Stratum lucidum of hippocampus

The stratum lucidum of the hippocampus is a layer of the hippocampus between the stratum pyramidale and the stratum radiatum. It is the tract of the mossy fiber projections, both inhibitory and excitatory from the granule cells of the dentate gyrus. One mossy fiber may make up to 37 connections to a single pyramidal cell, and innervate around 12 pyramidal cells on top of that. Any given pyramidal cell in the stratum lucidum may get input from as many as 50 granule cells.
Location.
The stratum lucidum is located within the CA3 region of the hippocampus distally to the dentate gyrus and proximally to the CA2 region. It is composed of a densely packed bundle of mossy fibers (unmyelinated) and spiny and aspiny interneurons that lie immediately above the CA3 pyramidal cell layer in the hippocampus, and immediately below the stratum radiatum. Most mossy fiber axons are perpendicular to the CA3 pyramidal region where they project and synapse to either the CA3 pyramidal cells or the stratum oriens below the pyramidal region. The interneurons of the stratum lucidum are generally found to be local circuit neurons remaining within the CA3 region. A majority of the interneuron axons remain within the stratum lucidum but some also extend to the stratum radiatum and stratum lacunosum-molecular above the radiatum as well as to the CA1 and hilur regions.
Composition.
Stratum pyramidale.
In hippocampus anatomy, the stratum pyramidale is one of seven layers, or stratums, that make up the entire neural structure. The stratum pyramidale is the third deepest hippocampal layer, and in relation to the stratum lucidum, is located underneath it. The stratum pyramidale houses cell bodies of the pyramidal neurons, which are the foundational excitatory neurons of the hippocampus. In the CA3 region of the hippocampus, the stratum pyramidale connects with the stratum lucidum by mossy fibers that run through both subfields.
Stratum radiatum.
The layer above the stratum lucidum.
Interneurons.
The types of neurons found in the stratum lucidum are called interneurons, neurons which form a connection between other neurons in a different location. This situation is described in the mossy fiber axon connection in the CA3 stratum lucidum region of the hippocampus as is in relation to Purkinje cells. The interneurons found in the stratum lucidum are of two classes, spiny and aspiny. Spiny neurons are a "special type of inhibitory cell", characterized by spiny projections on the dendrites of the cell. The axons of these neurons in the hippocampus terminate primarily in the stratum lucidum and stratum radiatum of CA3. Spiny neurons are of importance because of their "pivotal role in motor control, habit formation, and motivated behavior". They receive synaptic inputs from mossy fibers boutons, as well as multiple other synaptic terminals. The majority of axon collaterals of these neurons remain in the stratum lucidum and CA3 region, though in some cases axon collaterals of these neurons are observed migrating into the CA1 region of the hippocampus. Aspiny neurons, the second class of neurons found in the stratum lucidum, are another type of inhibitory cell similar to spiny neurons, though lacking dendrite projections. They make up the majority of the neuron composition in comparison to spiny neurons, about 63 percent. The somata of aspiny neurons are for the most part bipolar, generating 2–5 primary dendrites "that to a varying extent displayed varicose swellings in their course". Similar to spiny neurons, aspiny neuron dendrites "branch extensively in stratum lucidum and stratum radiatum of CA3", in contrast to spiny neurons, however, some dendrites "traversed stratum pyramidale and entered stratum oriens", the second deepest layer of the hippocampus. Additionally, what distinguishes aspiny neurons form spiny neurons is their higher maximal firing rates and narrower action potential half-widths than their spiny counterparts.
Function within the nervous system.
In the hippocampus, the stratum lucidum contains many neurons that act locally in local pathways. The spiny neurons of the stratum lucidum act in primary motor control as interneurons that relay to other neurons. The spiny and aspiny neurons act in both inhibitory and excitatory circuits.


Harderian gland

The Harderian gland is a gland found within the eye's orbit that occurs in tetrapods (reptiles, amphibians, birds and mammals) that possess a nictitating membrane.
The gland can be compound tubular or compound tubuloalveolar, and the fluid it secretes (mucous, serous or lipid) varies between different groups of animals. In some animals, it acts as an accessory to the lacrimal gland, secreting fluid that eases movement of the nictitating membrane. Research has proposed that the gland has several other functions, including that of a photoprotective organ, a location of immune response, a source of thermoregulatory lipids, a source of pheromones, a site of osmoregulation, inter alia. In mammals, the gland secretes an oily substance used to preen the fur. The presence or absence of this gland is one of the cues used by palaeontologists to determine when fur evolved in the ancestors of mammals.
The Harderian gland was first described in 1694 by Swiss anatomist Johann Jacob Harder (1656–1711). He documented his findings in a paper titled "Glandula nova lachrymalis una cum ductu excretorio in cervis et damis", ("A new lachrymal gland with an excretory duct in red and fallow deer", English translation).


Perisynaptic schwann cells

Perisynaptic schwann cells (also known as Terminal schwann cells or Teloglia) are Neuroglia found at the Neuromuscular junction (NMJ) with known functions in synaptic transmission, synaptogenesis, and nerve regeneration. These cells share a common ancestor with both Myelinating and Non-Myelinating Schwann Cells called Neural Crest cells. Perisynaptic Schwann Cells (PSCs) contribute to the tripartite synapse organization in combination with the pre-synaptic nerve and the post-synaptic muscle fiber. PSCs are considered to be the glial component of the Neuromuscular Junction (NMJ) and have a similar functionality to that of Astrocytes in the Central Nervous System. The characteristics of PSCs are based on both external synaptic properties and internal glial properties, where the internal characteristics of PSCs develop based on the associated synapse, for example: the PSCs of a fast-twitch muscle fiber differ from the PSCs of a slow-twitch muscle fiber even when removed from their natural synaptic environment. PSCs of fast-twitch muscle fibers have higher Calcium levels in response to synapse innervation when compared to slow-twitch PSCs. This balance between external and internal influences creates a range of PSCs that are present in the many Neuromuscular Junctions of the Peripheral Nervous System.
Discovery.
Perisynaptic (Terminal) Schwann Cells were first discovered by Louis-Antoine Ranvier in 1878 when he observed branching networks surrounding the motor end plate (neural portion of NMJ). He described PSCs as "arborisation nuclei" due to their many projections into the synapse seen under the microscope. These cells were distinguished from muscle fibre nuclei and the motor end plate, making the third component of the tripartite synaptic model. It was found that these newly discovered cells were present in nerve degeneration models, showing their non-neural nature. The proximity of PSCs to the motor end plate raised questions about their functionality, but little was known up until the vast research conducted in the past two decades.
Development.
The origin of Perisynaptic (Terminal) Schwann Cells was largely under question in the 1960s as there were arguments on whether the cells were of epithelial or glial descent, but the development of PSCs has been linked to Neural crest origin. As described above, PSCs are a type of non-myelinating Schwann cell, which develop from neural crest cells. The general series of developmental events can be summarized as this: Neural Crest cells develop into Schwann cell precursors which further develop into Immature Schwann cells which then differentiate into Myelinating Schwann cells and non-Myelinating schwann cells of which Perisynaptic Schwann cells are a subset.
Neural crest cells are found in the dorsal neural tube from which nerves and glia alike grow and Neural crest cells are the precursors to many various tissue types including enteric neurons and glia. Schwann cell precursors (a first derivative of Neural crest cells) are present as the nerve axon grows from the dorsal neural tube, but it has been shown that these glial precursors are not essential to axonal growth. The transition from neural crest cells to Schwann cell precursors is characterized by Sox10 and generally occurs around embryonic day 12-13 in rats. Schwann cell precursors then differentiate into Immature Schwann cells from which myelinating and non-myelinating Schwann cells are directly descended. These cells generally appear around embryonic day 13-15 in rats. The differentation of Immature Schwann cells occurs after birth and is dependent on the axons in which the glia are associated. This differentation is known to be reversible, as seen in regeneration models. Perisynaptic Schwann cells develop as non-myelinating Schwann cells and encapsulate the NMJ. PSCs can be attributed to glial lineage by the presence of Calcium binding proteins S100, Glial fibrillary acidic protein (GFAP), and Protein 0. These proteins are seen in other glial cells such as Myelinating Schwann cells and Neural Crest cells. While the lineage of non-Myelinating Schwann cells is known from neural crest cells, the exact development of PSCs from non-Myelinating Schwann cells is not fully understood.
Roles at the neuromuscular junction (NMJ).
Synaptogenesis.
Synaptogenesis is the formation of a synapse and in this case the Neuromuscular Junction is of interest. In this section, the focus is on the development of the NMJ from the outgrowth of axons during development. As mentioned in the development section, Schwann cell precursors accompany growing axons as they reach their associated muscles. It is now known that these PSC precursors are not essential to axonal growth, but when present they guide growth cones and help with the maintenance of NMJs after they are formed. After the initial nervous-muscle interface is formed, there is a striking growth in the number of PSCs at each newly developed NMJ. If, however, there is a lack of PSCs (for example in an ablated model) once the NMJ is formed, there is a lack of further axonal growth or even a retraction of axons can be observed. This is seen in a study on frog NMJs 8 and 12 days after ablation where there was a 44% retraction rate by the 12th day with no PSCs. This retraction shows that PSCs are not essential for the growth of axons, but are essential for the long-term maintenance of NMJs.
Cultures have been developed that simulate the functions of PSCs using various cell-derived factors in vitro. These cultures are used to understand the molecular basis for which PSCs promote synaptogenesis. From these cultures it has been found that TGF-ß1 (transforming growth factor-ß1) is essential for the development of synapses in vitro. This TGF-ß1 appears to stop nerve growth in order to promote the nerve-muscle synapse formation, however its role in vivo is unknown.
NMJ maintenance.
It is known that PSCs are essential for the maintenance of NMJs during development, but PSCs are essential for mature NMJ as well. In frog ablation models, there is observable difference in NMJ properties that arise approximately seven days after PSCs were selectively removed. These changes include both structural and functional abnormalities. In ablation models, samples were taken at regular intervals following removal of PSCs. Immediately following ablatio (at 5 hours), there were no noticeable differences in synaptic structure or functionality. Motor-end plate potentials were unaltered in the pre-ablated and the 5 hour ablated models, showing that PSCs are not essential for short-term maintenance of the NMJ. Approximately 13% of ablated NMJ were observed to be retracted partially or entirely one week after ablation and there was a 50% decrease in end plate potential frequency, meaning the NMJs were firing approximately half as often! This same ablation model cannot be performed in mammals, as the antibody mAB sA12 used in the frog model does not ablate mammalian PSCs. The mammalian PSC, when treated with antibodies against gangliosides in Miller-Fisher Syndrome, show not change in NMJ properties in the short-term, but long-term data has not collected. It can be gathered that PSCs play an important role in long-term maintenance of frog NMJ, but it is unknown if the same effects are true in mammalian NMJs.
NMJ transmission.
There are two proposed means by which PSCs can interact with the transmission at the NMJ. One means by which this may occur is through detecting and differentiating between synaptic transmissions, or, in a sense, “hearing” the transmission of the NMJ. The other is altering and participating in the transmission at the NMJ, or “talking” into the already existing message.
Listening to synaptic transmissions.
The first evidence that the PSCs may not only serve a supportive role, was the discovery of increased Calcium levels in PSCs during NMJ transmission. This increase in intracellular calcium levels is not observed in the myelinating Schwann cells that line the axon, but only in the PSCs present at the NMJ. This increase in intracellular calcium has since been linked to synaptic neurotransmitter release in the synapse, but the relationship between Calcium release and neurotransmitters present is not perfectly linear but more complex due to a plethora of extrinsic and intrinsic factors. This ability to respond to NMJ activity can be further explored by observing pre-synaptic simulation amplitude recognition, and pattern recognition in PSCs.
It is also known that at NMJ with multiple innervations, PSCs are able to detect transmissions from the “competing sources” . This differentiation is observed by various Calcium levels proportional to the simulation amplitude. These calcium changes were different for the two competing sources. The “stronger” impulse seen by the PSCs induced a higher level of intracellular Calcium, meaning PSCs are able to distinguish the stronger of two inputs in the NMJ.
Calcium levels also vary based on the pattern in which the stimulation is delivered. A study was performed to observe glial response to both a “burst” and “continuous” impulse and the responses were not seen to be the same. These two patterns were composed of: 1800 pulses of 20 Hz with recovery time, and 1800 pulses at 20 Hz continuously. Calcium levels in response to the “burst” pattern oscillated and the Calcium levels in response to the “continuous” pattern were constant.
These findings show that the PSCs are in fact able to “recognize” unique transmissions through the NMJ. These “recognitions” are characterized by the amplitude and duration of the intracellular Calcium increase.
Contributing to synaptic transmission.
 As a result of responding to NMJ transmission, it is also seen that PSCs can actually alter synaptic transmissions as well. The observed increase in Calcium seen above is possible due to PSCs protein receptors: ACh receptors, ATP Receptors, G-coupled receptors, and other receptors. Manipulation of PSCs G-coupled protein receptors lead to altered synaptic transmission. If G-coupled receptors were stimulated by GTP-like ligand, the result is seen as a decrease in neurotransmitter release. If a GDP-like ligand is used to stimulate the same G-coupled receptors, it is seen that there is a reduction in synapse depression. These changes show that PSCs are an play an active role in synaptic transmission. While these interactions are measurable, the impact of PSCs activity in the NMJ is not significant in relation to the pre-synaptic motor neuron impulse, meaning the alterations that PSCs make to NMJ activity is not significant.
NMJ regeneration.
PSCs have important roles in synaptogenesis during development as well as in the regeneration of nerve axons after nerve injury. If a nerve injury occurs, PSCs form PSC bridges which connect adjacent NMJ sites. The recovering axon grows along a scaffolding of basal lamina left from the damaged Schwann cells and reaches the proximal PSC site (nearest NMJ). PSC bridges connect adjacent NMJ sites and allow axonal growth from one NMJ to the other. This bridge is a shorter distance for axonal growth than the original route. Once the axon has innervated both sites, it continues growing in a retrograde direction (toward the injury site) to innervate other affected NMJs. PSCs have a large role in creating growth scaffolds from one injured NMJ to another. These PSC bridges are seen in vivo following complement-mediated injury in a murine model, showing that this role of PSCs are present in mammalian NMJs. It has also been seen that motor-end plate terminals are unstable without M2 ACh receptors and muscle fiber growth is uncontrolled in the absence of M5 ACh receptors. This shows that in NMJ regeneration, ACh receptors present on PSCs modulate and control growth.


