Brain Awareness Week

Brain Awareness Week is the global campaign to increase public awareness of the progress and benefits of brain research. It unites the efforts of partner organizations from around the world in a week-long celebration of the brain every year in mid-March. It was founded by the Dana Alliance for Brain Initiatives in 1995 and is coordinated by the Dana Foundation. Strategic partners include the Society for Neuroscience, the Federation of European Neuroscience Societies, and the International Brain Research Organization.
Types of events held each year are: lectures, panel discussions, neuroscience lab tours, art exhibitions, brain fairs, and lessons for school students. The Dana foundation offers free materials and event-planning advice on its website.
There is support from leading universities' neuroscience schools, neuroscience publishers, national neuroscience societies.


Trochlear nerve

The trochlear nerve (), also called the fourth cranial nerve or CN IV, is a motor nerve (a somatic efferent nerve) that innervates just one muscle: the superior oblique muscle of the eye, which operates through the pulley-like trochlea.
The trochlear nerve is unique among the cranial nerves in several respects:
Homologous trochlear nerves are found in all jawed vertebrates. The unique features of the trochlear nerve, including its dorsal exit from the brainstem and its contralateral innervation, are seen in the primitive brains of sharks.
The human trochlear nerve is derived from the basal plate of the embryonic midbrain. The words "trochlea" and "trochlear" (, ) come from Ancient Greek "trokhiléa", “pulley; block-and-tackle equipment”.
Structure.
The trochlear nerve emerges from the back (dorsal) brainstem, just below the inferior colliculus. It circles from behind around the brainstem and runs forward toward the eye in the subarachnoid space. It passes between the posterior cerebral artery and the superior cerebellar artery, and then pierces the dura just under free margin of the tentorium cerebelli, close to the crossing of the attached margin of the tentorium and within millimeters of the posterior clinoid process. It runs on the outer wall of the cavernous sinus. Finally, it enters the orbit through the superior orbital fissure and supplies the superior oblique muscle.
Nucleus.
The nucleus of the trochlear nerve is located in the caudal mesencephalon beneath the cerebral aqueduct. It is immediately below the nucleus of the oculomotor nerve (III) in the rostral mesencephalon.
The trochlear nucleus is unique in that its axons run dorsally and cross the midline before emerging from the brainstem posteriorly. Thus a lesion of the trochlear nucleus affects the "contralateral" eye. Lesions of all other cranial nuclei affect the "ipsilateral" side.
Function.
The trochlear nerve provides motor supply to the superior oblique muscle of the eye,
The trochlear nerve carries axons of type GSE, general somatic efferent, which innervate skeletal muscle of the superior oblique muscle.
The superior oblique muscle ends in a tendon that passes through a fibrous loop, the trochlea, located anteriorly on the medial aspect of the orbit. "Trochlea" means “pulley” in Latin; the fourth nerve is named after this structure.
Actions of the superior oblique muscle.
In order to understand the actions of the superior oblique muscle, it is useful to imagine the eyeball as a sphere that is constrained—like the trackball of a computer mouse—in such a way that only certain rotational movements are possible. Allowable movements for the superior oblique are (1) rotation in a vertical plane—looking down and up ("depression" and "elevation" of the eyeball) and (2) rotation in the plane of the face ("intorsion" and "extorsion" of the eyeball).
The body of the superior oblique muscle is located "behind" the eyeball, but the tendon (which is redirected by the trochlea) approaches the eyeball from the "front". The tendon attaches to the top (superior aspect) of the eyeball at an angle of 51 degrees with respect to the "primary position" of the eye (looking straight forward). The force of the tendon's pull therefore has two components: a forward component that tends to pull the eyeball downward (depression), and a medial component that tends to rotate the top of the eyeball toward the nose (intorsion).
The relative strength of these two forces depends on which way the eye is looking. When the eye is "adducted" (looking toward the nose), the force of depression increases. When the eye is "abducted" (looking away from the nose), the force of intorsion increases, while the force of depression decreases. When the eye is in the primary position (looking straight ahead), contraction of the superior oblique produces depression and intorsion in roughly equal amounts.
To summarize, the actions of the superior oblique muscle are (1) "depression" of the eyeball, especially when the eye is adducted; and (2) "intorsion" of the eyeball, especially when the eye is abducted. The clinical consequences of weakness in the superior oblique (caused, for example, by fourth nerve palsies) are discussed below.
This summary of the superior oblique muscle describes its most important functions. However, it is an oversimplification of the actual situation. For example, the tendon of the superior oblique inserts "behind" the equator of the eyeball in the frontal plane, so contraction of the muscle also tends to "abduct" the eyeball (turn it outward). In fact, each of the six extraocular muscles exerts rotational forces in "all three planes" (elevation-depression, adduction-abduction, intorsion-extorsion) to varying degrees, depending on which way the eye is looking. The relative forces change every time the eyeball moves—every time the direction of gaze changes. The central control of this process, which involves the continuous, precise adjustment of forces on twelve different tendons in order to point both eyes in exactly the same direction, is truly remarkable.
The recent discovery of soft tissue pulleys in the orbit—similar to the trochlea, but anatomically more subtle and previously missed—has completely changed and greatly simplified our understanding of the actions of the extraocular muscles. Perhaps the most important finding is that a two-dimensional representation of the visual field is sufficient for most purposes.
Clinical significance.
Vertical diplopia.
Injury to the trochlear nerve cause weakness of downward eye movement with consequent vertical diplopia (double vision). The affected eye drifts upward relative to the normal eye, due to the unopposed actions of the remaining extraocular muscles. The patient sees two visual fields (one from each eye), separated vertically. To compensate for this, patients learn to tilt the head forward (tuck the chin in) in order to bring the fields back together—to fuse the two images into a single visual field. This accounts for the “dejected” appearance of patients with “pathetic nerve” palsies.
Torsional diplopia.
Trochlear nerve palsy also affects torsion (rotation of the eyeball in the plane of the face). Torsion is a normal response to tilting the head sideways. The eyes automatically rotate in an equal and opposite direction, so that the orientation of the environment remains unchanged—vertical things remain vertical.
Weakness of intorsion results in torsional diplopia, in which two different visual fields, tilted with respect to each other, are seen at the same time. To compensate for this, patients with trochlear nerve palsies tilt their heads to the opposite side, in order to fuse the two images into a single visual field.
The characteristic appearance of patients with fourth nerve palsies (head tilted to one side, chin tucked in) suggests the diagnosis, but other causes must be ruled out. For example, torticollis can produce a similar appearance.
Causes.
The clinical syndromes can originate from both peripheral and central lesions.
Peripheral lesion.
A peripheral lesion is damage to the bundle of nerves, in contrast to a central lesion, which is damage to the trochlear nucleus. Acute symptoms are probably a result of trauma or disease, while chronic symptoms probably are congenital.
Acute palsy.
The most common cause of "acute" fourth nerve palsy is head trauma. Even relatively minor trauma can transiently stretch the fourth nerve (by transiently displacing the brainstem relative to the posterior clinoid process). Patients with minor damage to the fourth nerve will complain of “blurry” vision. Patients with more extensive damage will notice frank diplopia and rotational (torsional) disturbances of the visual fields. The usual clinical course is complete recovery within weeks to months.
Isolated injury to the fourth nerve can be caused by any process that stretches or compresses the nerve. A generalized increase in intracranial pressure—hydrocephalus, pseudotumor cerebri, hemorrhage, edema—will affect the fourth nerve, but the abducens nerve (VI) is usually affected first (producing horizontal diplopia, not vertical diplopia). Infections (meningitis, herpes zoster), demyelination (multiple sclerosis), diabetic neuropathy and cavernous sinus disease can affect the fourth nerve, as can orbital tumors and Tolosa–Hunt syndrome. In general, these diseases affect other cranial nerves as well. Isolated damage to the fourth nerve is uncommon in these settings.
Chronic palsy.
The most common cause of "chronic" fourth nerve palsy is a congenital defect, in which the development of the fourth nerve (or its nucleus) is abnormal or incomplete. Congenital defects may be noticed in childhood, but minor defects may not become evident until adult life, when compensatory mechanisms begin to fail. Congenital fourth nerve palsies are amenable to surgical treatment.
Central lesion.
Central damage is damage to the trochlear nucleus. It affects the "contralateral" eye. The nuclei of other cranial nerves generally affect "ipsilateral" structures (for example, the optic nerves - cranial nerves II - innervate both eyes).
The trochlear nucleus and its axons within the brainstem can be damaged by infarctions, hemorrhage, arteriovenous malformations, tumors and demyelination. Collateral damage to other structures will usually dominate the clinical picture.
The fourth nerve is one of the final common pathways for cortical systems that control eye movement in general. Cortical control of eye movement (saccades, smooth pursuit, accommodation) involves conjugate gaze, not unilateral eye movement.
Examination.
The trochlear nerve is tested by examining the action of its muscle, the superior oblique. When acting on its own this muscle depresses and abducts the eyeball. However, movements of the eye by the extraocular muscles are synergistic (working together). Therefore, the trochlear nerve is tested by asking the patient to look 'down and in' as the contribution of the superior oblique is greatest in this motion. Common activities requiring this type of convergent gaze are reading the newspaper and walking down stairs. Diplopia associated with these activities may be the initial symptom of a fourth nerve palsy.
Alfred Bielschowsky's head tilt test is a test for palsy of the superior oblique muscle caused by damage to cranial nerve IV (trochlear nerve).


Salamander Syncope

Salamander Syncope (1971) 24-minute work directed and produced by Hamid Naficy on 2-inch, color videotape and 16mm film for his Master of Fine Arts thesis at University of California, Los Angeles. Naficy produced the work in conjunction with the UCLA computer department. He collaborated over two years with six computer engineering students including internet pioneer Vint Cerf.
 Long ignored in scholarly circles, the film has begun to be discussed as an early example of computer-generated cinema, specifically experimental and countercultural cinema produced in the United States by an Iranian immigrant.
Influences.
The imagery in the film is abstract, generated by computers and subsequently manipulated with additional computers and video processing tools. It is thematically indebted to Stanley Kubrick's 1968 , with imagery such as the origin of modern humans and the development to the transcendent "Star Child" evoked through abstract computer-generated imagery. Naficy sought to represent "inner and outer consciousness." Naficy was also influenced the writings and ideas of Alan Watts, Aldous Huxley, Gene Youngblood, and Buckminster Fuller. In terms of contemporary experimental film and video, Naficy was only familiar with some of John Whitney's films at the time.
Soundtrack.
Fellow UCLA student Ken Yapkowitz's quadraphonic score combines the use of Moog synthesizers and recordings of Muslim preachers recorded at Naficy's uncle's house.


