Schaffer collateral

Schaffer collaterals are axon collaterals given off by CA3 pyramidal cells in the hippocampus. These collaterals project to area CA1 of the hippocampus and are an integral part of memory formation and the emotional network of the Papez circuit, and of the hippocampal trisynaptic loop. It is one of the most studied synapses in the world and named after the Hungarian anatomist-neurologist Károly Schaffer.
As a part of the hippocampal structures, Schaffer collaterals develop the limbic system, which plays a critical role in the aspects of learning and memory. The signals of information from the contralateral CA3 region leave via the Schaffer collateral pathways for the CA1 pyramidal neurons. Mature synapses contain fewer Schaffer collateral branches than those synapses that are not fully developed. Many scientists try to use the Schaffer collateral synapse as a sample synapse, a typical excitatory glutamatergic synapse in the cortex that has very well been studied in order to try to identify the rules of both the patterns of stimulation in electrical rules and the chemical mechanisms by which synapses get persistently stronger and which synapses get persistently weaker as well and to develop medication and treatment to cure the chronic diseases, such as dementia and Alzheimer's disease. Moreover, they believe that studying the Schaffer collateral can provide a whole range of understanding how Schaffer collaterals allow us to intervene with drug-treatments and with electrical-stimulation so that the quality of human experience can be improved.
Development.
"Schaffer collateral is the conductor of the orchestra, but not the actual instrument that plays the music" -
Dr. Patrick K. Stanton . The functional hippocampus stores long-term memories through synaptic plasticity in terms of storing information. The hippocampus in communication with the neocortex mediates memory degradation. Plastic changes occurring in the hippocampus are involved in directing the process of memory storage.
The Schaffer collateral is involved in activity-dependent plasticity and the information processes that always are processed through the hippocampus all the time. The Schaffer collateral clearly affects whether the target cells fire action potentials or not. However, at the same time, it is triggering the process that takes much longer whereby some synapses get stronger and some get weaker, and overall the patterns of synaptic strength of the network all evolve over time.
Moreover, Schaffer collateral axons develop excitatory synapses that are scattered over the dendritic arborization of hippocampal CA1 pyramidal neurons. In the early stage of long-term potentiation, Schaffer collaterals release glutamate that binds to AMPA receptors of CA1-dendrites. The process of developing a network of CA3-to-CA1 recurrent excitatory glutamatergic synapses alters the frequency of spontaneous action potentials in Schaffer collaterals. By adulthood, CA3 recurrent network activity is reduced, the frequency of spontaneous action potentials is decreased in Schaffer collaterals, and a single release locus synapse with one dendritic spine on a given CA1 pyramidal neuron can be developed by Schaffer collateral axons.
Location.
The Schaffer collateral is located between the CA3 region and CA1 region in the hippocampus. Schaffer collaterals are the axons of pyramidal cells that connect two neurons (CA3 and CA1) and transfer information from CA3 to CA1. The entorhinal cortex sends the main input to the dentate gyrus (perforant pathway). From the granule cells of the dentate gyrus, connections are made to the CA3 regions of the hippocampus via mossy fibers. CA3 sends the information signals to CA1 pyramidal cells via the Schaffer collateral and commissural fibers from the contralateral hippocampus as well.
Function.
Throughout the memory process in the hippocampus, Schaffer collaterals seem not to play a major role in the formation of actual memory, but it is clear that Schaffer collaterals assist the activity-dependent plasticity and the information processes that are always altered over the course of memory development in the hippocampus. Schaffer collaterals alter the development of the limbic system that is critical for learning and memory. The contralateral CA3 region sends information through Schaffer collateral to the CA1 pyramidal neurons.
Schaffer collateral and hippocampal synaptic plasticity.
Plastic changes occurring in the hippocampus are involved in directing the process by which memories get stored. Schaffer collaterals affect the hippocampus to develop short (Short-term Plasticity) and long term synaptic plasticity (Long-term Plasticity) in terms of storing information and changing in the efficiency of synaptic transmission following previous synaptic activity.
Long-term Potentiation.
Long-term potentiation (LTP) in the hippocampal formation is an example model for neural plasticity. Schaffer collateral synapses have been used as a sample synapse, a typical excitatory glutamatergic synapse in the cortex that has very well been studied in order to try to identify the rules of both the patterns of stimulation in electrical rules and the chemical mechanisms by which synapses get persistently stronger and which synapses get persistently weaker as well. LTPs are involved in how people store information and how they retrieve information and involve networks of memories that are involved in facts and in emotions as well because the hippocampus is the part of the limbic system connected to the amygdala.
LTP in the hippocampus is an important model for neural plasticity that contributes to learning and memory. Schaffer collaterals are the axons of the neurons in the CA3 regions of the hippocampus that form synapses in the CA1 regions.
The hippocampus is a part of the feedback process that sends signals to stop cortisol production. Thus, a damaged hippocampus can cause memory loss and inability of cognitive function. Furthermore, as the hippocampus is the region controlling learning and memory processes, the research on Schaffer collaterals may help to find treatments for diseases related to the hippocampus or its neural processing pathways such as Alzheimer's disease, a neurodegenerative disorder.
Long-term potentiation (LTP) of synaptic strength at Schaffer collateral synapses has largely been attributed to changes in the number and biophysical properties of AMPA receptors (AMPARs). Neuropsin has a regulatory effect on Schaffer collateral LTP in the rat hippocampus.
The functional hippocampus needs to store long-term memories. Once the memories are stored, they remain stored for a long time. Long-term changes in synaptic efficacy in the hippocampus can be induced by different patterns of stimulation generating presynaptic and postsynaptic depolarization The theta burst stimulation of Schaffer collaterals can be sufficient to induce LTP by promoting the formation of filamentous actin in CA1 dendrites. Within the mammalian brain, some patterns of synaptic activity produce long-term potentiation (LTP) which is a long-lasting increase in synaptic strength and long-term depression (LTD) which is a long-lasting decrease in synaptic strength.
LTP at Schaffer collateral-CA1 synapses and "SK2 channel plasticity".
Long-term plasticity in synapses of the hippocampus can be induced by different patterns of stimulation generating pre- and post-synaptic depolarization. These synaptic changes can clearly lead to modification in circuit function and to behavioral plasticity. Some patterns of synaptic activity produce an extensive increase in synaptic strength, also known as Long-Term Potentiation (LTP). In the hippocampus, LTP at Schaffer collateral-CA1 modulates the biophysical properties of AMPA receptors. Moreover, SK2, small-conductance Ca2+-activated K+ channel, changes the shape of excitatory postsynaptic potentials (EPSPs) by coupling with N-methyl D-aspartate receptors (NMDA receptors). The research by Lin MT, "et al." was designed to investigate whether SK2 channels participate in synaptic changes when an activity-dependent decrease contributes to LTP.
SK2 channels are ion channels that are activated by an increasing in the concentration of intracellular calcium and as a result of allowing K+ cation to cross the cell membrane. The double immunogold labeling identified that SK2 channels and NMDA cohabit within the postsynaptic density (PSD) of CA1 regions of the hippocampus. The authors used theta-burst pairing (TBP) to produce a rapid potentiation of synaptic strength and to evoke LTP that is induced simultaneously but whose expression levels vary inversely over time, and the result of the TBP induction was compared to the control group. The result showed that the TBP induction of LTP significantly increased EPSPs level. When the stimulus strength was reduced below the action potential threshold, apamin, a neurotoxin, was added to assess the contribution of SK2 activity to EPSPs. It resulted in an increase in the level of EPSPs with blockage of SK2 channels. The TBP induction of LTP abolishes SK2 channel contribution to EPSPs. When the induction of chemical LTP was applied, immunoparticles for SK2 were not found within the PSD of asymmetrical synapses. However, the SK2 immunoparticles were observed within intracellular membranes. The activation of protein kinase A (PKA) downregulates the surface expression of SK2 because PKA regulates the surface expression of AMPA receptors, a non-NMDA-type ionotropic transmembrane receptor, in the hippocampus. Therefore, PKA decreases the activity of LTP-dependent of SK2 channels. See Schaffer collateral#Long-term plasticity.
Short-term plasticity.
Short-term synaptic plasticity undergoes important age-dependent changes that have crucial implications during the development of the nervous system.
Vesicular release at "Schaffer Collateral".
Transmitters are released from pre-synaptic terminals through fusion of vesicles to the membrane, that are filled with neurotransmitters such as glutamate. Vesicles are exocytosed, with neurotransmitters reentering the presynaptic terminal for reuse. These fused vesicles then reenter preferentially back into the rapidly recycling pool for reuse. Additional vesicles within the reserve pool of the presynaptic terminal are released according to stronger amplitude depolarizations of the presynaptic axon due to greater spatial or temporal summation of action potentials, corresponding to greater calcium influx polarizing. Rate of endocytosis is dependent on rate at which vesicles are recycled into the recycling pool.
Multivesicular release (MVR) occurs at Schaffer collateral-CA1 synapses when P is elevated by facilitation and that MVR may be a phenomenon common to many synapses throughout the central nervous system.


Perihypoglossal nuclei

Perihypoglossal nuclei ("nuclei perihypoglossales"), called also perihypoglossal complex or perihypoglossal nuclear complex or satellite nuclei is a group of neurons in the floor of the fourth ventricle, in close proximity to the nucleus of the hypoglossal nerve in the gray substance of the medulla oblongata, all of which contain cells with characteristics suggestive of reticular connections.
The complex includes three nuclei: the intercalated nucleus, the nucleus prepositus, and the sublingual nucleus. The nucleus prepositus is the largest of the three.
Perihypoglossal nuclei receive afferents from the cerebral cortex, vestibular nuclei, accessory oculomotor nuclei, and paramedian pontine reticular formation. Efferent fibers of these nuclei terminates in cranial nerve nuclei involved in extraocular movement (oculomotor, trochlear, abducens), the cerebellum, and the thalamus. The perihypoglossal nuclei and their connections are part of a complex circuitry related to eye movements. Lesions in the nucleus prepositus impair the ability to keep the eyes fixed on a visual target, although conjugate movements are still performed accurately.


