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K2.3 contains 6 transmembrane domains, a pore-forming region, and intracellular N- and C- termini and is readily blocked by apamin. The gene for K2.3, KCNN3, is located on chromosome 1q21. | 0 | Neurochemistry |
Photocytes are found distributed unevenly near the plate cilia cells. Gastric cells form a barrier that keep the photocytes away from the opening of the radially canal which they are found to exist along. | 1 | Bioluminescence |
Metabolism and Hofmann elimination
Deacetylating vecuronium at position 3 results in a very active metabolite. In the case of rapacuronium the 3-deacylated metabolite is even more potent than rapacuronium. As long as the D-ring acetylcholine moiety is unchanged they retain their muscle relaxing effect. Mono-quaternary aminosteroids produced with deacylation in position 17 on the other hand are generally weak muscle relaxants. In the development of atracurium the main idea was to make use of Hofmann elimination of the muscle relaxant in vivo. When working with bisbenzyl-isoquinolinium types of molecules, inserting proper features into the molecule such as an appropriate electron withdrawing group then Hofmann elimination should occur at conditions in vivo. Atracurium, the resulting molecule, breaks down spontaneously in the body to inactive compounds and being especially useful in patients with kidney or liver failure. Cis-atracurium is very similar to atracurium except it is more potent and has a weaker tendency to cause histamine release.
Structure relations to onset time
The effect of structure on the onset of action is not very well known except that the time of onset appears inversely related to potency. In general mono-quaternary aminosteroids are faster than bis-quaternary compounds, which means they are also of lower potency. A possible explanation for this effect is that drug delivery and receptor binding are of a different timescale. Weaker muscle relaxants are given in larger doses so more molecules in the central compartment must diffuse into the effect compartment, which is the space within the mouth of the receptor, of the body. After delivery to the effect compartment then all molecules act quickly. Therapeutically this relationship is very inconvenient because low potency, often meaning low specificity can decrease the safety margin thus increasing the chances of side-effects. In addition, even though low potency usually accelerates onset of action, it does not guaranty a fast onset. Gallamine, for example, is weak and slow. When fast onset is necessary then succinylcholine or rocuronium are usually preferable.
Elimination
Muscle relaxants can have very different metabolic pathways and it is important that the drug does not accumulate if certain elimination pathways are not active, for example in kidney failure. | 0 | Neurochemistry |
Cells observed under the electron microscope after a technique involving rapid freezing of the cells followed by substitution of water with a polymer (Fast-freeze Fixation/Freeze Substitution) contain a large number of electron dense bodies around the cell periphery. These structures correspond in size and location to the fluorescent bodies confirmed to be scintillons by their light emission, and they show colocalization of anti-luciferase and anti-LBP labeling meaning both bioluminescence proteins are found in the structures. Scintillons appear as cytoplasmic drops hanging in the vacuolar space, as they are almost completely surrounded by the vacuolar membrane. This structure led to the proposal that a voltage gated proton channel in the vacuolar membrane could allow an action potential to be propagated along the vacuolar membrane. This would in turn let protons enter into the cytoplasm around all the scintillons in the cells virtually simultaneously producing an intense but brief flash of light. Voltage gated proton channels were subsequently identified in a dinoflagellate confirming their predicted existence. | 1 | Bioluminescence |
Catecholaminergic means "related to catecholamines". The catecholamine neurotransmitters include dopamine, epinephrine (adrenaline), and norepinephrine (noradrenaline).
A catecholaminergic agent (or drug) is a chemical which functions to directly modulate the catecholamine systems in the body or brain. Examples include adrenergics and dopaminergics. | 0 | Neurochemistry |
Luciferins have been shown to be largely conserved among different species while luciferases show a greater degree of diversity. Eighty percent of the species that exhibit bioluminescence exist in aquatic habitats. | 1 | Bioluminescence |
Neuromuscular blocking agents exert their effect by modulating the signal transmission in skeletal muscles. An action potential is, in other words, a depolarisation in neurone membrane due to a change in membrane potential greater than the threshold potential leads to an electrical impulse generation. The electrical impulse travels along the pre-synaptic neurone axon to synapse with the muscle at the neuromuscular junction (NMJ) to cause muscle contraction.
When the action potential reaches the axon terminal, it triggers the opening of the calcium ion gated channels, which causes the influx of Ca. Ca will stimulate the release of neurotransmitter in the neurotransmitter containing vesicles by exocytosis (vesicle fuses with the pre-synpatic membrane).
The neurotransmitter, acetylcholine(ACh) binds to the nicotinic receptors on the motor end plate, which is a specialised area of the muscle fibre's post-synaptic membrane. This binding causes the nicotinic receptor channels to open and allow the influx of Na into the muscle fibre.
Fifty percent of the released ACh is hydrolysed by acetylcholinesterase (AChE) and the remaining bind to the nicotinic receptors on the motor end plate. When ACh is degraded by AChE, the receptors are no longer stimulated and the muscle can be repolarised.
If enough Na enter the muscle fibre, it causes an increase in the membrane potential from its resting potential of -95mV to -50mV (above the threshold potential -55V) which causes an action potential to spread throughout the fibre. This potential travels along the surface of the sarcolemma. The sarcolemma is an excitable membrane that surrounds the contractile structures known as myofibrils that are located deep in the muscle fibre. For the action potential to reach the myofibrils, the action potential travels along the transverse tubules (T-tubules) that connects the sarcolemma and center of the fibre.
Later, action potential reaches the sarcoplasmic reticulum which stores the Ca needed for muscle contraction and causes Ca to be released from the sarcoplasmic reticulum. | 0 | Neurochemistry |
LAs may enhance the effects of depolarisation and nondepolarising NMBAs through pre and post-synaptic interactions at the NMJ. It may result in blood levels high enough to potentiate NMBA-induced neuromuscular block. Epidurally administered levobupivacaine and mepivacaine potentiate amino-steroidal NMBAs and delay recovery from neuromuscular blockade. | 0 | Neurochemistry |
Molecules synthesized in the cell bodies of neurons must be conveyed outward to the distal synapses. This is accomplished via fast anterograde transport. It has been found that APP can mediate interaction between cargo and kinesin and thus facilitate this transport. Specifically, a short peptide 15-amino-acid sequence from the cytoplasmic carboxy-terminus is necessary for interaction with the motor protein.
Additionally, it has been shown that the interaction between APP and kinesin is specific to the peptide sequence of APP. In a recent experiment involving transport of peptide-conjugated colored beads, controls were conjugated to a single amino acid, glycine, such that they display the same terminal carboxylic acid group as APP without the intervening 15-amino-acid sequence mentioned above. The control beads were not motile, which demonstrated that the terminal COOH moiety of peptides is not sufficient to mediate transport. | 0 | Neurochemistry |
Several compounds are known to promote the opening or activation of specific ion channels. These are classified by the channel on which they act:
*Calcium channel openers, such as Bay K8644
*Chloride channel openers, such as phenanthroline
*Potassium channel openers, such as minoxidil
*Sodium channel openers, such as DDT | 0 | Neurochemistry |
The method of transport of endocannabinoids through the cell membrane and cytoplasm to their respective degradation enzymes has been rigorously debated for nearly two decades, and a putative endocannabinoid membrane transporter was proposed. However, as lipophilic molecules endocannabinoids readily pass through the cell lipid bilayer without assistance and would more likely need a chaperone through the cytoplasm to the endoplasmic reticulum where the enzyme FAAH is located. More recently fatty acid-binding proteins (FABPs) and heat shock proteins (Hsp70s) have been described and verified as such chaperones, and their inhibitors have been synthesized. The inhibition of endocannabinoid reuptake raises the amount of those neurotransmitters available in the synaptic cleft and therefore increases neurotransmission. Following the increase of neurotransmission in the endocannabinoid system is the stimulation of its functions which, in humans, include: suppression of pain perception (analgesia), increased appetite, mood elevation and inhibition of short-term memory. | 0 | Neurochemistry |
There are a number of natural products with neurotrophic activity, which results from several mechanisms including enhancing BDNF gene transcription, upregulating the expression of BDNF and TrkB, and extracellular signal-regulated kinase (ERK) and CREB signalling.
The first discovered non-protein neurotrophic natural product was lactacystin, isolated from a culture broth of Streptomyces sp. Magnolol and honokiol, the main constituents of Magnolia officinalis and Magnolia obovata stem bark, have been reported to have neurotrophic activity in primary cultured rat cortical by enhancing the BDNF expression. Merrilactone A, jiadifenin, jiadifenolide, (1R,10S)-2-oxo-3,4-dehydroxyneomajucin, jiadifenoxolane A, (2R)-hydroxynorneomajucin, 11-O-debenzoyltashironin,tricycloillicinone, and bicycloillicinone, natural products of the Illicium family have been shown to promote neurite outgrowth in primary cultures of cortical neurons of fetal rats. Neurotrophic properties are also possessed by several members of the Lycopodium alkaloids (huperzine A, lyconadins, complanadine A and B, and nankakurine A and B). Studies have shown that huperazine A can elevate the levels of NGF and BDNF. Synthesis of NGF can be upregulated by administration of cyathanediterpenoids specifically erinacines, scabronines and cyrneines.
Some flavonoids, Isoflavonoids and neoflavonoids were found to have neuroprotective activity. Among the effective flavonoids, luteolin from Lonicera japonica sp., isorhamnetin from Opuntia ficus-indica, genistein from Genista tinctoria, and calycosin from Astragalus membranaceus showed the most promising effects by increasing the mRNA expression and protein secretion of NGF, GDNF, and BDNF. Paecilomycine A and spirotenuipesines A and B, members of the trichothecenes, isolated from the fruiting bodies of Paecilomycestenuipes, have significant neurotrophic profiles especially paecilomycine A which can stimulate the synthesis of neurotrophic factors. Polyprenylatedacylphloroglucinols (PPAPs) represented by hyperforin, hypericin and garsubellin A, have neurotrophic like properties. Hyperforin, isolated from the herb St. Johns wort (Hypericum perforatum'), can stimulate the upregulation of the TrkB receptor.
Beside natural products, there are some small molecules of natural origin that exert neurotrophic activities such as: Panaxytriol (promotes NGF-induced neurite outgrowth in PC-12 cells); 7,8-dihydroxyflavone (TrkB activator); Deoxygedunin (BDNF mimetic); Kansuinin E (promotes neurotrophic activity, most likely through TrkA activation); Tripchlorolide (stimulates expression of BDNF mRNA); Fucoxanthin (increases BDNF production and activates PKA/CREB pathway); Silibinin (Activate hippocampal ROS-BDNF-TrkB patway). | 0 | Neurochemistry |
The journal is abstracted and indexed in:
According to the Journal Citation Reports, the journal has a 2012 impact factor of 2.125. | 0 | Neurochemistry |
The green fluorescent protein (GFP) is a protein that exhibits green fluorescence when exposed to light in the blue to ultraviolet range. The label GFP traditionally refers to the protein first isolated from the jellyfish Aequorea victoria and is sometimes called avGFP. However, GFPs have been found in other organisms including corals, sea anemones, zoanithids, copepods and lancelets.
The GFP from A. victoria has a major excitation peak at a wavelength of 395 nm and a minor one at 475 nm. Its emission peak is at 509 nm, which is in the lower green portion of the visible spectrum. The fluorescence quantum yield (QY) of GFP is 0.79. The GFP from the sea pansy (Renilla reniformis) has a single major excitation peak at 498 nm. GFP makes for an excellent tool in many forms of biology due to its ability to form an internal chromophore without requiring any accessory cofactors, gene products, or enzymes / substrates other than molecular oxygen.
