Floor plate

The floor plate is a structure integral to the developing nervous system of vertebrate organisms. Located on the ventral midline of the embryonic neural tube, the floor plate is a specialized glial structure that spans the anteroposterior axis from the midbrain to the tail regions. It has been shown that the floor plate is conserved among vertebrates, such as zebrafish and mice, with homologous structures in invertebrates such as the fruit fly "Drosophila" and the nematode "C. elegans". Functionally, the structure serves as an organizer to ventralize tissues in the embryo as well as to guide neuronal positioning and differentiation along the dorsoventral axis of the neural tube.
Induction.
Induction of the floor plate during embryogenesis of vertebrate embryos has been studied extensively in chick and zebrafish and occurs as a result of a complex signaling network among tissues, the details of which have yet to be fully refined. Currently there are several competing lines of thought. First, floor plate differentiation may be mediated by inductive signaling from the underlying notochord, an axial mesoderm derived signaling structure. This is supported experimentally in chick, in which floor plate induction, as well as associative ventral nervous tissue differentiation, is mediated by the secreted signaling molecule sonic hedgehog (Shh). Shh is expressed in a gradient with highest concentration localized in the notochord and floor plate. "In vitro" tissue grafting experiments show that removal of this molecule prevents differentiation of the floor plate, whereas its ectopic expression induces differentiation of floor plate cells. An alternative view proposes that neural tube floor plate cells stem from precursor cells which migrate directly from axial mesoderm. Through chick – quail hybrid experiments as well as genetic interaction experiments in zebrafish, it appears that notochord and floor plate cells originate from a common precursor. Furthermore, in zebrafish, Nodal signaling is required for differentiation of medial floor plate cells whereas Shh is expendable. These data may indicate that the floor plate induction mechanism in amniotes and anamniotes differs. To reconcile these differences, a dual-mode induction model has been proposed in chick. In this model, exclusively ectodermal cells are induced to become medial floor plate during gastrulation by prechordal mesoderm, possibly through Nodal signaling. Later in development during neurulation, extended contact and interaction between notochord and fated floor plate cells causes differentiation, suggesting a cooperative effect between Nodal and Shh signaling.
Axon guidance.
In the development of the central nervous system, the decision of a neuron to cross or not cross the midline is critical. In vertebrates, this choice is mediated by the floor plate, and enables the embryo to develop successful left and right body halves with respect to nervous tissue. For example, while ipsilateral neurons do not cross the midline, commissural neurons cross the midline forming a single commissure. These particular neurons develop in the dorsal region of the neural tube and travel ventrally toward the floor plate. Upon reaching the floor plate, commissural neurons cross through the structure to emerge on the opposite side of the neural tube, whereupon they project anteriorly or posteriorly within the tube.
The signaling molecules guiding the growth and projections of commissural neurons have well studied homologs in invertebrates. In the Netrin/DCC chemoattraction pathway the C. elegans homologs are Unc-6/Unc-40 and Unc-5 while the Drosophila homologs are Netrin-A and Netrin-B/Frazzled and Dunc5. In the Slit/Robo chemoreppelant pathway the C. elegans homologs are Slt-1/Sax-3 whereas the Drosophila homologs are also known as Slit/Robo(1-3).
Glial fate mapping.
In the central nervous system (CNS), overall cell fate mapping is typically directed by the sonic hedgehog (Shh) morphogen signaling pathway. In the spinal cord, Shh is directed by both the notochord and floor plate regions which ultimately drives the organization of neural and glial progenitor populations. The specific glial populations impacted by Shh in these two regions include oligodendrocyte precursor cells (OPCs), oligodendrocytes, NG2+ cells, microglia, and astrocytes. The floor plate (FP) region of the spinal cord individually contributes to gliogenesis, or the formation of glial cells. Traditionally, progenitor cells are driven from their progenitor expansion phase, to the neurogenic phase, and ultimately to the gliogenic phase. From the gliogenic phase, the former progenitor cells can then become astrocytes, oligodendrocytes, or other more specialized glial cell types. Recently, there have been efforts to use conditional mutagenesis to selectively inactivate the Shh pathway specifically in the FP region to identify different roles of molecules involved in oligodendrocyte cell fate. Oligodendrocytes are the cells responsible for myelinating axons in the CNS.
Shh regulates Gli processing through two proteins, Ptch1 and Smo. When Shh is not active, Ptch1 is responsible for suppressing the pathway through the inhibition of Smo. Smo is crucial to the overall transduction of signal of the Shh pathway. If Smo is inhibited, the Shh pathway is also inactive, which ultimately represses gliogenesis. Specific factors such as Gli3 are required for oligodendrocyte cell fate. Since Shh regulates Gli processing, if Smo is compromised or inhibited by Ptch1, this inactivates the Shh pathway and prevents Gli processing which disrupts glial cell fate mapping. Shh signaling in the FP region is very important because it needs to be active in order for gliogenesis to occur. If Shh is inactivated within the FP region and activated in other regions of the spinal cord such as the Dbx or pMN domains, gliogenesis is compromised. But, when Shh is active in the FP region, gliogenesis is activated and glial cells begin migrating to their targeted destinations to function.
Spinal cord injury and axon regeneration.
The floor plate region aids in axon guidance, glial fate mapping, and embryogenesis. If this area of the spinal cord becomes injured, there could be serious complications to all contributing functions of this region, namely limited proliferation and production of the glial cells responsible for myelination and phagocytosis in the CNS. Spinal cord injury (SCI) also most often results in axon denudation or severance. Wnt signaling is a common signaling pathway involved in injury cases. Wnt signaling regulates regeneration after spinal cord injury. Immediately following injury, Wnt expression dramatically increases. Axon guidance is driven by Netrin-1 in the FP region of the spinal cord. During injury cases, specifically cases of axon severance, Wnt signaling is upregulated and axons begin to initiate regeneration and the axons are reguided through the FP regions using Shh and Wnt signaling pathways.
The spinal cord ependymal cells also reside in the FP region of the spinal cord. These cells are a neural stem cell population responsible for repopulating lost cells during injury. These cells have the capacity to differentiate into progenitor glial populations. During injury, a factor entitled Akhirin is secreted in the FP region. During spinal cord development, Akhirin is expressed solely on ependymal stem cells with latent stem cell properties and plays a key role in the development of the spinal cord. In the absence of Akhirin, stemness of these ependymal cells is not regulated. Injury compromises Akhirin expression and regulation and the cells of the FP region cannot properly be restored by the ependymal stem cell populations.


Street scene

A street scene is a basic model for epic theater set forth by Bertolt Brecht. It makes use of a simple, "natural" incident, such as could be seen on any street corner: an eyewitness demonstrating to a collection of people how a traffic accident took place. "The bystanders may not have observed what happened, or they may simply not agree with him, may 'see things a different way'; the point is that the demonstrator acts the behavior of driver or victim both in such a way that the bystanders are able to form an opinion about the incident." This model is set forth as the most primitive type of epic theater to be easily understood by the reader or listener.


Orphan (car)

The term orphan car accurately applies to any marque of motor vehicle built by a manufacturer that has discontinued business entirely. The term is sometimes inaccurately applied to a "discontinued marque" from a still-existing vehicle manufacturer (e.g. Oldsmobile) or a sub-marque (e.g. Thunderbird). In the case of a revived marque where a newer company resuscitates a discontinued brand (e.g. Maybach), only the original vehicles are accurately considered orphans.


Intercostobrachial nerve

The intercostobrachial nerves are cutaneous branches of the intercostal nerves.
Second intercostal nerve.
The lateral cutaneous branch of the second intercostal nerve does not divide, like the others, into an anterior and a posterior branch; it is named the intercostobrachial nerve. It pierces the Intercostalis externus and the Serratus anterior, crosses the axilla to the medial side of the arm, and joins with a filament from the medial brachial cutaneous nerve. It then pierces the fascia, and supplies the skin of the upper half of the medial and posterior part of the arm, communicating with the posterior brachial cutaneous branch of the radial nerve. It is often the source of referred cardiac pain.
The intercostabrachial nerve is also sometimes divided in axillary node clearance (ANC), such as that done for breast cancer surgery which requires the removal of the axillary nodes. Sensation to the cutaneous region supplied by the nerve is affected.
The size of the intercostobrachial nerve is in inverse relationship to that of the medial brachial cutaneous nerve.
Third intercostal nerve.
A second intercostobrachial nerve is frequently given off from the lateral cutaneous branch of the third intercostal; it supplies filaments to the axilla and medial side of the arm.