Dynamic response index

The Dynamic Response Index (DRI) is a measure of the likelihood of spinal damage arising from a vertical shock load such as might be encountered in a military environment (i.e., during a mine blast, or in an ejection seat). The DRI is a dimensionless number which is proportional to the maximum spinal compression suffered during the event.
The DRI is derived as the solution to an equation which models the human spine as a lumped single-degree-of-freedom spring-shock absorber system. The model uses an ordinary linear second-order differential equation with constant coefficients with spinal compression as the variable. The forcing function in the equation is the accelerative shock load delivered to the pelvis by the event. The equation is given below:
formula_1
In this equation, X denotes the spinal compression, and d2z/dt2 denotes the time-dependent shock acceleration (the input). The coefficients ω and ζ are the lumped spinal frequency and damping, ω = 52.90 radians/second, ζ = 0.224.
The DRI is defined in terms of the maximum spinal compression (Xmax) calculated from the differential equation, DRI = (ω2/G)·Xmax, where G is the acceleration of gravity (9.806 m/s2).
The DRI measure was derived from research on cadavers, as well as from “willing volunteers” (essentially, aviators who activated the ejection seat mechanism).
The limiting DRI value according to NATO STANAG 4569 is 17.7 with a 10% chance of serious injury. This corresponds to a maximum spinal compression of about 62 mm.
A simple rule of thumb for short duration shocks (much less than about a quarter of a cycle, which means much less than about 30 ms) is DRI = 3.96·ΔV, where ΔV is the total impulse delivered by the shock in units of meters per second. ΔV is simply the integral under the shock acceleration curve, equivalent to the “liftoff” velocity of the object undergoing shock loading. For a constant impulse, the DRI decreases as the duration of the pulse increases beyond about 30 ms.


Netupitant

Netupitant is an antiemetic drug. In the United States, the combination drug netupitant/palonosetron (trade name Akynzeo) is approved by the Food and Drug Administration for prevention of acute and delayed chemotherapy-induced nausea and vomiting, including highly emetogenic chemotherapy such as with cisplatin. In Europe, it is approved by the European Medicines Agency (EMA) for the same indication.
Adverse effects.
Side effects of the combination netupitant/palonosetron are similar to palonosetron alone, so that no common side effects can be attributed to netupitant.
headache,
weakness,
indigestion,
fatigue,
constipation, and
skin redness
Interactions.
Netupitant blood plasma levels are expected to increase when combined with inhibitors of the liver enzyme CYP3A4 and lowered when combined with inductors of this enzyme.
Being a CYP3A4 inhibitor itself, netupitant could also increase plasma levels of pharmaceuticals that are metabolized by CYP3A4. This effect has been observed with dexamethasone, the anti-cancer drugs docetaxel and etoposide, and to a minor (not clinically significant) extent with levonorgestrel, erythromycin and midazolam.
Pharmacology.
Mechanism of action.
Netupitant is a selective NK1 receptor antagonist.
Netupitant is a selective neurokinin 1 (NK1) receptor antagonist with potential antiemetic activity. Netupitant competitively binds to and blocks the activity of the human substance P/NK1 receptors in the central nervous system (CNS), thereby inhibiting NK1-receptor binding of the endogenous tachykinin neuropeptide substance P (SP), which may result in the prevention of chemotherapy-induced nausea and vomiting (CINV). SP is found in neurons of vagal afferent fibers innervating the brain-stem nucleus tractus solitarii and the area postrema, which contains the chemoreceptor trigger zone (CTZ), and may be elevated in response to chemotherapy. The NK-receptor is a G-protein receptor coupled to the inositol phosphate signal-transduction pathway and is found in both the nucleus tractus solitarii and the area postrema.
Pharmacokinetics.
Bioavailability is estimated to be over 60% for orally taken netupitant. Highest blood plasma concentrations are reached five hours after application. Availability is moderately (10–20%) increased when taken after a fatty meal. Netupitant and its main metabolites (called M1 and M3) are bound to plasma proteins to more than 99%, and M2 protein binding is 97%.
The substance is mainly metabolized by CYP3A4, and to a lesser extent by CYP2D6 and CYP2C9. The main metabolites are desmethyl-netupitant (M1), netupitant "N"-oxide (M2), and hydroxy-netupitant (M3); all three are pharmacologically active.
Netupitant and its metabolites are mainly excreted via the faeces. Biological half-life is 88 hours, significantly longer than that of the first NK1 receptor antagonist, aprepitant, which has a half-life of 9 to 13 hours.


Derek Amato

Derek Amato (born November 19, 1966) is an American composer and pianist who received a head injury on October 27, 2006, and subsequently became a musical savant. He is the only known musical savant to have developed savant syndrome through a brain injury.
At the age of 39, Amato dove into a shallow swimming pool and hit his head, resulting in major concussion and 35% hearing loss. Although he had played the guitar prior to his injury, the level of his musical ability suddenly progressed to the point where he was able to compose for piano. He has been diagnosed as experiencing a form of synesthesia.


Delta-Palutoxin

"delta"-Palutoxins (δ-palutoxins) consist of a homologous group of four insect-specific toxins from the venom of the spider "Pireneitega luctuosa" (also known as "Paracoelotes luctuosus"). They show a high toxicity against "Spodoptera litura" larvae by inhibiting sodium channels, leading to strong paralytic activity and eventually to the death of the insect.
Sources.
δ-Palutoxins are extracted from the venom of the spider "Pireneitega luctuosa". This venom has highest toxicity against "Spodoptera litura" larvae, which are a known cause of the crop pest in agriculture.
Chemistry.
There are four subfractions in the venom known to be active against the "Spodoptera litura" larvae: δ-palutoxin IT1, δ-palutxoin IT2, δ-palutoxin IT3, and δ-palutoxin IT4. These toxins are 36-37 amino acids long and show high homology. The concentrations of the different subtypes in the venom, molecular masses, and acidity level of the subtypes are listed below.
δ-Palutoxins are very compact proteins due to their four disulfide bridges. These bindings result in a disulfide pseudo-knot, characteristic for a class of toxins that contain the ‘inhibitor cystine knot motif’ (ICK). This motif is responsible for their high "in vivo" stability. Members of the ICK family are characterized by a triple-stranded, antiparallel ß-sheet structure, stabilized by disulfide bridges. Within this fold-class, the biological activities of the toxins are very diverse. The disulfide bonding pattern found in δ-Palutoxins is very similar to the pattern seen in µ-Agatoxins. This indicates strong homologies with the µ-Agatoxins from Agelenopsis aperta.
Target.
Voltage-gated sodium channels have neurotoxin binding sites on their α-subunit, which are called neurotoxin receptor sites 1-7. δ-Palutoxins bind to receptor site 4 of insect voltage-gated sodium channels. Receptor site 4 neurotoxins bind to the S1-S2 and S3-S4 extracellular loops in domain II of the α-subunit of the channel.
Mode of action.
δ-Palutoxin-IT1 and δ-palutoxin-IT2 inhibit the inactivation of voltage-gated sodium channels. As the voltage-dependence of the inactivation time constant was not affected, it has been proposed that the toxins act on the conversion from the closed to the inactivated state. The inhibition of inactivation results in excessive sodium influx. This leads to a high concentration of calcium in the muscles, which causes slow paralysis. This slow paralysis is characterized by muscle spasm and loss of water through the body wall. Eventually, the insects will die because they dry out. The effect of δ-palutoxins on voltage-gated sodium channels is similar to that seen in α-like scorpion toxins.
Toxicity.
The four δ-palutoxins show a strong paralytic activity against "Spodoptera litura" larvae but also against some other insects. The values for δ-palutoxin-IT1 to IT3 range from 9.5–24.7 µg per gram insect. δ-Palutoxin-IT1 is the most active toxin, followed by δ-palutoxin-IT2, and δ-palutoxin-IT4 has the lowest activity. δ-Palutoxins are insect selective, no persistent toxic effect was found on mice. The structural basis for the selectivity of these toxins for insects over the mammalian sodium ion channels is still largely unknown.


