Metamood

Meta-mood is a term used by psychologists to refer to an individual's awareness of their emotions. The term was first utilized by John D. Mayer and Peter Salovey who believed the experience of mood involved "direct" and "indirect" components. While the direct level refers to the simple appearance of mood - happiness, fear, anger, sadness, and surprise (often referred to as the six basic emotions, introduced by Paul Ekman), the indirect level, or the meta-mood experience, does not solely consist of the emotions experienced by an individual in the moment. Rather, it is a reflective state which involves additional thoughts and feelings about the mood itself. "I shouldn’t feel this way" or "I am thinking of ways to improve my mood" are examples of reflective thoughts during a meta-mood experience.
Meta-mood is also a facet of emotional intelligence. Alexithymia, or the inability to identify and describe one's own or others' emotions, is generally viewed as antagonistic to meta-mood, as individuals who have symptoms of alexithymia often have trouble describing and analyzing their emotions. People who are unreflective and emotionally stable have fewer meta-mood experiences and commonly do not need them. On the other hand, individuals who are generally self-aware and have high emotionality have highly developed meta-mood experiences. Studies have shown that individuals who are able to improve negative moods through meta-emotions are seen to possess healthier personalities than individuals who are not able to have such experiences.
Individual meta-mood experiences.
Variance in meta-mood reflective states among individuals helps determine the different mechanisms individuals utilize to recognize, monitor, and regulate their feelings and emotions. The means by which individuals recognize their current mood, distinguish between different feelings, and adjust their emotions is crucial for the understanding of adaptive strategies they use to cope with interpersonal conflict and stress in their life.
The measurement of trait meta-mood involves three main components: attention to feelings (the individual awareness of one's mood), clarity of feelings (the individual ability to distinguish between moods), and mood repair (the ability to regulate mood from a negative to positive state). Of all three components, mood repair is most important in achieving a healthy emotional mindset. Mood regulation takes place on both conscious and unconscious levels. Mayer et al. contends that "a negative mood that is evaluated as out of control, unacceptable, and long-lasting is devastating; but were the evaluations reversed so as to view the mood as under control and soon to change, the overall feeling would be far less destructive to one’s equanimity". Self-control and self-regulation are crucial components of emotional intelligence and are associated with positive cognitive responses to social interactions.
Coping strategies individuals use are central determinants of overall psychological well-being and mental health. Previous research has shown that meta-mood is linked to lower levels of depression and anxiety, and higher levels self-esteem. The perceived ability to distinguish and repair distressing moods or preserve positive moods predicts superior overall well-being. Emotional repair is also found to have direct links to the maintenance of subjective happiness. Meta-mood experiences, such as mood clarity and emotional repair, are high predictors of life satisfaction. Individuals who are prone to being open about their emotions and who recognize their negative and positive responses towards a variety of environmental stressors have a greater probability of experiencing higher levels of life satisfaction than individuals who withhold their emotions. Individuals who are aware of their emotional states and are able to regulate their cognitive and emotional responses, are able to turn their attention towards coping strategies in difficult situations and minimize the psychological impact of stressful events. Ultimately, individuals prone to meta-mood experiences are able to acknowledge and respond to external environmental demands more easily and recover from troubled situations at a quicker pace. However, individuals low on emotional intelligence often exhibit avoidance-oriented and emotion-oriented coping styles. In addition, individuals who are not able to regulate and repair negative mood states have higher reports of illness.
Implications for psychotherapy.
Comprehending and measuring the degree to which individuals are able to respond to and understand their emotions is an important precondition if one were to predict future behaviors, emotional disorders, and psychological maladjustments. Meta-mood experiences have possible implications for a variety of treatments and preventative measures within the field of clinical psychology and psychotherapy. Mood repair is key in tackling the harmful effects of anxiety, depression, and other psychological conditions. As such, a variety of studies concerning meta-mood experiences have accentuated the importance of positive psychology and stress management programs for assisting individuals in coping with distressing situations in daily life. In their study, Lourdes Rey et al. have argued that "it seems reasonable to assume that individuals might be able to be trained to acquire mood repair abilities, given the high similarity between mood repair and other traditional techniques like positive refocusing or learned optimism styles". Training individuals to be aware of their emotions, to be able to differentiate among different feelings, and consequently change their mood, is useful in psychotherapy because patients with meta-mood experiences are better equipped to handle difficult situations. Studies have shown that mindfulness intervention in colleges increases meta-mood experiences of students, and therefore leads to an improvement in student well-being. Mindfulness meditation consists of attentional training and focuses on developing insight into one's emotional experience. In addition, when patients believe that their mood and meta-mood experiences are understood, they are more willing to open up about their character, their fears, and their core beliefs.
Trait meta-mood scale.
The Trait Meta-Mood Scale (TMMS) is used to measure emotional beliefs and attitudes people have towards their own emotional experiences. The TMMS scale measures three cognitive components of emotional intelligence: attention to feelings, clarity of feelings, and mood repair. Scores on the TMMS are utilized to analyse stable individual differences in the manner through which individuals respond to their emotional states. Individuals who score high on the TMMS scale have less melancholic thoughts, lower levels of anxiety and depression, and lower rates of borderline personality disorders. In a 7-week study examining the link between meta-mood and subjective happiness, higher scores on the TMMS were associated with fewer negative psychological reactions to interpersonal conflicts, measured through cortisol and blood pressure changes.


Ethacizine

Ethacizine (ethacyzine) is a class Ic antiarrhythmic agent, related to moracizine. It is used in Russia and some other CIS countries for the treatment of severe and/or refractory ventricular and supraventricular arrhythmias, especially those accompanied by organic heart disease. It is also indicated as a treatment of refractory tachycardia associated with Wolff–Parkinson–White syndrome.
It is manufactured under the brand name Ethacizin (Этацизин) by Olainfarm.