Cipralisant

Cipralisant (GT-2331, tentative trade name Perceptin) is an extremely potent histamine H3 receptor ligand originally developed by Gliatech. Cipralisant was initially classified as a selective H3 antagonist, but newer research (2005) suggests also agonist properties, i. e. functional selectivity. Cipralisant seemed to be well tolerated during early testing, entering Phase II trials for ADHD in 2000.
The relatively recent cloning of human H3 receptor, as well as the discovery of its constitutive activity provided the ability to better assess the activity of H3 receptor ligands. Consequently, cipralisant was reassessed as an H3 receptor agonist in human and rat recombinant systems, showing functional selectivity and stimulating one type of G-protein coupled pathway while failing to activate other intracellular pathways.
Gliatech filed for bankruptcy in 2002, and its intellectual property was inherited by Merck. The development of cipralisant seems to have been suspended since 2003 but research is ongoing, and recently it has been shown that it is the (1"S",2"S")-enantiomer which is the biologically active one.


Sulcus limitans

The sulcus limitans is found in the fourth ventricle of the brain. It separates the cranial nerve motor nuclei (medial) from the sensory nuclei (lateral). It can also be located by searching laterally from the medial eminence. It is parallel to the median sulcus.


Talairach coordinates

Talairach coordinates, also known as Talairach space, is a 3-dimensional coordinate system (known as an 'atlas') of the human brain, which is used to map the location of brain structures independent from individual differences in the size and overall shape of the brain. It is still common to use Talairach coordinates in functional brain imaging studies and to target transcranial stimulation of brain regions. However, alternative methods such as the MNI Coordinate System (originated at the Montreal Neurological Institute and Hospital) have largely replaced Talairach for stereotaxy and other procedures.
History.
The coordinate system was first created by neurosurgeons Jean Talairach and Gabor Szikla in their work on the "Talairach Atlas" in 1967, creating a standardized grid for neurosurgery. The grid was based on the idea that distances to lesions in the brain are proportional to overall brain size (i.e., the distance between two structures is larger in a larger brain). In 1988 a second edition of the "Talairach Atlas" came out that was coauthored by Tournoux, and it is sometimes known as the Talairach-Tournoux system. This atlas was based on single post-mortem dissection of a human brain.
The "Talairach Atlas" uses Brodmann areas as the labels for brain regions.
Description.
The Talairach coordinate system is defined by making two anchors, the anterior commissure and posterior commissure, lie on a straight horizontal line. Since these two points lie on the midsagittal plane, the coordinate system is completely defined by requiring this plane to be vertical. Distances in Talairach coordinates are measured from the anterior commissure as the origin (as defined in the 1998 edition). The y-axis points posterior and anterior to the commissures, the left and right is the x-axis, and the z-axis is in the ventral-dorsal (down and up) directions. Once the brain is reoriented to these axes, the researchers must also outline the six cortical outlines of the brain: anterior, posterior, left, right, inferior, and superior. In the 1967 atlas the left is with positive coordinates while in the 1988 atlas the left has negative coordinates.
By defining standard anatomical landmarks that could be identified on different subjects (the anterior and posterior commissures), it became easier to spatially warp an individual brain image obtained through Magnetic Resonance Imaging (MRI), positron emission tomography (PET) and other imaging methods to this standard Talairach space. One can then make inferences about tissue identity at a specific location by referring to the atlas.
Brodmann regions in neuroscience.
The Brodmann area is an illustration of a cytoarchitectonic map of the human brain that was published by Korbinan Brodmann in his 1909 monogram. Brodmann's map splits the cerebral cortex into 43 differing parts, which become visible in cell-body stained histological sections. Years later, a large group of neuroscientists still utilize Brodmann's map for the localization of neuroimaging data that is obtained in living human brains.
Brodmann in relation to Talairach coordinates.
Some neuroimaging techniques, in fact, purported the use of Brodmann's area as a guideline for Talairach coordinates. Further, these technologies showcase that experimental tasks in a common reference space become possible through imaging the living human brain by registering function and having architectonic data performed and defined.
Brodmann's map proved useful in varying neuroimaging software packages and stereotaxic atlases, such as the Talairach atlas. This atlas also serves as a demonstration of the inherent problems (i.e., impressions of matches between areal borders and sulcal landmarks may lead to wrong conclusions in terms of localization of cytoarchitectonic borders or the usage of Brodmann's map without knowledge of the text that accompanies the drawing misleading researchers to false conclusions).
Conversion to other coordinate systems.
Montreal Neurological Institute (MNI) templates.
Another common atlas for the human brain is the Montreal Neurological Institute and Hospital (MNI) coordinate system, which is the template used for SPM and the International Consortium for Brain Mapping. Most neuroimaging software packages are able to convert from Talairach to MNI coordinates.
However, disparities between MNI and Talairach coordinates can impede the comparison of results across different studies. This problem is most prevalent in situations where coordinate disparities should be corrected to reduce error, such as coordinate-based meta-analyses. There is a possibility that these disparities can be assuaged through the Lancaster transform, which can be adopted in order to minimize the variability in the literature regarding spatial normalization strategies.
Non-linear registration.
Non-linear registration is the process of digitalizing Talairach coordinates and generating a non-linear map in an attempt to compensate for actual shape differences between the two, which would result in more accurate coordinate transformations.
The Talairach atlas is still commonly used in terms of the neuroimaging techniques that are available, but the lack of a three-dimensional model of the original brain makes it difficult for researchers to map locations from three-dimensional anatomical MRI images to the atlas automatically. Previous methods such as MNI have tried to assuage this issue through linear and piecewise mapping between the Talairach and the MNI template, but can only account for differences in overall brain orientation and size and thus cannot correctly account for actual shape differences.
Optimized high-resolution brain template (HRBT).
Current target brains are not suitable for current research (i.e., are average, can only be used in low-resolution MRI target brain mapping studies or are single brain). Optimized high-resolution brain template (HRBT), a high-resolution MRI target brain, is a technique that can aid in the issues named latter. This optimization can be performed to help reduce individual anatomical biases of the original ICBM HBRT. The optimized HRBT is more adept at anatomically matching groups of brains.


Pentagestrone acetate

Pentagestrone acetate (PGA), sold under the brand names Gestovis and Gestovister, is a progestin which was described in the literature in 1960 and was introduced by Vister in Italy in 1961. It is the 3-cyclopentyl enol ether of 17α-hydroxyprogesterone acetate. PGA, along with quingestrone (the 3-cyclopentyl enol ether of progesterone), is said to have very similar properties to those of dydrogesterone, a pure progestogen and close analogue of progesterone.
PGA is orally active, was provided in 10 and 20 mg capsules, and has been used to treat habitual abortion and menstrual disorders at a dosage of 10 to 20 mg/day. It has been said to have equivalent potency to intramuscular progesterone. The combination of 20 mg/day PGA and 100 μg/day mestranol is an effective ovulation inhibitor in women. The effective dosage of PGA in the menstrual delay test has been studied.
Chemistry.
PGA, also known as 17α-acetoxyprogesterone 3-cyclopentyl enol ether, is a synthetic pregnane steroid and a derivative of progesterone and 17α-hydroxyprogesterone.


Pre-locus coeruleus

Pre-locus coeruleus is a small nucleus in the brainstem. This small cluster of neurons also is referred to by the abbreviation "pre-LC". It was named "pre-LC" because it lies just rostral to (in front of) the locus coeruleus, which is commonly abbreviated "LC".
Definition.
The pre-locus coeruleus was first formally defined during the course of neuroanatomical tract-tracing and c-Fos experiments aimed at uncovering the connections and functions of aldosterone-sensitive HSD2 neurons in the nucleus of the solitary tract. First, HSD2 neurons were found to innervate the pre-LC, as evidenced by (1) dense labeling with an anterograde axonal tracer in pre-LC after that tracer had been injected into the nucleus of the solitary tract and (2) the complementary finding of retrograde labeling of HSD2 neurons after injection of a retrograde tracer into the pre-LC. Further, experimental conditions which activate the HSD2 neurons simultaneously activate a cluster of neurons in pre-LC, in the same location as axon terminals labeled with an anterograde tracer from the NTS.
Based on these observations, the pre-locus coeruleus ("pre-LC") was defined as the cluster of neurons which:
These features consistently and reliably identify a very specific subset of neurons in the dorsolateral pons, named the pre-locus coeruleus, or "pre-LC." Some investigators have used other terms including "precoeruleus," "peri5Me," and "pericoeruleus" to refer less specifically to regions of the brainstem anterior to the LC, but the term pre-LC very specifically refers to the group of neurons as defined above. Subsequently, it was discovered that every c-Fos-positive neuron in the pre-LC (after sodium deprivation) also expresses the transcription factor FOXP2. Given that sodium deprivation is a time-consuming experimental manipulation, and that FoxP2 is stably expressed without any experimental manipulation, this transcription factor can serve as a useful surrogate marker for labeling pre-LC neurons. However, FoxP2 expression is found in several nearby brain regions (not including the locus coeruleus, mesencephalic nucleus of the trigeminal, or laterodorsal tegmental nucleus), so it is not unique to the pre-LC. That is, every pre-LC neuron expresses FoxP2, but not every neuron that expresses FoxP2 is part of the pre-LC.
Location.
The name "pre-LC," as coined by Geerling and colleagues to refer to a very specific and molecularly defined cluster of neurons, refers specifically to neurons that lie medial to and intermingled with the mesencephalic nucleus of the trigeminal nerve and its tract at levels of the rostral pons that also contain the superior cerebellar peduncle. Pre-LC neurons in rats are found just rostral to one of the best-known nuclei in the brainstem, the LC, hence the name "pre-LC." The picture above shows the anatomic relationship between the pre-LC and LC. In this image, in the sagittal plane, the noradrenergic LC neurons are labeled in red, for TH (tyrosine hydroxylase, a catecholamine-synthetic enzyme found in all LC neurons). These red LC neurons and their rostral dendritic arborization are located caudal to (behind) all neurons in the pre-LC. The nuclei of pre-LC neurons are labeled in green, for FoxP2 (see above regarding FoxP2 as a marker for pre-LC neurons). Based on their shared connections, gene-expression, and c-Fos activity patterns, the pre-LC is probably related functionally to neurons in the parabrachial nucleus, which is located lateral to the pre-LC (out of the plane of section in this figure).
Connections.
The input connections of the pre-LC have not been studied comprehensively. As described above, the pre-LC receives heavy input from the HSD2 neuron subregion of the nucleus of the solitary tract; and this input appears to be functionally active based on c-Fos analysis . It also receives descending input from the paraventricular nucleus of the hypothalamus (PVH), as shown in the sagittal plane in the figure at right (red axon terminal labeling after injection into the PVH; LC neurons are labeled in blue, and the laterodorsal tegmental nucleus or LDT neurons is labeled in green).
The output connections of the pre-LC have been studied extensively, using anterograde axonal tracing experiments followed by retrograde axonal tracing experiments that utilized FoxP2 as a marker for the neurons in pre-LC. Pre-LC neurons project heavily to the diencephalon, particularly to subregions of the midline thalamus and the posterior and lateral hypothalamus.
Function.
To date, the function of pre-LC neurons remains unclear. Possibilities include inhibiting hunger and promoting sodium appetite, as discussed in references listed below.


