Flash suppression

Flash suppression is a phenomenon of visual perception in which an image presented to one eye is suppressed by a flash of another image presented to the other eye.
To observe flash suppression, a small image is first presented to one eye for about a second while a blank field is presented to the other eye. Then a different, small image is abruptly shown, "flashed", to the other, second eye at the location corresponding to the image to the first eye. The image to the first eye disappears, even though it is still presented, and only the new image is perceived. The new image to the second eye "suppresses" perception of the image to the first. For example, if a vehicle is shown to the left eye for 1 second, and then a face is abruptly flashed to the right eye, the observer consciously sees first a vehicle and then a face. Note that the face is seen while the picture of the car is still present. If the order of presentation is reversed, the order of percept is reversed. The phenomenon of flash suppression seemed to have been known since the 19th century. The phenomena was described by McDougall in 1901 (p598) and utilized for an EEG experiment by Lansing in 1964. In 1984, Jeremy Wolfe characterized flash suppression in a systematic psychophysics study.
Flash suppression is an example of illusions that render a highly visible image invisible and that are used to study the mechanisms of conscious and non-conscious visual processing (Koch, 2004). Related perceptual illusions include backward masking, binocular rivalry, motion induced blindness and motion-induced interocular suppression.
The brain basis of flash suppression has been studied using microelectrode recordings in the visual brain of the macaque monkey (Logothetis, 1998) and in the human medial temporal lobe (Kreiman, Koch & Fried, 2002).
Relationship with binocular rivalry.
Flash suppression occurs due to the conflict between the inputs to the two eyes. When this conflict is sustained without any abrupt events, binocular rivalry occurs. In both flash suppression and binocular rivalry, perceptual conflict between the two eyes is required for the perceptual effect. If two similar images are used, fusion of the two images is experienced, rather than flash suppression or binocular rivalry. Despite some similarities in perceptual consequences, the neuronal mechanisms responsible for the two illusions can be different. For example, the strength (depth) of flash suppression seems much stronger than that of binocular rivalry. Comparative studies of the two methods are needed.
Flash suppression has certain methodological advantages over binocular rivalry as a tool for probing conscious vision. Whereas the percept during binocular rivalry alternates stochastically, the percept during flash suppression is precisely controlled in time.
Although flash suppression allows one to present an image to someone without his or her seeing it consciously, it requires a to-be-erased image to be presented for a fraction of second before introduction of a new image. This requirement limits the usage of flash suppression for the study of nonconscious visual processing.
Continuous flash suppression.
A powerful variant of flash suppression is "continuous flash suppression", originally reported by Nao Tsuchiya and Christof Koch (2004) and Fang and He (2005)). Here a small, fixed image in the first eye—say a gray-scale fearful face—is completely suppressed by a stream of constantly changing images flashed into the second eye (say a series of colorful Mondrian-scenes replaced every 0.1 sec by a new Mondrian pattern). This suppression can last for minutes, a remarkable testament to the fact that humans often do not see what is directly in front of their eyes.
Continuous flash suppression is a useful method for psychologists and neuroscientists interested in studying the mechanisms of conscious and nonconscious visual processing. Whereas other visual illusions that render otherwise salient images invisible have their own shortcomings and advantages (Kim & Blake 2005), continuous flash suppression has a number of advantages for wiping images from conscious vision. It can erase an image presented at the fovea (which usually is much more resistant to perceptual suppression, unlike, for example, crowding), in every trial (unlike binocular rivalry), for a longer duration (>1 sec, unlike backward masking), with an excellent control of timing (unlike binocular rivalry). It has been widely exploited to tackle the scope and limits of unconscious processing (Sklar et al., 2012).
Generalized flash suppression.
The differences between flash suppression and binocular rivalry have been further emphasized by the finding that stimulus conflict between the two eyes is not a requirement to achieve visual suppression. The novel paradigm of generalized flash suppression (GFS) reported by Wilke, Logothetis and Leopold (2003) demonstrates that any visual stimulus can be rendered invisible when presented outside the fovea for a certain amount of time, followed by the addition of a distracting second stimulus in its vicinity.
This effect is strongest when the two stimuli are presented to (different regions in) opposite eyes, which suggests that it is somewhat related to binocular rivalry. At the same time, GFS shares similarities to Troxler's fading and motion induced blindness.
A recent study on the neuronal basis of GFS demonstrated that neuronal activity in early visual cortex was untouched by the perceptual effect, whereas neurons in higher areas altered their activity pattern during the illusion (Wilke et al. 2006). Authors report that the disappearance of the stimulus triggered changes in the local field potentials of all these areas, suggesting that the perception during flash suppression is reflected in large parts of the brain.
References.
Reviews
Flash suppression
Generalized Flash Suppression
Continuous Flash Suppression


Incremental computing

Incremental computing, also known as incremental computation, is a software feature which, whenever a piece of data changes, attempts to save time by only recomputing those outputs which depend on the changed data. When incremental computing is successful, it can be significantly faster than computing new outputs naively. For example, a spreadsheet software package might use incremental computation in its recalculation feature, to update only those cells containing formulas which depend (directly or indirectly) on the changed cells.
When incremental computing is implemented by a tool that can implement it for a variety of different pieces of code automatically, that tool is an example of a program analysis tool for optimization.
Static versus dynamic.
Incremental computing techniques can be broadly separated into two types of approaches:
"Static approaches" attempt to derive an incremental program from a conventional program P using, e.g., either manual design and refactoring, or automatic program transformations. These program transformations occur before any inputs or input changes are provided.
"Dynamic approaches" record information about executing program P on a particular input (I1) and use this information when the input changes (to I2) in order to update the output (from O1 to O2). The figure shows the relationship between program P, the change calculation function ΔP, which constitutes the core of the incremental program, and a pair of inputs and outputs, I1, O1 and I2, O2.
Specialized versus general-purpose approaches.
Some approaches to incremental computing are specialized, while others are general purpose.
Specialized approaches require the programmer to explicitly specify the algorithms and data structures that will be used to preserve unchanged sub-calculations.
General-purpose approaches, on the other hand, use language, compiler, or algorithmic techniques to give incremental behavior to otherwise non-incremental programs.
Static methods.
Program derivatives.
Given a computation formula_1 and a potential change formula_2, we can insert code before the change (the pre-derivative) and after the change (the post-derivative) to update the value of formula_3 faster than rerunning formula_4. Paige has written down a list of rules for formal differentiation of programs in SUBSETL.
View maintenance.
In database systems such as DBToaster, views are defined with relational algebra. Incremental view maintenance statically analyzes relational algebra to create update rules that quickly maintain the view in the presence of small updates, such as insertion of a row.
Dynamic methods.
Incremental computation can be achieved by building a dependency graph of all the data elements that may need to be recalculated, and their dependencies. The elements that need to be updated when a single element changes are given by the transitive closure of the dependency relation of the graph. In other words, if there is a path from the changed element to another element, the latter may be updated (depending on whether the change eventually reaches the element). The dependency graph may need to be updated as dependencies change, or as elements are added to, or removed from, the system. It is used internally by the implementation, and does not typically need to be displayed to the user.
Capturing dependencies across all possible values can be avoided by identifying subset of important values (e.g., aggregation results) across which dependencies can be tracked, and incrementally recomputing other dependent variables, hence balancing the amount of dependency information to be tracked with the amount of recomputation to be performed upon input change.
Partial evaluation can be seen as a method for automating the simplest possible case of incremental computing, in which an attempt is made to divide program data into two categories: that which can vary based on the program's input, and that which cannot (and the smallest unit of change is simply "all the data that can vary"). Partial evaluation can be combined with other incremental computing techniques.
With cycles in the dependency graph, a single pass through the graph may not be sufficient to reach a fixed point. In some cases, complete reevaluation of a system is semantically equivalent to incremental evaluation, and may be more efficient in practice if not in theory.