Kim Peek

Laurence Kim Peek (November 11, 1951December 19, 2009) was an American savant. Known as a "megasavant", he had an exceptional memory, but he also experienced social difficulties, possibly resulting from a developmental disability related to congenital brain abnormalities. He was the inspiration for the character Raymond Babbitt in the 1988 movie "Rain Man". Although Peek was diagnosed with Autism Spectrum Disorder and severe intellectual disability, he is now thought to have had FG syndrome. The Utah Film Center’s Peek Award is meant to honor his legacy.
Early life.
Laurence Kim Peek was born in Salt Lake City, Utah, with macrocephaly, damage to the cerebellum, and agenesis of the corpus callosum, a condition in which the bundle of nerves that connects the two hemispheres of the brain is missing; in Peek's case, secondary connectors such as the anterior commissure were also missing. There is speculation that his neurons made unusual connections due to the absence of a corpus callosum, resulting in an increased memory capacity. According to Peek's father, Fran (Francis) Peek, Kim was able to memorize things from the age of 16–20 months. He read books, memorized them, and then placed them upside down on the shelf to show that he had finished reading them, a practice he maintained all his life. He could speed through a book in about an hour and remember almost everything he had read, memorizing vast amounts of information in subjects ranging from history and literature, geography and numbers to sports, music and dates. Peek read by scanning the left page with his left eye, while reading the right page with his right eye. According to an article in "The Times" newspaper, he could accurately recall the contents of at least 12,000 books.
Peek lived in Murray, Utah, and spent a considerable amount of his time reading at the Salt Lake City Library and demonstrating his capabilities at schools, with great help from his father.
Peek did not walk until he was four years old, and even then in a sidelong manner. He could not button up his shirt and had difficulty with other ordinary motor skills, presumably due to his damaged cerebellum, which normally coordinates motor activities. In psychological testing, Peek yielded superior ability in the performance subtests and limited ability in the verbal subtests, resulting in his overall IQ of 87 not being considered a valid measure of his cognitive ability.
"Rain Man".
In 1984, screenwriter Barry Morrow met Peek in Arlington, Texas; the result of the meeting was the 1988 Academy Award winning film "Rain Man". The character of Raymond Babbitt, although inspired by Peek, was depicted as being autistic. Dustin Hoffman, who portrayed Babbitt in the film, met Peek and other savants to get an understanding of their nature and to play the role as accurately and methodically as possible. The movie led to a number of requests for appearances, which increased Peek's self-confidence. Barry Morrow gave Peek his Oscar statuette to carry with him and show at these appearances; it has since been referred to as the "Most Loved Oscar Statue" because it has been held by more people than any other. Peek also enjoyed approaching strangers and showing them his talent for calendar calculations by telling them on which day of the week they were born and what news items were on the front page of major newspapers that day. Peek also appeared on television. He travelled with his father, who took care of him and performed many motor tasks that Peek found difficult.
Scientific investigation.
In 2004, scientists at the Center for Bioinformatics Space Life Sciences at the NASA Ames Research Center examined Peek with a series of tests including computed tomography (CT scan) and magnetic resonance imaging (MRI). The intent was to create a three-dimensional view of his brain structure and to compare the images to MRI scans performed in 1988. These were the first tentative approaches in using non-invasive technology to further investigate Kim's savant abilities.
A 2008 study concluded that Peek probably had FG syndrome, a rare X chromosome-linked genetic syndrome that causes physical anomalies such as hypotonia (low muscle tone) and macrocephaly (abnormally large head).
Appearances.
"Cameo appearance in Rain Man movie at 2:06:30 -2:06:41. Man leaving Amtrak train station as Tom Cruise and Dustin Hoffman enter train station."
Death.
Peek died of a heart attack at his home on December 19, 2009, aged 58. His father, Fran, died on April 5, 2014, aged 88.
Tributes.
Barry Morrow put his own Oscar statuette on permanent loan to Salt Lake City in memory of Kim Peek, and put forward the money for the Peek Award, which "pays tribute to artists, media makers, and film subjects who are positively impacting our society's perception of people with disabilities" and is given out by the Utah Film Center.


DBL-583

DBL-583 is a selective dopamine reuptake inhibitor of the piperazine chemical class. It is the decanoate ester of a hydroxy vanoxerine. DBL-583 breaks down very slowly in the body, lasting for up to a month after a single injection.


Suboccipital nerve

The suboccipital nerve (first cervical dorsal ramus) is the dorsal primary ramus of the first cervical nerve (C1). It exits the spinal cord between the skull and the first cervical vertebra, the atlas.
It lies within the suboccipital triangle along with the vertebral artery, where the artery enters the foramen magnum.
It supplies muscles of the suboccipital triangle, the rectus capitis posterior major, obliquus capitis superior, and obliquus capitis inferior. The suboccipital nerve also innervates rectus capitis posterior minor.


