Urdu Language Urdu Essay Example

Urdu Language Urdu Paper The term Urdu and its origin The term Urdu derives from a Turkish word ordu meaning camp or army. The Urdu language developed between the Muslim soldiers of the Mughals armies who belonged to various ethnicities like Turks, Arabs, Persians, Pathans, Balochis, Rajputs, Jats and Afghans. These soldiers lived in close contact with each other and communicated in different dialects, which slowly and gradually evolved into present day Urdu. It is for this reason that Urdu is also referred to as Lashkari Zaban or language of the army. During its development Urdu language also assumed various names like the term Urdu-e-Maullah meaning the exalted army which was given by Emperor Shah Jahan and the term Rekhta meaning scattered (with Persian words) which was coined by the scholars for Urdu poetry. History and Evolution of Urdu Language Urdu arose in the contact situation which developed from the invasions of the Indian subcontinent by Turkic dynasties from the 11th century onwards, first as Sultan Mahmud of the Ghaznavid empire conqueredPunjab in the early 11th century, then when the Ghurids invaded northern India in the 12th century, and most ecisively with the establishment of the Delhi Sultanate. The official language of the Ghurids, Delhi Sultanate, the Mughal Empire, and their successor states, as well as the cultured language of poetry and literature, was Persian, while the language of religion was Arabic. Most of the Sultans and nobility in the Sultanate period were Turks from Central Asia who spoke Turkic as their mother tongue. The Mughals were also Chagatai, but later adopted Persian . Muzaffar Alam asserts that Persian became the lingua franca of the empire under Akbar for various political and ocial factors due to its non-sectarian and fluid nature. However, the armies, merchants, preachers, Sufis, and later the court, also incorporated the local people and the medieval Hindu literary language, Braj Bhasha. This new contact language soon incorporated other dialects, such as Haryanvi, Panjabi, and in the 17th century Khariboli, the dialect of the new capital at Delhi. By 1800, Khariboli had become dominant. The language went by several names over the years: Hindawi or Hindi, [language] of India; Dehlavi of Delhi;Hindustani, of Hindustan; and Zaban-e-Urdu, the language of he [army] camp, from which came the current name of Urdu around the year 1800. When Wali Mohammed Wali arrived in Delhi, he established Hindustani with a light smattering of Persian words, a register called Rekhta, for poetry; previously the language of poetry had been Persian. When the Delhi S ultanate expanded south to the Deccan Plateau, they carried their literary language with them, and it was influenced there by more southerly languages, producing the Dakhini dialect of Urdu. During this time Hindustani was the language of both Hindus and Muslims. We will write a custom essay sample on Urdu Language Urdu specifically for you for only $16.38 $13.9/page Order now We will write a custom essay sample on Urdu Language Urdu specifically for you FOR ONLY $16.38 $13.9/page Hire Writer We will write a custom essay sample on Urdu Language Urdu specifically for you FOR ONLY $16.38 $13.9/page Hire Writer The communal nature of the language lasted until it replaced Persian as the official language in 1837 and was made coofficial along with English in the British Raj. This triggered a Hindu backlash in northwestern India, which argued that the language should be written in the native Devanagari script. This Hindi replaced traditional Urdu as the official register of Bihar in 1881, establishing a sectarian divide of Urdu for Muslims and Hindi for Hindus, a divide that was formalized with the division of India and Pakistan after independence from the British, though there are Hindu poets who ontinue to write in Urdu to this day. Although there have been attempts to purge Urdu and Hindi, respectively, of their Sanskrit and Persian words, and new vocabulary draws primarily from Persian and Arabic for Urdu and Sanskrit for Hindi, this has primarily affected academic and literary vocabulary, and both national standards remain heavily influenced by both Persian and Sanskrit. English has exert ed a heavy influence on both as a co official language. Official status Urdu is the national and one of the two official languages of Pakistan, the other eing English, and is spoken and understood throughout the country, while the state-by-state languages (languages spoken throughout various regions) are the provincial languages. It is used in education, literature, office and court business. It holds in itself a repository of the cultural and social heritage of the country. Although English is used in most elite circles, andPunjabi has a plurality of native speakers, Urdu is the lingua franca and national language in Pakistan. Urdu is also one of the officially recognised languages in India and has official language tatus in the Indian states of Uttar Pradesh, Bihar,[32] Andhra Pradesh, Jharkhand, Jammu and Kashmir and the national capital, New Delhi. In Jammu and Kashmir, section 145 of the Kashmir Constitution provides: The