TsIV

TsIV is a toxin from the venom of the Brazilian scorpion "Tityus serrulatus" which slows the inactivation of sodium channels.
Etymology.
TsIV is named after the scorpion from which the toxin is isolated, namely "Tityus serrulatus" (Ts). Alternative names for the TsIV toxin are TsIV-5, Toxin-4, Tityustoxin IV, Ts-IV and Toxin IV.
Sources.
TsIV is one of a variety of toxins that can be isolated from the venom of the Brazilian scorpion "T.serrulatus". This species of scorpion belongs to the family Buthidae and has a wide geographic distribution from northeastern to southeastern Brazil.
Chemistry.
The composition of TsIV determined by spectrophotometry is as follows: 11 Asp, 2 Thr, 3 Ser, 2 Glu, 3 Pro, 4 Gly, 3 Ala, 8 Cys, 2 Val, 2 Ile, 3 Leu, 8/9 Tyr, 1 His, 9 Lys, 2 Trp. The amino acid composition of TsIV also shows great similarity with those of Ts III and Ts V. Ts III has one less Lys and Ts V has an additional Lys and Gly.
Target and mode of action.
TsIV belongs to the family of α-scorpion toxins, which are known to bind voltage dependently to site 3, located on domain IV of the sodium channel, and thereby slow the inactivation of sodium channels. This toxin is active against mammals.
The application of TsIV to neuroblastoma cells resulted in a slowing of inactivation and an increase in peak current without changing time to peak, leading to the shifting of both the steady-state activation and inactivation curves to more negative potentials. Based on the knowledge that TsIV belongs to the family of α-toxins, it is likely that the effect of TsIV on the inactivation of sodium channels is preceded by the binding of TsIV to site 3 of the sodium channel.
Toxicity.
The TsIV toxin, isolated from "T. serrulatus" venom, does not discriminate between tissue-specific sodium channel subtypes and has been found to effect sodium channels from rat ventricular myocytes, rat cortical neurons and mouse skeletal muscle cells. Clinical manifestations of T. serrulatus envenoming include local pain at the site of the sting and systemic manifestations such as vomiting, profuse sweating, psychomotor agitation or restlessness, sinus tachycardia or bradycardia, arterial hypertension or hypotension, cardiac arrhythmias other than sinus tachycardia or bradycardia, cardiac failure, shock, tachypnea, pulmonary oedema and laboratory abnormalities such as leukocytosis, hyperglycaemia and increased amylase enzyme activity.
Martin "et al". recorded the toxicity of TsIV as LD50 after subcutaneous (s.c.) and intracerebroventricular (i.c.v.) injection. The LD50 of TsIV per 20 g mouse was 0.4 µg for s.c. injection and 24 ng for i.c.v. injection.
Treatment.
In clinical practice, Tityus poisoning is treated by intravenous administration of heterologous antivenoms. These antivenoms are obtained by the immunisation of horses with a mix of venoms derived from "T.Serrulatus" and "T.Bahiensis".
Several preclinical studies have identified epitopes that are present in many different toxins from the "T. serrulatus" scorpion. This could lead to the development of an antidote that reacts with the same epitope located on these different toxins.
Additionally, studies examined reactivity between horse anti-Ts antisera and synthetically produced peptides that corresponded to the amino acid sequence of several Ts toxins, including TsIV. The aim of these studies was to ascertain the neutralizing potential of these antivenoms by examining their reactivity with different epitopes of "T.serrulatus" toxins.


Pulmonary branches of vagus nerve

The pulmonary branches of the vagus nerve can be divided into two groups: anterior and posterior.
Anterior.
The "Anterior Bronchial Branches" (rami bronchiales anteriores; anterior or ventral pulmonary branches), two or three in number, and of small size, are distributed on the anterior surface of the root of the lung.
They join with filaments from the sympathetic, and form the "anterior pulmonary plexus".
Posterior.
The "Posterior Bronchial Branches" (rami bronchiales posteriores; posterior or dorsal pulmonary branches), more numerous and larger than the anterior, are distributed on the posterior surface of the root of the lung; they are joined by filaments from the third and fourth (sometimes also from the first and second) thoracic ganglia of the sympathetic trunk, and form the "posterior pulmonary plexus".
Branches from this plexus accompany the ramifications of the bronchi through the substance of the lung.


Nucleus raphe pallidus

The nucleus raphe pallidus receives afferent connections from the periaqueductal gray, the Paraventricular nucleus of hypothalamus, central nucleus of the amygdala, lateral hypothalamic area, and parvocellular reticular nucleus.
Also, the nucleus raphe pallidus receives afferents from the medial preoptic area, median preoptic nucleus and lateral paragigantocellular reticular nuclei.
The nucleus raphe pallidus has recently been shown to be involved in the activation of a fever as an immunoreaction. It has been implied that the preoptic area is constantly inhibiting the raphe pallidus, especially the rostral portion, with GABA.
When the preoptic area receives immune signals from the body, the inhibition stops and the rostral portion of the nucleus raphe pallidus excites the intermediolateral cell column, which induces a fever.
The nucleus raphe pallidus has also been known to mediate the tachycardia response, an extremely high heart rate known to be incited by emotional or psychological stress.
Microinjections of a GABA-a antagonist into the nucleus raphe pallidus, induces an increased heart rate.
Conversely, microinjections of muscimol, a GABA-a agonist, inhibit tachycardia in rats under air-stress stimuli.
In both of these cases, GABA is mediating two different sympathetic responses, so clearly the nucleus raphe pallidus is a far more a complex nucleus than previously thought.