Coupon rate


Teen Titans Go! To the Movies

Teen Titans Go! To the Movies a 2018 American animated superhero musical comedy film based on the television series "Teen Titans Go!", which is adapted from the DC Comics superhero team of the same name. This film is written and produced by series developers Michael Jelenic and Aaron Horvath, and directed by series producer Peter Rida Michail and Horvath. The events of the film take place during the fifth season of the series. It is the most recent feature film to date from Warner Bros. Animation to be released theatrically outside of Warner Animation Group.
The film features the voices of Greg Cipes, Scott Menville, Khary Payton, Tara Strong, and Hynden Walch reprising their respective roles from the series, while Will Arnett (who also produced the film) and Kristen Bell join the cast. It was theatrically released in the United States and Canada on July 27, 2018 and became generally available on November 23, 2018, by Warner Bros. Pictures. The film was a box office success, grossing over $52.1 million worldwide against a $10 million budget, and received critical praise for its stylized animation quality, cast, score, humor, and storyline.
Plot.
In Jump City, the Teen Titans arrive to stop Balloon Man. When he fails to recognize them, the Teen Titans jump into a rap song to introduce themselves ("GO!") and become distracted, forcing the Justice League — Superman, Green Lantern and Wonder Woman — to intervene and defeat him. They criticize the Titans for their childishness and inability to take their positions as superheroes seriously, while raising the fact that they do not have a feature-length film to prove their legitimacy as superheroes.
While at the premiere of "Batman Again", the Titans' team leader, Robin, is derided by the audience after a misunderstanding leads him to believe they are making a film about him. At the rest of the team's suggestion, Robin resolves that in order to get a film made about him and the Titans, they need an arch-nemesis. Nearby, Slade breaks into S.T.A.R. Labs to steal a crystal. The Titans arrive and attempt to stop him, but he swiftly defeats and insults them.
The next day, Starfire, Cyborg, Raven and Beast Boy create a film to cheer up Robin, but he turns it off prematurely believing they are making fun of him. He declares that they will go to Hollywood to have a film made about them ("Upbeat Inspirational Song About Life"). Upon arriving at Warner Bros. Studios, they encounter director Jade Wilson, who is responsible for all the Superhero films being made. She turns down the Titans' request to be in a film ("My Superhero Movie"), explaining that the only way she would make one about them is if they were the only superheroes in the world. The Titans take her words literally, and go back in time to prevent the origins of the other superheroes ("Crystals" and "Back in Time"), but this only ends up ruining the present, forcing the Titans to go back in time again and undo their blunder.
Slade next arrives at Wayne Tech to infuse the crystal's power and the Titans arrive to stop him, this time putting up an actual fight. They secure the crystal, but Slade escapes, resolving to split Robin from his teammates.
The next day, Jade invites the Titans back to Hollywood and announces that she will make a movie about them due to their fight with Slade. While Robin is given a tour of the premises, Starfire, Raven, Cyborg and Beast Boy venture out and cause mischief ("Shenanigans"). They find a device labeled "DOOMSDAY" and try to destroy it, believing it to be a dangerous weapon. But Jade arrives and explains that D.O.O.M.S.D.A.Y. is an acronym for a new streaming service for the new movie she is making. She resolves to drop the rest of the Titans from the film and make it solely about Robin, who after a brief pause, accepts, much to the dismay of his team. Robin sadly tells them that they are holding each other back and believes they should go their separate ways.
Robin makes his movie, but soon begins to regret his decision and misses his friends. As he makes the final scene of his movie, he interacts with a prop version of the Titan Tower door panel, a light falls and knocks him out. He awakens and finishes the scene where Jade reveals that they are now in the tower for real, and that she is actually Slade himself in disguise. He steals the crystal back and traps Robin, telling him that having made numerous superhero movies was part of his plot to keep all the heroes busy while he invaded their cities to build D.O.O.M.S.D.A.Y., a device that can control minds and allow him to conquer the world. He then destroys the entire Titans Tower, but Robin safely manages to escape the exploding building. In the aftermath of the wreckage, Robin calls his friends and apologizes to them, who happily make peace with him.
At the premiere of "Robin: The Movie", the Titans arrive and unmask Slade, but Slade unleashes the crystal's power to control the other heroes and sends them after the Titans. Robin goes after Slade while the rest of the team leads off the heroes. However, Slade manages to use his new power to control Robin, and tells him to attack his friends. When he has them cornered, they show him the rest of the movie they made for him, revealing that they believe he is a real hero and their friend who united them from the beginning. This causes Robin to come to his senses. Slade attempts to fight them with a giant robot, but the team uses a song ("GO! (Battle Remix)") to take out Slade, though it is unknown what happened to him after he laughs at his defeat, altogether while also destroying the crystal, snapping the other heroes out of their trance. They all congratulate the Titans for their heroic efforts with Robin admitting that he has learned to be himself without needing a movie, When he tries to go on, everyone demands that they cut to the credits immediately with Robin attempting to stall so that "kids can ask their parents questions." Starfire breaks the fourth wall to say to go right to the credits, but Robin stops just before the film ends telling kids to "ask their parents where babies come from."
In a mid-credits scene, the Teen Titans from the 2003 series appear on a distorted screen telling the audience that they "found a way back". In a post-credits scene, the Challengers of the Unknown, who were trapped in a portal by Raven at the "Batman Again" premiere earlier in the film, are still trapped, with Professor Haley postulating that they missed the movie.
Production.
On September 25, 2017, Warner Bros. announced the film and its release date of July 27, 2018, with the show's cast reprising their roles. A month later, the film's title and teaser poster debuted, and it was announced that Will Arnett, who voices Batman in "The Lego Movie" franchise, and Kristen Bell had joined the cast. The film marks the first time Warner Bros. Animation has released a theatrical film since Warner Animation Group's formation in 2013 and also the first fully 2D animated theatrical feature from Warner Bros. Pictures since "Clifford's Really Big Movie".
On March 12, 2018, it was announced that musicians Lil Yachty and Halsey were part of the cast, as Green Lantern and Wonder Woman, respectively, with Nicolas Cage revealed as Superman the same day. Cage himself was originally slated to portray Superman in Tim Burton's canceled Superman film, "Superman Lives", in the 1990s. Jimmy Kimmel was announced to voice Batman in the film through an extended cut of the trailer.
Music.
The "Teen Titans Go! To the Movies" soundtrack was released on July 20, 2018. The soundtrack consists of songs that the cast sing throughout the movie that serve mostly as musical pop culture references and parodies, and the musical score composed by Jared Faber.
Release.
The film was released in theaters in the United States on July 27, 2018, by Warner Bros. Pictures and became generally available on November 23, 2018, followed by a United Kingdom bow a week later. It was released in Australian theaters on September 13, 2018. An early screening was held on June 22 at Vidcon 2018, for both badge members and YouTubers. The film was also shown at the San Diego Comic-Con International on July 20, 2018. DC Comics announced that Teen Titans Go! To the Movies hold a watch event on November 22, 2018 and release Teen Titans Go! To the Movies for general availability on the next day. The film's theatrical release was preceded by "#TheLateBatsby", a short film based on Lauren Faust's forthcoming "DC Super Hero Girls" television series. Teen Titans Go! To The Movies was generally available for download from MSDN and Technet on November 7 and for retail purchase from November 23, 2018. The film was set to make its network television premiere on TBS on September 12, 2020, but was removed from the schedule and replaced by an airing of "Sherlock Gnomes" for unknown reasons. The film made its official network television premiere on Cartoon Network on November 25, 2020.
Home media.
"Teen Titans Go! To the Movies" was released on digital copy on October 9, 2018 and was released on DVD and Blu-ray on October 30, 2018.
Reception.
Box office.
"Teen Titans Go! To the Movies" has grossed $29.6 million in the United States and Canada, and $22.3 million in other territories, for a total worldwide gross of $52 million, against a production budget of $10 million.
In the United States and Canada, "Teen Titans Go! To the Movies" was released alongside "", and was initially projected to gross around $14 million from 3,188 theaters in its opening weekend, with a chance to go as high as $19 million. However, after making $4.6 million on its first day (including $1 million from Thursday night previews), estimates were lowered to $10 million, and it ended up debuting to $10.5 million, finishing 5th at the box office.
Critical response.
On Rotten Tomatoes, the film has a "Certified fresh" rating of 91% based on 132 reviews, with an average rating of 7.25/10. The site's critical consensus reads, ""Teen Titans Go! To the Movies" distills the enduring appeal of its colorful characters into a charmingly light-hearted adventure whose wacky humor fuels its infectious fun – and belies a surprising level of intelligence." Several critics have called the movie, "Deadpool for kids". On Metacritic, the film has a score of 69 out of 100 based on reviews from 25 critics, indicating "generally favorable reviews". Audiences polled by CinemaScore gave the film an average grade of "B+" on an A+ to F scale.
Laura Prudom of IGN gave the film a score of 8/10, calling it a "gleefully unhinged deconstruction of superhero tropes that isn't afraid to take aim at the rest of DC's cinematic roster". Owen Glieberman of "Variety" said ""Teen Titans GO!" is fun in a defiantly super way, and that's a recommendation." Frank Scheck of "The Hollywood Reporter" wrote that "Considering the somberness that afflicts so many DC universe releases, the tongue-in-cheek, albeit admittedly juvenile humor of "Teen Titans Go! To the Movies" should come as a welcome relief to fans."
David Betancourt of "The Washington Post" opined, ""Teen Titans Go! To the Movies" is a laugh-a-minute ride that hits you with the jokes from the very first frame. From the cute shots at Marvel Studios to the self-deprecating tone on the state of DC movies, you’ll leave the theater with a new set of superhero abs from laughing so hard."
Brandon Katz of "The New York Observer" said that the film is "a fun parody of sorts that gently skewers our superhero obsessed culture, and while there may be one too many gags thrown in there which can get a bit tiresome after awhile, it's an enjoyable movie for both kids and adults." Brian Tallerico of RogerEbert.com rated the film 3/4 stars, saying "It's not a film designed to break ground or even offer too much social commentary on the role of superheroes in modern culture. It's built with the primary goal of making you laugh and forget your problems for just under 90 minutes, and it does exactly that."
GameSpot's Chris Hayner, while finding fault with what he deemed excessive toilet humor and some dragging in the film, said that "In a superhero movie landscape where the world is constantly being destroyed by massive CGI abominations, this is a refreshing change... it doesn't forget how funny and exciting these types of movies can be."
Sequel.
An episode of "Teen Titans Go!" premiered about a month after the film's release. The episode, titled "Tower Renovation", was about the Titans attempting to rebuild Titans Tower after Slade destroyed it in the events of the film.
In October 2018, Warner Bros. announced that a stand-alone sequel serving as a crossover featuring the Titans from both the "Teen Titans Go!" and the original 2003 versions entitled "Teen Titans Go! vs. Teen Titans" would premiere at San Diego Comic-Con 2019. The trailer was released on June 26, 2019, the film itself being digitally released on September 24, 2019 and physically released on October 15, 2019. The film premiered on Cartoon Network on February 17, 2020.


Richard Chelimo

Richard Chelimo (21 April 1972 – 15 August 2001) was a Kenyan long-distance runner, and a world record holder over 10,000 metres. However, he is best known as the silver medallist in the controversial 10,000m at the 1992 Olympics in Barcelona. He was also a world junior record holder in the 10,000m.
Family and tribe.
Chelimo, who was born in the Marakwet region of Kenya, was a member of the Kalenjin tribe (known by some as the "running tribe"). He came from a noted athletic family, even amongst the tribesmen, his cousin, Moses Kiptanui, was a three-time steeplechase world champion, whilst his brother, Ismael Kirui, was twice world champion over 5000 m.
Athletics career.
Chelimo's first international success was in the junior section of the 1990 world cross country championship in Aix-les-Bains, France, where he took silver. Though Chelimo received little attention due to the Kenyan domination of the event, their team won 10 successive junior titles.
However, it was not long before the athletic community took notice of Chelimo's talent. Later that year he won the gold medal in the 10,000 m at the world junior championships in Plovdiv, Bulgaria. Chelimo won the race by 12 seconds from his own brother, Kirui, who was only 15 at the time.
Chelimo was selected in the Kenyan senior squad for the 10,000 m at the 1991 world championships, which took place in Tokyo. As Kenya's second runner he was assigned the task of being pacemaker to Moses Tanui. He was successful in dragging Tanui clear of his main rival, Morocco's Khalid Skah, and on the final lap he allowed Tanui to sprint clear to take the gold medal.
The following year, at the Olympics, Chelimo met Skah again. With three laps remaining in the 10,000 m final the two athletes were clear and battling for the gold medal. At this point the pair came to lap another Moroccan athlete, Hammou Boutayeb, who stayed with the leaders even after being lapped. The rules state that a lapped runner cannot "assist" another runner but, although Boutayeb's actions were interpreted as unsportsmanlike by the crowd, it was not certain that there was any collusion, that Skah gained any advantage or that Chelimo was disadvantaged. Regardless, these events incensed the Spanish crowd, and the Swedish track judge Carl-Gustav Tollemar attempted to interfere with Boutayeb's run.
During the final 150 m Skah sprinted away from Chelimo to win the race, and was temporarily disqualified, making Chelimo the temporary Olympic champion. However, the Moroccans appealed against the disqualification and Skah was reinstated the next morning because the rule under which he was disqualified did not define a penalty.
In 1993 Chelimo broke the world junior and senior 10,000 m world record, in a time of 27:07.91 minutes, in Stockholm. He was to hold the senior world record for only five days before it was broken again by his compatriot Yobes Ondieki. He held the junior record for over 11 years before it was broken by Ugandan Boniface Kiprop Toroitich at a Golden League meeting on 3 September 2004, in a time of 27 min 04.00 s.
At the 1993 world championships in Stuttgart, Germany, Chelimo once again failed to win gold at a major championships. He managed only third place as he could not match the pace of Tanui and, a new star from Ethiopia, Haile Gebrselassie. This was another controversial race as Tanui lost a shoe after Gebreselassie stepped on his heel; the Ethiopian went on to win the race.
Life after athletics.
Chelimo retired from athletics in 1996; according to his cousin, Kiptanui, he retired after growing despondent following his failure to rise to the very top of the sport. He returned to his old job in the army and put on a lot of weight and began to drink excessively — a decline quite similar to that of Henry Rono. However, his friends Tanui and William Mutwol encouraged him to return to training and get back into shape. Chelimo eventually got back down to within 5 kg of his racing weight. He died of a brain tumour at the age of 29.


