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114-460: Neuroligins bind with the aid of Ca to the α-neurexin LNS (laminin, neurexin and sex hormone-binding globulin-like folding units) domains and to the β-neurexin LNS domain which then establishes a heterophilic trans-synaptic recognition code. Through the observation of the crystal structure of neuroligin-1, it was determined that neuroligin-1 forms a protein dimer when two neurexin-1 beta monomers bind to

228-412: A platinum plate which was used as the anode, the cathode being a platinum wire partially submerged into mercury. Electrolysis then gave calcium–mercury and magnesium–mercury amalgams, and distilling off the mercury gave the metal. However, pure calcium cannot be prepared in bulk by this method and a workable commercial process for its production was not found until over a century later. At 3%, calcium

342-434: A "steady state" with respect to calcium input and output. This has important climatological implications, as the marine calcium cycle is closely tied to the carbon cycle . Many calcium compounds are used in food, as pharmaceuticals, and in medicine, among others. For example, calcium and phosphorus are supplemented in foods through the addition of calcium lactate , calcium diphosphate , and tricalcium phosphate . The last

456-457: A defect in genes encoding neuroligin , a cell-adhesion molecule found in the post-synaptic membrane, has been linked to cases of autism and mental retardation. Finally, many of these signaling processes can be regulated by matrix metalloproteinases (MMPs) as the targets of many MMPs are these specific cell-adhesion molecules. The special structure found in the CNS that allows for multiple inputs

570-423: A dipositive ion with the stable electron configuration of a noble gas , in this case argon . Hence, calcium is almost always divalent in its compounds, which are usually ionic . Hypothetical univalent salts of calcium would be stable with respect to their elements, but not to disproportionation to the divalent salts and calcium metal, because the enthalpy of formation of MX 2 is much higher than those of

684-492: A gain-of-function mutation. This supports the claim that increased inhibitory synaptic transmission may contribute to human autism spectrum disorders. Mutations in NLGN4 have also been found in persons with X-linked autism. A frame shift mutation 1186T has been found to cause an early stop codon and premature protein truncation. This mutation results in intracellular retention of mutant proteins, possibly causing impaired function of

798-642: A gas had not been recognised by the ancient Romans. In 1789, Antoine Lavoisier suspected that lime might be an oxide of a fundamental chemical element . In his table of the elements, Lavoisier listed five "salifiable earths" (i.e., ores that could be made to react with acids to produce salts ( salis = salt, in Latin): chaux (calcium oxide), magnésie (magnesia, magnesium oxide), baryte (barium sulfate), alumine (alumina, aluminium oxide), and silice (silica, silicon dioxide)). About these "elements", Lavoisier reasoned: We are probably only acquainted as yet with

912-412: A high pressure of oxygen, and there is some evidence for a yellow superoxide Ca(O 2 ) 2 . Calcium hydroxide, Ca(OH) 2 , is a strong base, though not as strong as the hydroxides of strontium, barium or the alkali metals. All four dihalides of calcium are known. Calcium carbonate (CaCO 3 ) and calcium sulfate (CaSO 4 ) are particularly abundant minerals. Like strontium and barium, as well as

1026-666: A modification that occurs after transcription of mRNA, regulates neuroligins’ binding selectivity for α- or β-neurexins as well as the function of synapses. Alternative splicing in neuroligins occurs in the main functional domain, the acetylcholinesterase-homologous region. Because neuroligin has two conserved splice sites in this region, sites A and B, up to four different isoforms are possible for each neuroligin gene. Neurexins also undergo alternative splicing, and certain splice variants of neuroligins and neurexins are more selective for one another. Specific pairing of splice variants also affects synaptic function. For example, neuroligins lacking

1140-508: A part of the metallic substances existing in nature, as all those which have a stronger affinity to oxygen than carbon possesses, are incapable, hitherto, of being reduced to a metallic state, and consequently, being only presented to our observation under the form of oxyds, are confounded with earths. It is extremely probable that barytes, which we have just now arranged with earths, is in this situation; for in many experiments it exhibits properties nearly approaching to those of metallic bodies. It

1254-491: A process called synapse elimination. Furthermore, the post-synaptic end plate grows deeper and creates folds through invagination to increase the surface area available for neurotransmitter reception. At birth, Schwann cells form loose, unmyelinated covers over groups of synapses, but as the synapse matures, Schwann cells become dedicated to a single synapse and form a myelinated cap over the entire neuromuscular junction. The process of synaptic pruning known as synapse elimination

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1368-423: A rather high neutron flux to allow short-lived Ca to capture a neutron. Ca is produced by electron capture in the r-process in type Ia supernovae , where high neutron excess and low enough entropy ensures its survival. Ca and Ca are the first "classically stable" nuclides with a 6-neutron or 8-neutron excess respectively. Although extremely neutron-rich for such a light element, Ca is very stable because it

1482-471: A redistribution of pre-existing synaptic components. Evidence for this can be seen in the up-regulation of genes expressing vesicle proteins shortly after synapse formation as well as their localization at the synaptic terminal. Immature synapses are multiply innervated at birth, due to the high propensity for new axons to innervate at a pre-existing synapse. As the synapse matures, the synapses segregate and eventually all axonal inputs except for one retract in

1596-401: A result, when Ca does decay, it does so by double beta decay to Ti instead, being the lightest nuclide known to undergo double beta decay. Ca can also theoretically undergo double beta decay to Ti, but this has never been observed. The most common isotope Ca is also doubly magic and could undergo double electron capture to Ar , but this has likewise never been observed. Calcium is