Ganglion

A ganglion is a group of neuron cell bodies in the peripheral nervous system. In the somatic nervous system this includes dorsal root ganglia and trigeminal ganglia among a few others. In the autonomic nervous system there are both sympathetic and parasympathetic ganglia which contain the cell bodies of postganglionic sympathetic and parasympathetic neurons respectively.
A pseudoganglion looks like a ganglion, but only has nerve fibers and has no nerve cell bodies.
Structure.
Ganglia are primarily made up of somata and dendritic structures which are bundled or connected. Ganglia often interconnect with other ganglia to form a complex system of ganglia known as a plexus. Ganglia provide relay points and intermediary connections between different neurological structures in the body, such as the peripheral and central nervous systems.
Among vertebrates there are three major groups of ganglia:
In the autonomic nervous system, fibers from the central nervous system to the ganglia are known as preganglionic fibers, while those from the ganglia to the effector organ are called postganglionic fibers.
Basal ganglia.
The term "ganglion" refers to the peripheral nervous system.
However, in the brain (part of the central nervous system), the "basal ganglia" is a group of nuclei interconnected with the cerebral cortex, thalamus, and brainstem, associated with a variety of functions: motor control, cognition, emotions, and learning.
Partly due to this ambiguity, the Terminologia Anatomica recommends using the term basal nuclei instead of basal ganglia; however, this usage has not been generally adopted.
Pseudoganglion.
A pseudoganglion is a localized thickening of the main part or trunk of a nerve that has the appearance of a ganglion but has only nerve fibers and no nerve cell bodies.
Pseudoganglia are found in the teres minor muscle and radial nerve.


Spike (journalism)

Spiking is the act of withholding a story from publication for editorial, commercial, or political reasons. Its facts and grammar may be valid, but its content is deemed to be at odds with the interests of the paper, or the paper's interpretation of what is good for its community. A spiking may be permanent, or temporary, depending on what instigated it, and whether the objection(s) can be overcome.
Some examples would be a story that while factually correct would likely incite a powerful local politician, upset a valuable advertiser in that paper, or bring unwanted attention to a community. The editorial staff, or if preempted, the newspaper ownership or management, must balance all its interests against purely theoretical "journalistic integrity". Conflicts involving spiking often arise from stories being pursued as part of investigative journalism, or which threaten to bring on a libel lawsuit (that could prove expensive to fight even if groundless). Also late suspicions of plagiarism or other ethical violations on the part of the author, however brought to an editor's attention.
Spiking is not limited to print media, as stories for radio or television broadcast also are subject to it for the same reasons.


CBV Institute

The CBV Institute (), or formerly known as the "Canadian Institute of Chartered Business Valuators (CICBV)", is a Canadian business valuation organization. The CBV Institute is a not-for-profit valuation professional organization that establishes the practice standards, educational requirements, and ethical guidelines for its members.
The "Chartered Business Valuator (CBV)" or designation is a credential for business valuation professionals in Canada. CBVs are governed by The Canadian Institute of Chartered Business Valuators. CBVs quantify the value of a business, its securities, or its intangible assets. CBVs use a variety of valuation methodologies to arrive at a conclusion, and explain their approach, methodology and conclusions in an easy to understand manner. Various approaches used include asset-based approaches (liquidation, adjusted net book value), return-based approaches (capitalized earnings, capitalized cash flows, discounted cash flows), and market-based approaches (comparable company multiples). In the context of litigation, CBVs quantify the damages or losses arising in a legal dispute.
History.
The CBV Institute was founded in 1971 by 28 valuation professionals under the leadership of George Ovens. At the time, the introduction of taxation of capital gains in Canada facilitated the general need for business valuation.
Education Requirements.
After completing the institute's comprehensive Program of Studies (which includes six courses dealing with business valuation, Canadian taxation, the law, and litigation support), completion of the Membership Qualification Exam (held annually), and obtaining practical experience requirements, candidates are then admitted to the membership.
Students must take four courses as part of their education requirements:
and pick two electives from the following:
CBVs also have continuing professional development requirements. The Institute supports this requirement by organizing various webinars, regional workshops and national conferences that address current and evolving industry topics. CBVs are required to adhere to the Standard of Professional Practice as well as its Code of Conduct and Code of Ethics.
Course Exemptions.
The Institute grants various advanced standings to other organizations and university education partners:
National and International Partnership.
The CBV Institute forms various partnerships and relationship with organizations in Canada and the world to develop the business valuation profession and expand the CBV's international presence, including the following:


Nerve tract

A nerve tract is a bundle of nerve fibers (axons) connecting nuclei of the central nervous system. In the peripheral nervous system this is known as a nerve, and has associated connective tissue. The main nerve tracts in the central nervous system are of three types: association fibers, commissural fibers, and projection fibers. A tract may also be referred to as a commissure, decussation, or fasciculus. A commissure connects the two cerebral hemispheres at the same levels, while a decussation connects at different levels (crosses obliquely).
Types.
The nerve fibers in the central nervous system can be categorized into three groups on the basis of their course and connections. Different tracts may also be referred to as "projections" or "radiations".
Association fibers.
The tracts that connect cortical areas within the same hemisphere are called association tracts. Long association fibers connect different lobes of a hemisphere to each other whereas short association fibers connect different gyri within a single lobe. Among their roles, association tracts link perceptual and memory centers of the brain.
The cingulum is a major association tract. The cingulum forms the white matter core of the cingulate gyrus and links from this to the entorhinal cortex. Another major association tract is the superior longitudinal fasciculus (SLF) that has three parts.
Commissural fibers.
Commissural tracts connect corresponding cortical areas in the two hemispheres. They cross from one cerebral hemisphere to the other through bridges called commissures. The great majority of commissural tracts pass through the largest commissure the corpus callosum. A few tracts pass through the much smaller anterior and posterior commissures. Commissural tracts enable the left and right sides of the cerebrum to communicate with each other. Other commissures are the hippocampal commissure, and the habenular commissure.
Projection fibers.
Projection tracts connect the cerebral cortex with the corpus striatum, diencephalon, brainstem and the spinal cord. The corticospinal tract for example, carries motor signals from the cerebrum to the spinal cord. Other projection tracts carry signals upward to the cerebral cortex. Superior to the brainstem, such tracts form a broad, dense sheet called the internal capsule between the thalamus and basal nuclei, then radiate in a diverging, fanlike array to specific areas of the cortex.


Rubro-olivary tract

The rubro-olivary tract (rubroolivary fibers) is a tract which connects the inferior olive and the parvocellular red nucleus.
It is hypothesized that it uses both the corticospinal tract and rubrospinal tract.