Englitazone

Englitazone is a hypoglycemic agent of thiazolidinedione ("glitazone") class.


Activity-dependent plasticity

Activity-dependent plasticity is a form of functional and structural neuroplasticity that arises from the use of cognitive functions and personal experience; hence, it is the biological basis for learning and the formation of new memories. Activity-dependent plasticity is a form of neuroplasticity that arises from intrinsic or endogenous activity, as opposed to forms of neuroplasticity that arise from extrinsic or exogenous factors, such as electrical brain stimulation- or drug-induced neuroplasticity. The brain's ability to remodel itself forms the basis of the brain's capacity to retain memories, improve motor function, and enhance comprehension and speech amongst other things. It is this trait to retain and form memories that is associated with neural plasticity and therefore many of the functions individuals perform on a daily basis. This plasticity occurs as a result of changes in gene expression which are triggered by signaling cascades that are activated by various signaling molecules (e.g., calcium, dopamine, and glutamate, among many others) during increased neuronal activity.
The brain's ability to adapt toward active functions allows humans to specialize in specific processes based on relative use and activity. For example, a right-handed person may perform any movement poorly with his/her left hand but continuous practice with the non-dominant hand can cause one to become ambidextrous. Another example is if someone was born with a neurological disorder such as autism or had a stroke that resulted in a disorder, then they are capable of retrieving much of their lost function through practice, which in turn "rewires" the brain to mitigate neurological dysfunction.
History.
The idea of neural plasticity was first proposed during 1890 by William James in Principles of Psychology. During the first half of the 1900s, the word 'plasticity' was directly and indirectly rejected throughout science. Many scientists found it hard to receive funding because nearly everyone unanimously supported the fact that the brain was fully developed at adulthood and specific regions were unable to change functions after the critical period. It was believed that each region of the brain had a set and specific function. Despite this, several pioneers pushed the idea of plasticity through means of various experiments and research. There are others that helped to the current progress of activity-dependent plasticity but the following contributed very effective results and ideas early on.
Pioneers of activity-dependent plasticity.
The history of activity-dependent plasticity begins with Paul Bach y Rita. With conventional ideology being that the brain development is finalized upon adulthood, Bach y Rita designed several experiments in the late 1960s and 1970s that proved that the brain is capable of changing. These included a pivotal visual substitution method for blind people provided by tactile image projection in 1969. The basis behind this experiment was to take one sense and use it to detect another: in this case use the sense of touch on the tongue to visualize the surrounding. This experiment was years ahead of its time and led to many questions and applications. A similar experiment was reported again by Bach y Rita in 1986 where vibrotactile stimulation was delivered to the index fingertips of naive blindfolded subjects. Even though the experiment did not yield great results, it supported the study and proposed further investigations. In 1998, his design was even further developed and tested again with a 49-point electrotactile stimulus array on the tongue. He found that five sighted adult subjects recognized shapes across all sizes 79.8% of the time, a remarkable finding that has led to the incorporation of the tongue electrotactile stimulus into cosmetically acceptable and practical designs for blind people. In later years, he has published a number of other articles including "Seeing with the brain" in 2003 where Bach y Rita addresses the plasticity of the brain relative to visual learning. Here, images are enhanced and perceived by other plastic mechanisms within the realm of information passing to the brain.
Another pioneer within the field of activity-dependent plasticity is Michael Merzenich, currently a professor in neuroscience at the University of California, San Francisco. One of his contributions includes mapping out and documenting the reorganization of cortical regions after alterations due to plasticity. While assessing the recorded changes in the primary somatosensory cortex of adult monkeys, he looked at several features of the data including how altered schedules of activity from the skin remap to cortical modeling and other factors that affect the representational remodeling of the brain. His findings within these studies have since been applied to youth development and children with language-based learning impairments. Through many studies involving adaptive training exercises on computer, he has successfully designed methods to improve their temporal processing skills. These adaptive measures include word-processing games and comprehension tests that involve multiple regions of the brain in order to answer. The results later translated into his development of the Fast ForWord program in 1996, which aims to enhance cognitive skills of children between kindergarten and twelfth grade by focusing on developing "phonological awareness". It has proven very successful at helping children with a variety of cognitive complications. In addition, it has led to in depth studies of specific complications such as autism and intellectual disability and the causes of them. Alongside a team of scientists, Merzenich helped to provide evidence that autism probes monochannel perception where a stronger stimulus-driven representation dominates behavior and weaker stimuli are practically ignored in comparison.
Structure of neurons.
Neurons are the basic functional unit of the brain and process and transmit information through signals. Many different types of neurons can be identified based on their function, such as sensory neurons or motor neurons. Each responds to specific stimuli and sends respective and appropriate chemical signals to other neurons. The basic structure of a neuron is shown here on the right and consists of a nucleus that contains genetic information; the cell body, or the soma, which is equipped with dendritic branches that mostly receive the incoming inputs from other neurons; a long, thin axon that bears axon terminals which carry the output information to other neurons. The dendrites and axons are interfaced through a small connection called a synapse. This component of the neuron contains a variety of chemical messengers and proteins that allow for the transmission of information. It is the variety of proteins and effect of the signal that fundamentally lead to the plasticity feature.
Structures and molecular pathways involved.
Activity-dependent plasticity of one form or another has been observed in most areas of the brain. In particular, it is thought that the reorganization of sensory and motor maps involves a variety of pathways and cellular structures related to relative activity.
Many molecules have been implicated in synaptic plasticity. Notably, AMPA and NMDA receptors are key molecules in mechanisms of long and short-term potentiation between neurons. NMDA receptors can detect local activity due to activation and therefore modify signaling in the post-synaptic cell. The increased activity and coordination between pre- and post-synaptic receptors leads to more permanent changes and therefore result in plasticity. Hebb's postulate addresses this fact by stating that synaptic terminals are strengthened by correlated activity and will therefore sprout new branches. However, terminals that experience weakened and minimal activity will eventually lose their synaptic connection and deteriorate.
A major target of all molecular signaling is the inhibitory connections made by GABAergic neurons. These receptors exist at postsynaptic sites and along with the regulation of local inhibitory synapses have been found to be very sensitive to critical period alterations. Any alteration to the receptors leads to changed concentrations of calcium in the affected cells and can ultimately influence dendritic and axonal branching. This concentration change is the result of many kinases being activated, the byproduct of which may enhance specific gene expression.
In addition, it has been identified that the wg postsynaptic pathway, which is responsible for the coding and production of many molecules for development events, can be bidirectionally stimulated and is responsible for the downstream alteration of the postsynaptic neuron. When the wg presynaptic pathway is activated, however, it alters cytoskeletal structure through transcription and translation.
Cell adhesion molecules (CAMs) are also important in plasticity as they help coordinate the signaling across the synapse. More specifically, integrins, which are receptors for extracellular matrix proteins and involved with CAMs, are explicitly incorporated in synapse maturation and memory formation. They play a crucial role in the feedback regulation of excitatory synaptic strength, or long-term potentiation (LTP), and help to control synaptic strength by regulating AMPA receptors, which result in quick, short synaptic currents. But, it is the metabotropic glutamate receptor 1 (mGlu1) that has been discovered to be required for activity-dependent synaptic plasticity in associative learning.
Activity-dependent plasticity is seen in the primary visual cortex, a region of the brain that processes visual stimuli and is capable of modifying the experienced stimuli based on active sensing and arousal states. It is known that synaptic communication trends between excited and depressed states relative to the light/dark cycle. By experimentation on rats, it was found that visual experience during vigilant states leads to increased responsiveness and plastic changes in the visual cortex. More so, depressed states were found to negatively alter the stimulus so the reaction was not as energetic. This experiment proves that even the visual cortex is capable of achieving activity-dependent plasticity as it is reliant on both visual exploration and the arousal state of the animal.
Role in learning.
Activity-dependent plasticity plays a very important role in learning and in the ability of understanding new things. It is responsible for helping to adapt an individual's brain according to the relative amount of usage and functioning. In essence, it is the brain's ability to retain and develop memories based on activity-driven changes of synaptic strength that allow stronger learning of information. It is thought to be the growing and adapting quality of dendritic spines that provide the basis for synaptic plasticity connected to learning and memory. Dendritic spines accomplish this by transforming synaptic input into neuronal output and also by helping to define the relationship between synapses.
In recent studies, a specific gene has also been identified as having a strong role in synapse growth and activity-dependent plasticity: the microRNA 132 gene (miR132). This gene is regulated by the cAMP response element-binding (CREB) protein pathway and is capable of enhancing dendritic growth when activated. The miR132 gene is another component that is responsible for the brain's plasticity and helps to establish stronger connections between neurons.
Another plasticity-related gene involved in learning and memory is Arc/Arg3.1. The Arc gene is activity-regulated and the transcribed mRNA is localized to activated synaptic sites where the translated protein plays a role in AMPA receptor trafficking. Arc is a member of a class of proteins called immediate early genes (IEG) that are rapidly transcribed in response to synaptic input. Of the estimated 30-40 genes that comprise the total neuronal IEG response, all are prototypical activity-dependent genes and a number have been implicated in learning and memory. For example, zif268, Arc, beta-activin, tPA, Homer, and COX-2 have all been implicated in long-term potentiation (LTP), a cellular correlate of learning and memory.
Mechanisms involved.
There are a variety of mechanisms involved in activity-dependent plasticity. These include LTP, long-term depression (LTD), synaptic elimination, neurogenesis, and synaptogenesis. The mechanisms of activity-dependent plasticity result in membrane depolarization and calcium influx, which in turn trigger cellular changes that affect synaptic connections and gene transcription. In essence, neuronal activity regulates gene expression related to dendritic branching and synapse development. Mutations in activity-dependent transcription-related genes can lead to neurological disorders. Each of the studies' findings aims to help proper development of the brain while improving a wide variety of tasks such as speech, movement, comprehension, and memory. More so, the findings better explain the development induced by plasticity.
It is known that during postnatal life a critical step to nervous system development is synapse elimination. The changes in synaptic connections and strength are results from LTP and LTD and are strongly regulated by the release of brain-derived neurotrophic factor (BDNF), an activity-dependent synapse-development protein. In addition to BDNF, Nogo-66 receptors, and more specifically NgR1, are also involved in the development and regulation of neuronal structure. Damage to this receptor leads to pointless LTP and attenuation of LTD. Both situations imply that NgR1 is a regulator of synaptic plasticity. From experiments, it has been found that stimulation inducing LTD leads to a reduction in synaptic strength and loss of connections but, when coupled simultaneously with low-frequency stimulation, helps the restructuring of synaptic contacts. The implications of this finding include helping people with receptor damage and providing insight into the mechanism behind LTP.
Another research model of activity-dependent plasticity includes the excitatory corticostriatal pathway that is involved in information processing related to adaptive motor behaviors and displays long-lasting synaptic changes. The change in synaptic strength is responsible for motor learning and is dependent on the simultaneous activation of glutamatergic corticostriatal and dopaminergic nigrostriatal pathways. These are the same pathways affected in Parkinson's disease, and the degeneration of synapses within this disorder may be responsible for the loss of some cognitive abilities.
Relationship to behavior.
Intellectual disability.
Since plasticity is such a fundamental property of brain function due to its involvement in brain development, brain repair, and cognitive processes, its proper regulation is necessary for normal physiology. Mutations within any of the genes associated with activity-dependent plasticity have been found to positively correlate with various degrees of intellectual disability. The two types of intellectual disability related to plasticity depend on dysfunctional neuronal development or alterations in molecular mechanisms involved in synaptic organization. Complications within either of these types can greatly reduce brain capability and comprehension.
Stroke rehabilitation.
On the other hand, people with such conditions have the capacity to recover some degree of their lost abilities through continued challenges and use. An example of this can be seen in Norman Doidge's "The Brain That Changes Itself". Bach y Rita's father suffered from a disabling stroke that left the 65-year-old man half-paralyzed and unable to speak. After one year of crawling and unusual therapy tactics including playing basic children's games and washing pots, his father's rehabilitation was nearly complete and he went back to his role as a professor at City College in New York. This remarkable recovery from a stroke proves that even someone with abnormal behavior and severe medical complications can recover nearly all of the normal functions by much practice and perseverance.
Recent studies have reported that a specific gene, FMR1, is highly involved in activity-dependent plasticity and fragile X syndrome (FraX) is the result of this gene's loss of function. FMR1 produces FMRP, which mediates activity-dependent control of synaptic structure. The loss or absence of this gene almost certainly leads to both autism and intellectual disability. Dr. Gatto has found that early introduction of the product FMRP results in nearly complete restructuring of the synapses. This method is not as effective, though, when introduced into a mature subject and only partially accommodates for the losses of FMR1. The discovery of this gene provides a possible location for intervention for young children with these abnormalities as this gene and its product act early to construct synaptic architecture.
Stress.
A common issue amongst most people in the United States is high levels of stress and also disorders associated with continuous stress. Many regions of the brain are very sensitive to stress and can be damaged with extended exposure. More importantly, many of the mechanisms involved with increased memory retention, comprehension, and adaptation are thought to involve LTP and LTD, two activity-dependent plasticity mechanisms that stress can directly suppress. Several experiments have been conducted in order to discover the specific mechanisms for this suppression and also possible intervention methods. Dr. Li and several others have actually identified the TRPV1 channel as a target to facilitate LTP and suppress LTD, therefore helping to protect the feature of synaptic plasticity and retention of memory from the effects of stress.
Future studies.
The future studies and questions for activity-dependent plasticity are nearly endless because the implications of the findings will enable many treatments. Despite many gains within the field, there are a wide variety of disorders that further understanding of activity-dependent mechanisms of plasticity would help treat and perhaps cure. These include autism, different severities of intellectual disability, schizophrenia, Parkinson's disease, stress, and stroke. In addition to a better understanding of the various disorders, neurologists should and will look at the plasticity incurred by the immune system, as it will provide great insight into diseases and also give the basis of new immune-centered therapeutics. A better perspective of the cellular mechanisms that regulate neuronal morphology is the next step to discovering new treatments for learning and memory pathological conditions.


