The Approaches to Environmental Ethics Essay Example | Topics and Well Written Essays - 2500 words

The Approaches to Environmental Ethics - Essay Example As it tackles the natural environment, deep ecology concerns itself with all organisms – both plants and animals – within the biosphere and promotes equality, particularly in regard to the right to live of all organisms as a fundamental value. The deep ecology approaches to environmental ethics include â€Å"self realization,† â€Å"biocentrism† or â€Å"anti-anthropocentrism† as these ecologists espouse democracy in the biosphere among all organisms within (Devall etc 1995, p67). Self-realization beyond the concept of the modern Western self or for a narrow sense of individual salvation and that it supposedly has further maturity as it goes further than the egocentric cultural assumptions, values and conventional wisdom in its treatment of the environment (Devall etc 1995, p67). The main argument of the biocentric approach, meanwhile, is that â€Å"all things in the biosphere have an equal right to live and blossom and to reach their own individual forms of unfolding and self-realization within the larger Self-realization† (Devall etc 1995, p67).

The Marketing Environment Essay Example for Free

The Marketing Environment Essay The marketing environment surrounds and impacts upon the organization. There are three key elements to the marketing environment which are the internal environment, the microenvironment and the macroenvironment. Why are they important? Well marketers build both internal and external relationships. Marketers aim to deliver value to satisfied customers, so we need to assess and evaluate our internal business/corporate environment and our external environment which is subdivided into micro and macro. Internal Environment The internal environment has already been touched upon by other lessons on marketing teacher. For example, the lessons on internal marketing and also on the functions within an organization give a good starting point to look at our internal environment. A useful tool for quickly auditing your internal environment is known as the Five Ms which are Men, Money, Machinery, Materials and Markets. Here is a really quick example using British Airways. Looking internally at men, British Airways employees pilots, engineers, cabin crew, marketing managers, etc. Money is invested in the business by shareholders and banks for example. Machinery would include its aircraft but also access to air bridges and buses to ferry passengers from the terminal to the aircraft. Materials for a service business like British Airways would be aircraft fuel called kerosene (although if we were making aircraft materials would include aluminium, wiring, glass, fabric, and so on). Finally markets which we know can be both internal and external. Some might include a sixth M, which is minutes, since time is a valuable internal resource.