John Macadam

The Honorable Dr John Macadam (29 May 1827 – 2 September 1865), was a Scottish-Australian chemist, medical teacher, Australian politician and cabinet minister, and honorary secretary of the Burke and Wills expedition. The genus "Macadamia" (macadamia nut) was named after him in 1857. He died in Australia aged 38.
Early life.
John Macadam was born at Northbank, Glasgow, Scotland, on 29 May 1827, the son of William Macadam (1783-1853) and Helen, née Stevenson (1803-1857). His father was a Glasgow businessman, who owned a spinning and textile printing works in Kilmarnock, and was a burgess and a bailie (magistrate) of Glasgow. His fellow industrialists and he in the craft had developed, using chemistry, the processes for the large-scale industrial printing of fabrics for which these plants in the area became known.
John Macadam was privately educated in Glasgow; he studied chemistry at the Andersonian University (now the University of Strathclyde) and went for advanced study at the University of Edinburgh under Professor William Gregory. In 1846-47, he went on to serve as assistant to Professor George Wilson at the University of Edinburgh in his laboratory in Brown Square. He was elected a fellow of the Royal Scottish Society of Arts that year, and in 1848, a member of the Glasgow Philosophical Society. He then studied medicine at the University of Glasgow (LFPS, MD,1854; FFPSG,1855).
He was a member of what became a small dynasty of Scottish scientists and lecturers in analytical chemistry, which included, other than himself, his eldest half brother William Macadam, his immediate younger brother Stevenson Macadam (a younger brother Charles Thomas Macadam, although not involved as a scientist, was also indirectly involved in chemistry becoming a senior partner in a chemical fertiliser company) and nephews William Ivison Macadam and Stevenson J. C. G. Macadam, as well as the former nephew's daughter, his great niece Elison A. Macadam.
On 8 June 1855, aged 28, Macadam sailed for Melbourne in the Colony of Victoria, Australia, on the sailing ship "Admiral." He arrived on 8 September 1855.
Australian academic career.
In 1855 he was a lecturer on chemistry and natural science at Scotch College, having been engaged for the position before leaving Scotland.
In 1857 he was awarded an MD "ad eundem" from the University of Melbourne in acknowledgment of his MD from the University of Glasgow.
In 1857-1858 he also taught at Geelong Church of England Grammar School (now Geelong Grammar School). In 1858, he was appointed the Victorian government analytical chemist. In 1860 he became health officer to the City of Melbourne. He wrote several reports on public health.
On 3 March 1862 he was appointed as the first lecturer in medicine (chemistry and practical chemistry) at the University of Melbourne School of Medicine. For the next few years he held classes for a small number of medical students in the Analytical Laboratory behind the Public Library. He was also a member of the Board of Agriculture.
Political life.
He became a member of the legislative assembly of the self-governing Colony of Victoria as a radical and supporter of the Land Convention, representing Castlemaine.
He was postmaster-general of Victoria in 1861. He resigned from the legislature in 1864. He had sponsored bills on medical practitioners and adulteration of food which became law in 1862 and 1863.
Royal Society of Victoria.
Between 1857 and 1862, Macadam served as honorary secretary of the Philosophical Institute of Victoria, which later became the Royal Society of Victoria in 1860, and was appointed vice-president of it in 1863. He was editor of first five volumes of the society's "Transactions". He was active in erecting the Society's Meeting Hall (their present building) and was involved in the institute's initiative to obtain a royal charter. He saw both happen while he held office, when in January 1860, the Philosophical Institute became the Royal Society of Victoria and met in their new building.
Burke and Wills expedition.
Between 1857 and 1865, Macadam served as honorary secretary to the Exploration Committee of the Royal Society of Victoria, which organised the Burke and Wills expedition.
The expedition was organised by the society with the aim of crossing the continent of Australia from the south to the north coasts, map it, and collect scientific data and specimens. At that time, most of the interior of Australia had not been explored by the European settlers and was unknown to them.
In 1860–61, Robert O'Hara Burke and William John Wills led the expedition of 19 men with that intention, crossing Australia from Melbourne in the south, to the Gulf of Carpentaria in the north, a distance around 2,000 miles.
Three men ultimately travelled over 3,000 miles from Melbourne to the shores of the Gulf of Carpentaria and back to the Depot Camp at Cooper Creek. Seven men died in the attempt, including the leaders Burke and Wills. Of the four men who reached the north coast, only one, John King, survived with the help of the indigenous people to return to Melbourne.
This expedition became the first to cross the Australian continent. It was of great importance to the subsequent development of Australia and could be compared in importance to the Lewis and Clark Expedition overland to the North American Pacific Coast to the development of the United States.
After the heavy death toll of the expedition, initial criticism fell on the Royal Society, but it became clear that their foresight could not have prevented the deaths and this was then widely recognised when it became known that as Secretary of the Exploration Committee of the Burke and Wills expedition, Dr. Macadam had insisted on adequate provisions for their safety.
Macadamia.
The macadamia (genus Macadamia) nut was discovered by the European settlers, and subsequently the tree was named after him by his friend and colleague, Ferdinand von Mueller (1825-1896), Director of the Royal Botanic Gardens, Melbourne. The tree gave his name to macadamia nuts. The genus "Macadamia" was first described scientifically in 1857 by Dr. Mueller and he named the new genus in honour of his friend Dr John Macadam. Mueller had done a great deal of taxonomy of the flora, naming innumerable genera but chose this "...a beautiful genus dedicated to John Macadam, M.D. the talented and deserving secretary of our institute."
Australian rules football.
On 7 August 1858, John Macadam officiated as one of two umpires at a famous game of football played between Scotch College and Melbourne Grammar. It was co-umpired by Tom Wills and John Macadam. The two schools have competed annually ever since, lately for the Cordner–Eggleston Cup. This game was a predecessor to the modern game of Australian rules football and is commemorated by a statue depicting the game outside the Melbourne Cricket Ground.
Family.
On 18 September 1856, a year after he arrived from Scotland, he married Elizabeth Clark in Melbourne, Australia. She had arrived three days before the wedding with her maid on the "Admiral", the same ship on which he had travelled out a year earlier, which reached Hobson's Bay (Melbourne's port) on 15 September 1856, having set sail from London on 7 June 1856. Elizabeth Clark was probably born on 7 October 1832 in Barony parish Scotland, near Glasgow (her mother being Mary McGregor). She was the second daughter of John Clark, of Levenfield House in Alexandria, the Vale of Leven, a short distance north of Glasgow in West Dunbartonshire. His Levenfield Works were involved in similar work to Dr John Macadam’s father William Macadam in Kilmarnock in the then lucrative business of textile printing for domestic and European markets. The Clarks and Macadams must have become known to each other in Scotland because of their respective fathers' business connections. Elizabeth died in 1915, in Brighton, Victoria.
John and Elizabeth had two sons:
John Melnotte Macadam was born 29 August 1858 at Fitzroy, Melbourne, Australia, and died on 30 January 1859, aged 5 months (he was reburied with his father, whose monument bears the additional inscription: "In memory of his only children John Melnotte Macadam Born August 29, 1858 Died January 30, 1859" followed by an inscription to his second son below it).
William Castlemaine Macadam was born on 2 July 1860 and died 17 December 1865 at Williamstown, Victoria, Australia. He died aged five and had survived his father by a few months. The inscription on his father's burial monument under "His only children" has him listed under his elder brother (above), who died in infancy, but does not for some reason give William's date of death on it.
Death.
In 1865 Macadam died, aged 38, after a shipboard accident on the way to New Zealand to give evidence at the trial of Captain W. A. Jarvey, accused of fatally poisoning his wife. During the trip, Macadam fractured his ribs during a storm and later died on 2 September 1865. His medical-student assistant John Drummond Kirkland gave evidence at the trial in Macadam's place and Jarvey was convicted.
The "Australian News" commented, "At the time of his death, Dr Macadam was but 38 years of age; there can be little doubt that the various and onerous duties he discharged for the public must be attributed in great measure the shortening of his days." The "Australian Medical Journal" stated, "For some time it had been evident to his friends that his general health was giving way: that a frame naturally robust and vigorous was gradually becoming undermined by the incessant and harassing duties of the multifarious offices he filled." The inquest verdict (he died at sea) stated, "His death was caused by excessive debility and general exhaustion."
Funeral.
The funeral was large. The newspapers carried tributes and subsequently lengthier obituaries from learned societies were published, such as that in the "Australian Medical Journal" and elsewhere. The Melbourne "Leader" described the funeral: "The coffin was drawn by four horses. Four mourning coaches contained the chief mourners and the more intimate friends of the deceased gentleman. A large procession followed, in which were several members of Parliament, the members of the Royal Society, the Chief Justice; the Mayor and corporation of the city of Melbourne. A number of private carriages and the public wound up the procession...At the University, the chancellor, the vice-chancellor, and a number of the students, all in their academic robes, met the funeral cortege, and proceeded the remainder of the distance". The chief mourner was his youngest brother, George Robert Macadam (1837-1918). John Macadam's grave, surmounted by a marble obelisk, is in Melbourne General Cemetery.
Widow re-married.
After John Macadam and her children's deaths his widow, Elizabeth Clark, later remarried. She married the Reverend John Dalziel Dickie, who was pastor at Colac for 32 years. They married on 26 February 1868 They had four daughters. Elizabeth Dickie died aged 82 in 1915, in Brighton, Victoria, near Melbourne as the widow of the Rev. Dickie. He had died 25 December 1909.


Stromatoxin

Stromatoxin is a spider toxin that blocks certain delayed-rectifier and A-type voltage-gated potassium channels.
Etymology.
Stromatoxin was first identified in the venom of the African tarantula "Stromatopelma calceatum" (the featherleg baboon spider), from which it derives its name. The technical abbreviation for the toxin is ScTx1.
Chemistry.
Stromatoxin is a peptide consisting of 34 amino acids that belongs to the structural family of ‘inhibitor cystine knot’ spider peptides. The toxin was identified using a systematical screening of the effects of toxins of several species of tarantulas on Kv2-channels of "Xenopus laevis" (the African clawed frog) . Bioassay guided fractionation and chromatography identified stromatoxin as the functional component. The full sequence of the venom was obtained in a single run of Edman sequencing and confirmed by mass spectrometry. The sequence of this toxin is ‘dctrmfgacr rdsdccphlg ckptskycaw dgti’, for an explanation of these symbols, see the list of standard amino acids.
Target.
Stromatoxin blocks the delayed-rectifier type potassium channels Kv2.1, Kv2.2, Kv2.1/9.3 and the A-type potassium channel Kv4.2, with affinity (IC50) of 12.7 nM, 21.4 nM, 7.2 nM and 1.2 nM, respectively. No activity on Kv4.1 and Kv4.3 has been observed .
Mode of action.
 showed that the effect of stromatoxin on potassium channels is voltage-dependent, maximal inhibition is reached between –30 and 0 mV, while inhibition is only partial at values more positive than +10 mV. The toxin therefore acts as a gating modifier, shifting the activation of the channel to more depolarized potentials. Although the channel can still be activated, a much larger depolarization is needed.
By blocking potassium channels, stromatoxin has a wide range of actions. Its target channels can be found in cardiac tissue, neurons and smooth muscle cells. In cardiac cells, their role more specifically concerns the height and duration of the plateau phase of the action potential, repolarization of cell membranes, cardiac refractoriness and automaticity. In the nervous system, A-type and delayed rectifier voltage-gated potassium channels determine the membrane resting potential, the firing pattern, action potential duration and repolarization. Thus, they are implicated in membrane excitability, hormone release, and signal transduction and processing ,
The effect of the toxin strongly varies with the tissue in which the channels are expressed. Stromatoxin for example prohibits apoptosis in enterocytes and enhances myogenic constriction in (rat) cerebral arteries .
Toxicity.
No toxic effects of stromatoxin have been recorded "in vivo". injected stromatoxin in mice, but observed no neurotoxicity.


Marie Vieux-Chauvet

Marie Vieux-Chauvet (born Marie Vieux; September 16, 1916 – June 19, 1973), was a Haitian novelist, poet and playwright. Born and educated in Port-au-Prince, she is most famous for the novels "Fille d'Haïti" (1954), "La Danse sur le volcan" (1957), "Fonds des nègres" (1960), and "Amour, colère et folie" (1968). During her lifetime, she published under the name Marie Chauvet.
Family history.
Marie Vieux-Chauvet was born in Port-au-Prince, Haiti, on September 16, 1916, to Constant Vieux, a Haitian politician, and his wife Delia Nones, a woman originally from the Virgin Islands. Marie completed her studies at the l'Annexe de l'École Normale d'Institutrices and obtained a degree in elementary education in 1933. She married Aymon Charlier, a doctor, then divorced him. She later married Pierre Chauvet, a travel agent.
Work.
Vieux-Chauvet's works focus on class, color, race, gender, family structure and the upheaval of Haitian political, economic and social society during the United States occupation of Haiti and dictatorship of François Duvalier. Although she lived under heavy surveillance during Duvalier's dictatorship, Vieux-Chauvet persisted as a writer, hosting meetings of the "Les Araignées du Soir" (Evening Spiders), a group of poets and writers of which she was the only female.
Vieux-Chauvet sent a trilogy of novellas to France to be published as a single book titled "Amour, colère et folie "("Love, Anger, Madness"). "Amour, colère et folie" was published in 1968 by the prestigious publishing house Gallimard in Paris with the support of Simone de Beauvoir. The book was perceived as an attack on the Haitian dictator François Duvalier. Fearing the dictator's legions of Tonton Macoutes, she moved to New York City. Her husband, Pierre Chauvet, travelled to Haiti and bought all the copies of the book he could find. Vieux-Chauvet's daughters bought the remaining copies from Gallimard a few years later. She later remarried and worked as a housekeeper in Queens.
She died of brain cancer in the United States on June 19, 1973.
Extracts from her work appear in the anthologies "Her True-True Name" and "Daughters of Africa". An English translation of "Amour, colère et folie "("Love, Anger, Madness") by Rose-Myriam Réjouis and Val Vinokur was published in 2009 with an introduction by Haitian-American writer Edwige Danticat.


