Rab7a and CMT2b Essay -- Biology, Proteins, Cells

Rab7a and Charcot-Marie-Tooth Disease Type 2b The aim of this essay is to review recent research into the Rab7a gene mutations and the mechanistic causes of Charcot Marie Tooth disease type 2b. It will ascertain if there is a clear forerunner in terms of theory of pathology due to Rab7a mutations. Any specific potential treatments for CMT2b that have been discovered will also be investigated Rab7a is a gene that provides the instructions to make the protein Rab7. Rab7 is one of over sixty Rab proteins identified within mammalian cells, all of which belong to the Ras superfamily. All Rab proteins are involved with the endo/exocytic, secretory pathways and each one associates with its own specific membranes and organelles, although it may share a membrane with another Rab protein. Rab7 has been discovered to function in the late endosomes, lysosomes and the autophagosomes. Like all Rabs, Rab7 is a monomeric GTPase that cycles from an active, GTP-associated, membrane-bound state to a GDP-associated state that is found in the cytosol as part of a complex with the soluble Rab GDP-dissociation inhibitor (GDI). To activate Rab7, a membrane bound guanine nucleotide exchange factor (GEF) is needed. Once the Rab7 has gained a GTP at the loss of GDP and become anchored into a plasma membrane by a hydrophobic lipid anchor, two ‘switch’ regions conformationally change to allow recruitment and binding of other effector proteins that assist with vesicle transport, membrane tethering and fusion. See figure 1. Hydrolysis of GTP is accelerated by GTPase-activating factors (GAPs), and membrane insertion and extraction is partially coupled to nucleotide exchange (Grosshans et al, 2006) ... ...hin the cell may be particularly pronounced in the longer neurites of the extremities, providing support for Spinosa et al’s (2008) previous suggestion that CMT2b mutations affect the longer neurons due to the increased distance that molecules have to travel compared to other neurons. Valproic acid has been found to stimulate neurite growth in the presence of CMT2b-associated Rab7 mutants through Erk. Valproic acid (VPA) is a short-branched fatty acid, a mood stabiliser it is normally used to treat bi-polar disorder, and as an anticonvulsant (Manji et al, 2001 IN: Yamauchi et al, 2010). Yamauchi et al in 2006/2007 reported that VPA promoted neurite growth through the c-jun N-terminal kinase (JNK) pathways in mouse neuroblastoma cells. In 2010, Yamauchi et al studied the effect of VPA in a neuropathy model, again in mouse neuroblastoma cells (N1E-115 cells)