Circumventricular organs

Circumventricular organs (CVOs) (circum-: around ; ventricular: of ventricle) are structures in the brain characterized by their extensive and highly permeable capillaries, unlike those in the rest of the brain where there exists a blood–brain barrier (BBB) at the capillary level. Although the term "circumventricular organs" was originally proposed in 1958 by Austrian anatomist Helmut O. Hofer concerning structures around the brain ventricular system, the penetration of blood-borne dyes into small specific CVO regions was discovered in the early 20th century. The "permeable" CVOs enabling rapid neurohumoral exchange include the subfornical organ (SFO), the area postrema (AP), the vascular organ of lamina terminalis (VOLT), the median eminence, the pituitary neural lobe, and the pineal gland.
The circumventricular organs are midline structures around the third and fourth ventricles that are in contact with blood and cerebrospinal fluid, and they facilitate special types of communication between the central nervous system and peripheral blood. Additionally, they are an integral part of neuroendocrine function. Highly permeable capillaries allow the CVOs to act as an alternative route for peptides and hormones in the neural tissue to sample from and secrete to circulating blood. CVOs also have roles in body fluid regulation, cardiovascular functions, immune responses, thirst, feeding behavior and reproductive behavior.
CVOs can be classified as either sensory or secretory organs serving homeostatic functions and body water balance. The sensory organs include the area postrema, the subfornical organ, and the vascular organ of lamina terminalis, all having the ability to sense signals in blood, then pass that information neurally to other brain regions. Through their neural circuitry, they provide direct information to the autonomic nervous system from the systemic circulation. The secretory organs include the subcommissural organ (SCO), the pituitary gland, the median eminence, and the pineal gland. These organs are responsible for secreting hormones and glycoproteins into the peripheral blood using feedback from both the brain environment and external stimuli.
Circumventricular organs contain capillary networks that vary between one another and within individual organs both in density and permeability, with most CVO capillaries having a permeable endothelial cell layer, except for those in the subcommissural organ. Furthermore, all CVOs contain neural tissue, enabling a neuroendocrine role.
Although the choroid plexus also has permeable capillaries, it does not contain neural tissue; rather, its primary role is to produce cerebrospinal fluid (CSF), and therefore is typically not classified as a CVO.
Sensory organs.
Area postrema.
Anatomy.
The area postrema is located in the caudal medulla oblongata near the junction of the brainstem and the spinal cord. In humans and in most other mammals that have been studied, it consists of swellings on either wall of the fourth ventricle. In rodents and lagomorphs, however, the area postrema forms a midline structure dorsal to the obex. When viewed histologically for its capillary distribution and morphology, the area postrema has numerous subregions separated according to capillary permeability, rates of blood flow, and duration of blood transit through respective capillary beds.
Function.
Relatively little is known about the function of the area postrema in humans. However, there is strong evidence that the area postrema acts as the chemoreceptor trigger zone for vomiting, which is triggered by the presence of noxious stimulation from the blood. There is also evidence that the area postrema is the site at which angiotensin stimulates glucose metabolism, presumed efferent neural activity, blood pressure control, and thirst. The area postrema also has integrative capacities that enable it to send major and minor efferents to sections of the brain involved in the autonomic control of cardiovascular and respiratory activities.
Vascular organ of the lamina terminalis.
Anatomy.
Classified as a sensory circumventricular organ (along with the SFO and AP), the vascular organ of lamina terminalis (VOLT) is situated in the anterior wall of the third ventricle. Characteristically of the CVOs, it lacks the tight endothelial blood brain barrier. The vascular organ is further characterized by the afferent inputs from the subfornical organ (SFO), the median pre-optic nucleus (MnPO) region, the brainstem, and even the hypothalamus. Conversely, the vascular organ of the lamina terminalis maintains efferent projections to the stria medullaris and basal ganglia.
As a major player in the maintenance of the mammalian body fluid homeostasis, the VOLT features the primary neurons responsible for osmosensory balance. These neurons, in turn, feature angiotensin type I receptors, which are used by circulating angiotensin II to initiate water intake and sodium consumption. In addition to the angiotensin receptors, the neurons of the VOLT are also characterized by the presence of a nonselective cation channel deemed the transient receptor potential vanilloid 1, or TRPV1. Though there are other receptors within the TRPV family, a study by Ciura, Liedtke, and Bourque demonstrated that hypertonicity sensing operated via a mechanical mechanism of TRPV1 but not TRPV4. Despite a significant amount of data, the anatomy of the VOLT is not yet fully comprehended.
Function.
As previously mentioned, the vascular organ of lamina terminalis features neurons responsible for the homeostatic conservation of osmolarity. In addition, the fenestrated vasculature of the VOLT allows the astrocytes and neurons of the VOLT to perceive a wide variety of plasma molecules whose signals may be transduced into other regions of the brain, thereby eliciting autonomic and inflammatory reactions.
In experiments, mammalian VOLT neurons were shown to transduce hypertonicity by the activation of the TRPV1 nonselective cation channels. These channels are highly permeable to calcium and are responsible for membrane depolarization and increased action potential discharge. Stated simply, an increase in osmolarity results in a reversible depolarization of the VOLT neurons. This can be seen through the predominantly excitatory effects of ANG on the VOLT through the TRPV1 receptor. In this context, it is worthy to note the VOLT neurons typically feature a resting membrane potential in the range of -50 to -67 mV with input resistances ranging from 65 to 360 MΩ.
Despite a solid understanding of the VOLT’s role in the maintenance of body fluid homeostasis, other functions are less understood. For example, it is thought that the VOLT may also play a role in the regulation of LH secretion via a negative feedback mechanism. It is also hypothesized that the VOLT may be the mechanism through which pyrogens function to initiate a febrile response in the CNS. Finally, VOLT neurons have been observed to respond to temperature changes indicating that the organum vasculosum of the lamina terminalis is subject to different climates.
Subfornical organ (SFO).
Anatomy.
The subfornical organ is a sensory CVO situated on the underside of the fornix and lacking a BBB, the absence of which characterizes the circumventricular organs. Protruding into the third ventricle of the brain, the highly vascularized SFO can be divided into 3–4 anatomical zones, especially by its capillary density and structure. The central zone is composed exclusively of the glial cells and neuronal cell bodies. Conversely, the rostral and caudal areas are mostly made of nerve fibers while very few neurons and glial cells can be seen in this area. Functionally, however, the SFO may be viewed in two portions, the dorsolateral peripheral (pSFO) division and the ventromedial core segment.
As an important mechanism of both energy and osmotic homeostasis, the SFO has many efferent projections. In fact, SFO neurons have been experimentally shown to broadcast efferent projections to regions involved in cardiovascular regulation including the lateral hypothalamus with fibers terminating in the supraoptic (SON) and paraventricular (PVN) nuclei, and the anteroventral 3rd ventricle (AV3V) with fibers terminating in the VOLT and the median preoptic area. It seems that the most essential of all these connections is the SFO’s projections to the paraventricular hypothalamic nucleus. Based on their functional relevance, the SFO neurons can be branded as either GE, featuring nonselective cation channels, or GI, featuring potassium channels. While the afferent projections of the SFO are considered less important than the various efferent connections, it is still notable that the subfornical organ receives synaptic input from the zona incerta and arcuate nucleus.
Study of subfornical organ anatomy is still ongoing but evidence has demonstrated slow blood transit time which may facilitate the sensory capability of SFO, enabling increased contact time for blood-borne signals to penetrate its permeable capillaries and influence regulation of blood pressure and body fluids. This observation coincides with the fact that SFO neurons have been shown to be intrinsically osmosensitive. Finally, it has been established that SFO neurons maintain resting membrane potential in the range of -57 to -65 mV.
Function.
The subfornical organ is active in many bodily processes including, but not limited to, osmoregulation, cardiovascular regulation, and energy homeostasis. In a study by Ferguson, both hyper- and hypotonic stimuli facilitated an osmotic response. This observation demonstrated the fact that the SFO is involved in the maintenance of blood pressure. Featuring an AT1 receptor for ANG, the SFO neurons demonstrate an excitatory response when activated by ANG, therefore increasing blood pressure. The induction of the drinking response via the SFO can be antagonized, however, by the peptide, ANP. Additional research has demonstrated that the subfornical organ may be an important intermediary though which leptin acts to maintain blood pressure within normal physiological limits via descending autonomic pathways associated with cardiovascular control.
Recent research has focused on the subfornical organ as an area particularly important in the regulation of energy. The observation that subfornical neurons respond to a wide range of circulating energy balance signals, and that electrical stimulation of the SFO in rats resulted in food intake supports the SFO’s importance in energy homeostasis. Additionally, it is assumed that the SFO is the lone forebrain structure capable of constant monitoring of circulating concentrations of glucose. This responsiveness to glucose again serves to solidify the SFO’s integral role as a regulator of energy homeostasis.
Secretory organs.
Subcommissural organ.
Anatomy.
The subcommissural organ (SCO) is a small secretory organ located on the ventral surface of the posterior commissure near the anterior entrance of the cerebral aqueduct. It differs from other CVOs in that it lacks a high concentration of fenestrated capillaries, making its BBB less permeable. On the other hand, its role as a neuroendocrine structure associated with the ventricular system qualifies it for classification as a CVO. Related to its secretory function, the SCO is partially composed of ependymal cells. These ependymocytes are characterized by elongated cell bodies that contain secretory materials and are covered in cilia. The most prominent of these is the glycoprotein SCO-spondin.
Function.
The main function of the SCO is the secretion of the glycoprotein SCO-spondin, which is released into the third ventricle where it aggregates to create Reissner's fiber (RF). Reissner's fiber is a long fibrous projection that travels caudally through the Sylvian aqueduct and terminates in the spinal cord. This fiber is thought to contribute to the maintenance of the patency of the sylvian aqueduct.
While the function of the subcommissural organ is still under investigation, it has been hypothesized that it is also part of the mechanism of aldosterone secretion and CSF detoxification, along with osmoregulation. The SCO is innervated by many systems, the most common of which is associated with the serotonergic system. The serotonergic system influences water and sodium intake. During water deprivation it will also reduce its innervation to the SCO. The reduction of input to the SCO causes a marked decrease in RF production. This finding implies that the subcommissural organ and its associated Reissner's fiber are an integral part of fluid electrolyte balance and water homeostasis.
Pituitary gland.
Anatomy.
The pituitary gland is subdivided into two lobes, the anterior pituitary and the posterior pituitary (also known as the adenohypophysis and neurohypophysis respectively). Each one functions as a separate endocrine organ, and both are circumventricular organs. The anterior pituitary contains non-neural secretory cells derived from oral ectoderm which are indirectly controlled by "releasing hormones" from the median eminence of the hypothalamus, through the hypophyseal portal circulation. The posterior pituitary consists of axonal projections that directly extend from cell bodies in the hypothalamus, through the infundibulum.
It is located in the sella turcica of the sphenoid bone at the base of the skull.
Function.
The pituitary is sometimes referred to as the “master gland” because it has a crucial role in maintaining homeostasis and guiding the activity of other glands. The anterior lobe secretes growth hormone, prolactin and tropic hormones for the thyroid, gonads and adrenal glands. The posterior lobe stores and releases oxytocin and vasopressin, also known as antidiuretic hormone (ADH), which are produced in the hypothalamus.
Median eminence.
The median eminence (ME) is located in the inferior portion of the hypothalamus and is ventral to the third ventricle. While some publications do not list the ME as a CVO, when it is considered to be a circumventricular organ, it is classified as a secretory organ. The median eminence is rich in fenestrated capillaries, allowing for the passage of proteins and neurohormones. More specifically, the median eminence allows for the transport of neurohormones between the CSF and the peripheral blood supply. The major cell type that makes up the median eminence are specialized ependymal cells known as tanycytes. These contribute to the organ's ability to selectively allow macromolecules to pass from the central to the peripheral neuroendocrine systems. Ventromedial subregions of the bilateral hypothalamic arcuate nucleus display relatively high capillary permeability, indicating this nucleus may have moment-to-moment regulatory roles for sensing and neurally conveying hormonal signals.
Tanycytes line the floor of the third ventricle and can be characterized by a singular long projection that delves deep inside the hypothalamus. Tanycytes have been evolutionarily linked to radial glial cells of the central nervous system. The tanycytes of the median eminence are often found along the fenestrated peripheral capillaries. They are tightly packed on the capillaries, forming a seal between the third ventricle and the median eminence. This seal can be attributed to the tight junctions observed between tanycytes and functions to restrict the travel of molecules between the median eminence and the third ventricle. The median eminence is also closely linked to the transport of GnRH between the median eminence and the anterior pituitary. Neuronal projections of GnRH neurons actually end at the median eminence, allowing for its release into the portal blood system.
Pineal gland.
Anatomy.
Gross anatomy.
The morphology of the pineal gland varies greatly among mammals. The most commonly used classification for this gland takes into account its location relative to the diencephalon and the third ventricle of the brain, as well as its size and shape. Under these conditions, the human pineal gland is classified as type A. A type A pineal gland rests proximally to the posterior section of the diencephalon. It is located within 1-2mm of the midline of the brain.
The pineal gland starts to develop during the second month of gestation. In the average adult, the dimensions are as follow: 5-9mm in length, 1-5mm in width and 3-5mm in thickness. Its average weight is 100–180 mg.
The pineal gland consists of a central core made up of small lobes and a cortex that possesses a diffuse distribution of neurons. The principal cell type of the pineal is the pinealocyte sensu stricto. This type of cell has a prominent nucleus and a granular appearance.
Vascularization and innervation.
The level of vascularization in the pineal gland is high. It receives a large supply of blood from branches of the posterior choroidal arteries that derive from cerebral arteries in the posterior mesencephalon.
The pineal gland is innervated by fibers from the peripheral parasympathetic and sympathetic systems, in addition to fibers from the central nervous system. The most important set of fibers involved are the unmyelinated postganglionic sympathetic fibers from the superior cervical ganglia, which also form the bilateral nervi conarii. The second set of fibers enters the pineal gland anteriorly via the commissural peduncles. The third set of fibers is myelinated and forms the ventro-lateral pineal tract.
Function.
The pineal gland is considered a secretory organ and its activity shows circadian oscillations. Its main function – secretion of the hormone melatonin – rests when there is no input from the primary circadian pacemaker in the suprachiasmatic nuclei. Melatonin production is controlled by the previously mentioned circadian timing and is suppressed by light. Pineal tumors can affect sexual development, but the mechanism has yet to be established.
Other pineal substances.
Other peptides aside from melatonin have been detected in the pineal. They are most likely associated with a type of innervation deemed "pineal peptidergic innervation." These include vasopressin, oxytocin, VIP, NPY, peptide histidine isoleucine, calcitonin gene-related peptide, substance P and somatostatin.