official language of the State shall be Urdu but the Eng lish language shall unless the Legislature by law otherwise provides, continue to be used for all the official purposes of the State for which it was being used immediately before the commencement of the Constitution. As of 2010, the English language continues to be used as an official language for more than 90% of fficial work in Kashmir. There are ongoing efforts to make Kashmiri and Dogri, spoken as mother tongues by nearly 80% of the population of Indian-administered Kashmir, as official languages alongside English. The importance of Urdu in the Muslim world is visible in the Holy cities of Mecca and Medina in Saudi Arabia, where most informational signage is written in Arabic, English and Urdu, and sometimes in other languages. Importance: Urdu is one of the most popular languages which are having a history of hundreds of years back. Urdu language got lots of preferences in various historical aspects. Urdu is considered as the language used by many ancient kings and it was the only language for communication in certain regions of ancient kingdoms. Ancient regions of Persian kingdom were the main areas of Urdu language. Years after Urdu language have been spread to India as one of the language in certain regions of India. In India Urdu language has been mostly used by the Muslim community. After that Pakistan has been divided from India and declared as an independent country for the Muslim community. As a result Urdu became the national language of Pakistan. Pakistan s considered as the birth place of Urdu poetry as Urdu is the main language of the common people in Pakistan. Urdu poetries are written in different forms by various experienced Urdu poets. Among the various forms of Urdu poetries Ghazal plays an important role which is a popular art form around all over the world. Ghazal has certain rules in its writing and one of the main rules is that Ghazal should end with the same words used for its starting and this rule is called ‘Radeef’. Gair Muraddaf Ghazals are a variety of Ghazals which doesn’t have a radeef. Ham Radeef Ghazals are those Ghazals with same radeef. Urdu Ghazal is an important form of Ghazal which is very much popular all over the world. Importance of urdu in pakistan Urdu holds the status of the national language of Pakistan. It is also the official language of the country and the post is also shared by English. It is understood all over the country and is the best medium of communication anywhere in the country. Urdu has been in the region since the 11th century. The rulers of that time urged the population to learn how to read and write Urdu. It is an Indo-Aryan language and is derived from three different languages which are Arabic, Turkish and Persian. The letters used in Urdu language are similar to the ones used in Arabic and Persian (Farsi) language. Though the letters are the same but the dialect and accent differs a lot. The word Urdu means army. In old times the armies in this region comprised of people from different nationalities. All had different languages and could not understand each other. A language was required which could be understood by all. Urdu emerged as the medium that linked all and was understood by all. According to different researches carried out, Urdu is not only spoken in Pakistan but also in many other parts of the world. It is one of the 23 official languages of India. It is widely spoken in Bangladesh and also in many gulf countries. There are also hundreds and thousands of Urdu speakers in the European countries and Americas. In Pakistan not more than 8% people have their first language as Urdu but the rest of the population speaks and understands Urdu as the second language. The estimated number of native Urdu speakers in Pakistan is 10. 5 million and all over the world the figure is 50 million approximately. In Pakistan alone the people who understand and speak Urdu as the first or econd language is 104 million approximately. Urdu is included as a compulsory subject in the schools and colleges of Pakistan. Urdu poetry and literature is taught and given prime importance alongside English in the institutions. The Urdu literature has a rich history and it has seen very eminent and world renowned poets like Allama Muhammad Iqbal and Mirza Ghalib. It is not only poetry but also a lot of Islamic litera ture and Sharia literature has also been written Urdu. It was even before many other languages that Sharia and Islamic literature was written and also translated in this language. Urdu has emerged as a binding force which has kept the people of Pakistan close to each other. National language A national language is a language (or language variant, i. e. dialect) which has some connection—de facto or de jure—with a people and perhaps by extension the territory they occupy. The term is used variously. A national language may for instance represent the national identity of a nation or country. National language may alternatively be a designation given to one or more languages spoken as first languages in the territory of a country. C. M. B. Brann, with particular reference to Africa, suggests that there are four quite distinctive meanings for national language in a polity:[1] ?Territorial language (chthonolect, sometimes known as chtonolect[2]) of a particular people ?Regional language (choralect) ?Language-in-common or community language (demolect) used throughout a country ?Central language (politolect) used by government and perhaps having a symbolic value. http://en. wikipedia. org/wiki/Urdu http://www. theurdulanguage. com/Downfall. htm http://en. wikipedia. org/wiki/National_language