Dopamine reuptake inhibitor

A dopamine reuptake inhibitor (DRI) is a class of drug which acts as a reuptake inhibitor of the monoamine neurotransmitter dopamine by blocking the action of the dopamine transporter (DAT). Reuptake inhibition is achieved when extracellular dopamine not absorbed by the postsynaptic neuron is blocked from re-entering the presynaptic neuron. This results in increased extracellular concentrations of dopamine and increase in dopaminergic neurotransmission.
DRIs are used in the treatment of attention-deficit hyperactivity disorder (ADHD) and narcolepsy for their psychostimulant effects, and in the treatment of obesity and binge eating disorder for their appetite suppressant effects. They are sometimes used as antidepressants in the treatment of mood disorders, but their use as antidepressants is limited given that strong DRIs have a high abuse potential and legal restrictions on their use. Lack of dopamine reuptake and the increase in extracellular levels of dopamine have been linked to increased susceptibility to addictive behavior given increase in dopaminergic neurotransmission. The dopaminergic pathways are considered to be strong reward centers. Many DRIs such as cocaine are drugs of abuse due to the rewarding effects evoked by elevated synaptic concentrations of dopamine in the brain.
Society and culture.
History of use.
Until the 1950s, dopamine was thought to only contribute to the biosynthesis of norepinephrine and epinephrine. It was not until dopamine was found in the brain in similar levels as norepinephrine that the possibility was considered that its biological role might be other than the synthesis of the catecholamines.
Pharmacotherapeutic uses.
The following drugs have DRI action and have been or are used clinically specifically for this property: amineptine, dexmethylphenidate, difemetorex, fencamfamine, lefetamine, levophacetoperane, medifoxamine, mesocarb, methylphenidate, nomifensine, pipradrol, prolintane, and pyrovalerone. The following drugs are or have been used clinically and possess only weak DRI action, which may or may not be clinically-relevant: adrafinil, armodafinil, bupropion, mazindol, modafinil, nefazodone, sertraline, and sibutramine. The following drugs are or have been clinically used but only coincidentally have DRI properties: benzatropine, diphenylpyraline, etybenzatropine, ketamine, nefopam, pethidine (meperidine), and tripelennamine. The following are a selection of some particularly notably abused DRIs: cocaine, ketamine, MDPV, naphyrone, and phencyclidine (PCP). Amphetamines, including amphetamine, methamphetamine, MDMA, cathinone, methcathinone, mephedrone, and methylone, are all DRIs as well, but are distinct in that they also behave, and potentially more potently as dopamine releasing agents (DRAs) (due to Yerkes–Dodson's law, 'more potently stimulated' may not equal more optimally functionally stimulated). There are very distinct differences in the mode of action between dopamine releasers/substrates & dopamine re-uptake inhibitors; the former are functionally entropy-driven ("i.e." relating to hydrophobicity) and the latter are enthalpy-driven ("i.e." relating conformational change). Reuptake inhibitors such as cocaine induce hyperpolarization of cloned human DAT upon oocytes that are naturally found on neurons, whereas releasing agents induce de-polarization of the neuron membrane.
The wakefulness-promoting agent modafinil and its analogues (e.g., adrafinil, armodafinil) have been approved to treat narcolepsy and shift work sleep disorder. These act as weak (micromolar) DRIs, but this effect does not correlate with wakefulness-promoting effects, suggesting the effect is too weak to be of clinical significance. The conclusion is these drugs promote wakefulness via some other mechanism.
DRIs have been explored as potential antiaddictive agents in the context of replacement therapy strategies, analogous to nicotine replacement for treating tobacco addiction and methadone replacement in the case of opioid addiction. DRIs have been explored as treatment for cocaine addiction, and have shown to alleviate cravings and self-administration.
Monoamine reuptake inhibitors, including DRIs, have also shown effectiveness as therapy for excessive food intake and appetite control for obese patients. Though such pharmacotherapy is still available, the majority of stimulant anorectics marketed for this purpose have been withdrawn or discontinued due to adverse side effects such as hypertension, valvulopathy, and drug dependence.
List of DRIs.
Only DRIs which are selective for the DAT over the other monoamine transporters (MATs) are listed below. For a list of DRIs that act at multiple MATs, see other monoamine reuptake inhibitor pages such as NDRI and SNDRI.


Renshaw cell

Renshaw cells are inhibitory interneurons found in the gray matter of the spinal cord, and are associated in two ways with an alpha motor neuron.
In this way, the Renshaw cell action represents a negative feedback mechanism. A Renshaw cell may be supplied by more than one alpha motor neuron collateral and it may synapse on multiple motor neurons.
Function.
Although during embryonic development the Renshaw cells lack synapses from the dorsal root, prenatal and postnatal stages show the development of dorsal root originating synapses, which are functional and stimulate action potentials. But these decrease during development while acetylcholine motor axons begin to synapse and proliferate with Renshaw cells, ultimately being primarily stimulated by the motor neurons.
The Renshaw cells are ultimately excited by multiple antidromic motor neuron axons, where the majority of axons originate from synergist motor neurons, and in turn the Renshaw cell synapses with multiple neurons, eliciting IPSP in alpha motor, 1a inhibitory interneurons and gamma motor neurons. The antidromic collateral circuit back to the triggering motor neuron is known as “recurrent inhibition”. This homonymous inhibition is not universal. Whereas most initial experiments have been done on cats, it has been found that in man that proximal muscles of the hand and foot do not have homonymous inhibition. Heteronymous inhibition has been found to be dominant in the leg compared to the arm, where antagonist muscles work simultaneously. (Renshaw cells are activated by gamma motor neurons, but to a lesser extent).
The Renshaw cells not only synapse with homonymous and heteronymous nerves, but also with the Ia interneurones, which are stimulated by the Ia afferents from the same muscle group activated by the motor neurons, which have an inhibitory effect on the antagonist muscle group. This “recurrent facilitation” causes reduced inhibition of the reciprocal inhibition of the Ia interneuron of the antagonist group (Baret et al.; 2003), which may in turn also be inhibited by signals from the corticospinal tract.
It has been shown that:
The Renshaw cells may also be inhibited by both proprioceptive dorsal root afferents], antidromic ventral axons as well as “descending” inhibition. The hyperpolarization of Renshaw cells by afferent and descending neurons have been shown to be caused by the release of glycine, but GABA may also hyperpolarize the Renshaw cell - for a prolonged time relative to glycine. It has also been shown that glycine is the inhibitory transmitter released by the Renshaw cells.
In essence the Renshaw cells regulate the firing of the alpha motor neuron leaving the ventral horn. Conceptually they remove “noise” by dampening the firing frequency of over-excited neurons with a negative feedback loop, which prevents weakly excited alpha motor neurons from firing. Descending spinal cord nerves in turn regulate the Renshaw cells.
The rate of discharge of the Renshaw cell is broadly proportional to the rate of discharge of the associated motor neuron(s), and the rate of discharge of the motor neuron(s) is broadly inversely proportional to the rate of discharge of the Renshaw cell(s). Renshaw cells thus act as "limiters," or "governors," on the alpha motor neuron system, thus helping to prevent muscular damage from tetanus.
Renshaw cells utilize the neurotransmitter glycine as an inhibitory substance that synapses on the alpha motor neurons.
Clinical significance.
Renshaw cells are also the target of the toxin of "Clostridium tetani", a Gram positive, spore-forming anaerobic bacterium that lives in the soil, and causes tetanus. When wounds are contaminated with "C. tetani", the toxin travels to the spinal cord where it inhibits the release of glycine, an inhibitory neurotransmitter, from Renshaw cells. As a result, alpha motor neurons become hyperactive, and muscles constantly contract.
Strychnine poison also specifically acts on these cell's ability to control alpha motor neuron firing by binding to the glycine receptors on the alpha motor neuron and thus muscles continually contract and may prove fatal if the diaphragm is involved.
History.
The concept of the Renshaw cells was postulated by Birdsey Renshaw (1911–1948), when it was discovered that with antidromic signals from a motor neuron running collaterally back via the ventral root into the spinal cord, there were interneurons firing with a high frequency, resulting in inhibition. Later work by Eccles "et al.", provided evidence that these interneurons, which they called “Renshaw Cells,” are stimulated by acetylcholine from motor neurons (nicotinic receptor). Previous work by Renshaw and Lloyd had shown that this antidromic inhibition resembled direct inhibition from spinal nerves but resulted in relatively longer inhibition of 40-50 ms (compared to 15 ms). The antidromic stimulation of the nerve fiber also resulted in action potentials in the cell bodies of the motor neurons along with hyperpolarization of other groups of motor neurons. In the event where the initial stimulation of the motor neuron originated in a spinal tract the Renshaw cell spike occurred during the declining phase of the initial motor neuron soma spike giving an indication of the source and sequence of stimulation of the Renshaw cell.


Subclavian loop

Subclavian loop ("ansa subclavia"), also known as Vieussens' ansa after French anatomist Raymond Vieussens (1635-1715), is a nerve cord that is a connection between the middle and inferior cervical ganglion which is commonly fused with the first thoracic ganglion and is then called the stellate ganglion. The subclavian ansa forms a loop around the subclavian artery; whence its name. This communicating branch downwards anteromedial to the vertebral artery makes a loop around the subclavian artery from anterior to posterior and then lies medially to the internal thoracic artery respectively. Sometimes there are two communicating branches encompassing the vertebral artery, one from anterior and the other from posterior.


Bunaftine

Bunaftine (or bunaphtine) is an antiarrhythmic agent. It is classified in class III.


Midbrain tegmentum

The midbrain is anatomically delineated into the tectum (roof) and the tegmentum (floor). The midbrain tegmentum extends from the substantia nigra to the cerebral aqueduct in a horizontal section of the midbrain. It forms the floor of the midbrain that surrounds below the cerebral aqueduct as well as the floor of the fourth ventricle while the midbrain tectum forms the roof of the fourth ventricle. The tegmentum contains a collection of tracts and nuclei with movement-related, species-specific, and pain-perception functions. The general structures of midbrain tegmentum include red nucleus and the periaqueductal grey matter.
Unlike the midbrain tectum (which is a sensory structure located posteriorly), the midbrain tegmentum, which locates anteriorly, is related to a number of motor functions. Within the tegmentum, the red nucleus is in charge of motor coordination (specifically for limb movements) and the periaqueductal gray matter (PAG) contains critical circuits for modulating behavioral responses to pains. The substantia nigra (black substance) serves an important role in rewarding behaviors such as approaching desired objects. In addition, the substantia nigra forms reciprocal connections with the basal ganglia which are highly correlated with motor functions and learning.
The midbrain tegmentum is also an important part of the dopaminergic system which is essential for feelings of reward and pleasure. Two regions in the midbrain tegmentum are of particular interest. The first one is the substantia nigra which is an important part of the nigrostriatal pathway. This pathway serves to coordinate motor movements and when left unbalanced, motor deficits would follow. For instance, when the dopamine neurons are lost from the substantia nigra, the condition of extreme muscle rigidity occurs as in the Parkinson's disease. The second region is the ventral tegmental area (VTA; or simply ventral tegmentum) which is at the hub of the mesolimbic pathway. Specifically, the VTA is the origin of dopaminergic cell bodies from which signals reach the anterior parts of the brain (e.g., frontal lobes) as well as the posterior parts (e.g., cerebellum). Because of this pathway regulates the experience of reward and pleasure, it is not surprising to see that food and drugs affect it the most in terms of a loss of impulse control. That is, the mesolimbic pathway is essential in regulating drug addiction. The potential mechanism is through the associative learning of the environmental cues and reward. For instance, through each drug use, individuals increasingly associate the cues related to each drug use (e.g., the room in which the drug is taken or the people with which individuals take drug). Over time, the drug enhances the dopamine-related, classically-conditioned cues associated with drug taking. As a result, later encounters with these cues will produce and heighten dopamine activity and subsequently prompt individuals to crave drugs. Moreover, excessive mesolimbic dopamine activity plays a role in schizophrenia, a behavioral disorder characterized by delusions, hallucinations, blunted emotion, agitation, etc. On the other hand, a lack of mesolimbic dopamine activity may induce deficits in attention.