Ramus communicans

Ramus communicans (plural rami communicantes) is the Latin term used for a nerve which connects two other nerves, and can be translated as "communicating branch".
Structure.
When used without further definition, it almost always refers to a communicating branch between a spinal nerve and the sympathetic trunk. More specifically, it usually refers to one of the following :
The grey and white rami communicantes are responsible for conveying autonomic signals, specifically for the sympathetic nervous system. Their difference in coloration is caused by differences in myelination of the nerve fibres contained within, i.e. there are more myelinated than unmyelinated fibres in the white rami communicantes while the converse is true for the grey rami communicantes.
Gray ramus communicans.
The grey rami communicantes exist at every level of the spinal cord and are responsible for carrying postganglionic nerve fibres from the paravertebral ganglia to their destination, and for carrying those preganglionic nerve fibres which enter the paravertebral ganglia but do not synapse.
White ramus communicans.
The white rami communicantes exist only at the levels of the spinal cord where the intermediolateral cell column is present (T1-L2) and are responsible for carrying preganglionic nerve fibres from the spinal cord to the paravertebral ganglia.
Both ramus within the spinal nerve cross each other, being the white farther away from the intervertebral foramen when exiting the spinal nerve to enter the ganglia. (More so, some fibers from the white ramus may migrate to other ganglia without even synapsis on its level)


Special senses

In medicine and anatomy, the special senses are the senses that have specialized organs devoted to them:
The distinction between special and general senses is used to classify nerve fibers running to and from the central nervous system – information from special senses is carried in special somatic afferents and special visceral afferents. In contrast, the other sense, touch, is a somatic sense which does not have a specialized organ but comes from all over the body, most noticeably the skin but also the internal organs (viscera). Touch includes mechanoreception (pressure, vibration and proprioception), pain (nociception) and heat (thermoception), and such information is carried in general somatic afferents and general visceral afferents.
Vision.
Visual perception is the ability to interpret the surrounding environment using light in the visible spectrum reflected by the objects in the environment. The resulting perception is also known as visual perception, eyesight, sight, or vision (adjectival form: "visual", "optical", or "ocular"). The various physiological components involved in vision are referred to collectively as the visual system.
The visual system in animals allows individuals to assimilate information from their surroundings. The act of seeing starts when the cornea and then the lens of the eye focuses light from its surroundings onto a light-sensitive membrane in the back of the eye, called the retina. The retina is actually part of the brain that is isolated to serve as a transducer for the conversion of light into neuronal signals. Based on feedback from the visual system, the lens of the eye adjusts its thickness to focus light on the photoreceptive cells of the retina, also known as the rods and cones, which detect the photons of light and respond by producing neural impulses. These signals are processed via complex feedforward and feedback processes by different parts of the brain, from the retina upstream to central ganglia in the brain.
Note that up until now much of the above paragraph could apply to octopuses, mollusks, worms, insects and things more primitive; anything with a more concentrated nervous system and better eyes than say a jellyfish. However, the following applies to mammals generally and birds (in modified form): The retina in these more complex animals sends fibers (the optic nerve) to the lateral geniculate nucleus, to the primary and secondary visual cortex of the brain. Signals from the retina can also travel directly from the retina to the superior colliculus.
The perception of objects and the totality of the visual scene is accomplished by the visual association cortex. The visual association cortex combines all sensory information perceived by the striate cortex which contains thousands of modules that are part of modular neural networks. The neurons in the striate cortex send axons to the extrastriate cortex, a region in the visual association cortex that surrounds the striate cortex.
The human visual system perceives visible light in the range of wavelengths between 370 and 730 nanometers (0.00000037 to 0.00000073 meters) of the electromagnetic spectrum.
Hearing.
Hearing, or auditory perception, is the ability to perceive sound by detecting vibrations, changes in the pressure of the surrounding medium through time, through an organ such as the ear. Sound may be heard through solid, liquid, or gaseous matter. It is one of the traditional five senses; partial or total inability to hear is called hearing loss.
In humans and other vertebrates, hearing is performed primarily by the auditory system: mechanical waves, known as vibrations are detected by the ear and transduced into nerve impulses that are perceived by the brain (primarily in the temporal lobe). Like touch, audition requires sensitivity to the movement of molecules in the world outside the organism. Both hearing and touch are types of mechanosensation.
There are three main components of the human ear: the outer ear, the middle ear, and the inner ear.
Smell.
Smell, or olfaction, is a chemoreception that forms the sense of smell. Olfaction has many purposes, such as the detection of hazards, pheromones, and food. It integrates with other senses to form the sense of flavor. Olfaction occurs when odorants bind to specific sites on olfactory receptors located in the nasal cavity. Glomeruli aggregate signals from these receptors and transmit them to the olfactory bulb, where the sensory input will start to interact with parts of the brain responsible for smell identification, memory, and emotion. Often, land organisms will have separate olfaction systems for smell and taste (orthonasal smell and retronasal smell), but water-dwelling organisms usually have only one system.
In vertebrates, smells are sensed by olfactory sensory neurons in the olfactory epithelium. The olfactory epithelium is made up of at least six morphologically and biochemically different cell types. The proportion of olfactory epithelium compared to respiratory epithelium (not innervated, or supplied with nerves) gives an indication of the animal's olfactory sensitivity. Humans have about of olfactory epithelium, whereas some dogs have . A dog's olfactory epithelium is also considerably more densely innervated, with a hundred times more receptors per square centimeter.
Molecules of odorants passing through the superior nasal concha of the nasal passages dissolve in the mucus that lines the superior portion of the cavity and are detected by olfactory receptors on the dendrites of the olfactory sensory neurons. This may occur by diffusion or by the binding of the odorant to odorant-binding proteins. The mucus overlying the epithelium contains mucopolysaccharides, salts, enzymes, and antibodies (these are highly important, as the olfactory neurons provide a direct passage for infection to pass to the brain). This mucus acts as a solvent for odor molecules, flows constantly, and is replaced approximately every ten minutes.
Taste.
Taste is the sensation produced when a substance in the mouth reacts chemically with taste receptor cells located on taste buds in the oral cavity, mostly on the tongue. Taste, along with smell (olfaction) and trigeminal nerve stimulation (registering texture, pain, and temperature), determines flavors of food or other substances. Humans have taste receptors on taste buds (gustatory calyculi) and other areas including the upper surface of the tongue and the epiglottis. The gustatory cortex is responsible for the perception of taste.
The tongue is covered with thousands of small bumps called papillae, which are visible to the naked eye. Within each papilla are hundreds of taste buds. The exception to this is the filiform papillae that do not contain taste buds. There are between 2000 and 5000 taste buds that are located on the back and front of the tongue. Others are located on the roof, sides and back of the mouth, and in the throat. Each taste bud contains 50 to 100 taste receptor cells.
The sensation of taste includes five established basic tastes: sweetness, sourness, saltiness, bitterness, and umami. Scientific experiments have proven that these five tastes exist and are distinct from one another. Taste buds are able to differentiate among different tastes through detecting interaction with different molecules or ions. Sweet, umami, and bitter tastes are triggered by the binding of molecules to G protein-coupled receptors on the cell membranes of taste buds. Saltiness and sourness are perceived when alkali metal or hydrogen ions enter taste buds, respectively.
The basic tastes contribute only partially to the sensation and flavor of food in the mouth—other factors include smell, detected by the olfactory epithelium of the nose; texture, detected through a variety of mechanoreceptors, muscle nerves, etc.; temperature, detected by thermoreceptors; and "coolness" (such as of menthol) and "hotness" (pungency), through chemesthesis.
As taste senses both harmful and beneficial things, all basic tastes are classified as either aversive or appetitive, depending upon the effect the things they sense have on our bodies. Sweetness helps to identify energy-rich foods, while bitterness serves as a warning sign of poisons.
Among humans, taste perception begins to fade around 50 years of age because of loss of tongue papillae and a general decrease in saliva production. Humans can also have distortion of tastes through dysgeusia. Not all mammals share the same taste senses: some rodents can taste starch (which humans cannot), cats cannot taste sweetness but can taste ATP, and several other carnivores including hyenas, dolphins, and sea lions, have lost the ability to sense up to four of their ancestral five taste senses.