Role of E6AP in Malignancies and Tumorigenesis

Role of E6AP in Malignancies and Tumorigenesis INTRODUCTION Leukemia is a malignant hematological disorder characterized by proliferation of abnormal white cells that infiltrate the bone marrow, peripheral blood and other important organs. Leukemia arising from myeloid cells is known as Myeloid Leukemia which may either be chronic myeloid leukemia (CML) and/or acute myeloid leukemia (AML). AML is a complex disease caused by mutations, deregulated gene expression and epigenetic modifications leading to increased proliferation and decreased differentiation of hematopoietic progenitor cells. Several important molecular markers have been discovered in AML to better characterize patients. C/EBPÃŽ ± is an important regulator of Granulopoiesis. Several groups have reported mutations in the C/EBPÃŽ ± gene in a subset of patients with AML presenting with normal karyotypes. A significant percentage of AML patients without chromosomal translocations have demonstrated abnormalities in C/EBPÃŽ ± protein or function, suggesting that loss of transcriptional control is a common mechanism of leukemogenesis. Even in the setting of other proleukemogenic genetic abnormalities, such as the (8; 21) translocation, C/EBPÃŽ ± has been demonstrated to be aberrantly regulated, in this case by down regulation of expression. Functional alterations of C/EBPÃŽ ± in AML include mutations of the C/EBPÃŽ ± gene and deregulated expression of C/EBPÃŽ ± by chromosomal translocations. Further, post-transcriptional or post-translational suppression of C/EBPÃŽ ± has been demonstrated to be involved in hematopoietic malignancies. AML is also characterized as, a malignant disease of hematopoietic system in which cells accumulate in an undifferentiated state due to mutations that prevent their normal differentiation and allow undifferentiated cells to survive and proliferate. The molecular changes that occur in AML usually lead to either abnormal cell proliferation (FLT3 and Ras mutations) or block in differentiation (AML1/ETO, PML/RAR alpha, C/EBPalpha mutation s) or suppression of apoptosis (bcl2 overexpression). Despite of block in differentiation, native AML cells often show some morphological signs of differentiation that allow a classification into different subsets, and further differentiation may be induced by exposure to various soluble mediators, e.g., all trans-retinoic acid (ATRA) and several cytokines in t(15;17). All-trans retinoic acid (ATRA) is a derivative of vitamin A and it affects cellular development including haematopoiesis, in particular granulocytic differentiation. ATRA could induce a dose-dependent differentiation of HL-60 promyeloblasts to mature, functioning neutrophils. ATRA induces growth inhibition, differentiation, and apoptosis in cancer cells, including acute promyelocytic leukemia (APL). In APL, expression of promyelocytic leukemia protein retinoic acid receptor (PMLRARÃŽ ±) fusion protein, owing to the t (15; 17) reciprocal translocation, leads to a block in the promyelocytic stage of differentiation. E3 Ubiquitin ligases are a large family of proteins engaged in the regulation of protein turnover and activity through a multistep proteolytic cascade, called ubiquitination. Ubiquitination of a target protein involves 2 distinct steps: covalent attachment of multiple ubiquitin molecules to the protein substrates and degradation of the polyubiquitylated proteins by the 26S proteasome system. The first step is mediated by a cascade of 3 enzymes: ubiquitin activating enzyme (E1), ubiquitin conjugating enzyme (E2), and ubiquitin ligase (E3) [1, 2]. Ubiquitin is a 76-amino acid polypeptide that is highly conserved among eukaryotic organisms. It is first activated in an ATP-dependent manner via binding to E1 through a thioester bond between a cysteine residue at the active site of E1 and the C-terminal glycine (G76) of ubiquitin. Activated ubiquitin in an E1-ubiquitin complex is then transferred to E2, which also participates in the formation of a thioester bond between its active site cy steine residue and the G76 of ubiquitin. Finally, ubiquitin is covalently attached to the target protein through an is opeptide bond between the G76 of ubiquitin and the ÃŽ µ-amino group of an internal lysine residue of the target protein, in a reaction catalyzed by E3 ligase. Subsequent to the linkage of ubiquitin to the target protein, a polyubiquitin chain is formed in which the C-terminus of each ubiquitin moiety is linked to a specific lysine residue (most commonly Lys48) of the previous ubiquitin to form K48-linked polyubiquitylated conjugates which are rapidly recognized by the 19S regulatory subunit of the 26S proteasome and degraded by the 20S core particle [1-3]. There are approximately 600 E3 ligases in the human genome that can be classified into 3 major types the N-end rule ubiquitin ligases; HECT-type; and the RING-type, on the basis of domain structure and substrate recognition[1]. The N-end rule ubiquitin E3 ligases target protein substrates bearing specific destabilizing N-terminal residues, including Arg, Lys, His (type I) and Phe, Trp, Leu, Tyr, Ile (type II)[1]. The second type HECT (homology to E6AP C-Terminus) E3-ubiquitin protein ligases, found from yeast to humans range in size from 80kDa to more than 500kDa. They are characterised by the HECT domain, a C-terminal region of approximately 350 amino acids in length with significant similarity to C-terminus of E6AP. Unlike RING E3s which act as scaffolds facilitating interaction between E2s and substrates, HECT E3 ligases form an intermediate thioester bond with the ubiquitin C-terminus through an evolutionarily conserved cysteine residue before catalyzing substrate ubiquitination. Hence, HECT E3s play a direct catalytic role in the final attachment of ubiquitin moieties to target proteins. The N-terminus is highly variable and may be involved in substrate recognition. On the basis of distinct amino acid sequence motifs within the N-terminus, human HECT E3s can be classified into 3 sub-families: HECT E3s with RLDs (RCC1-like domains, termed as HERC (HECT and RCC-1like domain E3s), HECT E3s with WW domains (called Nedd4/Nedd4- like E3s), and HECT E3s that neither contain RLDs nor WW domains (called SI(ngle)- HECT E3s). E6AP, the prototype of HECT E3 family belongs to the third sub-family of HECT E3 ligases [3-5]. The third and the largest type of E3 ligase is the RING (Really Interesting New Gene) family. RING-based E3 ligases are specified by over 600 human genes surpassing 518 protein kinase genes. These are characterised by a classic C3H2C3 or C3HC4 RING finger domain with a characteristic linear sequence Cys-X2-Cys-X9-39-Cys-X1-3-His-X2-3-Cys/His-X2-Cys-X4-48-Cys-X2-Cys, where X can