Peristimulus time histogram

In neurophysiology, peristimulus time histogram and poststimulus time histogram, both abbreviated PSTH or PST histogram, are histograms of the times at which neurons fire. It is also sometimes called pre event time histogram or PETH. These histograms are used to visualize the rate and timing of neuronal spike discharges in relation to an external stimulus or event. The peristimulus time histogram is sometimes called perievent time histogram, and "post-stimulus" and "peri-stimulus" are often hyphenated.
The prefix "peri," for "through," is typically used in the case of periodic stimuli, in which case the PSTH show neuron firing times wrapped to one cycle of the stimulus. The prefix "post" is used when the PSTH shows the timing of neuron firings in response to a stimulus event or onset.
To make a PSTH, a spike train recorded from a single neuron is aligned with the onset, or a fixed phase point, of an identical stimulus repeatedly presented to an animal. The aligned sequences are superimposed in time, and then used to construct a histogram.
Construction procedure.
The optimal bin size (assuming an underlying Poisson point process) Δ is a minimizer of the formula, (2k-v)/Δ2,
where k and v are mean and variance of ki.


Glicaramide

Glicaramide (SQ-65993) is an orally bioavailable anti-diabetic medication. It has a similar potency as glibenclamide (glyburide) in the class of medication known as sulfonylureas. Its structure is similar since it has a cyclic acyl group which replaces the latter's 2-methoxy-5-chlorobenzyl. Same as glibenclamide, it is classified as a second-generation sulfonylurea. It may have more pronounced extra-pancreatic effects than glibenclamide or tolbutamide.


Copy propagation

In compiler theory, copy propagation is the process of replacing the occurrences of targets of direct assignments with their values. A direct assignment is an instruction of the form codice_1, which simply assigns the value of codice_2 to codice_3.
From the following code:
 y = x
 z = 3 + y
Copy propagation would yield:
 z = 3 + x
Copy propagation often makes use of reaching definitions, use-def chains and def-use chains when computing which occurrences of the target may be safely replaced. If all upwards exposed uses of the target may be safely modified, the assignment operation may be eliminated.
Copy propagation is a useful "clean up" optimization frequently used after other compiler passes have already been run. Some optimizations—such as classical implementations of elimination of common sub expressions—"require" that copy propagation be run afterwards in order to achieve an increase in efficiency.
Further reading.
Muchnick, Steven S. "Advanced Compiler Design and Implementation". Morgan Kaufmann. 1997.


Loop splitting

Loop splitting is a compiler optimization technique. It attempts to simplify a loop or eliminate dependencies by breaking it into multiple loops which have the same bodies but iterate over different contiguous portions of the index range.
Loop peeling.
Loop peeling is a special case of loop splitting which splits any problematic first (or last) few iterations from the loop and performs them outside of the loop body.
Suppose a loop was written like this:
 int p = 10;
 for (int i=0; i<10; ++i)
 y[i] = x[i] + x[p];
 p = i;
Notice that codice_1 only for the first iteration, and for all other iterations, codice_2. A compiler can take advantage of this by unwinding (or "peeling") the first iteration from the loop.
After peeling the first iteration, the code would look like this:
 y[0] = x[0] + x[10];
 for (int i=1; i<10; ++i)
 y[i] = x[i] + x[i-1];
This equivalent form eliminates the need for the variable codice_3 inside the loop body.
Loop peeling was introduced in gcc in version 3.4. More generalised loop splitting was added in GCC 7.
Brief history of the term.
Apparently the term was for the first time used by Cannings, Thompson and Skolnick in their 1976 paper on computational models for (human) inheritance. There the term was used to denote a method for collapsing phenotypic information onto parents. From there the term was used again in their papers, including their seminal paper on probability functions on complex pedigrees.
In compiler technology, the term first turned up in late 1980s papers on VLIW and superscalar compilation, including and.


Resorcylic acid lactone

Resorcylic acid lactones are a group of estrogenic compounds. They are lactones of resorcylic acid. Examples include the mycoestrogens (and synthetic analogues) zearalenone, zearalanone, zeranol (α-zearalanol), taleranol (β-zearalanol), α-zearalenol, and β-zearalenol.


Fcitx

Fcitx (, ) is an input method framework with extension support for the X Window System that supports multiple input method engines including Pinyin transcription, table-based input methods (e.g. Wubi method), fcitx-chewing for Traditional Chinese, fcitx-keyboard for layout-based ones, fcitx-mozc for Japanese, fcitx-hangul for Korean.
It supports UTF-8, GBK and GB 18030 character encodings, can run in Linux and FreeBSD, and supports XIM protocol, GTK+ (both 2 and 3) and Qt input method modules.
Before version 3.6, Fcitx used GBK encoding internally, which has been changed to UTF-8 in the 4.0 release. Since version 4.1, it has become highly modular, and has added support for Google Pinyin (which was ported from the Android version), fbterm, and KDE.


Jani Ingram

Jani Ingram is a Professor of Chemistry and Biochemistry at Northern Arizona University. Ingram researches the chemistry and health impacts of environmental pollutants, especially uranium and arsenic. Ingram is a member of the Navajo tribe, and the Naneesht’ezhi clan. She leads the Bridging Arizona Native American to Bachelor Degrees (NIH Bridges to Baccalaureate) program and the Native American Cancer Prevention Program. She promotes educational and professional opportunities for Native American students in Chemistry through a number of initiatives and for this work was awarded the 2018 American Chemical Society Award for Encouraging Disadvantaged Students into Careers in the Chemical Sciences.
Education.
Ingram began her academic studies at Yavapai Community College in Arizona where she earned an Associate's degree. She subsequently studied at New Mexico State University and earned a Bachelor’s degree in Chemistry. Her Ph.D. is in Chemistry from the University of Arizona.
Career and research.
Ingram's research areas are analytical chemistry and environmental chemistry. She specialises on environmental uranium and arsenic contamination and how they effect the food chain and water supplies of the Navajo nation. She also researches traditional Navajo food ingredients and their health benefits, for example juniper ash as a calcium source. In light of the Covid19 pandemic her research laboratory repurposed their facilities to produce hand sanitiser which was donated to the Navajo Nation.


Shape analysis (program analysis)

In program analysis, shape analysis is a static code analysis technique that discovers and verifies properties of linked, dynamically allocated data structures in (usually imperative) computer programs. It is typically used at compile time to find software bugs or to verify high-level correctness properties of programs. In Java programs, it can be used to ensure that a sort method correctly sorts a list. For C programs, it might look for places where a block of memory is not properly freed.
Applications.
Shape analysis has been applied to a variety of problems:
Example.
Shape analysis is a form of pointer analysis, although it is more precise than typical pointer analysis. Pointer analysis attempts to determine the set of objects to which a pointer can point (called the points-to set of the pointer). Unfortunately, these analysis are necessarily approximate (since a perfectly precise static analysis could solve the halting problem). Shape analysis can determine smaller (more precise) points-to sets.
Consider the following simple C++ program.
Item *items[10];
for (int i = 0; i < 10; ++i) {
 items[i] = new Item(...); // line [1]
process_items(items); // line [2]
for (int i = 0; i < 10; ++i) {
 delete items[i]; // line [3]
This program builds an array of objects, processes them in some arbitrary way, and then deletes them. Assuming that the codice_3 function is free of errors, it is clear that the program is safe: it never references freed memory, and it deletes all the objects that it has constructed.
Unfortunately, most pointer analyses have difficulty analyzing this program precisely. In order to determine points-to sets, a pointer analysis must be able to "name" a program's objects. In general, programs can allocate an unbounded number of objects; but in order to terminate, a pointer analysis can only use a finite set of names. A typical approximation is to give all the objects allocated on a given line of the program the same name. In the example above, all the objects constructed at line [1] would have the same name. Therefore, when the codice_4 statement is analyzed for the first time, the analysis determines that one of the objects named [1] is being deleted. The second time the statement is analyzed (since it is in a loop) the analysis warns of a possible error: since it is unable to distinguish the objects in the array, it may be that the second codice_4 is deleting the same object as the first codice_4. This warning is spurious, and the goal of shape analysis is to avoid such warnings.
Summarization and materialization.
Shape analysis overcomes the problems of pointer analysis by using a more flexible naming system for objects. Rather than giving an object the same name throughout a program, objects can change names depending on the program's actions. Sometimes, several distinct objects with different names may be "summarized," or merged, so that they have the same name. Then, when a summarized object is about to be used by the program, it can be "materialized"—that is, the summarized object is split into two objects with distinct names, one representing a single object and the other representing the remaining summarized objects. The basic heuristic of shape analysis is that objects that are being used by the program are represented using unique materialized objects, while objects not in use are summarized.
The array of objects in the example above is summarized in separate ways at lines [1], [2], and [3]. At line [1], the array has been only partly constructed. The array elements 0..i-1 contain constructed objects. The array element i is about to be constructed, and the following elements are uninitialized. Shape analysis can approximate this situation using a summary for the first set of elements, a materialized memory location for element i, and a summary for the remaining uninitialized locations, as follows:
After the loop terminates, at line [2], there is no need to keep anything materialized. The shape analysis determines at this point that all the array elements have been initialized:
At line [3], however, the array element codice_7 is in use again. Therefore, the analysis splits the array into three segments as in line [1]. This time, though, the first segment before codice_7 has been deleted, and the remaining elements are still valid (assuming the codice_4 statement hasn't executed yet).
Notice that in this case, the analysis recognizes that the pointer at index codice_7 has not been deleted yet. Therefore, it doesn't warn of a double deletion.


Imperatoxin

Imperatoxin I (IpTx) is a peptide toxin derived from the venom of the African scorpion "Pandinus imperator".
There are two subtypes of this toxin:
Imperatoxin A.
The toxin comes from the venom of the African scorpion "Pandinus imperator". The structure of IpTxa consists of:
The molecular weight of the toxin is 3.7 kDa.
IpTxa acts on the Ryanodine receptors (RyR), which are intracellular Ca2+ release channels mainly known for their role in regulating Ca2+ release from the sarcoplasmatic reticulum of striated muscles. The peptide acts better on RyR type 1 than on type 3. RyR type 2 seems to be insensitive to IpTxa.
The part of the peptide that looks like the II-III loop of the (DHPR) binds directly to RyR and enhances ryanodine binding to trigger Ca2+ release.
Imperatoxin I.
The toxin comes from the venom of the African scorpion "Pandinus imperator". The structure of IpTxi consists of:
The molecular weight of the toxin is 15 kDa.
Like IpTxa, IpTxi acts on RyR.
When an action potential reaches the muscle, RyR channels open and Ca2+ becomes available in the cell to induce contraction. The presence of Ca2+ induces the large subunit of IpTxi to hydrolyze the Sn2 fatty acyl bond from the membrane of the sarcoplasmatic reticulum. This process is executed by PLA2 activity. The freed fatty acids bind to the RyR itself or to a closely associated protein linked to gating. Binding of the RyR induces blocking of the channel. When the concentration of free fatty acids is low there will be an incomplete block of RyR; higher concentrations will give a complete block.
Because IpTxi also works on the RyR channels of the heart muscles, it could potentially be used as a drug against arrhythmia. This has not yet been proven, and must be studied "in vivo" first.