Hokkien kinship

Hokkien kinship system () is the kinship system for Hokkien language users.


Ten percent of the brain myth

The 10 percent of the brain myth asserts that humans generally use only 10 percent (or some other small percentage) of their brains. It has been misattributed to many celebrated people, notably Albert Einstein. By extrapolation, it is suggested that a person may harness this unused potential and increase intelligence.
Changes in grey and white matter following new experiences and learning have been shown, but it has not yet been proven what the changes are. The popular notion that large parts of the brain remain unused, and could subsequently be "activated", rests in folklore and not science. Though specific mechanisms regarding brain function remain to be fully described—e.g. memory, consciousness—the physiology of brain mapping suggests that all areas of the brain have a function and that they are used nearly all the time.
Origin.
A likely origin for the "ten percent myth" is the reserve energy theories of Harvard psychologists William James and Boris Sidis who, in the 1890s, tested the theory in the accelerated raising of child prodigy William Sidis. Thereafter, James told lecture audiences that people only meet a fraction of their full mental potential, which is considered a plausible claim. The concept gained currency by circulating within the self-help movement of the 1920s; for example, the book "Mind Myths: Exploring Popular Assumptions About the Mind and Brain" includes a chapter on the ten percent myth that shows a self-help advertisement from the 1929 "World Almanac" with the line "There is NO LIMIT to what the human brain can accomplish. Scientists and psychologists tell us we use only about TEN PERCENT of our brain power." This became a particular "pet idea" of science fiction writer and editor John W. Campbell, who wrote in a 1932 short story that "no man in all history ever used even half of the thinking part of his brain". In 1936, American writer and broadcaster Lowell Thomas popularized the idea—in a foreword to Dale Carnegie's "How to Win Friends and Influence People"—by including the falsely precise percentage: "Professor William James of Harvard used to say that the average man develops only ten percent of his latent mental ability".
In the 1970s, the Bulgarian-born psychologist and educator, Georgi Lozanov proposed the teaching method of suggestopedia believing "that we might be using only five to ten percent of our mental capacity". The origin of the myth has also been attributed to Wilder Penfield, the U.S.-born neurosurgeon who was the first director of Montreal Neurological Institute of McGill University.
According to a related origin story, the ten percent myth most likely arose from a misunderstanding (or misrepresentation) of neurological research in the late 19th century or early 20th century. For example, the functions of many brain regions (especially in the cerebral cortex) are complex enough that the effects of damage are subtle, leading early neurologists to wonder what these regions did. The brain was also discovered to consist mostly of glial cells, which seemed to have very minor functions. James W. Kalat, author of the textbook "Biological Psychology", points out that neuroscientists in the 1930s knew about the large number of "local" neurons in the brain. The misunderstanding of the function of local neurons may have led to the ten percent myth. The myth might have been propagated simply by a truncation of the idea that some use a small percentage of their brains at any given time. In the same article in "Scientific American", John Henley, a neurologist at the Mayo Clinic in Rochester, Minnesota states: "Evidence would show over a day you use 100 percent of the brain".
Although parts of the brain have broadly understood functions, many mysteries remain about how brain cells (i.e., neurons and glia) work together to produce complex behaviors and disorders. Perhaps the broadest, most mysterious question is how diverse regions of the brain collaborate to form conscious experiences. So far, there is no evidence that there is one site for consciousness, which leads experts to believe that it is truly a collective neural effort. Therefore, as with James's idea that humans have untapped cognitive potential, it may be that a large number of questions about the brain have not been fully answered.
Analysis.
Neurologist Barry Gordon describes the myth as false, adding, "we use virtually every part of the brain, and that (most of) the brain is active almost all the time." Neuroscientist Barry Beyerstein sets out six kinds of evidence refuting the ten percent myth:
In debunking the ten percent myth, "Knowing Neurons" editor Gabrielle-Ann Torre writes that using one hundred percent of one's brain would not be desirable either. Such unfettered activity would almost certainly trigger an epileptic seizure. Torre writes that, even at rest, a person likely uses as much of his or her brain as reasonably possible through the default mode network, a widespread brain network that is active and synchronized even in the absence of any cognitive task. Thus, "large portions of the brain are never truly dormant, as the 10% myth might otherwise suggest."
In popular culture.
Some proponents of the "ten percent of the brain" belief have long asserted that the "unused" ninety percent is capable of exhibiting psychic powers and can be trained to perform psychokinesis and extra-sensory perception. This concept is especially associated with the proposed field of "psionics" (psychic + electronics), a favorite project of the influential science fiction editor John W. Campbell, Jr in the 1950s and '60s. There is no scientifically verified body of evidence supporting the existence of such powers. Such beliefs remain widespread among New Age proponents to the present day.
In 1980, Roger Lewin published an article in "Science", "Is Your Brain Really Necessary?", about studies by John Lorber on cerebral cortex losses. He reports the case of a Sheffield University student who had a measured IQ of 126 and passed a Mathematics Degree but who had hardly any discernible brain matter at all since his cortex was extremely reduced by hydrocephalus. The article led to the broadcast of a Yorkshire Television documentary of the same title, though it was about a different patient who had normal brain mass distributed in an unusual way in a very large skull. Explanations were proposed for the first student's situation, with reviewers noting that Lorber's scans evidenced that the subject's brain mass was not absent, but compacted into the small space available, possibly compressed to a greater density than regular brain tissue.
Several books, films, and short stories have been written closely related to this myth. They include the 1986 film "Flight of the Navigator"; the novel "The Dark Fields" and its 2011 film adaptation, "Limitless" (claiming 20 percent rather than the typical 10 percent); the 1991 film "Defending Your Life"; the ninth book ("White Night") of Jim Butcher's book series "The Dresden Files"; the shōnen manga "Psyren"; and the 2014 film "Lucy"—all of which operate under the notion that the rest of the brain could be accessed through use of a drug. "Lucy" in particular depicts a character who gains increasingly godlike abilities once she surpasses 10 percent, though the film suggests that 10 percent represents brain capacity at a particular time rather than permanent usage.
The myth was examined on a 27 October 2010 episode of "MythBusters". The hosts used magnetoencephalography and functional magnetic resonance imaging to scan the brain of someone attempting a complicated mental task, and found that over 10%, as much as 35%, was used during the course of their test.
The ten percent brain myth occurs frequently in advertisements, and in entertainment media it is often cited as fact.
In the season 2 episode of "Fetch! With Ruff Ruffman", "Ruff's Case of Blues in the Brain", they debunked the theory.
In "Teen Titans Go!", Beast Boy attempts to solve a Find-It puzzle by unlocking more percentage of brain.