be any amino acid. The RING domain provides a docking site for the E2 enzyme, which mediate transfer of ubiquitin to the substrate, facilitating assembly of mono- or polyubiquitylated conjugates via different lysine residues of ubiquitin. The resulting modifications have a diverse range of biological functions, from proteasome-dependent proteolysis (Lys48- and Lys 11-linked polyubiquitin) to post-translational regulation of protein function, structure, assembly, and/or localization (Lys 63 and other linkages)[1, 6]. E3 ligases can also be classified into single subunit E3s (e.g. Mdm2, Cbl) and multi-subunit complexes (APC, SCF). E3 enzymes bind their target substrates through various protein-protein interaction domains (e.g. WD 40 repeats). However, for substrate recognition post-translational modifications such as phosphorylation or proteolytic cleavage are required[7]. The modified motif in the substrate is called degron. There are many different types of degrons (e.g. phosphodegron, PEST). Once modified, a degron in a substrate might be recognized by a specific E3 ligase, which forms the basis for its subsequent ubiquitination[8]. Through ubiquitin-mediated covalent modification of diverse range of cellular proteins, E3 ubiquitin ligases regulate several cellular functions or biological processes such as cell cycle progression, Oncogenesis, signal transduction, transcription regulation, DNA repair, endocytois, transport and development via proteolytic or non-proteolytic mechanisms [2, 9]. A direct molecular link between cell-cycle control, Oncogenesis and E3 ubiquitin ligase activity was supported by several clinical findings and wealth of experimental data on E6AP, SKP2 and FBW7, Nedd 4-1, Pirh2, CDC20, CDH1 and also on other E3 ligases [3, 10, 11]. Understanding the physiological role of E6-AP, the founding member of the HECT E3 family, is of interest because inactivation of UBE3A gene encoding E6AP has been associated with Angelman Syndrome, a hereditary neurological disorder. Moreover, in the case of cervical cancer, the E6/E6-AP complex not only targets p53 for ubiquitin-mediated degradation, but also targets other proteins, which is necessary for HPV-induced cervical carcinogenesis[12]. E6-AP forms a stable complex with the adaptor protein E6. The dimeric complex binds to and targets p53 for ubiquitin-mediated proteolysis, thus eventually interfering with the negative growth regulating activities of this tumor suppressor protein [13-15]. In addition, the expression of E6-AP protein is decreased in human invasive breast and prostate cancers compared with their adjacent normal tissues. This down-regulation of E6-AP is accompanied by the elevation of ER in breast and AR in prostate carcinomas[16]. Furthermore, in vivo data fro m E6-AP-knockout animals indicated that the expression levels of ER and AR are increased in E6-AP-null mammary and prostate glands, respectively, when compared with that of normal control animals, suggesting that E6-AP modulates the protein levels of ER in breast and AR in prostate glands [17]. E6AP, a 100-kDa cellular protein is a member of functionally related E3-ubiquitin-protein ligases defined by the domain homologous to the carboxy terminus hect domain.20 E3 ligases ubiquitinate and degrade several regulatory proteins including p53, p27, promyelocytic leukemia retinoic acid receptor ÃŽ ± and others, which serve as tumor suppressors and cell-cycle inhibitors. E6AP promotes C/EBPÃŽ ± ubiquitination leading to its proteasome-mediated degradation and thus functional inactivation. E6AP negatively regulate Granulopoiesis by targeting C/EBPÃŽ ± for degradation via ubiquitin proteasome pathway. Promyelocytic leukemia tumor suppressor (PML) has been recently identified as a target of catalytically active form of E6AP. PML tumor suppressor is essential for the formation of PML nuclear bodies. Recent studies have implicated role of PML and PML nuclear bodies in the regulation of growth inhibition, senescence and apoptosis. PML is down regulated in multiple human cancers and experimental data has correlated reduced PML activity and expression to E3 ubiquitin ligase activity of E6AP, regulating protein turnover and activity[18]. Recently, Annexin I involved in the inhibition of cell proliferation, regulation of cell differentiation, anti-inflammatory effects, cell death signalling, carcinogenesis has been identified as a novel target of E6AP in addition to classical substrates, including p53 tumor suppressor, PDZ domain-containing protein scribble, a transcriptional repressor of the gene encoding hTERT[19]. In addition, studies have also implicated the role of E6AP ubiquitin ligase activity in ubiquitin-dependent degradation of Peroxiredoxin1 and presumably open avenues to investigate the functional link between lack of E6AP expression and stability of Peroxiredoxin 1with regard to the pathogenesis of Angelman syndrome[20]. p53 is targeted for proteasomal degradation by mdm2 which is a p53 target gene containing E3 ubiquitin ligase activity[21]. While mdm2 targets p53 for degradation, mdm2 is self -ubiquitinated and degraded. Cyclin dependent kinase inhibitor p21waf/cip, another p53 target gene, is degraded by proteasome and GSK3 (glycogen synthase kinase 3) mediated phosphorylation [22]. Rb (Retinoblastoma) protein is a tumor suppressor and negatively regulates G1/S transition by interacting with E2F transcription factor. Rb protein is degraded in an ubiquitin dependent manner [23]. In addition, free E2F is also degraded in ubiquitin dependent manner by the 26S proteasome. Thus, collectively HECT domain containing E3 ligases are important for homeostasis of protein levels and defects in their function may lead to various diseases including cancer. Thus, wealth of experimental data and clinical findings identifying many substrates targeted by E3 ubiquitin ligases, indicate that the deregulation of Ubiquitin proteasome system in cell cycle control is tightly linked to malignancies and tumorigenesis. Due to the above relevance and role of E6AP in malignancies and tumorigenesis The project is based on the expression, purification and validation of GST tagged protein that is GST- E6AP. The current study includes Cell culture: HL-60 cells, a human promyelocytic leukemia cell line. HL-60 cells treated with 1uM ATRA for 0,24 and 48 hours. GST- E6AP Protein expression and purification: GST-E6AP Pull down: Objectives: 1) Expression of GST and GST-E6AP plasmids in BL21 strain of E.Coli 2) Purification of GST and GST-E6AP proteins from BL21 strain of E.Coli 3) Validation of expression through western blotting 4) To detect GST-E6AP protein interaction with whole cell lysates of HL-60 cells treated with 1ÃŽ ¼M ATRA for 0, 24 and 48 hrs GOMTI NAGAR EXTENSION, LUCKNOW

