Bioscience Holding Company, Inc., et al., Case No. 18-cv-12416, D. NJ.) was dismissed in the District court, but an appeal seeking to overturn the dismissal was filed. The suit was consolidated with another against Quincy Pharmaceuticals, Vanderwerff v. Quincy Bioscience (Case No. 17-cv-784, D. NJ), which was the lead case. On February 21, 2019, the United States Court of Appeals for the Second Circuit ruled that the FTC and the state of New York could proceed with their lawsuit against Quincy Bioscience for its claims that Prevagen can improve memory. The order came less than two weeks after the parties argued the case before a three-judge panel of the circuit, where company lawyers admitted they did not "dispute that if you look across the entire 211 people who completed the study there was no statistically significant difference". The court vigorously dismissed allegations by the company lawyers that the FTC pursued its action for political reasons. On March 23, 2020, a federal magistrate judge in the United States District Court for the Southern District of Florida entered a report and recommendations certifying a nationwide class action for the class of consumers who purchased Prevagen over the previous four years. The trial in the case was set for October 2020. Quincy Bioscience agreed to settle the claims that it misrepresented its Prevagen products as supporting brain health and helping with memory loss. Under the terms of the settlement, eligible purchasers applying by October 26, 2020 for purchases made from 2007 through July 31, 2020 could recover refunds of up to $70. Dr. Harriet Hall, writing for Science-Based Medicine, noted that the Quincy-sponsored study (known as "Madison Memory Study") was negative, but that the company utilized p-hacking to find favorable results. She wrote that their cited safety studies were all rat studies and their claim that apoaequorin crosses the blood–brain barrier was based solely on a dog study. The American Pharmacists Association warns that Apoaequorin "is unlikely to be absorbed to a significant degree; instead it degrades into amino acids".

Bioluminescence

Vargulin is oxidized by the Vargula luciferase, a 62 kDa enzyme, to produce blue light at 462 nm (max emission, detected with a 425 to 525 nm filter). The vargulin does not cross react with luciferases using coelenterazine or Firefly luciferin.

Bioluminescence

The channelosome (not to be confused with "channelome") is the collection of (usually) signalling proteins associated with an ion channel. The channelosome is frequently clustered within a lipid microdomain or caveolae. This collection of proteins may be involved with anchoring, phosphorylation or some other modulatory or support function. An example is neural KCNQ/M (Kv7) potassium channelosome (see Delmas & Brown, 2005).

Neurochemistry

Lithium is structurally similar to other cations such as sodium, potassium, magnesium and calcium, this causes lithium to activate potassium channels which inhibit neuromuscular transmission. Patients who take lithium can have a prolonged response to both depolarising and nondepolarising NMBAs.

Neurochemistry

SK channels (small conductance calcium-activated potassium channels) are a subfamily of calcium-activated potassium channels. They are so called because of their small single channel conductance in the order of 10 pS. SK channels are a type of ion channel allowing potassium cations to cross the cell membrane and are activated (opened) by an increase in the concentration of intracellular calcium through N-type calcium channels. Their activation limits the firing frequency of action potentials and is important for regulating afterhyperpolarization in the neurons of the central nervous system as well as many other types of electrically excitable cells. This is accomplished through the hyperpolarizing leak of positively charged potassium ions along their concentration gradient into the extracellular space. This hyperpolarization causes the membrane potential to become more negative. SK channels are thought to be involved in synaptic plasticity and therefore play important roles in learning and memory.

Neurochemistry

All bacterial luciferases are approximately 80 KDa heterodimers containing two subunits: α and β. The α subunit is responsible for light emission. The luxA and luxB genes encode for the α and β subunits, respectively. In most bioluminescent bacteria, the luxA and luxB genes are flanked upstream by luxC and luxD and downstream by luxE. The bioluminescent reaction is as follows: FMNH + O + R-CHO -> FMN + HO + R-COOH + Light (~ 495 nm) Molecular oxygen reacts with FMNH (reduced flavin mononucleotide) and a long-chain aldehyde to produce FMN (flavin mononucleotide), water and a corresponding fatty acid. The blue-green light emission of bioluminescence, such as that produced by Photobacterium phosphoreum and Vibro harveyi, results from this reaction. Because light emission involves expending six ATP molecules for each photon, it is an energetically expensive process. For this reason, light emission is not constitutively expressed in bioluminescent bacteria; it is expressed only when physiologically necessary.

Bioluminescence

Dinoflagellate luciferin is a chlorophyll derivative (i. e. a tetrapyrrole) and is found in some dinoflagellates, which are often responsible for the phenomenon of nighttime glowing waves (historically this was called phosphorescence, but is a misleading term). A very similar type of luciferin is found in some types of euphausiid shrimp.

Bioluminescence

Records of bioluminescence due to bacteria have existed for thousands of years. They appear in the folklore of many regions, including Scandinavia and the Indian subcontinent. Both Aristotle and Charles Darwin have described the phenomenon of the oceans glowing. Since its discovery less than 30 years ago, the enzyme luciferase and its regulatory gene, lux, have led to major advances in molecular biology, through use as a reporter gene. Luciferase was first purified by McElroy and Green in 1955. It was later discovered that there were two subunits to luciferase, called subunits α and β. The genes encoding these enzymes, luxA and luxB, respectively, were first isolated in the lux operon of Aliivibrio fisheri.

Bioluminescence

It has been concluded that acetylcholine and related compounds must be in the gauche (bent) configuration when bound to the nicotinic receptor. Beers and Reich's studies on cholinergic receptors in 1970 showed a relationship affecting whether a compound was muscarinic or nicotinic. They showed that the distance from the centre of the quaternary N atom to the van der Waals extension of the respective O atom (or an equivalent H-bond acceptor) is a determining factor. If the distance is 0.44 nm, the compound shows muscarinic properties—and if the distance is 0.59 nm, nicotinic properties dominate.)

Neurochemistry

The main advantage of FbFPs over GFP is their independence of molecular oxygen. Since all GFP derivatives and homologues require molecular oxygen for the maturation of their chromophore, these fluorescent proteins are of limited use under anaerobic or hypoxic conditions. Since FbFPs bind FMN as chromophore, which is synthesized independently of molecular oxygen, their fluorescence signal does not differ between aerobic and anaerobic conditions.<br /> Another advantage is the small size of FbFPs, which is typically between 100 and 150 amino acids. This is about half the size of GFP (238 amino acids). It could for example be shown that this renders them superior tags for monitoring tobacco mosaic virus infections in tobacco leaves.<br /> Due to their extraordinary long average fluorescence lifetime of up to 5.7 ns they are also very well suited for the use as donor domains in FRET systems in conjunction with e.g. YFP (see photophysical properties). A fusion of EcFbFP and YFP was e.g. used to develop the first genetically encoded fluorescence biosensor for oxygen (FluBO) The main disadvantage compared to GFP variants is their lower brightness (the product of ε and Φ). The commonly used EGFP (ε = 55,000 Mcm; Φ = 0.60 ) for example is approximately five times as bright as EcFbFP.<br /> Another disadvantage of the FbFPs is the lack of color variants to tag and distinguish multiple proteins in a single cell or tissue. The largest spectral shift reported for FbFPs so far is 10 nm. Although this variant (Pp2FbFP Q116V) can be visually distinguished from the others with the human eye, the spectral differences are too small for fluorescence microscopy filters.

Bioluminescence

The endocannabinoid system, broadly speaking, includes: * The endogenous arachidonate-based lipids, anandamide (N-arachidonoylethanolamide) and 2-AG, besides other N-acylethanolamines (NAEs); these are known as "endocannabinoids" and are physiological ligands for the cannabinoid receptors. Endocannabinoids are all eicosanoids. * The enzymes that synthesize and degrade the endocannabinoids, such as fatty acid amide hydrolase or monoacylglycerol lipase. * The cannabinoid receptors CB and CB, two G protein-coupled receptors that are located in the central and peripheral nervous systems. The neurons, neural pathways, and other cells where these molecules, enzymes, and one or both cannabinoid receptor types are all colocalized collectively comprise the endocannabinoid system. The endocannabinoid system has been studied using genetic and pharmacological methods. These studies have revealed that cannabinoids act as neuromodulators for a variety of processes, including motor learning, appetite, and pain sensation, among other cognitive and physical processes. The localization of the CB1 receptor in the endocannabinoid system has a very large degree of overlap with the orexinergic projection system, which mediates many of the same functions, both physical and cognitive. Moreover, CB1 is colocalized on orexin projection neurons in the lateral hypothalamus and many output structures of the orexin system, where the CB1 and orexin receptor 1 (OX1) receptors physically and functionally join to form the CB1–OX1 receptor heterodimer.

Neurochemistry

Allosteric modulators of small SK channels work by changing the apparent calcium sensitivity of the channels. Examples include: * Riluzole * Non-selective positive modulators of SK channels: EBIO (1-Ethyl-2-BenzimIdazolinOne), NS309 (6,7-dichloro-1H-indole-2,3-dione 3-oxime) * SK-2 and SK-3 selective positive modulators : CyPPA (NS6277; Cyclohexyl-(2-(3,5-dimethyl-Pyrazol-1-yl)-6-methyl-Pyrimidin-4-yl)-Amine) <br />

Neurochemistry

While the secretion of glucocorticoids in response to stressful stimuli is an adaptive response necessary for an organism to respond appropriately to a stressor, persistent secretion may be harmful. The endocannabinoid system has been implicated in the habituation of the hypothalamic-pituitary-adrenal axis (HPA axis) to repeated exposure to restraint stress. Studies have demonstrated differential synthesis of anandamide and 2-AG during tonic stress. A decrease of anandamide was found along the axis that contributed to basal hypersecretion of corticosterone; in contrast, an increase of 2-AG was found in the amygdala after repeated stress, which was negatively correlated to magnitude of the corticosterone response. All effects were abolished by the CB antagonist AM251, supporting the conclusion that these effects were cannabinoid-receptor dependent. These findings show that anandamide and 2-AG divergently regulate the HPA axis response to stress: while habituation of the stress-induced HPA axis via 2-AG prevents excessive secretion of glucocorticoids to non-threatening stimuli, the increase of basal corticosterone secretion resulting from decreased anandamide allows for a facilitated response of the HPA axis to novel stimuli.