Trancers

Trancers (also released as Future Cop) is a 1984 American science fiction action film directed by Charles Band and starring Tim Thomerson, Helen Hunt, and Art LaFleur. It is the first film in the "Trancers" series. Thomerson plays Jack Deth, a Philip Marlowe-esque police detective from the 23rd century who travels to the 1980s to bring his old nemesis to justice. The film portrays a unique method of time travel: people can travel back in time by injecting themselves with a drug that allows them to take over the body of an ancestor.
Plot.
Jack Deth is a police trooper in the 23rd century who has been hunting down Martin Whistler, a criminal mastermind who uses psychic powers to turn people into mindless "Trancers" and carry out his orders. Deth can identify a tranced individual by scanning them with a special bracelet. All trancers appear as normal humans at first, but once triggered, they become savage killers with twisted features.
Before he can be caught, Whistler escapes back in time using a drug-induced time-traveling technique. Whistler's consciousness travels down his ancestral bloodline, arrives in 1985, and takes over the body of a Los Angeles police detective named Weisling. Once Deth discovers what Whistler has done, he destroys Whistler's body—effectively leaving him trapped in the past with no vessel to return to—and chases after him through time the same way. Deth ends up in the body of one of his ancestors: a journalist named Phil Dethton.
With the help of Phil's girlfriend—a punk rock girl named Leena—Deth goes after Whistler, who has begun to "trance" other victims. Whistler plots to eliminate the future governing council members of Angel City (the future name of Los Angeles), who are being systematically wiped out of existence by Whistler's murder spree of their ancestors. Deth arrives too late to prevent most of the murders and can only safeguard Hap Ashby, a washed-up former pro baseball player, who is the ancestor of the last surviving council member, Chairman Ashe.
Deth is given some high-tech equipment, which is sent to him in the past: his sidearm (which contains two hidden vials of time drugs to send him and Whistler back to the future), and a "long-second" wristwatch, which temporarily slows time, stretching one second to 10. The watch has only enough power for one use, but he later receives another watch.
During the end fight with Whistler, one of the drug vials in Jack's gun breaks, leaving only one vial to get home. Jack is forced to make a choice: kill the innocent Weisling (who is possessed by the evil Whistler), or use the vial to send Whistler back to 2247, which would strand Jack in the present. Jack chooses to inject Weisling with the vial, saving the lieutenant's life but condemning Whistler to an eternity without a body to return to. Jack decides to remain with Leena in 1985, although observing him from the shadows is McNulty, his boss from the future, who has traveled down his own ancestral line, ending up in the body of a young girl.
Reception.
On Rotten Tomatoes the film has an approval rating of 83% based on reviews from 6 critics.
"Variety" described it as having a similar premise to "The Terminator" but falling short of that film. Kevin Thomas of the "Los Angeles Times" instead called it "a textbook example of efficient, effective exploitation film making".
Sequels.
The film received a direct-to-video sequel in 1991, titled "Trancers II: The Return of Jack Deth." Additionally, "" is chronologically set between the first and second films. The 20-minute short was a part of the unreleased 1988 anthology film "Pulse Pounders", but was released separately on DVD in 2013. The film has since started a franchise of six main films.


Ventral trigeminal tract

The ventral trigeminal tract, ventral trigeminothalamic tract, anterior trigeminal tract, or anterior trigeminothalamic tract, is a tract composed of second order neuronal axons. These fibers carry sensory information about discriminative and crude touch, conscious proprioception, pain, and temperature from the head, face, and oral cavity. The ventral trigeminal tract connects the two major components of the brainstem trigeminal complex – the principal, or main sensory nucleus and the spinal trigeminal nucleus, to the ventral posteromedial nucleus of the thalamus.
The ventral trigeminal tract is also called the anterior trigeminal lemniscus.
Structure.
The first order neurons (from the trigeminal ganglion) enter the pons and synapse in the principal (chief sensory) nucleus or spinal trigeminal nucleus. Axons of the second order neurons cross the midline and terminate in the ventral posteromedial nucleus of the contralateral thalamus (as opposed to the ventral posterolateral nucleus, as in the dorsal column medial lemniscus (DCML) system). The third order neuron in the thalamus then connects to the sensory cortex of the postcentral gyrus.