1710-448: A secondary signal. Eventually, immediate early genes (IEG) are activated by transcription factors and the proteins required for neuronal differentiation are translated. The NMDA receptor function is associated with the estrogen receptor in hippocampal neurons. Experiments conducted with estradiol show that exposure to the estrogen significantly increases synaptic density and protein concentration. Synaptic signaling during synaptogenesis

1824-488: A simple and accessible structure that allows for easy manipulation and observation. The synapse itself is composed of three cells: the motor neuron , the myofiber , and the Schwann cell . In a normally functioning synapse, a signal will cause the motor neuron to depolarize, by releasing the neurotransmitter acetylcholine (ACh). Acetylcholine travels across the synaptic cleft where it reaches acetylcholine receptors (AChR) on

1938-503: A single gene for neuroligin. The known neuroligin genes in Homo sapiens include NLGN1 , NLGN2 , NLGN3 , NLGN4X and NLGN5 (also known as NLGN4Y). Each gene has been found to have unique influences on synaptic transmission. Expression of neuroligins may differ between species. Neuroligin 1 is expressed specifically in the CNS at excitatory synapses. In humans, expression of neuroligin 1

2052-399: A synaptic cell adhesion molecule, and modifying the binding of the neuroligin protein to its presynaptic partners, neurexins, thus interrupting essential synaptic function. Other mutations of NLGN4 found in relation to autism spectrum disorders include a 2-bp deletion, 1253delAG, in the NLGN4 gene, which causes a frameshift and a premature stop codon. Another mutation is a hemizygous deletion in

2166-472: Is a cosmogenic nuclide , continuously produced through neutron activation of natural Ca. Many other calcium radioisotopes are known, ranging from Ca to Ca. They are all much shorter-lived than Ca, the most stable being Ca (half-life 163 days) and Ca (half-life 4.54 days). Isotopes lighter than Ca usually undergo beta plus decay to isotopes of potassium, and those heavier than Ca usually undergo beta minus decay to isotopes of scandium , though near

2280-438: Is a doubly magic nucleus , having 20 protons and 28 neutrons arranged in closed shells. Its beta decay to Sc is very hindered because of the gross mismatch of nuclear spin : Ca has zero nuclear spin, being even–even , while Sc has spin 6+, so the decay is forbidden by the conservation of angular momentum . While two excited states of Sc are available for decay as well, they are also forbidden due to their high spins. As

2394-497: Is a better conductor by mass than both due to its very low density. While calcium is infeasible as a conductor for most terrestrial applications as it reacts quickly with atmospheric oxygen, its use as such in space has been considered. The chemistry of calcium is that of a typical heavy alkaline earth metal. For example, calcium spontaneously reacts with water more quickly than magnesium and less quickly than strontium to produce calcium hydroxide and hydrogen gas. It also reacts with

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2508-444: Is a presumably activity-dependent process that involves competition between axons. Hypothetically, a synapse strong enough to produce an action potential will trigger the myonuclei directly across from the axon to release synaptotrophins that will strengthen and maintain well-established synapses. This synaptic strengthening is not conferred upon the weaker synapses, thereby starving them out. It has also been suggested that in addition to

2622-439: Is a very ductile silvery metal (sometimes described as pale yellow) whose properties are very similar to the heavier elements in its group, strontium , barium , and radium . A calcium atom has twenty electrons, with electron configuration [Ar]4s . Like the other elements placed in group 2 of the periodic table, calcium has two valence electrons in the outermost s-orbital, which are very easily lost in chemical reactions to form

2736-494: Is achieved through clustering of AChR, up-regulation of the AChR gene transcription in the post-synaptic nuclei, and down-regulation of the AChR gene in the non-synaptic nuclei. The signals that initiate post-synaptic differentiation may be neurotransmitters released directly from the axon to the myotube, or they may arise from changes activated in the extracellular matrix of the synaptic cleft. AChR experiences multimerization within

2850-424: Is also used as a polishing agent in toothpaste and in antacids . Calcium lactobionate is a white powder that is used as a suspending agent for pharmaceuticals. In baking, calcium phosphate is used as a leavening agent . Calcium sulfite is used as a bleach in papermaking and as a disinfectant, calcium silicate is used as a reinforcing agent in rubber, and calcium acetate is a component of liming rosin and

2964-421: Is also used to strengthen aluminium alloys used for bearings, for the control of graphitic carbon in cast iron , and to remove bismuth impurities from lead. Calcium metal is found in some drain cleaners, where it functions to generate heat and calcium hydroxide that saponifies the fats and liquefies the proteins (for example, those in hair) that block drains. Besides metallurgy, the reactivity of calcium

3078-532: Is directly responsible for AChR clustering in the post-synaptic membrane: rapsyn-deficient mutant mice fail to form AChR clusters. The increased concentration of AChR is not simply due to a rearrangement of pre-existing synaptic components. The axon also provides signals that regulate gene expression within the myonuclei directly beneath the synapse. This signaling provides for localized up-regulation of transcription of AChR genes and consequent increase in local AChR concentration. The two signaling molecules released by

3192-452: Is even possible that all the substances we call earths may be only metallic oxyds, irreducible by any hitherto known process. Calcium, along with its congeners magnesium, strontium, and barium, was first isolated by Humphry Davy in 1808. Following the work of Jöns Jakob Berzelius and Magnus Martin af Pontin on electrolysis , Davy isolated calcium and magnesium by putting a mixture of the respective metal oxides with mercury(II) oxide on

3306-505: Is exploited to remove nitrogen from high-purity argon gas and as a getter for oxygen and nitrogen. It is also used as a reducing agent in the production of chromium , zirconium , thorium , vanadium and uranium . It can also be used to store hydrogen gas, as it reacts with hydrogen to form solid calcium hydride , from which the hydrogen can easily be re-extracted. Calcium isotope fractionation during mineral formation has led to several applications of calcium isotopes. In particular,