Neuron

A neuron or nerve cell is an electrically excitable cell that communicates with other cells via specialized connections called synapses. It is the main component of nervous tissue in all animals except sponges and placozoa. Plants and fungi do not have nerve cells.
Neurons are typically classified into three types based on their function. Sensory neurons respond to stimuli such as touch, sound, or light that affect the cells of the sensory organs, and they send signals to the spinal cord or brain. Motor neurons receive signals from the brain and spinal cord to control everything from muscle contractions to glandular output. Interneurons connect neurons to other neurons within the same region of the brain or spinal cord. A group of connected neurons is called a neural circuit.
A typical neuron consists of a cell body (soma), dendrites, and a single axon. The soma is usually compact. The axon and dendrites are filaments that extrude from it. Dendrites typically branch profusely and extend a few hundred micrometers from the soma. The axon leaves the soma at a swelling called the axon hillock, and travels for as far as 1 meter in humans or more in other species. It branches but usually maintains a constant diameter. At the farthest tip of the axon's branches are axon terminals, where the neuron can transmit a signal across the synapse to another cell. Neurons may lack dendrites or have no axon. The term neurite is used to describe either a dendrite or an axon, particularly when the cell is undifferentiated.
Most neurons receive signals via the dendrites and soma and send out signals down the axon. At the majority of synapses, signals cross from the axon of one neuron to a dendrite of another. However, synapses can connect an axon to another axon or a dendrite to another dendrite.
The signaling process is partly electrical and partly chemical. Neurons are electrically excitable, due to maintenance of voltage gradients across their membranes. If the voltage changes by a large enough amount over a short interval, the neuron generates an all-or-nothing electrochemical pulse called an action potential. This potential travels rapidly along the axon, and activates synaptic connections as it reaches them. Synaptic signals may be excitatory or inhibitory, increasing or reducing the net voltage that reaches the soma.
In most cases, neurons are generated by neural stem cells during brain development and childhood. Neurogenesis largely ceases during adulthood in most areas of the brain.
Nervous system.
Neurons are the primary components of the nervous system, along with the glial cells that give them structural and metabolic support. The nervous system is made up of the central nervous system, which includes the brain and spinal cord, and the peripheral nervous system, which includes the autonomic and somatic nervous systems. In vertebrates, the majority of neurons belong to the central nervous system, but some reside in peripheral ganglia, and many sensory neurons are situated in sensory organs such as the retina and cochlea.
Axons may bundle into fascicles that make up the nerves in the peripheral nervous system (like strands of wire make up cables). Bundles of axons in the central nervous system are called tracts.
Anatomy and histology.
Neurons are highly specialized for the processing and transmission of cellular signals. Given their diversity of functions performed in different parts of the nervous system, there is a wide variety in their shape, size, and electrochemical properties. For instance, the soma of a neuron can vary from 4 to 100 micrometers in diameter.
The accepted view of the neuron attributes dedicated functions to its various anatomical components; however, dendrites and axons often act in ways contrary to their so-called main function.
Axons and dendrites in the central nervous system are typically only about one micrometer thick, while some in the peripheral nervous system are much thicker. The soma is usually about 10–25 micrometers in diameter and often is not much larger than the cell nucleus it contains. The longest axon of a human motor neuron can be over a meter long, reaching from the base of the spine to the toes.
Sensory neurons can have axons that run from the toes to the posterior column of the spinal cord, over 1.5 meters in adults. Giraffes have single axons several meters in length running along the entire length of their necks. Much of what is known about axonal function comes from studying the squid giant axon, an ideal experimental preparation because of its relatively immense size (0.5–1 millimeters thick, several centimeters long).
Fully differentiated neurons are permanently postmitotic however, stem cells present in the adult brain may regenerate functional neurons throughout the life of an organism (see neurogenesis). Astrocytes are star-shaped glial cells. They have been observed to turn into neurons by virtue of their stem cell-like characteristic of pluripotency.
Membrane.
Like all animal cells, the cell body of every neuron is enclosed by a plasma membrane, a bilayer of lipid molecules with many types of protein structures embedded in it. A lipid bilayer is a powerful electrical insulator, but in neurons, many of the protein structures embedded in the membrane are electrically active. These include ion channels that permit electrically charged ions to flow across the membrane and ion pumps that chemically transport ions from one side of the membrane to the other. Most ion channels are permeable only to specific types of ions. Some ion channels are voltage gated, meaning that they can be switched between open and closed states by altering the voltage difference across the membrane. Others are chemically gated, meaning that they can be switched between open and closed states by interactions with chemicals that diffuse through the extracellular fluid. The ion materials include sodium, potassium, chloride, and calcium. The interactions between ion channels and ion pumps produce a voltage difference across the membrane, typically a bit less than 1/10 of a volt at baseline. This voltage has two functions: first, it provides a power source for an assortment of voltage-dependent protein machinery that is embedded in the membrane; second, it provides a basis for electrical signal transmission between different parts of the membrane.
Histology and internal structure.
Numerous microscopic clumps called Nissl bodies (or Nissl substance) are seen when nerve cell bodies are stained with a basophilic ("base-loving") dye. These structures consist of rough endoplasmic reticulum and associated ribosomal RNA. Named after German psychiatrist and neuropathologist Franz Nissl (1860–1919), they are involved in protein synthesis and their prominence can be explained by the fact that nerve cells are very metabolically active. Basophilic dyes such as aniline or (weakly) haematoxylin highlight negatively charged components, and so bind to the phosphate backbone of the ribosomal RNA.
The cell body of a neuron is supported by a complex mesh of structural proteins called neurofilaments, which together with neurotubules (neuronal microtubules) are assembled into larger neurofibrils. Some neurons also contain pigment granules, such as neuromelanin (a brownish-black pigment that is byproduct of synthesis of catecholamines), and lipofuscin (a yellowish-brown pigment), both of which accumulate with age. Other structural proteins that are important for neuronal function are actin and the tubulin of microtubules. Class III β-tubulin is found almost exclusively in neurons. Actin is predominately found at the tips of axons and dendrites during neuronal development. There the actin dynamics can be modulated via an interplay with microtubule.
There are different internal structural characteristics between axons and dendrites. Typical axons almost never contain ribosomes, except some in the initial segment. Dendrites contain granular endoplasmic reticulum or ribosomes, in diminishing amounts as the distance from the cell body increases.
Classification.
Neurons vary in shape and size and can be classified by their morphology and function. The anatomist Camillo Golgi grouped neurons into two types; type I with long axons used to move signals over long distances and type II with short axons, which can often be confused with dendrites. Type I cells can be further classified by the location of the soma. The basic morphology of type I neurons, represented by spinal motor neurons, consists of a cell body called the soma and a long thin axon covered by a myelin sheath. The dendritic tree wraps around the cell body and receives signals from other neurons. The end of the axon has branching axon terminals that release neurotransmitters into a gap called the synaptic cleft between the terminals and the dendrites of the next neuron.
Structural classification.
Polarity.
Most neurons can be anatomically characterized as:
Other.
Some unique neuronal types can be identified according to their location in the nervous system and distinct shape. Some examples are:
Functional classification.
Direction.
Afferent and efferent also refer generally to neurons that, respectively, bring information to or send information from the brain.
Action on other neurons.
A neuron affects other neurons by releasing a neurotransmitter that binds to chemical receptors. The effect upon the postsynaptic neuron is determined by the type of receptor that is activated, not by the presynaptic neuron or by the neurotransmitter. A neurotransmitter can be thought of as a key, and a receptor as a lock: the same neurotransmitter can activate multiple types of receptors. Receptors can be classified broadly as "excitatory" (causing an increase in firing rate), "inhibitory" (causing a decrease in firing rate), or "modulatory" (causing long-lasting effects not directly related to firing rate).
The two most common (90%+) neurotransmitters in the brain, glutamate and GABA, have largely consistent actions. Glutamate acts on several types of receptors, and has effects that are excitatory at ionotropic receptors and a modulatory effect at metabotropic receptors. Similarly, GABA acts on several types of receptors, but all of them have inhibitory effects (in adult animals, at least). Because of this consistency, it is common for neuroscientists to refer to cells that release glutamate as "excitatory neurons", and cells that release GABA as "inhibitory neurons". Some other types of neurons have consistent effects, for example, "excitatory" motor neurons in the spinal cord that release acetylcholine, and "inhibitory" spinal neurons that release glycine.
The distinction between excitatory and inhibitory neurotransmitters is not absolute. Rather, it depends on the class of chemical receptors present on the postsynaptic neuron. In principle, a single neuron, releasing a single neurotransmitter, can have excitatory effects on some targets, inhibitory effects on others, and modulatory effects on others still. For example, photoreceptor cells in the retina constantly release the neurotransmitter glutamate in the absence of light. So-called OFF bipolar cells are, like most neurons, excited by the released glutamate. However, neighboring target neurons called ON bipolar cells are instead inhibited by glutamate, because they lack typical ionotropic glutamate receptors and instead express a class of inhibitory metabotropic glutamate receptors. When light is present, the photoreceptors cease releasing glutamate, which relieves the ON bipolar cells from inhibition, activating them; this simultaneously removes the excitation from the OFF bipolar cells, silencing them.
It is possible to identify the type of inhibitory effect a presynaptic neuron will have on a postsynaptic neuron, based on the proteins the presynaptic neuron expresses. Parvalbumin-expressing neurons typically dampen the output signal of the postsynaptic neuron in the visual cortex, whereas somatostatin-expressing neurons typically block dendritic inputs to the postsynaptic neuron.
Discharge patterns.
Neurons have intrinsic electroresponsive properties like intrinsic transmembrane voltage oscillatory patterns. So neurons can be classified according to their electrophysiological characteristics:
Multimodel Classification.
Since 2012 there has been a push from the cellular and computational neuroscience community to come up with a universal classification of neurons that will apply to all neurons in the brain as well as across species. this is done by considering the 3 essential qualities of all neurons: electrophysiology, morphology, and the individual transcriptome of the cells. besides being universal this classification has the advantage of being able to classify astrocytes as well. A method called Patch-Seq in which all 3 qualities can be measured at once is used extensively by the Allen Institute for Brain Science.
Connectivity.
Neurons communicate with each other via synapses, where either the axon terminal of one cell contacts another neuron's dendrite, soma or, less commonly, axon. Neurons such as Purkinje cells in the cerebellum can have over 1000 dendritic branches, making connections with tens of thousands of other cells; other neurons, such as the magnocellular neurons of the supraoptic nucleus, have only one or two dendrites, each of which receives thousands of synapses.
Synapses can be excitatory or inhibitory, either increasing or decreasing activity in the target neuron, respectively. Some neurons also communicate via electrical synapses, which are direct, electrically conductive junctions between cells.
When an action potential reaches the axon terminal, it opens voltage-gated calcium channels, allowing calcium ions to enter the terminal. Calcium causes synaptic vesicles filled with neurotransmitter molecules to fuse with the membrane, releasing their contents into the synaptic cleft. The neurotransmitters diffuse across the synaptic cleft and activate receptors on the postsynaptic neuron. High cytosolic calcium in the axon terminal triggers mitochondrial calcium uptake, which, in turn, activates mitochondrial energy metabolism to produce ATP to support continuous neurotransmission.
An autapse is a synapse in which a neuron's axon connects to its own dendrites.
The human brain has some 8.6 x 1010 (eighty six billion) neurons. Each neuron has on average 7,000 synaptic connections to other neurons. It has been estimated that the brain of a three-year-old child has about 1015 synapses (1 quadrillion). This number declines with age, stabilizing by adulthood. Estimates vary for an adult, ranging from 1014 to 5 x 1014 synapses (100 to 500 trillion).