Neurochemistry

The helicoradian (Loreyu in Navi) is a carnivorous plant that has red spiral-leaves. The plants are up to tall and, when touched, instantly curl and collapse into themselves. They are zooplantae, part animal, part plant. They are first seen when Jake wanders off into a forest of helicoradia and touches multiple leaves, at which they retract and coil up to reveal a hammerhead titanothere behind. According to Avatar designer Craig Shoji, the behavior and design of the helicoradian' was based on the Christmas tree worms, tube worms that reside on coral reefs. In the video games, the species has the ability to heal the player.

Bioluminescence

In the 1920s, the Russian embryologist Alexander Gurwitsch reported "ultraweak" photon emissions from living tissues in the UV-range of the spectrum. He named them "mitogenetic rays" because his experiments convinced him that they had a stimulating effect on cell division. In the 1970s Fritz-Albert Popp and his research group at the University of Marburg (Germany) showed that the spectral distribution of the emission fell over a wide range of wavelengths, from 200 to 750 nm. Popps work on the biophoton emissions statistical properties, namely the claims on its coherence, was criticised for lack of scientific rigour. One biophoton mechanism focuses on injured cells that are under higher levels of oxidative stress, which is one source of light, and can be deemed to constitute a "distress signal" or background chemical process, but this mechanism is yet to be demonstrated. The difficulty of teasing out the effects of any supposed biophotons amid the other numerous chemical interactions between cells makes it difficult to devise a testable hypothesis. A 2010 review article discusses various published theories on this kind of signaling. The hypothesis of cellular communication by biophotons was highly criticised for failing to explain how could cells detect photonic signals several orders of magnitude weaker than the natural background illumination.

Bioluminescence

Mice treated with tetrahydrocannabinol (THC) show suppression of long-term potentiation in the hippocampus, a process that is essential for the formation and storage of long-term memory. These results may concur with anecdotal evidence suggesting that smoking cannabis impairs short-term memory. Consistent with this finding, mice without the CB receptor show enhanced memory and long-term potentiation indicating that the endocannabinoid system may play a pivotal role in the extinction of old memories. One study found that the high-dose treatment of rats with the synthetic cannabinoid HU-210 over several weeks resulted in stimulation of neural growth in the rats' hippocampus region, a part of the limbic system playing a part in the formation of declarative and spatial memories, but did not investigate the effects on short-term or long-term memory. Taken together, these findings suggest that the effects of endocannabinoids on the various brain networks involved in learning and memory may vary.

Neurochemistry

The photocyte of Arachnocampa luminosa was found to contain a circular nucleus, and large amounts of ribosomes, smooth endoplasmic reticulum, mitochondria, and microtubules. Instead of having photocyte granules, the photocytes of the organism were shown to undergo the luciferase reaction in their cytoplasm. The cells do not have a golgi apparatus or rough endoplasmic reticulum and were found to be 250 micrometers by 120 micrometers overall with a depth of 25 to 30 micrometers.

Bioluminescence

The term photoprotein was first used to describe the unusual chemistry of the luminescent system of Chaetopterus (a marine Polychaete worm). This was meant to distinguish them from other light-producing proteins because these do not exhibit the usual luciferin-luciferase reaction.

Bioluminescence

This study examined the clinical history of the CSF and urine of two Greek siblings who were both diagnosed with SR deficiency. Both siblings displayed delayed psychomotor development and a movement disorder. The diagnosis was confirmed by measuring the SR enzyme activity and mutation analysis. The mutation analysis of the gene was performed using genomic DNA isolated from blood samples. The results concluded that both patients have low concentrations of HVA and HIAA and high concentrations of sepiapterin in the CSF, but neopterin and biopterin were abnormal in only one sibling. The results of this research indicates that when diagnosing the SR deficiency, the quantification of sepiapterin in the CSF is more important and indicative of SR deficiency than using neopterin and biopterin alone. The results also show that the urine concentrations of neurotransmitter metabolites are abnormal in patients with this disorder. This finding may provide an initial and easier indication of the deficiency before CSF analysis is performed.

Neurochemistry

One group of researchers applied the field of neuroproteomics to examine how different proteins affect the initial growth of neuritis. The experiment compared the protein activity of control neurons with the activity of neurons treated with nerve growth factor (NGF) and JNJ460, an “immunophilin ligand.” JNJ460 is an offspring of another drug that is used to prevent immune attack when organs are transplanted. It is not an immunosuppressant, however, but rather it acts as a shield against microglia. NGF promotes neuron viability and differentiation by binding to TrkA, a tyrosine receptor kinase. This receptor is important in initiating intracellular metabolic pathways, including Ras, Rak, and MAP kinase. Protein differentiation was measured in each cell sample with and without treatment by NGF and JNJ460. A peptide mixture was made by washing off unbound portions of the amino acid sequence in a reverse column. The resulting mixture was then suspended a peptide mixture in a bath of cation exchange fluid. The proteins were identified by splicing them with trypsin and then searching through the results of passing the product through a mass spectrometer. This applies a form of liquid chromatography mass spectrometry to identify proteins in the mixture JNJ460 treatment resulted in an increase in “signal transduction” proteins, while NGF resulted in an increase in proteins associated with the ribosome and synthesis of other proteins. JNJ460 also resulted in more structural proteins associated with intercellular growth, such as actin, myosin, and troponin. With NGF treatment, cells increased protein synthesis and creation of ribosomes. This method allows the analysis of all of the protein patterns overall, rather than a single change in an amino acid. Western blots confirmed the results, according to the researchers, though the changes in proteins were not as obvious in their protocol. The main significance to these findings are that JNJ460 are NGF are distinct processes that both control the protein output of the cell. JNJ460 resulted in increased neuronal size and stability while NGF resulted in increased membrane proteins. When combined, they significantly increase a neuron’s chance of growth. While JNJ460 may “prime” some parts of the cell for NGF treatment, they do not work together. JNJ460 is thought to interact with Schwann cells in regenerating actin and myosin, which are key players in axonal growth. NGF helps the neuron grow as a whole. These two proteins do not play a part in communication with other neurons, however. They merely increase the size of the membrane down which a signal can be sent. Other neurotrophic factor proteomes are needed to guide neurons to each other to create synapses.

Neurochemistry

Luciferase is a generic term for the class of oxidative enzymes that produce bioluminescence, and is usually distinguished from a photoprotein. The name was first used by Raphaël Dubois who invented the words luciferin and luciferase, for the substrate and enzyme, respectively. Both words are derived from the Latin word lucifer, meaning "lightbearer", which in turn is derived from the Latin words for "light" (lux) and "to bring or carry" (ferre).Luciferases are widely used in biotechnology, for bioluminescence imaging microscopy and as reporter genes, for many of the same applications as fluorescent proteins. However, unlike fluorescent proteins, luciferases do not require an external light source, but do require addition of luciferin, the consumable substrate.

Bioluminescence

An opioidergic agent (or drug) is a chemical which functions to directly modulate the opioid neuropeptide systems (i.e., endorphin, enkephalin, dynorphin, nociceptin) in the body or brain. Examples include opioid analgesics such as morphine and opioid antagonists such as naloxone. Opioidergics also comprise allosteric modulators and enzyme affecting agents like enkephalinase inhibitors.

Neurochemistry

Vargulin, also called Cypridinid luciferin, Cypridina luciferin, or Vargula luciferin, is the luciferin found in the ostracod Cypridina hilgendorfii, also named Vargula hilgendorfii. These bottom dwelling ostracods emit a light stream into water when disturbed presumably to deter predation. Vargulin is also used by the midshipman fish, Porichthys.

Bioluminescence

It is commonly known that drug addiction involves permanent synaptic plasticity of various neuronal circuits. Neuroproteomics is being applied to study the effect of drug addiction across the synapse. Research is being conducted by isolating distinct regions of the brain in which synaptic transmission takes place and defining the proteome for that particular region. Different stages of drug abuse must be studied, however, in order to map out the progression of protein changes along the course of the drug addiction. These stages include enticement, ingesting, withdrawal, addiction, and removal. It begins with the change in the genome through transcription that occurs due to the abuse of drugs. It continues to identify the most likely proteins to be affected by the drugs and focusing in on that area. For drug addiction, the synapse is the most likely target as it involves communication between neurons. Lack of sensory communication in neurons is often an outward sign of drug abuse, and so neuroproteomics is being applied to find out what proteins are being affected to prevent the transport of neurotransmitters. In particular, the vesicle releasing process is being studied to identify the proteins involved in the synapse during drug abuse. Proteins such as synaptotagmin and synaptobrevin interact to fuse the vesicle into the membrane. Phosphorylation also has its own set of proteins involved that work together to allow the synapse to function properly. Drugs such as morphine change properties such as cell adhesion, neurotransmitter volume, and synaptic traffic. After significant morphine application, tyrosine kinases received less phosphorylation and thus send fewer signals inside the cell. These receptor proteins are unable to initiate the intracellular signaling processes that enable the neuron to live, and necrosis or apoptosis may be the result. With more and more neurons affected along this chain of cell death, permanent loss of sensory or motor function may be the result. By identifying the proteins that are changed with drug abuse, neuroproteomics may give clinicians even earlier biomarkers to test for to prevent permanent neurological damage. Recently, a novel terminology (Psychoproteomics) has been coined by the University of Florida researchers from Dr. Mark S Gold Lab. Kobeissy et al. defined Psychoproteomics as integral proteomics approach dedicated to studying proteomic changes in the field of psychiatric disorders, particularly substance-and drug-abuse neurotoxicity.

Neurochemistry

Firefly luciferase is the light-emitting enzyme responsible for the bioluminescence of fireflies and click beetles. The enzyme catalyses the oxidation of firefly luciferin, requiring oxygen and ATP. Because of the requirement of ATP, firefly luciferases have been used extensively in biotechnology.