Poem One Perfect Rose Essays

Poem One Perfect Rose Essays Poem One Perfect Rose Paper Poem One Perfect Rose Paper Most women believe that men do not have the ability to love or show their love in any fashion. For decades, women have believed that they will ultimately have to settle for a man that might be able to reach their level, only If that woman took the time to teach him correctly. Another notion that women hold is: if a man gives a flower or writes a poem, he is in some strange way degrading her or Just trying to get into her pants. On the flip, side I constantly see women being abused and still going back to their men only because he said, I love you. I believe that is why women have been arced to be on the defensive. The Poem One perfect Rose(Up 82) has brought to my attention: I as a man of little wealth, that doesnt put me In a profitable position with the average woman that wants a limousine as opposed to a flower. In the first line, Parker (the writer) says, A single flower he sent me, since we met. Whether they met yesterday or five years ago remains unknow n. It is apparent that the speaker and many other women of that time lost their respect for something so sentimental. I have always thought off rose, or any gift from the heart, as something o be cherished rather than taken for granted. Maybe Parsers speaker should wonder if she is worthy enough to receive a perfect rose. l knew the language of the flowerer; / my fragile leaves, it said, Shish heart enclose means a great deal. This sentence seems to convey that she realizes the significance of one perfect rose(at least for a brief moment). She regards the rose as a messenger, someone to reveal the Importance or significance of an act or feeling. Parker proceeds by saying, Love long has taken for his amulet. Although women eight not see it, a simple gesture of giving a single rose could signify much more. She does not seem to understand that the man might be trying to convey more than just a simple affection. This poem was written In 1937, and yet, the content of the writing still seems to apply to attitudes women display as of late. But can a woman be so shallow that she passes by the beauty of a r ose to get to something bigger and better. In past poems and stories, the beauty of a woman has been compared to the undefiled image of a rose. But to be given A perfect rose should have been an honor rather than a reverts. Ask yourself one quick question: what gift have you received in your lifetime that could be meaningless to everyone else but you regarded it as the most precious object you have ever obtained? I really like the way the flirts two stanzas differ from the last. The first two seem like they would have been written by a sweet elegant writer of the 10th century, along with William Shakespeare. The latter sounds like a sarcastic daddies girl that has had everything given to her on a silver platter, with no use for a single rose. By the last Tanta she crushes the roses heart, the symbol of his love, by inferring that it is useless compared to One Perfect limousine. She seems to think of the rose as Just a rose, out a Limousine as something AT greater value. Winy a Limousine? Winy not a finely cut diamond? I dont know any woman that would not Jump at the chance at a diamond. The limousine signifies what she really wants but has never had: a commitment. She does not want something that will eventually be tossed out and forgotten. Instead, she wants something built to last, something reliable. Nevertheless, no one ever gave her a limousine. When I first read this work I was sure that I would never see eye-to-eye with the speaker but instead I Just became more concerned with Parker, whom may have been trapped feeling the same way. I hope that Parker did not take what the speaker wished genuinely because it makes the poem much stronger to think that she is making Jest of her own gender. Or better yet, that she had caught herself in similar instances before. Sometimes, for women, the best a man can give is never good enough. Every man that has had to deal with womans antics has had to realize what his part n their relationship is and where he should leave well enough alone. Men that break that unwritten law have always had to pay in the past. Example, Seasons little mishap with Media. Women have always been the mystery of every mans life. From Adam and Eve to Sunny and Cheer, men have always been on the outside looking in. A lot of the time, women want men to predict what they want or need, instead of Just coming out with it. I cannot see an end to this madness without the breakdown of the communication barrier between the two sexes. As far as I can see, men will always be left in the dark.