Mechanisms for propagating action potentials.
In 1937 John Zachary Young suggested that the squid giant axon could be used to study neuronal electrical properties. It is larger than but similar to human neurons, making it easier to study. By inserting electrodes into the squid giant axons, accurate measurements were made of the membrane potential.
The cell membrane of the axon and soma contain voltage-gated ion channels that allow the neuron to generate and propagate an electrical signal (an action potential). Some neurons also generate subthreshold membrane potential oscillations. These signals are generated and propagated by charge-carrying ions including sodium (Na+), potassium (K+), chloride (Cl−), and calcium (Ca2+).
Several stimuli can activate a neuron leading to electrical activity, including pressure, stretch, chemical transmitters, and changes of the electric potential across the cell membrane. Stimuli cause specific ion-channels within the cell membrane to open, leading to a flow of ions through the cell membrane, changing the membrane potential. Neurons must maintain the specific electrical properties that define their neuron type.
Thin neurons and axons require less metabolic expense to produce and carry action potentials, but thicker axons convey impulses more rapidly. To minimize metabolic expense while maintaining rapid conduction, many neurons have insulating sheaths of myelin around their axons. The sheaths are formed by glial cells: oligodendrocytes in the central nervous system and Schwann cells in the peripheral nervous system. The sheath enables action potentials to travel faster than in unmyelinated axons of the same diameter, whilst using less energy. The myelin sheath in peripheral nerves normally runs along the axon in sections about 1 mm long, punctuated by unsheathed nodes of Ranvier, which contain a high density of voltage-gated ion channels. Multiple sclerosis is a neurological disorder that results from demyelination of axons in the central nervous system.
Some neurons do not generate action potentials, but instead generate a graded electrical signal, which in turn causes graded neurotransmitter release. Such non-spiking neurons tend to be sensory neurons or interneurons, because they cannot carry signals long distances.
Neural coding.
Neural coding is concerned with how sensory and other information is represented in the brain by neurons. The main goal of studying neural coding is to characterize the relationship between the stimulus and the individual or ensemble neuronal responses, and the relationships among the electrical activities of the neurons within the ensemble. It is thought that neurons can encode both digital and analog information.
All-or-none principle.
The conduction of nerve impulses is an example of an all-or-none response. In other words, if a neuron responds at all, then it must respond completely. Greater intensity of stimulation, like brighter image/louder sound, does not produce a stronger signal, but can increase firing frequency. Receptors respond in different ways to stimuli. Slowly adapting or tonic receptors respond to steady stimulus and produce a steady rate of firing. Tonic receptors most often respond to increased intensity of stimulus by increasing their firing frequency, usually as a power function of stimulus plotted against impulses per second. This can be likened to an intrinsic property of light where greater intensity of a specific frequency (color) requires more photons, as the photons can't become "stronger" for a specific frequency.
Other receptor types include quickly adapting or phasic receptors, where firing decreases or stops with steady stimulus; examples include skin which, when touched causes neurons to fire, but if the object maintains even pressure, the neurons stop firing. The neurons of the skin and muscles that are responsive to pressure and vibration have filtering accessory structures that aid their function.
The pacinian corpuscle is one such structure. It has concentric layers like an onion, which form around the axon terminal. When pressure is applied and the corpuscle is deformed, mechanical stimulus is transferred to the axon, which fires. If the pressure is steady, stimulus ends; thus, typically these neurons respond with a transient depolarization during the initial deformation and again when the pressure is removed, which causes the corpuscle to change shape again. Other types of adaptation are important in extending the function of a number of other neurons.
Etymology and spelling.
The German anatomist Heinrich Wilhelm Waldeyer introduced the term "neuron" in 1891, based on the ancient Greek νεῦρον "neuron" 'sinew, cord, nerve'.
The word was adopted in French with the spelling "neurone". That spelling was also used by many writers in English, but has now become rare in American usage and uncommon in British usage.
History.
The neuron's place as the primary functional unit of the nervous system was first recognized in the late 19th century through the work of the Spanish anatomist Santiago Ramón y Cajal.
To make the structure of individual neurons visible, Ramón y Cajal improved a silver staining process that had been developed by Camillo Golgi. The improved process involves a technique called "double impregnation" and is still in use.
In 1888 Ramón y Cajal published a paper about the bird cerebellum. In this paper, he stated that he could not find evidence for anastomosis between axons and dendrites and called each nervous element "an absolutely autonomous canton." This became known as the neuron doctrine, one of the central tenets of modern neuroscience.
In 1891, the German anatomist Heinrich Wilhelm Waldeyer wrote a highly influential review of the neuron doctrine in which he introduced the term "neuron" to describe the anatomical and physiological unit of the nervous system.
The silver impregnation stains are a useful method for neuroanatomical investigations because, for reasons unknown, it stains only a small percentage of cells in a tissue, exposing the complete micro structure of individual neurons without much overlap from other cells.
Neuron doctrine.
The neuron doctrine is the now fundamental idea that neurons are the basic structural and functional units of the nervous system. The theory was put forward by Santiago Ramón y Cajal in the late 19th century. It held that neurons are discrete cells (not connected in a meshwork), acting as metabolically distinct units.
Later discoveries yielded refinements to the doctrine. For example, glial cells, which are non-neuronal, play an essential role in information processing. Also, electrical synapses are more common than previously thought, comprising direct, cytoplasmic connections between neurons. In fact, neurons can form even tighter couplings: the squid giant axon arises from the fusion of multiple axons.
Ramón y Cajal also postulated the Law of Dynamic Polarization, which states that a neuron receives signals at its dendrites and cell body and transmits them, as action potentials, along the axon in one direction: away from the cell body. The Law of Dynamic Polarization has important exceptions; dendrites can serve as synaptic output sites of neurons and axons can receive synaptic inputs.
Compartmental modelling of neurons.
Although neurons are often described of as "fundamental units" of the brain, they perform internal computations. Neurons integrate input within dendrites, and this complexity is lost in models that assume neurons to be a fundamental unit. Dendritic branches can be modeled as spatial compartments, whose activity is related due to passive membrane properties, but may also be different depending on input from synapses. Compartmental modelling of dendrites is especially helpful for understanding the behavior of neurons that are too small to record with electrodes, as is the case for "Drosophila melanogaster".
Neurons in the brain.
The number of neurons in the brain varies dramatically from species to species. In a human, there are an estimated 10–20 billion neurons in the cerebral cortex and 55–70 billion neurons in the cerebellum. By contrast, the nematode worm "Caenorhabditis elegans" has just 302 neurons, making it an ideal model organism as scientists have been able to map all of its neurons. The fruit fly "Drosophila melanogaster", a common subject in biological experiments, has around 100,000 neurons and exhibits many complex behaviors. Many properties of neurons, from the type of neurotransmitters used to ion channel composition, are maintained across species, allowing scientists to study processes occurring in more complex organisms in much simpler experimental systems.
Neurological disorders.
Charcot–Marie–Tooth disease (CMT) is a heterogeneous inherited disorder of nerves (neuropathy) that is characterized by loss of muscle tissue and touch sensation, predominantly in the feet and legs extending to the hands and arms in advanced stages. Presently incurable, this disease is one of the most common inherited neurological disorders, with 36 in 100,000 affected.
Alzheimer's disease (AD), also known simply as "Alzheimer's", is a neurodegenerative disease characterized by progressive cognitive deterioration, together with declining activities of daily living and neuropsychiatric symptoms or behavioral changes. The most striking early symptom is loss of short-term memory (amnesia), which usually manifests as minor forgetfulness that becomes steadily more pronounced with illness progression, with relative preservation of older memories. As the disorder progresses, cognitive (intellectual) impairment extends to the domains of language (aphasia), skilled movements (apraxia), and recognition (agnosia), and functions such as decision-making and planning become impaired.
Parkinson's disease (PD), also known as "Parkinson disease", is a degenerative disorder of the central nervous system that often impairs motor skills and speech. Parkinson's disease belongs to a group of conditions called movement disorders. It is characterized by muscle rigidity, tremor, a slowing of physical movement (bradykinesia), and in extreme cases, a loss of physical movement (akinesia). The primary symptoms are the results of decreased stimulation of the motor cortex by the basal ganglia, normally caused by the insufficient formation and action of dopamine, which is produced in the dopaminergic neurons of the brain. Secondary symptoms may include high level cognitive dysfunction and subtle language problems. PD is both chronic and progressive.
Myasthenia gravis is a neuromuscular disease leading to fluctuating muscle weakness and fatigability during simple activities. Weakness is typically caused by circulating antibodies that block acetylcholine receptors at the post-synaptic neuromuscular junction, inhibiting the stimulative effect of the neurotransmitter acetylcholine. Myasthenia is treated with immunosuppressants, cholinesterase inhibitors and, in selected cases, thymectomy.
Demyelination.
Demyelination is the act of demyelinating, or the loss of the myelin sheath insulating the nerves. When myelin degrades, conduction of signals along the nerve can be impaired or lost, and the nerve eventually withers. This leads to certain neurodegenerative disorders like multiple sclerosis and chronic inflammatory demyelinating polyneuropathy.
Axonal degeneration.
Although most injury responses include a calcium influx signaling to promote resealing of severed parts, axonal injuries initially lead to acute axonal degeneration, which is rapid separation of the proximal and distal ends, occurring within 30 minutes of injury. Degeneration follows with swelling of the axolemma, and eventually leads to bead like formation. Granular disintegration of the axonal cytoskeleton and inner organelles occurs after axolemma degradation. Early changes include accumulation of mitochondria in the paranodal regions at the site of injury. Endoplasmic reticulum degrades and mitochondria swell up and eventually disintegrate. The disintegration is dependent on ubiquitin and calpain proteases (caused by influx of calcium ion), suggesting that axonal degeneration is an active process that produces complete fragmentation. The process takes about roughly 24 hours in the PNS and longer in the CNS. The signaling pathways leading to axolemma degeneration are unknown.
Neurogenesis.
Neurons are born through the process of neurogenesis, in which neural stem cells divide to produce differentiated neurons. Once fully differentiated neurons are formed, they are no longer capable of undergoing mitosis. Neurogenesis primarily occurs in the embryo of most organisms.
Adult neurogenesis can occur and studies of the age of human neurons suggest that this process occurs only for a minority of cells, and that the vast majority of neurons in the neocortex forms before birth and persists without replacement. The extent to which adult neurogenesis exists in humans, and its contribution to cognition are controversial, with conflicting reports published in 2018.
The body contains a variety of stem cell types that have the capacity to differentiate into neurons. Researchers found a way to transform human skin cells into nerve cells using transdifferentiation, in which "cells are forced to adopt new identities".
During neurogenesis in the mammalian brain, progenitor and stem cells progress from proliferative divisions to differentiative divisions. This progression leads to the neurons and glia that populate cortical layers. Epigenetic modifications play a key role in regulating gene expression in differentiating neural stem cells, and are critical for cell fate determination in the developing and adult mammalian brain. Epigenetic modifications include DNA cytosine methylation to form 5-methylcytosine and 5-methylcytosine demethylation. These modifications are critical for cell fate determination in the developing and adult mammalian brain. DNA cytosine methylation is catalyzed by DNA methyltransferases (DNMTs). Methylcytosine demethylation is catalyzed in several stages by TET enzymes that carry out oxidative reactions (e.g. 5-methylcytosine to 5-hydroxymethylcytosine) and enzymes of the DNA base excision repair (BER) pathway.
At different stages of mammalian nervous system development two DNA repair processes are employed in the repair of DNA double-strand breaks. These pathways are homologous recombinational repair used in proliferating neural precursor cells, and non-homologous end joining used mainly at later developmental stages
Nerve regeneration.
Peripheral axons can regrow if they are severed, but one neuron cannot be functionally replaced by one of another type (Llinás' law).