Bioluminescence

:For a synthetic analogue see also 3,5-Difluoro-4-hydroxybenzylidene imidazolinone. Mechanistically, the process involves base-mediated cyclization followed by dehydration and oxidation. In the reaction of 7a to 8 involves the formation of an enamine from the imine, while in the reaction of 7b to 9 a proton is abstracted. The formed HBI fluorophore is highlighted in green. The reactions are catalyzed by residues Glu222 and Arg96. An analogous mechanism is also possible with threonine in place of Ser65.

Bioluminescence

A natural neuroactive substance (NAS) is a chemical synthesized by neurons that affects the actions of other neurons or muscle cells. Natural neuroactive substances include neurotransmitters, neurohormones, and neuromodulators. Neurotransmitters work only between adjacent neurons through synapses. Neurohormones are released into the blood and work at a distance. Some natural neuroactive substances act as both transmitters and as hormones.

Neurochemistry

Neuromelanin gives specific brain sections, such as the substantia nigra or the locus coeruleus, distinct color. It is a type of melanin and similar to other forms of peripheral melanin. It is insoluble in organic compounds, and can be labeled by silver staining. It is called neuromelanin because of its function and the color change that appears in tissues containing it. It contains black/brown pigmented granules. Neuromelanin is found to accumulate during aging, noticeably after the first 2–3 years of life. It is believed to protect neurons in the substantia nigra from iron-induced oxidative stress. It is considered a true melanin due to its stable free radical structure and it avidly chelates metals.

Neurochemistry

Many new monomeric versions of EosFP have been developed that offer advantages over wild type EosFP. Developed by a team at the Janelia Farm Research Campus at Howard Hughes Medical Institute, mEos4 has higher photostability and longer imaging abilities than EosFP. It is also highly resistant to chemical fixatives such as PFA, gluteraldehyde and OsO4 which are used to preserve samples. mEos4 is effective at higher temperatures than EosFP, phot-converts at an increased rate and has a higher emission amplitude in both green and red fluorescent states. Applications for the mEos4 protein include photoactivation localization microscopy (PALM), correlative light/ electron microscopy (CLEM), protein activity indication and activity integration (post-hoc imaging for protein activity over time).

Bioluminescence

The L-alanine derivative β-methylamino-L-alanine (BMAA) has long been identified as a neurotoxin which was first associated with the amyotrophic lateral sclerosis/parkinsonism–dementia complex (Lytico-bodig disease) in the Chamorro people of Guam. The widespread occurrence of BMAA can be attributed to cyanobacteria which produce BMAA as a result of complex reactions under nitrogen stress. Following research, excitotoxicity appears to be the likely mode of action for BMAA which acts as a glutamate agonist, activating AMPA and NMDA receptors and causing damage to cells even at relatively low concentrations of 10 μM. The subsequent uncontrolled influx of Ca then leads to the pathophysiology described above. Further evidence of the role of BMAA as an excitotoxin is rooted in the ability of NMDA antagonists like MK801 to block the action of BMAA. More recently, evidence has been found that BMAA is misincorporated in place of L-serine in human proteins. A considerable portion of the research relating to the toxicity of BMAA has been conducted on rodents. A study published in 2016 with vervets (Chlorocebus sabaeus) in St. Kitts, which are homozygous for the apoE4 (APOE-ε4) allele (a condition which in humans is a risk factor for Alzheimers disease), found that vervets orally administered BMAA developed hallmark histopathology features of Alzheimers Disease including amyloid beta plaques and neurofibrillary tangle accumulation. Vervets in the trial fed smaller doses of BMAA were found to have correlative decreases in these pathology features. This study demonstrates that BMAA, an environmental toxin, can trigger neurodegenerative disease as a result of a gene/environment interaction. While BMAA has been detected in brain tissue of deceased ALS/PDC patients, further insight is required to trace neurodegenerative pathology in humans to BMAA.

Neurochemistry

LncRNA has evolved rather recently from those of other species but still maintains some functionality. With regards to this specific form, researchers believe that it can serve as a diagnostic and predictive biomarker for cancers where its normal expression is altered. Much work is still required to fully understand the function and regulatory mechanisms of BC200 RNA but new approaches may seek to develop probes for human BC200 RNA that will assist in developing novel pharmaceuticals. As RNA polymerase III is responsible for transcribing BC200 RNA, it can also serve as a potential target for addressing disease where the expression of it is elevated.

Neurochemistry

The availability of GFP and its derivatives has thoroughly redefined fluorescence microscopy and the way it is used in cell biology and other biological disciplines. While most small fluorescent molecules such as FITC (fluorescein isothiocyanate) are strongly phototoxic when used in live cells, fluorescent proteins such as GFP are usually much less harmful when illuminated in living cells. This has triggered the development of highly automated live-cell fluorescence microscopy systems, which can be used to observe cells over time expressing one or more proteins tagged with fluorescent proteins. There are many techniques to utilize GFP in a live cell imaging experiment. The most direct way of utilizing GFP is to directly attach it to a protein of interest. For example, GFP can be included in a plasmid expressing other genes to indicate a successful transfection of a gene of interest. Another method is to use a GFP that contains a mutation where the fluorescence will change from green to yellow over time, which is referred to as a fluorescent timer. With the fluorescent timer, researchers can study the state of protein production such as recently activated, continuously activated, or recently deactivated based on the color reported by the fluorescent protein. In yet another example, scientists have modified GFP to become active only after exposure to irradiation giving researchers a tool to selectively activate certain portions of a cell and observe where proteins tagged with the GFP move from the starting location. These are only two examples in a burgeoning field of fluorescent microcopy and a more complete review of biosensors utilizing GFP and other fluorescent proteins can be found here For example, GFP had been widely used in labelling the spermatozoa of various organisms for identification purposes as in Drosophila melanogaster, where expression of GFP can be used as a marker for a particular characteristic. GFP can also be expressed in different structures enabling morphological distinction. In such cases, the gene for the production of GFP is incorporated into the genome of the organism in the region of the DNA that codes for the target proteins and that is controlled by the same regulatory sequence; that is, the gene's regulatory sequence now controls the production of GFP, in addition to the tagged protein(s). In cells where the gene is expressed, and the tagged proteins are produced, GFP is produced at the same time. Thus, only those cells in which the tagged gene is expressed, or the target proteins are produced, will fluoresce when observed under fluorescence microscopy. Analysis of such time lapse movies has redefined the understanding of many biological processes including protein folding, protein transport, and RNA dynamics, which in the past had been studied using fixed (i.e., dead) material. Obtained data are also used to calibrate mathematical models of intracellular systems and to estimate rates of gene expression. Similarly, GFP can be used as an indicator of protein expression in heterologous systems. In this scenario, fusion proteins containing GFP are introduced indirectly, using RNA of the construct, or directly, with the tagged protein itself. This method is useful for studying structural and functional characteristics of the tagged protein on a macromolecular or single-molecule scale with fluorescence microscopy. The Vertico SMI microscope using the SPDM Phymod technology uses the so-called "reversible photobleaching" effect of fluorescent dyes like GFP and its derivatives to localize them as single molecules in an optical resolution of 10 nm. This can also be performed as a co-localization of two GFP derivatives (2CLM). Another powerful use of GFP is to express the protein in small sets of specific cells. This allows researchers to optically detect specific types of cells in vitro (in a dish), or even in vivo (in the living organism). Genetically combining several spectral variants of GFP is a useful trick for the analysis of brain circuitry (Brainbow). Other interesting uses of fluorescent proteins in the literature include using FPs as sensors of neuron membrane potential, tracking of AMPA receptors on cell membranes, viral entry and the infection of individual influenza viruses and lentiviral viruses, etc. It has also been found that new lines of transgenic GFP rats can be relevant for gene therapy as well as regenerative medicine. By using "high-expresser" GFP, transgenic rats display high expression in most tissues, and many cells that have not been characterized or have been only poorly characterized in previous GFP-transgenic rats. GFP has been shown to be useful in cryobiology as a viability assay. Correlation of viability as measured by trypan blue assays were 0.97. Another application is the use of GFP co-transfection as internal control for transfection efficiency in mammalian cells. A novel possible use of GFP includes using it as a sensitive monitor of intracellular processes via an eGFP laser system made out of a human embryonic kidney cell line. The first engineered living laser is made by an eGFP expressing cell inside a reflective optical cavity and hitting it with pulses of blue light. At a certain pulse threshold, the eGFP's optical output becomes brighter and completely uniform in color of pure green with a wavelength of 516 nm. Before being emitted as laser light, the light bounces back and forth within the resonator cavity and passes the cell numerous times. By studying the changes in optical activity, researchers may better understand cellular processes. GFP is used widely in cancer research to label and track cancer cells. GFP-labelled cancer cells have been used to model metastasis, the process by which cancer cells spread to distant organs.

Bioluminescence

Aequorin is a holoprotein composed of two distinct units, the apoprotein that is called apoaequorin, which has an approximate molecular weight of 21 kDa, and the prosthetic group coelenterazine, the luciferin. This is to say, apoaequorin is the enzyme produced in the photocytes of the animal, and coelenterazine is the substrate whose oxidation the enzyme catalyzes. When coelenterazine is bound, it is called aequorin. Notably, the protein contains three EF hand motifs that function as binding sites for Ca ions. The protein is a member of the superfamily of the calcium-binding proteins, of which there are some 66 subfamilies. The crystal structure revealed that aequorin binds coelenterazine and oxygen in the form of a peroxide, coelenterazine-2-hydroperoxide. The binding site for the first two calcium atoms show a 20 times greater affinity for calcium than the third site. However, earlier claims that only two EF-hands bind calcium were questioned when later structures indicated that all three sites can indeed bind calcium. Thus, titration studies show that all three calcium-binding sites are active but only two ions are needed to trigger the enzymatic reaction. Other studies have shown the presence of an internal cysteine bond that maintains the structure of aequorin. This has also explained the need for a thiol reagent like beta mercaptoethanol in the regeneration of the protein since such reagents weaken the sulfhydryl bonds between cysteine residues, expediting the regeneration of the aequorin. Chemical characterization of aequorin indicates the protein is somewhat resilient to harsh treatments. Aequorin is heat resistant. Held at 95 °C for 2 minutes the protein lost only 25% activity. Denaturants such as 6-M urea or 4-M guanidine hydrochloride did not destroy the protein.