Chrystal Meekers Momma (1980) Essay Example | Topics and Well Written Essays - 500 words

Chrystal Meekers Momma (1980) - Essay Example The poem by Meeker can be realized as dealing with a child’s recognition of how a mother gives up anything and everything for the sake of her child. Whereas the poet deals with poverty and despair affecting the family, the mother’s unconditional sacrifice for the children is the central theme of the poem, and she gladly starves herself in order to make the children contented. Therefore, a reflective exploration of the poem â€Å"Momma† by Crystal Meeker makes clear that the poet compellingly deals with the true meaning of motherhood through the skillful use of literary devices. In a profound analysis of the poem â€Å"Momma†, it becomes lucid that Crystal Meeker’s major intention in writing the poem has been to glorify the true meaning of motherhood and the poet’s use of literary devices such as hyperbole, imagery, simile, etc. has helped him to convey his message persuasively. Significantly, any careful reader is reminded of a mother’s unconditional love and sacrifice for the well-being of her children and family. In this poem, Meeker magnificently presents a family facing the realities of poverty and the unlimited love and sacrifice of the mother becomes obvious to the reader. In order to present the life of the family, the poet employs hyperbole when he suggests that mother and daughter did not always meet eye to eye: â€Å"they clawed their womanhoods out of each other† (line 3).

Analyzing Othello Essay Example | Topics and Well Written Essays - 250 words

Analyzing Othello - Essay Example Lago was careful enough to burn the match on both ends. He had taken both Othello and Cassio into complete confidence. He knew Othello was aware of his real battle skills and earned Cassio’s sincerity by offering him handkerchief. Lago very carefully made Othello feel that Cassio had conducted adultery with Desdemona. In such circumstances, whatever Desdemona had to say in her defense would not matter. Lago’s strategy was too wisely constructed and carefully practiced for Othello to escape. Therefore, it is irrational to call Othello unjust in his display of haste and violence towards Desdemona. On the other hand, Othello also did not trust whatever Lago told him unless he had a solid proof for that. Othello had been very angry with Lago for having uttered humiliating and disdainful remarks about his wife when Lago accused Desdemona to have made love with Cassio. Othello’s rage can be estimated from the fact that he had warned Lago that he would kill him if he di d not provide Othello with a solid proof about Desdemona and Cassio’s relationship. When Lago remained successful in providing Othello with a solid proof of his assertion, Othello can not be blamed for not having suspected Lago instead of Cassio. Works cited: Shakespear, William. Othello, the moor of Venice: A tragedy. London: J. Tonson. 1743, Print.

PROGRESS REPORT FOR CO-OP Essay Example | Topics and Well Written Essays - 5250 words - 1

PROGRESS REPORT FOR CO-OP - Essay Example However, despite the progress that the company has been making, training employees remains its main activity in a bid to remain competitive and keep pace with rivals. When this company was under the leadership of Steve Jobs, it had adopted a distribution channel system that encompassed intermediaries who were authorized dealers. The strategy worked with excellence in most parts of the world, lately, the strategy seems not to be working as expected since competitors have changed tact, and adopted strategies that give them competitive advantages above Apple Inc. The company has been on a mission to recruit and train cashiers, public relation personnel in their different stores (Wentland, 2007), managers and other employees, so that they can help tackle the prevailing marketing and management challenges. At the same time, the company is recruiting and training ambitious young people so that they can add creativity and innovativeness that was left void when its creative genius and founder, Steve Jobs passed on. Apple Inc. offers electronics and related products, with its main area of interest being development of computer hardwares and softwares. The company has been doing this by use of creative young people who understand the current needs of the market as well as their ability to read strategies of competitors and counter them. However, in the recent past, the company has not been able to effectively tackle issues of technology development as well as marketing because the systems that have been adopted by clients have outdone its strategies in a great way. This is the main constraint that the company has been facing, something that has prompted a serious concern for training of new and dynamic workers who can turn round the fortunes of the company. The training program that has been developed is aimed at training managers on