In cell and molecular biology, the GFP gene is frequently used as a reporter of expression. It has been used in modified forms to make biosensors, and many animals have been created that express GFP, which demonstrates a proof of concept that a gene can be expressed throughout a given organism, in selected organs, or in cells of interest. GFP can be introduced into animals or other species through transgenic techniques, and maintained in their genome and that of their offspring. To date, GFP has been expressed in many species, including bacteria, yeasts, fungi, fish and mammals, including in human cells. Scientists Roger Y. Tsien, Osamu Shimomura, and Martin Chalfie were awarded the 2008 Nobel Prize in Chemistry on 10 October 2008 for their discovery and development of the green fluorescent protein.
Most commercially available genes for GFP and similar fluorescent proteins are around 730 base-pairs long. The natural protein has 238 amino acids. Its molecular mass is 27 kD. Therefore, fusing the GFP gene to the gene of a protein of interest can significantly increase the proteins size and molecular mass, and can impair the proteins natural function or change its location or trajectory of transport within the cell. | 1 | Bioluminescence |
The integration of knowledge concerning the molecular and cellular actions of a drug within the brain circuitry leads to an overall understanding of a neurological drug's action mechanisms. This understanding of drug action in turn can be extrapolated to account for system-wide or clinical manifestations which are observed as symptoms. The clinical effects of a neural drug are due to both immediate changes in homeostasis and long-term neural adaptations characterized by the phenomena neural plasticity.
The most basic and fundamental neurological phenomena in neuropharmacology is the binding of a drug or neurologically active substance to a cellular target. One assay to determine the extent at which a ligand binds to its receptor is the radioligand binding assay (RBA), in which specific binding of a radioactively-labeled ligand is denoted by the difference between saturated and non-saturated tissue samples. While the RBA assay assumes that the tissue prepared has just one molecular target per ligand, in actuality this may not be the case. For example, serotonin binds to many diverse serotonin receptors which makes the RIA assay quite difficult to interpret. Because many receptors are essentially enzymes, the field of pharmakinetics utilizes the Michaelis–Menten equation to describe drug affinity (dissociation constant K) and total binding (B). Although K and B can be determined pictorially in a normal or logarithmic plot of ligand binding vs drug concentration, Scatchard plots allow for mathematical representation of several ligand binding sites, each with its own K.
Drug potency is the measure of binding strength between a drug and a specific molecular target, whereas drug efficacy describes the biological effect exerted by the drug itself, at either a cellular or organismal level. Because drugs range widely in their potency and efficacy, drugs have been categorized on the spectrum of agonists and antagonists. Agonists bind to receptors and elicit the same effects as an endogenous neurotransmitter. For example, morphine is an agonist of the opioid receptor family. Conversely, antagonists bind to a receptor and elicit no cellular change. Naloxone, an antagonist of the opioid receptors, exerts a biological effect only be interfering with endogenous neurotransmitter (morphine) binding. Inverse agonists bind to receptors and elicit the opposite effect that an agonist would. The spectrum of drug continuum also includes partial agonists and partial inverse agonists, which comprise the wide majority of neurological clinical treatments. The ultimate clinical effect of a drug can be analyzed with a dose-response curve. | 0 | Neurochemistry |
Luciferin is widely used in science and medicine as a method of in vivo imaging, using living organisms to non-invasively detect images and in molecular imaging. The reaction between luciferin substrate paired with the receptor enzyme luciferase produces a catalytic reaction, generating bioluminescence. This reaction and the luminescence produced is useful for imaging such as detecting tumors from cancer or capable of measuring gene expression. | 1 | Bioluminescence |
Functional Ensemble of Temperament (FET) is a neurochemical model suggesting specific functional roles of main neurotransmitter systems in the regulation of behaviour. | 0 | Neurochemistry |
Conformational study on neuromuscular blocking drugs is relatively new and developing. Traditional SAR studies do not specify environmental factors on molecules. Computer-based conformational searches assume that the molecules are in vacuo, which is not the case in vivo. Solvation models take into account the effect of a solvent on the conformation of the molecule. However, no system of solvation can mimic the effect of the complex fluid composition of the body.
The division of muscle relaxants to rigid and non-rigid is at most qualitative. The energy required for conformational changes may give a more precise and quantitative picture. Energy required for reducing onium head distance in the longer muscle relaxant chains may quantify their ability to bend and fit its receptive sites. Using computers it is possible to calculate the lowest energy state conformer and thus most populated and best representing the molecule. This state is referred to as the global minimum. The global minimum for some simple molecules can be discovered quite easily with certainty. Such as for decamethonium the straight line conformer is clearly the lowest energy state. Some molecules, on the other hand, have many rotatable bonds and their global minimum can only be approximated. | 0 | Neurochemistry |
Two functional groups contribute significantly to aminosteroidal neuromuscular blocking potency, it is presumed to enable them to bind the receptor at two points. A bis-quaternary two point arrangement on A and D-ring (binding inter-site) or a D-ring acetylcholine moiety (binding at two points intra-site) are most likely to succeed. A third group can have variable effects. The quaternary and acetyl groups on the A and D ring of pipecuronium prevent it from binding intra-site (binding to two points at the same site). Instead, it must bind as bis-quaternary (inter-site). These structures are very dissimilar from acetylcholine and free pipecuronium from nicotinic or muscarinic side-effects linked to acetylcholine moiety. Also, they protect the molecule from hydrolysis by cholinesterases, which explain its nature of kidney excretion. The four methyl-groups on the quaternary N atoms make it less lipophilic than most aminosteroids. This also affects pipecuroniums metabolism by resisting hepatic uptake, metabolism, and biliary excretion. The length of the molecule (2.1 nm, close to ideal) and its rigidness make pipecuronium the most potent and clean one-bulk bis-quaternary. Even though the N-N distance (1.6 nm) is far away from what is considered ideal, its onium heads are well-exposed, and the quaternary groups help to bring together the onium heads to the anionic centers of the receptors without chirality issues.
Adding more than two onium heads in general does not add to potency. Though the third onium head in gallamine seems to help position the two outside heads near the optimum molecular length, it can interfere unfavorably and gallamine turns out to be a weak muscle relaxant, like all multi-quaternary compounds.
Considering acetylcholine a quaternizing group larger than methyl and an acyl group larger than acetyl would reduce the molecule's potency. The charged N and the carbonyl O atoms are distanced from structures they bind to on receptive sites and, thus, decrease potency. The carbonyl O in vecuronium for example is thrust outward to appose the H-bond donor of the receptive site. This also helps explain why gallamine, rocuronium, and rapacuronium are of relatively low potency.
In general, methyl quaternization is optimal for potency but, opposing this rule, the trimethyl derivatives of gallamine are of lower potency than gallamine. The reason for this is that gallamine has a suboptimal N-N distance. Substituting the ethyl groups with methyl groups would make the molecular length also shorter than optimal. Methoxylation of tetrahydroisoquinolinium agents seems to improve their potency. How methoxylation improves potency is still unclear.
Histamine release is a common attribute of benzylisoquinolinium muscle relaxants. This problem generally decreases with increased potency and smaller doses. The need for larger doses increases the degree of this side-effect. Conformational or structural explanations for histamine release are not clear. | 0 | Neurochemistry |
Parkinsons disease is caused by the loss of dopamine stimulation to the basal ganglia of the midbrain, resulting in tremor at rest and bradykinesia. In some rare forms, protein aggregation of alpha-synuclein and parkin can elicit symptoms of Parkinsons disease. For a variety of drugs, restoring dopamine to the central nervous system remains the target therapy. Because dopamine cannot pass the blood brain barrier on its own, the dopamine precursor L-DOPA is used in its stead. However, synaptic plasticity renders this treatment decreasingly effective with time. Another treatment option is bromocriptine, which directly stimulates D Dopamine Receptors. Bromocriptine is less effective than L-Dopa in reducing symptoms, but provides less dyskinesia. Often, the two drugs are used in concert with one another.
New approaches to treatment include deep brain simulation and cell transplantation with stem cells. Deep brain stimulation offsets symptoms rather than cures, and stem cell studies have been extremely disappointing, despite relative success with animal models. Gene therapy may provide a novel route to introduce new dopamine production via viral-medicated gene transfection, but clinical trials are yet to be completed. | 0 | Neurochemistry |
Biocurious planned to tweak the biobrick containing six genes, including luciferin-regenerating enzyme and luciferase from fireflies. During initial development, they would use Agrobacterium to test the transfer of the genetic circuit. When producing the final product, they intended to instead use a gene gun to avoid issues related to regulation of GM plants. Over the course of the project, several plants were mentioned as being recipients, including Arabidopsis thaliana, Nicotiana tabacum, and roses. Issues surrounding the production included the difficulty of moving the six component genes of the metabolic pathway, increasing the dim light produced by the plant following insertion, and preventing the pathway from being silenced. | 1 | Bioluminescence |
Neuromodulation also refers to an emerging class of medical therapies that target the nervous system for restoration of function (such as in cochlear implants), relief of pain, or control of symptoms, such as tremor seen in movement disorders like Parkinson's disease. The therapies consist primarily of targeted electrical stimulation, or infusion of medications into the cerebrospinal fluid using intrathecal drug delivery, such as baclofen for spasticity. Electrical stimulation devices include deep brain stimulation systems (DBS), colloquially referred to as "brain pacemakers", spinal cord stimulators (SCS) and vagus nerve stimulators (VNS), which are implanted using minimally invasive procedures, or transcutaneous electrical nerve stimulation and scrambler therapy devices, which are fully external, among others. | 0 | Neurochemistry |
p75NTR is a member of the tumor necrosis factor receptor superfamily. p75NTR/LNGFR was the first member of this large family of receptors to be characterized, that now contains about 25 receptors, including tumor necrosis factor 1 (TNFR1) and TNFR2, Fas, RANK, and CD40.
All members of the TNFR superfamily contain structurally related cysteine-rich modules in their ECDs. p75NTR is an unusual member of this family due to its propensity to dimerize rather than trimerize, because of its ability to act as a tyrosine kinase co-receptor, and because the neurotrophins are structurally unrelated to the ligands, which typically bind TNFR family members. Indeed, with the exception of p75NTR, essentially all members of the TNFR family preferentially bind structurally related trimeric Type II transmembrane ligands, members of the TNF ligand superfamily. | 0 | Neurochemistry |
It was found that the luciferase enzyme produced in fireflies is localized to the peroxisome within the photocytes. When mammalian cells were modified to produce the enzyme, it was found that they were targeted to the mammalian peroxisome as well. Because protein targeting to peroxisomes is not well understood, this finding is valuable for its potential to aid in the determination of peroxisome targeting mechanisms. If the cell produces a large amount of luciferase, some of the protein ends up in the cytoplasm. It is unknown what feature of the luciferase enzyme causes it to be targeted to the peroxisome since no particular protein sequences related to peroxisome targeting have been discovered. | 1 | Bioluminescence |
Julian Voss-Andreae, a German-born artist specializing in "protein sculptures," created sculptures based on the structure of GFP, including the 1.70 m (56") tall "Green Fluorescent Protein" (2004) and the 1.40 m (47") tall "Steel Jellyfish" (2006). The latter sculpture is located at the place of GFPs discovery by Shimomura in 1962, the University of Washingtons Friday Harbor Laboratories. | 1 | Bioluminescence |
Bioluminescence in bacteria can be regulated through a phenomenon known as autoinduction or quorum sensing. Quorum sensing is a form of cell-to-cell communication that alters gene expression in response to cell density. Autoinducer is a diffusible pheromone produced constitutively by bioluminescent bacteria and serves as an extracellular signalling molecule. When the concentration of autoinducer secreted by bioluminescent cells in the environment reaches a threshold (above 10 cells per mL), it induces the expression of luciferase and other enzymes involved in bioluminescence. Bacteria are able to estimate their density by sensing the level of autoinducer in the environment and regulate their bioluminescence such that it is expressed only when there is a sufficiently high cell population. A sufficiently high cell population ensures that the bioluminescence produced by the cells will be visible in the environment.