Thermometric titration

A thermometric titration is one of a number of instrumental titration techniques where endpoints can be located accurately and precisely without a subjective interpretation on the part of the analyst as to their location. Enthalpy change is arguably the most fundamental and universal property of chemical reactions, so the observation of temperature change is a natural choice in monitoring their progress. It is not a new technique, with possibly the first recognizable thermometric titration method reported early in the 20th century (Bell and Cowell, 1913). In spite of its attractive features, and in spite of the considerable research that has been conducted in the field and a large body of applications that have been developed; it has been until now an under-utilized technique in the critical area of industrial process and quality control. Automated potentiometric titration systems have pre-dominated in this area since the 1970s. With the advent of cheap computers able to handle the powerful thermometric titration software, development has now reached the stage where easy to use automated thermometric titration systems can in many cases offer a superior alternative to potentiometric titrimetry.
Comparison between potentiometric and thermometric titrations..
Potentiometric titrimetry has been the predominant automated titrimetric technique since the 1970s, so it is worthwhile considering the basic differences between it and thermometric titrimetry.
Potentiometrically-sensed titrations rely on a free energy change in the reaction system. Measurement of a free energy dependent term is necessary.
Where:
In order for a reaction to be amenable to potentiometric titrimetry, the free energy change must be sufficient for an appropriate sensor to respond with a significant inflection (or "kink") in the titration curve where sensor response is plotted against the amount of titrant delivered.
However, free energy is just one of three related parameters in describing any chemical reaction:
where:
For any reaction where the free energy is not opposed by the entropy change, the enthalpy change will be significantly greater than the free energy. Thus a titration based on a change in temperature (which permits observation of the enthalpy change) will show a greater inflection than will curves obtained from sensors reacting to free energy changes alone.
Thermometric titrations.
In the thermometric titration, titrant is added at a known constant rate to a titrand until the completion of the reaction is indicated by a change in temperature. The endpoint is determined by an inflection in the curve generated by the output of a temperature measuring device.
Consider the titration reaction:
Where:
At completion, the reaction produces a molar heat of reaction Δ"H"r which is shown as a measurable temperature change Δ"T". In an ideal system, where no losses or gains of heat due to environmental influences are involved, the progress of the reaction is observed as a constant increase or decrease of temperature depending respectively on whether Δ"H"r is negative (indicating an exothermic reaction) or positive (indicating an endothermic reaction). In this context, environmental influences may include (in order of importance):
If the equilibrium for the reaction lies far to the right (i.e. a stoichiometric equilibrium has been achieved), then when all analyte has been reacted by the titrant continuing addition of titrant will be revealed by a sharp break in the temperature/volume curve. Figures 1a and 1b illustrate idealized examples.
The shape of experimentally obtained thermometric titration plots will vary from such idealized examples, and some of the environmental influences listed above may have impacts. Curvature at the endpoint might be observed. This can be due to insensitivity of the sensor or where thermal equilibrium at the endpoint is slow to occur. It can also occur where the reaction between titrant and titrand does not proceed to stoichiometric completion. The determinant of the degree to which a reaction will proceed to completion is the free energy change. If this is favourable, then the reaction will proceed to be completion and be essentially stoichiometric. In this case, the sharpness of the endpoint is dependent on the magnitude of the enthalpy change. If it is unfavourable, the endpoint will be rounded regardless of the magnitude of the enthalpy change. Reactions where non-stoichiometric equilibria are evident can be used to obtain satisfactory results using a thermometric titration approach. If the portions of the titration curve both prior to and after the endpoint are reasonably linear, then the intersection of tangents to these lines will accurately locate the endpoint. This is illustrated in Figure 2.
Consider the reaction for the equation "a"A + "b"B = "p"P which is non-stoichiometric at equilibrium. Let A represent the titrant, and B the titrand. At the beginning of the titration, the titrand B is strongly in excess, and the reaction is pushed towards completion. Under these conditions, for a constant rate of titrant addition the temperature increase is constant and the curve is essentially linear until the endpoint is approached. In a similar manner, when the titrant is in excess past the endpoint, a linear temperature response can also be anticipated. Thus intersection of tangents will reveal the true endpoint.
An actual thermometric titration plot for the determination of a strong base with a strong acid is illustrated in Figure 3.
The most practical sensor for measuring temperature change in titrating solutions has been found to be the thermistor. Thermistors are small solid state devices which exhibit relatively large changes in electrical resistance for small changes in temperature. They are manufactured from sintered mixed metal oxides, with lead wires enabling connection to electrical circuitry. The thermistor is encapsulated in a suitable electrically insulating medium with satisfactory heat transfer characteristics and acceptable chemical resistance. Typically for thermistors used for chemical analysis the encapsulating medium is glass, although thermistors encapsulated in epoxy resin may be used in circumstances where either chemical attack (e.g., by acidic fluoride-containing solutions) or severe mechanical stress is anticipated. The thermistor is supported by suitable electronic circuitry to maximize sensitivity to minute changes in solution temperature. The circuitry in the Metrohm 859 Titrotherm thermometric titration interface moldule is capable of resolving temperature changes as low as 10−5 K.
A critical element in modern automated thermometric titrimetry is the ability to locate the endpoint with a high degree of reproducibility. It is clearly impractical and insufficient for modern demands of accuracy and precision to estimate the inflection by intersection of tangents. This is done conveniently by derivatization of the temperature curve. The second derivative essentially locates the intersection of tangents to the temperature curve immediately pre- and post- the breakpoint.
Thermistors respond quickly to small changes in temperature such as temperature gradients in the mixed titration solution, and thus the signal can exhibit a small amount of noise. Prior to derivatization it is therefore necessary to digitally smooth (or “filter”) the temperature curve in order to obtain sharp, symmetrical second derivative “peaks” which will accurately locate the correct inflection point. This is illustrated in Figure 5. The degree of digital smoothing is optimized for each determination, and is stored as a method parameter for application every time a titration for that particular analysis is run.
Because enthalpy change is a universal characteristic of chemical reactions, thermometric endpoint sensing can be applied to a wide range of titration types, e.g.
Further, since the sensor is not required to interact with the titration solution electrochemically, titrations in non-conducting media can be performed, as can titrations using reactions for which no convenient or cost-effective potentiometric sensor is available.
Thermometric titrations generally demand rapid reaction kinetics in order to obtain sharp reproducible endpoints. Where reaction kinetics are slow, and direct titrations between titrant and titrand are not possible, indirect or back-titrations often can be devised to solve the problem.
Catalytically enhanced endpoints can be used in some instances where the temperature change at the endpoint is very small and endpoints would not be detected satisfactorily by the titration software.
The suitability of a particular chemical reaction as a candidate for a thermometric titration procedure can generally be predicted on the basis of the estimated amount of analyte present in the sample and the enthalpy of the reaction. However, other parameters such as the kinetics of the reaction, the sample matrix itself, heats of dilution and losses of heat to the environment can affect the outcome. A properly designed experimental program is the most reliable way of determining the viability of a thermometric titration approach. Successful applications for thermometric titrations are generally where titrant-titrand reaction kinetics are fast, and chemical equilibria are stoichiometric or nearly so.
Apparatus and setup for automated thermometric titrimetry.
A suitable setup for automated thermometric titrimetry comprises the following:
Figure 6 illustrates a modern automated thermometric titration system based on the Metrohm 859 Titrotherm interface module with Thermoprobe sensor, Metrohm 800 Dosino dispensing devices and a computer running the operational software.
Figure 7 is a schematic of the relationship between components in automated thermometric titration system.
A = dosing device