Binocular vision

In biology, binocular vision is a type of vision in which an animal has two eyes capable of facing the same direction to perceive a single three-dimensional image of its surroundings. Neurological researcher Manfred Fahle has stated six specific advantages of having two eyes rather than just one:
Other phenomena of binocular vision include utrocular discrimination (the ability to tell which of two eyes has been stimulated by light), eye dominance (the habit of using one eye when aiming something, even if both eyes are open), allelotropia (the averaging of the visual direction of objects viewed by each eye when both eyes are open), binocular fusion or singleness of vision (seeing one object with both eyes despite each eye's having its own image of the object), and binocular rivalry (seeing one eye's image alternating randomly with the other when each eye views images that are so different they cannot be fused).
Binocular vision helps with performance skills such as catching, grasping, and locomotion. It also allows humans to walk over and around obstacles at greater speed and with more assurance. Optometrists and/or orthoptists are eyecare professionals who fix binocular vision problems.
Etymology.
The term "binocular" comes from two Latin roots, "bini" for double, and "oculus" for eye.
Field of view and eye movements.
Some animals - usually, but not always, prey animals - have their two eyes positioned on opposite sides of their heads to give the widest possible field of view. Examples include rabbits, buffaloes, and antelopes. In such animals, the eyes often move independently to increase the field of view. Even without moving their eyes, some birds have a 360-degree field of view.
Some other animals - usually, but not always, predatory animals - have their two eyes positioned on the front of their heads, thereby allowing for binocular vision and reducing their field of view in favor of stereopsis. However, front-facing eyes are a highly evolved trait in vertebrates, and there are only three extant groups of vertebrates with truly forward-facing eyes: primates, carnivorous mammals, and birds of prey.
Some predator animals, particularly large ones such as sperm whales and killer whales, have their two eyes positioned on opposite sides of their heads, although it is possible they have some binocular visual field.
Other animals that are not necessarily predators, such as fruit bats and a number of primates also have forward-facing eyes. These are usually animals that need fine depth discrimination/perception; for instance, binocular vision improves the ability to pick a chosen fruit or to find and grasp a particular branch.
The direction of a point relative to the head (the angle between the straight ahead position and the apparent position of the point, from the egocenter) is called visual direction, or version. The angle between the line of sight of the two eyes when fixating a point is called the absolute disparity, binocular parallax, or vergence demand (usually just vergence). The relation between the position of the two eyes, version and vergence is described by Hering's law of visual direction.
In animals with forward-facing eyes, the eyes usually move together. Eye movements are either conjunctive (in the same direction), version eye movements, usually described by their type: saccades or smooth pursuit (also nystagmus and vestibulo-ocular reflex). Or they are disjunctive (in opposite direction), vergence eye movements. The relation between version and vergence eye movements in humans (and most animals) is described by Hering's law of equal innervation.
Some animals use both of the above strategies. A starling, for example, has laterally placed eyes to cover a wide field of view, but can also move them together to point to the front so their fields overlap giving stereopsis. A remarkable example is the chameleon, whose eyes appear as if mounted on turrets, each moving independently of the other, up or down, left or right. Nevertheless, the chameleon can bring both of its eyes to bear on a single object when it is hunting, showing vergence and stereopsis.
Binocular summation.
Binocular summation is the process by which the detection threshold for a stimulus is lower with two eyes than with one. There are various types of possibilities when comparing binocular performance to monocular. Neural binocular summation occurs when the binocular response is greater than the probability summation. Probability summation assumes complete independence between the eyes and predicts a ratio ranging between 9-25%. Binocular inhibition occurs when binocular performance is less than monocular performance. This suggests that a weak eye affects a good eye and causes overall combined vision. Maximum binocular summation occurs when monocular sensitivities are equal. Unequal monocular sensitivities decrease binocular summation. There are unequal sensitivities of vision disorders such as unilateral cataract and amblyopia. Other factors that can affect binocular summation include are, spatial frequency, stimulated retinal points, and temporal separation.
Binocular interaction.
Apart from binocular summation, the two eyes can influence each other in at least three ways.
Singleness of vision.
Once the fields of view overlap, there is a potential for confusion between the left and right eye's image of the same object. This can be dealt with in two ways: one image can be suppressed, so that only the other is seen, or the two images can be fused. If two images of a single object are seen, this is known as double vision or diplopia.
Fusion of images (commonly referred to as 'binocular fusion') occurs only in a small volume of visual space around where the eyes are fixating. Running through the fixation point in the horizontal plane is a curved line for which objects there fall on corresponding retinal points in the two eyes. This line is called the empirical horizontal horopter. There is also an empirical vertical horopter, which is effectively tilted away from the eyes above the fixation point and towards the eyes below the fixation point. The horizontal and vertical horopters mark the centre of the volume of singleness of vision. Within this thin, curved volume, objects nearer and farther than the horopters are seen as single. The volume is known as Panum's fusional area (it's presumably called an area because it was measured by Panum only in the horizontal plane). Outside of Panum's fusional area (volume), double vision occurs.
Eye dominance.
When each eye has its own image of objects, it becomes impossible to align images outside of Panum's fusional area with an image inside the area. This happens when one has to point to a distant object with one's finger. When one looks at one's fingertip, it is single but there are two images of the distant object. When one looks at the distant object it is single but there are two images of one's fingertip. To point successfully, one of the double images has to take precedence and one be ignored or suppressed (termed "eye dominance"). The eye that can both move faster to the object and stay fixated on it is more likely to be termed as the dominant eye.
Stereopsis.
The overlapping of vision occurs due to the position of the eyes on the head (eyes are located on the front of the head, not on the sides). This overlap allows each eye to view objects with a slightly different viewpoint. As a result of this overlap of vision, binocular vision provides depth. Stereopsis (from stereo- meaning "solid" or "three-dimensional", and opsis meaning “appearance” or “sight”) is the impression of depth that is perceived when a scene is viewed with both eyes by someone with normal binocular vision. Binocular viewing of a scene creates two slightly different images of the scene in the two eyes due to the eyes' different positions on the head. These differences, referred to as binocular disparity, provide information that the brain can use to calculate depth in the visual scene, providing a major means of depth perception. There are two aspects of stereopsis: the nature of the stimulus information specifying stereopsis, and the nature of the brain processes responsible for registering that information. The distance between the two eyes on an adult is almost always 6.5 cm and that is the same distance in shift of an image when viewing with only one eye. Retinal disparity is the separation between objects as seen by the left eye and the right eye and helps to provide depth perception. Retinal disparity provides relative depth between two objects, but not exact or absolute depth. The closer objects are to each other, the retinal disparity will be small. If the objects are farther away from each other, then the retinal disparity will be larger. When objects are at equal distances, the two eyes view the objects as the same and there is zero disparity.
Allelotropia.
Because the eyes are in different positions on the head, any object away from fixation and off the plane of the horopter has a different visual direction in each eye. Yet when the two monocular images of the object are fused, creating a Cyclopean image, the object has a new visual direction, essentially the average of the two monocular visual directions. This is called allelotropia.
The origin of the new visual direction is a point approximately between the two eyes, the so-called cyclopean eye. The position of the cyclopean eye is not usually exactly centered between the eyes, but tends to be closer to the dominant eye.
Binocular rivalry.
When very different images are shown to the same retinal regions of the two eyes, perception settles on one for a few moments, then the other, then the first, and so on, for as long as one cares to look. This alternation of perception between the images of the two eyes is called binocular rivalry. Humans have limited capacity to process an image fully at one time. That is why the binocular rivalry occurs. Several factors can influence the duration of gaze on one of the two images. These factors include context, increasing of contrast, motion, spatial frequency, and inverted images. Recent studies have even shown that facial expressions can cause longer attention to a particular image. When an emotional facial expression is presented to one eye, and a neutral expression is presented to the other eye, the emotional face dominates the neutral face and even causes the neutral face to not been seen.
Disorders.
To maintain stereopsis and singleness of vision, the eyes need to be pointed accurately. The position of each eye in its orbit is controlled by six extraocular muscles. Slight differences in the length or insertion position or strength of the same muscles in the two eyes can lead to a tendency for one eye to drift to a different position in its orbit from the other, especially when one is tired. This is known as phoria. One way to reveal it is with the cover-uncover test. To do this test, look at a cooperative person's eyes. Cover one eye of that person with a card. Have the person look at your finger tip. Move the finger around; this is to break the reflex that normally holds a covered eye in the correct vergence position. Hold your finger steady and then uncover the person's eye. Look at the uncovered eye. You may see it flick quickly from being wall-eyed or cross-eyed to its correct position. If the uncovered eye moved from out to in, the person has esophoria. If it moved from in to out, the person has exophoria. If the eye did not move at all, the person has orthophoria. Most people have some amount of exophoria or esophoria; it is quite normal. If the uncovered eye also moved vertically, the person has hyperphoria (if the eye moved from down to up) or hypophoria (if the eye moved from up to down). Such vertical phorias are quite rare. It is also possible for the covered eye to rotate in its orbit, such a condition is known as cyclophoria. They are rarer than vertical phorias. Cover test may be used to determine direction of deviation in cyclophorias also.
The cover-uncover test can also be used for more problematic disorders of binocular vision, the tropias. In the cover part of the test, the examiner looks at the first eye as he or she covers the second. If the eye moves from in to out, the person has exotropia. If it moved from out to in, the person has esotropia. People with exotropia or esotropia are wall-eyed or cross-eyed respectively. These are forms of strabismus that can be accompanied by amblyopia. There are numerous definitions of amblyopia. A definition that incorporates all of these defines amblyopia as a unilateral condition in which vision in worse than 20/20 in the absence of any obvious structural or pathologic anomalies, but with one or more of the following conditions occurring before the age of six: amblyogenic anisometropia, constant unilateral esotropia or exotropia, amblyogenic bilateral isometropia, amblyogenic unilateral or bilateral astigmatism, image degradation. When the covered eye is the non-amblyopic eye, the amblyopic eye suddenly becomes the person's only means of seeing. The strabismus is revealed by the movement of that eye to fixate on the examiner's finger. There are also vertical tropias (hypertropia and hypotropia) and cyclotropias.
Binocular vision anomalies include: diplopia (double vision), visual confusion (the perception of two different images superimposed onto the same space), suppression (where the brain ignores all or part of one eye's visual field), horror fusionis (an active avoidance of fusion by eye misalignment), and anomalous retinal correspondence (where the brain associates the fovea of one eye with an extrafoveal area of the other eye).
Binocular vision anomalies are among the most common visual disorders. They are usually associated with symptoms such as headaches, asthenopia, eye pain, blurred vision, and occasional diplopia. About 20% of patients who come to optometry clinics will have binocular vision anomalies. The most effective way to diagnosis vision anomalies is with the near point of convergence test. During the NPC test, a target, such as a finger, is brought towards the face until the examiner notices that one eye has turned outward and/or the person has experienced diplopia or doubled vision.
Up to a certain extent, binocular disparities can be compensated for by adjustments of the visual system. If, however, defects of binocular vision are too great – for example if they would require the visual system to adapt to overly large horizontal, vertical, torsional or aniseikonic deviations – the eyes tend to avoid binocular vision, ultimately causing or worsening a condition of strabismus.