3420-571: Is expressed in CNS neurons, as well as a variety of glial cells in mice and rats and the brain, heart, skeletal muscle, placenta and pancreas in humans. Neuroligin 4X is expressed in the heart, liver, skeletal muscle, pancreas and low levels in the brain. Neuroligin 5 (or 4Y), located on the Y chromosome, is only 19 amino acids different from neuroligin 4X. Neuroligin mRNA are present in human endothelial cells from large blood vessels and in Dorsal Root Ganglions . Alternative splicing ,

3534-465: Is less reactive than strontium or barium, the oxide–nitride coating that results in air is stable and lathe machining and other standard metallurgical techniques are suitable for calcium. In the United States and Canada, calcium is instead produced by reducing lime with aluminium at high temperatures. Calcium cycling provides a link between tectonics , climate , and the carbon cycle . In

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3648-431: Is low before birth and increases between postnatal days 1-8 and remains high through adulthood. This postnatal increase during active synaptogenesis corresponds to increased expression of postsynaptic density protein-95 (PSD-95). Neuroligin 2 is mainly concentrated at inhibitory synapses in the CNS, but in mice and humans it may also be expressed in tissues such as the pancreas, lung, endothelia, uterus and colon. Neuroligin 3

3762-453: Is more complicated and involves the bicarbonate ion (HCO 3 ) that forms when CO 2 reacts with water at seawater pH : At seawater pH, most of the dissolved CO 2 is immediately converted back into HCO 3 . The reaction results in a net transport of one molecule of CO 2 from the ocean/atmosphere into the lithosphere . The result is that each Ca ion released by chemical weathering ultimately removes one CO 2 molecule from

3876-415: Is not only activity-dependent, but is also dependent on the environment in which the neurons are located. For instance, brain-derived neurotrophic factor (BDNF) is produced by the brain and regulates several functions within the developing synapse, including enhancement of transmitter release, increased concentration of vesicles, and cholesterol biosynthesis. Cholesterol is essential to synaptogenesis because

3990-417: Is particularly important during an individual's critical period , during which there is a certain degree of synaptic pruning due to competition for neural growth factors by neurons and synapses. Processes that are not used, or inhibited during their critical period will fail to develop normally later on in life. The neuromuscular junction (NMJ) is the most well-characterized synapse in that it provides

4104-498: Is the dendritic spine , the highly dynamic site of excitatory synapses. This morphological dynamism is due to the specific regulation of the actin cytoskeleton, which in turn allows for regulation of synapse formation. Dendritic spines exhibit three main morphologies: filopodia, thin spines, and mushroom spines. The filopodia play a role in synaptogenesis through initiation of contact with axons of other neurons. Filopodia of new neurons tend to associate with multiply synapsed axons, while

4218-510: Is the fifth most abundant element in the Earth's crust , and the third most abundant metal behind aluminium and iron . It is also the fourth most abundant element in the lunar highlands . Sedimentary calcium carbonate deposits pervade the Earth's surface as fossilized remains of past marine life; they occur in two forms, the rhombohedral calcite (more common) and the orthorhombic aragonite (forming in more temperate seas). Minerals of

4332-458: Is the fifth most abundant element in Earth's crust, and the third most abundant metal, after iron and aluminium . The most common calcium compound on Earth is calcium carbonate , found in limestone and the fossilised remnants of early sea life; gypsum , anhydrite , fluorite , and apatite are also sources of calcium. The name derives from Latin calx " lime ", which was obtained from heating limestone. Some calcium compounds were known to

4446-422: Is the result of axonal contact instead of the cause, the structural patterns of muscle fibers can be attributed to both myotatic growth as well as axonal innervation. The preliminary contact formed between the motoneuron and the myotube generates synaptic transmission almost immediately, but the signal produced is very weak. There is evidence that Schwann cells may facilitate these preliminary signals by increasing

4560-425: Is the second-most common isotope. The other four natural isotopes, Ca, Ca, Ca, and Ca, are significantly rarer, each comprising less than 1% of all natural calcium. The four lighter isotopes are mainly products of the oxygen-burning and silicon-burning processes, leaving the two heavier ones to be produced via neutron capture processes. Ca is mostly produced in a "hot" s-process , as its formation requires

4674-507: Is through use of the neurotransmitter acetylcholine and its receptor. The CNS homolog is glutamate and its receptors, and one of special significance is the N-methyl-D-aspartate (NMDA) receptor. It has been shown that activation of NMDA receptors initiates synaptogenesis through activation of downstream products. The heightened level of NMDA receptor activity during development allows for increased influx of calcium, which acts as

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4788-503: Is used to make metallic soaps and synthetic resins. Calcium is on the World Health Organization's List of Essential Medicines . Foods rich in calcium include dairy products such as milk and yogurt , cheese , sardines , salmon , soy products, kale , and fortified breakfast cereals . Because of concerns for long-term adverse side effects, including calcification of arteries and kidney stones , both

4902-431: Is very soluble in water, 85% of extracellular calcium is as dicalcium phosphate with a solubility of 2.00  mM , and the hydroxyapatite of bones in an organic matrix is tricalcium phosphate with a solubility of 1000 μM. Calcium is a common constituent of multivitamin dietary supplements , but the composition of calcium complexes in supplements may affect its bioavailability which varies by solubility of

5016-487: The United States (about 2000 to 4000 tonnes per year). Canada and France are also among the minor producers. In 2005, about 24000 tonnes of calcium were produced; about half of the world's extracted calcium is used by the United States, with about 80% of the output used each year. In Russia and China, Davy's method of electrolysis is still used, but is instead applied to molten calcium chloride . Since calcium