Ataxia Telangiectasia Mutated in Glucose Transport

Ataxia Telangiectasia Mutated in Glucose Transport A role for ataxia telangiectasia mutated in insulin-independent stimulation of glucose transport Abstract Literature reports suggest that ataxia telangiectasia mutated (ATM) can activate the AMP-activated protein kinase (AMPK), a protein that can stimulate glucose transport in skeletal muscle. We hypothesized that 5-aminoimidazole-4-carboxamide ribonucleotide (AICAR), an AMPK activator, would increase glucose transport in mouse extensor digitorum longus (EDL) muscles in an ATM-dependent manner. AICAR-stimulated glucose transport was prevented by the ATM inhibitor KU-55933 and in ATM-deficient (ATM-/-) muscle despite normal stimulation of AMPK phosphorylation. S231 of TBC1D1 matches the sequence motif of ATM substrates, and phosphorylation of this site is known to inhibit TBC1D1 and lead to increased glucose transport. Accordingly, we assessed TBC1D1 phosphorylation and found that AICAR-stimulated phosphorylation of TBC1D1 at S231did not occurin ATM-/- muscle. However, activation of ATM without activation of AMPK was insufficient to increase TBC1D1 phosphorylation.The data suggest that AT M plays a role in AICAR stimulated glucose transport downstream of AMPK. Keywords: AMP-activated protein kinase; ataxia telangiectasia mutated; TBC1D1; AICAR; glucose transport; skeletal muscle Introduction The serine-threonine kinase ataxia telangiectasia mutated (ATM) appears to play a role in glucose homeostasis. For example, recent genome-wide association studies have found that genetic variations near the ATM gene are related to glycemic responses to metformin [1, 2], a commonly-prescribed drug for blood glucose control. While the mechanism for metformin’s effect on blood glucose levels is under debate [3-6], it is known that metformin acutely stimulates glucose transport into skeletal muscle concomitant with activation of the AMP-activated protein kinase (AMPK) [7]. Activation of AMPK is sufficient to stimulate insulin-independent glucose transport into skeletal muscle [8, 9]. Intriguingly, ATM dependence has been reported for activation of AMPK in response to DNA damage or insulin-like growth factor 1 in HeLa cells and fibroblasts, exposure of lung cancer cells to ionizing radiation,exposure of lymphoblaststo H2O2, or treatment of HeLa cells and mouse embryonic fibroblasts with the adenosine analog AICAR [10-14]. Despite these suggestive data on the role of ATM upstream of AMPK, the potential role of ATM in AMPK-dependent stimulation of glucose transport has not previously been investigated in skeletal muscle, the predominant whole-body storage depot for glucose. Accordingly, the purpose of this study was to test the hypothesis that glucose uptake stimulated by the AMPK activator AICAR would be dependent on ATM in skeletal muscle. Methods Materials Antibodies against TBC1D1, AMPK, phosphorylated AMPKÃŽ ± T172 (P-AMPK), and phosphorylated ATM S1981 (P-ATM) were purchased from Cell Signaling Technology (Beverly, MA, USA). Antibodies against phosphorylated TBC1D1 (P-TBC1D1) S237 (S231 in mouse) were purchased from EMD Millipore Corporation (Billerica, MA, USA). Antibodies against tubulin and ATM were obtained from Sigma-Aldrich Corporation (St. Louis, MO, USA). Horseradish peroxidase-conjugated secondary antibodies were obtained from Pierce Biotechnology (Rockford, IL, USA). The ATM inhibitor KU-55933 was a generous gift from Dr. Graeme Smith (KuDOSPhramaceuticals, Cambridge, UK). The AMPK inhibitor Compound C was provided by Merck Co., Inc. (Rahway, NJ, USA). Doxorubicin was purchased from Sigma-Aldrich Corporation. Radiolabeled 2-deoxyglucose and mannitol were purchased from American Radiolabeled Chemicals, Inc. (St. Louis, MO, USA). Collection and Processing of Animal Muscle All procedures using live animals were approved by the Saint Louis University Institutional Animal Care and Use Committee. Transgenic mice expressing a truncation mutation of ATM [15] were obtained from The Jackson Laboratory (Bar Harbor, ME, USA). Mice that were heterozygous for the transgene were used to breed wild type (ATM+/+) and ATM deficient (ATM-/) mice. After weaning, each mouse was anesthetized