Bioluminescence

In Avatar, the Navi are an indigenous species that live on Pandora. They are humanoid in appearance and are tall, having pairs of eyes, ears, arms, legs and feet like humans, as well as a nose, a mouth, and expressions recognizable to humans. The Navi differ from humans in having blue striped skin, pointed and mobile ears, large eyes, catlike noses and tails, and hands each with three fingers and a thumb (hybrid avatars, on the other hand, retain the five-fingered hands of their human DNA). While taller than humans, they have narrower proportions in body frame. Their bones are reinforced with naturally occurring carbon fiber. The Navi also have a distinctive tendril feature protruding from the back of their heads, surrounded by hair (resembling a long plait or queue), feeding directly into the brain. This organ allows them to connect with other organisms, transferring electrochemical signals such as thoughts and memories. In the original script, Cameron refers to these as "Jubilees", although the word is not used in the film and may be changed by the time the novel is published. The Navi were initially conceived to be more alien in appearance. Cameron recalled when one of the main characters, Neytiri, was originally drawn, she had gills and other protuberances. In addition to feline features, the species were redesigned to seem more human so audiences could better relate to them. The sequel, Avatar: The Way of Water, introduces Navi from the Metkayina tribe with a number of qualities that distinguish them from the blue-skinned Omatikaya clan in Avatar'. The Metkayina have evolved characteristics conducive to an aquatic lifestyle of swimming and diving. These adaptations include green/teal skin, stronger arms, thicker tails, inner eyelids. According to Cameron, the appearance of the Navi character Neytiri had some specific inspirations and requirements: she was inspired by Raquel Welchs character in Fantastic Voyage and by Vampirella, noting in the latters case, "the fact [Vampirella] didnt exist didnt bother me because we have these quintessential female images in our mind, and in the case of the male mind, theyre grossly distorted. When you see something that reflects your id, it works for you.... Right from the beginning I said, Shes got to have tits, even though that makes no sense because her race, the Navi, arent placental mammals. I designed her costumes based on a taparrabo, a loincloth worn by Mayan Indians." This is somewhat of a non-sequitur because both marsupials (kangaroos, etc.) and monotremes (platypuses, etc.) are non-placental and yet both lactate. This objective of making the Navi as humanlike as possible can also be seen as an explanation as to why they are quadrupedal despite having evolved from common ancestors of the hexapodal lemurs seen in the film. Cameron has described Avatar as more "science fantasy" than true science fiction and has said that he would explain in the novel for the film why in the fictional universe the Na'vi look like humans.

Bioluminescence

Neurotrophin mimetics are small molecules or peptide like molecules that can modulate the action of the neurotrophin receptor. One of the main causes of neurodegeneration involves changes in the expression of neurotrophins (NTs) and/or their receptors (TrkA, TrkB, TrkC and p75NTR). Indeed, these imbalances or changes in their activity, lead to neuronal damage resulting in neurological and neurodegenerative conditions. The therapeutic properties of neurotrophins attracted the focus of many researchers during the years, but the poor pharmacokinetic properties, such as reduced bioavailability and low metabolic stability, the hyperalgesia, the inability to penetrate the blood–brain barrier and the short half-lives render the large neurotrophin proteins not suitable to be implemented as drugs. For this reason, several efforts have been made to develop neurotrophin mimetics (small molecules and peptidomimetics) that can modulate the action of the neurotrophin receptors (Trks and p75NTR) and possess drug-like pharmacokinetic and pharmacodynamic profiles. Specifically, these mimetics can be classified as TrkA and TrkB receptor agonists and p75NTR modulators/antagonists.

Neurochemistry

The first PAFP, Kaede (protein), was isolated from Trachyphyllia geoffroyi in a cDNA library screen designed to identify new fluorescent proteins. A fluorescent green protein derived from this screen was serendipitously discovered to have sensitivity to ultraviolet light--

Bioluminescence

Firefly luciferin is the luciferin found in many Lampyridae species. It is the substrate of beetle luciferases (EC 1.13.12.7) responsible for the characteristic yellow light emission from fireflies, though can cross-react to produce light with related enzymes from non-luminous species. The chemistry is unusual, as adenosine triphosphate (ATP) is required for light emission, in addition to molecular oxygen.

Bioluminescence

A thorough review of trace amine-associated receptors that discusses the historical evolution of this research particularly well is that of Grandy.

Neurochemistry

There are over 300 types of ion channels just in the cells of the inner ear. Ion channels may be classified by the nature of their gating, the species of ions passing through those gates, the number of gates (pores), and localization of proteins. Further heterogeneity of ion channels arises when channels with different constitutive subunits give rise to a specific kind of current. Absence or mutation of one or more of the contributing types of channel subunits can result in loss of function and, potentially, underlie neurologic diseases.

Neurochemistry

James Camerons core idea for the Avatars fictional creatures was for them to be "superslick and aerodynamic, and be like a race car with racing stripes". Neville Page worked on Avatar as the lead creature designer. He, Wayne Barlowe (author, artist, and initial lead creature designer), and Yuri Bartoli (concept designer and supervising virtual art director) adapted Camerons conceptions of the fauna into a design that served three purposes: to appear expressive, to function with animation technology, and to seem realistic. He and creature designer Wayne Barlowe sought to base the design of Pandora's creatures on race cars, but they struggled to adapt the concept. Page drew on his education in automotive design, recognizing the irony that race cars were based on real-life animals in having "bone lines". Existing automotive designs drew from seashells, turtle shells, and insects, so the designers returned the design to the fictional creatures. They found that the prime challenge in designing most creatures was to give them organic appearances, including skin texture. Some creatures were also designed to have special breathing holes located in the trachea, copying how cars have intakes. Challenges that the creatures posed for visual effects technicians were to form "walk and run" cycles for six-legged creatures and to impart credible flying for creatures that had four wings. Many of the animals also have four eyes, with an apparent major and minor eye on either side of their head. The fictional creatures are not connected telepathically according to Cameron and the designers. However, even though they discussed the idea of the creatures being part of Pandoras "Worldmind", they preferred to interpret the creatures as having heightened instincts. Page explained, "Animals are hooked up to this planet. Were the ones who are detached.... The way I dealt with it was, We have so much rich [material] here to reference, that we don't have to dream up a whole new process of animal awareness." The fictional moon has less gravity than Earth, so the creatures larger sizes match their environment. Most Pandoran wildlife is hexapodal, or six-legged. Much of the fauna and flora is bioluminescent, which is seen in creatures on Earth such as fireflies, many deep sea animals, and some microscopic algae. The aforementioned breathing holes, located on multiple parts of a creatures body other than the mouth, are similar to spiracles in some of Earths animals. The flying reptile-like creatures in the film can be compared to extinct flying reptiles such as pterosaurs and to the modern gliding lizard Draco sumatranus'.

Bioluminescence

Due to the potential for widespread usage and the evolving needs of researchers, many different mutants of GFP have been engineered. The first major improvement was a single point mutation (S65T) reported in 1995 in Nature by Roger Tsien. This mutation dramatically improved the spectral characteristics of GFP, resulting in increased fluorescence, photostability, and a shift of the major excitation peak to 488 nm, with the peak emission kept at 509 nm. This matched the spectral characteristics of commonly available FITC filter sets, increasing the practicality of use by the general researcher. A 37 °C folding efficiency (F64L) point mutant to this scaffold, yielding enhanced GFP (EGFP), was discovered in 1995 by the laboratories of Thastrup and Falkow. EGFP allowed the practical use of GFPs in mammalian cells. EGFP has an extinction coefficient (denoted ε) of 55,000 Mcm. The fluorescence quantum yield (QY) of EGFP is 0.60. The relative brightness, expressed as ε•QY, is 33,000 Mcm. Superfolder GFP (sfGFP), a series of mutations that allow GFP to rapidly fold and mature even when fused to poorly folding peptides, was reported in 2006. Many other mutations have been made, including color mutants; in particular, blue fluorescent protein (EBFP, EBFP2, Azurite, mKalama1), cyan fluorescent protein (ECFP, Cerulean, CyPet, mTurquoise2), and yellow fluorescent protein derivatives (YFP, Citrine, Venus, YPet). BFP derivatives (except mKalama1) contain the Y66H substitution.They exhibit a broad absorption band in the ultraviolet centered close to 380 nanometers and an emission maximum at 448 nanometers. A green fluorescent protein mutant (BFPms1) that preferentially binds Zn(II) and Cu(II) has been developed. BFPms1 have several important mutations including and the BFP chromophore (Y66H),Y145F for higher quantum yield, H148G for creating a hole into the beta-barrel and several other mutations that increase solubility. Zn(II) binding increases fluorescence intensity, while Cu(II) binding quenches fluorescence and shifts the absorbance maximum from 379 to 444 nm. Therefore, they can be used as Zn biosensor. Chromophore binding. The critical mutation in cyan derivatives is the Y66W substitution, which causes the chromophore to form with an indole rather than phenol component. Several additional compensatory mutations in the surrounding barrel are required to restore brightness to this modified chromophore due to the increased bulk of the indole group. In ECFP and Cerulean, the N-terminal half of the seventh strand exhibits two conformations. These conformations both have a complex set of van der Waals interactions with the chromophore. The Y145A and H148D mutations in Cerulean stabilize these interactions and allow the chromophore to be more planar, better packed, and less prone to collisional quenching. Additional site-directed random mutagenesis in combination with fluorescence lifetime based screening has further stabilized the seventh β-strand resulting in a bright variant, mTurquoise2, with a quantum yield (QY) of 0.93. The red-shifted wavelength of the YFP derivatives is accomplished by the T203Y mutation and is due to π-electron stacking interactions between the substituted tyrosine residue and the chromophore. These two classes of spectral variants are often employed for Förster resonance energy transfer (FRET) experiments. Genetically encoded FRET reporters sensitive to cell signaling molecules, such as calcium or glutamate, protein phosphorylation state, protein complementation, receptor dimerization, and other processes provide highly specific optical readouts of cell activity in real time. Semirational mutagenesis of a number of residues led to pH-sensitive mutants known as pHluorins, and later super-ecliptic pHluorins. By exploiting the rapid change in pH upon synaptic vesicle fusion, pHluorins tagged to synaptobrevin have been used to visualize synaptic activity in neurons. Redox sensitive GFP (roGFP) was engineered by introduction of cysteines into the beta barrel structure. The redox state of the cysteines determines the fluorescent properties of roGFP.