5130-418: The carboxyl groups of glutamic acid or aspartic acid residues; through interacting with phosphorylated serine , tyrosine , or threonine residues; or by being chelated by γ-carboxylated amino acid residues. Trypsin , a digestive enzyme, uses the first method; osteocalcin , a bone matrix protein, uses the third. Some other bone matrix proteins such as osteopontin and bone sialoprotein use both

5244-509: The contraction of muscles , nerve conduction, and the clotting of blood. As a result, intra- and extracellular calcium levels are tightly regulated by the body. Calcium can play this role because the Ca ion forms stable coordination complexes with many organic compounds, especially proteins ; it also forms compounds with a wide range of solubilities, enabling the formation of the skeleton . Calcium ions may be complexed by proteins through binding

5358-502: The cytoskeleton components needed to localize synaptic vesicles. Neurexin is necessary for containing the voltage-gated Ca channels that are required for the release of vesicles, while neuroligin binds neurexin in order to localize the necessary neurotransmitter receptors and proteins for postsynaptic specialization. At the postsynaptic site, neuroligins are networked to specialized proteins that stimulate specific neurotransmitter receptors and channels to densely occupy specialized regions of

5472-450: The endoplasmic reticulum . The small amount of mutant protein that reached the cell membrane demonstrated diminished binding activity for neurexin-1, consistent with a loss of function. The mutant gene has been cloned and was introduced into mice, resulting in impaired social interactions, enhanced spatial learning abilities and increased inhibitory synaptic transmission. Deleting NLGN3 did not produce these effects, thus indicating R451C to be

5586-496: The nuclear drip lines , proton emission and neutron emission begin to be significant decay modes as well. Like other elements, a variety of processes alter the relative abundance of calcium isotopes. The best studied of these processes is the mass-dependent fractionation of calcium isotopes that accompanies the precipitation of calcium minerals such as calcite , aragonite and apatite from solution. Lighter isotopes are preferentially incorporated into these minerals, leaving

5700-455: The oxygen and nitrogen in air to form a mixture of calcium oxide and calcium nitride . When finely divided, it spontaneously burns in air to produce the nitride. Bulk calcium is less reactive: it quickly forms a hydration coating in moist air, but below 30% relative humidity it may be stored indefinitely at room temperature. Besides the simple oxide CaO, calcium peroxide , CaO 2 , can be made by direct oxidation of calcium metal under

5814-467: The physiological and biochemical processes of organisms and cells : in signal transduction pathways where they act as a second messenger ; in neurotransmitter release from neurons ; in contraction of all muscle cell types; as cofactors in many enzymes ; and in fertilization . Calcium ions outside cells are important for maintaining the potential difference across excitable cell membranes , protein synthesis, and bone formation. Calcium

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5928-548: The plasma membrane of the myofiber, the sarcolemma . As the AChRs open ion channels , the membrane depolarizes, causing muscle contraction. The entire synapse is covered in a myelin sheath provided by the Schwann cell to insulate and encapsulate the junction. Another important part of the neuromuscular system and central nervous system are the astrocytes . While originally they were thought to have only functioned as support for

6042-424: The 1997 observation by Skulan and DePaolo that calcium minerals are isotopically lighter than the solutions from which the minerals precipitate is the basis of analogous applications in medicine and in paleoceanography. In animals with skeletons mineralized with calcium, the calcium isotopic composition of soft tissues reflects the relative rate of formation and dissolution of skeletal mineral. In humans, changes in

6156-510: The 69 known proteins mutated in X-linked autism encode postsynaptic proteins, Neuroligins included. Additionally, maternal antibodies against Y-chromosome neuroligin NLGN4Y have been implicated in the fetal development of male homosexuality. A mutated NLGN3 gene, R451C, has been cloned. The mutant has been shown to cause defective neuroligin trafficking and retention of the mutant protein in

6270-492: The B splice insert and β-neurexins with the S4 insert promote differentiation of inhibitory, GABAergic synapses. On the other hand, neuroligins with the B insert and β-neurexins lacking the S4 insert promote differentiation of excitatory, glutamatergic synapses. The A insert may promote neuroligin localization and function at inhibitory synapses, but the mechanisms are unknown. Neurexin and neuroligin work together to gather and maintain

6384-454: The CNS often receive multiple inputs that must be processed and integrated for successful transfer of information. Muscle fibers are innervated by a single input and operate in an all or none fashion. Coupled with the plasticity that is characteristic of the CNS neuronal connections, it is easy to see how increasingly complex CNS circuits can become. The main method of synaptic signaling in the NMJ

6498-1099: The E/I ratio, and a decrease in the PSD-95/neuroligin ratio had the opposite effect. Also, overexpression of PSD-95 redirects neuroligin-2 from excitatory to inhibitory synapses, strengthening excitatory input and reducing inhibitory input. These interactions of neuroligin, neurexin and interacting proteins such as PSD-95 point to a potential regulatory mechanism that controls development and balance of excitatory and inhibitory synapses, governed by homeostatic feedback mechanisms. Neuroligin dysfunction has been implicated in autism spectrum disorders . Different genetic alterations have been detected in neuroligin genes in patients with ASD, including point mutations , missense mutations and internal deletions . In studies done on family members with X-linked autism, specific mutations of NLGN3 and NLGN4 have been identified. These mutations have been shown to affect how neuroligins function and have been shown to interfere with synaptic transmission. 19 of

6612-473: The E/I ratio. In fact, an imbalance in the E/I ratio is thought to be involved in autistic spectrum disorders. Neuroligin 1 localizes at excitatory synapses, neuroligin 2 at inhibitory synapses and neuroligin 3 at both. Reduction in the levels of neuroligins 1, 2 and 3 results in a strong reduction of inhibitory input but little reduction in excitatory input. In addition, Neuroligins interacts with PSD-95 , an intracellular protein that anchors synaptic proteins in