with ketamine/xylazine (55 mg ketamine and 5.5 mg xylazine per kg), and a tail sample was obtained for genotyping as previously described [15, 16]. Mice were anesthetized with sodium pentobarbital (50 mg/kg) and extensor digitorum longus (EDL) muscles were removed and incubated in vitro as described previously [16, 17]. The incubation media for the muscle consisted of Krebs Henseleit bicarbonate buffer (KHB) containing 8 mM glucose and 32 mM mannitol. Vials containing EDL muscles were gassed with 95% O2 : 5% CO2 and kept gently shaking at 35 ºC. Muscles were incubated for one hour to allow recovery from dissection. Muscles were then transferred into KHB containing 32 mM mannitol and 8 mM glucose in the presence of 0.1% dimethyl sulfoxide vehicle (DMSO) or 1  µM KU-55933, a concentration sufficient to inhibit ATM [18, 19] but low enough to avoid inhibition of phosphatidylinositol 3-kinase [19]. After 30 minutes, muscles were incubated in KHB with 8 mM glucose and the absence or presence of 2 mM AICAR for one hour with the continued presence of DMSO or KU and 32 mM or 30 mM mannitol to keep osmolarity constant across media. At this point, some muscles were blotted and clamp-frozen with aluminum tongs cooled in liquid nitrogen and stored at -80  ºC for later western blot analysis. Other muscles were subjected to 2-deoxyglucose (2DG) uptake assays as described below. In parallel procedures, EDL muscles from wild-type or ATM-deficient animals were allowed to recover in vitro for one hour, incubated in KHB containing mannitol as described above and in the absence or presence of 2 mM AICAR for one hour and then either clamp-frozen or subjected to 2DG uptake assays as previously reported [16, 17] and briefly described below. 2DG uptake Muscles were washed at 30  ºC in glucose-free KHB containing 40 mM mannitol in the absence or presence of KU-55933 (DMSO vehicle) or, for procedures with the ATM-/- mice, in medium containing neither KU nor DMSO. Muscles were then incubated in KHB containing 4 mM 2DG, 2  µCi/ml 3H-2DG, 36 mM mannitol, 0.3  µCi/ml 14C-mannitol, and 0.1% DMSO or 1  µM KU-55933 if they had been present in earlier incubations. Muscles were clamp-frozen and stored at -80  ºC. Muscles were then homogenized in Kontes ground glass tubes in ice-cold buffer containing protease and phosphatase inhibitors (50 mM HEPES, pH 7.4, 2 mM Na3VO4, 150 mM NaF,10  µg/ml leupeptin, 10  µg/ml aprotinin, 0.5  µg/mL pepstatin and 1 mM phenymethylsulfonylflouride). Homogenates were centrifuged at 4  ºC for 10 minutes at 14,000Ë £g, and supernatant protein concentration was analyzed by the bicinchoninic acid (BCA) method (Pierce Protein Technologies, Rockland, IL, USA). Supernatant aliquots and aliquots of the incubation media were mixed with Ultima Gold XR scintillation fluid (Perkin Elmer, Boston, MA, USA), and samples were assessed by scintillation counting (TriCarb 3110TR, Perkin Elmer, Boston, MA, USA). The disintegrations per minute (DPM) of 14C-mannitol were used to measure the extracellular volume, and intracellular 2DG was calculated from 3H DPM after accounting for 3H DPM in the extracellular space. 2DG transport was expressed as nmol 2DG/mg protein/10 minutes. Western Blotting Samples were homogenized, centrifuged, assayed for protein content as described above, diluted in Laemmli sample buffer containing dithiothreitol, and boiled for 5 minutes. Samples were then analyzed using SDS-PAGE as described previously [20]. Samples were run on 4-20% Tris-HEPES gels (Pierce) and then transferred onto nitrocellulose membranes. After transfer, membranes were blocked with 5% non-fat dry milk in Tris-buffered saline containing 0.1% Tween. Proteins on the nitrocellulose membranes were probed with primary and secondary antibodies described in the Materials section and then visualized using enhanced chemiluminescence (Western Lightning; PerkinElmer, Waltham, MA, USA). Western blots were quantified using TotalLab software purchased from TotalLab Nonlinear Dynamics (Newcastle on Tyre, UK). For probing ATM and P-ATM, samples were run on 3-8% Tris-Acetate gels (Invitrogen, Carlsbad, CA, USA) alongside HiMark (Invitrogen) molecular weight markers. Statistics Data were analyzed by ANOVA with post hoc LSD comparisons. A level of P Results AICAR-stimulated glucose transport ATM’s role in AICAR stimulated glucose transport was assessed in isolated EDL muscle by using either ATM deficient mice or by using the specific ATM inhibitor, KU-55933. As shown in figure 1A, ATM protein was present in only background levels in EDL from ATM-/- mice. As shown in