Ideas And Issues In “The Visit” And “A Chronicle Of A Death Foretold” Essay

Many works of contemporary literature discuss ideas and topics which are seen in the world around us today. These themes are either directly demonstrated or implied. Two works as such are â€Å"The Visit† by Friedrich Durrenmatt and â€Å"A Chronicle of a Death Foretold† by Gabriel Garcia Marquez. The issues raised in these two books are justice, communication, tradition, and moral values. Tradition is the ongoing obligation to commit to something, which is an act that has existed for many years. More often than not, tradition helps keep a community in one piece, much like laws do. In other cases, tradition obligates people and makes them do things they normally wouldn’t do. In â€Å"A Chronicle of a Death Foretold†, tradition is one of the forces that drives the Vicario twins to kill Santiago Nasar and therefore clean their family’s name. However, the Vicario brothers try to escape tradition. They had a debt which they greatly doubted and criticized. They know what the whole town expects them to do. But on the other side, their everyday life and friendship with Santiago Nasar, their victim, fills them with haste to fulfill tradition and do their pre-said duty. In â€Å"The Visit†, it’s tradition in the first place that brings the much anticipated lady Zachanassian to Guellen. So, in other words, tradition kills Ill as well as Santiago Nasar. Intertwined with the complications of tradition are the moral values behind any clearly human act. The only reason tradition has always been so difficult to adhere to is because of the moral issues behind the acts that tradition is composed of. This is seen in both pieces. In â€Å"A Chronicle of a Death Foretold†, the Vicario brothers are in a state of great misfortune not only because of the shame inflicted upon the Vicario family name but also because of the deed the have to carry out. However they also want their duty to be done. In an attempt to combine both, the twins unsuccessfully try to be caught whilst looking for Santiago Nasar. In other words, they seek someone to stop them by telling the whole town of their intentions. â€Å"†¦ ,in reality it seemed that the Vicario brothers had done nothing right with a view to killing Santiago Nasar immediately and without any public spectacle, but had done much more than could be imagined to have someone stop them from killing him, and they had failed† (p. 56). In â€Å"The Visit†, the town tries to hold its moral values despite the ironic reward the people and state will get if they do not. Later on in the book, even though Guellen has completely lost its morality and plans on doing Maddamme Zachanassian’s bidding and killing Ill, the townspeople will not admit, whatsoever that they have lost their towns values. Moreover, they blame Ill for not having any morality and tell him that if he had any values he would use a gun on himself outright. Ill, however denies the Mayor’s suggestion. â€Å"Mayor: Pity. You’re missing a chance to redeem yourself and be a more or less decent human being. † (p. 81) Tradition and the morality behind it are the two most ancient forms of justice. Today, justice is defined by laws and mainly is democratic and clear. But every person has their own form of justice for things, often acquiring either guilt or praise thereafter; or none of the two. Self-justice is reflexively self-justifying. In â€Å"The Chronicle of a Death Foretold†, the Vicario brothers want Justice. However, their morality, as discussed above, does not allow them to justify their family’s shame by killing Santiago Nasar. For the sake of tradition they kill Santiago anyway. Pablo and Pedro Vicario tell everybody they come across that they will kill Santiago Nasar, hoping to get caught.. That way, they would have done their justice and duty as the brothers of Angela Vicario, the violated girl, by attempting to kill Santiago and not actually slaying him. They do not commit a crime the do not want to commit and which they consider immoral. Also, when Santiago appears to them, the Vicario twins do not face him head on. Instead they give him a chance of escape by remaining of the opposite side of the street and giving him a head-start through their body language. Clara Zachanassian in â€Å"The Visit† loses all of her moralities during her childhood as a prostitute and thus ends up defying the right and wrong of justice. Therefore, she goes ahead and offers money for an assassination. The townspeople of Guellen try to force back their moralities but fail to do so. As a result they take an alternative route to solving their problem. They masquerade the immorality of the crime of murder as justice. What follows is that they kill Ill with their bare hands. For justice and tradition to be enforced, a clear communication line must be drawn. Communication is what leads to the smooth flow of traditions and miscommunication to their collapse of justice. Morality has to do with a person’s ability to communicate to oneself what they truly consider right or wrong; in this case it is contributed to justice and questionable traditions. Pedro and Pablo Vicario’s failure to alert the whole town of Riochacha of their imminent crime is a result of poor communication. They misinterpreted the ability of the townspeople to pass on information and the rate in which the news would diffuse their way to Santiago Nasar or to the police. However they did not take one aspect of tradition into account: â€Å"But most of those who could have done something to prevent the crime and did not consoled themselves with the pretext that affairs of honor are sacred monopolies [according to tradition], giving access only to those who are part of the drama. † (p. 114). So, according to tradition, most people in town could not tell the authorities, nor anyone for that matter, about the Vicario twins and on top of that they could justify themselves by blaming it on the town’s ethics. â€Å"Destiny makes us invisible† (Quote, Gabriel Garcia Marquez, 1928) The town of Guellen, on the other hand, had a level of communication between them far better than any other. They could communicate through the sub-conscious. It is not exactly stated that the Guelleners had actually decided upon killing Ill, so this could be assumed. They were very well organized and swift in killing Ill, as they were able to put many new products they wanted, more than needed, on account. As is clear, tradition, morality and justice are all connectable aspects which are usually bound together by a means of communication. Situations become elaborate and complications arise. â€Å"The Chronicle of a Death Foretold† and â€Å"The Visit† are two great examples of a situation that results from the combinations of those four issues.

Motivation, As The Causes Of Our Behaviour - 1644 Words

Motivation Introduction Mitchell (1982, p.82) describes motivation as â€Å"the degree to which an individual wants and chooses to engage in certain specified behaviours†. Hence, in general, behaviour is determined by certain motives, thus, Vroom and Deci (1992, p.33) considered motivation â€Å"as the causes of our behaviour†. Moreover, according to Mullins (2013, p.245) motivation is concerned with question â€Å"why do people do what they do?†, because motivation is an inner driving force which leads to particular action to achieve some aim and fulfil some need. In other words, Chartered Management Institute (cited in Mullins, 2013, p.246) observes that, â€Å"the aim of management is to give people what they really want most from work†. Motivation is a complex subject and traditionally has been cast as an individual phenomenon, because, the uniqueness of each individual is a reflection of different needs, values, attitudes and goals. In that case, Mitchell (1982, p.81) assumes that all of the main motivational theories allow in one way or another for uniqueness to be demonstrated. Furthermore, different theories of motivation purpose different reasons but almost all of them emphasise an individual and intentional choice of behaviour analysis. As a consequence, Handy (1999, p.29) stresses that if individual behaviour could be analysed and understood, then the individual motives could be predicted and could be influenced. However, no certain formula exists. On the other hand, even theShow MoreRelatedTheories of Motivation1011 Words   |  5 PagesTheories of Motivation Arousal: * A person’s state of alertness and mental and physical activation. Arousal Theory: * People are motivated to maintain an optimal level of arousal. * The optimal level is different for all of us. 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