Multi-subject instructional period

In an educational milieu MSIP can be defined as the either the "Manitoba School Improvement Plan" or the Multi-Subject Instructional Period. For the purpose of this article the acronym MSIP will be used exclusively to refer to the multi-subject instructional period.
The Manitoba School Improvement Project dates from 1994, when it was established as a result of the vision of the Walter and Duncan Gordon Foundation, a Canadian charitable foundation. The Foundation was interested in enhancing education fm was begun. Established initially with a very definite urban focus, the program has in recent years expanded to not only include the province's rural community but other Canadian jurisdictions.
MSIP promotes an alternative academic schedule for high school students. Students in Canada generally attend high schools where the school year is divided into two semesters consisting of four period days. Class time can vary slightly but most classes last between 70 and 76 minutes. Instead of the standard four 75-minute periods found in the semestered school MSIP schools adopt five 60-minute periods including one 60-minute multi-subject instructional period.
How MSIP works.
Students attend their regular four classes each day plus a one-hour supervised MSIP class. Students in any one MSIP class are arranged in multi-grade formation with varied levels of ability. Their course selections determine their timetable and where the MSIP class will fall. In many cases the MSIP class begins with 20 minutes of silent literacy work - reading or writing complementing the movement to improve literacy skills. The rest of the period students may use for work on assignments, make up work they missed due to absences or get help in areas where they are falling behind.
Students have the ability to move within the school environment during their MSIP period to seek extra help, use computer and research resources, attend guidance counselling appointments and meet with subject teachers where possible. The flexibility of this format alleviates the disruption normally associated with the typical semesterted schedule.
Structural Benefits.
Resources: MSIP increases students’ access to learning resources. During their MSIP, students are allowed to travel to an area like a computer lab to do research, to a science lab to complete an assignment, or see a teacher for academic support. MSIP schools report
that on any given period approximately 5% of students travel to an area outside of the
MSIP class. Schools experiencing timetabling difficulties due to a shortage of lab space and gymnasium facilities have in effect created more facility opportunities with this 5 period system.
Timetable Conflicts: One of the early goals of the MSIP schedule was to deal with the increased number of conflicts students were experiencing in a shrinking school. Having 5 slots to place classes reduces the probability of class overlaps.
Educational Benefits.
Studies of existing MSIP schools show improvement in students' inductive thinking abilities, improved group interactions skills and an improvement in students’ abilities to memorize information. For many non-academic students MSIP also provides shorter classes making it easier for students to focus and complete homework in their MSIP class before going home.
Student-Centered Learning is a by-product of the MSIP period. The MSIP format demands that students be self-directed and organized each day by creating an environment of student autonomy - students are in charge of their own agenda. Homework, research and even group meetings are scheduled by the student during their MSIP period. This results in an increased level of responsibility and ownership over their own learning.
Mastering Learning: Research emphasizes the need for “do time” for consolidation of learning; MSIP provides this time. Each day students will have 60 minutes of ‘do time’ to complete homework, prepare for tests, and work on projects and assignments. This time will promote ‘mastering’ learning and prepare students to learn new concepts and skills, thus improving overall performance.


Hexachrome

Hexachrome is a discontinued six-color printing process designed by Pantone Inc. In addition to custom CMYK inks, Hexachrome uses orange and green inks to expand the color gamut for better color reproduction. It is therefore also known as a CMYKOG process.
Hexachrome was discontinued by Pantone in 2008 when Adobe Systems stopped supporting the HexWare plugin software. While the details of Hexachrome were not secret, its use was limited by trademark and patent to those obtaining a license from Pantone. The inventor of Hexachrome is Richard Herbert, who is also the president of Pantone Inc.
Software.
In order to use the Hexachrome process in a digital printing process, Pantone produced a plugin for Adobe Photoshop that allowed the designer to work in an RGB color space more typical of computer work. The plug in was called HexWare, which contained a set of Adobe plug-ins used by printers and designers who used the Hexachrome system. Older versions of QuarkXPress and Adobe InDesign also came with the Hexachrome system already installed and enabled.
Purpose.
The main purpose of Hexachrome was to create a printing ink system that could depict brighter and clearer pictures by being able to produce more accurate colors. Using this system instead of the CMYK ink system prints also allowed for more accurate skin tones and pastels. The Hexachrome system let users print images from computer screens that were not able to be accurately duplicated before. As well as producing overall better quality than previous systems, Hexachrome also increased efficiency as it produced many more spot colors. Having more spot colors increased efficiency by allowing the press to use one ink set for all jobs, rather than one specified ink set for each job. Keeping a printer configured for Hexachrome also eliminated the number of washes required on the printer; therefore saving times and simplifying printing production.
Users.
Hexachrome was used by software companies including Aldus Corporation, Adobe Systems, and Quark and printer manufacturers including HP, Epson, and Xerox.


Thoracic spinal nerve 4

The thoracic spinal nerve 4 (T4) is a spinal nerve of the thoracic segment.
It originates from the spinal column from below the thoracic vertebra 4 (T4).


Omega-Grammotoxin SIA

"omega"-Grammotoxin SIA (ω-grammotoxin SIA) is a protein toxin that inhibits P, Q, and N voltage-gated calcium channels (Ca2+ channels) in neurons.
Sources.
The source of ω-grammotoxin SIA is the venom of a tarantula spider ("Grammostola rosea").
Chemistry.
Amino acid sequence: Asp-Cys-Val-Arg-Phe-Trp-Gly-Lys-Cys-Ser-Gln-Thr-Ser-Asp-Cys-Cys-Pro-His-Leu-Ala-Cys-Lys-Ser-Lys-Trp-Pro-Arg-Asn-Ile-Cys-Val-Trp-Asp-Gly-Ser-Val
Molecular formula: C177H268N52O50S6
ω-Grammotoxin SIA can be purified from "Grammostola rosea" venom by reverse phase high performance liquid chromatography.
Target.
ω-Grammotoxin SIA is a 36 amino acid residue protein toxin from spider venom that inhibits P, Q, and N-type voltage-gated calcium channels in neurons. It binds to the channels with high affinity (if closed). It also binds to potassium channels but with lower affinity than to the calcium channels.
The toxin binding site has high affinity when channels are in closed states and low affinity when channels are activated. (4)
Mode of action.
It is believed that ω-grammotoxin SIA inhibits channel function by binding with high affinity to closed, resting states of the channel and that bound toxin makes it more difficult for channels to be opened by depolarization, so much larger depolarizations are required for channel activation.


Refractory period

Refractory period is a period immediately following a stimulus during which further stimulation has no effect. It may specifically refer to:


Wilson Bryan Key

Wilson Bryan Key Ph.D. (January 31, 1925 – October 8, 2008) was the author of several books about subliminal messages and subliminal advertising.
Career.
Key obtained his doctorate in communications from the University of Denver and taught journalism for a short period of time at the University of Western Ontario. He was a colleague and friend of Marshall McLuhan.
In a 1990 Reno, Nevada, court case against Judas Priest regarding subliminal messages and a suicide pact between two young men gained international attention. Key advised the plaintiffs lawyer to hire Bill Nickloff, an audio engineer, to find the subliminal messaging; however, the Judge found that the band and the label, CBS Corporation., were not responsible.
Death.
Key died following complications resulting from surgery. He is interred at the Northern Nevada Veteran's Memorial Cemetery in Fernley, Nevada. He was survived by his wife and three daughters.
Criticism.
His results and conclusions have been challenged, in books including the following:


Mid-fusiform sulcus

The mid-fusiform sulcus is a shallow sulcus that divides the fusiform gyrus into lateral and medial partitions. Functionally, the MFS divides both large-scale functional maps and identifies fine-scale functional regions such as the anterior portion of the fusiform face area.
Anatomy.
Cytoarchitectonically, the lateral and medial sides of the MFS are dissociable. The anterior and posterior portion of the MFS also have different long-range connections. The vertical occipital fasciculus terminates in the posterior aspects of the MFS, while the arcuate fasciculus terminates in the anterior portions of the MFS.
History.
The mid-fusiform sulcus was first identified in 1896 by Gustav Retzius. Retzius is known for many other discoveries such as Cajal-Retzius cells. He first identified the MFS as the sulcus sagittalis gyri fusiformis. Since his label, there have been several other proposed labels, but the MFS nomenclature is the most widely accepted in present day.