Effector (biology)

In biochemistry, an effector molecule is usually a small molecule that selectively binds to a protein and regulates its biological activity. In this manner, effector molecules act as ligands that can increase or decrease enzyme activity, gene expression, or cell signaling. Effector molecules can also directly regulate the activity of some mRNA molecules (riboswitches).
In some cases, proteins can be considered to function as effector molecules, especially in cellular signal transduction cascades.
The term "effector" is used in other fields of biology. For instance, the effector end of a neuron is the terminus where an axon makes contact with the muscle or organ that it stimulates or suppresses.
Examples.
Allosteric effectors can bind to regulatory proteins involved in RNA transcription in order to change its activity. In this way activator proteins become active to bind to the DNA to promote RNA Polymerase and repressor proteins become inactive and RNA polymerase can bind to the DNA.
Bacterial effector proteins are injected by bacterial cells, usually pathogens, into the cells of their host. The injection is mediated by specialized secretion systems, e.g. the type III secretion system (TTSS or T3SS).
Fungal effectors are secreted by pathogenic or beneficial fungi into and around host cells by invasive hyphae to disable defense components or facilitate colonization. Protein secretion systems in fungi involve the Spitzenkörper.
Plant pathogenic fungi use two distinct effector secretion systems and each secretory pathway is specific to an effector family:


Retinal mosaic

Retinal mosaic is the name given to the distribution of any particular type of neuron across any particular layer in the retina. Typically such distributions are somewhat regular; it is thought that this is so that each part of the retina is served by each type of neuron in processing visual information.
The regularity of retinal mosaics can be quantitatively studied by modelling the mosaic as a spatial point pattern. This is done by treating each cell as a single point and using spatial statistics such as the Effective Radius, Packing Factor and Regularity Index.
Using adaptive optics, it is nowadays possible to image the photoreceptor mosaic (i.e. the distribution of rods and cones) in living humans, enabling the detailed study of photoreceptor density and arrangement across the retina.
In the fovea (where photoreceptor density is highest) the spacing between adjacent receptors is about 6-8 micrometer. This corresponds to an angular resolution of approximately 0.5 arc minute, effectively the upper limit of human visual acuity.


Obligate

As an adjective, obligate means "by necessity" (antonym "facultative") and is used mainly in biology in phrases such as:


Stub period

In finance, in particular with reference to bonds and swaps, a stub period is a length of time over which interest accrues are not equal to the usual interval between bond coupons.
These periods normally occur because the interval between coupons does not fit neatly into the period for which the bond was issued, thus sometimes a bond's final or first coupon period may be adjusted to make the bond start and mature on the desired dates.


Moracizine

Moracizine or moricizine, sold under the trade name Ethmozine, is an antiarrhythmic of class IC. It was used for the prophylaxis and treatment of serious and life-threatening ventricular arrhythmias, but was withdrawn in 2007 for commercial reasons.
Pharmacology.
Moracizine, a phenothiazine derivative, undergoes extensive first-pass metabolism and is also extensively metabolized after it has entered the circulation. It may have pharmacologically active metabolites. A clinical study has shown that moracizine is slightly less effective than encainide or flecainide in suppressing ventricular premature depolarizations. Compared with disopyramide and quinidine, moracizine was equally or more effective in suppressing premature ventricular contractions, couplets, and nonsustained ventricular tachycardia.
In the Cardiac Arrhythmia Suppression Trial (CAST), a large study testing the influence of antiarrhythmics on mortality, showed a statistically non-significant increase of mortality from 5.4 to 7.2% under moracizine. This is in line with other class IC antiarrhythmics.


Ansa cervicalis

The ansa cervicalis (or ansa hypoglossi in older literature) is a loop of nerves that are part of the cervical plexus. It lies superficial to the internal jugular vein in the carotid triangle. Its name means "handle of the neck" in Latin.
Branches from the ansa cervicalis innervate most of the infrahyoid muscles, including the sternothyroid muscle, sternohyoid muscle, and the omohyoid muscle. Note that the thyrohyoid muscle, which is also an infrahyoid muscle and the geniohyoid muscle which is a suprahyoid muscle are innervated by cervical spinal nerve 1 via the hypoglossal nerve.
Roots.
Two roots make up the ansa cervicalis, a superior root, and an inferior root.
The superior root of the ansa cervicalis is formed from cervical spinal nerve 1 of the cervical plexus. These nerve fibers travel in the hypoglossal nerve before separating in the carotid triangle to form the superior root.
The superior root goes around the occipital artery and then descends on the carotid sheath. It sends off branches to the superior belly of the omohyoid muscle, and the upper parts of the sternothyroid and sternohyoid muscles and is then joined by the inferior root.
The inferior root of the ansa cervicalis, also known as descendens cervicalis, is formed by fibers from spinal nerves C2 and C3.
The inferior root gives off branches to the inferior belly of the omohyoid muscle, and the lower parts of the sternothyroid and sternohyoid muscles.


Ordinary (lecture)

An Ordinary was a type of lecture given in universities of the Middle Ages. Lectures were distinguished by the time of day they were conducted: an "ordinary" was conducted by fully qualified professors on fundamental texts in the morning, while "extraordinary" lectures were given in the afternoon by bachelors (the medieval equivalent of a graduate student) on less important texts.


Nose whistle

A nose whistle (also called a "nose flute" or a "humanatone") is a wind instrument played with the nose and mouth cavity. Often made of wood, they are also constructed with plastic, clay, or sheet metal.
History.
Nose whistles were used traditionally by various South American indigenous groups in the Amazon rainforest, such as the Nambikwara. While representing fertility or war by some groups within the Nambikwara, the nose flute ("ta tãu sư" in Nambikwaran) was not used as a ritual instrument, and was more commonly a children's toy. The Piaroa by contrast used the instrument ("Chuvo" in Wötʰïhä tivene) alongside other flutes in ritual situations, where it represented masculinity and was played during wartime.
In spite of its ethnic background, models were conceived and patented in the 19th and 20th centuries. James J. Stivers, co-founder of the Humanatone Company, is credited to coining this instrument as a "Humanatone". Operating out of New York City, his nose whistles were made of tin plates.
Today, nose whistles are often sold as children's novelties and are made of plastic, although enthusiasts use techniques to modify instruments for easier use by adults, as well as better sound. Using beeswax to extend the nose cup to accommodate an adult's larger maxilla is one such technique.
Acoustics.
The nose blows air into the instrument's open nose cup, from where it is channeled through an air duct towards a sharp edge (fipple) positioned over the player's mouth opening. The placement of the edge helps to create a vortex that excites the acoustic field into the player's mouth cavity. The pitch and tone is then changed by the musician via moving their mouth and tongue, as well as variating air flow, and perhaps also using a small hole in the plate for a tremolo. As the mouth cavity is the functional resonance chamber determining the tone of the instrument (as opposed to the chamber's volume being altered by holes or buttons, as is the case with flutes and recorders), the nose whistle produces tones along a glissando.