B = thermometric sensor

C = stirring device

D = thermometric titration interface module

E = computer
Types of thermometric titration.
Applications for thermometric titrimetry are drawn from the major groupings, namely:
Because the sensor does not interact electrically or electrochemically with the solution, electrical conductance of the titrating medium is not a pre-requisite for a determination. Titrations may be carried out in completely non-conducting, non-polar media if required. Further, titrations may be carried out in turbid solutions or even suspensions of solids, and titrations where precipitates are reaction products can be contemplated. The range of possible thermometric titration applications far exceeds the actual experience of this writer, and the reader will be referred to the appropriate literature in some instances.
Acid–base titrations.
Determination of fully dissociated acids and bases..
The heat of neutralization of a fully dissociated acid with a fully dissociated base is approximately –56kJ/mol. The reaction is thus strongly exothermic, and is an excellent basis for a wide range of analysis in industry. An advantage for the industrial analyst is that the use of stronger titrants (1 to 2 mol/L) permits a reduction in the amount of sample preparation, and samples can often be directly and accurately dispensed into the titration vessel prior to titration.
Titration of weak acids.
Weakly dissociated acids yield sharp thermometric endpoints when titrated with a strong base. For instance, bicarbonate can be unequivocally determined in the company of carbonate by titrating with hydroxyl (Δ0Hr=-40.9 kJ/mol).
Titration of acid mixtures.
Mixtures of complex acids can be resolved by thermometric titration with standard NaOH in aqueous solution. In a mixture of nitric, acetic and phosphoric acids used in the fabrication of semi-conductors, three endpoints could be predicted on the basis of the dissociation constants of the acids:
The key to determine the amount of each acid present in the mixture is the ability to obtain an accurate value for the amount of phosphoric acid present, as revealed by titration of the third proton of H3PO4.
Figure 10 illustrates a titration plot of this mixture, showing 3 sharp endpoints.
Titration of complex alkaline solutions.
The thermometric titrimetric analysis of sodium aluminate liquor (“Bayer liquor”) in the production of alumina from bauxite is accomplished in an automated two titration sequence. This is an adaptation of a classic thermometric titration application (VanDalen and Ward, 1973). In the first titration, tartrate solution is added to an aliquot of liquor to complex aluminate, releasing one mole of hydroxyl for each mole of aluminate present. This is titrated acidimetrically along with “free” hydroxyl present and the carbonate content (as a second endpoint). The second titration is preceded by the automatic addition of fluoride solution. The alumina-tartrate complex is broken in favour of the formation of an aluminium fluoride complex and the concomitant release of three moles of hydroxyl for each mole of aluminium present, which are then titrated acidimetrically. The whole determination can be completed in less than 5 minutes.
Non-aqueous acid–base titrations.
Non-aqueous acid–base titrations can be carried out advantageously by thermometric means.
Acid leach solutions from some copper mines can contain large quantities of Fe(III) as well as Cu(II). The “free acid” (sulfuric acid) content of these leach solutions is a critical process parameter. While thermometric titrimetry can determine the free acid content with modest amounts of Fe(III), in some solutions the Fe(III) content is so high as to cause serious interference. Complexation with necessarily large amounts of oxalate is undesirable due to the toxicity of the reagent. A thermometric titration was devised by diluting the aliquot with propan-2-ol and titration with standard KOH in propan-2-ol. Most of the metal content precipitated prior to the commencement of the titration, and a clear, sharp endpoint for the sulfuric acid content was obtained.
Catalyzed endpoint thermometric acid–base titrations.
The determination of trace acids in organic matrices is a common analytical task assigned to titrimetry. Examples are Total Acid Number (TAN) in mineral and lubricating oils and Free Fatty Acids (FFA) in edible fats and oils. Automated potentiometric titration procedures have been granted standard method status, for example by ASTM for TAN and AOAC for FFA. The methodology is similar in both instances. The sample is dissolved in a suitable solvent mixture; say a hydrocarbon and an alcohol which also must contain a small amount of water. The water is intended to enhance the electrical conductivity of the solution. The trace acids are titrated with standard base in an alcohol. The sample environment is essentially hostile to the pH electrode used to sense the titration. The electrode must be taken out of service on a regular basis to rehydrate the glass sensing membrane, which is also in danger of fouling by the oily sample solution.
A recent thermometric titrimetric procedure for the determination of FFA developed by Cameiro "et al." (2002) has been shown to be particularly amenable to automation. It is fast, highly precise, and results agree very well with those obtained by the official AOAC method. The temperature change for the titration of very weak acids such as oleic acid by 0.1 mol/L KOH in propan-2-ol is too small to yield an accurate endpoint. In this procedure, a small amount of paraformaldehyde as a fine powder is added to the titrand before the titration. At the endpoint, the first excess of hydroxyl ions catalyzes the depolymerization of paraformaldehyde. The reaction is strongly endothermic and yields a sharp inflection. The titration plot is illustrated in Figure 13. The speed of this titration coupled with its precision and accuracy makes it ideal for the analysis of FFA in biodiesel feedstocks and product.
Redox titrations.
Titrations with permanganate and dichromate.
Redox reactions are normally strongly exothermic, and can make excellent candidates for thermometric titrations. In the classical determination of ferrous ion with permanganate, the reaction enthalpy is more than double that of a strong acid/strong base titration:Δ0"H"r =
−123.9 kJ/mol of Fe. The determination of hydrogen peroxide by permanganate titration is even more strongly exothermic at Δ0"H"r =
−149.6 kJ/mol H2O2
Titrations with thiosulfate.
In the determination of hypochlorite (for example in commercial bleach formulations), a direct titration with thiosulfate can be employed without recourse to an iodometric finish.
Thermometric iodometric titrations employing thiosulfate as a titrant are also practical, for example in the determination of Cu(II). In this instance, it has been found advantageous to incorporate the potassium iodide reagent with the thiosulfate titrant in such proportions that iodine is released into solution just prior to its reduction by thiosulfate. This minimizes iodine losses during the course of the titration.
Titrations with hypochlorite.
While relatively unstable and requiring frequent standardization, sodium hypochlorite has been used in a very rapid thermometric titration method for the determination of ammonium ion. This is an alternative to the classical approach of ammonia distillation from basic solution and consequent acid–base titration. The thermometric titration is carried out in bicarbonate solution containing bromide ion (Brown et al., 1969).
Complexometric (EDTA) titrations.
Thermometric titrations employing sodium salts of ethylenediaminetetra-acetic acid (EDTA) have been demonstrated for the determination of a range of metal ions. Reaction enthalpies are modest, so titrations are normally carried out with titrant concentrations of 1 mol/L. This necessitates the use of the tetra-sodium salt of EDTA rather than the more common di-sodium salt which is saturated at a concentration of only approximately 0.25 mol/L.
An excellent application is the sequential determination of calcium and magnesium. Although calcium reacts exothermically with EDTA (heat of chelation ~-23.4 kJ/mol), magnesium reacts endothermically with a heat of chelation of ~+20.1 kJ/mol. This is illustrated in the titration plot of EDTA with calcium and magnesium in sea water (Figure 14). Following the solution temperature curve, the breakpoint for the calcium content (red-tagged endpoint) is followed by a region of modest temperature rise due to competition between the heats of dilution of the titrant with the solution, and the endothermic reaction of Mg2+ and EDTA. The breakpoint for the consumption of Mg2+ (blue-tagged endpoint) by EDTA is revealed by upswing in temperature caused purely by the heat of dilution.
Direct EDTA titrations with metal ions are possible when reaction kinetics are fast, for example zinc, copper, calcium and magnesium. However, with slower reaction kinetics such as those exhibited by cobalt and nickel, back-titrations are used. Titrations for cobalt and nickel are carried out in an ammoniacal environment; buffered with ammonia:ammonium chloride solution. An excess of EDTA is added, and is back-titrated with Cu(II) solution. It is postulated that the breakpoint is revealed by the difference in reaction enthalpies between the formation of the Cu-EDTA complex, and that for the formation of the Cu-amine complex.
A catalyzed endpoint procedure to determine trace amounts of metal ions in solution (down to approximately 10 mg/L) employs 0.01 mol/L EDTA. This has been applied to the determination of low level Cu(II) in specialized plating baths, and to the determination of total hardness in water. The reaction enthalpies of EDTA with most metal ions are often quite low, and typically titrant concentrations around 1 mol/L are employed with commensurately high amounts of titrand in order to obtain sharp, reproducible endpoints. Using a catalytically indicated endpoint, very low EDTA titrant concentrations can be used. A back-titration is used. An excess of EDTA solution is added. The excess of EDTA is back-titrated with a suitable metal ion such as Mn2+ or Cu2+. At the endpoint, the first excess of metal ion catalyzes a strongly exothermic reaction between a polyhdric phenol (such as resorcinol) and hydrogen peroxide.
Precipitation titrations.
Thermometric titrimetry is particularly suited to the determination of a range of analytes where a precipitate is formed by reaction with the titrant. In some cases, an alternative to traditional potentiometric titration practice can be offered. In other cases, reaction chemistries may be employed for which there is no satisfactory equivalent in potentiometric titrimetry.
Titrations with silver nitrate.
Thermometric titrations of silver nitrate with halides and cyanide are all possible. The reaction of silver nitrate with chloride is strongly exothermic. For instance, the reaction enthalpy of Ag+ with Cl− is a high −61.2 kJ/mol. This permits convenient determination of chloride with commonly available standard 0.1 mol/L AgNO3. Endpoints are very sharp, and with care, chloride concentrations down to 15 mg/L can be analyzed. Bromide and chloride may be determined in admixture.
Titration of sulfate.
Sulfate may be rapidly and easily titrated thermometrically using standard solutions of Ba2+ as titrant. Industrially, the procedure has been applied to the determination of sulfate in brine (including electrolysis brines), in nickel refining solutions and particularly for sulfate in wet process phosphoric acid, where it has proven to be quite popular. The procedure can also be used to assist in the analysis of complex acid mixtures containing sulfuric acid where resorting to titration in non-aqueous media is not feasible.
The reaction enthalpy for the formation of barium sulfate is a modest −18.8 kJ/mol. This can place a restriction on the lower limit of sulfate in a sample which can be analyzed.
Titration of aluminium with fluoride.
Thermometric titrimetry offers a rapid, highly precise method for the determination of aluminium in solution. A solution of aluminium is conditioned with acetate buffer and an excess of sodium and potassium ions. Titration with sodium or potassium fluoride yields the exothermic precipitation of an insoluble alumino-fluoride salt.
Because 6 mole of fluoride react with one mole of aluminium, the titration is particularly precise, and a coefficient of variance (CV) of 0.03 has been achieved in the analysis of alum.
When aluminium ion (say as aluminium nitrate) is employed as the titrant, fluoride can be determined using the same chemistry. This titration is useful in the determination of fluoride in complex acid mixtures used as etchants in the semi-conductor industry.
Titration of total orthophosphate.
Orthophosphate ion can be conveniently thermometrically titrated with magnesium ions in the presence of ammonium ion. An aliquot of sample is buffered to approximately pH10 with an NH3/NH4Cl solution.
The reaction:
Is exothermic. CV’s of under 0.1 have been achieved in test applications. The procedure is suitable for the determination of orthophosphate in fertilizers and other products.
Titration of nickel.
Nickel can be titrated thermometrically using di-sodium dimethylglyoximate as titrant. The chemistry is analogous to the classic gravimetric procedure, but the time taken for a determination can be reduced from many hours to a few minutes. Potential interferences need to be considered.
Titration of anionic and cationic surfactants.
Anionic and cationic surfactants can be determined thermometrically by titrating one type against the other. For instance, benzalkonium chloride (a quaternary type cationic surfactant) may be determined in cleaners and algaecides for swimming pools and spas by titrating with a standard solution of sodium dodecyl sulfate. Alternatively, anionic surfactants such as sodium lauryl sulfate can be titrated with cetyl pyridinium chloride.
Titration of non-ionic surfactants.
When an excess of Ba2+ is added to a non-ionic surfactant of the alkyl propylene oxide derivative type, a pseudo-cationic complex is formed. This may be titrated with standard sodium tetraphenylborate. Two moles tetraphenylborate react with one mole of the Ba2+/ non-ionic surfactant complex.
Miscellaneous aqueous titrations.
Titration of fluoride with boric acid.
Acidic solutions of fluoride (including hydrofluoric acid) can be determined by a simple thermometric titration with boric acid.
The titration plot illustrated in Figure 19 shows that the endpoint is quite rounded, suggesting that the reaction might not proceed to stoichiometric equilibrium. However, since the regions of the temperature curve immediately before and after the endpoint are quite linear, the second derivative of this curve (representing the intersection of tangents) will accurately locate the endpoint. Indeed, excellent precision can be obtained with this titration, with a CV of less than 0.1.
Determination of formaldehyde.
Formaldehyde can be determined in electroless copper plating solutions by the addition of an excess of sodium sulfite solution and titrating the liberated hydroxyl ion with standard acid.
References.
solutions. "Anal. Chem." 45 (13) 2248-2251, (1973)