Parasympathetic nervous system

The parasympathetic nervous system (PSNS) is one of the three divisions of the autonomic nervous system, the others being the sympathetic nervous system and the enteric nervous system.
The autonomic nervous system is responsible for regulating the body's unconscious actions. The parasympathetic system is responsible for stimulation of "rest-and-digest" or "feed and breed" activities that occur when the body is at rest, especially after eating, including sexual arousal, salivation, lacrimation (tears), urination, digestion, and defecation. Its action is described as being complementary to that of the sympathetic nervous system, which is responsible for stimulating activities associated with the fight-or-flight response.
Nerve fibres of the parasympathetic nervous system arise from the central nervous system. Specific nerves include several cranial nerves, specifically the oculomotor nerve, facial nerve, glossopharyngeal nerve, and vagus nerve. Three spinal nerves in the sacrum (S2-4), commonly referred to as the pelvic splanchnic nerves, also act as parasympathetic nerves.
Owing to its location, the parasympathetic system is commonly referred to as having "craniosacral outflow", which stands in contrast to the sympathetic nervous system, which is said to have "thoracolumbar outflow".
Structure.
The parasympathetic nerves are autonomic or "visceral" branches of the peripheral nervous system (PNS). Parasympathetic nerve supply arises through three primary areas:
As in the sympathetic nervous system, efferent parasympathetic nerve signals are carried from the central nervous system to their targets by a system of two neurons. The first neuron in this pathway is referred to as the preganglionic or presynaptic neuron. Its cell body sits in the central nervous system and its axon usually extends to synapse with the dendrites of a postganglionic neuron somewhere else in the body. The axons of presynaptic parasympathetic neurons are usually long, extending from the CNS into a ganglion that is either very close to or embedded in their target organ. As a result, the postsynaptic parasympathetic nerve fibers are very short.
Cranial nerves.
The oculomotor nerve is responsible for a number of parasympathetic functions related to the eye. The oculomotor PNS fibers originate in the Edinger-Westphal nucleus in the central nervous system and travel through the superior orbital fissure to synapse in the ciliary ganglion located just behind the orbit (eye). From the ciliary ganglion the postganglionic parasympathetic fibers leave via short ciliary nerve fibers, a continuation of the nasociliary nerve (a branch of ophthalmic division of the trigeminal nerve (CN V1)). The short ciliary nerves innervate the orbit to control the ciliary muscle (responsible for accommodation) and the iris sphincter muscle, which is responsible for miosis or constriction of the pupil (in response to light or accommodation). There are two motors that are part of the oculomotor nerve known as the somatic motor and visceral motor. The somatic motor is responsible for moving the eye in precise motions and for keeping the eye fixated on an object. The visceral motor helps constrict the pupil.
The parasympathetic aspect of the facial nerve controls secretion of the sublingual and submandibular salivary glands, the lacrimal gland, and the glands associated with the nasal cavity. The preganglionic fibers originate within the CNS in the superior salivatory nucleus and leave as the intermediate nerve (which some consider a separate cranial nerve altogether) to connect with the facial nerve just distal (further out) to it surfacing the central nervous system. Just after the facial nerve geniculate ganglion (general sensory ganglion) in the temporal bone, the facial nerve gives off two separate parasympathetic nerves. The first is the greater petrosal nerve and the second is the chorda tympani. The greater petrosal nerve travels through the middle ear and eventually combines with the deep petrosal nerve (sympathetic fibers) to form the nerve of the pterygoid canal. The parasympathetic fibers of the nerve of the pterygoid canal synapse at the pterygopalatine ganglion, which is closely associated with the maxillary division of the trigeminal nerve (CN V2). The postganglionic parasympathetic fibers leave the pterygopalatine ganglion in several directions. One division leaves on the zygomatic division of CN V2 and travels on a communicating branch to unite with the lacrimal nerve (branch of the ophthalmic nerve of CN V1) before synapsing at the lacrimal gland. These parasympathetic to the lacrimal gland control tear production.
A separate group of parasympathetic leaving from the pterygopalatine ganglion are the descending palatine nerves (CN V2 branch), which include the greater and lesser palatine nerves. The greater palatine parasympathetic synapse on the hard palate and regulate mucus glands located there. The lesser palatine nerve synapses at the soft palate and controls sparse taste receptors and mucus glands. Yet another set of divisions from the pterygopalatine ganglion are the posterior, superior, and inferior lateral nasal nerves; and the nasopalatine nerves (all branches of CN V2, maxillary division of the trigeminal nerve) that bring parasympathetic innervation to glands of the nasal mucosa. The second parasympathetic branch that leaves the facial nerve is the chorda tympani. This nerve carries secretomotor fibers to the submandibular and sublingual glands. The chorda tympani travels through the middle ear and attaches to the lingual nerve (mandibular division of trigeminal, CN V3). After joining the lingual nerve, the preganglionic fibers synapse at the submandibular ganglion and send postganglionic fibers to the sublingual and submandibular salivary glands.
The glossopharyngeal nerve has parasympathetic fibers that innervate the parotid salivary gland. The preganglionic fibers depart CN IX as the tympanic nerve and continue to the middle ear where they make up a tympanic plexus on the cochlear promontory of the mesotympanum. The tympanic plexus of nerves rejoin and form the lesser petrosal nerve and exit through the foramen ovale to synapse at the otic ganglion. From the otic ganglion postganglionic parasympathetic fibers travel with the auriculotemporal nerve (mandibular branch of trigeminal, CN V3) to the parotid salivary gland.
Vagus nerve.
The vagus nerve, named after the Latin word "vagus" (because the nerve controls such a broad range of target tissues – "vagus" in Latin literally means "wandering"), has parasympathetic functions that originate in the dorsal nucleus of the vagus nerve and the nucleus ambiguus in the CNS. The vagus nerve is an unusual cranial parasympathetic in that it doesn't join the trigeminal nerve in order to get to its target tissues. Another peculiarity is that the vagus has an autonomic ganglion associated with it at approximately the level of C1 vertebra. The vagus gives no parasympathetic to the cranium. The vagus nerve is hard to track definitively due to its ubiquitous nature in the thorax and abdomen so the major contributions will be discussed. Several parasympathetic nerves come off the vagus nerve as it enters the thorax. One nerve is the recurrent laryngeal nerve, which becomes the inferior laryngeal nerve. From the left vagus nerve the recurrent laryngeal nerve hooks around the aorta to travel back up to the larynx and proximal esophagus while, from the right vagus nerve, the recurrent laryngeal nerve hooks around the right subclavian artery to travel back up to the same location as its counterpart. These different paths are a direct result of embryological development of the circulatory system. Each recurrent laryngeal nerve supplies the trachea and the esophagus with parasympathetic secretomotor innervation for glands associated with them (and other fibers that are not PN).
Another nerve that comes off the vagus nerves approximately at the level of entering the thorax are the cardiac nerves. These cardiac nerves go on to form cardiac and pulmonary plexuses around the heart and lungs. As the main vagus nerves continue into the thorax they become intimately linked with the esophagus and sympathetic nerves from the sympathetic trunks to form the esophageal plexus. This is very efficient as the major function of the vagus nerve from there on will be control of the gut smooth muscles and glands. As the esophageal plexus enter the abdomen through the esophageal hiatus anterior and posterior vagus trunks form. The vagus trunks then join with preaortic sympathetic ganglion around the aorta to disperse with the blood vessels and sympathetic nerves throughout the abdomen. The extent of the parasympathetic in the abdomen include the pancreas, kidneys, liver, gall bladder, stomach and gut tube. The vagus contribution of parasympathetic continues down the gut tube until the end of the midgut. The midgut ends two thirds of the way across the transverse colon near the splenic flexure.
Pelvic splanchnic nerves.
The pelvic splanchnic nerves, S2-4, work in tandem to innervate the pelvic viscera. Unlike in the cranium, where one parasympathetic is in charge of one particular tissue or region, for the most part the pelvic splanchnics each contribute fibers to pelvic viscera by traveling to one or more plexuses before being dispersed to the target tissue. These plexuses are composed of mixed autonomic nerve fibers (parasympathetic and sympathetic) and include the vesical, prostatic, rectal, uterovaginal, and inferior hypogastric plexuses. The preganglionic neurons in the pathway do not synapse in a ganglion as in the cranium but rather in the walls of the tissues or organs that they innervate. The fiber paths are variable and each individual's autonomic nervous system in the pelvis is unique. The visceral tissues in the pelvis that the parasympathetic nerve pathway controls include those of the urinary bladder, ureters, urinary sphincter, anal sphincter, uterus, prostate, glands, vagina, and penis. Unconsciously, the parasympathetic will cause peristaltic movements of the ureters and intestines, moving urine from the kidneys into the bladder and food down the intestinal tract and, upon necessity, the parasympathetic will assist in excreting urine from the bladder or defecation. Stimulation of the parasympathetic will cause the detrusor muscle (urinary bladder wall) to contract and simultaneously relax the internal sphincter muscle between the bladder and the urethra, allowing the bladder to void. Also, parasympathetic stimulation of the internal anal sphincter will relax this muscle to allow defecation. There are other skeletal muscles involved with these processes but the parasympathetic plays a huge role in continence and bowel retention.
A study published in 2016, suggests that all sacral autonomic output may be sympathetic; indicating that the rectum, bladder and reproductive organs may only be innervated by the sympathetic nervous system. This suggestion is based on detailed analysis of 15 phenotypic and ontogenetic factors differentiating sympathetic from parasympathetic neurons in the mouse. Assuming that the reported findings most likely applies to other mammals as well, this perspective suggests a simplified, bipartite architecture of the autonomic nervous system, in which the parasympathetic nervous system receives input from cranial nerves exclusively and the sympathetic nervous system from thoracic to sacral spinal nerves.
Emerging evidence in mouse models is suggesting that the previously held notion of the sacral spinal nerves being parasympathetic is incorrect, and that they may actually be sympathetic.
Function.
Sensation.
The afferent fibers of the autonomic nervous system, which transmit sensory information from the internal organs of the body back to the central nervous system, are not divided into parasympathetic and sympathetic fibers as the efferent fibers are. Instead, autonomic sensory information is conducted by general visceral afferent fibers.
General visceral afferent sensations are mostly unconscious visceral motor reflex sensations from hollow organs and glands that are transmitted to the CNS. While the unconscious reflex arcs normally are undetectable, in certain instances they may send pain sensations to the CNS masked as referred pain. If the peritoneal cavity becomes inflamed or if the bowel is suddenly distended, the body will interpret the afferent pain stimulus as somatic in origin. This pain is usually non-localized. The pain is also usually referred to dermatomes that are at the same spinal nerve level as the visceral afferent synapse.
Vascular effects.
Heart rate is largely controlled by the heart's internal pacemaker activity. Considering a healthy heart, the main pacemaker is a collection of cells on the border of the atria and vena cava called the sinoatrial node. Heart cells exhibit automaticity which is the ability to generate electrical activity independent of external stimulation. As a result, the cells of the node spontaneously generate electrical activity that is subsequently conducted throughout the heart, resulting in a regular heart rate.
In absence of any external stimuli, sinoatrial pacing contributes to maintain the heart rate in the range of 60-100 beats per minute (bpm). At the same time, the two branches of the autonomic nervous system act in a complementary way increasing or slowing the heart rate. In this context, the vagus nerve acts on sinoatrial node slowing its conduction thus actively modulating vagal tone accordingly. This modulation is mediated by the neurotransmitter acetylcholine and downstream changes to ionic currents and calcium of heart cells.
The vagus nerve plays a crucial role in heart rate regulation by modulating the response of sinoatrial node; vagal tone can be quantified by investigating heart rate modulation induced by vagal tone changes. As a general consideration, increased vagal tone (and thus vagal action) is associated with a diminished and more variable heart rate. The main mechanism by which the parasympathetic nervous system acts on vascular and cardiac control is the so-called respiratory sinus arrhythmia (RSA). RSA is described as the physiological and rhythmical fluctuation of heart rate at the respiration frequency, characterized by heart rate increase during inspiration and decrease during expiration.
Sexual activity.
Another role that the parasympathetic nervous system plays is in sexual activity. In males, the cavernous nerves from the prostatic plexus stimulate smooth muscles in the fibrous trabeculae of the coiled helicine arteries of penis to relax and allow blood to fill the two corpora cavernosa and the corpus spongiosum of the penis, making it rigid to prepare for sexual activity. Upon emission of ejaculate, the sympathetics participate and cause peristalsis of the ductus deferens and closure of the internal urethral sphincter to prevent semen from entering the bladder. At the same time, parasympathetics cause peristalsis of the urethral muscle, and the pudendal nerve causes contraction of the bulbospongiosus (skeletal muscle is not via PN), to forcibly emit the semen. During remission the penis becomes flaccid again. In the female, there is erectile tissue analogous to the male yet less substantial that plays a large role in sexual stimulation. The PN cause release of secretions in the female that decrease friction. Also in the female, the parasympathetics innervate the fallopian tubes, which helps peristaltic contractions and movement of the oocyte to the uterus for implantation. The secretions from the female genital tract aid in sperm migration. The PN (and SN to a lesser extent) play a significant role in reproduction.
Receptors.
The parasympathetic nervous system uses chiefly acetylcholine (ACh) as its neurotransmitter, although peptides (such as cholecystokinin) can be used. The ACh acts on two types of receptors, the muscarinic and nicotinic cholinergic receptors. Most transmissions occur in two stages: When stimulated, the preganglionic neuron releases ACh at the ganglion, which acts on nicotinic receptors of postganglionic neurons. The postganglionic neuron then releases ACh to stimulate the muscarinic receptors of the target organ.
Types of muscarinic receptors.
The five main types of muscarinic receptors:
Types of nicotinic receptors.
In vertebrates, nicotinic receptors are broadly classified into two subtypes based on their primary sites of expression: muscle-type nicotinic receptors (N1) primarily for somatic motor neurons; and neuronal-type nicotinic receptors (N2) primarily for autonomic nervous system.
Relationship to sympathetic nervous system.
Sympathetic and parasympathetic divisions typically function in opposition to each other. The sympathetic division typically functions in actions requiring quick responses. The parasympathetic division functions with actions that do not require immediate reaction. A useful mnemonic to summarize the functions of the parasympathetic nervous system is SSLUDD (sexual arousal, salivation, lacrimation, urination, digestion and defecation).
Clinical significance.
The functions promoted by activity in the parasympathetic nervous system are associated with our day-to-day living. The parasympathetic nervous system promotes digestion and the synthesis of glycogen, and allows for normal function and behavior.
Parasympathetic action helps in digestion and absorption of food by increasing the activity of the intestinal musculature, increasing gastric secretion, and relaxing the pyloric sphincter.It is called the “rest and digest” division of the ANS.
Boyesen, founder of Biodynamic Psychology, modeled a therapy based on a particular form of massage, which uses sounds coming from the intestine, auscultated with a stethoscope, as feedback to understand the moment of transition from sympathetic to parasympathetic nervous function.
History.
The terminology ‘Parasympathetic nervous system’ was introduced by Langley in 1921. He was the first person who put forward the concept of PNS as the second division of the autonomic nervous system.