Wasabi receptor toxin

Wasabi receptor toxin (WaTx) is the active component of the venom of the Australian black rock scorpion "Urodacus manicatus". WaTx targets TRPA1, also known as the wasabi receptor or irritant receptor. WaTx is a cell-penetrating toxin that stabilizes the TRPA1 channel open state while reducing its Ca2+-permeability, thereby eliciting pain and pain hypersensitivity without the neurogenic inflammation that typically occurs in other animal toxins.
Etymology.
This scorpion toxin was named WaTx because it targets TRPA1 in a similar fashion as plant-derived irritants, such as mustard oil and wasabi. These irritants activate the TRPA1 channel in peripheral primary afferent sensory neurons, subsequently eliciting their pungent taste as well as sinus clearing and eye stinging.
Sources.
WaTx originates from the venom of the Australian Black Rock Scorpion ("Urodacus manicatus").
Chemistry.
Family.
WaTx belongs to the κ-KTx family, as it shows similarities in the disulfide bonding pattern. The KTx family is classified into four subfamilies: α-, β-, γ-, and κ-KTx. Unlike other KTx subfamilies, κ-KTx scorpion toxins form cysteine-stabilized α-helical hairpins (Cs α/α), whereas κ-KTx spider and crab toxins form cysteine-stabilized antiparallel β-sheets (Cs β/β).
Structure.
WaTx is a macromolecule with an estimated weight of 3.86 kDa, which consists of 33 amino-acid residues. Its amino-acid sequence is as follows:
The pattern of cysteine residues in the amino acid sequence, which is underlined above, indicates an independent Cys1-Cys4, Cys2-Cys3 disulfide bonding pattern. The two disulfide bridges connect two parallel α-helices with a β-turn. The disulfide bonding pattern stabilizes the rigid and compact helical hairpin structure at two points, contributing to the stable tertiary structure of the protein.
The hairpin contains four basic residues that enable passive diffusion across the membrane. Two features of the protein structure have been associated with cell-penetrating properties that are uncommon for peptide toxins. Firstly, a patch (or predominance) of basic residues is located at the open end of the hairpin, where the amino- and carboxy-terminal meet. Secondly, the amino-terminal in WaTx exhibits a dense dipole moment. Other proteins with the ability to penetrate the plasma membrane include HIV Tat and "Drosophila" penetratin. However, these proteins have no sequence resemblance to WaTx.
Homology.
The amino-acid sequence of WaTx bears little resemblance to other peptides in terms of homology. Although the toxin was discovered to be cell-penetrating, there is no sequence similarity to classical cell-penetrating peptides (CPPs).
Target.
WaTx targets TRPA1, one of about 30 transient receptor potential channels. WaTx is both potent and selective for TRPA1. Other known TRP-channels are not activated by the toxin. WaTx has an effect on human TRPA1 (hTRPA1), while it does not have an effect on to rat and snake TRPA1 (rsTRPA1).
Mode of action.
WaTx penetrates the plasma membrane instead of following standard routes, subsequently accessing the inferior part of the cell. The basic residues and dipole moment on the helical hairpin structure enable the passive diffusion of WaTx.
Once the toxin arrives in the cell, it activates TRPA1 via an intracellular domain in the lower part of voltage-sensing segments S1-S4 called ‘the allosteric nexus’. The allosteric nexus is located at the region where the TRP-like domain, pre-S1 helix and cysteine-rich S4-S5 linker meet. This inner cavity is a common binding site to reactive electrophilic ligands—and now WaTx. This locus is a key regulatory site for stimulus integration and propagates conformational changes to the channel’s gate. When activated, the open-state TRPA1 allows the flow of positively charged sodium and calcium ions into the cell.
Electrophilic ligands make covalent modifications to specific cysteine residues in the cytoplasmic amino-terminus that increase the probability of channel opening. Although both Na+ and Ca2+ can enter TRPA1, the channel normally has a preference towards Ca2+ and the intracellular calcium concentration increases more rapidly than the sodium concentration. WaTx interacts differently with the channel compared to reactive electrophiles. WaTx non-covalently binds to the allosteric nexus and initiates interactions with an integrated complex between the N-terminal cysteine-rich linker (S4-S5) and C-terminal TRP-like domains. This prevents the open channel from closing, as opposed to increasing the probability of opening, and results in a prolonged duration of the channel's open state. With WaTx bound in open state, TRPA1 lacks a preference for Ca2+ over Na+, which accounts for the lower calcium permeability. Consequently, both electrophilic ligands and WaTx trigger a pain response, but the calcium levels that result from WaTx are too low to initiate subsequent neuropeptide release and neurogenic inflammation. This suggests that WaTx may act only to open the ion permeation gate of TRPA1, without dilating the selectivity filter (dilation of the selectivity filter having been proposed to underlie enhanced calcium permeability of TRPA1 after activation by classical electrophilic irritants).
Toxicity.
WaTx elicits acute thermal and mechanical hypersensitivity. This response has been proven phenotypically proven by injecting WaTx in the hind paw of mice, which leads to dose-dependent nocifensive behavior. However, WaTx does not cause the local edema that is typical for noxious electrophiles. This lack of swelling indicates that WaTx fails to promote the release of calcitonin gene-related peptide (CGRP)—a hallmark of neurogenic inflammation.
Treatment.
There is no immediate danger after being stung by an Australian Black Rock Scorpion. The wound should be washed and cleaned, after which medical advice should be sought.
Therapeutic use.
So far, there are no pharmacologicals based on (the mode of action of) WaTx. However, understanding the mechanisms of WaTx’s interaction with TRPA1 may aid in the development of therapeutics targeting TRPA1, which is considered a promising target for treating pain, itch and neurogenic inflammation syndromes that involve nociception.


Hippocampus anatomy

Hippocampus anatomy describes the physical aspects and properties of the hippocampus, a neural structure in the medial temporal lobe of the brain. It has a distinctive, curved shape that has been likened to the sea-horse monster of Greek mythology and the ram's horns of Amun in Egyptian mythology. This general layout holds across the full range of mammalian species, from hedgehog to human, although the details vary. For example, in the rat, the two hippocampi look similar to a pair of bananas, joined at the stems. In primate brains, including humans, the portion of the hippocampus near the base of the temporal lobe is much broader than the part at the top. Due to the three-dimensional curvature of this structure, two-dimensional sections such as shown are commonly seen. Neuroimaging pictures can show a number of different shapes, depending on the angle and location of the cut.
Topologically, the surface of a cerebral hemisphere can be regarded as a sphere with an indentation where it attaches to the midbrain. The structures that line the edge of the hole collectively make up the so-called limbic system (Latin "limbus" =
"border"), with the hippocampus lining the posterior edge of this hole. These limbic structures include the hippocampus, cingulate cortex, olfactory cortex, and amygdala. Paul MacLean once suggested, as part of his triune brain theory, that the limbic structures constitute the neural basis of emotion. While most neuroscientists no longer believe in the concept of a unified "limbic system", these regions are highly interconnected and do interact with one another.
Basic hippocampal circuit.
Starting at the dentate gyrus and working inward along the S-curve of the hippocampus means traversing a
series of narrow zones. The first of these, the dentate gyrus (DG), is actually a separate
structure, a tightly packed layer of small granule cells wrapped around the end of the hippocampus proper, forming a pointed wedge in some cross-sections, a semicircle in others. Next
come a series of "Cornu Ammonis" areas: first CA4 (which underlies the dentate gyrus), then CA3, then
a very small zone called CA2, then CA1. The CA areas are all filled with densely packed Pyramidal cells similar to those found in the neocortex. After CA1 comes an area called the subiculum. After this comes a pair of ill-defined areas called the presubiculum and parasubiculum, then a
transition to the cortex proper (mostly the entorhinal area of the cortex). Most anatomists
use the term "hippocampus proper" to refer to the four CA fields, and hippocampal formation
to refer to the hippocampus proper plus dentate gyrus and subiculum.
The major signaling pathways flow through the hippocampus and combine to form a loop. Most external input comes from the adjoining entorhinal cortex, via the axons of the so-called perforant path. These axons arise from layer 2 of the entorhinal cortex (EC), and terminate in the dentate gyrus and CA3. There is also a distinct pathway from layer 3 of the EC directly to CA1, often referred to as the temporoammonic or TA-CA1 pathway. Granule cells of the DG send their axons (called "mossy fibers") to CA3. Pyramidal cells of CA3 send their axons to CA1. Pyramidal cells of CA1 send their axons to the subiculum and deep layers of the EC. Subicular neurons send their axons mainly to the EC. The perforant path-to-dentate gyrus-to-CA3-to-CA1 was called the trisynaptic circuit by Per Andersen, who noted that thin slices could be cut out of the hippocampus perpendicular to its long axis, in a way that preserves all of these connections. This observation was the basis of his "lamellar hypothesis", which proposed that the hippocampus can be thought of as a series of parallel strips, operating in a functionally independent way. The lamellar concept is still sometimes considered to be a useful organizing principle, but more recent data, showing extensive longitudinal connections within the hippocampal system, have required it to be substantially modified.
Perforant path input from EC layer II enters the dentate gyrus and is relayed to region CA3 (and to mossy cells, located in the hilus of the dentate gyrus, which then send information to distant portions of the dentate gyrus where the cycle is repeated). Region CA3 combines this input with signals from EC layer II and sends extensive connections within the region and also sends connections to strata radiatum and oriens of ipsilateral and contralateral CA1 regions through a set of fibers called the Schaffer collaterals, and commissural
pathway, respectively. Region CA1 receives input from the CA3 subfield, EC layer III and the nucleus reuniens of the thalamus (which project only to the terminal apical dendritic tufts in the stratum lacunosum-moleculare). In turn, CA1 projects to the subiculum as well as sending information along the aforementioned output paths of the hippocampus. The subiculum is the final stage in the pathway, combining information from the CA1 projection and EC layer III to also send information along the output pathways of the hippocampus.
The hippocampus also receives a number of subcortical inputs. In "Macaca fascicularis", these inputs include the amygdala (specifically the anterior amygdaloid area, the basolateral nucleus, and the periamygdaloid cortex), the medial septum and the diagonal band of Broca, the claustrum, the substantia innominata and the basal nucleus of Meynert, the thalamus (including the anterior nuclear complex, the laterodorsal nucleus, the paraventricular and parataenial nuclei, the nucleus reuniens, and the nucleus centralis medialis), the lateral preoptic and lateral hypothalamic areas, the supramammillary and retromammillary regions, the ventral tegmental area, the tegmental reticular fields, the raphe nuclei (the nucleus centralis superior and the dorsal raphe nucleus), the nucleus reticularis tegementi pontis, the periaqueductal gray, the dorsal tegmental nucleus, and the locus coeruleus.
The hippocampus also receives direct monosynaptic projections from the cerebellar fastigial nucleus.
Major fiber systems in the rat.
Angular bundle.
These fibers start from the ventral part of entorhinal cortex (EC) and contain commissural (EC◀▶Hippocampus) and Perforant path (excitatory EC▶CA1, and inhibitory EC◀▶CA2) fibers. They travel along the septotemporal axis of the hippocampus. Perforant path fibers, as the name suggests, perforate subiculum before going to the hippocampus (CA fields) and dentate gyrus.
Fimbria-fornix pathway.
Fimbria-fornix fibers are the hippocampal and subicular gateway "to" and "from" subcortical brain regions. Different parts of this system are given different names:
At the circuit level, the "alveus" contains axonal fibers from the DG and from Pyramidal neurons of CA3, CA2, CA1 and subiculum (CA1 ▶ subiculum and CA1 ▶ entorhinal projections) that collect in the temporal hippocampus to form the fimbria/fornix, one of the major outputs of the hippocampus. In the rat, some medial and lateral entorhinal axons (entorhinal ▶ CA1 projection) pass through alveus towards the CA1 stratum lacunosum moleculare without making a significant number of en passant boutons on other CA1 layers (Temporoammonic alvear pathway). Contralateral entorhinal ▶ CA1 projections almost exclusively pass through alveus. The more septal the more ipsilateral entorhinal-CA1 projections that take alvear pathway (instead of perforant path). Although subiculum sends axonal projections to alveus, subiculum ▶ CA1 projection passes through strata oriens and moleculare of subiculum and CA1. Cholinergic and GABAergic projections from MS-DBB to CA1 also pass through Fimbria. Fimbria stimulation leads to cholinergic excitation of CA1 O-LMR cells.
It is also known that extracellular stimulation of "fimbria" stimulates CA3 Pyramidal cells antidromically and orthodromically, but it has no impact on dentate granule cells. Each CA1 Pyramidal cell also sends an axonal branch to fimbria.
Hippocampal commissures.
Hilar mossy cells and CA3 Pyramidal cells are the main origins of hippocampal commissural fibers. They pass through hippocampal commissures to reach contralateral regions of hippocampus. Hippocampal commissures have dorsal and ventral segments. Dorsal commissural fibers consists mainly of entorhinal and presubicular fibers to or from the hippocampus and dentate gyrus. As a rule of thumb, one could say that each cytoarchitectonic field that contributes to the commissural projection also has a parallel associational fiber that terminates in the ipsilateral hippocampus. The inner molecular layer of dentate gyrus (dendrites of both granule cells and GABAergic interneurons) receives a projection that has both associational and commissural fibers mainly from hilar mossy cells and to some extent from CA3c Pyramidal cells. Because this projection fibers originate from both ipsilateral and contralateral sides of hippocampus they are called associational/commissural projections. In fact, each mossy cell innervates both the ipsilateral and contralateral dentate gyrus. The well known trisynaptic circuit of the hippocampus spans mainly horizontally along the hippocampus. However, associational/commissural fibers, like CA2 Pyramidal cell associational projections, span mainly longitudinally (dorsoventrally) along the hippocampus.
Commissural fibers that originate from CA3 Pyramidal cells go to CA3, CA2 and CA1 regions. Like mossy cells, a single CA3 Pyramidal cell contributes to both commissural and associational fibers, and they terminate on both principal cells and interneurons. A weak commissural projection connects both CA1 regions together. Subiculum has no commissural inputs or outputs. In comparison with rodents, hippocampal commissural connections are much less abundant in the monkey and humans. Although excitatory cells are the main contributors to commissural pathways, a GABAergic component has been reported among their terminals which were traced back to hilus as origin. Stimulation of commissural fibers stimulates DG hilar perforant path-associated (HIPP) and CA3 trilaminar cells antidromically.
Hippocampal cells and layers.
Hippocampus proper.
The hippocampus proper is composed of a number of subfields. Though terminology varies among authors, the terms most frequently used are dentate gyrus and the cornu ammonis (literally "Amun's horns", abbreviated CA). The dentate gyrus contains the fascia dentata and the hilus, while the CA is differentiated into fields CA1, CA2, CA3, and CA4.
However, the region known as CA4 is in fact the "deep, polymorphic layer of the dentate gyrus" (as clarified by Theodor Blackstad (1956) and by David Amaral (1978)).
Cut in cross section, the hippocampus is a C-shaped structure that resembles a ram's horns. The name "cornu ammonis" refers to the Egyptian deity Amun, who has the head of a ram. The horned appearance of the hippocampus is caused by cell density differentials and the existence of varying degrees of neuronal fibers.
In rodents, the hippocampus is positioned so that, roughly, one end is near the top of the head (the dorsal or septal end) and one end near the bottom of the head (the ventral or temporal end). As shown in the figure, the structure itself is curved and subfields or regions are defined along the curve, from CA4 through CA1 (only CA3 and CA1 are labeled). The CA regions are also structured depthwise in clearly defined strata (or layers):
Dentate gyrus.
The dentate gyrus is composed of a similar series of strata:
For an up-to-date "knowledge base" of hippocampal formation neuronal types, their biomarker profile, active and passive electrophysiological parameters, and connectivity one can refer to Hippocampome.org.