6726-456: The NLGN4 gene encompassing exons 4, 5 and 6. The 757-kb deletion was predicted to result in a significantly truncated protein. Calcium Calcium is a chemical element ; it has symbol Ca and atomic number 20. As an alkaline earth metal , calcium is a reactive metal that forms a dark oxide-nitride layer when exposed to air. Its physical and chemical properties are most similar to its heavier homologues strontium and barium . It

6840-604: The U.S. Institute of Medicine (IOM) and the European Food Safety Authority (EFSA) set Tolerable Upper Intake Levels (ULs) for combined dietary and supplemental calcium. From the IOM, people of ages 9–18 years are not to exceed 3 g/day combined intake; for ages 19–50, not to exceed 2.5 g/day; for ages 51 and older, not to exceed 2 g/day. EFSA set the UL for all adults at 2.5 g/day, but decided

6954-567: The absence of steric hindrance , smaller group 2 cations tend to form stronger complexes, but when large polydentate macrocycles are involved the trend is reversed. Though calcium is in the same group as magnesium and organomagnesium compounds are very widely used throughout chemistry, organocalcium compounds are not similarly widespread because they are more difficult to make and more reactive, though they have recently been investigated as possible catalysts . Organocalcium compounds tend to be more similar to organoytterbium compounds due to

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7068-425: The active zone, and polarization of the pre-synaptic membrane. These changes are thought to be mediated by neurotrophin and cell adhesion molecule release from muscle cells, thereby emphasizing the importance of communication between the motoneuron and the myotube during synaptogenesis. Like post-synaptic differentiation, pre-synaptic differentiation is thought to be due to a combination of changes in gene expression and

7182-488: The alkali metals and the divalent lanthanides europium and ytterbium , calcium metal dissolves directly in liquid ammonia to give a dark blue solution. Due to the large size of the calcium ion (Ca ), high coordination numbers are common, up to 24 in some intermetallic compounds such as CaZn 13 . Calcium is readily complexed by oxygen chelates such as EDTA and polyphosphates , which are useful in analytic chemistry and removing calcium ions from hard water . In

7296-444: The amount of spontaneous neurotransmitter release through small molecule signals. After about a week, a fully functional synapse is formed following several types of differentiation in both the post-synaptic muscle cell and the pre-synaptic motoneuron. This pioneer axon is of crucial importance because the new axons that follow have a high propensity for forming contacts with well-established synapses. The most noticeable difference in

7410-423: The ancients, though their chemistry was unknown until the seventeenth century. Pure calcium was isolated in 1808 via electrolysis of its oxide by Humphry Davy , who named the element. Calcium compounds are widely used in many industries: in foods and pharmaceuticals for calcium supplementation , in the paper industry as bleaches, as components in cement and electrical insulators, and in the manufacture of soaps. On

7524-439: The axon are calcitonin gene-related peptide (CGRP) and neuregulin , which trigger a series of kinases that eventually lead to transcriptional activation of the AChR genes. Repression of the AChR gene in the non-synaptic nuclei is an activity-dependent process involving the electrical signal generated by the newly formed synapse. Reduced concentration of AChR in the extrasynaptic membrane in addition to increased concentration in

7638-424: The axons may non-specifically innervate muscle fibers and cause the muscles to acquire the characteristics of the axon that innervates them. In this path, a "fast" motoneuron can convert any muscle fiber into a fast-twitch muscle fiber. There is evidence for both selective and non-selective paths in synapse formation specificity, leading to the conclusion that the process is a combination of several factors. Although

7752-441: The axons of motoneurons achieve this specificity, one in which the axons actively recognize the muscles that they innervate and make selective decisions based on inputs, and another that calls for more indeterminate innervation of muscle fibers. In the selective paths, the axons recognize the fiber type, either by factors or signals released specifically by the fast or slow-twitch muscle fibers. In addition, selectivity can be traced to

7866-453: The bone-forming action of parathyroid hormone being antagonised by calcitonin , whose secretion increases with increasing plasma calcium levels. Synaptogenesis Synaptogenesis is the formation of synapses between neurons in the nervous system . Although it occurs throughout a healthy person's lifespan , an explosion of synapse formation occurs during early brain development , known as exuberant synaptogenesis . Synaptogenesis

7980-519: The calcium isotopic composition of urine have been shown to be related to changes in bone mineral balance. When the rate of bone formation exceeds the rate of bone resorption, the Ca/ Ca ratio in soft tissue rises and vice versa. Because of this relationship, calcium isotopic measurements of urine or blood may be useful in the early detection of metabolic bone diseases like osteoporosis . A similar system exists in seawater, where Ca/ Ca tends to rise when

8094-438: The clustering of receptors, localized up-regulation of protein synthesis at the active sites, and neuronal pruning through synapse elimination. Despite these similarities in structure, there is a fundamental difference between the two connections. The CNS synapse is strictly neuronal and does not involve muscle fibers: for this reason the CNS uses different neurotransmitter molecules and receptors. More importantly, neurons within

8208-1010: The developing embryo. Recently data have emerged showing that the Wnt protein family has roles in the later development of synapse formation and plasticity . Wnt contribution to synaptogenesis has been verified in both the central nervous system and the neuromuscular junction . Wnt family members contribute to synapse formation in the cerebellum by inducing presynaptic and postsynaptic terminal formation. This brain region contains three main neuronal cell types- Purkinje cells , granule cells and mossy fiber cells. Wnt-3 expression contributes to Purkinje cell neurite outgrowth and synapse formation. Granule cells express Wnt-7a to promote axon spreading and branching in their synaptic partner, mossy fiber cells. Retrograde secretion of Wnt-7a to mossy fiber cells causes growth cone enlargement by spreading microtubules . Furthermore, Wnt-7a retrograde signaling recruits synaptic vesicles and presynaptic proteins to