Rhombomere

In the vertebrate embryo, a rhombomere is a transiently divided segment of the developing neural tube, within the hindbrain region (a neuromere) in the area that will eventually become the rhombencephalon. The rhombomeres appear as a series of slightly constricted swellings in the neural tube, caudal to the cephalic flexure. In human embryonic development, the rhombomeres are present by day 29.
Function.
In the early developmental stages of the neural tube, segmentation of the neuroepithelium occurs. This segmentation turns into a series of neuromeres. Each segment is called a rhombomere. Every rhombomere develops its own set of ganglia and nerves. Later on in development, rhombomeres form the rhombocephalon, which forms the hindbrain in vertebrates. Each rhombomere expresses its own unique set of genes, which has been shown to influence postnatal rhythmic behaviors, such as respiration, mastication, and walking. In mice, it was shown that the patterning of the neural tube into rhombomeric segments may regulate spatial and temporal appearance of the central pattern generator. Rhombomeres are considered self-governing developmental units, with certain aspects of the rhombomere phenotype being determined at the time of formation. Each rhombomere expresses a unique combination of transcription factors, and so each rhombomeric domain has its own distinct molecular cues that could, theoretically, establish rhombomere-specific patterns of neuronal differentiation. Some of these neuronal populations have been identified in some species. Many of the mature hindbrain nuclei can occupy either one or several rhombomere-derived regions. Vestibular nuclei have been shown to span all the rhombomeres, some correlating with the boundaries of the rhombomeres. Using phosphorylated retrograde labeling, it has been shown that vestibulospinal groups correspond mostly to single rhombomeres rather than over several rhombomeric regions. It has also been shown that the vestibule-ocular groups can either relate to single or multiple rhombomeres, as long as the rhombomeres are closely related. The conclusion drawn was that segmentation of the hindbrain contributes to the way axons project within the vestibular complex. Finally, vestibulospinal neurons have been shown to differentiate in three neighboring rhombomeres, specifically r4, r5, and r6. While vestibule-ocular neurons differentiate across seven, the least differentiated in f4. The method of this differentiate is still unknown, with many types of proteins involved in both the migration, expression of proteins, and for neuron growth and apoptosis. The types of receptors, as well, can vary their activity to be cell-specific.
Rhombomeres determine the pattern of the following maturation of the rhombencephalon into its final parts. The final parts are defined as the pons, cerebellum and medulla.
Cells that form the boundaries of the rhombomere bulges proliferate much faster than those in the middle. It is very difficult for cells to cross from one rhombomere to another, so cells tend to stay within one rhombomere. Each rhombomere eventually gives rise to one or more vestibular neuron types. However, it is not necessarily dependent on segmentation. The motor nerves form depending on rhombomeric patterns, but each nerve can come from either one rhombomere or a pair of rhombomeres that are neighbors. Furthermore, the correct development of the various pharyngeal arches is believed to depend on interactions with specific rhombomeres. With these mechanisms, neural crest cells, for instance, from each rhombomere give rise to different ganglia, or clusters of neurons. Many of these rhombomeres have been mapped to an extent in species other than human. For example, r2 has been shown to give rise to the trigeminal ganglion, while r4 has been shown to give rise to the geniculate ganglion as well as spiral and Scarpa's ganglia. r5 and r6 gives rise to the abducens nerve, and the lower part of r6 and the upper part of r7 gives rise to the petrosal ganglion. Finally, the border of r7 that is not in contact with r6 gives rise to the jugular/nodose ganglia. These mappings, however, cannot be applied cross species.
Studies have shown that the number of neurons in the hindbrain increase as a species evolves. For example, a mouse has more neurons than a slug, but a chimp has more neurons than a mouse. One can assume that part of this comes from having to adapt to an increase in the size of the species. Also, in some species, the rhombomeres are obviously segmented and stay this way for an extended period of time. In other species, the segmentation eventually disappears. For example, rhombomeres are detectable by light microscopy in Swiss/Webster strain of mice for up to embryonic day (E)10.5, but they disappear at E11.5. Many rhombomeres, if compared across species, do not form into the same things. For example, r2 and r3 have been mapped to the trigeminal motoneurons in many species. However, not all species have this correlation.
Each rhombomere has its own set of receptors, and the same receptors can cause different actions. For example, one study showed that there are proteins called Gli1, Gli2, and Gli3 that affect ventral hindbrain development, and are also required for motoneuron development and correct neural patterning in the hindbrain. However, how important are they and what their specific roles are was unclear. By mutating the proteins Gli2 and Gli3, which were especially studied, it was found that Gli2 and Gli3 contain both activation and repression domains, while Gli1 only had activation domains, which were entirely transcriptional. Gli2 was also found to be a stronger activator while Gli3 was a strong repressor. Gli2 and Gli3 had overlapping functions that concerned the patterning of the ventral spinal cord which was important for correct organization and formation of the motoneurons. This was shown when mutation of the Gli3 protein showed only a slight decrease in expression of Olig2, while when the Gli2 protein was mutated, the expression of Olig2 was not detected. Olig2 is normally expressed in the ventral area of the neural tube. Mutations in the Gli2 protein causes more severe damage in the ventral patterning of the hindbrain than that of the spinal cord. This shows that Gli2 performs different functions in the hindbrain that Gli3 is unable to substitute. Gli2 and Gli3 in a developing hindbrain also have distinct functions in the Shh (sonic hedgehog) signal transduction. This is caused by differential modulation of gene expression that is specific to each rhombomere. Finally, studies have shown that in rhombomere 4, the ventral patterning is less affected by the mutation of Gli2. This shows that this particular rhombomere has different requirements for Gli proteins.
The Hox gene also has been shown to play a part in the formation of the cranial motor nerves. The fate of a rhombomere has been shown to be affected by differential expression of the Hox gene. With mutations in the Hox gene, the cranial motor nerves formed in different locations than normal or simply did not form altogether. One possibility for this was that the Hox gene was somehow involved in regionalization within the neural tube, and that expression of this particular gene correlated with the amount of migration that occurred. However, no correlation could be found. Many studies showed small amounts of correlation, but there were equal amounts showing a complete lack of correlation. The amount of correlation that occurred was not enough to draw a concrete conclusion from. This, however, could have happened because studies have only drawn data points from a limited window of time. Another possibility for this lack of correlation is that most studies were based on in situ hybridization, which only maps the location of transcripts rather than proteins. A third possibility is that studies focused on rhombomeres as landmarks, and therefore correlated expression domains to these. While studies were unable to show a relationship between closely related neurons from the rhombomeres and Hox gene expression, the Hox gene is still an important factor when it comes to specification of the neuronal phenotype. The Hox gene was expressed rostrocaudally in the same sequence that was physically within the chromosome and its transcription was regulated by retinoic acid. The Hox gene has been identified in all vertebrates, and the number of Hox genes expressed increases as the vertebrate species diverge farther away from the invertebrate species. Certain neuron groups relate to Hox gene expression. At the r4 level, Hoxb1 is suspected to bestow rhombomere 4 cell identity.
Rhombomeres have also been shown to be able to affect the position that reticulospinal and branchiomotor neurons grow in. Each rhombomere can cause a repeated pattern of rhombomere-specific neurons, including reticulospinal neurons, many of which share properties such as mediolateral location. Reticulospinal neurons also occupy different areas in rhombomeres in different species. It was found in one study that reticular neurons in the lamprey hindbrain, which included isthmic, bulbar, and Mauthner cells, developed in conserved rhombomere-specific positions, similar to those in the zebrafish. In different species, however, reticulospinal neurons occupy different areas in rhombomeres. The trigeminal and facial motor nuclei were also shown to not correlate well with the rhombomere boundaries in the lamprey.
Several studies have shown that the fibroblast growth factor (FGF) is secreted from the midbrain-rhombomere 1 boundary. These proteins instruct cell behavior in the surrounding neuroectoderm. However, the mechanism behind the integration of the signal and the actions that follow remains unclear. Studies have shown that the FGF receptors, or FGFRs act partially redundantly to support cell survival in the dorsal ectoderm, promote r1 tissue identity, and regulate the production of ventral neuronal populations, including the midbrain dopaminergic neurons. In mice, while mutations of the fgfr2 and fgfr3 did not interfere with the development of the midbrain and r1, mutation of fgfr1 caused midbrain and r1 defects.
Studies have shown that the earliest serotonergic neurons were started in the anterior rhombomeres. The most dorsal group of neurons originated from rhombomere 1, and the posterior raphe—which forms from the rhombomeres—is believed to derive from the posterior rhombomeres at a slightly later stage of embryonic development.
Rhombomeres also lead to the creation of vestibular projection neurons, which are probably produced relatively early in the developmental stages of the brain stem.
In the rhombomeres, members of the T-box transcription factor family, have been linked to the proper development of migrating cells. While the hindbrain is developing, trigeminal cell bodies have been shown to migrate dorsolaterally within rhombomeres 2 and 3, while facial cells move dorsolaterally into r5 near the pial surface. Neurons that form the facial nucleus are produced in r4, but move along the anteroposterior axis of the hindbrain into r6, after which they move dorsolaterally. The vestibuloacoustic neurons are also produced in r4. However, they have a unique migration pattern, where their cell bodies cross the midline to the contralateral side. From this one can conclude that multiple subclasses of motor neurons are produced in specific locations in the developing hindbrain. All of them are related by the expression of Tbx20. Motor neurons produced in the hindbrain have Tbx20 selectively expressed. In Tbx20 mutations, the patterning of the regions of the rhombomeres and motor neurons were normal when they were conditional mutations and the neurons were post-mitotic. Tbx20 mutants pre-mitotic showed many cell migration deficiencies, including abnormal dorsolateral migration of the trigeminal cells, arrested tangential migration of the facial neurons, and a lack of transmedian migration of vestibuloacoustic cells. However, hindbrain motor neurons lacking Tbx20 retained the ability to extend neurites into the periphery. The complete elimination of Tbx20 does not cause trigeminal and facial neurons to switch to hypoglossal neurons. Facial neurons have been shown to migrate tangentially from r4 to r6, while trigeminal neurons that are produced in r2 migrate dorsolaterally non-radially. Vestibuloacoustic cells migrate along the midline at r4 contralaterally in the hindbrain. Tbx20 seems to have context-dependent transcriptional activity. This means that it is able to control different cell migration programs specific to different types of cells. It must be able to regulate these patterns by different means.
While many studies have been done on rhombomeres where rhombomeres are grafted cross species, imprecision can occur. One possible source is damage to the rhombomere during the removal, transportation, or grafting process. Another possible source is the mixture of the cells from different species after the rhombomeres have been grafted on, which could lead to the contamination of one rhombomeric region with another, most likely from the neighboring rhombomeres.


Don Caruth

Donald T. Caruth (May 23, 1950 – May 1, 2010) was the minority leader of the West Virginia Senate and a former member of the West Virginia House of Delegates. He represented the 10th district, serving with Jesse O. Guills. His residence was in Athens, West Virginia, a town in Mercer County, where he died from brain cancer 22 days from his 60th birthday.


Goniopora toxin

Goniopora toxin (GPT) is a polypeptide toxin from the marine "Goniopora" species coral. Two toxins from this source have been identified, one acting on sodium channels and one acting on calcium channels.
Chemistry.
The toxin acting on Na channels has a molecular weight of 12 kDa and consists of 105 amino acids. The GPT that acts on Ca channels has a molecular weight of 19 kDa; its structure is as of yet unknown.
Mode of action.
The 12 kDa GPT inhibits the inactivation of Na channels. This results in a maintained open state of the channel and allows for more Na influx. As a result, the action potential duration is prolonged. The maintained open state of sodium channels induces a longer-lasting action potential, which allows for persistent activation of calcium channels and more calcium influx. The prolongation of the action potential and its subsequent positive inotropic effect can be influenced by stimulus frequency; at higher frequencies (1 Hz), the effects of GPT were suppressed. Furthermore, the effects of GPT on the sodium channels depend on the membrane potential of the cell preceding GPT binding, suggesting that the effects of GPT are potential-dependent. Also, in the presence of GPT, sodium channels are activated in response to an unusually small depolarizing stimulus. The 19 kDa GPT stimulates Ca influx and its activity can be prevented in the presence of a calcium channel blocker. This suggests that GPT directly activates Ca channels or indirectly activates Ca by influencing sodium currents.
GPT effects in different species.
Frequency-dependent effects of GPT were studied on bullfrog atrial muscle. Application of GPT on the muscle showed broadening of action potential duration and showed a positive inotropic effect. When the stimulus frequency was increased, the effects of GPT were considerably suppressed as opposed to low-frequency stimulation. Also, the action potential was prolonged when long intervals of stimulation (1-3 min), in the presence of GPT, were used. In addition, when the cell membrane was hyperpolarized, the effects of GPT also increased, suggesting a potential-dependent effect on GPT toxicity.
Various GPT concentrations (10 – 100 nM) were added to guinea-pig blood vessels, which induced a contraction of the thoracic aorta, portal vein, and mesenteric and femoral arteries via an action on the innervation of the vessels.
In neuroblastoma cells, even a small depolarizing stimulus can cause activation of sodium channels in the presence of GPT.
In the rabbit myocardium GPT enhances atrial contractility and induce arrhythmias at concentrations above 30 nM. The action potential duration was irreversibly prolonged, but there was no effect on the amplitude of the action potential or an effect on the resting membrane potential.
In guinea-pig ventricular cells, the 12 kDa GPT prolonged the action potential by acting on sodium channels, again with no effect on action potential amplitude and the resting membrane potential.
At a concentration of 1.7 μM, the 19 kDa GPT induced contraction of the guinea pig ileum. This contraction was inhibited by a calcium channel blocker.
In cultured chick cardiac cells the 19 kDa GPT induced an activation of calcium influx. The concentration that resulted in a half-maximum activation of calcium influx was 5.3 μM.
Toxicity and treatment.
GPT is highly toxic, with a lethal dose found in mice of 0.3-0.5 mg/kg when the 12 kDa GPT was injected intraperitoneally. Symptoms consist of hypersensitivity, paralysis of hind limbs, diarrhea, rigidity of the entire body, and GPT can lead to a blue or purple discoloration of the skin. Tetrodotoxin, a sodium channel blocker, can be administered to suppress the prolonged action potential. Ca-channel blockers (e.g. nitrendipine and desmethoxyverapamil) can be used to suppress the effects of the calcium channel toxin.