Subject: Hemmingway-The Sun Also Rises :: essays papers

Subject: Hemmingway-The Sun Also Rises In the novel The Sun Also Rises, by Ernest Hemingway, a reader is forced to decide weather the spite that the Jake has for Chon originates from Jake ¹s racist background, or his deeply seeded jealousy of Chon for having a brief affair with Brett. Even though it is clear that Jake has racist views, the hatred he has for his former friend Chon Chon is strictly based on the jealousy he feels towards Chon for the weekend he spent with Brett. Jake goes in to great detail about Chon ¹s early life. He speaks highly and admiringly of Chon, but in a condescending way. A reader get her first hint on page one that Jake has some racist feelings toward Chon. He speaks of how Chon's nose was flattened in a boxing match and concluded the sentence with  ³...and it certainly improved his nose ² (11). This can be taken as a reference to the stereotypical  ³Jew ² nose that is often associated with Jewish people. Jake and Chon are close friends, and Jake likes him up to the point where he becomes involved with Brett. Jake goes on and on about all of the relationship mistakes in Chon ¹s life. There is an hint of jealousy that appears in Jake's tone. He states that women began to become attracted to Chon as he got older, and that it  ³changed him so that he was not so pleasant to have around ² (16). There is racism in Jake ¹s tone, but Jake ¹s problem with Chon is is strictly one of jealousy. By this time Jake has already developed an extreme distaste for Chon ¹s endeavors with women, but these feelings their peak when Chon and Lady Brett have a brief affair. Jake, having unconditional love for Brett, blames the entire incident on Chon. In turn, Chon makes as point to rub it in Jake ¹s face. Jake says  ³...it was giving him pleasure to be able to talk with the understanding that I knew there was something between them ² (106). Jake has a great deal of trouble dealing with this. It has nothing to do with the fact that Chon is Jewish, Jake is merely jealous of him. It would not be manly for Jake to openly admit his jealousy, and blame the jealousy on his harsh feelings toward Chon. As a result Jake falls back on the fact that