List of idioms of improbability

There are many idioms of improbability, or adynata, used to denote that a given event is impossible or extremely unlikely to occur.


Dauricine

Dauricine is a plant metabolite, chemically classified as a phenol, an aromatic ether, and an isoquinoline alkaloid. It has been isolated from the Asian vine Menispermum "dauricum", commonly known as Asian moonseed, and the North American vine Menispermum "canadense", commonly known as Canadian moonseed. Scientists Tetsuji Kametani and Keiichiro Fukumoto of Japan are credited with being the first to synthesize dauricine in 1964, using both the Arndt-Eistert reaction and Bischler-Napieralski reaction to do so. Dauricine has been studied "in vitro" for its potential to inhibit cancer cell growth and to block cardiac transmembrane Na+, K+, and Ca2+ ion currents.


Summer term

Summer term is the summer academic term at many British schools and universities and elsewhere in the world.
In the UK, 'Summer term' runs from the Easter holiday until the end of the academic year in June or July, and thus corresponds to the Easter term at Cambridge University, and Trinity term at Oxford, and some other places. 'Summer term' is defined in some UK statutory instruments, such as the Education (Assessment Regulations) (Foundation to Key Stage 3) Order (Northern Ireland) 2007, which says:
"summer term" means the period commencing immediately after the Easter holiday and ending with the school year.
The Education (National Curriculum) (Key Stage 1 Assessment Arrangements) (England) Order 2004 says more simply:
"summer term" means the final term of the school year.
Covering the possibility of six-term academic years, the School Finance (England) Regulations 2008 say
"summer term" means the third term of the school year where a school has three terms, or the fifth and sixth terms where a school has six terms


Monoclonality

Monoclonality is the term describing cells produced from a single ancestral cell by repeated cellular replication. Thus "monoclonal cells" can be said to form a single clone. The term "monoclonal" comes from the Ancient Greek "monos", meaning "alone" or "single", and "klon", meaning "twig".
The process of replication can occur "in vivo", or may be stimulated "in vitro" for laboratory manipulations. The use of the term typically implies that there is some method to distinguish between the cells of the original population from which the single ancestral cell is derived, such as a random genetic alteration, which is inherited by the progeny.
Common usages of this term include:


Felodipine

Felodipine is a medication of the calcium channel blocker type which is used to treat high blood pressure.
It was patented in 1978 and approved for medical use in 1988.
Medical uses.
Felodipine is used to treat high blood pressure and stable angina.
It should not be used for people who are pregnant, have acute heart failure, are having a heart attack, have an obstructed heart valve, or have obstructions that block bloodflow out of the heart.
For people with liver failure the dose needs to be lowered, because felodipine is cleared by the liver.
Adverse effects.
The only very common side effect, occurring in more than 1/10 people, is pain and swelling in the arms and legs.
Common side effects, occurring in between 1% and 10% of people, include flushing, headache, heart palpitations, dizziness and fatigue.
Felodipine can exacerbate gingivitis.
Interactions.
Felodipine is metabolized by cytochrome P450 3A4, so substances that inhibit or activate CYP3A4 can strongly effect how much felodipine is present.
CYP3A4 inhibitors, which increase the amount of felodipine available per dose, include cimetidine, erythromycin, itraconazole, ketoconazole, HIV protease inhibitors, and grapefruit juice.
CYP3A4 activators, which decrease the amount of felodipine available per dose, include phenytoin, carbamazepine, rifampicin, barbiturates, efavirenz, nevirapine, and Saint John's wort.
Mechanism of action.
Felodipine is a calcium channel blocker. Felodipine has additionally been found to act as an antagonist of the mineralocorticoid receptor, or as an antimineralocorticoid.
Different calcium channels are present in vascular tissue and cardiac tissue; an "in vitro" study on human vascular and cardiac tissues comparing how selective various calcium channel blockers are for vascular compared to cardiac tissue found the following vascular/cardiac tissue ratios: mibefradil 41, felodipine 12; nifedipine 7, amlodipine 5, and verapamil 0.2.
Chemistry.
Felodipine is a member of the 1,4-dihydropyridine class of calcium channel blockers. It is a racemic mixture, and is insoluble in water but is soluble in dichloromethane and ethanol.
History.
The Swedish company Hässle, a division of Astra AB, discovered felodipine; it filed a patent application in 1979 claiming felodipine as an antihypertensive drug. Astra partnered this drug and others with Merck & Co. in the US under a 1982 agreement between the companies. The drug was approved by the FDA in 1991 after a three and a half year review; the drug entered a very crowded market the included the other calcium channel blockers nifedipine, verapamil, nicardipine, and isradipine. The FDA gave the drug a 1C rating, meaning that it found little difference between felodipine and the drugs already approved for the same use.
In 1994 Astra AB and Merck changed their partnership to a joint venture called Astra Merck, and in 1998 Astra (by that time, AstraZeneca) bought out Merck's rights in the joint venture.
The first generics became available in Sweden in 2003 and in the US in 2004.
In April 2016, AstraZeneca announced that they were selling the right to market felodipine in China to China Medical System Holdings for $310 million; AZ would continue to manufacture the drug.
Society and culture.
As of 2016, felodipine was marketed under many brand names worldwide: Auronal, Cardioplen, Catrazil, Dewei, Dilahex, Enfelo, Erding, Fedil, Fedisyn, Feldil, Felicipin, Felo, Felocard, Felocor, Feloday, Felodil, Felodin, Felodip, Felodipin, Felodipina, Felodipine, Felodipino, Felodistad, Felogard, Felohexal, Felop, Felopine, Felostad, Feloten, Felotens, Felpin, Flodicar, Flodil, Keliping, Keydipin, Lodistad, Modip, Munobal, Nirmadil, Parmid, Penedil, Perfudal, Phelop, Phenodical, Plendil, Plentopine, Polo, Presid, Preslow, Prevex, Renedil, Sistar, Splendil, Stapin, Topidil, Vascalpha, Versant, and XiaoDing.
The combination of felodipine and candesartan was marketed as Atacand.
The combination of felodipine and ramipril was marketed as Delmuno, Tazko, Triacor, Triapin, Triasyn, Tri-Plen, Unimax, and Unitens.
The combination of felodipine and enalapril was marketed as Lexxel.
The combination of felodipine and metoprolol was marketed as Logimat, Logimax, and Mobloc.