Enfant terrible

Enfant terrible (; ; "unruly child") is a French expression, traditionally referring to a child who is terrifyingly candid by saying embarrassing things to parents or others. However, the expression has drawn multiple usage in careers of art, fashion, music, and other creative arts. In these careers, it implies a successful, and often young, "genius" who is very unorthodox, striking, and in some cases, offensive, or rebellious.
The "Oxford English Dictionary", 2nd edition, gives the definition: "A child who embarrasses his elders by untimely remarks; transf. a person who compromises his associates or his party by unorthodox or ill-considered speech or behaviour; loosely, one who acts unconventionally."
One of "Webster's Dictionary" definitions of "enfant terrible" is "a usually young and successful person who is strikingly unorthodox, innovative, or avant-garde".


Glomerulus (cerebellum)

 The cerebellar glomerulus is a small, intertwined mass of nerve fiber terminals in the granular layer of the cerebellar cortex. It consists of post-synaptic granule cell dendrites and pre-synaptic Golgi cell axon terminals surrounding the pre-synaptic terminals of mossy fibers.
Function.
The cerebellar glomeruli are the first "processing station" for afferent nerve fibers entering the cerebellum. Input comes from the mossy fibers, which terminate there and synapse with the Golgi and granule cell fibers. The Golgi cells regulate the glomeruli with inhibitory signals, while information is passed on to the granule and Golgi cells from the mossy fiber.
Structure.
A cerebellar glomerulus is about 2.5 um in diameter, and is wrapped by glial sheathing. Glomeruli are centered on the large axonal terminals of glutamatergic afferent mossy fibers. Each terminal comes into contact with dendrites from 50–60 different granule cells. The granule cells themselves each have a single or multiple dendrites, and each participates in a different glomerulus. Glomeruli also contain the GABAergic (inhibitory) synapses of Golgi cells onto granule cells, and the glutamatergic (excitatory) synapses from mossy fibers onto Golgi cells. Each glomerulus contains approximately 50 granule cell dendrites, 210 total dendritic digits and 230 synaptic junctions.
Velate astrocytes.
Velate astrocytes are glia that sheath the glomeruli. They are protoplasmic astrocytes with extremely thin veil-like processes that spread out and overlap each other. Researchers Sanford Palay and Victoria Chan-Palay noted that the sheath does not penetrate into the deeper part of the glomeruli or come into contact with the mossy fiber. Instead it forms a capsule, through which the neural processes of the granule and Golgi cells penetrate. The purpose of the glial sheath is still unknown, though multiple functions have been proposed, including structural support, electrophysiological insulation, and chemical equilibrium maintenance in the interstitial fluid, while creating a chemical barrier to the further outgrowth of granule and Golgi cell fibers. Research conducted by David Eagleman suggests that the glial sheath limits the supply of extracellular calcium to regulate signaling.


On the rag


Neuroblast

In vertebrates, a neuroblast or primitive nerve cell is a postmitotic cell that does not divide further, and which will develop into a neuron after a migration phase. In invertebrates such as "Drosophila," neuroblasts are neural progenitor cells which divide asymmetrically to produce a neuroblast, and a daughter cell of varying potency depending on the type of neuroblast. Vertebrate neuroblasts differentiate from radial glial cells and are committed to becoming neurons. Neural stem cells, which only divide symmetrically to produce more neural stem cells, transition gradually into radial glial cells. Radial glial cells, also called radial glial progenitor cells, divide asymmetrically to produce a neuroblast and another radial glial cell that will re-enter the cell cycle.
This mitosis occurs in the germinal neuroepithelium (or germinal zone), when a radial glial cell divides to produce the neuroblast. The neuroblast detaches from the epithelium and migrates while the radial glial progenitor cell produced stays in the lumenal epithelium. The migrating cell will not divide further and this is called the neuron's birthday. Cells with the earliest birthdays will only migrate a short distance. Those cells with later birthdays will migrate further to the more outer regions of the cerebral cortex. The positions that the migrated cells occupy will determine their neuronal differentiation.
Formation.
Neuroblasts are formed by the asymmetric division of radial glial cells. They start to migrate as soon as they are born. Neurogenesis can only take place when neural stem cells have transitioned into radial glial cells.
Differentiation.
Neuroblasts are mainly present as precursors of neurons during embryonic development; however, they also constitute one of the cell types involved in adult neurogenesis. Adult neurogenesis is characterized by neural stem cell differentiation and integration in the mature adult mammalian brain. This process occurs in the dentate gyrus of the hippocampus and in the subventricular zones of the adult mammalian brain. Neuroblasts are formed when a neural stem cell, which can differentiate into any type of mature neural cell (i.e. neurons, oligodendrocytes, astrocytes, etc.), divides and becomes a transit amplifying cell. Transit amplifying cells are slightly more differentiated than neural stem cells and can divide asymmetrically to produce postmitotic neuroblasts and glioblasts, as well as other transit amplifying cells. A neuroblast, a daughter cell of a transit amplifying cell, is initially a neural stem cell that has reached the "point of no return." A neuroblast has differentiated such that it will mature into a neuron and not any other neural cell type. Neuroblasts are being studied extensively as they have the potential to be used therapeutically to combat cell loss due to injury or disease in the brain, although their potential effectiveness is debated.
Migration.
In the embryo neuroblasts form the middle mantle layer of the neural tube wall which goes on to form the grey matter of the spinal cord. The outer layer to the mantle layer is the marginal layer and this contains the myelinated axons from the neuroblasts forming the white matter of the spinal cord. The inner layer is the ependymal layer that will form the lining of the ventricles and central canal of the spinal cord.
In humans, neuroblasts produced by stem cells in the adult subventricular zone migrate into damaged areas after brain injuries. However, they are restricted to the subtype of small interneuron-like cells, and it is unlikely that they contribute to functional recovery of striatal circuits.
Clinical significance.
There are several disorders known as neuronal migration disorders that can cause serious problems. These arise from a disruption in the pattern of migration of the neuroblasts on their way to their target destinations. The disorders include, lissencephaly, microlissencephaly, pachygyria, and several types of gray matter heterotopia.
Neuroblast development in Drosophila.
In the fruit fly model organism "Drosophila melanogaster," a neuroblast is a neural progenitor cell which divides asymmetrically to produce a neuroblast and either a neuron, a ganglion mother cell (GMC), or an intermediate neural progenitor, depending on the type of neuroblast. During embryogenesis, embryonic neuroblasts delaminate from either the procephalic neuroectoderm (for brain neuroblasts), or the ventral nerve cord neuroectoderm (for abdominal neuroblasts). During larval development, optic lobe neuroblasts are generated from a neuroectoderm called the Outer Proliferation Center. There are more than 800 optic lobe neuroblasts, 105 central brain neuroblasts, and 30 abdominal neuroblasts per hemisegment (a bilateral half of a segment).
Neuroblasts undergo three known division types. Type 0 neuroblasts divide to give rise to a neuroblast, and a daughter cell which directly differentiates into a single neuron or glia. Type I neuroblasts give rise to a neuroblast and a ganglion mother cell (GMC), which undergoes a terminal division to generate a pair of sibling neurons. This is the most common form of cell division, and is observed in abdominal, optic lobe, and central brain neuroblasts. Type II neuroblasts give rise to a neuroblast and a transit amplifying Intermediate Neural Progenitor (INP). INPs divide in a manner similar to type I neuroblasts, producing an INP and a ganglion mother cell. While only 8 type II neuroblasts exist in the central brain, their lineages are both much larger and more complex than type I neuroblasts. The switch from pluripotent neuroblast to differentiated cell fate is facilitated by the proteins Prospero, Numb, and Miranda. Prospero is a transcription factor that triggers differentiation. It is expressed in neuroblasts, but is kept out of the nucleus by Miranda, which tethers it to the cell basal cortex. This also results in asymmetric division, where Prospero localizes in only one out of the two daughter cells. After division, Prospero enters the nucleus, and the cell it is present in becomes the GMC.
Neuroblasts are capable of giving rise to the vast neural diversity present in the fly brain using a combination of spatial and temporal restriction of gene expression that give progeny born from each neuroblast a unique identity depending both their parent neuroblast and their birth date. This is partly based on the position of the neuroblast along the Anterior/Posterior and Dorsal/Ventral axes, and partly on a temporal sequence of transcription factors that are expressed in a specific order as neuroblasts undergo sequential divisions.


Haugh (OE)

Haugh and Scots "hauch", from Old English "halh", "healh", is a term referring to a low-lying meadow in a river valley.
An example is Derwenthaugh, which is situated in the Metropolitan Borough of Gateshead, Tyne and Wear. It had previously been part of County Durham, but it became incorporated into the metropolitan county of Tyne and Wear and Borough of Gateshead in 1974. The area is now a country park.


Nilestriol

Nilestriol () (brand name Wei Ni An; developmental code name LY-49825), also known as nylestriol (, ), is a synthetic estrogen which was patented in 1971 and is marketed in China. It is the 3-cyclopentyl ether of ethinylestriol, and is also known as ethinylestriol cyclopentyl ether (EE3CPE). Nilestriol is a prodrug of ethinylestriol, and is a more potent estrogen in comparison. It is described as a slowly-metabolized, long-acting estrogen and derivative of estriol. Nilestriol was assessed in combination with levonorgestrel for the potential treatment of postmenopausal osteoporosis, but this formulation ultimately was not marketed.