8322-472: The entire muscle membrane. Note that this affects gene transcription at a distance: the receptors that are embedded within the post-synaptic membrane are not susceptible to repression. Although the mechanisms regulating pre-synaptic differentiation are unknown, the changes exhibited at the developing axon terminal are well characterized. The pre-synaptic axon shows an increase in synaptic volume and area, an increase of synaptic vesicles, clustering of vesicles at

8436-671: The filopodia of mature neurons tend to sites devoid of other partners. The dynamism of spines allows for the conversion of filopodia into the mushroom spines that are the primary sites of glutamate receptors and synaptic transmission. Rats raised with environmental enrichment have 25% more synapses than controls. This effect occurs whether a more stimulating environment is experienced immediately following birth, after weaning, or during maturity. Stimulation effects not only synaptogenesis upon pyramidal neurons but also stellate ones. The ( Wnt ) family, includes several embryonic morphogens that contribute to early pattern formation in

8550-399: The first and the second. Direct activation of enzymes by binding calcium is common; some other enzymes are activated by noncovalent association with direct calcium-binding enzymes. Calcium also binds to the phospholipid layer of the cell membrane , anchoring proteins associated with the cell surface. As an example of the wide range of solubility of calcium compounds, monocalcium phosphate

8664-747: The first type include limestone , dolomite , marble , chalk , and iceland spar ; aragonite beds make up the Bahamas , the Florida Keys , and the Red Sea basins. Corals , sea shells , and pearls are mostly made up of calcium carbonate. Among the other important minerals of calcium are gypsum (CaSO 4 ·2H 2 O), anhydrite (CaSO 4 ), fluorite (CaF 2 ), and apatite ([Ca 5 (PO 4 ) 3 X], X = OH, Cl, or F).gre The major producers of calcium are China (about 10000 to 12000 tonnes per year), Russia (about 6000 to 8000 tonnes per year), and

8778-415: The formation of bone by allowing and enhancing the deposition of calcium ions there, allowing rapid bone turnover without affecting bone mass or mineral content. When plasma calcium levels fall, cell surface receptors are activated and the secretion of parathyroid hormone occurs; it then proceeds to stimulate the entry of calcium into the plasma pool by taking it from targeted kidney, gut, and bone cells, with

8892-548: The hippocampus mitigates these activity dependent effects by reducing dendritic arborization and subsequently, synaptic complexity. Similar mechanisms of action by Wnts in the central nervous system are observed in the neuromuscular junction (NMJ) as well. In the Drosophila NMJ mutations in the Wnt5 receptor Derailed (drl) reduce the number of and density of synaptic active zones. The major neurotransmitter in this system

9006-423: The hippocampus. NMDA glutamate receptor activation increases Wnt2 expression. Long term potentiation (LTP) due to NMDA activation and subsequent Wnt expression leads to Fz-5 localization at the postsynaptic active zone. Furthermore, Wnt7a and Wnt2 signaling after NMDA receptor mediated LTP leads to increased dendritic arborization and regulates activity induced synaptic plasticity. Blocking Wnt expression in

9120-432: The hypothetical MX. This occurs because of the much greater lattice energy afforded by the more highly charged Ca cation compared to the hypothetical Ca cation. Calcium, strontium, barium, and radium are always considered to be alkaline earth metals ; the lighter beryllium and magnesium , also in group 2 of the periodic table, are often included as well. Nevertheless, beryllium and magnesium differ significantly from

9234-417: The information for children and adolescents was not sufficient to determine ULs. Calcium is an essential element needed in large quantities. The Ca ion acts as an electrolyte and is vital to the health of the muscular, circulatory, and digestive systems; is indispensable to the building of bone in the form of hydroxyapatite ; and supports synthesis and function of blood cells. For example, it regulates

9348-535: The initial contact between the axons and dendrites for a synapse. Neurexins and neuroligins then reinforce the contact. In addition to the selectivity of splice variants, the levels of neuroligins, neurexins, and other interacting proteins present on the pre- and postsynaptic membranes influence the differentiation and balance of synapses. As synapses form during synaptogenesis , they differentiate into one of two categories: excitatory or inhibitory. Excitatory synapses increase probability of firing an action potential in

9462-404: The lateral position that the axons are predeterminately arranged in order to link them to the muscle fiber that they will eventually innervate. The hypothesized non-selective pathways indicate that the axons are guided to their destinations by the matrix through which they travel. Essentially, a path is laid out for the axon and the axon itself is not involved in the decision-making process. Finally,

9576-433: The lipid rafts that it forms provide a scaffold upon which numerous signaling interactions can occur. BDNF-null mutants show significant defects in neuronal growth and synapse formation. Aside from neurotrophins, cell-adhesion molecules are also essential to synaptogenesis. Often the binding of pre-synaptic cell-adhesion molecules with their post-synaptic partners triggers specializations that facilitate synaptogenesis. Indeed,

9690-501: The most common isotope of calcium in nature is Ca, which makes up 96.941% of all natural calcium. It is produced in the silicon-burning process from fusion of alpha particles and is the heaviest stable nuclide with equal proton and neutron numbers; its occurrence is also supplemented slowly by the decay of primordial K . Adding another alpha particle leads to unstable Ti, which decays via two successive electron captures to stable Ca; this makes up 2.806% of all natural calcium and