Lateral inhibition

In neurobiology, lateral inhibition is the capacity of an excited neuron to reduce the activity of its neighbors. Lateral inhibition disables the spreading of action potentials from excited neurons to neighboring neurons in the lateral direction. This creates a contrast in stimulation that allows increased sensory perception. It is also referred to as lateral antagonism and occurs primarily in visual processes, but also in tactile, auditory, and even olfactory processing. Cells that utilize lateral inhibition appear primarily in the cerebral cortex and thalamus and make up lateral inhibitory networks (LINs). Artificial lateral inhibition has been incorporated into artificial sensory systems, such as vision chips, hearing systems, and optical mice. An often under-appreciated point is that although lateral inhibition is visualised in a spatial sense, it is also thought to exist in what is known as "lateral inhibition across abstract dimensions." This refers to lateral inhibition between neurons that are not adjacent in a spatial sense, but in terms of modality of stimulus. This phenomenon is thought to aid in colour discrimination.
History.
The concept of neural inhibition (in motor systems) was well known to Descartes and his contemporaries.
Sensory inhibition in vision was inferred by Ernst Mach in 1865 as depicted in his mach band.
Inhibition in single sensory neurons was discovered and investigated starting in 1949 by Haldan K. Hartline when he used logarithms to express the effect of Ganglion receptive fields. His algorithms also help explain the experiment conducted by David H. Hubel and Torsten Wiesel that expressed a variation of sensory processing, including lateral inhibition, within different species.
In 1956, Hartline revisited this concept of lateral inhibition in horseshoe crab (Limulus polyphemus) eyes, during an experiment conducted with the aid of Henry G Wagner and Floyd Ratliff. Hartline explored the anatomy of ommatidia in the horseshoe crab because of their similar function and physiological anatomy to photoreceptors in the human eye. Also, they are much larger than photoreceptors in humans, which would make them much easier to observe and record. Hartline contrasted the response signal of the ommatidium when a single concentrated beam of light was directed at one receptor unit as opposed to three surrounding units. He further supported his theory of lateral inhibition as the response signal of one unit was stronger when the surrounding units were not exposed to light.
Sensory inhibition.
Georg von Békésy, in his book "Sensory Inhibition", explores a wide range of inhibitory phenomena in sensory systems, and interprets them in terms of sharpening.
Visual inhibition.
Lateral inhibition increases the contrast and sharpness in visual response. This phenomenon already occurs in the mammalian retina. In the dark, a small light stimulus will enhance the different photoreceptors (rod cells). The rods in the center of the stimulus will transduce the "light" signal to the brain, whereas different rods on the outside of the stimulus will send a "dark" signal to the brain due to lateral inhibition from horizontal cells. This contrast between the light and dark creates a sharper image. (Compare unsharp masking in digital processing). This mechanism also creates the Mach band visual effect.
Visual lateral inhibition is the process in which photoreceptor cells aid the brain in perceiving contrast within an image. Electromagnetic light enters the eye by passing through the cornea, pupil, and the lens (optics). It then bypasses the ganglion cells, amacrine cells, bipolar cells, and horizontal cells in order to reach the photoreceptors rod cells which absorb light. The rods become stimulated by the energy from the light and release an excitatory neural signal to the horizontal cells.
This excitatory signal, however, will only be transmitted by the rod cells in the center of the ganglion cell receptive field to ganglion cells because horizontal cells respond by sending an inhibitory signal to the neighboring rods to create a balance that allows mammals to perceive more vivid images. The central rod will send the light signals directly to bipolar cells which in turn will relay the signal to the ganglion cells. Amacrine cells also produce lateral inhibition to bipolar cells and ganglion cells to perform various visual computations including image sharpening. The final visual signals will be sent to the thalamus and cerebral cortex, where additional lateral inhibition occurs.
Tactile inhibition.
Sensory information collected by the peripheral nervous system is transmitted to specific areas of the primary somatosensory area in the parietal cortex according to its origin on any given part of the body. For each neuron in the primary somatosensory area, there is a corresponding region of the skin that is stimulated or inhibited by that neuron. The regions that correspond to a location on the somatosensory cortex are mapped by a homonculus. This corresponding region of the skin is referred to as the neuron's receptive field. The most sensitive regions of the body have the greatest representation in any given cortical area, but they also have the smallest receptive fields. The lips, tongue, and fingers are examples of this phenomenon. Each receptive field is composed of two regions: a central excitatory region and a peripheral inhibitory region. One entire receptive field can overlap with other receptive fields, making it difficult to differentiate between stimulation locations, but lateral inhibition helps to reduce that overlap. When an area of the skin is touched, the central excitatory region activates and the peripheral region is inhibited, creating a contrast in sensation and allowing sensory precision. The person can then pinpoint exactly which part of the skin is being touched. In the face of inhibition, only the neurons that are most stimulated and least inhibited will fire, so the firing pattern tends to concentrate at stimulus peaks. This ability becomes less precise as stimulation moves from areas with small receptive fields to larger receptive fields, e.g. moving from the fingertips to the forearm to the upper arm.
Auditory inhibition.
Similarities between sensory processes of the skin and the auditory system suggest lateral inhibition could play a role in auditory processing. The basilar membrane in the cochlea has receptive fields similar to the receptive fields of the skin and eyes. Also, neighboring cells in the auditory cortex have similar specific frequencies that cause them to fire, creating a map of sound frequencies similar to that of the somatosensory cortex. Lateral inhibition in tonotopic channels can be found in the inferior colliculus and at higher levels of auditory processing in the brain. However, the role that lateral inhibition plays in auditory sensation is unclear. Some scientists found that lateral inhibition could play a role in sharpening spatial input patterns and temporal changes in sensation, others propose it plays an important role in processing low or high tones.
Lateral inhibition is also thought to play a role in suppressing tinnitus. Tinnitus can occur when damage to the cochlea creates a greater reduction of inhibition than excitation, allowing neurons to become aware of sound without sound actually reaching the ear. If certain sound frequencies that contribute to inhibition more than excitation are produced, tinnitus can be suppressed. Evidence supports findings that high-frequency sounds are best for inhibition and therefore best for reducing some types of tinnitus.
In mustached bats, evidence supports the hypothesis that lateral inhibitory processes of the auditory system contribute to improved auditory information processing. Lateral inhibition would occur in the medial and dorsal divisions of the medial geniculate nucleus of mustached bats, along with positive feedback. The exact functions of these regions are unclear, but they do contribute to selective auditory processing responses. These processes could play a role in auditory functioning of other mammals, such as cats.
Embryology.
In embryology, the concept of lateral inhibition has been adapted to describe processes in the development of cell types. Lateral inhibition is described as a part of the Notch signaling pathway, a type of cell–cell interaction. Specifically, during asymmetric cell division one daughter cell adopts a particular fate that causes it to be copy of the original cell and the other daughter cell is inhibited from becoming a copy. Lateral inhibition is well documented in flies, worms and vertebrates. In all of these organisms, the transmembrane proteins Notch and Delta (or their homologues) have been identified as mediators of the interaction. Research has been more commonly associated with Drosophila, the fruit fly. Synthetic embryologists have also been able to replicate lateral inhibition dynamics in developing bacterial colonies, creating stripes and regular structures.
Neuroblast with slightly more Delta protein on its cell surface will inhibit its neighboring cells from becoming neurons. In flies, frogs, and chicks, Delta is found in those cells that will become neurons, while Notch is elevated in those cells that become the glial cells.


Taenia thalami

In the front, superior surface of the thalamus but separate from the inner, medial surface by a salient margin is the taenia thalami (Latin for "flat band" of the thalamus). The bottom epithelial lining of the third ventricle is in between the tela choroidea and the taenia thalami.


Mytatrienediol

Mytatrienediol (developmental code name SC-6924; former tentative brand names Manvene, Anvene), also known as 16α-methyl-16β-epiestriol 3-methyl ether or 16β-hydroxy-16α-methylestradiol 3-methyl ether, is a synthetic steroidal estrogen medication and an estrogen ether which was derived from estriol and was developed for clinical use in the late 1950s but was never marketed. It was investigated as a weak and mildly estrogenic medication for men to treat atherosclerosis, improve serum lipid profiles, and reduce the risk of myocardial infarction. However, while preclinical research supported the profile of mytatriendiol as a weak estrogen, the medication was found in clinical trials to produce estrogenic side effects including feminization, breast pain, and gynecomastia in men similarly and comparably to other estrogens such as ethinylestradiol and conjugated estrogens, and its side effects ultimately precluded its use. The medication was also studied to treat bone pain in patients with multiple myeloma, metastatic bone disease, and osteoporosis, with effectiveness seen.