Hot stamping

Hot stamping or foil stamping is a printing method of relief printing in which pre-dried ink or foils are transferred to a surface at high temperatures. The method has diversified since its rise to prominence in the 19th century to include a variety of processes. After the 1970s, hot stamping became one of the most important methods of decoration on the surface of plastic products.
Process.
In a hot stamping machine, a die is mounted and heated, with the product to be stamped placed beneath it. A metallized or painted roll-leaf carrier is inserted between the two, and the die presses down through it. The dry paint or foil used is impressed into the surface of the product. The dye-stamping process itself is non-polluting because the materials involved are dry. Pressure and heat cause the relevant sections of the foil to become detached from the carrier material and become bonded with the printing surface.
Tools.
Along with foil stamping machines, among the commonly used tools in hot stamping are dies and foil. Dies may be made of metal or silicone rubber, and they may be shaped directly or cast. They can carry high levels of detail to be transferred to the surface and may be shaped to accommodate irregularities in the surface.
Foils are multilayered coatings that transfer to the surface of the product. Non-metallic foils consist of an adherence base, a color layer, and a release layer. Metallic foils replace the color layer with a layer of chrome or vacuum-metallized aluminum. Metallic foil construction has a metal-like sheen and is available in different metal shades such as gold, silver, bronze, and copper. Pigment foil does not have a metallic sheen but may be glossy or matte. Holographic foil paper includes a 3-dimensional image to provide a distinctive appearance to specific areas of a digitally printed application. Printing is often done on leather or paper.
Different hot stamping machines serve different purposes, but the most common hot stamping machines are simple up-and-down presses. Three of the most common brands are Kwikprint, Kingsley, and Howard. However, for more industrial applications Kluge and Heidelberg presses are more commonly used.
History.
In the 19th century, hot stamping became a popular method of applying gold tooling or embossing in book printing on leather and paper. The first patent for hot stamping was recorded in Germany by Ernst Oeser in 1892.
From the 1950s onward, the method became a popular means of marking plastic . Hot Stamping technology for plastic is used for electric components (TV frames, audio components, refrigerators etc), cosmetic containers (lipstick, cream, mascara, shampoo bottle etc), automobile parts (interior and exterior materials).
As of 1998, it was one of the most commonly used methods of security printing.
Foil stamping can be used to make Radio-frequency identification (RFID) tags, although screen printing is faster and cheaper.


Orestrate

Orestrate (), also known as estradiol 3-propionate 17β-(1-cyclohexenyl) ether, is an estrogen medication and estrogen ester which was never marketed. It is the C3 propionate ester and C17β-(1-cyclohexenyl) ether of estradiol.


Ventral posteromedial nucleus

The ventral posteromedial nucleus (VPM) is a nucleus of the thalamus.
Inputs and outputs.
The VPM contains synapses between second and third order neurons from the anterior (ventral) trigeminothalamic tract and posterior (dorsal) trigeminothalamic tract. These neurons convey sensory information from the face and oral cavity. Third order neurons in the trigeminothalamic systems project to the postcentral gyrus.
The VPM also receives taste afferent information from the solitary tract and projects to the cortical gustatory area.
Subareas.
VPMpc.
The parvicellular part of the ventroposterior medial nucleus (VPMpc) is argued by some as not an actually part of the VPM, because it does not project to the somatosensory cortex as the remainder of the VPM does, and therefore should be called the ventromedial nucleus (VMb) instead.


Journal of Clinical Neurophysiology

The Journal of Clinical Neurophysiology is a bimonthly peer-reviewed medical journal covering clinical neurophysiology. It was established in 1984. It is the official journal of the American Clinical Neurophysiology Society (previously the American Electroencephalographic Society). It is published by Lippincott Williams & Wilkins and the editor-in-chief is Aatif M. Husain (Duke University).
Abstracting and indexing.
The journal is abstracted and indexed in:
According to the "Journal Citation Reports", the journal has a 2017 impact factor of 1.982, ranking it 132nd out of 192 journals in the category "Clinical Neurology" and 201st out of 256 journals in the category "Neurosciences".


Perforant path

In the brain, the perforant path or perforant pathway provides a connectional route from the entorhinal cortex to all fields of the hippocampal formation, including the dentate gyrus, all CA fields (including CA1), and the subiculum.
Though it arises mainly from entorhinal layers II and III, the perforant path comprises a smaller component that originates in deep layers V and VI.
There is a major dichotomy with respect to the laminar origin and related terminal distribution: neurons in layer II (and possibly layer VI) project to the dentate gyrus and CA3, whereas layer III (and possibly layer V) cells project to CA1 and the subiculum via the temporoammonic pathway.
In addition to playing a role in spatial memory learning generally, the temporoammonic branch (TA-CA1) of the perforant path mediates spatial memory consolidation. The temporoammonic pathway has also been implicated in stress-based animal models of depression.
It may also play a role in temporal lobe seizures.
In rats.
In rats, pyramidal and stellate cells in layer II of entorhinal cortex project through the subiculum of the hippocampus, giving rise to the name "perforant pathway". These glutamatergic fibers form a laminar pattern and terminate in the dentate gyrus and cornu ammonis 3 (CA3) region of the hippocampus. Fibers arising in the lateral portions of the entorhinal cortex show enkephalin immunoreactivity, whereas medial portions appear to contain cholecystokinin. Additionally, pyramidal cells in layer III of the entorhinal cortex send topographic projections along the perforant pathway which branch into the subiculum and CA1.
In mice.
In mice, the projection to CA1, and the subiculum all come primarily from EC layer III.
According to Suh et al. (2011 Science 334:1415) the projection to CA3 and dentate gyrus in mice is primarily from layer II of entorhinal cortex, and forms a trisynaptic path with hippocampus (dentate gyrus to CA3 to CA1), distinguished from the direct (monosynaptic) perforant path from Layer III of entorhinal cortex to CA1 and subiculum.