Scott reagent


Protomap (neuroscience)

The Protomap is a primordial molecular map of the functional areas of the mammalian cerebral cortex during early embryonic development, at a stage when neural stem cells are still the dominant cell type. The protomap is a feature of the ventricular zone, which contains the principal cortical progenitor cells, known as radial glial cells. Through a process called 'cortical patterning', the protomap is patterned by a system of signaling centers in the embryo, which provide positional information and cell fate instructions. These early genetic instructions set in motion a development and maturation process that gives rise to the mature functional areas of the cortex, for example the visual, somatosensory, and motor areas.
The term protomap was coined by Pasko Rakic. The "protomap hypothesis" was opposed by the "protocortex hypothesis", which proposes that cortical proto-areas initially have the same potential, and that regionalization in large part is controlled by external influences, such as axonal inputs from the thalamus to the cortex. However, a series of papers in the year 2000 and in 2001 provided strong evidence against the protocortex hypothesis, and the protomap hypothesis has been well accepted since then. The protomap hypothesis, together with the related radial unit hypothesis, forms our core understanding of the embryonic development of the cerebral cortex. Once the basic structure is present and cortical neurons have migrated to their final destinations, many other processes contribute to the maturation of functional cortical circuits.


Nortilidine

Nortilidine is the major active metabolite of tilidine. It is formed from tilidine by demethylation in the liver. The racemate has opioid analgesic effects roughly equivalent in potency to that of morphine. The (1R,2S) isomer has NMDA antagonist activity. The drug also acts as a dopamine reuptake inhibitor. The reversed-ester of nortilidine is also known, as is the corresponding analogue with the cyclohexene ring replaced by cyclopentane, which have almost identical properties to nortilidine.
Use.
Nortilidine has been sold as a designer drug, first being identified in Poland in May 2020.


Medial vestibulospinal tract

The medial vestibulospinal tract is one of the descending spinal tracts of the ventromedial funiculus of the spinal cord. It is found only in the cervical spine and above.
The medial part of the vestibulospinal tract is the smaller part, and is primarily made of fibers from the medial vestibular nucleus. It projects bilaterally down the spinal cord and triggers the ventral horn of the cervical spinal circuits, particularly controlling lower motor neurons associated with the spinal accessory nerve (CN XI). Additionally, the pathway projects superiorly to the paramedian pontine reticular formation, indirectly innervating the nuclei of CN VI and III. Through this superior projection, the medial vestibulospinal tract is involved in "yoking" the eyes together in response to rapid movement of the head. Thus, cumulatively it controls head and whole body orientation.


Coupon yield


Functional cerebral distance

Functional Cerebral Distance is a neuropsychological principle developed by Marcel Kinsbourne. It states that, "...separate control centers that are functionally close together (i.e., highly connected in functional cerebral space) will conflict if they are independently engaged in unrelated activity." In other words, when a person attempts to perform multiple tasks associated with functionally close brain structures, interference occurs and performance is affected.
The concept of functional cerebral distance is the basis for some research into hostility. According to the Direction Model, anger activates the left prefrontal cortex. Counting also activates similar functional cerebral space, creating competition between the two activities according to Kinsbourne. This is the basis behind "counting to 10" when one is feeling angry or frustrated.
Kinsbourne's work is also the basis for Capacity Theory, which postulates that diminished right frontal lobe capacity is the cause for overly hostile individuals. This is based on the knowledge that the right frontal lobe is responsible for regulating negative emotion. The capacity model suggests that it is harder for hostile individuals to maintain stable levels of cerebral activation after experiencing physiological and cognitive right frontal stressors.


Social Purpose Education

Social Purpose Education was developed at The Northern College for Residential and Community Adult Education by Lou Mycroft and the TeachNorthern teacher education team in 2010. The Workers Educational Association also use the term to describe a similar, empowerment approach to adult education.
Social Purpose Education as a pedagogy is concerned with social change via the growth in confidence, agency and self-belief of individuals. As such, it can be said to be in the tradition of transformational leadership, rather than the transformational learning of Jack Mezirow, as the desired impact is intended to be on communities, rather than remaining within the individual. This makes it a particularly effective pedagogy for workforce development programmes. Social Purpose Education combines pro-social pedagogies such as The Thinking Environment, Restorative Practice, Community Philosophy and Non-Violent Communication with open digital approaches, designed to build "communities of praxis". It comprises four cornerstones of praxis:
1. Teaching (to) Your Values
Social Purpose Education is explicitly values-based. Participants are invited to regularly check in with their personal values and how these connect with practice principles. The language of values continues to be explicated throughout. Values work is the cornerstone of any transformational education programme, such as the Thinking Environment, Training for Transformation, and Freirean based education (see, for example, the Paulo Freire Institute and Highlander Center).
2. Reflexive Practice
Reflexion is defined as a broader practice than the commonly understood practice reflection. Introspection is cut with making connections with theory and with the experience of other participants (students, colleagues), leading to an experience of praxis which avoids solipsism and connects with broader social, political and economic factors. In this way, it leans towards the 'Four Lenses' work of Stephen Brookfield.
3. Win/Win/Win
Inspired by Nigel Cutts’s leadership handbook ‘Love at Work', which is in turn inspired by the Thinking Environment, Win/Win/Win refers to the impact of social purpose education on the teacher, the student and the wider communities of both. It is an element of what Hannah Arendt called vita activa, or the active life.
4. Embedding Diversity
An assumption of social purpose education is that it has a responsibility to challenge the social, political and economic "status quo", by using a posthuman approach to challenge axiomatic thinking. Gramsci and others wrote about ‘"hegemony"’ – a difficult word to say, spell or understand but one which has no equal in explicating the cultural blindness of contexts and organisations which, without even realising, can exclude diversity by assuming we are all the same.


Conductometry

Conductometry is a measurement of electrolytic conductivity to monitor a progress of chemical reaction. Conductometry has notable application in analytical chemistry, where conductometric titration is a standard technique. In usual analytical chemistry practice, the term "conductometry" is used as a synonym of "conductometric titration", while the term conductimetry is used to describe non-titrative applications. Conductometry is often applied to determine the total conductance of a solution or to analyze the end point of titrations that include ions.
History.
Conductive measurements began as early as the 18th century, when Andreas Baumgartner noticed that salt and mineral waters from Bad Gastein in Austria conducted electricity. As such, using conductometry to determine water purity, which is often used today to test the effectiveness of water purification systems, began in 1776. Friedrich Kohlrausch further developed conductometry in the 1860s when he applied alternating current to water, acids, and other solutions. It was also around this time when Willis Whitney, who was studying the interactions of sulfuric acid and chromium sulfate complexes, found the first conductometric endpoint. These finding culminated into potentiometric titrations and the first instrument for volumetric analysis by Robert Behrend in 1883 while titrating chloride and bromide with HgNO3. This development allowed for testing the solubility of salts and hydrogen ion concentration, as well as acid/base and redox titrations. Conductometry was further improved with the development of the glass electrode, which began in 1909.
Titration.
Conductometric titration is a type of titration in which the electrolytic conductivity of the reaction mixture is continuously monitored as one reactant is added. The equivalence point is the point at which the conductivity undergoes a sudden change. Marked increase or decrease in conductance are associated with the changing concentrations of the two most highly conducting ions—the hydrogen and hydroxyl ions. The method can be used for titrating coloured solutions or homogeneous suspension (e.g.: wood pulp suspension), which cannot be used with normal indicators.
Acid-base titrations and redox titrations are often performed in which common indicators are used to locate the end point e.g., methyl orange, phenolphthalein for acid base titrations and starch solutions for iodometric type redox process. However, electrical conductance measurements can also be used as a tool to locate the end point.
Example: titration of an HCl solution with the strong base NaOH. As the titration progresses, the protons are neutralized to form water by the addition of NaOH. For each amount of NaOH added equivalent amount of hydrogen ions is removed. Effectively, the mobile H+ cation is replaced by the less-mobile Na+ ion, and the conductivity of the titrated solution as well as the measured conductance of the cell fall. This continues until the equivalence point is reached, at which one obtains a solution of sodium chloride, NaCl. If more base is added, an increase in conductivity or conductance is observed, since more ions Na+ and OH− are being added and the neutralization reaction no longer removes an appreciable amount of H+. Consequently, in the titration of a strong acid with a strong base, the conductance has a minimum at the equivalence point. This minimum can be used, instead of an indicator dye, to determine the endpoint of the titration. The conductometric titration curve is a plot of the measured conductance or conductivity values as a function of the volume of the NaOH solution added. The titration curve can be used to graphically determine the equivalence point.
For reaction between a weak acid and a weak base in the beginning conductivity decreases a bit as the few available H+ ions are used up. Then conductivity increases slightly up to the equivalence point volume, due to contribution of the salt cation and anion.(This contribution in case of a strong acid-strong base is negligible and is not considered there.)After the equivalence point is achieved the conductivity increases rapidly due to the excess OH- ions.


Heteropodatoxin

Heteropodatoxins are peptide toxins from the venom of the giant crab spider "Heteropoda venatoria", which block Kv4.2 voltage-gated potassium channels.
Sources.
Heteropodatoxins are purified from the venom of the giant crab spider, "Heteropoda venatoria" .
Chemistry.
Heteropodatoxins contain an Inhibitor Cystine Knot (ICK) motif, which consist of a compact disulfide-bonded core, from which four loops emerge . There are three different heteropodatoxins :
These three toxins are structurally similar peptides of 29-32 amino acids . They show sequence similarity to Hanatoxins, which can be isolated from the venom of the Chilean rose tarantula Grammostola rosea .
Target.
Heteropodatoxins block A-type, transient voltage-gated potassium channels. All three toxins have been shown to block the potassium channel Kv4.2 . Recombinant heteropodatoxin-2 blocks the potassium channels Kv4.1, Kv4.2 and Kv4.3, but not Kv1.4, Kv2.1, or Kv3.4 .
Mode of action.
Heterpodatoxin-2 most likely acts as a gating modifier of the Kv4.2 channels . It shifts the voltage dependence of the activation and the inactivation of the Kv4.3 potassium channel to more positive values. As a result, in the presence of the toxin this channel has a higher probability of being inactivated and a larger depolarization is needed to open the channel. However, heterpodatoxin-2 did not affect the voltage dependence of the Kv4.1 channel, suggesting that the precise mechanism of block remains to be elucidated and a role as a pore blocker cannot be excluded . The voltage dependence of Kv4.2 block varies among the three different heteropodatoxins. It is less voltage dependent for HpTx1 than for HpTx2 or HpTx3 .
Toxicity.
The giant crab spider can cause a locally painful bite.