figure 1B, AICAR increased glucose transport in muscle from wild type mice(P AICAR-stimulated phosphorylation of AMPK It has previously been reported that ATM plays a role in AICAR-stimulated AMPK phosphorylation in HeLa cells and mouse embryonic fibroblasts [12]. Thus, we assessed phosphorylation of AMPK to determine whether ATM’s role in AICAR-stimulated glucose transport was through an influence on AMPK phosphorylation. As shown in figure 2A, AICAR-stimulated AMPK phosphorylation was normal in muscle from ATM-/- mice. Likewise, AICAR-stimulated AMPK phosphorylation was unaffected by the ATM inhibitor KU-55933 (figure 2B). Phosphorylation of TBC1D1 The RabGTPase activating protein (GAP) TBC1D1 is required for stimulation of glucose transport by AICAR [21]. Furthermore, phosphorylation of mouse TBC1D1 at S231 (corresponding to S237 of human TBC1D1) in response to AICAR occurs concomitant with an increase in glucosetransport [22-24], and S231 phosphorylation appears to be necessary to convey insulin-responsiveness to TBC1D1 [25]. Intriguingly, S231 and the surrounding amino acids (F-S-Q) match the consensushydrophobic-serine/threonine-glutamine (à ¯Ã‚ Ã¢â‚¬  -S/T-Q) motif of ATM targets [26, 27]. While phosphorylation of this site is increased by the AMPK activators phenformin and AICAR [28], and the site is an in vitro target of AMPK [28], this does not rule out the possibility that another kinase could act on the site. Thus, we hypothesized that S231 phosphorylation in response to AICAR would be dependent on ATM. As shown in figure3, AICAR increased phosphorylation of TBC1D1 S231 in EDL from wild type mice (P Discussion The new information provided by this study is that AICAR-stimulated glucose uptake in skeletal muscle is dependent on ATM. Additionally, this role for ATM in AICAR-stimulated glucose uptake does not involve an effect at the level of AMPK phosphorylation but instead is associated with altered phosphorylation of TBC1D1, downstream of AMPK. Based on data that the ATM inhibitor KU-55933 blunted activation of AMPK by metformin in a hepatoma cell line, Zhou et al proposed that ATM acts upstream of AMPK [2]. However, two independent groups have shown that KU-55933 prevents AMPK activation by metformin through inhibition of the cation transporter responsible for metformin uptake rather than through inhibition of ATM [3, 4]. In hepatocytes, ultraviolet light irradiation stimulated phosphorylation of the ATM target H2AX, but had no effect on AMPK activity [4]. Additionally, caffeine, which inhibits ATM,suppressed phosphorylation of H2AX but not activation of AMPK by metformin [4] . Finally, while hydrogen peroxide activated both AMPK and ATM in HEK293 cells, KU-55933 prevented ATM autophosphorylation but did not interfere with AMPK activity [4]. Together, these data [4] suggest that ATM does not act upstream of AMPK, at least in hepatocytes or HEK293 cells. While it has been reported that ATM acts upstream of AMPK inHeLa cells, lung cancer cells, fibroblasts, lymphoblasts, and embryonic fibroblasts [10-14], it seems unlikely that tissues corresponding to these cell lines would play a meaningful role in glucose homeostasis. Intriguingly, however, the increase in insulin sensitivity and a concomitant increase in autophosphorylated ATM in L6 myotubes in response to serum starvation was found to be dependent on AMPK, while inhibition of ATM prevented increased insulin action but not an increase in AMPK phosphorylation in serum starved myotubes [18]. Together, the data from serum-starved myotubes [18]suggest that ATM could act downstream of AMPK in regulation of glucose transport. The current data showing blunted glucose transport despite normal phosphorylation of AMPK in response to AICAR in ATM-deficient skeletal muscle or muscle exposed to KU-55933 are consistent with the idea of ATM acting downstream of AMPK. AMPK is a heterotrimerof ÃŽ ±, ÃŽ ², and ÃŽ ³ subunits, each with multiple isoforms [30]. The two main activating upstream kinases for AMPK are liver kinase B1 (LKB1) and calcium/calmodulin-dependent kinase kinase ÃŽ ² [31], though there are some reports that ATM-dependent phosphorylation of AMPK does not require LKB1 [11, 32] and could indeed be through direct phosphorylation of AMPK by ATM [11]. Intriguingly, LKB1 is an in vitro substrate for ATM [33], suggesting a potential mechanism for the ATM-dependent phosphorylation of AMPK [14]. However, phosphorylation of LKB1 by ATM does not affect LKB1 activity in vitro or LKB1 localization in vivo [33], so the precise role of LKB1 phosphorylation in activation of