Bass saxophone

The bass saxophone is one of the largest members of the saxophone family—larger than the more commonly encountered baritone saxophone. The modern bass saxophone is a transposing instrument pitched in B, an octave below the tenor saxophone. The bass saxophone is not a commonly used instrument, but it is heard on some 1920s jazz recordings; in free jazz; in saxophone choirs; and occasionally in concert bands.
The instrument was first used in 1844, both by Hector Berlioz in an arrangement of his "Chant sacre", and by Georges Kastner in his opera "Le Dernier Roi de Juda". In the 1950s and 1960s it enjoyed a brief vogue in orchestrations for musical theater: Leonard Bernstein’s original score for "West Side Story" includes bass saxophone, as does Meredith Willson’s "Music Man" and Sandy Wilson’s "The Boy Friend". Australian composer Percy Grainger and American composer Warren Benson have championed the use of the instrument in their music for concert band.
Although bass saxophones in C were made for orchestral use, modern instruments are in B. This puts them a perfect fourth below the baritone and an octave lower than the tenor. Music is written in treble clef, just as for the other saxophones, with the pitches sounding two octaves and a major second lower than written. As with most other members of the saxophone family, the lowest written note is the B below the staff—sounding as a concert A in the first octave (~ 51.9 Hz). German wind instrument maker Benedikt Eppelsheim has made bass saxophones to low A, similarly to the extension in the baritone saxophone. This sounds as a concert G in the first octave (~ 49 Hz).
Until the start of the 21st century, the largest existing member of the saxophone family was the rare contrabass, pitched in E, a perfect fifth lower than the bass. Inventor Adolphe Sax had a patent for a subcontrabass saxophone (or "bourdon" saxophone), but apparently never built a fully functioning instrument. In 1999, Benedikt Eppelsheim introduced the subcontrabass tubax, a modified saxophone pitched in B an octave below the bass saxophone.
In jazz.
The bass saxophone enjoyed some measure of popularity in jazz combos and dance bands between World War I and World War II, primarily providing bass lines, although players occasionally took melodic solos. Notable players of this era include Billy Fowler, Coleman Hawkins, Otto Hardwicke (of the Duke Ellington orchestra), Adrian Rollini (who was a pioneer bass sax solos in the 1920s into the 1930s), Min Leibrook, Spencer Clark, Charlie Ventura and Vern Brown of the Six Brown Brothers. The bass sax became more scarce in standard jazz band instrumentation during the mid-to-late 1920s. Sheet music of the period shows many bands photographed with a bass sax in their collection of instruments. It was sometimes played by the tuba or string bass player rather a member of the sax section.
American bandleader Boyd Raeburn (1913–1966), who led an avant-garde big band in the 1940s, was a sometime bass saxophonist. In Britain, the leader of the Oscar Rabin Band also played it. Harry Gold, a member of Rabin's band, played bass saxophone in his own band, "Pieces of Eight". American bandleader Stan Kenton's "Mellophonium Orchestra" (1960–1963) featured fourteen brass players and used a saxophone section of one alto, two tenors, baritone, and bass on Johnny Richards' compositions. Joel Kaye played baritone and bass saxophone in that band. The ensemble recorded several successful albums, winning two Grammys. The Lawrence Welk Band featured Bill Page soloing on bass sax on several broadcasts during the 1960s. Shorty Rogers's "Swingin' Nutcracker" (recorded for RCA Victor in 1960) featured a bass saxophone on four of the movements (played by Bill Hood).
The 1970s traditional jazz band The Memphis Nighthawks built their sound around diminutive bass saxophonist Dave Feinman. Some revivalist bass saxophonists performing today in the 1920s–1930s style are Vince Giordano and Bert Brandsma, leader of the Dixieland Crackerjacks. Jazz players using the instrument in a more contemporary style include Roscoe Mitchell, Anthony Braxton, Peter Brötzmann, J. D. Parran, Hamiet Bluiett, James Carter, Stefan Zeniuk, Michael Marcus (musician) Vinny Golia, Joseph Jarman, Brian Landrus, Urs Leimgruber, Tony Bevan, and Scott Robinson, although none of these players use it as their primary instrument.
Jan Garbarek plays a bass sax on the 1973 album Red Lanta.
In rock.
Bass saxophonists in rock include:
In classical music.
The bass saxophone is sometimes used as an instrument in concert bands, typically in arrangements made before 1950. It is used most frequently in saxophone choirs, specifically those in the direct legacy of teacher-soloist Sigurd Rascher.
It is rarely used in orchestral music, though several examples exist. The earliest extant work to employ it is William Henry Fry's "sacred symphony" "Hagar In the Wilderness" (1853), which also calls for soprano saxophone and was written for Louis-Antoine Jullien's orchestra during its American tour. It was also used by Richard Strauss in his "Sinfonia Domestica", where included in the music are parts for four saxophones including a bass saxophone in C. Arnold Schoenberg wrote for the bass sax in his one-act opera "Von Heute auf Morgen", and Karlheinz Stockhausen includes a part for it in the saxophone section of "Lucifer's Dance", the third scene of "Samstag aus Licht".


Multipolar neuron

A multipolar neuron is a type of neuron that possesses a single axon and many dendrites (and dendritic branches), allowing for the integration of a great deal of information from other neurons. These processes are projections from the neuron cell body. Multipolar neurons constitute the majority of neurons in the central nervous system. They include motor neurons and interneurons/relaying neurons are most commonly found in the cortex of the brain and the spinal cord. Peripherally, multipolar neurons are found in autonomic ganglia.


Thoraco-abdominal nerves

The anterior divisions of the seventh, eighth, ninth, tenth, and eleventh thoracic intercostal nerves are continued anteriorly from the intercostal spaces into the abdominal wall; hence they are named thoraco-abdominal nerves (or thoracicoabdominal intercostal nerves).
They have the same arrangement as the upper ones as far as the anterior ends of the intercostal spaces, where they pass behind the costal cartilages, and between the Obliquus internus and Transversus abdominis, to the sheath of the Rectus abdominis, which they perforate.
They supply the Rectus abdominis and end as the anterior cutaneous branches of the abdomen; they supply the skin of the front of the abdomen.
The lower intercostal nerves supply the Intercostales and abdominal muscles; the last three send branches to the Serratus posterior inferior. About the middle of their course they give off lateral cutaneous branches.
These pierce the Intercostales externi and the Obliquus externus abdominis, in the same line as the lateral cutaneous branches of the upper thoracic nerves, and divide into anterior and posterior branches, which are distributed to the skin of the abdomen and back; the anterior branches supply the digitations of the Obliquus externus abdominis, and extend downward and forward nearly as far as the margin of the Rectus abdominis; the posterior branches pass backward to supply the skin over the Latissimus dorsi.


Terbequinil

Terbequinil (SR-25776) is a stimulant and nootropic drug which acts as a partial inverse agonist at benzodiazepine sites on the GABAA receptor. In human trials it was found to partially reverse the sedative and amnestic effects of the hypnotic drug triazolam with only slight effects when administered by itself.


Gary M. Hieftje

Gary M. Hieftje is an analytical chemist, Distinguished Professor, and the Robert & Marjorie Mann Chair of Chemistry at Indiana University in Bloomington, Indiana. Gary M. Hieftje received his A.B. degree at Hope College in Holland, Michigan in 1964, and his PhD from University of Illinois at Urbana–Champaign in 1969. In 1969, he started his career in teaching and research at Indiana University. Hieftje was named a Distinguished Professor in 1985, and entered emeritus status in 2018. As of 2018, Dr. Hieftje has been involved in over 600 publications.
Research in the Hieftje Group mainly focuses on studying and improving the mechanisms and methods of atomic emission and absorption, fluorescence, and mass spectrometry. He also works to develop new methods of analysis for atoms, molecules, and biomolecules. His group even developed an online computer program to control their experiments. Some areas of interest to his research are: finding new applications of lasers, linear response theory, near-infrared correlation methods of analysis, time-resolved luminescence, and fiber-optic sensors.
He has received many awards in his career, including the American Chemical Society (ACS) Award in Analytical Chemistry sponsored by Fisher Scientific Company in 1987, and the Robert Boyle Prize for Analytical Science in 2010. Professor Hieftje has authored many books. Perhaps, the most well-known is “Chemical Separations and Measurements - The Theory and Practice of Analytical Chemistry” with colleagues Dennis G. Peters and John M. Hayes published by Saunders in Philadelphia in 1974.


Dyadic kinship term

Dyadic kinship terms (abbreviated or ) are kinship terms in a few languages that express the relationship between individuals as they relate one to the other. In English, there are a few set phrases for such situations, such as "they are father and son", but there is not a single "dyadic term" that can be used the way "they are cousins" can; even the latter is not truly dyadic, as it does not necessarily mean that they are cousins "to each other." The few, and uncommon, English dyadic terms involve in-laws: co-mothers-in-law, co-fathers-in-law, co-brothers-in-law, co-sisters-in-law, co-grandmothers, and co-grandfathers.
Examples of dyadic terms for blood kin include Kayardild (Australian) "ngamathu-ngarrba" "mother and child", derived from "ngamathu" "mother", and "kularrin-ngarrba" "brother and sister", from "kularrin" "cross-sibling", with the dyadic suffix "-ngarrba." Not all such terms are derived; the Ok language Mian has a single unanalysable root "lum" for "father and child".
Dyadic blood-kin terms are rare in Indo-European languages. Examples are Icelandic and Faroese, which have the terms "feðgar" "father and son", "feðgin" "father and daughter", "mæðgin" "mother and son", "mæðgur" "mother and daughter".
Chinese and Japanese use compound nouns to make dyadic terms, such as (in Japanese) 親子 "oyako" 'parent and child', 兄弟 "kyōdai" 'brothers; siblings', 姉妹 "shimai" 'sisters', and 夫婦 "fūfu" 'husband and wife'.
The languages which have such terms are concentrated in the western Pacific. There are at least ten in New Guinea, including Oksapmin, Menya, and the Ok languages; fifteen or more Austronesian languages, from Taiwan to New Caledonia; and at least sixty in Australia, such as Kayardild above. There are sporadic examples in Northern Eurasia, including a few Turkic and Uralic languages, Yukaghir, and Ainu; depending on definitions, the Yi languages of Southeast Asia may also be said to have such terms. Elsewhere they are rare, or at least have not been described. Known languages include Athabaskan (Koyukon and Carrier), Pomo, and Southern Paiute in North America, Quechua, Paezan (Nasa Yuwe), and Cariban (Tiriyo) in South America, Adyghe in the Caucasus, and Khoe (Kxoe, Gǀwi) in southern Africa.