Robadope reagent


Cardiac neural crest

Neural crest cells are multipotent cells required for the development of cells, tissues and organ systems.
A subpopulation of neural crest cells are the cardiac neural crest complex. This complex refers to the cells found amongst the midotic placode and somite 3 destined to undergo epithelial-mesenchymal transformation and migration to the heart via pharyngeal arches 3, 4 and 6.
The cardiac neural crest complex plays a vital role in forming connective tissues that aid in outflow septation and modelling of the aortic arch arteries during early development. Ablation of the complex often leads to impaired myocardial functioning similar to symptoms present in DiGeorge syndrome. Consequently, the removal of cardiac crest cells that populate in pharyngeal arches has flow on effects on the thymus, parathyroid and thyroid gland.
Neural crest cells are a group of temporary, multipotent (can give rise to some other types of cells but not all) cells that are pinched off during the formation of the neural tube (precursor to the spinal cord and brain) and therefore are found at the dorsal (top) region of the neural tube during development. They are derived from the ectoderm germ layer, but are sometimes called the fourth germ layer because they are so important and give rise to so many other types of cells. They migrate throughout the body and create a large number of differentiated cells such as neurons, glial cells, pigment-containing cells in skin, skeletal tissue cells in the head, and many more.
Cardiac neural crest cells (CNCCs) are a type of neural crest cells that migrate to the circumpharyngeal ridge (an arc-shape ridge above the pharyngeal arches) and then into the 3rd, 4th and 6th pharyngeal arches and the cardiac outflow tract (OFT).
They extend from the otic placodes (the structure in developing embryos that will later form the ears) to the third somites (clusters of mesoderm that will become skeletal muscle, vertebrae and dermis).
The cardiac neural crest cells have a number of functions including creation of the muscle and connective tissue walls of large arteries; parts of the cardiac septum; parts of the thyroid, parathyroid and thymus glands. They differentiate into melanocytes and neurons and the cartilage and connective tissue of the pharyngeal arches. They may also contribute to the creation of the carotid body, the organ which monitors oxygen in the blood and regulates breathing.
Pathway of the migratory cardiac neural crest cell.
Induction.
Neural induction is the differentiation of progenitor cells into their final designation or type. The progenitor cells which will become CNCCs are found in the epiblast about Henson's node. Progenitor cells are brought into the neural folds. Molecules such as Wnt, fibroblast growth factor (FGF) and bone morphogenetic protein (BMP) provide signals which induce the progenitor cells to become CNCCs. Little is known about the signal cascade that promotes neural crest induction. However, it is known that an intermediate level of BMP is required: if BMP is too high or too low, the cells do not migrate.
Initial migration.
After induction, CNCCs lose their cell to cell contacts. This allows them to move through the extracellular matrix and interact with its components. The CNCCs, with the assistance of their filopodia and lamellipodia (actin containing extensions of cytoplasm that allow a cell to probe its path of migration), leave the neural tube and migrate along a dorsolateral pathway to the circumpharyngeal ridge. Along this pathway, CNCCs link together to form a stream of migrating cells. Cells at the front of the migration stream have a special polygonal shape and proliferate at a faster rate than trailing cells.
Development.
The cardiac neural crest originates from the region of cells between somite 3 and the midotic placode that migrate towards and into the cardiac outflow tract.
The cells migrate from the neural tube to populate pharyngeal arches 3, 4 and 6 with the largest population of the outflow tract originating from those in pharyngeal arches 4.
From here, a subpopulation of cells will develop into the endothelium of the aortic arch arteries while others will migrate into the outflow tract to form the aorticopulmonary and truncal septa. Other ectomesenchymal cells will form the thymus and parathyroid glands.
Epithelial-mesenchymal transition.
Prior to migration, during a process known as epithelial-mesenchymal transition, there is a loss of cell contact, remodelling of the cytoskeleton and increased motility and interaction with extracellular components in the matrix. An important step in this process is the suppression of adhesion protein E-cadherin present on epithelial cells to initiate the migration process. This suppression mechanism occurs via the growth factor BMP signalling to turn on a transcriptional repressor Smad-interacting protein 1 (Sip1) and marks the beginning of the epithelial-mesenchymal transition.
Early migration.
During migration, crest cells destined for pharyngeal arches maintain contact with each other via lamellipodia and filopodia. Short range local contact is maintained with lamellipodia whilst long range non-local contact is maintained with filopodia. During this process, connexin 43 (Cx43) regulates cell interaction by regulating the formation of channels known as gap junctions. Impaired Cx43 function in transgenic mice leads to altered coronary artery patterns and abnormal outflow tracts. Further gap junction signalling is dependent on a cadherin mediated cell adhesion formed during cross talking with p120 catenin signalling.
Appropriate outflow tract formation relies on a morphogen concentration gradient set up by fibroblast growth factor (FGF) secreting cells. Cardiac crest cells furthest away from FGF secreting cells will receive lower concentrations of FGF8 signalling than cells closer to FGF secreting cells. This allows for appropriate formation of the outflow tract. Cells located in rhombomeres 3and 5 undergo programmed cell death under signalling cues from semaphorins. The lack of cells in this region results in the formation of crest-free zones.
The process of migration requires a permissive extracellular matrix. The enzyme arginyltransferase creates this environment by adding an arginyl group onto newly synthesised proteins during post-translational modification. This process aids cells motility and ensures proteins the proteins contained within the actin cytoskeleton is prepped for migration.
Circumpharyngeal ridge.
Cell migration towards the circumpharyngeal ridge is forced to paused to allow for the formation of the caudal pharyngeal arches. Little is known about this pausing mechanism, but studies conducted in chicks have uncovered the role of mesoderm expressed factors EphrinB3 and EphrinB4 in forming fibronectin attachments.
Caudal pharynx and arch artery condensation.
Pharyngeal arches are tissues composed of mesoderm-derived cells enclosed by an external ectoderm and an internal endoderm. Once the caudal pharyngeal arches are formed, cardiac neural crest complexes will migrate towards these and colonise in arches 3, 4 and 6. Cells leading this migration maintain contact with the extracellular matrix and contain filopodia which act as extensions towards the ectodermal pharyngeal arches. A range of secreted factors ensure appropriate directionality of the cells. FGF8 acts as a chemotactic attraction in directing cellular movement towards pharyngeal arch 4.
A second signalling pathway that directs crest cell movement are the family of endothelin ligands. Migrating cardiac neural crest cells will populate at the correct pharyngeal arches under signalling guidance from EphrinA and Ephrin B variations. This corresponds with receptor expression at the pharyngeal arches. Pharyngeal arch 3 expresses EphrinA and EphrinB1 receptors and pharyngeal arch 2 expresses EphrinB2 and allows for the binding of EphrinA and EphrinB variations to guide migration of the cardiac neural crest cells.
Aortic arch remodelling.
The aortic arch arteries transport blood from the aorta to the head and trunk of the embryo. Normally, early development of the outflow tract begins with a single vessel that forms bilateral symmetrical branches at the aortic sac within pharyngeal arches. This process requires the elongation of the outflow tract as a prerequisite to ensure the correct series of looping and cardiac alignment. The cardiac neural crest complex then colonises in the truncal cushion and is localised to the subendothelial layer prior to spiralisation of the endocardial cushion to form the conotruncal ridges. This later undergoes remodelling to form the left-sided aortic pattern present in adult hearts. The group of cells found in the third aortic arch gives rise to common carotid arteries. Cells found in the fourth aortic arch differentiates to form the distal aortic arch and right subclavian artery, whilst cells in the sixth aortic arch develops into the pulmonary arteries. Cardiac neural crest cells express "Hox" genes that supports the development of arteries 3, 4 and 6 and the simultaneous regression of arteries 1 and 2. The ablation of "Hox" genes on cardiac neural crest cells causes defective outflow septation.
Ablation of cardiac neural crest complex.
Cardiac outflow anomalies.
One of the main cardiac outflow anomalies present during cardiac neural crest complex ablation is persistent truncus arteriosus. This arises when the arterial trunk fails to divide and cause the separation of pulmonary artery and aorta. This results in a lack of aorticopulmonary septum as the vessels which would normally disappear during normal development remains and interrupts the carotid vessels. The malformation of the heart and its associated great vessels depends on the extent and location of the cardiac neural crest complex ablation. Complete removal of cardiac neural crests results in persistent truncus arteriosus characterised in most cases by the presence of just one outflow valve and a ventricular septal defect. Mesencephalic neural crest cells interfere with normal development of cardiac outflow septation as its presence leads to persistent truncus arteriosus. However, the addition of trunk neural crest cells results in normal heart development.
Other outcomes of cardiac outflow anomalies includes Tetralogy of Fallot, Eisenmenger's complex, transposition of the great vessels and double outlet right ventricle.
Aortic arch arteries anomalies.
Overriding aorta is caused by the abnormal looping during early development of the heart and is accompanied with ventricular septal defects. Instead of abnormal formation of the aorticopulmonary septum, partial removal of cardiac neural crest results in an overriding aorta, whereby the misplacement of the aorta is found over the ventricular septum as opposed to the left ventricle. This results in a reduction of oxygenated blood as the aorta receives some deoxygenated blood from the flow of the right ventricle. There is a reduction in the quantity of endothelial tubes of ectomesenchyme in pharyngeal arches that surround the aortic arch arteries.
Other outcomes of aortic arch artery anomalies includes a double aortic arch, variable absence of the carotid arteries and left aortic arch.
Functional changes to the heart.
Functional changes to the heart becomes apparent well before structural changes are observed in the phenotype of ablated chicks. This is due to the embryo compromising morphological changes to the heart to maintain cardiac functioning via vasodilation. Despite an increase in embryonic stroke volume and cardiac output, this compensation of decreased contraction results in misalignment of the development vessels due to incomplete looping of the cardiac tube.
In an adult heart, myocardium contraction occurs via excitation-contraction coupling whereby cellular depolarisation occurs and allows an influx of calcium via voltage-gated calcium channels. A subsequent reuptake of calcium into the sarcoplasmic reticulum causes a decrease in intracellular calcium to cause myocardium relaxation. The removal of the cardiac neural crest complex causes a reduction in contractility of the myocardium. In embryos containing persistent truncus arteriosus, there is a significant 2-fold reduction in calcium currents, thereby interrupting the cardiac excitation-contraction coupling process to cause a reduction in contractility.
Pulmonary venous system.
During cardiogenesis, migration of the cardiac neural crest complex occurs prior to the development of the pulmonary system. There is no visible difference in the pulmonary veins of chick embryos that developed persistent truncus arteriosus and embryos with an intact cardiac neural crest complex. Ablation of the cardiac neural crest complex do not play a role in the systemic or pulmonary venous system as no visible venous defects is observed.
Derivative development.
Due to its population in pharyngeal arches, removal of the cardiac neural crest complex has flow on effects on the thymus, parathyroid and thyroid gland.
Location.
Into the pharyngeal arches and Truncus arteriosus (embryology), forming the aorticopulmonary septum and the smooth muscle of great arteries.
Anterior of the aorta to become the four pre-aortic ganglia: (celiac ganglion, superior mesenteric ganglion, inferior mesenteric ganglion and aortical renal ganglia).
Pause at the circumpharyngeal ridge.
At the circumpharyngeal arch the CNCCs must pause in their migration while the pharyngeal arches form.
Migration to the pharyngeal arches.
The CNCCs continue their migration into the newly formed pharyngeal arches, particularly the third, fourth and sixth arches. In the pharyngeal arches the CNCCs assist in the formation of the thyroid and parathyroid glands.
The leading cells have long filopodia that assist migration while cells in the middle of the migration have protrusions at their front and back allowing them to interact and communicate with leading cells, trailing cells and receive signals from the extracellular matrix.
A variety of growth factors and transcription factors in the extracellular matrix signal cells and direct them toward a specific arch. For example, signalling by FGF8 directs CNCCS to the fourth arch and keeps the cells viable.
Migration to the cardiac outflow tract.
The cardiac outflow tract is a temporary structure in the developing embryo that connects the ventricles with the aortic sac. Some CNCCs migrate beyond the pharyngeal arches to the cardiac outflow tract. CNCCS in the cardiac outflow tract contribute to the formation of the cardiac ganglia and mesenchyme at the junction of the subaortic and sub pulmonary myocardium (muscular heart tissue) of the outflow tract. A smaller portion of the CNCCs migrate to the proximal outflow tract where they help to close the ventricular outflow septum.
Molecular pathways.
Many signaling molecules are required for the differentiation, proliferation, migration and apoptosis of the CNCCs. The molecular pathways involved include the Wnt, Notch, BMP, FGF8 and GATA families of molecules. In addition to these signaling pathways, these processes are also mediated by environmental factors including blood flow, shear stress, and blood pressure.
The CNCCs interact with the cardiogenic mesoderm cells of the primary and secondary heart fields, which are derived from the cardiac crescent and will give rise to the endocardium, myocardium, and epicardium. The CNCCs themselves are the precursors to vascular smooth muscle cells and cardiac neurons.
For example, CNCCs are required for the formation of the aorticopulmonary septum (APS) that directs cardiac outflow into two tracts: the pulmonary trunk and the aorta of the developing heart. This is an example of remodelling which is dependent on signalling back and forth between CNCCs and the cardiogenic mesoderm. If this signalling is disrupted or there are defects in the CNCCS, cardiovascular anomalies may develop. These anomalies include persistent truncus arteriosus (PTA), double outlet right ventricle (DORV), tetralogy of Fallot and DiGeorge syndrome.
Wnt.
Wnt proteins are extracellular growth factors that activate intracellular signalling pathways. There are two types of pathways: canonical and non-canonical. The classic canonical Wnt pathway involves B-catenin protein as a signaling mediator. Wnt maintains B-catenin by preventing against Proteasome degradation. Thus, B-catenin is stabilized in the presence of Wnt and regulates gene transcription through interaction with TCF/LEF transcription factors. The canonical Wnt/B-catenin pathway is important for control of cell proliferation. The non-canonical Wnt pathway is independent of B-catenin and has an inhibitory effect on canonical Wnt signaling.
Wnt signaling pathways play a role in CNCC development as well as OFT development. In mice, decrease of B-catenin results in a decrease in the proliferation of CNCCs. Downregulation of the Wnt coreceptor Lrp6 leads to a reduction of CNCCs in the dorsal neural tube and in the pharyngeal arches, and results in ventricular, septal, and OFT defects. Canonical Wnt signaling is especially important for cell cycle regulation of CNCC development and the initiation of CNCC migration. Non-canonical Wnt signaling plays a greater role in promoting cardiac differentiation and OFT development.
Notch.
Notch is a transmembrane protein whose signaling is required for differentiation of CNCCs to vascular smooth muscle cells and for proliferation of cardiac myocytes (muscle cells of the heart). In mice, disruption of Notch signaling results in aortic arch branching defects and pulmonary stenosis, as well as a defect in the development of the smooth muscle cells of the sixth aortic arch artery, which is the precursor to the pulmonary artery. In humans, mutations in Notch most often result in bicuspid aortic valve disease and calcification of the aortic valve.
Bone morphogenetic proteins.
Bone morphogenetic proteins (BMPs) are required for neural crest cell migration into the cardiac cushions (precursors to heart valves and septa) and for differentiation of neural crest cells to smooth muscle cells of the aortic arch arteries. In neural crest–specific Alk2-deficient embryos, the cardiac cushions of the outflow tract are deficient in cells because of defects in neural crest cell migration.
Fibroblast growth factor 8.
Fibroblast growth factor 8 (FGF8) transcription factors are essential for regulating the addition of secondary heart field cells into the cardiac outflow tract. FGF8 mouse mutants have a range of cardiac defects including underdeveloped arch arteries and transposition of the great arteries.
GATA.
GATA transcription factors, which are complex molecules that bind to the DNA sequence "GATA", play a critical role in cell lineage differentiation restriction during cardiac development. The primary function of GATA6 in cardiovascular development is to regulate the morphogenetic patterning of the outflow tract and aortic arch. When GATA6 is inactivated in CNCCs, various cardiovascular defects such as persistent truncus arteriorus and interrupted aortic arch may occur. This phenotype (anomaly) was also observed when GATA6 was inactivated within vascular smooth muscle cells. GATA6 in combination with Wnt (Wnt2-GATA6) plays a role in the development of the posterior pole of the heart (the inflow tract).
CNCCS and ischaemic heart disease.
There is interest amongst researchers as to whether CNCCs can be used to repair human heart tissue. Heart attacks in humans are common and their rate of mortality is high. There are emergency treatments that hospitals can administer, such as angioplasty or surgery, but after that patients will likely be on medication for the long term and are more susceptible to heart attacks in the future. Other complications of heart attacks include cardiac arrhythmias and heart failure.
Although CNCCs are important in embryos, some CNCCs are retained in a dormant state to adulthood where they are called "neural crest stem cells". In 2005, Tomita transplanted neural crest stem cells from mammal hearts to the neural crest of chick embryos. These CNCCs were shown to migrate into the developing heart of the chick using the same dorsolateral pathway as the CNCCs, and differentiate into neural and glial cells.
Tamura's study of 2011 examined the fate of CNCCs after a heart attack (myocardial infarction) in young mice. The CNCCs in the young mice were tagged with enhanced green fluorescent protein (EGFP) and then traced. Tagged CNCCs were concentrated in the cardiac outflow tract, and some were found in the ventricular myocardium. These cells were also shown to be differentiating into cardiomyocytes as the heart grew. Although less were found, these EGFP-labelled CNCCs were still present in the adult heart. When a heart attack was induced, the CNCCs aggregated in the ischemic border zone area (an area of damaged tissue that can still be saved) and helped contribute to the regeneration of the tissue to some extent via differentiation into cardiomyocytes to replace the necrotic tissue.