A well known example of quorum sensing is that which occurs between Aliivibrio fischeri and its host. This process is regulated by LuxI and LuxR, encoded by luxI and luxR respectively. LuxI is autoinducer synthase that produces autoinducer (AI) while LuxR functions as both a receptor and transcription factor for the lux operon. When LuxR binds AI, LuxR-AI complex activates transcription of the lux operon and induces the expression of luciferase. Using this system, A. fischeri has shown that bioluminescence is expressed only when the bacteria are host-associated and have reached sufficient cell densities.
Another example of quorum sensing by bioluminescent bacteria is by Vibrio harveyi, which are known to be free-living. Unlike Aliivibrio fischeri, V. harveyi do not possess the luxI/luxR regulatory genes and therefore have a different mechanism of quorum sensing regulation. Instead, they use the system known as three-channel quorum sensing system. Vibrio use small non-coding RNAs called Qrr RNAs to regulate quorum sensing, using them to control translation of energy-costly molecules. | 1 | Bioluminescence |
Sepiapterin reductase deficiency is an inherited pediatric disorder characterized by movement problems, and most commonly displayed as a pattern of involuntary sustained muscle contractions known as dystonia. Symptoms are usually present within the first year of age, but diagnosis is delayed due to physicians lack of awareness and the specialized diagnostic procedures. Individuals with this disorder also have delayed motor skills development including sitting, crawling, and need assistance when walking. Additional symptoms of this disorder include intellectual disability, excessive sleeping, mood swings, and an abnormally small head size. SR deficiency is a very rare condition. The first case was diagnosed in 2001, and since then there have been approximately 30 reported cases. At this time, the condition seems to be treatable, but the lack of overall awareness and the need for a series of atypical procedures used to diagnose this condition pose a dilemma. | 0 | Neurochemistry |
The kinetics of labeled derivatives of apamin were studied in vitro and in vivo in mice by Cheng-Raude et al. This shed some light on the kinetics of apamin itself. The key organ for excretion is likely to be the kidney, since enrichment of the labeled derivatives was found there. The peptide apamin is small enough to pass the glomerular barrier, facilitating renal excretion. The central nervous system, contrarily, was found to contain only very small amounts of apamin. This is unexpected, as this is the target organ for neurotoxicity caused by apamin. This low concentration thus appeared to be sufficient to cause the toxic effects.
However, these results disagree with a study of Vincent et al. After injection of a supralethal dose of radioactive acetylated apamin in mice, enrichment was found in the spinal cord, which is part of the target organ. Some other organs, including kidney and brain, contained only small amounts of the apamin derivative. | 0 | Neurochemistry |
Ion channels may be classified by gating, i.e. what opens and closes the channels. For example, voltage-gated ion channels open or close depending on the voltage gradient across the plasma membrane, while ligand-gated ion channels open or close depending on binding of ligands to the channel. | 0 | Neurochemistry |
Recent studies have shown that SK channels do not only regulate afterhyperpolarization, they also have an effect on synaptic plasticity. This is the activity-dependent adaptation of the strength of synaptic transmission. Synaptic plasticity is an important mechanism underlying learning and memory processes. Apamin is expected to influence these processes by inhibiting SK channels. It has been shown that apamin enhances learning and memory in rats and mice. This may provide a basis for the use of apamin as a treatment for memory disorders and cognitive dysfunction. However, due to the risk of toxic effects, the therapeutic window is very narrow.
SK channel blockers may have a therapeutic effect on Parkinson's disease. Dopamine, which is depleted in this disease, will be released from midbrain dopaminergic neurons when these SK channels are inhibited. SK channels have also been proposed as targets for the treatment of epilepsy, emotional disorders and schizophrenia. | 0 | Neurochemistry |
The noradrenaline system consists of around 15,000 neurons, primarily in the locus coeruleus. This is diminutive compared to the more than 100 billion neurons in the brain. As with dopaminergic neurons in the substantia nigra, neurons in the locus coeruleus tend to be melanin-pigmented. Noradrenaline is released from the neurons, and acts on adrenergic receptors. Noradrenaline is often released steadily so that it can prepare the supporting glial cells for calibrated responses. Despite containing a relatively small number of neurons, when activated, the noradrenaline system plays major roles in the brain including involvement in suppression of the neuroinflammatory response, stimulation of neuronal plasticity through LTP, regulation of glutamate uptake by astrocytes and LTD, and consolidation of memory. | 0 | Neurochemistry |
Acetylcholine (ACh) is a neurotransmitter found in the brain, neuromuscular junctions and the autonomic ganglia.
Muscarinic receptors are used in the following roles: | 0 | Neurochemistry |
BC200 RNA is expressed in the dendrites as ribonucleoprotein particles. Protein synthesis at the synapses of neurons contribute to neuronal plasticity and help prevent neuronal degradation. Small, non-coding RNAs such as BC200 RNA work to repress translation by inhibiting its initiation. During eukaryotic translation, the preinitiation complex binds mRNA and scans the coding strand for a start codon. This step is often subject to the control of a family of initiation factors and these factors are often a target for translational regulators. Poly(A)-binding protein (PABP) has been shown to bind to BC200 RNA further confirming their role as regulators of protein biosynthesis in synapses.
BC200 RNA targets an ATP-dependent RNA helicase called eukaryotic initiation factor 4A (eIF4A). eIF4A requires energy from ATP hydrolysis to unwind the double helix and initiate translation. However, BC200 RNA interferes with the transmission of energy after hydrolysis by changing the conformation of eIF4A, and thus the energy needed to unwind the double helix is never appropriately supplied and initiation of translation is inhibited.
This highly localized uncoupling of the ATPase activity, and subsequently the unwinding of the RNA duplex is proposed to have evolved as a result of the growing complexity of postsynaptic neurons and neuronal activities. Non-coding RNA molecules evolve at a much faster rate than gene-encoding proteins; thus, the sustained conservation of the BC200 RNA transcript indicates its importance for nervous system function. | 0 | Neurochemistry |
Bioluminescent bacteria are most abundant in marine environments during spring blooms when there are high nutrient concentrations. These light-emitting organisms are found mainly in coastal waters near the outflow of rivers, such as the northern Adriatic Sea, Gulf of Trieste, northwestern part of the Caspian Sea, coast of Africa and many more. These are known as milky seas. Bioluminescent bacteria are also found in freshwater and terrestrial environments but are less wide spread than in seawater environments. They are found globally, as free-living, symbiotic or parasitic forms and possibly as opportunistic pathogens. Factors that affect the distribution of bioluminescent bacteria include temperature, salinity, nutrient concentration, pH level and solar radiation. For example, Aliivibrio fischeri grows favourably in environments that have temperatures between 5 and 30 °C and a pH that is less than 6.8; whereas, Photobacterium phosphoreum thrives in conditions that have temperatures between 5 and 25 °C and a pH that is less than 7.0. | 1 | Bioluminescence |
The property of photoconverted fluorescence Kaede protein was serendipitously discovered and first reported by Ando et al. in Proceedings of the United States National Academy of Sciences. An aliquot of Kaede protein was discovered to emit red fluorescence after being left on the bench and exposed to sunlight. Subsequent verification revealed that Kaede, which is originally green fluorescent, after exposure to UV light is photoconverted, becoming red fluorescent. It was then named Kaede. | 1 | Bioluminescence |
p75NTR serves as a regulator for actin assembly. Ras homolog family member A (RhoA) causes the actin cytoskeleton to become rigid which limits growth cone mobility and inhibits neuronal elongation in the developing nervous system. p75NTR without a ligand bound activates RhoA and limits actin assembly, but neurotrophin binding to p75NTR can inactivate RhoA and promote actin assembly. p75NTR associates with the Rho GDP dissociation inhibitor (RhoGDI), and RhoGDI associates with RhoA. Interactions with Nogo can strengthen the association between p75NTR and RhoGDI. Neurotrophin binding to p75NTR inhibits the association of RhoGDI and p75NTR, thereby suppressing RhoA release and promoting growth cone elongation (inhibiting RhoA actin suppression). | 0 | Neurochemistry |
Cys-loop receptors have structural elements that are well conserved, with a large extracellular domain (ECD) harboring an alpha-helix and 10 beta-strands. Following the ECD, four transmembrane segments (TMSs) are connected by intracellular and extracellular loop structures. Except the TMS 3-4 loop, their lengths are only 7-14 residues. The TMS 3-4 loop forms the largest part of the intracellular domain (ICD) and exhibits the most variable region between all of these homologous receptors. The ICD is defined by the TMS 3-4 loop together with the TMS 1-2 loop preceding the ion channel pore. Crystallization has revealed structures for some members of the family, but to allow crystallization, the intracellular loop was usually replaced by a short linker present in prokaryotic cys-loop receptors, so their structures as not known. Nevertheless, this intracellular loop appears to function in desensitization, modulation of channel physiology by pharmacological substances, and posttranslational modifications. Motifs important for trafficking are therein, and the ICD interacts with scaffold proteins enabling inhibitory synapse formation. | 0 | Neurochemistry |
* Alzate O. "Neuroproteomics." Frontiers in Neuroscience Series (October 2010) C.R.C. Press.
* Abul-Husn, Noura S., Lakshmi A. Devi. "Neuroproteomics of the Synapse and Drug Addiction." The Journal of Pharmacology and Experimental Therapeutics 138 (2006): 461-468.
* Becker, Michael, Jens Schindler, Hans G. Nothwang. "Neuroproteomics - the Tasks Lying Ahead." Electrophoresis 27 (2006): 2819-2829.
* Butcher, James. "Neuroproteomics Comes of Age." The Lancet Neurology 6 (2007): 851-852.
* Kim, Sandra I., Hans Voshol, Jan van Oostrum, Terri G. Hastings, Michael Casico, Marc J. Glucksmann. “Neuroproteomics: Expression Profiling of the Brain’s Proteomes in Health and Disease.” Neurochemical Research 29 (2004): 1317-1331
* Kobeissy, Firas H., Andrew K. Ottens, Zhiqun Zhang, Ming Cheng Liu, Nancy D. Denslow, Jitendra R. Dave, Frank C. Tortella, Ronald L. Hayes, Kevin K. Wang. "Novel Differential Neuroproteomics Analysis of Traumatic Brain Injury in Rats." Molecular & Cellular Proteomics 5 (2006): 1887-1898.
* Liu, Tong, Veera D'mello, Longwen Deng, Jun Hu, Michael Ricardo, Sanqiang Pan, Xiaodong Lu, Scott Wadsworth, John Siekierka, Raymond Birge, Hong Li. "A Multiplexed Proteomics Approach to Differentiate Neurite Outgrowth Patterns." Journal of Neuroscience Methods 158 (2006): 22-29.
* Ottens, Andrew K., Firas H. Kobeissy, Erin C. Golden, Zhiqun Zhang, William E. Haskins, Su-Shing Chen, Ronald L. Hayes, Kevin K. Wang, Nancy D. Denslow. "Neuroproteomics in Neurotrauma." Mass Spectrometry Reviews 25 (2006): 380-406.
* Ottens, Andrew K. "The methodology of neuroproteomics." Methods Mol Biol. (2009) 566:1-21.