Internal globus pallidus

The internal globus pallidus (GPi or medial globus pallidus; in rodents its homologue is known as the entopeduncular nucleus) and the external globus pallidus (GPe) make up the globus pallidus. The GPi is one of the output nuclei of the basal ganglia (the other being the substantia nigra pars reticulata). The GABAergic neurons send their axons to the ventral anterior nucleus (VA) and the ventral lateral nucleus (VL) in the dorsal thalamus, to the centromedian complex, and to the pedunculopontine complex.
The efferent bundle is constituted first of the ansa and lenticular fasciculus, then crosses the internal capsule as the Edinger's comb system then arrives at the laterosuperior corner of the subthalamic nucleus and constitutes the field H2 of Forel, then H, and suddenly changes its direction to form field H1 that goes to the inferior part of the thalamus. The distribution of axonal islands is widespread in the lateral region of the thalamus. The innervation of the central region is done by collaterals.
The internal globus pallidus contains GABAergic neurons, which allow for its inhibitory function. As the GPi, along with the substantia nigra pars reticulata, forms the output of the basal ganglia, these neurons extend to the thalamus, the centromedian complex and the pedunculopontine complex.
Function.
The GPi acts to tonically inhibit the ventral lateral nucleus and ventral anterior nucleus of the thalamus. As these two nuclei are needed for movement planning, this inhibition restricts movement initiation and prevents unwanted movements.
Direct pathway.
The GPi receives inhibitory GABAergic signals from the striatum by way of striatopallidal fibres, when a movement requirement is signaled from the cerebral cortex. As the GPi is one of the direct output centers of the basal ganglia, this causes disinhibition of the thalamus, increasing overall ease of initiating and maintaining movement. As this pathway only contains one synapse (from the striatum to the internal globus pallidus), it is known as the direct pathway.
The direct pathway is modulated by stimulation of the GPi by the external globus pallidus and subthalamic nucleus, via the indirect pathway.
Clinical significance.
Dysfunction of the internal globus pallidus has been correlated to Parkinson's disease, Tourette syndrome, and tardive dyskinesia.
The internal globus pallidus is the target of deep brain stimulation (DBS) for these diseases. Deep brain stimulation sends regulated electrical pulses to the target. In patients with tardive dyskinesia treated with DBS, most people reported more than a 50% improvement in symptoms. Tourette syndrome patients have also benefited from this treatment, showing over 50% improvement in tic severity (compulsive disabling motor tics are symptoms of Tourette patients). The GPi is also considered a "highly effective target for neuromodulation" when using deep brain stimulation on Parkinson's disease patients.
There is seen to be only some involvement in Huntington's disease with mostly the external globus pallidus being affected.


GJA8

Gap junction alpha-8 protein is a protein that in humans is encoded by the "GJA8" gene. It is also known as connexin 50.
Interactions.
GJA8 has been shown to interact with Tight junction protein 1.


Tengah

Tengah is an Indonesian and Malay word meaning "Central". It can be found in topography, e.g.


Sensory nerve

A sensory nerve, (or afferent nerve) is a general anatomic term for a nerve which contains predominantly somatic afferent nerve fibers. Afferent nerve fibers in a sensory nerve carry sensory information toward the central nervous system (CNS) from different sensory receptors of sensory neurons in the peripheral nervous system.
A motor nerve carries information from the CNS to the PNS, and both types of nerve are called peripheral nerves.
Afferent nerve fibers link the sensory neurons throughout the body, in pathways to the relevant processing circuits in the central nervous system.
Afferent nerve fibers are often paired with efferent nerve fibers from the motor neurons (that travel from the CNS to the PNS), in mixed nerves. Stimuli cause nerve impulses in the receptors and alter the potentials, which is known as sensory transduction.
Spinal cord entry.
Afferent nerve fibers leave the sensory neuron from the dorsal root ganglia of the spinal cord, and motor commands carried by the efferent fibers leave the cord at the ventral roots. The dorsal and some of the ventral fibers join as spinal nerves or mixed nerves.
Nerve damage.
Damage to the sensory nerve causes a wide range of symptoms because of the number of functions performed by the nerve. Traumatic injuries and other damages to the sensory nerves may lead to peripheral neuropathy, with problems such as reduced position sense causing poorer coordination and balance, in addition to reduced sensitivity to temperature change and pain, leading to further problems.
The ability to feel pain or changes in temperature can be affected by damage to the fibers in the sensory nerve. This can cause a failure to notice injuries such as a cut or that a wound is becoming infected. There may also be a lack of detection of heart attacks or other serious conditions. The lack of detection of pain and other sensations is a particularly large problem for those with diabetes, which contributes to the rate of lower limb amputations among this population. Overall, the poor sensation and detection may lead to changes in skin, hair, joint, and bone damage over the years for many people.


Cobatoxin

Cobatoxin is a toxin present in the venom of the scorpion "Centruroides noxius". It blocks two potassium channel subtypes; voltage-gated and calcium-activated channels.
Etymology.
Coba is a region in Mexico where the "Centruroides noxius" scorpion is found.
Sources.
Cobatoxin 1 and 2 are both found in the venom of the "Centruroides noxius" scorpion.
Chemistry.
Structure.
Cobatoxin is a 32-residue toxin with 3 disulfide bridges, which are located on C1-C4, C2-C5 and C3- C6 (Cys3-Cys22, Cys8-Cys27, and Cys12-Cys29). The peptide backbone is folded according to an α/β scaffold, both α-helical and two-stranded β-sheet structures are present. Cobatoxin 1 has a rod-like shape due to an extended N-terminus.
Family.
Cobatoxin 1 and 2 both belong to the α-KTx family. The α-KTx family is part of the K+-channel-specific scorpion toxins (KTx), which consists of 3 families; α, β, and γ. These 3 families differ in structure.
Target.
Cobatoxin 1 and 2 both block the Kv1.1 K+-channels in mice and the Shaker B K+ channels in insects, which are voltage-dependent K+-channels (Selisko, 1998).
Other voltage-dependent K+-channels that are blocked by Cobatoxin 1 are the Kv1.2 K+-channels in rats and Kv1.3 K+-channels in mice. Cobatoxin 1 also blocks the IKCa1 Ca2+-activated K+-channel.
Mode of action.
Cobatoxin 1 is a pore-blocking toxin. The interaction between cobatoxin 1 and the Kv1.2 channel is first esthablished by four salt bridges, which are formed between side chains of the four Kv1.2 α-subunits and amino acids residues of cobatoxin 1. This way a stable complex is formed, named the toxin-ring. Next, a tighter interaction is formed by a hydrophobic interaction between cobatoxin 1 and the α-subunit. Then the Lys21 side chain of cobatoxin 1 blocks the pore by entering the P-domain of the ion channel, which is the selectivity filter.
Toxicity.
The of cobatoxin 1 after intracerebroventricular injection in mice is 500±45 ng.


Posterior branches of cervical nerves

The posterior branches of cervical nerves branch from the dorsal rami of the cervical nerves.
Branches.
First.
The posterior division of the first cervical or suboccipital nerve is larger than the anterior division, and emerges above the posterior arch of the atlas and beneath the vertebral artery. It enters the suboccipital triangle and supplies the muscles which bound this triangle, viz., the Rectus capitis posterior major, and the Obliquus capitis superior and Obliquus capitis inferior; it gives branches also to the Rectus capitis posterior minor and the Semispinalis capitis. A filament from the branch to the Obliquus capitis inferior joins the posterior division of the second cervical nerve.
The nerve occasionally gives off a cutaneous branch which accompanies the occipital artery to the scalp, and communicates with the greater and lesser occipital nerves.
Second.
The posterior division of the second cervical nerve is much larger than the anterior division, and is the greatest of all the cervical posterior divisions. It emerges between the posterior arch of the atlas and the lamina of the axis, below the Obliquus capitis inferior. It supplies a twig to this muscle, receives a communicating filament from the posterior division of the first cervical, and then divides into a large medial and a small lateral branch.
Third.
The posterior division of the third cervical is intermediate in size between those of the second and fourth.
The posterior division of the suboccipital, and the medial branches of the posterior division of the second and third cervical nerves are sometimes joined by communicating loops to form the posterior cervical plexus.
Fourth through eighth.
The posterior divisions of the lower five cervical nerves divide into medial and lateral branches.


International Society for Autonomic Neuroscience

The International Society for Autonomic Neuroscience is a scientific society of researchers studying the autonomic nervous system. The society organizes scientific meetings, publishes a scientific journal, and supports students through awards and travel grants. It is a non-profit and non-governmental organization.
History.
The society was founded in 1995, because it was felt that the key international society covering neuroscience, the International Brain Research Organization, was not sufficiently representing research on this part of the nervous system. The first president was Geoffrey Burnstock. Elsewhere, it has been claimed that the society originated because of the "Journal of Autonomic Neuroscience", presumably because discussions amongst the early editors identified lack of scientific exchange, at an international level, amongst researchers in the field.
Initially, scientific meetings were organized every 3 years, before settling into a biennial pattern. Meetings have been held in Australia, the United Kingdom, Japan, Canada, France, Brazil, Germany and Italy.
Journal.
The official journal of the society is "". This journal publishes the congress abstracts and supports student poster and presentation prizes.
Collaboration with regional societies.
The society collaborates with several autonomic regional societies, having similar aims, in organizing joint meetings. These societies include:


Voltage-gated proton channel

Voltage-gated proton channels are ion channels that have the unique property of opening with depolarization, but in a strongly pH-sensitive manner. The result is that these channels open only when the electrochemical gradient is outward, such that their opening will only allow protons to leave cells. Their function thus appears to be acid extrusion from cells.
Another important function occurs in phagocytes (e.g. eosinophils, neutrophils, and macrophages) during the respiratory burst. When bacteria or other microbes are engulfed by phagocytes, the enzyme NADPH oxidase assembles in the membrane and begins to produce reactive oxygen species (ROS) that help kill bacteria. NADPH oxidase is electrogenic, moving electrons across the membrane, and proton channels open to allow proton flux to balance the electron movement electrically.
The functional expression of Hv1 in phagocytes has been well characterized in mammals, and recently in zebrafish, suggesting its important roles in the immune cells of mammals and non-mammalian vertebrates.
A group of small molecule inhibitors of the Hv1 channel are shown as chemotherapeutics and anti-inflammatory agents.
When activated, the voltage-gated proton channel HV1 can allow up to 100,000 hydrogen ions across the membrane each second. Whereas most voltage-gated ion channels contain a central pore that is surrounding by alpha helices and the voltage-sensing domain (VSD), voltage-gated hydrogen channels contain no central pore, so their voltage-sensing regions (VSD) carry out the job of bringing acidic protons across the membrane. As mentioned, these voltage-gated hydrogen channels only carry outward current, meaning they are used to move acidic protons out of the membrane. As a result, the opening of voltage-gated hydrogen channels usually hyperpolarize the cell membrane, or makes the membrane potential more negative.
A recent discovery has shown that the voltage-gated proton channel Hv1 is highly expressed in human breast tumor tissues that are metastatic, but not in non-metastatic breast cancer tissues. Because it has also been found to be highly expressed in other cancer tissues, the study of the voltage-gated proton channel has led many scientists to wonder what its importance is in cancer metastasis. However, much is still being discovered concerning the structure and function of the voltage-gated proton channel.