Tobii Technology

Tobii (formerly known as Tobii Technology AB) is a Swedish high-technology company that develops and sells products for eye control and eye tracking.
History.
John Elvesjo, Mårten Skogö and Henrik Eskilsson founded the company in 2001. All three founders play an active role in the company: Henrik Eskilsson is the CEO, John Elvesjö is vice president and CTO, and Mårten Skogö is Chief Science Officer. The Tobii Group consists of three business units: Tobii Dynavox from an acquisition of US based DynaVox, Tobii Pro, and Tobii Tech. Tobii is based in Stockholm, Sweden, with offices in the US, Japan, China, Germany, Norway and Ukraine. Tobii became publicly traded on April 22, 2015, trading on the Stockholm Stock Exchange.
In 2007, the company got $14 million in venture capital from Investor Growth Capital. In May 2009, Investor, Amadeus Capital Partners and Northzone Ventures invested an additional $16 million, and at the start of 2012, Intel Capital invested $21 million.
In 2008, Tobii won the Swedish Grand Award of Design together with the design company Myra Industriell Design, for the technology and design in their eye controlled screens. In 2010, Tobii won the SIME Grand Prize for having the most innovative technology concept. In 2011, Tobii Glasses won the red dot design award, an international product design competition and later the same year, Tobii won the Bully Award. In 2012, Tobii took home the award for best prototype at the consumer technology tradeshow 2012 CES and Laptop Magazine named Tobii the winner in its best new technology category.
Products.
Tobii's products are sold directly and through resellers and partners worldwide. People with communication disabilities use Tobii Dynavox's technical devices and language tools (AAC devices) to communicate. Due to their high cost, they are often the goal of charity drives.
Tobii Pro has products that are widely used for research in the academic community, and to conduct usability studies and market surveys of commercial products.
Tobii Tech is the business unit that partners with others to integrate eye tracking and eye control in different industry applications and fields such as advanced driver assistance, consumer computing and gaming.
At the Consumer Electronics Show 2012, they demonstrated the Tobii Gaze, an infrared light based eye tracking device that makes it possible for users to use their eyes to point and interact with a standard computer.
In 2014, Tobii partnered with Danish SteelSeries and launched their first eye tracking system for consumers: the Tobii EyeX and the SteelSeries Sentry Eye Tracker. Several video games from major publishers were released in 2015-16 with support for Tobii's consumer devices, with varying levels of success.


Oleshky

Oleshky (; formerly "Tsiurupynsk") is a city in Kherson Oblast (province) of Ukraine, located on the left bank of the Dnieper River. It is the oldest city of the oblast and one of the oldest in the southern Ukraine. Oleshky serves as the administrative center of Oleshky Raion. Population:
Geography.
The city is located in southern Ukraine. The Konka River goes through the town before falling into the Dnipro. The Oleshky Sands are located in a close proximity to the town.
History.
The city of Oleshye (Oleshia) has been known since the 11th century, when it was a part of Kyivan Rus, but the area itself has been known since antiquity. Herodotus mentioned Scythian forests in the mouth of the Dnieper in the 5th century BCE, which were called "Oleshye" (from the Slavic word for "forest") by the Slavs. The city, which appeared later, took its name from the area, and the later form of the name (Oleshky) is also related.
In 1711–1728, Oleshky was the capital of the Zaporizhian Host under the protection of the Crimean Khanate. In 1784, the settlement of Oleshky was established; by 1790, it became a part of the Kinburn palanka of the Black-Sea Cossacks. In 1802, the settlement was granted town status and became the seat of an uyezd in Taurida Governorate. In 1928, the town was given name, after Alexander Tsiurupa, the former Soviet Trade Minister and the chief of Gosplan who was born in the city.
On 21 November 2007, the city council adopted resolution No.296 to restore the name Oleshky. The city council deputies and district councils, as well as the local Cossacks, wrote a letter to then president Victor Yushchenko requesting that the petition be carried out.
It wasn't before 19 May 2016 that the Verkhovna Rada adopted the resolution to rename Tsiurupynsk as Oleshky and conform to the law prohibiting names of Communist origin after a 9-year campaign by the city council and residents.