Bioluminescence

The effect of non-depolarizing neuromuscular-blocking drugs may be reversed with acetylcholinesterase inhibitors, neostigmine, and edrophonium, as commonly used examples. Of these, edrophonium has a faster onset of action than neostigmine, but it is unreliable when used to antagonize deep neuromuscular block. Acetylcholinesterase inhibitors increase the amount of acetylcholine in the neuromuscular junction, so a prerequisite for their effect is that the neuromuscular block is not complete, because in case every acetylcholine receptor is blocked then it does not matter how much acetylcholine is present. Sugammadex is a newer drug for reversing neuromuscular block by rocuronium and vecuronium in general anaesthesia. It is the first selective relaxant binding agent (SRBA).

Neurochemistry

Since these drugs may cause paralysis of the diaphragm, mechanical ventilation should be at hand to provide respiration. In addition, these drugs may exhibit cardiovascular effects, since they are not fully selective for the nicotinic receptor and hence may have effects on muscarinic receptors. If nicotinic receptors of the autonomic ganglia or adrenal medulla are blocked, these drugs may cause autonomic symptoms. Also, neuromuscular blockers may facilitate histamine release, which causes hypotension, flushing, and tachycardia. Succinylcholine may also trigger malignant hyperthermia in rare cases in patients who may be susceptible. In depolarizing the musculature, suxamethonium may trigger a transient release of large amounts of potassium from muscle fibers. This puts the patient at risk for life-threatening complications, such as hyperkalemia and cardiac arrhythmias. Other effects include myalgia, increased intragastric pressure, increased intraocular pressure, increased intracranial pressure, cardiac dysrhythmias (bradycardia is the most common type) and allergic reactions. As a result, it is contraindicated for patients with susceptibility to malignant hyperthermia, denervating conditions, major burns after 48 hours, and severe hyperkalemia. For nondepolarizing NMBAs except vecuronium, pipecuronium, doxacurium, cisatracurium, rocuronium and rapacuronium, they produce certain extent of cardiovascular effect. Moreover, Tubocurarine can produce hypotension effect while Pancuronium can lead to moderate increase in heart rate and small increase in cardiac output with little or no increase in systemic vascular resistance, which is unique in nondeploarizing NMBAs. Certain drugs such as aminoglycoside antibiotics and polymyxin and some fluoroquinolones also have neuromuscular blocking action as their side-effect.

Neurochemistry

Foxfire is the bioluminescence created by some species of fungi present in decaying wood. While there may be multiple different luciferins within the kingdom of fungi, 3-hydroxy hispidin was determined to be the luciferin in the fruiting bodies of several species of fungi, including Neonothopanus nambi, Omphalotus olearius, Omphalotus nidiformis, and Panellus stipticus.

Bioluminescence

* J.G. Nicholls, A.R. Martin, B.G. Wallace and P.A. Fuchs. "From Neuron to Brain". 4th ed. Sinauer Associates, Sunderland, MA.

Neurochemistry

The p75 neurotrophin receptor (p75NTR) was first identified in 1973 as the low-affinity nerve growth factor receptor (LNGFR) before discovery that p75NTR bound other neurotrophins equally well as nerve growth factor. p75NTR is a neurotrophic factor receptor. Neurotrophic factor receptors bind Neurotrophins including Nerve growth factor, Neurotrophin-3, Brain-derived neurotrophic factor, and Neurotrophin-4. All neurotrophins bind to p75NTR. This also includes the immature pro-neurotrophin forms. Neurotrophic factor receptors, including p75NTR, are responsible for ensuring a proper density to target ratio of developing neurons, refining broader maps in development into precise connections. p75NTR is involved in pathways that promote neuronal survival and neuronal death.

Neurochemistry

Neurochemical Research is a monthly peer-reviewed scientific journal covering neurochemistry. It was established in 1976 and is published by Springer Science+Business Media. The editor-in-chief is Arne Schousboe (University of Copenhagen).

Neurochemistry

Urinary VMA is elevated in patients with tumors that secrete catecholamines. These urinalysis tests are used to diagnose an adrenal gland tumor called pheochromocytoma, a tumor of catecholamine-secreting chromaffin cells. These tests may also be used to diagnose neuroblastomas, and to monitor treatment of these conditions. Norepinephrine is metabolised into normetanephrine and VMA. Norepinephrine is one of the hormones produced by the adrenal glands, which are found on top of the kidneys. These hormones are released into the blood during times of physical or emotional stress, which are factors that may skew the results of the test.

Neurochemistry

Neuromelanin-containing neurons in the substantia nigra degenerate during Parkinsons disease. Motor symptoms of Parkinsons disease are caused by cell death in the substantia nigra, which may be partly due to oxidative stress. This oxidation may be relieved by neuromelanin. Patients with Parkinsons disease had 50% the amount of neuromelanin in the substantia nigra as compared to similar patients of their same age, but without Parkinsons. The death of neuromelanin-containing neurons in the substantia nigra, pars compacta, and locus coeruleus have been linked to Parkinsons disease and also have been visualized in vivo' with neuromelanin imaging. Neuromelanin has been shown to bind neurotoxic and toxic metals that could promote neurodegeneration.

Neurochemistry

Monoamine nuclei are clusters of cells that primarily use monoamine neurotransmitters to communicate. The raphe nuclei, ventral tegmental area, and locus coeruleus have been included in texts about monoamine nuclei. These nuclei receive a variety of inputs including from other monoamines, as well as from glutaminergic, GABAergic, and substance p related pathways. The catacholaminergic pathways mainly project upwards into the cortical and limbic regions, power sparse descending axons have been observed in animals models. Both ascending and descending serotonergic pathways project from the raphe nuclei. Raphe nuclei in the obscurus, pallid us, and magnus descend into the brainstem and spinal cord, while the raphe ponds, raphe dorsals, and nucleus centralism superior projected up into the medial forebrain bundle before branching off. Monoamine nuclei have been studied in relation to major depressive disorder, with some abnormalities observed, however MAO-B levels appear to be normal during depression in these regions.

Neurochemistry

HOCPCA (3-hydroxycyclopent-1-enecarboxylic acid) is a compound with an affinity for the GHB receptor 39 times greater than that of GHB itself.

Neurochemistry

A different perspective on Alzheimers is revealed by a mouse study that has found that APP possesses ferroxidase activity similar to ceruloplasmin, facilitating iron export through interaction with ferroportin; it seems that this activity is blocked by zinc trapped by accumulated Aβ in Alzheimers. It has been shown that a single nucleotide polymorphism in the 5'UTR of APP mRNA can disrupt its translation. The hypothesis that APP has ferroxidase activity in its E2 domain and facilitates export of Fe(II) is possibly incorrect since the proposed ferroxidase site of APP located in the E2 domain does not have ferroxidase activity. As APP does not possess ferroxidase activity within its E2 domain, the mechanism of APP-modulated iron efflux from ferroportin has come under scrutiny. One model suggests that APP acts to stabilize the iron efflux protein ferroportin in the plasma membrane of cells thereby increasing the total number of ferroportin molecules at the membrane. These iron-transporters can then be activated by known mammalian ferroxidases (i.e. ceruloplasmin or hephaestin).

Neurochemistry

There are many biologically active chemicals which elicit an effect on the nervous system. Neurotransmitters and similarly functioning biochemical messengers elicit effects on postsynaptic neurons at neuronal synapses. Excitatory Amino Acids include Glutamate, whereas inhibitory Amino Acids include GABA and Glycine. Additionally, catecholamines, serotonin, acetylcholine, histamine, and orexins have widely-projecting effects and are often referred to as neuromodulators. Neuropeptides include bradykinin, cholecystokinin, corticotropin-releasing factor (CRF), galanin, MCH, MSH, Neuropeptide Y (NPY), Neurotensin, Opioids, orexin, oxytocin, somatostatin, tachykinins, TRH, CUP, and vasopressin. Purines, endogenous cannabinoids, gasses, neurotrophic factors, chemokines, and VEGF are all classified as atypical neurotransmitters. Major receptors of neurotransmitters include AMPA receptors, NMDA receptors, and Kainate Receptors.

Neurochemistry

The mountain banshee (Ikran in Navi) is an airborne predator which lives in mountainous territory on Pandora. Navi warriors attempt to bond with a banshee, a dangerous and required rite of passage. They are cousins to the great leonopteryx and they are scientifically known by xenobiologists as Pterodactylus giganteus. A banshee bonds to a Navi warrior for life. They are four-winged creatures that, like the leonopteryx and direhorse, have a biologically produced carbon fiber flexing on the skin. Neytiri had a banshee named Seze (translated from the language of the Navi roughly as "blue flower"). Page spent the most time designing the banshee for the film so it would be convincing when it flew or perched. The designer said, "The hardest thing of all was having a Navi on top of it and flying it. You had to backwards engineer it. It was like designing and engineering an aircraft." Barlowe, who contributed to the banshees design, was influenced by manta rays and skates as well as relatively little-known pterosaurs and plesiosaurs that had "many, unique aerodynamic and hydrodynamic" characteristics. Like the color scheme for the great leonopteryx, color schemes based on Earth animals were used for various banshees, though Page was inspired by Art Nouveau prints to warp the schemes so they would not look familiar to film audiences.

Bioluminescence

Monoaminergic cell groups refers to collections of neurons in the central nervous system that have been demonstrated by histochemical fluorescence to contain one of the neurotransmitters serotonin, dopamine, norepinephrine or epinephrine. Thus, it represents the combination of catecholaminergic cell groups and serotonergic cell groups.