Aureochromes

Aureochromes are blue light photoreceptors as well as transcription factors found only in stramenopiles so far.
Description.
It was first discovered in "Vaucheria frigida" in 2007 by Takahashi et.al. Photosynthetic eukaryotes mainly convert sunlight into energy via photosynthesis, but light also is important for movement and development, regulation of biological activities. The effective wavelength for light responses in photosynthetic eukaryotes is mainly in the red light (RL) and blue light (BL) regions (Mohr 1980; Furuya 1993). The red/far-red receptor phytochrome and phytochrome-mediated responses like suppression of hypocotyl growth have been studied intensively. BL-induced responses may include phototropism and chloroplast photo-relocation movement (Christie 2007). Various BL receptors have been discovered in green plants. Takahashi et.al isolated BL receptors from the Xanthophyceae alga, Vaucheria in 2007 and named it Aureochrome (Latin meaning: aureus = gold). This new class of blue light photoreceptors is unique in a way because of the presence of a bZIP (DNA binding domain) along with LOV (light perception) domain which makes it function as transcription factor as well as photoreceptor as shown by Takahashi et al. in 2007.
Four orthologues of aureochromes have been identified in model diatom "P. tricornutum", i.e. AUREO 1a, 1b, 1c and 2. Aureo1a recognizes the sequence TGACGT, which is the typical binding site for certain subfamilies of bZIP transcription factors. It was also shown that PtAUREO1a and 1c are regulated in a light-independent circadian rhythm and that they are capable of forming homodimers and heterodimers which recognize the ACGT core sequence within the aureochrome. The photoreactions of AUREO 1 protein have been studied recently by Tsuguyoshi et al (2011) and they concluded that the AUREO1-LOV exists in equilibrium between the monomer and dimer. Huysman et al. showed that Aureo1a is involved in regulation of expression of diatom-specific cyclin dsCYC2 which is involved in G1 to S phase transition after dark arrest in 2013. Aureo1a, indeed is shown to function as a repressor of high light acclimation.


William Hurst Rees

William Hurst Rees (12 April 1917 – 6 January 2004) was a leading British valuation surveyor, a Member of the Lands Tribunal from 1973 until his retirement in 1989. He was the originator and editor of the first five editions of "Valuation: Principles into Practice" (now in its sixth edition of 2008), the leading handbook for students and practitioners of valuation in the UK.
Bill Rees was born in Bushey, Hertfordshire and educated at Watford Grammar School for Boys. He began his professional life with Salter Rex & Co while studying for a professional degree at the College of Estate Management in London. During the Second World War he joined the Royal Artillery and later transferred to the Royal Engineers, with which he served during the Normandy landings. When discharged after the war he had achieved the rank of Major.
After the war he became a lecturer at the College of Estate Management, the leading British institution of higher learning in the fields of property, and from 1948 to 1951 was Head of the Valuation Department. In 1949 he became joint author, with David Lawrence and Harold May, of the second edition of "Modern Methods of Valuation" and subsequently edited the next four editions. In 1951 he moved to Richard Ellis as head of the valuation department. During this period he acted for Mrs Harvey in the "Harvey" v "Crawley" case, which gave rise to the concept of Crawley costs. In 1961 he became senior partner of Turner Rudge & Turner, where he stayed until he became a member of the Lands Tribunal in 1973, where he gave lead decisions in a number of important cases. In 1978 he devised and edited the first five editions of "Valuation: Principles into Practice".


Isradipine

Isradipine (tradenames DynaCirc, Prescal) is a calcium channel blocker of the dihydropyridine class. It is usually prescribed for the treatment of high blood pressure in order to reduce the risk of stroke and heart attack.
It was patented in 1978 and approved for medical use in 1989.
Medical uses.
Isradipine is given as either a 2.5 mg or 5 mg capsule.
Side effects.
Common side effects include:
Serious side effects include:
Drug interactions.
It is advised that those using Isradipine not take Anzemet (Dolasetron), as both agents can cause a dose-dependent PR interval and QRS complex prolongation.
Itraconazole exhibits a negative inotropic effect on the heart and thus could spur an additive effect when used concomitantly with Isradipine. Onmel/Sporanox also inhibits an important cytochrome liver enzyme (CYP 450 3A4) which is needed to metabolize Isradipine and other Calcium Channel Blockers. This will increase plasma levels of Isradipine and could cause an unintentional overdose of the medication. Caution is advised when administering both agents together.
Tizanidine demonstrates anti-hypertensive effects and should be avoided in patients taking Isradipine due to the possibility of synergism between both medications.
The anti-biotic Rifampin lowered plasma concentrations of Isradipine to below detectable limits.
Cimetidine increased Isradipine mean peak plasma levels. A downward dose adjustment may be necessary with this particular instance of polypharmacy.
Severe hypotension was reported with Fentanyl anesthesia when it was combined with other Calcium Channel Blockers. Even though Isradipine, another Calcium Channel Blocker, has not been used in conjunction with Fentanyl anesthesia in any studies, caution is advised.
"Note: There was no significant interaction between Isradipine and Warfarin (Coumadin), Isradipine and Microzide Hydrochlorothiazide, Isradipine and Lanoxin (Digoxin), and Isradipine and Nitrostat (Nitroglycerin)."
Overdose.
Symptoms of an Isradipine overdose include:
Stereochemistry.
Isradipine contains a stereocenter and consists of two enantiomers, more precisely atropisomers. This is a racemate, i.e. a 1: 1 mixture of (" R ") - and the (" S ") - Form:


Propaedeutics

Propaedeutics or propedeutics (from Ancient Greek , "propaídeusis", "preparatory education") is a historical term for an introductory course into an art or science. The etymology of propedeutics comprises the Latin prefix "pro", meaning earlier, rudimentary, or in front of, and the Greek "paideutikós", which means "pertaining to teaching". As implied by the etymology, propaedeutics may be defined more particularly as the knowledge necessary before, or for the learning of, a discipline, but not which is sufficient for proficiency.
In medicine, the terms "propedeutics"/"propedeutic" specifically refers to the preliminary collection of data about a patient by observation, palpation, temperature measurement, etc., without specialized diagnostic procedures.
The 1851 "Encyclopaedia Americana" writes that it is:
...a term used by the Germans to indicate the knowledge which is necessary or useful for understanding
or practising an art or science, or which unfolds its nature and extent, and the method of learning it. It is applied,
therefore, not only to special introductions to particular branches of study, but also to auxiliary sciences, logic, philology, etc., and the encyclopaedic views of particular branches of science which facilitate
an insight into the relations of the parts. Such a survey can be presented only by one who has studied a science in
all its ramifications. The term propaedeutics is often, of course, merely relative : thus philology belongs to the propaedeutics of history, while it is itself the main study of a certain class of scholars. The term, however, in its common use, is generally restricted to the body of knowledge, and of rules necessary for the study of some particular science — rules which originate in the application of the general laws of science or art to a particular department.
Thus we find in the catalogues of lectures to be delivered in German universities medical propaedeutics, &c., enumerated.
Netherlands.
In the Netherlands, propedeuse (spelled propaedeuse until a spelling change of the Dutch language in 1996) is a propaedeutic diploma issued after the first year of studies, often referred to as "P" by students. Universities and "universities of applied sciences" are not forced by law to make use of this propaedeutic diploma, but it is quite common. The diploma is not a recognized degree and thus grants no rights outside the Dutch educational system. It has remained in use after the introduction of the Bologna process and the international bachelor-master system in the Netherlands.
When in use at an educational institution, the propaedeutic diploma is a mandatory diploma which a student acquires by successfully completing all subjects (60 credits) and study requirements of the first year. This first year is therefore also known as the "propedeuse" or the "propedeutische fase" (literally, "propaedeutical phase"). Some study programs require the student to score sufficient on an additional examination.
History.
The propaedeutic diploma was introduced as a means to determine whether students were suited for studying in the direction of their choice. and traditionally signifies that a student is officially accepted at a university. To symbolize this, schools may choose to organize an annual formal event where the propaedeutic diploma is awarded, mostly in early October, although this tradition is on a decline for financial reasons.
Educational reforms in 1982 emphasized the orientational, selecting and referring function. The difference between "hogescholen(university of applied sciences)" and universities was diminished so that the "propedeutische fase" became a commonly used name for the first year in all tertiary education. It became possible to enroll at university with a "hogeschool propaedeutic diploma". This method is often used by students who did not obtain the required secondary education. University students can also enroll at a different university or "hogeschool" for the same or a similar study program.
At the end of the first year, an educational institution is obligated to issue advice on a student's suitability, whether the institution awards the propaedeutic diploma or not. In the vast majority of cases, this will be positive advice. The two possible consequences of not obtaining the propaedeutic diploma in one year are a "negatief advies" (literally, "negative advice") which implies that the university or "hogeschool" recommends the student to enroll in a different study program, and a "bindend negatief advies" (literally, "binding negative advice") which prohibits the student from continuing or re-enrolling for the same study program at the institution. Furthermore, most "hogescholen (university of applied sciences)" have included in their statutes that should a student fail to meet the requirements for the propaedeutic diploma within a set period of time, usually set at two years, the student cannot continue to obtain a bachelor's degree.
Analogies.
In the UK, the Certificate of Higher Education is roughly equivalent to the propaedeutic diploma, being earned after the first year of the three-year course of study culminating in a baccalaureate degree.
In the US, the equivalent of the propaedeutic diploma lies somewhere between an undergraduate certificate and an associate degree. Undergraduate certificates can be completed in as little as one semester (one-half of one academic year or about four months) and do not necessarily lead or contribute to any degree. Associate degrees (e.g. AA, AS) are typically earned after the first two years of the four- to five-year (in the US) course of study culminating in a baccalaureate degree; however, students matriculated in a bachelor's degree program are not usually awarded the associate degree en route (as is often the case when a doctoral student is awarded a master's degree en route). Additionally, there are first professional associate degrees (e.g. AAS, AGS) that do not necessarily lead or contribute to a bachelor's.


Nuclei colliculi superioris

Nuclei colliculi superioris are groups of large cells in the middle gray layer of the superior colliculus and more laterally near the midbrain tegmentum.


VUF-8430

VUF-8430 is a histamine agonist selective for the H4 subtype.