Literary Exploration on of Mice and Men

Literary Exploration In life we are part of many roles that create dangers we face that may lie beyond our understanding. Even though these roles are hard to understand, they can give meaning to our life. In John's Steinbeck â€Å"Of Mice and Men,† we see these men's day to day lives, the main character; George takes care of his friend Lennie who has difficulties understanding the rules of the world we live in. Through the story there are many ups and downs mostly involving Lennie, who is trying to see through the eyes of George and to do and be as George is.For this reason George is constantly trying to think of what is best for Lennie. Through all of this they face even more dangers and still try to find a way to raise money for a farm to call their own. George and Lennie show how the dangers we face can affect our lives for the better while everything fails around them. Danger is important in our lives, because it gives us the drive to go through day to day lives. Often whe n struggling with dangers we find hope and we look to the outside world for assurance and escape from our worries or pain.George and Lennie find dangers from the very start of the novel because of they are forced to run from one of many problems Lennie causes. In the novel Steinbeck gives Lennie a purpose of taking care of the â€Å"rabbits† and in doing this it shows Lennie that to him his purpose in life is to take care of the â€Å"Rabbits. † In the novel a quote that show that the dangers they ran from at the very beginning are far behind them, â€Å"Guys like us, that work on ranches ,are the loneliest guys in the world. They got no families. They don't belong no place†¦We're gonna have a little house an' a couple of acres an' a cow and some pigs and live off the fatta the land†¦ We'll have a big vegetable patch and a rabbit hutch and chickens†¦Ã¢â‚¬  this quote shows how George and Lennie strive to have a better life. Even though George knows tha t these dreams will never come true, â€Å"let’s have different color rabbits, George†¦ Red and blue and green rabbits†¦ sure fluffy ones. † As you begin to read on in the novel, it almost seems as if, their hopes and dreams are starting to come true. â€Å"you know a place like that? †Ã¢â‚¬ ¦Ã¢â‚¬â„¢Maybe we could do her right now? †¦Ã¢â‚¬ In one month. †Ã¢â‚¬ ¦ But then Lennie unknowingly is killing everything he touches and the dangers they ran from are coming back just as before , â€Å"Why he’s dead. † She cried â€Å"I was just playing with him†¦ and he was gonna make like he was gonna bite me†¦an’ I made like I was gonna smack him†¦ an’†¦an’ I done it. An’ then he was dead. † And because of this and Curly’s wife George is faced with a big decision. George must learn that Lennie is dangerous to others that are around him because he does not know his own streng th, and that him and Lennie cannot keep running forever.However, hope can be taken as well, which is shown in the novel by a stable buck named Crooks. â€Å"A guy sets alone out here at night, maybe readin’ books or thinkin’ or stuff like that. Sometimes he gets thinkin’, an’ he got nothing to tell him what’s so an’ what ain’t so. Maybe if he sees somethin’, he don’t know whether it’s right or not. He can’t turn to some other guy and ask him if he sees it too. He can’t tell. He got nothing to measure by. I seen things out here. I wasn’t drunk. I don’t know if I was asleep. If some guy was with me, he could tell me I was asleep, an’ then it would be all right.But I jus’ don’t know. † Crooks speaks these words to Lennie, on the night that Lennie visits Crooks in his room. The old stable-hand admits to the very loneliness that George described in the novel. As a black man with a physical handicap, Crooks is forced to live in the barn whitch is on the ranch life. He is not even allowed to enter the white men’s bunkhouse, or join them in a game of cards. His bitterness usually comes out through his bitter, caustic wit, but in this passage he displays a sad, touching side. Crooks’s desire for a friend by whom to â€Å"measure† something.Because these men feel such loneliness, it is not surprising that the promise of a farm of their own and a life filled with strong, brotherly bonds. â€Å"I seen hundreds of men come by on the road an’ on the ranches, with their bindles on their back an’ that same damn thing in their heads . . . every damn one of ’em’s got a little piece of land in his head. An’ never a God damn one of ’em ever gets it. Just like heaven. Ever’body wants a little piece of lan’. I read plenty of books out here. Nobody never gets to heaven, and nobody g ets no land. In this passage , after Lennie shares with Crooks his plan to buy a farm with George and raise rabbits, Crooks tries to deflate Lennie’s hopes which creates dangers that may lie beyond our understanding. He relates that â€Å"hundreds† of men have passed through the ranch, all of them with dreams like Lennie’s. Not one of them, he emphasizes with bitterness, ever succeeds to make that dream come true. Crooks shows a sense of reality, telling again of Lennie’s childlikeness , and that the dream of a farm is, after all, only a dream.This moment show’s off Crook’s character, and how a lifetime of loneliness and cruelty can lead to bitterness. It also furthers Steinbeck’s disturbing thought’s that those who have strength and power in the world are not the only ones responsible for cruelty. As Crooks shows, even though he was hurt by others, he seeked out Lennie and attacked him because he is even weaker than Crooks is. Sometimes in life we have difficulty in decisions that makes us question our morals even deeper our character. Curley’s wife enters the barn and try’s to console Lennie. What you got covered up there? † She admits that the life with Curley is a disappointment, and wishes that she had followed her dream of becoming a movie star â€Å"Coulda been in the movies, an’ had nice clothes-all them nice clothes like they wear. An’ I coulda sat in them big hotels, an’ had pitchers took of me†. Lennie tells her that he loves petting soft things, and she offers to let him feel her hair. When he grabs too tightly, she cries out. Lennie becomes sacred and tried to silence her, he unknowingly breaks her neck.Lennie flees back to a pool of the Salinas River that George has told Lennie of the meeting place that should either of them get into trouble they are to meet. As Candy discover what has happened and gather together a lynch party, George joins Le nnie. Much to Lennie’s surprise, George is not mad at him for doing â€Å"a bad thing. † George begins to tell Lennie the story of the farm they will have together. As he describes the rabbits that Lennie will tend, the sound of the approaching men grows louder. George shoots Lennie in the back of the head.When the other men arrive, George lets them believe that Lennie had the gun, and George wrestled it away from him and shot him. Only Slim understands what has really happened, that George has killed his friend out of mercy â€Å"Goerge raised the gun and listened to the voices†Ã¢â‚¬ ¦ â€Å"le’s do it now. Le’s get that place now. † Slim consolingly leads him away, and the other men, completely puzzled, watch them leave. Lennie is an illustration of how, as we go through life, every human’s personality will be given its test however, it is up to the person to either grow from the knowledge or be crushed as a result.

