Alzheimer’s Disease Biological Causes

Alzheimers Disease Biological Causes Alzheimer’s disease is driven by two processes: extracellular deposits of beta amyloid and intracellular accumulation of tau protein.[9] â€Å"It is characterized by accumulation of amyloid-ÃŽ ² peptide, generated by proteolytic processing of the amyloid precursor protein (APP) by ÃŽ ²- and ÃŽ ³-secretase.†[10p554] The APP gene provides instructions for making APP. This protein is found in many tissues and organs including the brain and the spinal cord. It plays a role in cell growth, formation of new synapses, differentiation of neurons, cell adhesion, calcium metabolism, and protein trafficking.[10] The length of APP varies between 695 to 770 amino acids. Protein breakdown generates AÃŽ ², a 39- to 42-amino acid peptide. This form is the primary component of amyloid plaques found in the brains of AD.[10] APP may be processed via a non-amyloidogenic pathway that prevents AÃŽ ² formation or through a toxic, amyloidgenic pathway, resulting in AÃŽ ² plaque formation. In the non-amyloidogenic pathway, APP is processed in peripheral cells. In this pathway, APP is cleaved by an enzyme called ÃŽ ±-secretase followed by ÃŽ ³-secretase. These are integral membrane proteins where cleavage by ÃŽ ±-secretase occurs within the AÃŽ ² domain. Cleavage by ÃŽ ±-secretase prevents AÃŽ ² formation and releases the extracellular secreted APP ÃŽ ± fragment.[11] Research shows that secreted APP ÃŽ ± protects neurons, regulates stem cell production, plays a role in brain development, and promotes the formation of synapses and cell adhesion. The remaining C-terminal fragment of APP then undergoes either lysosome degradation or ÃŽ ³-secretase cleavage, which generates p3 and the APP intracellular domain.[11] In the amyloidogenic pathway, APP is primarily processed in neuronal cells. Within this pathway, APP is cleaved by ÃŽ ²-site APP cleaving enzyme 1 ( BACE1 ), followed by ÃŽ ³-secretase. BACE1 initiates the production of the toxic AÃŽ ² that plays a crucial role ea rly in the pathogenesis of AD.[11] Cleavage of APP by BACE1 releases the extracellular secreted APP ÃŽ ² fragment which is thought to assist with axon pruning and cell death.[12] BACE1 cuts APP to produce a membrane-bound C-terminal fragment C99 that is further processed by ÃŽ ³-secretase to generate AÃŽ ². The site of ÃŽ ³-secretase cleavage within the transmembrane domain of APP can vary and determines the type of AÃŽ ² that is produced, AÃŽ ² 39-42. Once produced, AÃŽ ² is usually secreted into the extracellular space via exocytosis.[12] AÃŽ ² is a major component of plaques that are found in both intracellular and extracellular locations. AÃŽ ² 42 is considered to be one of the main causes of these plaques because it clumps together more quickly than other isoforms, forming clusters and fibrils.[10] In individuals with AD, elevated concentrations of AÃŽ ² plaques can lead to many cellular dysfunctions. The presence of AÃŽ ² plaques alone is not enough to diagnose AD since ma ny people without cognitive decline have plaques. Tau is a protein in the microtubule-associated protein family. It has several physiological functions in healthy axons including microtubule assembly and stability, vesicle transport, neuronal outgrowth and neuronal polarity. This protein consists of 352 to 441 amino acids and presents in various isoforms in the brain.[10] In AD, tau protein is hyperphosphorylated, causing disruption in microtubule transport and loss of neuronal transmission. Tau phosphorylation is the addition of phosphate to a tau protein through regulation of tau kinases. In humans, the tau gene is positioned on chromosome 17. In a normal brain, there are two to three moles of phosphate per one mole of tau, indicating that this amount of phosphorylation is necessary for tau to perform its normal biological functions. When tau becomes hyperphosphorylated, the ratio of phosphate to tau increases three to four fold compared to normal phosphorylation levels. This incr eased amount of phosphate alters the function of tau, making it insoluble and lacking affinity for microtubules. This leads to the degradation of the microtubules and neuronal cell death.[10]

The Yes Men Fix the World (2009) movie Essay Example | Topics and Well Written Essays - 500 words

The Yes Men Fix the World (2009) movie - Essay Example Recently university had named its renovated baseball stadium after Alex Rodriguez as he had donated $3.9 million for upgrading the field. The university’s ethical considerations are being challenged. The star athletes like Alex Rodriguez, Ryan Braun, Gio Gonzalez and five other prominent people associated with university and its programs have recently come under investigation for use of banned drugs (Schmidt, 2013). Moreover, various newspaper report claim that they have also links with clinics like Biogenesis that helps them to get performance enhancing drugs. Jimmy Goins the conditioning coach of Miami is suspected of providing drugs to the players. The university has therefore become nexus for drug mafia and is presently under investigation by NCAA. Yes person would initiate a sustained campaign against the athlete program of University of Miami for providing performance enhancing drug to its players. They would do so by using 3 news write-ups about the new research initiative started by university in the area of performance enhancement of athletes. Appiah’s idea of culture mainly relies on empowering people and letting them be the master of their decisions (Appiah, 2006). He says that often the excruciating circumstances of the people become major planks for the developed world to exploit and force their own attitude and ideas in the name for preserving cultures and cultural identities. He believes that ethics, morality and cultural paradigms are critical aspects which become extraneous not because people actually want to but due to lack of resources which makes them opt for new tools of survival. The prank is closely linked to Appiah’s ideas as it indirectly targets the ethical lassitude of the modern academia and its changing priorities for competing in different areas of human interaction. Schmidt, Michael S. Drug Enquiry Focuses on Athletes’ Ties to Team at University of

The duty to accommodate the injured and the disabled employees Essay

The duty to accommodate the injured and the disabled employees - Essay Example Three steps processes used to determine if the employer has made conscientious efforts on accommodation of the less fortunate employee: first is to know if the employee can perform his or her existing job. If the employee cannot, then establish if he or she can perform his or her current job if modified, if still he or she cannot, then determine if he or she can perform any other job existing re-bundled or modified job (David Morton Rayside, 2007). Disability is something that hinders an individual in undertaking life important functions. It may mean mental, psychological, physical, or even habitual. Of all the most complicated, as many employers claim, is mental incapacitation especially when the employee has to get into contact with clients, and habitual disabilities like drug dependency and alcoholism. They tend to be tricky even more than other health complications (David Morton Rayside, 2007). The importance of Human Rights Legislation, as it relates to disability is to protect those who are perceive or actually materially impaired through illness. The said disabilities include physical conditions, congenital deformities, asthma, epilepsy, hypertension, speech impediments, alcoholism and drug dependency, obesity and AIDS or AIDS related complex and any other medical, psychological or physical condition. However the duty to accommodate does not imply a guaranteed job for unemployed disabled person. If a person cannot reaso nably perform the essential duties and requirements after employment, there will be no findings for discrimination (David Morton Rayside, 2007). Accommodation is now a deeply entrenched feature in Canadian labor law. It has been enthusiastically practiced since the start of this decade, but it is already spawning or accelerating three outstanding trends in the arbitration system that are changing the very face of labor adjudication in