Neurochemistry

Biophotons may be detected with photomultipliers or by means of an ultra low noise CCD camera to produce an image, using an exposure time of typically 15 minutes for plant materials. Photomultiplier tubes have been used to measure biophoton emissions from fish eggs, and some applications have measured biophotons from animals and humans. Electron Multiplying CCD (EM-CCD) optimized for the detection of ultraweak light have also been used to detect the bioluminescence produced by yeast cells at the onset of their growth. The typical observed radiant emittance of biological tissues in the visible and ultraviolet frequencies ranges from 10 to 10 W/cm with a photon count from a few to nearly 1000 photons per cm in the range of 200 nm to 800 nm.

Bioluminescence

Through research done on nicotinic acetylcholine receptors it has been determined that the channels are activated through allosteric interactions between the binding and gating domains. Once the agonist binds it brings about conformational changes (including moving a beta sheet of the amino-terminal domain, and outward movement from loops 2, F and cys-loop which are tied to the M2-M3 linker and pull the channel open). Electron microscopy (at 9 Å) shows that the opening is caused by rotation at the M2 domain, but other studies on crystal structures of these receptors has shown that the opening could be a result from a M2 tilt which leads to pore dilation and a quaternary turn of the entire pentameric receptor.

Neurochemistry

Between 1915 and 1993, 235 sightings of milky seas were documented, most of which are concentrated in the northwestern Indian Ocean near to Somalia. The luminescent glow is concentrated on the surface of the ocean and does not mix evenly throughout the water column. In 1985, a research vessel in the Arabian Sea took water samples during milky seas. Their conclusions were that the effect was caused by the bacterium Vibrio harveyi. Mareel is typically caused by Noctiluca scintillans (popularly known as "sea sparkle"), a dinoflagellate that glows when disturbed and is found in oceans throughout much of the world. In July 2015, at Alleppey, Kerala, India, the phenomenon occurred and the National Institute of Oceanography and Kerala Fisheries Department researched it, finding that the glittering waves were the result of Noctiluca scintillans. In 2005, Steven Miller of the Naval Research Laboratory in Monterey, California, was able to match 1995 satellite images with a first-hand account of a merchant ship. U.S. Defense Meteorological Satellite Program showed the milky area to be approximately (roughly the size of Connecticut). The luminescent field was observed to glow over three consecutive nights. While monochromatic photos make this effect appear white, Monterey Bay Aquarium Research Institute scientist Steven Haddock (an author of a milky seas effect study) has commented, "the light produced by the bacteria is actually blue, not white. It is white in the graphic because of the monochromatic sensor we used, and it can appear white to the eye because the rods in our eye (used for night vision) dont discriminate color." In Shetland (where generally caused by Noctiluca scintillans'), mareel has sometimes been described as being green, rather than the traditional blue or white milky seas effect seen by the rest of the world. It is not known whether this difference depends on the area, or simply a perception of a cyanic colour as being green.

Bioluminescence

According to legend, Puerto Mosquito is named after the Mosquito, the name of one of pirate Roberto Cofresí's ships. The bio bay was proclaimed a National Natural Landmark in 1980.

Bioluminescence

A glycinergic agent (or drug) is a chemical which functions to directly modulate the glycine system in the body or brain. Examples include glycine receptor agonists, glycine receptor antagonists, and glycine reuptake inhibitors.

Neurochemistry

The luciferases of fireflies – of which there are over 2000 species – and of the other Elateroidea (click beetles and relatives in general) are diverse enough to be useful in molecular phylogeny. In fireflies, the oxygen required is supplied through a tube in the abdomen called the abdominal trachea. One well-studied luciferase is that of the Photinini firefly Photinus pyralis, which has an optimum pH of 7.8.

Bioluminescence

TrkB agonists have received extensive interest from the scientific community resulting in the synthesis and biological evaluation of a large number of mimetics. Deoxygedunin, with a selective TrkB activity, is able to promote axon regeneration in topical treatments. Furthermore, it shows efficacy in two Parkinsons disease (PD) animal models, leading to the protection of locomotor function and the reduction of neuronal death in dopaminergic neurons. A number of studies corroborated that the flavonoid 7,8-Dihydroxyflavone (7,8-DHF) shows neuroprotection in PD and Huntingtons disease (HD) models together with antioxidant activity and enhancement of motor neuronal survival, motor function and spine density in amyotrophic lateral sclerosis (ALS) model. The benzothiazole riluzole exerts neuroprotective effects by increasing BDNF and GDNF levels with improvement of motor neuron survival. It has been approved for the treatment of ALS and delays the onset of ventilator-dependence or tracheostomy in some people and may increase survival by two to three months. Furthermore, several combinations of riluzole with other drugs are in clinical trials (NCT02588677, NCT03127267). Brimonidine exerts neuroprotective effects in retinal ganglion cells (RGCs) through up-regulation of the expression of BDNF in these cells. It is used in the treatment of glaucoma as eye drops to reduce intraocular pressure (IOP) under the brand name Lumify®. Different drugs, used against PD also behave as neurotrophin mimetics such as rotigotine, selegiline, rasagiline, memantine and levodopa interacting with TrkB and increasing BDNF expression. Furthermore, of particular note, the groups of F. Longo and S. Massa discovered small molecule neurotrophic mimetics exhibiting specificity for TrkB at nanomolar concentrations. In particular, LM22A-4, prevents neuronal death in in vitro models of AD, HD and PD. Among the peptidomimetic TrkB agonists, the dimeric dipeptide GSB-106 showed neurotrophic and neuroprotective effects by specific activation of TrkB and its signaling pathways. Furthermore, the tricyclic dimeric peptide TDP6 acts as a TrkB agonist mimicking BDNF and induces autophosphorylation of TrkB in primary oligodendrocyte cultures, leading to oligodendrocyte myelination. Regarding DHEA derivatives, the C17-spiroepoxy analogue, BNN-20, binds with high affinity to TrkB, showing antiapoptotic activity in vitro. Its neuroprotective activity was analyzed in the Weaver mouse genetic model of PD in which long term administration of BNN-20 protects the dopaminergic neurons by mimicking BDNF and induces antiapoptotic, antioxidant and anti-inflammatory effects.

Neurochemistry

* Cocaine, for example, blocks the reuptake of dopamine, leaving these neurotransmitters in the synaptic gap for longer. * AMPT prevents the conversion of tyrosine to L-DOPA, the precursor to dopamine; reserpine prevents dopamine storage within vesicles; and deprenyl inhibits monoamine oxidase (MAO)-B and thus increases dopamine levels.

Neurochemistry

The final STQ-77/FET framework classifies temperament traits and their neurochemical biomarkers into 12 components: nine components regulating the formal functional aspects of behaviour (energetic, dynamic and orientational) each assessed in three domains (intellectual, physical and social-verbal); also three components related to emotionality (Neuroticism, Impulsivity and Satisfaction (Self-Confidence)) (see Figure) The FET framework summarized existing literature showing the nine non-emotionality traits are regulated by the monoamines (MA) (noradrenalin, dopamine, serotonin), acetylcholine and neuropeptide systems, whereas the three emotionality-related traits emerge as a dysregulation of opioid receptors systems that have direct control over MA systems. Importantly, the FET model suggests that there is no one-to-one correspondence between the neurotransmitter systems underlying temperament traits (or mental disorders) but instead specific ensemble relationships between these systems emerge as temperament traits. The FET framework is based only on the strongest consensus points in the research studying the role of neurotransmitter in behavioural regulation and the components of temperament; it doesn't list more controversial links between these multiple systems. Neurotransmitter systems: 5-HT: serotonin; DA: dopamine; NE: noradrenalin; ACh: acetylcholine; Glu: glutamate; OXY: oxytocin; VSP: vasopressin; NP: Neuropeptides; KOR, MOR, DOR: kappa-, mu- and delta-opioid receptors correspondingly; sANS - sympathetic autonomic nervous system; HPA - hypothalamic–pituitary–adrenal axis. The FET points out that opioid receptor systems are involved not only in regulation of emotional dispositions but also amplify three non-emotionality aspects of behaviour (KOR for orientation, DOR for integration of actions and MOR of approval-maintenance of behaviour). This involvement was confirmed for MOR systems that bind endorphins: experiments show that MOR overstimulation influences hypothalamic serotonin and Brain-derived neurotrophic factor release and affecting endurance aspects of behaviour. The interplay within hormonal systems and its interaction with serotonin also appeared to be a factor is social emotions, such as shame and guilt

Neurochemistry

Firefly luciferase bioluminescence color can vary between yellow-green (λ = 550 nm) to red (λ = 620). There are currently several different mechanisms describing how the structure of luciferase affects the emission spectrum of the photon and effectively the color of light emitted. One mechanism proposes that the color of the emitted light depends on whether the product is in the keto or enol form. The mechanism suggests that red light is emitted from the keto form of oxyluciferin, while green light is emitted from the enol form of oxyluciferin. However, 5,5-dimethyloxyluciferin emits green light even though it is constricted to the keto form because it cannot tautomerize. Another mechanism proposes that twisting the angle between benzothiazole and thiazole rings in oxyluciferin determines the color of bioluminescence. This explanation proposes that a planar form with an angle of 0° between the two rings corresponds to a higher energy state and emits a higher-energy green light, whereas an angle of 90° puts the structure in a lower energy state and emits a lower-energy red light. The most recent explanation for the bioluminescence color examines the microenvironment of the excited oxyluciferin. Studies suggest that the interactions between the excited state product and nearby residues can force the oxyluciferin into an even higher energy form, which results in the emission of green light. For example, Arg 218 has electrostatic interactions with other nearby residues, restricting oxyluciferin from tautomerizing to the enol form. Similarly, other results have indicated that the microenvironment of luciferase can force oxyluciferin into a more rigid, high-energy structure, forcing it to emit a high-energy green light.