Cerebral vasospasm

Cerebral vasospasm is the prolonged, intense vasoconstriction of the larger conducting arteries in the subarachnoid space which is initially surrounded by a clot.
Significant narrowing of the blood vessels in the brain develops gradually over the first few days after the aneurysmal rupture. This kind of narrowing usually is maximal in about a week's time following intracerebral haemorrhage.
Vasospasm is the one of the leading causes of death after the aneurysmal rupture along with the effect of the initial haemorrhage and later bleeding.


Epidural venous plexus

The epidural venous plexus is a network of interconnecting veins located in the anterior epidural space, in the outermost part of the spinal canal. It runs from the skull base to the sacrum. It is surrounded by very little fat, although the levels increase towards the lower levels of the spine.


Paul J. Bailey

Paul J. Bailey (April 5, 1922 – October 18, 2001) was an American jockey in Thoroughbred racing who, on June 26, 1959, set a New York Racing Association record with five wins from five mounts on a single racecard at Belmont Park in Elmont, New York. It would be another 21 years before anyone matched that feat when both Jeffrey Fell and Jorge Velásquez did it during the month of June in 1980.
Early success in Western Canada.
Paul Bailey began his professional riding career 1944 when he got his first win at a track in Oregon. He got his first win on a track in Oregon. For a few years during the latter part of the 1940s, he rode on the fall circuit n Western Canada. Such was his success that after winning 18 of 36 starts with four seconds and five third-place finishes, a "Winnipeg Tribune" newspaper story referring to his "phenomenal" performance said that "at Polo Park he acts as though the fall meets were staged for his special benefit."
At that same track, Paul Bailey won back-to-back editions of the Canadian Derby, taking the 1947 race aboard Sir Berrill and in what Assiniboia Downs racing historian Bob Gates called "one of the greatest horse races ever run in Manitoba", Bailey won his second Canadian Derby in 1948 aboard the filly Victory Gift for owner Scotty Kennedy and trainer Bert Blake.
Bailey's success in Western Canada opened the door to the big tracks on the East Coast of the United States. Of his three mounts in the Kentucky Derby, his best result came in the 1951 edition when he rode Royal Mustang to a strong second place, finishing a head back of winner, Count Turf.
Paul Bailey retired from racing in 1968. He died at his Florida home on October 18, 2001 as the result of a brain tumor.


Thoracic spinal nerve 7

The thoracic spinal nerve 7 (T7) is a spinal nerve of the thoracic segment.
It originates from the spinal column from below the thoracic vertebra 7 (T7).


Show car

A show car, sometimes called a dream car, is a custom-made automobile created specifically for public display, rather than sale. They are shown at auto shows and other exhibitions. Show cars can either come from car companies or from private individuals.
Corporate show cars generally fall into one of three categories:
Privately owned show cars are cars extensively cared for by their owners primarily for the purpose of entering car shows and can be production models or custom-made.
History.
The creation of show cars dates back to at least the 1920s, but reached its zenith in the United States in the 1950s, when most major U.S. automakers began to exhibit wild, fanciful dream cars. The preeminent dream car maker was GM, which displayed its work at a series of traveling Motorama shows, mounted at great expense and attracting much publicity. In the 1960s American show cars became substantially more mundane, slight variations on typical production models (with exceptions like Chevrolet's Mako Shark prototype). The practice of building them fell on hard times during the 1970s, when automotive whimsy was a low priority compared to safety, emissions control, and fuel economy. The practice was revived in the 1980s, and remains strong today both in the U.S. and abroad.


Arachnoid trabeculae

The arachnoid trabeculae are delicate strands of connective tissue that loosely connect the two innermost layers of the meninges – the arachnoid mater and the pia mater. They are found within the subarachnoid space where cerebrospinal fluid is also found. Embryologically, the trabeculae are the remnants of the common precursor that forms both the arachnoid and pial layers of the meninges.


Bulgarian vocabulary

The lexis of Bulgarian, a South Slavic language, consists of native words, as well as borrowings from Russian, French, and to a lesser extent English, Greek, Ottoman Turkish, Arabic and other languages.
Native lexical items.
Around three-quarters of the vocabulary in the standard academic dictionaries of Bulgarian consist of native lexical items. Some 2,000 of these items are directly inherited from proto-Slavonic through Old and Middle Bulgarian. These include much of the most common and basic vocabulary of the language, for example body parts (Bulgarian: ръка “hand”) or cardinal numbers (Bulg.: две “two”). The number of words derived from the direct reflexes of proto-Slavonic is more than 20 times greater, accounting for more than 40,000 entries (for example, ръчен “manual”; двуместен “double-place”).
The old Bulgar language has otherwise left only slight traces in Modern Bulgarian. Apart from a small corpus of proper names (for example, Борис “Boris”; Крум “Krum”) and military and administrative titles from the time of the First Bulgarian Empire, only a handful of Bulgar words has survived in Modern Bulgarian. Words which are considered to be almost certainly of Bulgar origin are, for example: бъбрек “kidney”, бисер “pearl”, кумир “idol”, чертог “castle”. Some of these words even spread to other Slavic languages through Old Church Slavonic.
Patterns of borrowing.
As of the beginning of the 1960s, loanwords amounted to some 25% of the vocabulary of the standard dictionary of Bulgarian.
The most important source of loanwords in recent centuries has been Russian. Two other important sources of borrowing were Latin and Medieval and Modern Greek, each accounting for around a quarter of all borrowings. French vocabulary contribution to the Bulgarian language totals around 15% and Ottoman Turkish (along with Arabic and Persian) totalled around 14%, whereas loanwords from Russian accounted for 10% of the borrowings. Lesser but still significant influence was exerted by Italian (around 4%), German (around 4%) and English (around 2%).
Character of borrowing.
Loanwords from Greek were the first to enter the lexis of Bulgarian, as early as the time of Old Bulgarian, (for example, икона “icon” or патриарх “patriarch”) as a product of the influence of the liturgical language of the Orthodox Church. During the period of Ottoman rule, Bulgarian adopted from Greek both common lexical material (хиляда “a thousand”) and international vocabulary of Greek origin (граматика “grammar”). The loanwords from Latin were adopted into the language mainly in the second half of the 19th and the first half of the 20th centuries, many Latin terms entered the language through Romanian, Aromanian, and Megleno-Romanian during Bulgarian Empires. The vast majority of them are international terms in the areas of politics, civil administration, medicine, law, etc. (for example, администрация “administration”). Borrowings from French cover a similar time span and are concentrated in the areas of social and political life, military affairs, cooking, the arts, etc. (бюфет “buffet”).
Loanwords from Turkish (and through Turkish from Arabic and Persian) are a legacy of the period of Ottoman rule (1422–1878) and are divided into two stylistic layers. The first one is neutral and is represented by a corpus of some 800 words, mostly items of clothing, foods and household items (чорап “sock”; чекмедже “drawer”). The remainder consists of colloquial or slightly vulgar terms which occur particularly often in expressive speech and frequently have a humoristic or even pejorative nuance. They generally have neutral native synonyms (cf акъл from Turkish vs ум from common Slavic, both meaning “wits, intelligence”). There is a fluent transition between this group and a large amount of more or less obsolete words that only occur in archaic or dialectal speech.
English is the only language that has significantly influenced Bulgarian since the 1950s. The share of English borrowings at present is much larger than the 2% in the 1960s and most likely lies between 10% and 15% of all borrowings. The impact of English is particularly strong in technology, sports, dress, the arts, music and popular culture: корнер “corner” (football), пънк “punk”.
As of the beginning of the 1960s, loanwords amounted to some 25% of the vocabulary of the standard dictionary of Bulgarian. The most frequent source of loanwords in recent centuries has been Russian. Two other important sources of borrowing were Latin and Greek, each accounting for around a quarter of all borrowings, more specifically, Latin (around 26%) and Greek (around 23%). French vocabulary contribution to the Bulgarian language totals around 15% and Ottoman Turkish (along with Arabic and Persian) totalled around 14%, whereas loanwords from Russian accounted for 10% of the borrowings. Lesser but still significant influence was exerted by Italian (around 4%), German (around 4%) and English (around 2%).
Examples.
Some very frequent expressions have been borrowed from other languages. Most of them are somewhat informal.
Comparison with other Slavic languages.
Most Slavic languages demonstrate a higher degree of shared vocabulary with one another than English does with the Germanic family due to the number of Romance loans in English on the one hand, and on the other hand due to the influences on Slavic languages of Russian or Church Slavonic, which was a Southeast Slavic language. The adoption of Church Slavonic morphology and vocabulary was used to enrich other Slavic languages. It is especially pronounced in Russian, which today consists of mixed native and Church Slavonic (South Slavic) vocabulary, analogically to the Romance vocabulary of English, but in Russian the Church Slavonisms are not perceived as foreign due to their Slavic roots. An estimated 55% of Russian, incl. vocabulary, syntactic features, etc. goes back to the Church Slavonic language, known as Old Bulgarian, while 70% of Church Slavonic words are common to all Slavic languages. Some authors argue that the Southeast Slavic language Church Slavonic is the "passkey" to the Russian nation and language.


End of Course Test

The End of Course Test (EOCT, EOC, or EOC Test) is an academic assessment conducted in many states by the State Board of Education. Georgia, for example, tests from the ninth to twelfth grades, and North Carolina tests for any of the four core class subjects (math, science, social studies, and English).
North Carolina schools administer an EOCT in English II, Math I (Algebra I), and Biology.<ref>


Posterolateral sulcus of spinal cord

On either side of the posterior median sulcus of the spinal cord, and at a short distance from it, the posterior nerve roots are attached along a vertical furrow named the posterolateral sulcus. The portion of the medulla spinalis which lies between this and the posterior median sulcus is named the posterior funiculus.