* Southey, Bruce R., Andinet Amare, Tyler A. Zimmerman, Sandra L. Rodriguez, Jonathan V. Sweedler. "NeuroPred: a Tool to Predict Cleavage Sites in Neuropeptide Precursors and Provide the Masses of the Resulting Peptides." Nucleic Acids Research 34 (2006): 267-272.
* Tribl, F, K Marcus, G Bringmann, H.E. Meyer, M Gerlach, P Riederer. "Proteomics of the Human Brain: Sub-Proteomes Might Hold the Key to Handle Brain Complexity." Journal of Neural Transmission 113 (2006): 1041-1054.
* Williams, Kenneth, Terence Wu, Christopher Colangelo, Angus C. Nairn. "Recent Advances in Neuroproteomics and Potential Application to Studies of Drug Addiction." Neuropharmacology 47 (2004): 148-166.
* Kobeissy, Firas H., Sadasivan S, Liu J, Mark S Gold, Kevin K. Wang. "Psychiatric research: psychoproteomics, degradomics and systems biology." Expert Rev Proteomics 5 (2008): 293-314. | 0 | Neurochemistry |
Firefly luciferase is thought to be a homolog of long-chain fatty acyl-CoA synthetase because of its ability to synthesize luciferyl-CoA from CoA and dehydroluciferyl-AMP. Inouye tested this hypothesis in 2010 by expressing the cDNA of Photinus pyralis and Lychocoriolaus lateralis luciferses in E. coli through cold shock gene expression. The resulting enzymes were then exposed to long-chain fatty acids, short-chain fatty acids, amino acids, and imino acids. Unsurprisingly, Inouye found that the luciferases only showed adenylation activity when exposed to long-chain fatty acids.
The gene product of CG6178 in Drosophila was also found to have high amino acid sequence similarity with firefly luciferase. While it did show high adenyltation activity when exposed to long-chain fatty acids, there was no luminescence when exposed to oxygen and LH-AMP– further suggesting that luciferase emerged as a long-chain fatty acyl-CoA homolog due to gene duplication. | 1 | Bioluminescence |
Coelenterazine is found in radiolarians, ctenophores, cnidarians, squid, brittle stars, copepods, chaetognaths, fish, and shrimp. It is the prosthetic group in the protein aequorin responsible for the blue light emission. | 1 | Bioluminescence |
Inhaled anesthetics inhibit nicotinic acetylcholine receptors (nAChRs) and potentiate neuromuscular blockage with nondepolarising NMBAs. It depends on the type of volatile anesthetic (desflurane > sevoflurane > isoflurane > nitrous oxide), the concentration and the duration of exposure. | 0 | Neurochemistry |
As all other fluorescent proteins, Kaede can be the regional optical markers for gene expression and protein labeling for the study of cell behaviors.
One of the most useful applications is the visualization of neurons. Delineation of an individual neuron is difficult due to the long and thin processes which entangle with other neurons. Even when cultured neurons are labeled with fluorescent proteins, they are still difficult to identify individually because of the dense package.
In the past, such visualization could be done conventionally by filling neurons with Lucifer yellow or sulforhodamine, which is a laborious technique.[1] After the discovery of Kaede protein, it was found to be useful in delineating individual neurons. The neurons are transfected by Kaede protein cDNA, and are UV irradiated. The red, photoconverted Kaede protein has free diffusibility in the cell except for the nucleus, and spreads over the entire cell including dendrites and axon. This technique help disentangle the complex networks established in a dense culture. Besides, by labeling neurons with different colors by UV irradiating with different duration times, contact sites between the red and green neurons of interest are allowed to be visualized.
The ability of visualization of individual cells is also a powerful tool to identify the precise morphology and migratory behaviors of individual cells within living cortical slices. By Kaede protein, a particular pair of daughter cells in neighboring Kaede-positive cells in the ventricular zone of mouse brain slices can be followed. The cell-cell borders of daughter cells are visualized and the position and distance between two or more cells can be described.
As the change in the fluorescent colour is induced by UV light, marking of cells and subcellular structures is efficient even when only a partial photoconversion is induced. | 1 | Bioluminescence |
Brain cytoplasmic 200 long-noncoding RNA (or BC200 lncRNA) is a 200 nucleotide RNA transcript found predominantly in the brain with a primary function of regulating translation by inhibiting its initiation. As a long non-coding RNA, it belongs to a family of RNA transcripts that are not translated into protein (ncRNAs). Of these ncRNAs, lncRNAs are transcripts of 200 nucleotides or longer and are almost three times more prevalent than protein-coding genes. Nevertheless, only a few of the almost 60,000 lncRNAs have been characterized, and little is known about their diverse functions (transcriptional interference, chromatin remodeling, splicing, translation regulation, interaction with miRNAs and siRNAs, and mRNA degradation). BC200 is one lncRNA that has given insight into their specific role in translation regulation, and implications in various forms of cancer as well as Alzheimer's disease.
The accepted gene symbol for the BC200-coding gene is BCYRN1, for Brain cytoplasmic RNA 1. | 0 | Neurochemistry |
Evidence for the role of the endocannabinoid system in food-seeking behavior comes from a variety of cannabinoid studies. Emerging data suggests that THC acts via CB receptors in the hypothalamic nuclei to directly increase appetite. It is thought that hypothalamic neurons tonically produce endocannabinoids that work to tightly regulate hunger. The amount of endocannabinoids produced is inversely correlated with the amount of leptin in the blood. For example, mice without leptin not only become massively obese but express abnormally high levels of hypothalamic endocannabinoids as a compensatory mechanism. Similarly, when these mice were treated with an endocannabinoid inverse agonists, such as rimonabant, food intake was reduced. When the CB receptor is knocked out in mice, these animals tend to be leaner and less hungry than wild-type mice. A related study examined the effect of THC on the hedonic (pleasure) value of food and found enhanced dopamine release in the nucleus accumbens and increased pleasure-related behavior after administration of a sucrose solution. A related study found that endocannabinoids affect taste perception in taste cells. In taste cells, endocannabinoids were shown to selectively enhance the strength of neural signaling for sweet tastes, whereas leptin decreased the strength of this same response. While there is need for more research, these results suggest that cannabinoid activity in the hypothalamus and nucleus accumbens is related to appetitive, food-seeking behavior. | 0 | Neurochemistry |
The harmful effects of glutamate on the central nervous system were first observed in 1954 by T. Hayashi, a Japanese scientist who stated that direct application of glutamate caused seizure activity, though this report went unnoticed for several years. D. R. Lucas and J. P. Newhouse, after noting that "single doses of [20–30 grams of sodium glutamate in humans] have ... been administered intravenously without permanent ill-effects", observed in 1957 that a subcutaneous dose described as "a little less than lethal", destroyed the neurons in the inner layers of the retina in newborn mice. In 1969, John Olney discovered that the phenomenon was not restricted to the retina, but occurred throughout the brain, and coined the term excitotoxicity. He also assessed that cell death was restricted to postsynaptic neurons, that glutamate agonists were as neurotoxic as their efficiency to activate glutamate receptors, and that glutamate antagonists could stop the neurotoxicity.
In 2002, Hilmar Bading and co-workers found that excitotoxicity is caused by the activation of NMDA receptors located outside synaptic contacts. The molecular basis for toxic extrasynaptic NMDA receptor signaling was uncovered in 2020 when Hilmar Bading and co-workers described a death signaling complex that consists of extrasynaptic NMDA receptor and TRPM4. Disruption of this complex using NMDAR/TRPM4 interface inhibitors (also known as ‚interface inhibitors‘) renders extrasynaptic NMDA receptor non-toxic. | 0 | Neurochemistry |
This term could be used to describe the action of acetylcholine on nicotinic receptors, glutamate on NMDA receptors or GABA on GABAa receptors. | 0 | Neurochemistry |
Trace amines are an endogenous group of trace amine-associated receptor 1 (TAAR1) agonists – and hence, monoaminergic neuromodulators – that are structurally and metabolically related to classical monoamine neurotransmitters. Compared to the classical monoamines, they are present in trace concentrations. They are distributed heterogeneously throughout the mammalian brain and peripheral nervous tissues and exhibit high rates of metabolism. Although they can be synthesized within parent monoamine neurotransmitter systems, there is evidence that suggests that some of them may comprise their own independent neurotransmitter systems.
Trace amines play significant roles in regulating the quantity of monoamine neurotransmitters in the synaptic cleft of monoamine neurons with . They have well-characterized presynaptic amphetamine-like effects on these monoamine neurons via TAAR1 activation; specifically, by activating TAAR1 in neurons they promote the release and prevent reuptake of monoamine neurotransmitters from the synaptic cleft as well as inhibit neuronal firing. Phenethylamine and amphetamine possess analogous pharmacodynamics in human dopamine neurons, as both compounds induce efflux from vesicular monoamine transporter 2 (VMAT2) and activate TAAR1 with comparable efficacy.
Like dopamine, norepinephrine, and serotonin, the trace amines have been implicated in a vast array of human disorders of affect and cognition, such as ADHD, depression and schizophrenia, among others. Trace aminergic hypo-function is particularly relevant to ADHD, since urinary and plasma phenethylamine concentrations are significantly lower in individuals with ADHD relative to controls and the two most commonly prescribed drugs for ADHD, amphetamine and methylphenidate, increase phenethylamine biosynthesis in treatment-responsive individuals with ADHD. A systematic review of ADHD biomarkers also indicated that urinary phenethylamine levels could be a diagnostic biomarker for ADHD. | 0 | Neurochemistry |
According to Entertainment Weekly, "The Navi can commune with animals on their planet by literally plugging their braid into the creatures nerve systems. To become a warrior, a Navi must tame and ride a flying creature known as Ikran." The Navi also use this neural bonding system, called "tsaheylu", to mate with a "life partner", a bond that, when made, cannot be broken in the Navis lifetime. This is akin to human marriage.
The Navi way of life revolves around their religion, and the Home Tree. The Navi sleep in hammocks in large groups for comfort and as a warning system.
Conceived for the film was the Navi language, a constructed language often spoken by the actors when they played Navi characters. The Navi language was created by communications professor emeritus and linguistics consultant Paul Frommer of the University of Southern California. He designed the language so as to be speakable by human actors, combining syntactic and grammatical rules from other existing languages. Frommer created over a thousand words for the Navi language and coached the actors who narrated Navi characters. When communicating to humans in the film, Navi characters – especially Neytiri – speak in accented and broken English.
Human visitors see the Navi as possessing a religion, whose chief and possibly sole deity is a benevolent goddess known as Eywa. The Navi are able to physically connect to Eywa when they use their braids to connect to the Tree of Souls and other similar flora which function as the global brain's interfaces. Eywa is said to have a connection to all things Pandoran.