Bioluminescence

Work on aequorin began with E. Newton Harvey in 1921. Though Harvey was unable to demonstrate a classical luciferase-luciferin reaction, he showed that water could produce light from dried photocytes and that light could be produced even in the absence of oxygen. Later, Osamu Shimomura began work into the bioluminescence of Aequorea in 1961. This involved tedious harvesting of tens of thousands of jellyfish from the docks in Friday Harbor, Washington. It was determined that light could be produced from extracts with seawater, and more specifically, with calcium. It was also noted during the extraction the animal creates green light due to the presence of the green fluorescent protein, which changes the native blue light of aequorin to green. While the main focus of his work was on the bioluminescence, Shimomura and two others, Martin Chalfie and Roger Tsien, were awarded the Nobel Prize in 2008 for their work on green fluorescent proteins.

Bioluminescence

The purpose of both the (primary) bioluminescence (from aequorins action on luciferin) and the (secondary) fluorescence of GFP in jellyfish is unknown. GFP is co-expressed with aequorin in small granules around the rim of the jellyfish bell. The secondary excitation peak (480 nm) of GFP does absorb some of the blue emission of aequorin, giving the bioluminescence a more green hue. The serine 65 residue of the GFP chromophore is responsible for the dual-peaked excitation spectra of wild-type GFP. It is conserved in all three GFP isoforms originally cloned by Prasher. Nearly all mutations of this residue consolidate the excitation spectra to a single peak at either 395 nm or 480 nm. The precise mechanism of this sensitivity is complex, but, it seems, involves donation of a hydrogen from serine 65 to glutamate 222, which influences chromophore ionization. Since a single mutation can dramatically enhance the 480 nm excitation peak, making GFP a much more efficient partner of aequorin, A. victoria appears to evolutionarily prefer the less-efficient, dual-peaked excitation spectrum. Roger Tsien has speculated that varying hydrostatic pressure with depth may affect serine 65s ability to donate a hydrogen to the chromophore and shift the ratio of the two excitation peaks. Thus, the jellyfish may change the color of its bioluminescence with depth. However, a collapse in the population of jellyfish in Friday Harbor, where GFP was originally discovered, has hampered further study of the role of GFP in the jellyfish's natural environment. Most species of lancelet are known to produce GFP in various regions of their body. Unlike A. victoria, lancelets do not produce their own blue light, and the origin of their endogenous GFP is still unknown. Some speculate that it attracts plankton towards the mouth of the lancelet, serving as a passive hunting mechanism. It may also serve as a photoprotective agent in the larvae, preventing damage caused by high-intensity blue light by converting it into lower-intensity green light. However, these theories have not been tested. GFP-like proteins have been found in multiple species of marine copepods, particularly from the Pontellidae and Aetideidae families. GFP isolated from Pontella mimocerami has shown high levels of brightness with a quantum yield of 0.92, making them nearly two-fold brighter than the commonly used EGFP isolated from A. victoria.

Bioluminescence

Chemi-excitation via oxidative stress by reactive oxygen species or catalysis by enzymes (i.e., peroxidase, lipoxygenase) is a common event in the biomolecular milieu. Such reactions can lead to the formation of triplet excited species, which release photons upon returning to a lower energy level in a process analogous to phosphorescence. That this process is a contributing factor to spontaneous biophoton emission has been indicated by studies demonstrating that biophoton emission can be increased by depleting assayed tissue of antioxidants or by addition of carbonyl derivatizing agents. Further support is provided by studies indicating that emission can be increased by addition of reactive oxygen species.

Bioluminescence

In spite of the usefulness in cell tracking and cell visualization of Kaede, there are some limitations. Although Kaede will shift to red upon the exposure of UV or violet light and display a 2,000-fold increase in red-to-green fluorescence ratio, using both the red and green fluorescence bands can cause problems in multilabel experiments. The tetramerization of Kaede may disturb the localization and trafficking of fusion proteins. This limits the usefulness of Kaede as a fusion protein tag.

Bioluminescence

Neuromelanin is found in higher concentrations in humans than in other primates. Neuromelanin concentration increases with age, suggesting a role in neuroprotection (neuromelanin can chelate metals and xenobiotics) or senescence.

Neurochemistry

Neurotrophins are a family of proteins that induce the survival, development, and function of neurons. They belong to a class of growth factors, secreted proteins that can signal particular cells to survive, differentiate, or grow. Growth factors such as neurotrophins that promote the survival of neurons are known as neurotrophic factors. Neurotrophic factors are secreted by target tissue and act by preventing the associated neuron from initiating programmed cell death – allowing the neurons to survive. Neurotrophins also induce differentiation of progenitor cells, to form neurons. Although the vast majority of neurons in the mammalian brain are formed prenatally, parts of the adult brain (for example, the hippocampus) retain the ability to grow new neurons from neural stem cells, a process known as neurogenesis. Neurotrophins are chemicals that help to stimulate and control neurogenesis.

Neurochemistry

It was discovered that bioluminescent snails are able to exercise a great deal of control over light emission, but the way in which they exercise control over it is still unknown. Phuphania have even been shown to be able to preserve their ability to produce light even after long periods of hibernation. It is currently unknown how these snails are able to maintain their ability to produce light for long periods of time, but theories have been proposed possibly relating it to the way certain fungi are able to maintain their bioluminescence.

Bioluminescence

Endocannabinoids are known to influence synaptic plasticity, and are in particular thought to mediate long-term depression (LTD, which refers to neuronal firing, not psychological depression). Short-term depression (STD) has also been described (see the next paragraph). First reported in the striatum, this system is known to function in several other brain structures such as the nucleus accumbens, amygdala, hippocampus, cerebral cortex, cerebellum, ventral tegmental area (VTA), brain stem, and superior colliculus. Typically, these retrograde transmitters are released by the postsynaptic neuron and induce synaptic depression by activating the presynaptic CB1 receptors. It has further been suggested that different endocannabinoids, i.e., 2-AG and anandamide, might mediate different forms of synaptic depression through different mechanisms. The study conducted with the bed nucleus of the stria terminalis found that the endurance of the depressant effects was mediated by two different signaling pathways based on the type of receptor activated. 2-AG was found to act on presynaptic CB receptors to mediate retrograde STD following activation of L-type calcium channeles, while anandamide was synthesized after mGluR5 activation and triggered autocrine signalling onto postsynapic TRPV1 receptors that induced LTD. These findings provide the brain a direct mechanism to selectively inhibit neuronal excitability over variable time scales. By selectively internalizing different receptors, the brain may limit the production of specific endocannabinoids to favor a time scale in accordance with its needs.

Neurochemistry

Schizophrenia is a psychological disorder in which a patient experiences symptoms including hallucinations, delusions, amotivation, social withdrawal, cognitive defects, and poor working memory. Heredity and gene inheritance is a highly important risk factor, especially for identical twins. Schizophrenia is anatomically characterized by a deterioration and loss of gray matter in the temporal and frontal regions of the cerebral cortex, though the exact mechanism is unknown. What is known is that the main two neurotransmitter systems implicated in schizophrenia are the dopamine and glutamate pathways. Dopamine became a candidate for research when it was clinically noticed that antipsychotic drugs which are dopamine D receptor antagonists were noted to be quite successful in treating schizophrenia as well. Increased levels of dopamine in people with schizophrenia tend to induce paranoid delusions, ideas of reference, and auditory hallucinations. The same dopaminergic pathway is also involved in psychosis. Glutamate has become a candidate for treatment focus because glutamate blocks some NMDA receptors which, on their own, induce schizophrenic behavior. In animal models, NMDA antagonists increase glutamate release in the prefrontal cortex. It is postulated that this is a homeostatic response to NMDA receptor blockade, which in turn increases psychotic symptoms. A class of NMDA receptor antagonists have been denoted dissociative anesthetics because they produce a sense of depersonalization and dissociation of subjective experience from various forms of sensory input stimuli. As such, variants such as Ketamine (Angel Dust/Special K) and Phencyclidine (PCP) have become a commonly abused street-drug. These drugs are no longer used due to harmful behavioral and addictive effects.

Neurochemistry

The direhorse (Pali in Navi ) is a bioluminescent, hexapodal, superficially equine animal. It is scientifically known as Equidirus hoplites. The Navi use the direhorse to hunt. The direhorse was conceived and designed by Cameron and Stan Winston Studios. The direhorse is grey with blue stripes and stands tall, long. The Navi "break" a direhorse by connecting the fleshy tip of their hair to the animals antennae. Xenobiologists call this a neural whip. Once intertwined, the Navi rider can communicate motor commands instantly through the neural interface; however, this connection does not lead to a lifelong, exclusive bond, as it does with the mountain banshee. Cameron described the creature as a "six-legged alien Clydesdale with moth-like antennae". The direhorse uses its long tongue to eat the sap out of pitcher plants.

Bioluminescence

* Anandamide * 2-Arachidonoylglycerol * 2-Arachidonyl glyceryl ether * Oleamide * Oleoylethanolamide * Virodhamine * Docosatetraenoylethanolamide * Stearoylethanolamide * N-Arachidonylglycine * Arachidonoyl serotonin * N-Arachidonoyl dopamine * N-Acylethanolamine

Neurochemistry

The photophysical properties of the FbFPs are determined by the chromophore itself and its chemical surrounding in the protein. The extinction coefficient (ε) is around 14.200 Mcm at 450 nm for all described FbFPs, which is slightly higher than that of free FMN (ε = 12.200 Mcm ). The Fluorescence-Quantum yield (Φ) varies significantly between different FbFPs and ranges from 0.2 (phiLOV2.1) to 0.44 (EcFbFP and iLOV). This represents an almost twofold increase compared to free FMN (Φ = 0.25).<br /> The difference to free FMN is even more significant in the case of the photostabaility, the proteins resistance to bleach out during prolonged and intense irradiation with blue light. Based on the bleaching-halftime (the times it takes to reduce the initial fluorescence intensity to 50% upon illumination) the genetically engineered variant phiLOV2.1 is approximately 40x as stable as free FMN. This stabilizing effect can be observed for almost all FbFPs, although it is usually in the range of 5x - 10x.<br /> The average fluorescence lifetime of FbFPs is in the range of 3.17 (Pp2FbFP) and 5.7 ns (e.g. EcFbFP). They are thereby much longer than the ones of GFP derivatives, which are usually between 1,5 and 3 ns. FbFPs are therefore well suited as donor domains in Förster resonance energy transfer (FRET) systems in conjunction with GFP derivatives like YFP as acceptor domains.