AMPK remains uncertain. Clearly, there are cell-type differences in the role of ATM upstream of AMPK, and perhaps these are influenced by factors including the expression profile of AMPK subunit isoforms or the subcellular localizations of ATM, AMPK, and LKB1. The current study, as the first to demonstrate a role of ATM in insulin-independent glucose transport, adds to the growing body of literature suggesting a role for ATM in glucoregulation. For example, young mice that lack functional ATM are hyperglycemic compared to wild-type animals during oral glucose tolerance tests [34]. Likewise, for mice with an ApoE-/- background, animals that have only one allele ofATMthat codes for functional protein are hyperglycemic during intraperitoneal glucose tolerance tests and insulin tolerance tests compared to mice with two wild-type ATM alleles [35]. Finally, inhibition of ATM decreases insulin-stimulated glucose uptake in muscle-derived cell lines [16, 32], and insulin-stimulated glucose uptake is blunted in L6 cells expressing kinase-dead ATM and in mouse skeletal muscle from animals deficient in ATM [16, 32]. Quite interestingly, while ATM plays a role upstream of Akt in response to insulin in some cell lines and in glycolytic skeletal muscle [ 16, 20, 36], the point of influence of ATM in insulin signaling leading to glucose transport in oxidative muscle is downstream of Akt at theRabGAP AS160/TBC1D4 [16, 20]which, like TBC1D1, acts on Rabs 2A, 8A, 8B, 10, and 14 [37]. Thus, ATM influences both insulin-stimulated phosphorylation of AS160 [16, 20] and AICAR-stimulated phosphorylation of TBC1D1 in skeletal muscle. In summary, this study provides the first evidence for a role of ATM in AICAR-stimulated glucose uptake by skeletal muscle. Thus, ATM plays key roles in both insulin-dependent [16]and insulin-independent stimulation of glucose uptake in skeletal muscle, suggesting a basis for the association of ATM variants with glycemic profiles recently reported [2, 7].

Railroads in Hamlet Essay -- American History Hamlet North Carolina Pa

Railroads in Hamlet Hamlet. By definition, a hamlet is a small, desolate town, with less people than a village. In 1931, the town of Hamlet, North Carolina did not fit this description. It in fact was a bustling town full of varied industry and agricultural projects, as depicted in a newspaper article from the Raleigh News and Observer in 1931. In this article, Hamlet is described as being anything but a small, desolate town, showing its importance mainly being in the railroad industry. Though the descriptions in the article, it is easy to see what an important place Hamlet was in 1931 for the Railroad industry. In the 1920’s, the country was experiencing â€Å"the most explosive decade of the century,† or, as it has been called, â€Å"The Roaring Twenties† (Wang). Everything great was happening for the country in everything from music to politics and fashion to the stock market. That was until one ‘Black Thursday’ on October 24, 1929 when the stock market crashed (Wang). This started what is now commonly known as The Great Depression. Jobs were lost, people starting starving, suicide was attempted, and the country just started coming to a halt with people being too worn out and depressed to do much of anything. The country stayed this way for almost ten years. It would not be until many years later that Franklin Roosevelt would put in place the New Deal and turn the country back around (Wang). But, through all the stresses and hard times the country was facing, Hamlet seemed to prosper, growing in population size and industrial importance (Hamle t). In 1900, 4000 miles of railroads crossed over North Carolina in many directions (Trelease 32). The expansion of the railroad system did so much for Nort... ...ked like back then. Also, a great history of Hamlet is given. This article clears up some misconception of the doom and glom lifestyles that are always associated with the Great Depression. Lastly, this article teaches the lesson of never giving up even when the odds are against you. If you close your eyes and listen, you can almost see the train coming and hear the whistles blowing. Works Cited â€Å"Hamlet: Important Agricultural Outlet Has Its Own Varied Industries.† News and Observer 20 Dec. 1931 no edition or page number known. Shelton-Roberts, Cheryl. â€Å"The Hamlet Railroad Station.† Our State Jan. 1999: 41-44. Trelease, Allen. â€Å"Railroads in North Carolina, 1900.† Tar Heel Junior Historian Fall 1999: 32-33. Wang, Henru, Chris Gotterba, and Jeff Wu. â€Å"The 1920’s Experience.† 24 Apr. 2002.