Hadrucalcin

Hadrucalcin is a peptide toxin from the venom of the scorpion "Hadrurus gertschi". Hadrucalcin modifies the Ryanodine receptor channels RyR1 and RyR2, found in the sarcoplasmic reticulum, to a long-lasting subconductance state, thus inducing the release of calcium from the sarcoplasmic reticulum.
Source and etymology.
Hadrucalcin (HdCa, alternative spelling: Hadrucalcine) is obtained from the venom gland of the scorpion "Hadrurus gertschi", endemic to Guerrero, Mexico. Hadrucalcin is named after the scorpion that produces the peptide and its similarity to other toxins of the scorpion calcin family.
Chemistry.
Hadrucalcin is a peptide toxin from the scorpion calcin family. The mature hadrucalcin peptide is composed of 35 amino acids, whereas other members of the scorpion calcin family are composed of 33 amino acids. Based on the high degree of sequence similarity with maurocalcin, it is predicted that hadrucalcin folds along an inhibitor cystine knot motif, with disulfide bonds between positions 5 and 19, 12 and 23 and 18 and 34 of the mature peptide. Hadrucalcin has a molecular weight of 4190.5 Da. The most notable difference between hadrucalcin and other members of the scorpion calcin family is that hadrucalcin lacks two positive charged lysine residues (at positions 8 and 22 in other scorpion calcine toxins), that were previously thought to be important for affinity with RyR1. Instead, Hadrucalcin has two Lysine residues at positions 3 and 7 of the mature peptide, near the otherwise neutral N-terminal, resulting in a relatively low degree of amphiphilicity.
Target and Mode of Action.
Hadrucalcin targets ryanodine receptor channels RyR1 and RyR2, found in the sarcoplasmic reticulum of skeletal muscle cells and cardiac muscle cells respectively. By inducing a long-lasting subconductance state in RyR1 (35% of full conductance) and RyR2 (50% of full conductance), hadrucalcin increases the total ion flow over these channels. Within a few seconds, hadrucalcin is able to permeate the cell membrane of ventricular myocytes and induce the release of calcium from the sarcoplasmic reticulum. Despite functional effects on both channels, hadrucalcin only enhances the binding of ryanodine to RyR1 (EC50 = 37.8nM Hadrucalcin), but not to RyR2, suggesting the binding sites for hadrucalcin are structurally different in RyR1 and RyR2. The exact interacting sites of hadrucalcin on the ryanodine receptors are unknown.
Therapeutic Use.
Maurocalcin is the first proven example of a scorpion toxin that can act as a vector for large compounds. Hadrucalcin appears to be an even more potent cell penetrating peptide. A Hadrucalcin derivative has been used as a carrier for nanobiosensors.


Clothed female, naked male

Clothed female, naked male (CFNM) is a genre of nudity based on the real or imagined interaction of one or more nude men and one or more clothed women.
In classical antiquity, the portrayal of nude male form in art (including the exposure of genitals) was considered to be more acceptable than that of the naked female form. By the Renaissance, this view had reversed.
Feminist authors Christina Hoff Sommers and Naomi Wolf have written that women's sexual liberation has led many women to a role reversal wherein they view men as sex objects in a manner similar to what they criticize in men's treatment of women.


Hippocampus proper

The hippocampus proper refers to the actual structure of the hippocampus which is made up of four regions or subfields. The subfields CA1, CA2, CA3, and CA4 use the initials of cornu Ammonis, an earlier name of the hippocampus.
Structure.
There are four regions in the hippocampus proper which form a neural circuit called the trisynaptic circuit.
CA1.
CA1 is the first region in the hippocampal circuit, from which a major output pathway goes to layer V of the entorhinal cortex. Another significant output is to the subiculum.
CA2.
CA2 is a small region located between CA1 and CA3. It receives some input from layer II of the entorhinal cortex via the perforant path. Its pyramidal cells are more like those in CA3 than those in CA1. It is often ignored due to its small size.
CA3.
CA3 receives input from the mossy fibers of the granule cells in the dentate gyrus, and also from cells in the entorhinal cortex via the perforant path. The mossy fiber pathway ends in the stratum lucidum. The perforant path passes through the stratum lacunosum and ends in the stratum moleculare. There are also inputs from the medial septum and from the diagonal band of Broca which terminate in the stratum radiatum, along with commisural connections from the other side of the hippocampus.
The pyramidal cells in CA3 send some axons back to the dentate gyrus hilus, but they mostly project to regions CA2 and CA1 via the Schaffer collaterals. There are also a significant number of recurrent connections that terminate in CA3. Both the recurrent connections and the Schaffer collaterals terminate preferentially in the septal area in a dorsal direction from the originating cells. CA3 also sends a small set of output fibers to the lateral septum.
The region is conventionally divided into three divisions. CA3a is the part of the cell band that is most distant from the dentate (and closest to CA1). CA3b is the middle part of the band nearest to the fimbria and fornix connection. CA3c is nearest to the dentate, inserting into the hilus. CA3 overall, has been considered to be the “pacemaker” of the hippocampus. Much of the synchronous bursting activity associated with interictal epileptiform activity appears to be generated in CA3. Its excitatory collateral connectivity seems to be mostly responsible for this. CA3 uniquely, has pyramidal cell axon collaterals that ramify extensively with local regions and make excitatory contacts with them. CA3 has been implicated in a number of working theories on memory and hippocampal learning processes. Slow oscillatory rhythms (theta-band; 3–8 Hz) are cholinergically driven patterns that depend on coupling of interneurons and pyramidal cell axons via gap junctions, as well as glutaminergic (excitatory) and GABAergic (inhibitory) synapses. Sharp EEG waves seen here are also implicated in memory consolidation.
CA4.
CA4 is often called the hilus or hilar region if considered as a part of the dentate gyrus. Unlike the pyramidal neurons in CA1 and CA3, the neurons here include mossy cells that primarily receive inputs from the granule cells in the dentate gyrus in the form of mossy fibers.
They also receive a small number of connections from pyramidal cells in CA3. They, in turn, project back into the dentate gyrus at distant septotemporal levels.


Aprindine

Aprindine is a Class 1b antiarrhythmic agent.