Bioluminescence

The uses of bioluminescence and its biological and ecological significance for animals, including host organisms for bacteria symbiosis, have been widely studied. The biological role and evolutionary history for specifically bioluminescent bacteria still remains quite mysterious and unclear. However, there are continually new studies being done to determine the impacts that bacterial bioluminescence can have on our constantly changing environment and society. Aside from the many scientific and medical uses, scientists have also recently begun to come together with artists and designers to explore new ways of incorporating bioluminescent bacteria, as well as bioluminescent plants, into urban light sources to reduce the need for electricity. They have also begun to use bioluminescent bacteria as a form of art and urban design for the wonder and enjoyment of human society. One explanation for the role of bacterial bioluminescence is from the biochemical aspect. Several studies have shown the biochemical roles of the luminescence pathway. It can function as an alternate pathway for electron flow under low oxygen concentration, which can be advantageous when no fermentable substrate is available. In this process, light emission is a side product of the metabolism. Evidence also suggests that bacterial luciferase contributes to the resistance of oxidative stress. In laboratory culture, luxA and luxB mutants of Vibrio harveyi, which lacked luciferase activity, showed impairment of growth under high oxidative stress compared to wild type. The luxD mutants, which had an unaffected luciferase but were unable to produce luminescence, showed little or no difference. This suggests that luciferase mediates the detoxification of reactive oxygen. Bacterial bioluminescence has also been proposed to be a source of internal light in photoreactivation, a DNA repair process carried out by photolyase. Experiments have shown that non-luminescent V. harveyi mutants are more sensitive to UV irradiation, suggesting the existence of a bioluminescent-mediated DNA repair system. Another hypothesis, called the "bait hypothesis", is that bacterial bioluminescence attracts predators who will assist in their dispersal. They are either directly ingested by fish or indirectly ingested by zooplankton that will eventually be consumed by higher trophic levels. Ultimately, this may allow passage into the fish gut, a nutrient-rich environment where the bacteria can divide, be excreted, and continue their cycle. Experiments using luminescent Photobacterium leiognathi and non-luminescent mutants have shown that luminescence attracts zooplankton and fish, thus supporting this hypothesis.

Bioluminescence

The molecular mechanisms of CB-mediated changes to the membrane voltage have also been studied in detail. Cannabinoids reduce calcium influx by blocking the activity of voltage-dependent N-, P/Q- and L-type calcium channels. In addition to acting on calcium channels, activation of Gi/o and Gs, the two most commonly coupled G-proteins to cannabinoid receptors, has been shown to modulate potassium channel activity. Recent studies have found that CB activation specifically facilitates potassium ion flux through GIRKs, a family of potassium channels. Immunohistochemistry experiments demonstrated that CB is co-localized with GIRK and Kv1.4 potassium channels, suggesting that these two may interact in physiological contexts. In the central nervous system, CB receptors influence neuronal excitability, reducing the incoming synaptic input. This mechanism, known as presynaptic inhibition, occurs when a postsynaptic neuron releases endocannabinoids in retrograde transmission, which then bind to cannabinoid receptors on the presynaptic terminal. CB receptors then reduce the amount of neurotransmitter released, so that subsequent excitation in the presynaptic neuron results in diminished effects on the postsynaptic neuron. It is likely that presynaptic inhibition uses many of the same ion channel mechanisms listed above, although recent evidence has shown that CB receptors can also regulate neurotransmitter release by a non-ion channel mechanism, i.e., through Gi/o-mediated inhibition of adenylyl cyclase and protein kinase A. Direct effects of CB receptors on membrane excitability have been reported, and strongly impact the firing of cortical neurons. A series of behavioral experiments demonstrated that NMDAR, an ionotropic glutamate receptor, and the metabotropic glutamate receptors (mGluRs) work in concert with CB to induce analgesia in mice, although the mechanism underlying this effect is unclear.

Neurochemistry

The biggest advantage of GFP is that it can be heritable, depending on how it was introduced, allowing for continued study of cells and tissues it is expressed in. Visualizing GFP is noninvasive, requiring only illumination with blue light. GFP alone does not interfere with biological processes, but when fused to proteins of interest, careful design of linkers is required to maintain the function of the protein of interest. Moreover, if used with a monomer it is able to diffuse readily throughout cells.

Bioluminescence

Vagusstoff (literally translated from German as "Vagus Substance") refers to the substance released by stimulation of the vagus nerve which causes a reduction in the heart rate. Discovered in 1921 by physiologist Otto Loewi, vagusstoff was the first confirmation of chemical synaptic transmission and the first neurotransmitter ever discovered. It was later confirmed to be acetylcholine, which was first identified by Sir Henry Hallett Dale in 1914. Because of his pioneering experiments, in 1936 Loewi was awarded the Nobel Prize in Physiology or Medicine, which he shared with Dale.

Neurochemistry

Increased endocannabinoid signaling within the central nervous system promotes sleep-inducing effects. Intercerebroventricular administration of anandamide in rats has been shown to decrease wakefulness and increase slow-wave sleep and REM sleep. Administration of anandamide into the basal forebrain of rats has also been shown to increase levels of adenosine, which plays a role in promoting sleep and suppressing arousal. REM sleep deprivation in rats has been demonstrated to increase CB1 receptor expression in the central nervous system. Furthermore, anandamide levels possess a circadian rhythm in the rat, with levels being higher in the light phase of the day, which is when rats are usually asleep or less active, since they are nocturnal.

Neurochemistry

BC200 RNA has been found to be a factor in numerous types of cancer. Although this type of RNA is normally expressed in neurons, it has been detected in cancers of the breast, cervix, esophagus, lungs, ovaries, parotid glands, tongue, and the colon. In certain cancers, expression of BC200 RNA is upregulated. This occurs in esophageal squamous cell carcinoma (ESCC) and higher expression is considered to be a predictor of poor prognosis and may serve as a predictive biomarker for the disease. It was also discovered to be overexpressed in tumor cells of colorectal cancer where the transcript is located just next to a known oncogene, epithelial cell adhesion molecule (EpCAM). Here, expression of BC200 RNA and EpCAM are believed to be correlated as they both play a role in cell migration and invasion. Conversely, research has indicated that BC200 RNA is downregulated in ovarian cancer, as it is a tumor suppressor in normal ovarian cells controlling proliferative ability.

Neurochemistry

Bioluminescent bacteria are light-producing bacteria that are predominantly present in sea water, marine sediments, the surface of decomposing fish and in the gut of marine animals. While not as common, bacterial bioluminescence is also found in terrestrial and freshwater bacteria. These bacteria may be free living (such as Vibrio harveyi) or in symbiosis with animals such as the Hawaiian Bobtail squid (Aliivibrio fischeri) or terrestrial nematodes (Photorhabdus luminescens). The host organisms provide these bacteria a safe home and sufficient nutrition. In exchange, the hosts use the light produced by the bacteria for camouflage, prey and/or mate attraction. Bioluminescent bacteria have evolved symbiotic relationships with other organisms in which both participants benefit close to equally. Another possible reason bacteria use luminescence reaction is for quorum sensing, an ability to regulate gene expression in response to bacterial cell density.

Bioluminescence

The first symptoms of apitoxin (bee venom), that are now thought to be caused by apamin, were described back in 1936 by Hahn and Leditschke. Apamin was first isolated by Habermann in 1965 from Apis mellifera, the Western honey bee. Apamin was named after this bee. Bee venom contains many other compounds, like histamine, phospholipase A2, hyaluronidase, MCD peptide, and the main active component melittin. Apamin was separated from the other compounds by gel filtration and ion exchange chromatography.

Neurochemistry

The red chromophore, which is generated by cleavage of the peptide backbone, has an absorption maxima at 571 nm and an emission maxima at 581 nm, in its anionic form. The break in the peptide backbone that leads to this chromophore is between His-62 Nα and Cα. The observed red fluorescence occurs due to an extension of the chromophore's π-conjugation where the His-62 imidazole ring connects to the imidazolinone. The hydrogen bond patterns of the red and green chromophores are almost identical.

Bioluminescence

In excitotoxicity, nerve cells suffer damage or death when the levels of otherwise necessary and safe neurotransmitters such as glutamate become pathologically high, resulting in excessive stimulation of receptors. For example, when glutamate receptors such as the NMDA receptor or AMPA receptor encounter excessive levels of the excitatory neurotransmitter, glutamate, significant neuronal damage might ensue. Excess glutamate allows high levels of calcium ions (Ca) to enter the cell. Ca influx into cells activates a number of enzymes, including phospholipases, endonucleases, and proteases such as calpain. These enzymes go on to damage cell structures such as components of the cytoskeleton, membrane, and DNA. In evolved, complex adaptive systems such as biological life it must be understood that mechanisms are rarely, if ever, simplistically direct. For example, NMDA in subtoxic amounts induces neuronal survival of otherwise toxic levels of glutamate. Excitotoxicity may be involved in cancers, spinal cord injury, stroke, traumatic brain injury, hearing loss (through noise overexposure or ototoxicity), and in neurodegenerative diseases of the central nervous system such as multiple sclerosis, Alzheimers disease, amyotrophic lateral sclerosis (ALS), Parkinsons disease, alcoholism, alcohol withdrawal or hyperammonemia and especially over-rapid benzodiazepine withdrawal, and also Huntington's disease. Other common conditions that cause excessive glutamate concentrations around neurons are hypoglycemia. Blood sugars are the primary glutamate removal method from inter-synaptic spaces at the NMDA and AMPA receptor site. Persons in excitotoxic shock must never fall into hypoglycemia. Patients should be given 5% glucose (dextrose) IV drip during excitotoxic shock to avoid a dangerous build up of glutamate around NMDA and AMPA neurons. When 5% glucose (dextrose) IV drip is not available high levels of fructose are given orally. Treatment is administered during the acute stages of excitotoxic shock along with glutamate antagonists. Dehydration should be avoided as this also contributes to the concentrations of glutamate in the inter-synaptic cleft and "status epilepticus can also be triggered by a build up of glutamate around inter-synaptic neurons."

Neurochemistry