Political power is exceedingly diffused, with each clan being a sovereign entity under either the diarchical rule of both a temporal chieftain (known as an Oloeyktan) and a spiritual chieftain (known as a Tsahik), or the monarchical rule of a single individual who holds the two separate offices simultaneously. The numerous clans are seemingly only ever brought together as a tribe by Toruk Makto, a messianic war chief whose office is both non-permanent and apparently the only one with an authority that covers the entire race of Navi. By the time of the film, there had only been five Toruk Maktos in the history of the tribe, and the last one had ruled no fewer than four generations before the present day. This may be due to the fact that the Toruk Maktos seem to draw their power from a situation of explicitly external danger, and therefore are not really necessary for the day to day internal running of the tribal clans. Succession to the various offices is smooth, however, based more on popular recognition and customary worthiness than on anything else, and respect for hierarchical superiors appears to be high. | 1 | Bioluminescence |
When p75NTR initiates apoptosis, NGF binding to Tropomyosin receptor kinase A (TrkA) can negate p75NTR apoptotic effects. p75NTR c-Jun kinase pathway activation (which causes apoptosis) is suppressed when NGF binds to TrkA. p75NTR activation of NF-kB, which promotes survival, is unaffected by NGF binding to TrkA. | 0 | Neurochemistry |
Huntington's disease is a disease characterized by minor coordination problems, jerking eye movements, and uncontrollable movement of peripheral limbs. Symptoms generally occur at the age of 40, and are often accompanied by depression and psychosis. The disease is caused by a mutation in the Huntingtin gene, on chromosome 4, which causes abnormally large numbers of glutamate residues in the protein. Via an unknown mechanism, this accumulation leads to neurodegeneration in the caudate nucleus and putamen, selectively destroying GABAergic neurons which project to the globus pallidus. There is also significant necrosis in the thalamus and cerebral cortex. Cholinergic interneurons and dopaminergic neurons in the midbrain are largely unaffected.
Treatment for Huntington's disease is extremely limited due to the lack of knowledge concerning the pathogenesis of protein accumulation, though drugs used include dopamine receptor antagonists to minimize tremors and antidepressants to ameliorate symptoms of psychosis and depression. | 0 | Neurochemistry |
It is known that muscarinic acetylcholine receptors also appear on the pre-synaptic membrane of somatic neurons in the neuro-muscular junction, where they are involved in the regulation of acetylcholine release. | 0 | Neurochemistry |
Mutations in K2.3 are suspected to be a possible underlying cause for several neurological disorders, including schizophrenia, bipolar disorder, Alzheimer's disease, anorexia nervosa and ataxia as well as myotonic muscular dystrophy. | 0 | Neurochemistry |
Channels differ with respect to the ion they let pass (for example, Na, K, Cl), the ways in which they may be regulated, the number of subunits of which they are composed and other aspects of structure. Channels belonging to the largest class, which includes the voltage-gated channels that underlie the nerve impulse, consists of four or sometimes five subunits with six transmembrane helices each. On activation, these helices move about and open the pore. Two of these six helices are separated by a loop that lines the pore and is the primary determinant of ion selectivity and conductance in this channel class and some others. The existence and mechanism for ion selectivity was first postulated in the late 1960s by Bertil Hille and Clay Armstrong. The idea of the ionic selectivity for potassium channels was that the carbonyl oxygens of the protein backbones of the "selectivity filter" (named by Bertil Hille) could efficiently replace the water molecules that normally shield potassium ions, but that sodium ions were smaller and cannot be completely dehydrated to allow such shielding, and therefore could not pass through. This mechanism was finally confirmed when the first structure of an ion channel was elucidated. A bacterial potassium channel KcsA, consisting of just the selectivity filter, "P" loop, and two transmembrane helices was used as a model to study the permeability and the selectivity of ion channels in the Mackinnon lab. The determination of the molecular structure of KcsA by Roderick MacKinnon using X-ray crystallography won a share of the 2003 Nobel Prize in Chemistry.
Because of their small size and the difficulty of crystallizing integral membrane proteins for X-ray analysis, it is only very recently that scientists have been able to directly examine what channels "look like." Particularly in cases where the crystallography required removing channels from their membranes with detergent, many researchers regard images that have been obtained as tentative. An example is the long-awaited crystal structure of a voltage-gated potassium channel, which was reported in May 2003. One inevitable ambiguity about these structures relates to the strong evidence that channels change conformation as they operate (they open and close, for example), such that the structure in the crystal could represent any one of these operational states. Most of what researchers have deduced about channel operation so far they have established through electrophysiology, biochemistry, gene sequence comparison and mutagenesis.
Channels can have single (CLICs) to multiple transmembrane (K channels, P2X receptors, Na channels) domains which span plasma membrane to form pores. Pore can determine the selectivity of the channel. Gate can be formed either inside or outside the pore region. | 0 | Neurochemistry |
The nomenclature of modified GFPs is often confusing due to overlapping mapping of several GFP versions onto a single name. For example, mGFP often refers to a GFP with an N-terminal palmitoylation that causes the GFP to bind to cell membranes. However, the same term is also used to refer to monomeric GFP, which is often achieved by the dimer interface breaking A206K mutation. Wild-type GFP has a weak dimerization tendency at concentrations above 5 mg/mL. mGFP also stands for "modified GFP," which has been optimized through amino acid exchange for stable expression in plant cells. | 1 | Bioluminescence |
Coelenterazine was simultaneously isolated and characterized by two groups studying the luminescent organisms sea pansy (Renilla reniformis) and the cnidarian Aequorea victoria, respectively. Both groups independently discovered that the same compound was used in both luminescent systems. The molecule was named after the now-obsolete phylum coelenterata. Likewise, the two main metabolites – coelenteramide and coelenteramine – were named after their respective functional groups. While coelenterazine was first discovered in Aequorea victoria, it was later shown that they do not synthesize coelenterazine, but obtain it through their diet, largely from crustaceans and copepods. | 1 | Bioluminescence |
The developing embryo expresses cannabinoid receptors early in development that are responsive to anandamide secreted in the uterus. This signaling is important in regulating the timing of embryonic implantation and uterine receptivity. In mice, it has been shown that anandamide modulates the probability of implantation to the uterine wall. For example, in humans, the likelihood of miscarriage increases if uterine anandamide levels are too high or low. These results suggest that intake of exogenous cannabinoids (e.g., cannabis) can decrease the likelihood for pregnancy for women with high anandamide levels, and alternatively, it can increase the likelihood for pregnancy in women whose anandamide levels were too low. | 0 | Neurochemistry |
Milky seas (Somali: Kaluunka iftiima; English: Milky seas), also called mareel, is a luminous phenomenon in the ocean in which large areas of seawater (up to ) appear to glow translucently (in varying shades of blue). Such occurrences glow brightly enough at night to be visible from satellites orbiting Earth.
Mariners and other seafarers have reported that the ocean often emits a visible glow which extends for miles at night. In 2005, scientists announced that for the first time, they had obtained photographic evidence of this glow. It is most likely caused by bioluminescence. | 1 | Bioluminescence |
Common applications of BLI include in vivo studies of infection (with bioluminescent pathogens), cancer progression (using a bioluminescent cancer cell line), and reconstitution kinetics (using bioluminescent stem cells).
Researchers at UT Southwestern Medical Center have shown that bioluminescence imaging can be used to determine the effectiveness of cancer drugs that choke off a tumor's blood supply. The technique requires luciferin to be added to the bloodstream, which carries it to cells throughout the body. When luciferin reaches cells that have been altered to carry the firefly gene, those cells emit light.
The BLT inverse problem of 3D reconstruction of the distribution of bioluminescent molecules from data measured on the animal surface is inherently ill-posed. The first small animal study using BLT was conducted by researchers at the University of Southern California, Los Angeles, USA in 2005. Following this development, many research groups in USA and China have built systems that enable BLT.
Mustard plants have had the gene that makes fireflies' tails glow added to them so that the plants glow when touched. The effect lasts for an hour, but an utra-sensitive camera is needed to see the glow. | 1 | Bioluminescence |
This receptor is found mediating slow EPSP at the ganglion in the postganglionic nerve, is common in exocrine glands and in the CNS.
It is predominantly found bound to G proteins of class G, which use upregulation of phospholipase C and, therefore, inositol trisphosphate and intracellular calcium as a signaling pathway. A receptor so bound would not be susceptible to CTX or PTX. However, G (causing a downstream decrease in cAMP) and G (causing an increase in cAMP) have also been shown to be involved in interactions in certain tissues, and so would be susceptible to PTX and CTX, respectively. | 0 | Neurochemistry |
The symbiotic relationship between the Hawaiian bobtail squid Euprymna scolopes and the marine gram-negative bacterium Aliivibrio fischeri has been well studied. The two organisms exhibit a mutualistic relationship in which bioluminescence produced by A. fischeri helps to attract pray to the squid host, which provides nutrient-rich tissues and a protected environment forA. fischeri. Bioluminescence provided by A. fischeri also aids in the defense of the squid E. scolopes by providing camouflage during its nighttime foraging activity. Following bacterial colonization, the specialized organs of the squid undergo developmental changes and a relationship becomes established. The squid expels 90% of the bacterial population each morning, because it no longer needs to produce bioluminescence in the daylight. This expulsion benefits the bacteria by aiding in their dissemination. A single expulsion by one bobtail squid produces enough bacterial symbionts to fill 10,000m of seawater at a concentration that is comparable to what is found in coastal waters. Thus, in at least some habitats, the symbiotic relationship between A. fischeri and E. scolopes plays a key role in determining the abundance and distribution of E. scolopes. There is a higher abundance of A. fischeri in the vicinity of a population of E. scolopes and this abundance markedly decreases with increasing distance from the host's habitat.
Bioluminescent Photobacterium species also engage in mutually beneficial associations with fish and squid. Dense populations of P. kishitanii, P. leiogathi, and P. mandapamensis can live in the light organs of marine fish and squid, and are provided with nutrients and oxygen for reproduction in return for providing bioluminescence to their hosts, which can aid in sex-specific signaling, predator avoidance, locating or attracting prey, and schooling.<!-- Empty reference | 1 | Bioluminescence |
Nociception is the form of somatic sensation that detects potentially tissue-damaging noxious stimuli. Peripheral nociceptors uniquely express transient receptor potentials which are sensitive to potentially-damaging mechanical, chemical, or thermal stimuli. Nociceptors also contain receptors for pain and inflammatory-related mediators or cytokines. Peripheral nociceptors transmit noxious stimuli to the dorsal root ganglia, the dorsal horn, and further to the trigeminal ganglia in the brain. Pain has both a localizing somatic sensory component and an aversive emotional and motivational component. Pain travels through a variety of pathways via first pain on Alpha Delta fibers and second pain on slowly conducting C-fibers.
The dorsal horn of the spinal cord serves as a major integration center for both ascending nociceptive information and descending antinociceptive influences from the brain. Plasticity within the dorsal horn is mediated by NMDA glutamate receptors and key in the initiation of chronic pain by decreasing the excitability threshold in nociceptive pathways. Additionally, damage to neurons in nociceptive pathways leads to neuropathic pain. Three families in northern Pakistan were congenitally unable to perceive pain due to their homozygous loss of function mutation in the SCN9A gene which codes for the voltage-gated sodium channel Na1.7 . This key finding allowed pharmacologists to begin researching if the Na1.7 is a substantial molecular target for analgesic (antipain) medications.
Sensitization, in the clinical sense of the word, is a phenomenon in which nociceptors in an area beyond a tissue injury exhibit decreased thresholds for activation. Sensitization can be initiated by inflammatory prostaglandins or leukotrienes and are therefore the targets of nonsteroidal anti-inflammatory (NSAIDs) which block key enzymes in their synthesis. Additionally, opioid drugs suppress nociceptions by binding to endogenous opioid receptors. | 0 | Neurochemistry |
Green fluorescent protein may be used as a reporter gene.