Paramyotonia congenita

Paramyotonia congenita (PC), is a rare congenital autosomal dominant neuromuscular disorder characterized by “paradoxical” myotonia. This type of myotonia has been termed paradoxical because it becomes worse with exercise whereas classical myotonia, as seen in myotonia congenita, is alleviated by exercise. PC is also distinguished as it can be induced by cold temperatures. Although more typical of the periodic paralytic disorders, patients with PC may also have potassium-provoked paralysis. PC typically presents within the first decade of life and has 100% penetrance. Patients with this disorder commonly present with myotonia in the face or upper extremities. The lower extremities are generally less affected. While some other related disorders result in muscle atrophy, this is not normally the case with PC. This disease can also present as hyperkalemic periodic paralysis and there is debate as to whether the two disorders are actually distinct.
Symptoms and signs.
Patients typically complain of muscle stiffness that can continue to focal weakness. This muscle stiffness cannot be walked off, in contrast to myotonia congenita. These symptoms are increased (and sometimes induced) in cold environments. For example, some patients have reported that eating ice cream leads to a stiffening of the throat. For other patients, exercise consistently induces symptoms of myotonia or weakness. Typical presentations of this are during squatting or repetitive fist clenching. Some patients also indicate that specific foods are able to induce symptoms of paramyotonia congenita. Isolated cases have reported that carrots and watermelon are able to induce these symptoms. The canonical definition of this disorder precludes permanent weakness in the definition of this disorder. In practice, however, this has not been strictly adhered to in the literature.
Pathophysiology.
Paramyotonia congenita (as well as hyperkalemic periodic paralysis and the potassium-aggravated myotonias) is caused by mutations in a sodium channel, SCN4A. The phenotype of patients with these mutations is indicated in Table 1. These mutations affect fast inactivation of the encoded sodium channel. There are also indications that some mutations lead to altered activation and deactivation. The result of these alterations in channel kinetics is that there is prolonged inward (depolarizing) current following muscle excitation. There is also the introduction of a “window current” due to changes in the voltage sensitivity of the channel’s kinetics. These lead to a general increase in cellular excitability, as shown in figure 1.
There has been one study of a large number of patients with paramyotonia congenita. Of 26 kindreds, it found that 17 (71%) had a mutation in SCN4A while 6 (29%) had no known mutation. There is no large difference between these two groups except that patients with no known mutation have attacks precipitated less by cold but more by hunger, are much more likely to have normal muscle biopsies, and show less decreased compound muscle action potentials when compared to patients with known mutations.
<br>
Diagnosis.
Diagnosis of paramyotonia congenita is made upon evaluation of patient symptoms and case history. Myotonia must increase with exercise or movement and usually must worsen in cold temperatures. Patients that present with permanent weakness are normally not characterized as having PC. Electromyography may be used to distinguish between paramyotonia congenita and myotonia congenita., Clinicians may also attempt to provoke episodes or myotonia and weakness/paralysis in patients in order to determine whether the patient has PC, hyperkalemic periodic paralysis, or one of the potassium-aggravated myotonias. Genomic sequencing of the SCN4A gene is the definitive diagnostic determinant.
Treatment.
Some patients do not require treatment to manage the symptoms of paramyotonia congenita. Others require treatment for their muscle stiffness and often find mexiletine to be helpful. Others have found acetazolamide to be helpful as well. Avoidance of myotonia triggering events is also an effective method of mytonia prevention.
Epidemiology.
Paramyotonia congenita is considered an extremely rare disorder, though little epidemiological work has been done. Prevalence is generally higher in European-derived populations and lower among Asians. Epidemiological estimates have been provided for the German population. There, it was estimated that the prevalence of PC is between 1:350,000 (0.00028%) and 1:180,000 (0.00056%). However, the German population of patients with PC is not uniformly distributed across the country. Many individuals with PC herald from the Ravensberg area in North-West Germany, where a founder effect seems to be responsible for most cases. The prevalence here is estimated at 1:6000 or 0.017%.
History.
Originally thought to be separate from hyperkalemic periodic paralysis and the sodium channel myotonias, there is now considerable disagreement as to whether these disorders represent separate entities or overlapping phenotypes of a complex disorder spectrum. It was once thought that paramyotonia congenita was more common in males. Observation of the most recent generation has shown this to be untrue. On average, half of children in a family inherit the disorder regardless of gender.


Neurosecretion

Neurosecretion is the storage, synthesis and release of hormones from neurons. These neurohormones, produced by neurosecretory cells, are normally secreted from nerve cells in the brain that then circulate into the blood. These neurohormones are similar to nonneural endocrine cells and glands in that they also regulate both endocrine and nonendocrine cells. Neurosecretion cells synthesize and package their product in vesicles and exocytose them at axon endings just as normal neurons do, but release their product farther from their target than normal neurons (which release their neurotransmitters short distances at synapses), typically releasing their neurohormones into the circulatory system to reach their distant targets.
Discovery.
In 1928, Ernst Scharrer hypothesized that neurosecretory neurons in the hypothalamus of teleost fish, Phoxinus laevis, had secretory activity similar to that of endocrine gland cells. As more became known about neurosecretory cells, the difference between the actions of nerve communication and endocrine hormone release become less clear. Like the average neuron, these cells conduct electrical impulses along the axon but unlike these neurons, neurosecretion produces neurohormones that are released into the body’s circulation. Combining the properties of the nervous and endocrine, these cells have the capacity to affect nerves through chemical messengers. Neurosecretion is a broad area of study and must be further observed to be better understood.
Insects.
Insects play a large role in what is known about neurosecretion. In simpler organisms neurosecretion mechanisms regulate the heart, the process of metamorphosis, and directly influences the development of the gonadal function. In more advanced organisms the gonadal function is manipulated by the intermediary endocrine processes. Axons from neurosecretory cells trace to corpora cardiaca and corpora allata and produce and secrete a brain hormone which insect physiologists suspect is bound to a large carrier protein. Although the function is unknown, there are a multitude of these cells found in the ventral ganglia of the nerve cord. Neurosecretory cells, found in clusters in the medial and lateral parts of the brain, control corpora allata activity by producing juvenile hormone during the larval or nymphal instars, the phase between periods of molting in insects. The production of this hormone inhibits the insect during the conversion to maturity and reactivating once the fully-grown adult is prepared for reproduction. The 3rd International Symposium on Neurosecretion at the University of Bristol discussed the intracellular structure of the neurosecretory cells and the migration path to the target organs or vascular fluid areas by neurosecretory granules. More is being discovered on the identification of granules in hormones and the linking of their development with the organism’s physiologic state.


Somatotopic arrangement

Somatotopy is the point-for-point correspondence of an area of the body to a specific point on the central nervous system. Typically, the area of the body corresponds to a point on the primary somatosensory cortex (postcentral gyrus). This cortex is typically represented as a sensory homunculus which orients the specific body parts and their respective locations upon the homunculus. Areas such as the appendages, digits, penis, and face can draw their sensory locations upon the somatosensory cortex. The areas which are finely controlled (e.g., the digits) have larger portions of the somatosensory cortex whereas areas which are coarsely controlled (e.g., the trunk) have smaller portions. Areas such as the viscera do not have sensory locations on the post central gyrus.
Macaques, a kind of monkey, already exhibit somatotopy in their somatosensory and motor systems at birth.
Sensorimotor mapping of the human cerebellum.
Functional magnetic resonance imaging (fMRI) was employed to determine areas of activation in the cerebellar cortex in humans during a series of motor tasks. The activation areas for movements of lips, tongue, hands, and feet were determined and found to be sharply confined to lobules and sublobules and their sagittal zones in the rostral and caudal spinocerebellar cortex. The activation mapped as two distinct homunculoid representations. One, a more extended representation, was located upside down in the superior cerebellum, and a second one, doubled and smaller, in the inferior cerebellum.


Beta-3 adrenergic receptor

The beta-3 adrenergic receptor (β3-adrenoceptor), also known as ADRB3, is a beta-adrenergic receptor, and also denotes the human gene encoding it.
Function.
Actions of the β3 receptor include
It is located mainly in adipose tissue and is involved in the regulation of lipolysis and thermogenesis. Some β3 agonists have demonstrated antistress effects in animal studies, suggesting it also has a role in the central nervous system (CNS). β3 receptors are found in the gallbladder, urinary bladder, and in brown adipose tissue. Their role in gallbladder physiology is unknown, but they are thought to play a role in lipolysis and thermogenesis in brown fat. In the urinary bladder it is thought to cause relaxation of the bladder and prevention of urination.
Mechanism of action.
Beta adrenergic receptors are involved in the epinephrine- and norepinephrine-induced activation of adenylate cyclase through the action of the G proteins of the type Gs.
Interactions.
Beta-3 adrenergic receptor has been shown to interact with Src.


Allocortex

The allocortex or heterogenetic cortex, and neocortex are the two types of cerebral cortex in the brain. The allocortex is the much smaller area of cortex taking up just ten per cent; the neocortex takes up the remaining 90 per cent. It is characterized by having just three or four cortical layers, in contrast with the six layers of the neocortex. There are three subtypes of allocortex: the paleocortex, the archicortex, and the periallocortex – a transitional zone between the neocortex and the allocortex.
The specific regions of the brain usually described as belonging to the allocortex are the olfactory system, and the hippocampus.
Allocortex is termed heterogenetic cortex, because during development it never has the six-layered architecture of homogenetic neocortex. It differs from hetero"typic" cortex, a type of cerebral cortex, which during prenatal development, passes through a six-layered stage to have fewer layers, such as in Brodmann area 4 that lacks granule cells.
Structure.
The allocortex has three or four layers of neuronal cell bodies, in contrast to the six layers of the neocortex. There are three subtypes of allocortex: the paleocortex, archicortex and periallocortex.
Paleocortex is a type of thin, primitive cortical tissue that consists of three cortical laminae (layers of neuronal cell bodies). The two granular layers II and IV of neocortex are absent in paleocortex. The main areas of paleocortex are the olfactory bulb, olfactory tubercle and piriform cortex.
Archicortex is a type of cortical tissue that consists of four laminae (layers of neuronal cell bodies). The main areas of archicortex are the hippocampus and dentate gyrus.
Periallocortex is a transitional form between neocortex and either paleo- or archi-cortex. It thus can be either peripaleocortex (anterior insular cortex) or periarchicortex (entorhinal cortex, presubicular cortex, retrosplenial, supracallosal, and subgenual areas).
Because the number of laminae that compose a type of cortical tissue seems to be directly proportional to both the information-processing capabilities of that tissue and its phylogenetic age, and also because olfaction is a major sensory modality in phylogenetically early animals, paleocortex is thought to be the most primitive form of cortex.