Julius Caesar As A Real Person Verses Julius Caesar In Shakespeare’s Play

Julius Caesar As A Real Person Verses Julius Caesar In Shakespeare’s Play A picture worth a thousand words, a lived through moment is priceless. How many times writers try to give descriptions of a human in a book? They try to write a play or a book about someone great, and fit it into the few pounds of paper. They present their imagination to the audience as clear as they can, but, does it really transform the words written - into the picture or an experience? How can the words build a time machine in seconds, and let one travel back in time? The answer still stands, but Shakespeare in his play The Tragedy of Julius Caesar had been able to do it, or at least made an attempt. With this play he had been able to carry people back and forth in time. In the next few minutes one will experience, relive, and compare the Julius Caesar in Shakespeare's play with the true Julius Caesar.Bust of Julius Caesar from the British MuseumThe interpretation of the facts must be left to each person seeking the true Caesar.Shakespeare worked; he worked either on portraying th e image of Julius Caesar or on the play. He strived to understand, to comprehend who was the true Julius Caesar, what was on his mind, heart, and what Caesar felt. How Caesar reacted to problems, and what his emotions were based on. In this play Shakespeare had given out a true tragic to the audience, which backs-up its title The Tragedy of Julius Caesar. "Although Caesar himself is not the hero of the play, he is the catalyst of the action and the person around whom the plot revolves." (Wells, 9) In Shakespeare's play Caesar appeared as a man who had become strongly committed to the popular cause and highly experienced in the exercise of power. The people in fact missed him more...