9804-409: The myotube following contact with the motoneuron is the increased concentration of AChR in the plasma membrane of the myotube in the synapse. This increased amount of AChR allows for more effective transmission of synaptic signals, which in turn leads to a more-developed synapse. The density of AChR is > 10,000/μm and approximately 10/μm around the edge. This high concentration of AChR in the synapse

9918-434: The neighbouring group 2 metals. It crystallises in the face-centered cubic arrangement like strontium and barium; above 443 °C (716 K), it changes to a body-centered cubic . Its density of 1.526 g/cm (at 20 °C) is the lowest in its group. Calcium is harder than lead but can be cut with a knife with effort. While calcium is a poorer conductor of electricity than copper or aluminium by volume, it

10032-399: The neural crest and are led by the axons to their destination. Upon reaching it, they form a loose, unmyelinated covering over the innervating axons. The movement of the axons (and subsequently the Schwann cells) is guided by the growth cone, a filamentous projection of the axon that actively searches for neurotrophins released by the myotube. The specific patterning of synapse development at

10146-512: The neuroligin-1's two opposite surfaces. This forms a heterotetramer, which contains an interface for binding Ca. The interaction of neuroligin and neurexin to form a heterotetramer is monitored by alternatively spliced sites located near the binding interface for Ca in both the neuroligin-1 and the neurexin-1 beta. Subsequently, the presence of native neuroligin dimers was confirmed in neurons through biochemical detection , which included heterodimers composed of different neuroligin species, increasing

10260-414: The neuromuscular junction shows that the majority of muscles are innervated at their midpoints. Although it may seem that the axons specifically target the midpoint of the myotube, several factors reveal that this is not a valid claim. It appears that after the initial axonal contact, the newly formed myotube proceeds to grow symmetrically from that point of innervation. Coupled with the fact that AChR density

10374-440: The neurons, they play an important role in functional plasticity of synapses. During development, each of the three germ layer cell types arises from different regions of the growing embryo. The individual myoblasts originate in the mesoderm and fuse to form a multi-nucleated myotube. During or shortly after myotube formation, motoneurons from the neural tube form preliminary contacts with the myotube. The Schwann cells arise from

10488-525: The only element with two primordial doubly magic isotopes. The experimental lower limits for the half-lives of Ca and Ca are 5.9 × 10 years and 2.8 × 10 years respectively. Apart from the practically stable Ca, the longest lived radioisotope of calcium is Ca. It decays by electron capture to stable K with a half-life of about 10 years. Its existence in the early Solar System as an extinct radionuclide has been inferred from excesses of K: traces of Ca also still exist today, as it

10602-419: The other hand increases the compound's solubility, volatility, and kinetic stability. Natural calcium is a mixture of five stable isotopes ( Ca, Ca, Ca, Ca, and Ca) and one isotope with a half-life so long that it is for all practical purposes stable ( Ca , with a half-life of about 4.3 × 10  years). Calcium is the first (lightest) element to have six naturally occurring isotopes. By far

10716-400: The other hand, the metal in pure form has few applications due to its high reactivity; still, in small quantities it is often used as an alloying component in steelmaking, and sometimes, as a calcium–lead alloy, in making automotive batteries. Calcium is the most abundant metal and the fifth-most abundant element in the human body . As electrolytes , calcium ions (Ca ) play a vital role in

10830-428: The other members of the group in their physical and chemical behavior: they behave more like aluminium and zinc respectively and have some of the weaker metallic character of the post-transition metals , which is why the traditional definition of the term "alkaline earth metal" excludes them. Calcium metal melts at 842 °C and boils at 1494 °C; these values are higher than those for magnesium and strontium,

10944-477: The plaster in the tomb of Tutankhamun . The ancient Romans instead used lime mortars made by heating limestone (CaCO 3 ). The name "calcium" itself derives from the Latin word calx "lime". Vitruvius noted that the lime that resulted was lighter than the original limestone, attributing this to the boiling of the water. In 1755, Joseph Black proved that this was due to the loss of carbon dioxide , which as

11058-423: The post-synaptic density of excitatory synapses, and gephyrin , the respective scaffolding protein of inhibitory post-synapses. In addition, neuroligin 2 and 4 specifically interact with collybistin a protein that regulates the localization of gephyrin. The level of PSD-95 appears to influence the balance of excitatory and inhibitory inputs. An increase in the ratio of PSD-95 to neuroligin resulted in an increase in

11172-436: The post-synaptic membrane helps ensure the fidelity of signals sent by the axon by localizing AChR to the synapse. Because the synapse begins receiving inputs almost immediately after the motoneuron comes into contact with the myotube, the axon quickly generates an action potential and releases ACh. The depolarization caused by AChR induces muscle contraction and simultaneously initiates repression of AChR gene transcription across

11286-509: The post-synaptic membrane largely due to the signaling molecule Agrin . The axon of the motoneuron releases agrin, a proteoglycan that initiates a cascade that eventually leads to AChR association. Agrin binds to a muscle-specific kinase ( MuSK ) receptor in the post-synaptic membrane, and this in turn leads to downstream activation of the cytoplasmic protein Rapsyn . Rapsyn contains domains that allow for AChR association and multimerization, and it

11400-427: The postsynaptic membrane by a cleft containing specialized extracellular material. Both structures exhibit localized vesicles at the active sites, clustered receptors at the post-synaptic membrane, and glial cells that encapsulate the entire synaptic cleft. In terms of synaptogenesis, both synapses exhibit differentiation of the pre- and post-synaptic membranes following initial contact between the two cells. This includes

11514-435: The postsynaptic neuron and are often glutamatergic , or synapses in which the neurotransmitter glutamate is released. Inhibitory synapses decrease probability of firing an action potential in the postsynaptic neuron and are often GABAergic , in which the neurotransmitter GABA is released. Especially during early development, neurons must receive an appropriate balance of excitatory vs. inhibitory synaptic input, referred to as