Meridian (perimetry, visual field)

Meridian (plural: "meridians") is used in perimetry and in specifying visual fields. According to IPS Perimetry Standards 1978 (2002): "Perimetry is the measurement of [an observer's] visual functions ... at topographically defined loci in the visual field. The visual field is that portion of the external environment of the observer [in which when he or she is] steadily fixating ...[he or she] can detect visual stimuli."
In perimetry, the observer's eye is considered to be at the centre of an imaginary sphere. More precisely, the centre of the sphere is in the centre of the pupil of the observer's eye. The observer is looking at a point, the fixation point, on the interior of the sphere. The visual field can be considered to be all parts of the sphere for which the observer can see a particular test stimulus. If we consider this surface to be that on which an observer can see anything, then it is a section of the sphere somewhat larger than a hemisphere. In reality it is smaller than this, and irregular, because when the observer is looking straight ahead, his or her nose blocks vision of some possible parts of the surface. In perimetric testing, a section of the imaginary sphere is realized as a hemisphere in the centre of which is a fixation point. Test stimuli can be displayed on the hemisphere.
To specify loci in the visual field, a polar coordinate system is used, all expressed from the observer's perspective. The origin corresponds to the point on which the observer is fixating. The polar angle is considered to be zero degrees when a locus is horizontally to the right of the fixation point and to increase to a maximum of 360 degrees going anticlockwise. Distance from the origin is given in degrees of visual angle; it's a measure of eccentricity. Each polar axis is a meridian of the visual field. For example, the horizontal meridian runs from the observer's left, through the fixation point, and to the observer's right. The vertical meridian runs from above the observer's line of sight, through the fixation point, and to below the observer's line of sight.
Another way of thinking of the maximum visual field is to think of all of the retina that can be reached by light from the external environment. The visual field in this case is all of the external environment that can project light onto the retina. Meridians correspond to sections of great circles passing through the centre of the fovea. In an analogy to Meridian (geography), in which meridians are lines of longitude, the North pole might correspond to the fovea, Greenwich would correspond to a retinal location about 39 degrees to the left of the fovea (because the retinal image is inverted, this corresponds to a location in the visual field to the observer's right), and the South pole would correspond to the centre of the pupil.
The meridian of the visual field has been found to influence the folding of the cerebral cortex. In both the V1 and V2 areas of macaques and humans the vertical meridian of their visual field tends to be represented on the cerebral cortex's convex gyri folds whereas the horizontal meridian is tends to be represented in their concave sulci folds.
References.
IPS Perimetry Standards 1978. (2002). Author. Department of Ophthalmology & Visual Sciences, The University of Iowa. Retrieved March 4, 2005, from http://webeye.ophth.uiowa.edu/ips/GEN-INFO/standards/STANDARD.HTM


Pons

The pons (Latin for "bridge") is part of the brainstem that in humans and other bipeds lies inferior to the midbrain, superior to the medulla oblongata and anterior to the cerebellum.
The pons is also called the pons Varolii ("bridge of Varolius"), after the Italian anatomist and surgeon Costanzo Varolio (1543–75). This region of the brainstem includes neural pathways and tracts that conduct signals from the brain down to the cerebellum and medulla, and tracts that carry the sensory signals up into the thalamus.
Structure.
The pons is in the brainstem situated between the midbrain and the medulla oblongata, and in front of the cerebellum. A separating groove between the pons and the medulla is the inferior pontine sulcus. The superior pontine sulcus separates the pons from the midbrain. The pons can be broadly divided into two parts: the basilar part of the pons (ventral pons), and the pontine tegmentum (dorsal pons). Running down the midline of the ventral surface is the basilar sulcus, a groove for the basilar artery. Most of the pons is supplied by the pontine arteries, which arise from the basilar artery. A smaller portion of the pons is supplied by the anterior and posterior inferior cerebellar arteries.
The pons in humans measures about in length. Most of it appears as a broad anterior bulge above the medulla. Posteriorly, it consists mainly of two pairs of thick stalks called cerebellar peduncles. They connect the cerebellum to the pons (middle cerebellar peduncle) and midbrain (superior cerebellar peduncle).
Development.
During embryonic development, the metencephalon develops from the rhombencephalon and gives rise to two structures: the pons and the cerebellum. The alar plate produces sensory neuroblasts, which will give rise to the solitary nucleus and its special visceral afferent (SVA) column; the cochlear and vestibular nuclei, which form the special somatic afferent (SSA) fibers of the vestibulocochlear nerve, the spinal and principal trigeminal nerve nuclei, which form the general somatic afferent column (GSA) of the trigeminal nerve, and the pontine nuclei which relays to the cerebellum.
Basal plate neuroblasts give rise to the abducens nucleus, which forms the general somatic efferent fibers (GSE); the facial and motor trigeminal nuclei, which form the special visceral efferent (SVE) column, and the superior salivatory nucleus, which forms the general visceral efferent fibers (GVE) of the facial nerve.
Nuclei.
A number of cranial nerve nuclei are present in the pons:
Function.
The functions of these four cranial nerves (V-VIII) include regulation of respiration, control of involuntary actions, sensory roles in hearing, equilibrium, and taste, and in facial sensations such as touch and pain, as well as motor roles in eye movement, facial expressions, chewing, swallowing, and the secretion of saliva and tears.
The pons contains nuclei that relay signals from the forebrain to the cerebellum, along with nuclei that deal primarily with sleep, respiration, swallowing, bladder control, hearing, equilibrium, taste, eye movement, facial expressions, facial sensation, and posture.
Within the pons is the pneumotaxic center consisting of the subparabrachial and the medial parabrachial nuclei. This center regulates the change from inhalation to exhalation.
The pons is implicated in sleep paralysis, and may also play a role in generating dreams.
Other animals.
Evolution.
The pons first evolved as an offshoot of the medullary reticular formation. Since lampreys possess a pons, it has been argued that it must have evolved as a region distinct from the medulla by the time the first agnathans appeared, 505 million years ago.


Ganglion mother cell

Ganglion mother cells (GMCs) are cells involved in neurogenesis, in non-mammals, that divide only once to give rise to two neurons, or one neuron and one glial cell or two glial cells, and are present only in the central nervous system. They are also responsible for transcription factor expression. While each ganglion mother cell necessarily gives rise to two neurons, a neuroblast can asymmetrically divide multiple times. GMCs are the progeny of type I neuroblasts. Neuroblasts asymmetrically divide during embryogenesis to create GMCs. GMCs are only present in certain species and only during the embryonic and larval stages of life. Recent research has shown that there is an intermediate stage between a GMC and two neurons. The GMC forms two ganglion cells which then develop into neurons or glial cells. Embryonic neurogenesis has been extensively studied in Drosophila melanogaster embryos and larvae.
Mitotic division of Neuroblasts in Drosophila.
The daughter cells of a neuroblast have two decidedly different neural fates. This is accomplished by neural fate determinants, important proteins that segregate asymmetrically. Most notable are Numb and Prospero. These proteins are evenly distributed in the neuroblast until mitosis occurs and they segregate totally into the newly formed GMC During Mitosis Numb and Prospero localize to the basal cortex from which the GMC buds off.
Both of these proteins co-function with adapter proteins that facilitate their transition to the basal cortex during Mitosis. These proteins are Miranda and Pon.
These four proteins act to inhibit self-renewal (the cell cycle) and promote differentiation (especially Prospero), which is why GMCs divide into their differentiated progeny instead of more GMCs. Cell cycle progression is inhibited by Prospero because it activates cyclin-dependent kinase inhibitor (CKI).
The vital differentiating proteins that are segregated into the daughter neuroblast and not the GMC are Bazooka, aPKC, Inscutable, and Partner of Inscutable (Pins). The proteins (with the exception of aPKC) form a ternary complex at the apical cortex independent of the proteins that segregate towards the basal cortex. The protein aPKC promotes self-renewal, encouraging the neuroblast to keep dividing and carry out its lineage.
Research has suggested that certain tumor-suppressing proteins (Lgl, Dlg, or Brat) play a critical role in the asymmetric segregation of neural fate determinants and their localization to the basal cortex . In clonal lines of neuroblasts that had been manipulated so that they lacked Lgl activity, Miranda did not segregate asymmetrically, but was evenly distributed throughout the cortex.
The temporal regulation of neuroblast asymmetric division is controlled by proteins Hunchback (Hb) and sevenup (svp). After division svp accumulates in both daughter cells and down-regulates Hb. In the GMC Prospero down-regulates svp, inhibiting the temporal trigger of cellular division.
Type II Neuroblasts.
Type I neuroblasts have been more thoroughly observed and researched than type II. The main difference between them is that type II gives rise do a different kind of GMC (a Transit Amplifying GMC or TA-GMC, also known as intermediate progenitors), and its lineages are generally much longer. TA-GMCs exhibits a different transcription factor from a generic GMC, Deadpan (Generic GMCs do in fact have Deadpan, but not outside of the nucleus). Type II neuroblasts do not contain detectable levels of Prospero. Unlike GMCs, TA-GMCs divide four to eight times, each time producing another TA-GMC and a generic GMC (which goes on to produce two neurons), which is why type II neuroblasts have a larger progeny than type I. Type II neuroblasts contribute a far larger population of neurons to the Drosophlia brain. Recent research has shown that type II lineages are more susceptible to tumor formation than type I. When experimentally knocking out proteins such as Numb or the tumor suppressing protein Brat the entire larval brain results in tumor formation only within type II lineages. Tumor formation occurs when TA-GMCs revert to type II neuroblasts resulting in a highly increased cellular proliferation. The tumor phenotype can be suppressed with the introduction of ectopic Prospero. One of the main differences (perhaps the main difference) between type I and II neuroblasts is the presence of Prospero, suggesting that the introduction of Prospero can cause a type II neuroblast to transform into a type I identity. It is also possible that Prospero simply inhibits the proliferation of type II neuroblasts without transforming them. Type I neuroblasts that have had the gene encoding for Prospero knocked out leads to tumor formation.
Embryonic neural development in Drosophila.
During the embryonic development of Drosophila, neuroblasts delaminate from their respective positions in the embryo and move towards the interior forming a ventral monolayer of cells, known as the neurogenic region. The region is bilaterally symmetrical. The equivalent regions of neuronal growth in other common animal models do not have this symmetrical property, which makes Drosophila preferable for neurogenic study. The neurogenic region is composed of neuroblasts that divide and migrate throughout embryonic development. A larva embryo will contain about 30 neuroblasts per hemisegment of neurogenic tissue. At a certain point, a neuroblast will undergo asymmetric cell division giving rise to a neuroblast and a ganglion mother cell. Each neuroblast can be traced through a lineage using methods such as green fluorescent protein transgene expression in order to investigate mechanisms of cellular diversity. A neuroblast lineage can produce as few as 3 GMCs or up to 20. Research has been conducted to observe the movement of neuroblasts and GMCs in the neurogenic region during embryonic development using molecular markers.
Specific Neuroblast lineages of interest.
In Drosophila, each neural stem cell has been identified and categorized according to their location. Many neuroblasts, but not all, have also had their lineages identified (which GMCs they produce, and which subsequent neurons or glial cells the GMCs produce). For instance the first five GMCs of NB7-1 (the neuroblast located in the 7th row and first column of the cortex) sequentially generate the U1-U5 motor neurons, and then subsequently 30 interneurons. The first GMC of NB4-2 is known to produce motor neuron RP2.
Post-embryonic neural development in Drosophila.
The Drosophila CNS is composed of two brain hemispheres and the ventral ganglion. Each hemisphere is composed of a laterally located Optic lobe (OL) and a medially located, generic Cerebrum (CB). At the end of embryonic development neuroblasts become quiescent, but re-enter their cell cycles during later specific larval stages. The most complex structures in the insect/Drosophila brain, the central complex and the mushroom bodies, are responsible for associative learning and memory and do form during post-embryonic development. Each OL is generated from three neuroepithelia called LPC (laminar precursor cells), OPC (outer proliferation center, and IPC (inner proliferation center). The OPC and IPC becomes asymmetric. Most of the development of the OL occurs at the end of the larval stage. Prospero plays a different role in post embryonic neurogenesis than it did in the embryonic phase. Prospero is post-embryonically upregulated in order to promote neurons to exit the cell cycle, after GMCs differentiate during the embryogenesis Prospero is nearly undetectable.
GMCs and mammalian neurogenic research.
Mammalian neurogenic research has influenced further studies. Although there is no exact equivalent of GMCs in mammalian neurogenesis, mammalian neural stem cells do produce transit amplifying progenitors that expand neural population (similar to TA-GMCs). An ortholog of Prospero in vertebrates (Prox1) is present in newly differentiating neurons and inhibits neural progenitor proliferation. This is similar to Prospero's effect type II neuroblasts that have expressed a tumor forming phenotype. The Prox1 protein is currently being studied as a candidate tumor suppression gene.
Transcription factor expression.
A common example of a transcription factor in neuroblasts is Deadpan, which promotes neural proliferation in the Optic lobe. A previously described transcription factor in GMCs is Prospero or Pros, a transcriptional repressor. It down-regulates cell cycle gene expression to restrict GMCs to one terminal mitosis. Pros is also present in young neurons, preventing mitotic action. Prospero is not present in the progeny of GMCs and is thought to act as a timer, promoting prospective neurons out of their cell cycle.
Implications.
Studying neurogenesis in animal models such as Drosophila comes with many advantages and leads to a better understanding of relevant human neurogenic analogs such as neural stem cells. By obtaining a better understanding of how GMCs function and the role they play in neurogenesis, it may be possible to better understand their analogs in mammals.