T-type calcium channel

T-type calcium channels are low voltage activated calcium channels that become deinactivated during cell membrane hyperpolarization but then open to depolarization. The entry of calcium into various cells has many different physiological responses associated with it. Within cardiac muscle cell and smooth muscle cells voltage-gated calcium channel activation initiates contraction directly by allowing the cytosolic concentration to increase. Not only are T-type calcium channels known to be present within cardiac and smooth muscle, but they also are present in many neuronal cells within the central nervous system. Different experimental studies within the 1970s allowed for the distinction of T-type calcium channels (transient opening calcium channels) from the already well-known L-type calcium channels (Long-Lasting calcium channels). The new T-type channels were much different from the L-type calcium channels due to their ability to be activated by more negative membrane potentials, had small single channel conductance, and also were unresponsive to calcium antagonist drugs that were present. These distinct calcium channels are generally located within the brain, peripheral nervous system, heart, smooth muscle, bone, and endocrine system.
The distinct structures of T-type calcium channels are what allow them to conduct in these manners, consisting of a primary α1 subunit. The α1 subunit of T-type channels is the primary subunit that forms the pore of the channel, and allows for entry of calcium.
T-type calcium channels function to control the pace-making activity of the SA Node within the heart and relay rapid action potentials within the thalamus. These channels allow for continuous rhythmic bursts that control the SA Node of the heart.
Pharmacological evidence of T-type calcium channels suggest that they play a role in several forms of cancer, absence epilepsy, pain, and Parkinson's disease. Further research is continuously occurring to better understand these distinct channels, as well as to create drugs to selectively target these channels.
Function.
Like any other channel in a cell membrane, the primary function of the T-type voltage gated calcium channel is to allow passage of ions, in this case calcium, through the membrane when the channel is activated. When membrane depolarization occurs in a cell membrane where these channels are embedded, they open and allow calcium to enter the cell, which leads to several different cellular events depending on where in the body the cell is found. As a member of the Cav3 subfamily of voltage-gated calcium channels, the function of the T-type channel is important for the repetitive firing of action potentials in cells with rhythmic firing patterns such as cardiac muscle cells and neurons in the thalamus of the brain. T-type calcium channels are activated in the same range as voltage-gated sodium channels, which is at about -55 mV. Because of this very negative value at which these channels are active, there is a large driving force for calcium going into the cell. The T-type channel is regulated by both dopamine and other neurotransmitters, which inhibit T-type currents. Additionally, in certain cells angiotensin II enhances the activation of T-type channels.
Heart.
This is important in the aforementioned depolarization events in the pace-making activity of the sinoatrial (SA) Node in the heart and in the neuron relays of the thalamus so that quick transmission of action potentials can occur. This is very important for the heart when stimulated by the sympathetic nervous system that causes the heart rate to increase, in that not only does the T-type calcium channel provide an extra depolarization punch in addition to the voltage gated sodium channels to cause a stronger depolarization, but it also helps provide a quicker depolarization of the cardiac cells.
Fast-acting.
Another important facet of the T-type voltage gated calcium channel is its fast voltage-dependent inactivation compared to that of other calcium channels. Therefore, while they help provide stronger and quicker depolarization of cardiac muscle cells and thalamus nerve cells, T-type channels also allow for more frequent depolarization events. This is very important in the heart in the simple fact that the heart is better apt to increase its rate of firing when stimulated by the sympathetic nervous system innervating its tissues. Although all of these functions of the T-type voltage gated calcium channel are important, quite possibly the most important of its functions is its ability to generate potentials that allow for rhythmic bursts of action potentials in cardiac cells of the sinoatrial node of the heart and in the thalamus of the brain. Because the T-type channels are voltage dependent, hyperpolarization of the cell past its inactivation voltage will close the channels throughout the SA node, and allow for another depolarizing event to occur. The voltage dependency of the T-type channel contributes to the rhythmic beating of the heart.
Structure.
Voltage-gated calcium channels are made up of several subunits. The α1 subunit is the primary subunit that forms the transmembrane pore of the channel. The α1 subunit also determines the type of calcium channel. The β, α2δ, and γ subunits, present in only some types of calcium channels, are auxiliary subunits that play secondary roles in the channel.
α1 Subunit.
The α1 subunit of T-type calcium channels is similar in structure to the α subunits of K+(potassium ion) channels, Na+(sodium ion) channels, and other Ca2+(calcium ion) channels. The α1 subunit is composed of four domains (I-IV), with each domain containing 6 transmembrane segments (S1-S6). The hydrophobic loops between the S5 and S6 segments of each domain form the pore of the channel. The S4 segment contains a high quantity of positively charged residues and functions as the voltage sensor of the channel opening or closing based on the membrane potential. The exact method by which the S4 segment controls the opening and closing of the channel is currently unknown.
Auxiliary subunits.
The β, α2δ, and γ subunits are auxiliary subunits that affect channel properties in some calcium channels. The α2δ subunit is a dimer with an extracellular α2 portion linked to a transmembrane δ portion. The β subunit is an intracellular membrane protein. The α2δ and β subunits have an effect on the conductance and kinetics of the channel. The γ subunit is a membrane protein that has an effect on the voltage sensitivity of the channel. Current evidence shows that isolated T-type α1 subunits have similar behavior to natural T-type channels, suggesting that the β, α2δ, and γ subunits are absent from T-type calcium channels and the channels are made up of only an α1 subunit.
Variation.
There are three known types of T-type calcium channels, each associated with a specific α1 subunit.
Pathology.
When these channels are not functioning correctly, or are absent from their usual domains, several issues can result.
Cancer.
T-type Calcium channels are expressed in different human cancers such as breast, colon, prostate, insulinoma, retinoblastoma, leukemia, ovarian, and melanoma, and they also play key roles in proliferation, survival, and the regulation of cell cycle progression in these forms of cancer . This was demonstrated through studies that showed that down regulating T-type channel isoforms, or just blocking the T-type calcium channels caused cytostatic effects in cancer cells such as gliomas, breast, melanomas, and ovarian, esophageal, and colorectal cancers .
Some of the most notorious forms of cancer tumors contain cancer stem cells (CSC), which makes them particularly resistant to any cancer therapy . Furthermore, there is evidence that suggests that the presence of the CSC in human tumors may be associated with the expression of T-type calcium channels in the tumors.
Epilepsy.
The major disease that involves the T-type calcium channel is absence epilepsy. This disease is caused by mutations of T-type calcium channel itself. When an individual has this disease, they will move in and out of a sleep-like state, even during normal activities. Experiments on the Genetic Absence Epilepsy Rat of Strasbourg (GAERS) suggested that absence epilepsy in the rat was linked to T-type channel protein expression. In fact, neurons isolated from the reticular nucleus of the thalamus of the GAERS showed 55% greater T-type currents, and these currents were attributed to an increase in the Cav3.2 mRNA, according to Tally et al. suggesting that T-type protein expression was up regulated in the GAERS. Further experiments on the GAERS showed that, indeed, the expression of T-type calcium channels play a key role in seizures caused by absence epilepsy in the GAERS. Also, other evidence suggest that T-type calcium channel expression is not only up regulated in absence epilepsy, but also in other forms of epilepsy as well.
Pain.
The Cav3.2 isoform of T-type calcium channels has been found to involve in pain in animal models with acute pain and chronic pain: neuropathic pain (PDN), inflammatory pain and visceral pain.
Parkinson's disease.
Increased neuronal bursting occurs throughout the central motor system in both human forms and animals models of Parkinson's disease. T-type calcium channels are highly expressed in basal ganglia structures as well as neurons in the motor areas of the thalamus and are thought to contribute to normal and pathological bursting by means of low-threshold spiking. Basal ganglia recipient neurons in the thalamus are particularly interesting because they are directly inhibited by the basal ganglia output. Consistent with the standard rate model of the basal ganglia, the increased firing in basal ganglia output structures observed in Parkinson's disease would exaggerate the inhibitory tone in thalamocortical neurons. This may provide the necessary hyperpolarization to de-inactivate T-type calcium channels, which can result in rebound spiking. In normal behavior, bursting likely plays a role in increasing the likelihood of synaptic transmission, initiating state changes between rest and movement, and might signal neural plasticity due to the intracellular cascades brought on by the rapid influx of calcium. While these roles are not mutually exclusive, most attractive is the hypothesis that persistent bursting promotes a motor state resistant to change, potentially explaining the akinetic symptoms of Parkinson's disease.
As a drug target.
Calcium channel blockers (CCB) such as mibefradil can also block L-type calcium channels, other enzymes, as well as other channels. Consequently, research is still being conducted to design highly selective drugs that can target T-type calcium channels alone.
Cancer.
Furthermore, since T-type calcium channels are involved in proliferation, survival and cell cycle progression of these cells, they are potential targets for anticancer therapy. Like mentioned above, blockage or down regulation of the T-type calcium channels causes cytostasis in tumors; but this blockage or down regulation of the T-channels may also induce cytotoxic effects. Consequently, it is not yet clear what the benefits or disadvantages of targeting T-type calcium channels in anticancer therapy are. On the other hand, a combined therapy involving administration of a T-type channel antagonist followed by cytotoxic therapy is currently in its clinical trial phase.
Painful Diabetic Neuropathy (PDN).
In addition, drugs used for treating PDN are associated with serious side effects and target specifically the CaV3.2 isoform (responsible for development of neuropathic pain in PDN) could reduce side effects. As a result, research to improve or design new drugs is currently on-going.
Parkinson's disease.
T-type calcium channels represent an alternative approach to Parkinson's disease treatment as their primary influence is not concerning the central dopaminergic system. For example, they offer great potential in reducing side effects of dopamine replacement therapy, such as levodopa-induced dyskinesia. The co-administration of T-type calcium channel blockers with standard Parkinson's disease medications is most popular in Japan, and several clinical studies have shown significant efficacy. However, most of these drugs are experimental and operate in a non-specific manner, potentially influencing sodium channel kinetics as well as dopamine synthesis. Novel T-type calcium channel inhibitors have recently been discovered which more selectively target the CaV3.3 channel sub-type expressed in central motor neurons, showing robust modulation in a rodent and primate models of Parkinson's disease.


Lateral reticular nucleus

The lateral reticular nucleus, of the lateral funiculus, can be divided into three subnuclei, the parvocellular, magnocellular and the "subtrigeminal". As is typical of the reticular formation, none of these are very distinct subnuclei, but rather blurred distinctions between cell types and location. The lateral reticular nucleus sends all of its projections to the cerebellum.
All of these efferent pathways are projected in an ipsilateral manner to the cerebellum, the most abundant of which are those to the vermis.
This nucleus is also involved in the mediation of inspiration (in-breathing) with a part of the ventral r. nucleus.
The afferent pathways to the LRN come from the spinal cord and higher brain structures.
Most of the afferents come from the ipsilateral dorsal horn of the spinal cord and project exclusively to the parts of the LRN that do not receive input from the cortex.
The spinal cord projections terminate mostly in the parvocellular region along with the adjacent magnocellular cells.
This implies that most input from the spinal cord is relayed into the vermis.