For example, GFP can be used as a reporter for environmental toxicity levels. This protein has been shown to be an effective way to measure the toxicity levels of various chemicals including ethanol, p-formaldehyde, phenol, triclosan, and paraben. GFP is great as a reporter protein because it has no effect on the host when introduced to the host's cellular environment. Due to this ability, no external visualization stain, ATP, or cofactors are needed. With regards to pollutant levels, the fluorescence was measured in order to gauge the effect that the pollutants have on the host cell. The cellular density of the host cell was also measured. Results from the study conducted by Song, Kim, & Seo (2016) showed that there was a decrease in both fluorescence and cellular density as pollutant levels increased. This was indicative of the fact that cellular activity had decreased. More research into this specific application in order to determine the mechanism by which GFP acts as a pollutant marker. Similar results have been observed in zebrafish because zebrafish that were injected with GFP were approximately twenty times more susceptible to recognize cellular stresses than zebrafish that were not injected with GFP. | 1 | Bioluminescence |
The bright blue hues produced by the microorganisms during nights of very little moonlight or new moon attracts tourists to the bio bay. It is one of the three bio bays in Puerto Rico; the other two are Laguna Grande in Fajardo and La Parguera in Lajas. The bay and its surrounding mangrove forest are protected by the Vieques Bioluminescent Bay Natural Reserve and no swimming is allowed. Guided tours allow visitors to kayak in the bay and observe the bioluminescence. The bio bay is located near the beach community of Esperanza, between the barrios of Puerto Ferro and Puerto Real in Vieques, Puerto Rico. | 1 | Bioluminescence |
APP undergoes extensive post-translational modification including glycosylation, phosphorylation, sialylation, and tyrosine sulfation, as well as many types of proteolytic processing to generate peptide fragments. It is commonly cleaved by proteases in the secretase family; alpha secretase and beta secretase both remove nearly the entire extracellular domain to release membrane-anchored carboxy-terminal fragments that may be associated with apoptosis. Cleavage by gamma secretase within the membrane-spanning domain after beta-secretase cleavage generates the amyloid-beta fragment; gamma secretase is a large multi-subunit complex whose components have not yet been fully characterized, but include presenilin, whose gene has been identified as a major genetic risk factor for Alzheimer's.
The amyloidogenic processing of APP has been linked to its presence in lipid rafts. When APP molecules occupy a lipid raft region of membrane, they are more accessible to and differentially cleaved by beta secretase, whereas APP molecules outside a raft are differentially cleaved by the non-amyloidogenic alpha secretase. Gamma secretase activity has also been associated with lipid rafts. The role of cholesterol in lipid raft maintenance has been cited as a likely explanation for observations that high cholesterol and apolipoprotein E genotype are major risk factors for Alzheimer's disease. | 0 | Neurochemistry |
The hexapede (Yerik in Navi) are hexapodal deer-like creatures. They are dark blue herbivores with white and yellow stripes. Twin horn structures sheathe a thin, patterned membrane structure. Their small, sloped skull is topped by this light-colored fan structure. This fan has an eye pattern on it similar to those found in actual insects. A skin membrane hangs under the jaw and runs the length of the neck. Twin lines of dark hairlike bristles run down the hexapedes back. The antennae are at the back at the head. As a threat display, the hexapede flares up its twin membrane structure like a satellite dish and retracts both lips. It is scientifically known as Sexcruscervus caeruleus. | 1 | Bioluminescence |
Alba, a green-fluorescent rabbit, was created by a French laboratory commissioned by Eduardo Kac using GFP for purposes of art and social commentary. The US company Yorktown Technologies markets to aquarium shops green fluorescent zebrafish (GloFish) that were initially developed to detect pollution in waterways. NeonPets, a US-based company has marketed green fluorescent mice to the pet industry as NeonMice. Green fluorescent pigs, known as Noels, were bred by a group of researchers led by Wu Shinn-Chih at the Department of Animal Science and Technology at National Taiwan University. A Japanese-American Team created green-fluorescent cats as proof of concept to use them potentially as model organisms for diseases, particularly HIV. In 2009 a South Korean team from Seoul National University bred the first transgenic beagles with fibroblast cells from sea anemones. The dogs give off a red fluorescent light, and they are meant to allow scientists to study the genes that cause human diseases like narcolepsy and blindness. | 1 | Bioluminescence |
Neurotrophins that interact with p75NTR include NGF, NT-3, BDNF, and NT-4/5. Neurotrophins activating p75NTR may initiate apoptosis (for example, via c-Jun N-terminal kinases signaling, and subsequent p53, Jax-like proteins and caspase activation). This effect can be counteracted by anti-apoptotic signaling by TrkA.
Neurotrophin binding to p75NTR, in addition to apoptotic signaling, can also promote neuronal survival (for example, via NF-kB activation). There are multiple targets of Akt that could play a role in mediating p75NTR-dependent survival, but one of the more intriguing possibilities is that Ant-induced phosphorylation of IkB kinase 1 (IKK1) plays a role in the induction of NF-kB. | 0 | Neurochemistry |
Scintillons have been extensively purified from L. polyedra by centrifugation, and these purified scintillon preparations contain luciferase and luciferin binding protein as the only detectable protein components. The amount of luciferase, LBP and luciferin all vary over the course of a daily (circadian) period, as do the number of scintillons in the cell. These observations suggest that the circadian control of bioluminescence involves a daily synthesis and degradation of luciferase and LBP. When synthesized, these two proteins aggregate together and migrate to the vacuole membrane where LBP binds luciferin and the scintillons acquires an ability to produce light upon stimulation. | 1 | Bioluminescence |
A FMN-binding fluorescent protein (FbFP), also known as a LOV-based fluorescent protein, is a small, oxygen-independent fluorescent protein that binds flavin mononucleotide (FMN) as a chromophore.
They were developed from blue-light receptors (so called LOV-domains) found in plants and various bacteria. They complement the GFP-derivatives and –homologues and are particularly characterized by their independence of molecular oxygen and their small size. FbFPs absorb blue light and emit light in the cyan-green spectral range. | 1 | Bioluminescence |
Medications can adjust the release of brain neurotransmitters in cases of depression, anxiety disorder, schizophrenia and other mental disorders because an imbalance within neurotransmitter systems can emerge as consistent characteristics in behaviour compromising people's lives. All people have a weaker form of such imbalance in at least one of such neurotransmitter systems that make each of us distinct from one another. The impact of this weak imbalance in neurochemistry can be seen in the consistent features of behaviour in healthy people (temperament). In this sense temperament (as neuro-chemically-based individual differences) and mental illness represents varying degrees along the same continuum of neurotransmitter imbalance in neurophysiological systems of behavioural regulation.
In fact, multiple temperament traits (such as Impulsivity, sensation seeking, neuroticism, endurance, plasticity, sociability or extraversion) have been linked to brain neurotransmitters and hormone systems.
By the end of the 20th century, it became clear that the human brain operates with more than a dozen neurotransmitters and a large number of neuropeptides and hormones. The relationships between these different chemical systems are complex as some of them suppress and some of them induce each other's release during neuronal exchanges. This complexity of relationships devalues the old approach of assigning "inhibitory vs. excitatory" roles to neurotransmitters: the same neurotransmitters can be either inhibitory or excitatory depending on what system they interact with. It became clear that an impressive diversity of neurotransmitters and their receptors is necessary to meet a wide range of behavioural situations, but the links between temperament traits and specific neurotransmitters are still a matter of research. Several attempts were made to assign specific (single) neurotransmitters to specific (single) traits. For example, dopamine was proposed to be a neurotransmitter of the trait of Extraversion, noradrenaline was linked to anxiety, and serotonin was thought to be a neurotransmitter of an inhibition system. These assignments of neurotransmitter functions appeared to be an oversimplification when confronted by the evidence of much more diverse functionality.
Research groups led by Petra Netter in Germany, Lars Farde in Karolinska Institute in Sweden and Trevor Robbins in Cambridge, UK had most extensive studies of the links between temperament/personality traits or dynamical properties of behavior and groups of neurotransmitters. | 0 | Neurochemistry |
* Selective serotonin reuptake inhibitors (SSRIs) such as fluoxetine are widely used antidepressants that specifically block the reuptake of serotonin with less effect on other transmitters.
* Tricyclic antidepressants also block reuptake of biogenic amines from the synapse, but may primarily effect serotonin or norepinephrine or both. They typically take four to six weeks to alleviate any symptoms of depression. They are considered to have immediate and long-term effects.
* Monoamine oxidase inhibitors allow reuptake of biogenic amine neurotransmitters from the synapse, but inhibit an enzyme which normally destroys (metabolizes) some of the transmitters after their reuptake. More of the neurotransmitters (especially serotonin, noradrenaline and dopamine) are available for release into synapses. MAOIs take several weeks to alleviate the symptoms of depression.
Although changes in neurochemistry are found immediately after taking these antidepressants, symptoms may not begin to improve until several weeks after administration. Increased transmitter levels in the synapse alone does not relieve the depression or anxiety. | 0 | Neurochemistry |
NF-kB is a transcription factor that can be activated by p75NTR. Nerve growth factor (NGF) is a neurotrophin that promotes neuronal growth, and, in the absence of NGF, neurons die. Neuronal death in the absence of NGF can be prevented by NF-kB activation. Phosphorylated IκB kinase binds to and activates NF-kB before separating from NF-kB. After separation, IκB degrades and NF-kB continues to the nucleus to initiate pro-survival transcription. NF-kB also promotes neuronal survival in conjunction with NGF.
NF-kB activity is activated by p75NTR, and is not activated via Trk receptors. NF-kB activity does not effect Brain-derived neurotrophic factor promotion of neuronal survival. | 0 | Neurochemistry |
According to the United States National Library of Medicines medical subject headings, the term neurotrophin may be used as a synonym for neurotrophic factor, but the term neurotrophin is more generally reserved for four structurally related factors: nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), neurotrophin-3 (NT-3), and neurotrophin-4 (NT-4). The term neurotrophic factor' generally refers to these four neurotrophins, the GDNF family of ligands, and ciliary neurotrophic factor (CNTF), among other biomolecules. Neurotrophin-6 and neurotrophin-7 also exist, but are only found in zebrafish. | 0 | Neurochemistry |
The reaction catalyzed by bacterial luciferase is also an oxidative process:
* FMNH + O + RCHO → FMN + RCOOH + HO + light
In the reaction, molecular oxygen oxidizes flavin mononucleotide and a long-chain aliphatic aldehyde to an aliphatic carboxylic acid. The reaction forms an excited hydroxyflavin intermediate, which is dehydrated to the product FMN to emit blue-green light.
Nearly all of the energy input into the reaction is transformed into light. The reaction is 80% to 90% efficient. In comparison, the incandescent light bulb only converts about 10% of its energy into light and a 150 lumen per Watt (lm/W) LED converts 20% of input energy to visible light. | 1 | Bioluminescence |
In this class it is worthwhile to highlight the small non-peptide molecules LM22A-24 and LM11A-31 developed by Longo and Massa. Through the modulation of p75NTR activity, these compounds downregulate degenerative and upregulate trophic signaling. In particular, LM11A-31 was found to inhibit several pathophysiological mechanisms involved in AD and related to p75NTR. Oral administration in AD mice models reduces degeneration of cholinergic neurites. Furthermore, by a direct activation of p75NTR signaling and inhibition of apoptotic pathway, it improves motor function in a spinal cord injury (SCI) mice model and leads to an antiapoptotic effect in mice after traumatic brain injury (TBI). In February 2017, a phase 2 clinical trial started focusing on the evaluation of the safety of LM11A-31 in mild to moderate AD (NCT03069014). This study was completed in June 2020, but the results have not been published yet.