SN-2

SN-2 is a chemical compound which acts as an "agonist" (i.e. channel opener) for the TRPML3 calcium channel, with high selectivity for TRPML3 and no significant activity at the related TRPML1 and TRPML2 channels. It has demonstrated antiviral activity in an "in vitro" model.


Francis Allegra

Francis Marion Allegra (October 14, 1957 – August 27, 2015) was an American federal judge on the United States Court of Federal Claims.
Early life and education.
Allegra grew up in Cleveland, Ohio, and graduated from St. Edward High School in Lakewood, Ohio. He graduated from Borromeo College of Ohio in 1978, with a degree in philosophy, and then, in 1981, received his Juris Doctor (magna cum laude) from the Cleveland-Marshall Law School at Cleveland State University. Following graduation, he served as a law clerk to Chief Trial Judge Philip R. Miller of the U.S. Court of Claims from 1981 to 1982.
Professional career.
From 1982 to 1984, Allegra was an associate at the Cleveland law firm of Squire, Sanders, and Dempsey, where he specialized in tax and bond work. In 1984, he joined the Appellate Section of the Tax Division of the U.S. Department of Justice. From 1984 through 1994, he was an appellate litigator, handling many of the Tax Division's most complex cases in Federal courts of appeals throughout the country. During this period, Allegra steadily rose through the ranks of the Tax Division ranks, becoming first a Special Assistant to the Assistant Attorney General of the Tax Division and then Counselor to the Assistant Attorney General of the Tax Division.
In 1994, Allegra was appointed Counselor to the Associate Attorney General (the third-highest-ranking official at the Justice Department). Shortly after that, he was appointed Deputy Associate Attorney General. In the latter role, Allegra worked with the Tax and Antitrust Divisions, as well as with the National Economic and Domestic Policy Councils at the White House.
Federal judicial service.
On October 22, 1998, at the age of forty-one, Allegra was appointed by President Bill Clinton to be a judge on the United States Court of Federal Claims. Over his judicial career, he has issued more than 250 published opinions, on topics including tax, government contracts, intellectual property, takings, and military and civilian employment. From 2003 through 2010, Allegra was a member of the Information Technology Committee of the Judicial Conference of the United States. Allegra assumed senior status on October 22, 2013.
Allegra was an adjunct professor at the Georgetown University Law Center, where he taught Litigation with the Federal Government and a seminar on sovereign immunity. In 2012, Georgetown awarded him the Charles Fahy Distinguished Adjunct Professor Award, which is given annually to an adjunct professor who has made an extraordinary contribution to the Law Center. Allegra was also a frequent lecturer at Federal Judicial Center programs and other programs involving intellectual property, tax, government contracts and the use of technology in judging. He was considered an expert on issues involving electronic discovery.
In the fall of 2013, Allegra co-authored (with Daniel B. Garrie), "Plugged in: Guidebook to Software and the Law".
Personal life.
Allegra married his wife, Regina, in 1996. The couple had two sons. He was an avid mineral collector, who wrote a column—Legal Nuggets—for the "Mineralogical Record". He was also active in Italian-American affairs, particularly with the Sons of Italy. He was a former President of the Sons of Italy International Lodge #2522. He was a co-founder of the Friends of Charles Bonaparte.
Allegra died on August 27, 2015, of brain cancer.


Mesencephalic locomotor region

The mesencephalic locomotor region (MLR) is a functionally defined area of the midbrain that is associated with the initiation and control of locomotor movements in vertebrate species.
Neuroanatomical organization.
The MLR was first described by Shik and colleagues in 1966 when they observed that electrical stimulation of a region of the midbrain in decerebrate cats produced walking and running behavior on a treadmill. Twenty-eight years later, Masdeu and colleagues described the presence of a MLR in humans. It is now widely acknowledged that, along with other motor control centers of the brain, the MLR plays an active role in initiating and modulating the spinal neural circuitry to control posture and gait. Anatomically, as the name suggests, the MLR is located in the mesencephalon (or midbrain), ventral to the inferior colliculus and near the cuneiform nucleus. Although identifying the exact anatomical substrates of the MLR has been subject to considerable debate, the pedunculopontine nucleus (PPN), cuneiform nucleus, and midbrain extrapyramidal area are thought to form the neuroanatomical basis of the MLR. Nuclei within the MLR receive inputs from the substantia nigra of the basal ganglia and neural centers within the limbic system. Projections from the MLR descend via the medullary and pontine reticulospinal tracts to act on spinal motor neurons supplying the trunk and proximal limb flexors and extensors.
The PPN within the MLR is composed of a diverse population of neurons containing the neurotransmitters gamma-amino-butyric acid (GABA), glutamate, and acetylcholine (ACh). Results from animal and clinical studies suggest that cholinergic neurons in the PPN play a crucial role in modulating both the rhythm of locomotion and postural muscle tone. Glutamatergic and cholinergic inputs from the MLR may be responsible for regulating the excitability of reticulospinal neurons that in turn project to spinal central pattern generators to initiate stepping.
Clinical significance.
The integration of motor and sensory information during walking involves communication between cortical, subcortical, and spinal circuits. Step-like motor patterns of the lower extremities can be induced through activation of the spinal circuitry alone; however, supraspinal input is necessary for functional bipedal walking in humans. Pathologies of the nuclei within the MLR have been associated with a combination of clinical features that are unique to midbrain dysfunction and can be differentiated from other subcortical neurological conditions such as those associated with Parkinsonism and cerebellar lesions.
In a clinical case series, three adult males with isolated lesions of the MLR presented with gait hesitation and gait ataxia characterized by stepping that lacked uniform direction, amplitude, and rhythmicity. Although gait hesitation and ataxia are also clinical features of Parkinson's disease and lesions of the cerebellum, respectively, the authors noted that the patients did not display any other common signs or symptoms associated with these neurological conditions, suggesting that pathologies of the midbrain can produce gait disturbances even when cerebellar and basal ganglia function are intact. In a study investigating high-level gait and balance disorders in elderly adults who had no evidence of rheumatologic, orthopedic, or neurologic disease, brain imaging data revealed an association between reduced gray matter density of the PPN and cuneiform nucleus and impaired gait initiation, step execution, and postural control. Additionally, among eighteen individuals with Parkinson's disease who either did or did not experience Freezing of Gait, functional magnetic resonance imaging revealed reduced activity in the MLR and supplementary motor area among those individuals who experienced episodic gait hesitation. Freezing of Gait has also been associated with functional reorganization of supraspinal locomotor networks whereby altered connectivity and communication between the supplementary motor area and MLR were observed. These findings suggest that the MLR does in fact play a unique role in human locomotion, especially with respect to step initiation and motor planning.
Deep brain stimulation.
Given the role of the MLR in gait initiation and postural control, researchers and clinicians have investigated the effects of targeted deep brain stimulation (DBS) on gait disturbances in clinical populations. Plaha and Gill reported significant improvements in gait dysfunction and postural instability in two patients with advanced Parkinson's disease who were treated using DBS electrodes implanted in the region of the PPN. Likewise, in a more recent study, six patients with Parkinson's disease demonstrated improvements in posture, gait, and postural stability following 6 months of DBS to the PPN and subthalamic nucleus. Bachmann and colleagues applied DBS to the MLR in rats with chronic, incomplete spinal cord injury and reported improved hindlimb function and near normal restoration of locomotor function following treatment.