Tenocyclidine

Tenocyclidine (TCP) was discovered by a team at Parke-Davis in the late 1950s. It is a dissociative anesthetic drug with psychostimulant and hallucinogenic effects. It is similar in effects to phencyclidine (PCP) but is considerably more potent. TCP has slightly different binding properties to PCP, with more affinity for the NMDA receptors, but less affinity for the sigma receptors. Because of its high affinity for the PCP site of the NMDA receptor complex, the 3H radiolabelled form of TCP is widely used in research into NMDA receptors.
TCP acts primarily as an NMDA receptor antagonist which blocks the activity of the NMDA receptor, however its increased psychostimulant effects compared to PCP suggests it also has relatively greater activity as a dopamine reuptake inhibitor (DRI). Due to its similarity in effects to PCP, TCP was placed into the Schedule I list of illegal drugs in the 1970s, although it was only briefly used in the 1970s and 1980s and is now little known.


5-HT7 receptor

The 5-HT7 receptor is a member of the GPCR superfamily of cell surface receptors and is activated by the neurotransmitter serotonin (5-hydroxytryptamine, 5-HT) The 5-HT7 receptor is coupled to Gs (stimulates the production of the intracellular signaling molecule cAMP) and is expressed in a variety of human tissues, particularly in the brain, the gastrointestinal tract, and in various blood vessels. This receptor has been a drug development target for the treatment of several clinical disorders. The 5-HT7 receptor is encoded by the "HTR7" gene, which in humans is transcribed into 3 different splice variants.
Function.
When the 5-HT7 receptor is activated by serotonin, it sets off a cascade of events starting with release of the stimulatory G protein Gs from the GPCR complex. Gs in turn activates adenylate cyclase which increases intracellular levels of the second messenger cAMP.
The 5-HT7 receptor plays a role in smooth muscle relaxation within the vasculature and in the gastrointestinal tract. The highest 5-HT7 receptor densities are in the thalamus and hypothalamus, and it is present at higher densities also in the hippocampus and cortex. The 5-HT7 receptor is involved in thermoregulation, circadian rhythm, learning and memory, and sleep. It is also speculated that this receptor may be involved in mood regulation, suggesting that it may be a useful target in the treatment of depression.
Variants.
Three splice variants have been identified in humans (designated h5-HT7(a), h5-HT7(b), and h5-HT7(d)), which encode receptors that differ in their carboxy terminals. The h5-HT7(a) is the full length receptor (445 amino acids), while the h5-HT7(b) is truncated at amino acid 432 due to alternative splice donor site. The h5-HT7(d) is a distinct isoform of the receptor: the retention of an exon cassette in the region encoding the carboxyl terminal results a 479-amino acid receptor with a c-terminus markedly different from the h5-HT7(a). A 5-HT7(c) splice variant is detectable in rat tissue but is not expressed in humans. Conversely, rats do not express a splice variant homologous to the h5-HT7(d), as the rat 5-HT7 gene lacks the exon necessary to encode this isoform. Drug binding affinities are similar across the three human splice variants; however, inverse agonist efficacies appear to differ between the splice variants.
Discovery.
In 1983, evidence for a 5-HT1-like receptor was first found. Ten years later, 5-HT7 receptor was cloned and characterized. It has since become clear that the receptor described in 1983 is 5-HT7.
Clinical significance.
This receptor gene is a candidate locus for involvement in autism and other neuropsychiatric conditions.
Ligands.
Numerous orthosteric ligands of moderate to high affinity are known. Signaling biased ligands were discovered and developed in 2018.
Agonists.
Agonists mimic the effects of the endogenous ligand, which is serotonin at the 5-HT7 receptor (↑cAMP).
Antagonists.
Neutral antagonists (also known as silent antagonists) bind the receptor and have no intrinsic activity but will block the activity of agonists or inverse agonists. Inverse agonists inhibit the constitutive activity of the receptor, producing functional effects opposite to those of agonists (at the 5-HT7 receptor: ↓cAMP). Neutral antagonists and inverse agonists are typically referred to collectively as "antagonists" and, in the case of the 5-HT7 receptor, differentiation between neutral antagonists and inverse agonists is problematic due to differing levels inverse agonist efficacy between receptor splice variants. For instance, mesulergine and metergoline are reported to be neutral antagonists at the h5-HT7(a) and h5-HT7(d) receptor isoforms but these drugs display marked inverse agonist effects at the h5-HT7(b) splice variant.
Inactivating antagonists.
Inactivating antagonists are non-competitive antagonists that render the receptor persistently insensitive to agonist, which resembles receptor desensitization. Inactivation of the 5-HT7 receptor, however, does not arise from the classically described mechanisms of receptor desensitization via receptor phosphorylation, beta-arrestin recruitment, and receptor internalization. Inactivating antagonists all likely interact with the 5-HT7 receptor in an irreversible/pseudo-irreversible manner, as is the case with [3H]risperidone.


Median aperture

The median aperture (also known as the medial aperture, and foramen of Magendie) drains cerebrospinal fluid (CSF) from the fourth ventricle into the cisterna magna. The two other openings of the fourth ventricle are the lateral apertures (also called the foramina of Luschka), one on the left and one on the right, which drain cerebrospinal fluid into the cerebellopontine angle cistern. The median foramen on axial images is posterior to the pons and anterior to the caudal cerebellum. It is surrounded by the obex and gracile tubercles of the medulla, tela choroidea of the fourth ventricle and its choroid plexus, which is attached to the cerebellar vermis.
Eponym.
The foramen of Magendie is named for François Magendie, who first described it.


Piscivorin

Piscivorin is a component of snake venom secreted by the Eastern Cottonmouth ("Agkistrodon piscivorus piscivorus"). It is a member of the cysteine-rich secretory protein (CRISP) family, which blocks voltage-dependent calcium channels.
Etymology.
The name of piscivorin comes from the snake species name piscivorus, which is derived from the Latin words "pisces" and "vorare", meaning 'fish' and 'to devour' respectively.
Sources.
Piscivorin is produced in the venom glands of the Eastern Cottonmouth snake ("Agkistrodon piscivorus piscivorus"), which populates the Eastern United States. Typically, crude venom from the Eastern Cottonmouth contains approximately 1.25% of piscivorin.
Biochemistry.
Piscivorin belongs to the cysteine-rich secretory protein (CRISP) family, which are secreted as single-chain proteins with molecular masses between 20 and 30 kDa. They display significant amino acid sequence homology. Sixteen cysteine residues, forming 8 disulfide bonds, are strictly conserved in CRISPs. Ten of these cysteine residues are clustered into the C-terminal part of the protein.
The molecular mass of piscivorin is 24.842 kDa. The nucleotide sequence of piscivorin cDNA spans 1323 bp, containing an open reading frame of 240 codons.
Piscivorin has the following amino acid sequence.
Target and mode of action.
Piscivorin reduces high potassium-evoked smooth muscle contraction, but does not inhibit caffeine-stimulated contraction of smooth muscle. Since caffeine normally causes contraction through the release of Ca2+ from the sarcoplasmic reticulum, this differential effect indicates that piscivorin is an L-type calcium channel blocker. At a concentration of 1 μM, its effect on depolarization-induced smooth muscle contraction is weaker than of the related CRISP family toxins ablomin, triflin or latisemin. A sequence comparison of piscivorin and other CRISP family proteins suggests that the Glu186 residue is the crucial site for the blocking of the calcium channels.
Unlike some other CRISP family proteins, piscivorin does not block cyclic nucleotide-gated channels.


Idioms in American Sign Language

American Sign Language (ASL) is the main language of members of the deaf community in the United States. One component of their language is the use of idioms. The validity of these idioms have often been questioned or confused with metaphorical language. The term "idiom" can be defined as, "A speech form or an expression of a given language that is peculiar to itself grammatically or cannot be understood from the individual meanings of its elements," (Idiom, 2007). The following examples are written in ASL "glossing". These idioms further validate ASL as a language unique and independent of English. Idioms in ASL bond people in the Deaf community because they are expressions that only in-group members can understand.
Examples.
"Train go sorry" is one of the most widely used idioms and is similar to the English idiom "You missed the boat". Another variation of this idiom is "Cigarette-gone".
"Cow-it" is roughly translated into "I don't care for [something]".
"I-I-I," the letter, not "me," signed repeatedly with alternating hands on the chest is an idiom that is translated into the English word "egotistical".
However, even examples like "Cow-it" and "I-I-I" remain controversial. There is ambiguity in defining and identifying idioms in American Sign Language as little is known of ASL's use of idioms. Cokely & Baker-Shenk write, "it is interesting to note that ASL seems to have very few widely-used idioms, according to the standard definition of ‘idiom.’"
In their examination of how interpreters approach ASL idioms Santiago and Barrick (2007) cite Rosenthal's (1978) definition of idiom to frame their research:
"1. Idioms consist of at least two or more words, which may or may not be contiguous, inflected or in a specific order. 2. Idioms are recurrent constructs...(Some degree of recurrence is necessary to distinguish idioms from metaphors and other style figures)."
This is important because some constructs like "Cow-it" and "Cigarette-gone" may not have the incidence of recurrence needed to be considered ASL idioms.
Some authors have noticed that many signs that people often think are idioms in ASL i.e., "Out of sight," "On the fence," "Funny None/Funny Zero," are either sign compounds with transparent meaning ("Funny none" means "not funny") or single-sense lexical items that either cannot be translated into English by using a single lexical item, or whose translation requires an English idiom. According to Battison in Valli and Lucas 1998, "We can show that things that are often called sign ‘idioms’: are often just ordinary signs that are difficult to translate into English." When compared to the sign "Succeed," which is made with two movements, the sign "At last" is one sharp movement and has historically been called an ASL idiom for the very reason of its non-translatability. But Battison purports that because the "two signs are made differently (they) have different meanings...they are two separate signs." By "misusing" the term "idiom" in application to American Sign Language, the result is an "obscure" understanding of how "the language really works and it make(s) it seem as if the language is unstructured and simple. Of course, nothing could be further from the truth."