Another drug belonging to the class of p75NTR antagonists is THX-B, which inhibits NGF-p75NTR binding and prevents the death of RGCs in axotomy and glaucoma. In addition, in combination with LM22A-24, THX-B delays the loss of retinal structure, prevents RGC degeneration and preserves ganglion cell layer-inner plexiform layer thickness with a better efficacy compared to LM22A-24. Finally, a p75NTR antagonist, EVT901, was able to improve functional outcomes in two models of traumatic brain injury. Furthermore it was found to reduce inflammation in vivo in the TGFAD344 rat model of AD. | 0 | Neurochemistry |
Anandamide and N-arachidonoyl dopamine (NADA) have been shown to act on temperature-sensing TRPV1 channels, which are involved in thermoregulation. TRPV1 is activated by the exogenous ligand capsaicin, the active component of chili peppers, which is structurally similar to endocannabinoids. NADA activates the TRPV1 channel with The high potency makes it the putative endogenous TRPV1 agonist. Anandamide has also been found to activate TRPV1 on sensory neuron terminals, and subsequently cause vasodilation. TRPV1 may also be activated by methanandamide and arachidonyl-2'-chloroethylamide (ACEA). | 0 | Neurochemistry |
Neurotrophin-3, or NT-3, is a neurotrophic factor, in the NGF-family of neurotrophins. It is a protein growth factor that has activity on certain neurons of the peripheral and central nervous system; it helps to support the survival and differentiation of existing neurons, and encourages the growth and differentiation of new neurons and synapses. NT-3 is the third neurotrophic factor to be characterized, after NGF and BDNF.
NT-3 is unique among the neurotrophins in the number of neurons it has potential to stimulate, given its ability to activate two of the receptor tyrosine kinase neurotrophin receptors (TrkC and TrkB). Mice born without the ability to make NT-3 have loss of proprioceptive and subsets of mechanoreceptive sensory neurons. | 0 | Neurochemistry |
VMA is found in the urine, along with other catecholamine metabolites, including homovanillic acid (HVA), metanephrine, and normetanephrine. In timed urine tests the quantity excreted (usually per 24 hours) is assessed along with creatinine clearance, and the quantity of cortisols, catecholamines, and metanephrines excreted is also measured. | 0 | Neurochemistry |
The cys-loop receptors are named after a characteristic loop formed by a disulfide bond between two cysteine residues in the N terminal extracellular domain.
They are part of a larger family of pentameric ligand-gated ion channels that usually lack this disulfide bond, hence the tentative name "Pro-loop receptors".
A binding site in the extracellular N-terminal ligand-binding domain gives them receptor specificity for (1) acetylcholine (AcCh), (2) serotonin, (3) glycine, (4) glutamate and (5) γ-aminobutyric acid (GABA) in vertebrates. The receptors are subdivided with respect to the type of ion that they conduct (anionic or cationic) and further into families defined by the endogenous ligand. They are usually pentameric with each subunit containing 4 transmembrane helices constituting the transmembrane domain, and a beta sheet sandwich type, extracellular, N terminal, ligand binding domain. Some also contain an intracellular domain like shown in the image.
The prototypic ligand-gated ion channel is the nicotinic acetylcholine receptor. It consists of a pentamer of protein subunits (typically ααβγδ), with two binding sites for acetylcholine (one at the interface of each alpha subunit). When the acetylcholine binds it alters the receptor's configuration (twists the T2 helices which moves the leucine residues, which block the pore, out of the channel pathway) and causes the constriction in the pore of approximately 3 angstroms to widen to approximately 8 angstroms so that ions can pass through. This pore allows Na ions to flow down their electrochemical gradient into the cell. With a sufficient number of channels opening at once, the inward flow of positive charges carried by Na ions depolarizes the postsynaptic membrane sufficiently to initiate an action potential.
A bacterial homologue to an LIC has been identified, hypothesized to act nonetheless as a chemoreceptor. This prokaryotic nAChR variant is known as the GLIC receptor, after the species in which it was identified; loeobacter igand-gated on hannel. | 0 | Neurochemistry |
To improve its biophysical properties, derivatives of coelenterazine have been synthesized by means of different procedures including multicomponent strategies. | 1 | Bioluminescence |
Dinoflagellate luciferase is a multi-domain eukaryote protein, consisting of an N-terminal domain, and three catalytic domains, each of which preceded by a helical bundle domain. The structure of the dinoflagellate luciferase catalytic domain has been solved. The core part of the domain is a 10 stranded beta barrel that is structurally similar to lipocalins and FABP.
The N-terminal domain is conserved between dinoflagellate luciferase and luciferin binding proteins (LBPs). It has been suggested that this region may mediate an interaction between LBP and luciferase or their association with the vacuolar membrane.
The helical bundle domain has a three helix bundle structure that holds four important histidines that are thought to play a role in the pH regulation of the enzyme. There is a large pocket in the β-barrel of the dinoflagellate luciferase at pH 8 to accommodate the tetrapyrrole substrate but there is no opening to allow the substrate to enter. Therefore, a significant conformational change must occur to provide access and space for a ligand in the active site and the source for this change is through the four N-terminal histidine residues. At pH 8, it can be seen that the unprotonated histidine residues are involved in a network of hydrogen bonds at the interface of the helices in the bundle that block substrate access to the active site and disruption of this interaction by protonation (at pH 6.3) or by replacement of the histidine residues by alanine causes a large molecular motion of the bundle, separating the helices by 11Å and opening the catalytic site. Logically, the histidine residues cannot be replaced by alanine in nature but this experimental replacement further confirms that the larger histidine residues block the active site. Additionally, three Gly-Gly sequences, one in the N-terminal helix and two in the helix-loop-helix motif, could serve as hinges about which the chains rotate in order to further open the pathway to the catalytic site and enlarge the active site.
A dinoflagellate luciferase is capable of emitting light due to its interaction with its substrate (luciferin) and the luciferin-binding protein (LBP) in the scintillon organelle found in dinoflagellates. The luciferase acts in accordance with luciferin and LBP in order to emit light but each component functions at a different pH. Luciferase and its domains are not active at pH 8 but they are extremely active at the optimum pH of 6.3 whereas LBP binds luciferin at pH 8 and releases it at pH 6.3. Consequently, luciferin is only released to react with an active luciferase when the scintillon is acidified to pH 6.3. Therefore, in order to lower the pH, voltage-gated channels in the scintillon membrane are opened to allow the entry of protons from a vacuole possessing an action potential produced from a mechanical stimulation. Hence, it can be seen that the action potential in the vacuolar membrane leads to acidification and this in turn allows the luciferin to be released to react with luciferase in the scintillon, producing a flash of blue light. | 1 | Bioluminescence |
The human trace amines include:
While not trace amines themselves, the classical monoamines norepinephrine, serotonin, and histamine are all partial agonists at the human TAAR1 receptor; dopamine is a high-affinity agonist at human TAAR1. and are endogenous amines in humans, however, their human TAAR1 binding has not been determined | 0 | Neurochemistry |
Exogenous excitotoxins refer to neurotoxins that also act at postsynaptic cells but are not normally found in the body. These toxins may enter the body of an organism from the environment through wounds, food intake, aerial dispersion etc. Common excitotoxins include glutamate analogs that mimic the action of glutamate at glutamate receptors, including AMPA and NMDA receptors. | 0 | Neurochemistry |
Scintillons are not identical in different species. Scintillons isolated from dinoflagellates belonging to the genus Pyrocystis such as P. lunula (previously Dissodinium lunula) or P. noctiluca are less dense than those of L. polyedra and do not contain LBP. Little is known about the structure or composition of scintillons in species other than L. polyedra. | 1 | Bioluminescence |
Biosynthesis of coelenterazine in Metridia starts from two molecules of tyrosine and one molecule of phenylalanine, and some researchers believe this comes in the form of a cyclized "Phe-Tyr-Tyr" (FYY) peptide.
Many members of the genus Metridia also produce luciferases that use this compound, some of which are secreted into extracellular space, an unusual property for luciferases. | 1 | Bioluminescence |
The Hometrees (Kelutral in Navi) are great enough to house hundreds of clan members. The trees are honeycombed with natural hollows and alcoves in which the Navi sleep, eat, weave, dance, and celebrate their connection to Eywa. Adult Hometrees are more than tall, and roughly in diameter. The Omaticaya inhabit a Giant Hometree, standing roughly tall. A distinguishable feature of the movie landscape, the tree itself is central to the movie story arc. Like many sacred sites on Pandora, the Giant Hometree sits above a large deposit of unobtanium. It is destroyed by the humans using rockets and missiles, which leads to the Navi clans alliance against the humans. | 1 | Bioluminescence |
A partial extraction procedure was developed in 1935 which involved reacting the compound with benzoyl chloride to allow it to be separated from the water-soluble components. The compound was first isolated and purified to crystals by Osamu Shimomura. The structure of the compound was confirmed some years later. Feeding experiments suggest that the compound is synthesized in the animal from three amino-acids: tryptophan, isoleucine, and arginine. | 1 | Bioluminescence |
Muscarinic acetylcholine receptors belong to a class of metabotropic receptors that use G proteins as their signaling mechanism. In such receptors, the signaling molecule (the ligand) binds to a monomeric receptor that has seven transmembrane regions; in this case, the ligand is ACh. This receptor is bound to intracellular proteins, known as G proteins, which begin the information cascade within the cell.
By contrast, nicotinic receptors form pentameric complexes and use a ligand-gated ion channel mechanism for signaling. In this case, binding of the ligands with the receptor causes an ion channel to open, permitting either one or more specific types of ions (e.g., K, Na, Ca) to diffuse into or out of the cell. | 0 | Neurochemistry |
Since the emitted light can be easily detected with a luminometer, aequorin has become a useful tool in molecular biology for the measurement of intracellular Ca levels. The early successful purification of aequorin led to the first experiments involving the injection of the protein into the tissues of living animals to visualize the physiological release of calcium in the muscle fibers of a barnacle. Since then, the protein has been widely used in many model biological systems, including zebrafish, rats, mice, and cultured cells.
Cultured cells expressing the aequorin gene can effectively synthesize apoaequorin; however, recombinant expression yields only the apoprotein. Therefore it is necessary to add coelenterazine into the culture medium of the cells to obtain a functional protein and thus use its blue light emission to measure Ca concentration. Coelenterazine is a hydrophobic molecule, and therefore is easily taken up across plant and fungal cell walls, as well as the plasma membrane of higher eukaryotes, making aequorin suitable as a Ca reporter in plants, fungi, and mammalian cells.
Aequorin has a number of advantages over other Ca indicators. Because the protein is large, it has a low leakage rate from cells compared to lipophilic dyes such as DiI. It lacks phenomena of intracellular compartmentalization or sequestration as is often seen for Voltage-sensitive dyes, and does not disrupt cell functions or embryo development. Moreover, the light emitted by the oxidation of coelenterazine does not depend on any optical excitation, so problems with auto-fluorescence are eliminated. The primary limitation of aequorin is that the prosthetic group coelenterazine is irreversibly consumed to produce light, and requires continuous addition of coelenterazine into the media. Such issues led to developments of other genetically encoded calcium sensors including the calmodulin-based sensor cameleon, developed by Roger Tsien and the troponin-based sensor, TN-XXL, developed by Oliver Griesbeck. | 1 | Bioluminescence |
Ligand-gated ion channels are likely to be the major site at which anaesthetic agents and ethanol have their effects, although unequivocal evidence of this is yet to be established. In particular, the GABA and NMDA receptors are affected by anaesthetic agents at concentrations similar to those used in clinical anaesthesia.
By understanding the mechanism and exploring the chemical/biological/physical component that could function on those receptors, more and more clinical applications are proven by preliminary experiments or FDA. Memantine is approved by the U.S. F.D.A and the European Medicines Agency for the treatment of moderate-to-severe Alzheimers disease, and has now received a limited recommendation by the UKs National Institute for Health and Care Excellence for patients who fail other treatment options. Agomelatine, is a type of drug that acts on a dual melatonergic-serotonergic pathway, which have shown its efficacy in the treatment of anxious depression during clinical trials, study also suggests the efficacy in the treatment of atypical and melancholic depression. | 0 | Neurochemistry |
In earlier years it was thought that apamin was a rather nontoxic compound (LD = 15 mg/kg in mice) compared to the other compounds in bee venom. The current lethal dose values of apamin measured in mice are given below. There are no data known specific for humans.