11628-412: The postsynaptic terminal during the maturation of the synapse. Because all developing synapses contain neurexins and neuroligins, developing cells can make many different connections to other cells. Neuroligin is sufficient to form new functional presynaptic terminals in vitro. However, evidence suggests that additional adhesion molecules, such as immunoglobulin-domain and cadherin family proteins, mediate

11742-889: The potential heterogeneity of endogenous neuroligin core dimer complexes. The extracellular domain of NLGN consists mostly of a region that is homologous to acetylcholinesterases , but the amino acids important for catalysis in AChE are not conserved in NLGN, which lack esterase activity. Furthermore, this AChE homologous region is crucial for the proper function of NLGN. Neuroligins have been identified in both vertebrates and invertebrates, including humans, rodents, chickens, Drosophila melanogaster , Caenorhabditis elegans , honeybees and Aplysia . Three genes for neuroligin expression have been found in mice and rats, while humans express five genes. Drosophila express four genes, honeybees express five genes, and both C. elegans and Aplysia express

11856-408: The rate of removal of Ca by mineral precipitation exceeds the input of new calcium into the ocean. In 1997, Skulan and DePaolo presented the first evidence of change in seawater Ca/ Ca over geologic time, along with a theoretical explanation of these changes. More recent papers have confirmed this observation, demonstrating that seawater Ca concentration is not constant, and that the ocean is never in

11970-407: The salt involved: calcium citrate , malate , and lactate are highly bioavailable, while the oxalate is less. Other calcium preparations include calcium carbonate , calcium citrate malate , and calcium gluconate . The intestine absorbs about one-third of calcium eaten as the free ion , and plasma calcium level is then regulated by the kidneys . Parathyroid hormone and vitamin D promote

12084-421: The similar ionic radii of Yb (102 pm) and Ca (100 pm). Most of these compounds can only be prepared at low temperatures; bulky ligands tend to favor stability. For example, calcium di cyclopentadienyl , Ca(C 5 H 5 ) 2 , must be made by directly reacting calcium metal with mercurocene or cyclopentadiene itself; replacing the C 5 H 5 ligand with the bulkier C 5 (CH 3 ) 5 ligand on

12198-500: The simplest terms, mountain-building exposes calcium-bearing rocks such as basalt and granodiorite to chemical weathering and releases Ca into surface water. These ions are transported to the ocean where they react with dissolved CO 2 to form limestone ( CaCO 3 ), which in turn settles to the sea floor where it is incorporated into new rocks. Dissolved CO 2 , along with carbonate and bicarbonate ions, are termed " dissolved inorganic carbon " (DIC). The actual reaction

12312-522: The steel and become small and spherical, improving castability, cleanliness and general mechanical properties. Calcium is also used in maintenance-free automotive batteries , in which the use of 0.1% calcium– lead alloys instead of the usual antimony –lead alloys leads to lower water loss and lower self-discharging. Due to the risk of expansion and cracking, aluminium is sometimes also incorporated into these alloys. These lead–calcium alloys are also used in casting, replacing lead–antimony alloys. Calcium

12426-401: The study of synaptogenesis within the central nervous system (CNS) is much more recent than that of the NMJ, there is promise of relating the information learned at the NMJ to synapses within the CNS. Many similar structures and basic functions exist between the two types of neuronal connections. At the most basic level, the CNS synapse and the NMJ both have a nerve terminal that is separated from

12540-587: The surficial system (atmosphere, ocean, soils and living organisms), storing it in carbonate rocks where it is likely to stay for hundreds of millions of years. The weathering of calcium from rocks thus scrubs CO 2 from the ocean and atmosphere, exerting a strong long-term effect on climate. The largest use of metallic calcium is in steelmaking , due to its strong chemical affinity for oxygen and sulfur . Its oxides and sulfides, once formed, give liquid lime aluminate and sulfide inclusions in steel which float out; on treatment, these inclusions disperse throughout

12654-473: The surrounding solution enriched in heavier isotopes at a magnitude of roughly 0.025% per atomic mass unit (amu) at room temperature. Mass-dependent differences in calcium isotope composition are conventionally expressed by the ratio of two isotopes (usually Ca/ Ca) in a sample compared to the same ratio in a standard reference material. Ca/ Ca varies by about 1- 2‰ among organisms on Earth. Calcium compounds were known for millennia, though their chemical makeup

12768-479: The synaptic active zone . Wnt-5a performs a similar function on postsynaptic granule cells; this Wnt stimulates receptor assembly and clustering of the scaffolding protein PSD-95 . In the hippocampus Wnts in conjunction with cell electrical activity promote synapse formation. Wnt7b is expressed in maturing dendrites, and the expression of the Wnt receptor Frizzled (Fz), increases highly with synapse formation in

12882-492: The synaptotrophins released to the synapse exhibiting strong activity, the depolarization of the post-synaptic membrane causes release of synaptotoxins that ward off weaker axons. A remarkable aspect of synaptogenesis is the fact that motoneurons are able to distinguish between fast and slow-twitch muscle fibers; fast-twitch muscle fibers are innervated by "fast" motoneurons, and slow-twitch muscle fibers are innervated by "slow" motoneurons. There are two hypothesized paths by which

12996-516: Was not understood until the 17th century. Lime as a building material and as plaster for statues was used as far back as around 7000 BC. The first dated lime kiln dates back to 2500 BC and was found in Khafajah , Mesopotamia . About the same time, dehydrated gypsum (CaSO 4 ·2H 2 O) was being used in the Great Pyramid of Giza . This material would later be used for

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