Pioneer neuron

A pioneer neuron is a cell that is a derivative of the preplate in the early stages of corticogenesis of the brain. Pioneer neurons settle in the marginal zone of the cortex and project to sub-cortical levels. In the rat, pioneer neurons are only present in prenatal brains. Unlike Cajal-Retzius cells, these neurons are reelin-negative.
Pioneer neurons are born in the ventricular neuroepithelium all over the cortical primordium. In the rat cortex, they appear at embryonic day (E) 11.5 in the lateral aspect of the telencephalic vesicle and cover its whole surface on E12. These cells, which show intense immunoreactivity for calbindin and calretinin, are characterized by their large size and axonal projection. They remain in the marginal zone after the formation of the cortical plate; they project first into the ventricular zone, and then into the subplate and the internal capsule. Therefore, these cells are the origin of the earliest efferent pathway of the developing cortex.
Function.
It is thought that axons of pioneer neurons, pioneer axons, serve as a pathway for additional neurons that develop later in the embryo and project their axons to the appropriate target. In many systems pioneer neurons are eliminated by programmed cell-death and are not present in the adult.


Frank Altimari

Frank Xavier Altimari (September 4, 1928 – July 19, 1998) was a United States Circuit Judge of the United States Court of Appeals for the Second Circuit and previously was a United States District Judge of the United States District Court for the Eastern District of New York.
Education and career.
Born in Queens, New York, Altimari attended St. Francis College in Brooklyn. He received a Bachelor of Laws from Brooklyn Law School in 1951. He served as an attorney in private practice in Jamaica, New York from 1951 to 1965. During this period, he also was a law professor at St. Francis College from 1954 to 1963, and served on the school board in Westbury, New York from 1963 to 1965.
State judicial service.
Altimari's judicial career began when he was elected to the Nassau County District Court in 1965. After serving on that court for four years, he was elected to the Nassau County Court for a term beginning in 1970 and then as a Justice of the New York State Supreme Court (the trial court of New York), on which he served from 1974 to 1982. He also again taught at St. Francis College from 1972 to 1973.
Federal judicial service.
Altimari was nominated by President Ronald Reagan on November 23, 1982, to a seat on the United States District Court for the Eastern District of New York vacated by Judge Edward Raymond Neaher. He was confirmed by the United States Senate on December 10, 1982, and received his commission on December 10, 1982. His service terminated on December 23, 1985, due to his elevation to the Second Circuit.
Altimari was nominated by President Reagan on October 23, 1985, to a seat on the United States Court of Appeals for the Second Circuit vacated by Judge Ellsworth Van Graafeiland. He was confirmed by the Senate on December 16, 1985, and received his commission on December 17, 1985. He assumed senior status on January 1, 1996. His service terminated on July 19, 1998, due to his death of brain cancer in Old Westbury, New York.


Hexestrol diacetate

Hexestrol diacetate (JAN) (brand names Retalon Lingual, Robal, Sintestrol, Sintofolin) is a synthetic, nonsteroidal estrogen of the stilbestrol group related to diethylstilbestrol. It is an ester of hexestrol, and was discovered in 1939.


Latisemin

Latisemin is a cysteine-rich secretory protein that can be isolated from the venom of the Black-banded sea krait, a sea snake indigenous to the warmer waters of the western Pacific Ocean. It is a toxin that inhibits cyclic nucleotide-gated ion channels and blocks L-type calcium channels, thereby reducing smooth muscle contraction.
Sources.
Latisemin is a component of the venom produced by the Erabu sea snake ("Laticauda semifasciata") of the family Elapidae and the Laticauda genus. These sea snakes inhabit coral reef areas in the seas of Southern Japan, Southeast Asia, and Australia. Though highly venomous, this snake is comparatively unaggressive, and is in fact caught and eaten in Erabu soup in Japan.
Biochemistry.
Latisemin has a molecular weight of 24 kDa and consists of 217 amino acids. It belongs to the CRISP (cysteine-rich secretory protein) glycoprotein subfamily, which are single chain polypeptides containing strictly conserved cysteines (cysteines not oxidised to cystine and thus not providing disulfide bond support to tertiary protein structure). They are secretory proteins, meaning they are secreted from cells into extracellular fluid.
Target.
Latisemin strongly blocks depolarization- (but not caffeine-) induced smooth muscle contraction, suggesting that it blocks L-type calcium channels. Its mode of action is similar to that of some other snake venom toxins from the CRISP family, like ablomin from the Japanese Mamushi snake and triflin from the Habu snake. They also inhibit cyclic nucleotide-gated ion channels.
See also.
Other snake venom proteins in the CRISP family:


Reaction of degeneration

Reaction of degeneration is a medical condition caused by a change in the electrical response of the muscles due to muscle denervation.


Clinical neurophysiology

Clinical neurophysiology is a medical specialty that studies the central and peripheral nervous systems through the recording of bioelectrical activity, whether spontaneous or stimulated. It encompasses both research regarding the pathophysiology along with clinical methods used to diagnose diseases involving both central and peripheral nervous systems.
Examinations in the clinical neurophysiology field are not limited to tests conducted in a laboratory. It is thought of as an extension of a neurologic consultation. Tests that are conducted are concerned with measuring the electrical functions of the brain, spinal cord, and nerves in the limbs and muscles. It can give the precise definition of site, the type and degree of the lesion, along with revealing the abnormalities that are in question. Due to these abilities, clinical neurophysiology is used to mainly help diagnose diseases rather than treat them.
In some countries it is a part of neurology or psychiatry, for example the United States and Germany. In other countries it is an autonomous specialty, such as Spain, Portugal, Italy, the United Kingdom, Finland, Sweden and Norway.
Hospitals that have neurologists and neurosurgeons tend to house clinical neurophysiology departments. Usually these tend to be larger hospitals that are able to employ more specialized staff units. In hospitals that possess clinical neurophysiology facilities, the major diagnostic modalities employed include:
In the United States.
The pathway to becoming a clinical neurophysiologist in the U.S. includes completing an undergraduate degree, medical school, and postgraduate medical education, usually in neurology. Following the completion of an accredited residency program, clinicians may choose to enter a fellowship in Clinical Neurophysiology. Programs may expose their fellows to the broad spectrum of electrodiagnostic neurophysiologic studies, or may focus on a single area such as EEG or electrodiagnostic medicine. Clinical neurophysiology fellowships are generally 1–2 years in duration and may lead to board certification in one or more subspecialty areas.
In the United Kingdom.
There are two healthcare professionals who typically perform neurophysiological investigations in the UK. These are medical staff trained in clinical neurophysiology, and clinical physiologists who undertake four years of practical training whilst undertaking an honours degree. Physiologists perform the majority of EEGs, evoked potentials and a portion of the nerve conduction studies. They are then clinically reported either by the physiology staff or the medical staff. Their professional organisations are the British Society for Clinical Neurophysiology and the Association of Neurophysiological Scientists
Relationship to electrodiagnostic medicine.
Electrodiagnostic medicine is a subset of clinical neurophysiology. Electrodiagnostic medicine focuses only on the peripheral nervous system and not the central nervous system. Whereas a clinical neurophysiologist is trained to perform all the following studies EEG, intraoperative monitoring, nerve conduction studies, EMG and evoked potentials, and electrodiagnostic physician focuses mainly on nerve conduction studies, needle EMG, and evoked potentials. The American Board of Psychiatry and Neurology provides certification examination in clinical neurophysiology. The American Board of Electrodiagnostic Medicine provides certification in EDX medicines. The American Board of Clinical Neurophysiology certifies in electroencephalography (EEG), Evoked Potentials (EP), Polysomnography (PSG), Epilepsy Monitoring, and Neurologic Intraoperative Monitoring (NIOM). In the US physicians typically specialize in EEG or EDX medicine but not both.
Neurophysiologists in hospitals.
Hospitals that have neurologists and neurosurgeons tend to house clinical neurophysiology departments. Usually these tend to be larger hospitals that are able to employ more specialized staff units.
Clinical neurophysiologists are responsible for analyzing and writing reports on tests that take place within the department. They must also interpret the results that they receive and convey this information to the doctor that referred the patient to the particular neurophysiologist. Many tests involve carrying out an EMG to read the evoked potential recordings. Nerve conduction recordings are extremely common as well.


Netoglitazone

Netoglitazone (also called MCC-555) is a hypoglycemic agent belonging to the thiazolidinedione group.