Intraperitoneal (mouse) LD: 3.8 mg/kg
Subcutaneous (mouse) LD: 2.9 mg/kg
Intravenous (mouse) LD: 4 mg/kg
Intracerebral (mouse) LD: 1800 ng/kg
Parenteral (mouse) LD: 600 mg/kg | 0 | Neurochemistry |
IV dose 1-1.5mg/kg or 3 to 5 x ED
Paralysis occurs in one to two minutes.
Clinical duration of action (time from drug administration to recovery of single twich to 25% of baseline) is 7-12 minutes.
If IV access is unavailable, intramuscular administration 3-4mg/kg. Paralysis occurs at 4 minutes.
Use of succinylcholine infusion or repeated bolus administration increase the risk of Phase II block and prolonged paralysis. Phase II block occurs after large doses (>4mg/kg). This occurs when the post-synaptic membrane action potential returns to baseline in spite of the presence of succinylcholine and causes continued activation of nicotinic acetylcholine receptors. | 0 | Neurochemistry |
There are two distinctive features of ion channels that differentiate them from other types of ion transporter proteins:
#The rate of ion transport through the channel is very high (often 10 ions per second or greater).
#Ions pass through channels down their electrochemical gradient, which is a function of ion concentration and membrane potential, "downhill", without the input (or help) of metabolic energy (e.g. ATP, co-transport mechanisms, or active transport mechanisms).
Ion channels are located within the membrane of all excitable cells, and of many intracellular organelles. They are often described as narrow, water-filled tunnels that allow only ions of a certain size and/or charge to pass through. This characteristic is called selective permeability. The archetypal channel pore is just one or two atoms wide at its narrowest point and is selective for specific species of ion, such as sodium or potassium. However, some channels may be permeable to the passage of more than one type of ion, typically sharing a common charge: positive (cations) or negative (anions). Ions often move through the segments of the channel pore in a single file nearly as quickly as the ions move through the free solution. In many ion channels, passage through the pore is governed by a "gate", which may be opened or closed in response to chemical or electrical signals, temperature, or mechanical force.
Ion channels are integral membrane proteins, typically formed as assemblies of several individual proteins. Such "multi-subunit" assemblies usually involve a circular arrangement of identical or homologous proteins closely packed around a water-filled pore through the plane of the membrane or lipid bilayer. For most voltage-gated ion channels, the pore-forming subunit(s) are called the α subunit, while the auxiliary subunits are denoted β, γ, and so on. | 0 | Neurochemistry |
*Glutamate is the most common neurotransmitter. Most neurons secrete with glutamate or GABA. Glutamate is excitatory, meaning that the release of glutamate by one cell usually causes adjacent cells to fire an action potential. (Note: Glutamate is chemically identical to the MSG commonly used to flavor food.)
*GABA is an example of an inhibitory neurotransmitter.
* Monoamine neurotransmitters:
**Dopamine is a monoamine neurotransmitter. It plays a key role in the functioning of the limbic system, which is involved in emotional function and control. It also is involved in cognitive processes associated with movement, arousal, executive function, body temperature regulation, and pleasure and reward, and other processes.
**Norepinephrine, also known as noradrenaline, is a monoamine neurotransmitter that is involved in arousal, pain perception, executive function, body temperature regulation, and other processes.
**Epinephrine, also known as adrenaline, is a monoamine neurotransmitter that plays in fight-or-flight response, increases blood flow to muscles, output of the heart, pupil dilation, and glucose.
**Serotonin is a monoamine neurotransmitter that plays a regulatory role in mood, sleep, appetite, body temperature regulation, and other processes.
**Histamine is a monoamine neurotransmitter that is involved in arousal, pain, body temperature regulation, and appetite.
* Trace amines act as neuromodulators in monoamine neurons via binding to TAAR1.
*Acetylcholine assists motor function and is involved in memory.
*Nitric oxide functions as a neurotransmitter, despite being a gas. It is not grouped with the other neurotransmitters because it is not released in the same way.
*Endocannabinoids act in the endocannabinoid system to control neurotransmitter release in a host of neuronal tissues, including the hippocampus, amygdala, basal ganglia, and cerebellum.
* Eicosanoids act as neuromodulators via the Arachidonic acid cascade. | 0 | Neurochemistry |
Gating also includes activation and inactivation by second messengers from the inside of the cell membrane – rather than from outside the cell, as in the case for ligands.
*Some potassium channels:
**Inward-rectifier potassium channels: These channels allow potassium ions to flow into the cell in an "inwardly rectifying" manner: potassium flows more efficiently into than out of the cell. This family is composed of 15 official and 1 unofficial member and is further subdivided into 7 subfamilies based on homology. These channels are affected by intracellular ATP, PIP, and G-protein βγ subunits. They are involved in important physiological processes such as pacemaker activity in the heart, insulin release, and potassium uptake in glial cells. They contain only two transmembrane segments, corresponding to the core pore-forming segments of the K and K channels. Their α subunits form tetramers.
**Calcium-activated potassium channels: This family of channels is activated by intracellular Ca and contains 8 members.
**Tandem pore domain potassium channel: This family of 15 members form what are known as leak channels, and they display Goldman-Hodgkin-Katz (open) rectification. Contrary to their common name of Two-pore-domain potassium channels, these channels have only one pore but two pore domains per subunit.
*Two-pore channels include ligand-gated and voltage-gated cation channels, so-named because they contain two pore-forming subunits. As their name suggests, they have two pores.
*Light-gated channels like channelrhodopsin are directly opened by photons.
*Mechanosensitive ion channels open under the influence of stretch, pressure, shear, and displacement.
*Cyclic nucleotide-gated channels: This superfamily of channels contains two families: the cyclic nucleotide-gated (CNG) channels and the hyperpolarization-activated, cyclic nucleotide-gated (HCN) channels. This grouping is functional rather than evolutionary.
**Cyclic nucleotide-gated channels: This family of channels is characterized by activation by either intracellular cAMP or cGMP. These channels are primarily permeable to monovalent cations such as K and Na. They are also permeable to Ca, though it acts to close them. There are 6 members of this family, which is divided into 2 subfamilies.
**Hyperpolarization-activated cyclic nucleotide-gated channels
*Temperature-gated channels: Members of the transient receptor potential ion channel superfamily, such as TRPV1 or TRPM8, are opened either by hot or cold temperatures. | 0 | Neurochemistry |
Sleep arousal are active brain processes medicated and associated with specific brain regions. Despite the fact that various stages of sleep are discrete and quantifiable, the exact function of sleep is unknown. Sleep is controlled both by circadian rhythms and the homeostatic drive produced by wakefulness. Circadian rhythms are produced in the suprachiasmatic nucleus by pacemaker cells which contain transcriptional regulation "clock genes" which have been highly conserved throughout evolution.
Non-REM sleep is initiated by neurons in the preoptic and anterior hypothalamic area, whereas REM sleep is eventually elicited by the cells in the pontine tegmentum. Electroencephalography is used to analyze brain wave patterns during sleep and has the capability to differentiate between REM sleep from non-REM sleep. REM sleep cycles mimic conscious brain patterns to an extent. Night Terrors, for example, involve the partial arousal out of non-REM sleep. Similarly, REM Behavior Disorder occurs when patients have fits of violent behavior during REM sleep. Benzodiazepines are the most common treatments for sleep-related disorders.
Dyssomnia is a class of sleep disorders which includes Primary insomnia, primary hypersomnia, narcolepsy, breathing-related sleep disorders, circadian rhythm sleep disorder, and other conditions. Primary insomnia is a disorder in which a patient has difficulty initiating and maintaining sleep. Behavior modification and a reduction in neurologically active substances such as caffeine and alcohol seem to be among the most promising treatments. Although the mechanism is unknown, brain plasticity and behavior modification are utilized to train patients to only go to bed when tired, associating the bed itself with a sleepy state.
Narcolepsy is a condition characterized by abnormal transitions between REM and non-REM cycles during sleep and the awake cycle. Cataplexy, on the other hand, is an involuntary loss of muscle tone during wakefulness. The mechanism of narcolepsy is unknown, though recent findings suggest that orexin neurons in the lateral and posterior hypothalamus may play a critical role in reinforcing wakefulness. Narcolepsy is often treated with psychostimulants or tricyclic antidepressants in order to suppress REM sleep patterns. Sleep apnea is a common breathing disorder during sleep and is related to a disability in the central respiratory drive mechanisms. Parasomnias are a class represented by nightmares, sleep terrors, night terrors, schizophrenia, certain mood disorders, and other conditions which arise during Stage 4 of sleep.
General anesthetics typically induce non-REM sleep characterized by amnesia, analgesia, immobility, and hypnosis by facilitating the inhibition of excitatory ion channels or the excitation of inhibitory ligand-gated channels. | 0 | Neurochemistry |
Ion channels are also classified according to their subcellular localization. The plasma membrane accounts for around 2% of the total membrane in the cell, whereas intracellular organelles contain 98% of the cell's membrane. The major intracellular compartments are endoplasmic reticulum, Golgi apparatus, and mitochondria. On the basis of localization, ion channels are classified as:
* Plasma membrane channels
**Examples: Voltage-gated potassium channels (Kv), Sodium channels (Nav), Calcium channels (Cav) and Chloride channels (ClC)
* Intracellular channels, which are further classified into different organelles
**Endoplasmic reticulum channels: RyR, SERCA, ORAi
**Mitochondrial channels: mPTP, KATP, BK, IK, CLIC5, Kv7.4 at the inner membrane and VDAC and CLIC4 as outer membrane channels. | 0 | Neurochemistry |
The prolemuris (Syaksyuk in Navi) are blue, hexapodal creatures based on Earths lemurs. They have two eyes, small nostrils, and their two upper arms on each side are partially fused. Like most Pandoran creatures, they have a queue on the back of their heads. They have lateral skin membranes on each side of the body. They have large eyes and grow 1.5 meters tall. | 1 | Bioluminescence |
mEosFP is another monomeric Eos variant that folds effectively at 37 degrees Celsius. Where tdEos (tandem dimer) cannot fuse to targets such as histones, tubulin, intermediate filaments and gap junctions, and mEos (monomeric) which can only be used successfully at 30 degrees Celsius, mEos2 is an engineered variant that can fold effectively at 37 degrees Celsius and successfully label targets intolerant to fusion from other fluorescent protein dimers . mEos2 shows almost identical spectral properties, brightness, pKa, photoconversion, contrast and maturation properties to WT Eos. The localization precision of mEos2 is twice as great as other monomeric fluorescent proteins. | 1 | Bioluminescence |
Ion channels are pore-forming membrane proteins that allow ions to pass through the channel pore. Their functions include establishing a resting membrane potential, shaping action potentials and other electrical signals by gating the flow of ions across the cell membrane, controlling the flow of ions across secretory and epithelial cells, and regulating cell volume. Ion channels are present in the membranes of all cells. Ion channels are one of the two classes of ionophoric proteins, the other being ion transporters.
The study of ion channels often involves biophysics, electrophysiology, and pharmacology, while using techniques including voltage clamp, patch clamp, immunohistochemistry, X-ray crystallography, fluoroscopy, and RT-PCR. Their classification as molecules is referred to as channelomics. | 0 | Neurochemistry |