Cellular Metabolism and the Immune Response Control

Cellular Metabolism and the Immune Response Control PRESTES, A. F. R. O.1; KONDO, F. V.2; HUETE, G. C.3; MURILLO, O.4 Keywords: mTOR, metabolism, Akt, immune system, regulation, mitochondria, inflammatory and anti-inflammatory I. Introduction Metabolism and immune system: The metabolic system was seen only as a system of power generation and metabolites for the functioning of cells. Today we know that changes in metabolic regulation may interfere directly in diseases that involve inflammatory processes. Thus, knowledge of the relationship between metabolism and cell signaling helps in understanding metabolic disorders, cancer, and also in the study of immune response (1,2). The relationship between metabolic and regulatory aspects of the immune system is not yet fully known. Even with major discoveries on the subject, the metabolism of many cells of the immune system is unknown (1,2). The metabolic changes during phagocytosis of three types of immune cells from pigs, leukocytes and peritoneal exudate monocytes and alveolar macrophages. In this study it was observed that macrophages depend on oxidative phosphorylation to produce energy during phagocytosis, whereas the other two cells only use glycolysis to produce energy (3). Another study confirms the close relationship between immune system and metabolism, which showed that incubation of dendritic cells (differentiated in vitro) with LPS provides an increase in glucose consumption, increased formation of lactate and reduction in oxygen consumption. Furthermore, these changes also reflected in increased CD86 co-stimulatory molecule indicating a functional modulation of these cells (4). The need for meta bolic resources to build active components of the immune system, the messenger function of certain classes of metabolites and metabolites, and the intimate relationship between parasite and mammalian defense mechanism, which is probably immune regulatory events are reflected in the metabolism (5). The metabolic profile of the cells of the immune system is also important to provide a tool that generates a systemic metabolic description induced by the parasite in the host, promoting a new direction of the immune response during infection by the parasite (5). In most biological systems, there is a stimulus that triggers an effector response, which usually makes the system back to the starting point. Although having different primary functions, the immune system and metabolic pathways are arranged in the same manner as in serum glucose levels in thermogenesis or bacterial infection, where the lipopolysaccharide stimulates TLR-4 receptor, which promotes the release of TNF-ÃŽ ±, improving bactericidal activity and vascular permeability reducing infection (2). Metabolism and associated pathways Akt/PI3K/mTOR: As well as the metabolic pathways generate energy, the means of regulation of protein synthesis involves several intracellular signaling pathways such as Akt as Akt (serine/threonine kinase), expressed in heart, lung, brain and skeletal muscle. Various stimuli, such as cytokines, growth factors and hormones, are responsible for the phosphorylation and activation of Akt, which is composed of three members, Akt1, Akt2 and Akt3 (6). The Akts proteins are recruited to the plasma membrane by PI3K, which acts as a lipid kinase. The Akt/PI3K pathway operates in promoting cell survival through evasion of apoptosis and cell proliferation through activation of mTOR in response to nutrient availability and to stimulation by growth factors. The mTOR protein stimulates translation that is required for cell cycle progression (7). mTORC1 activation is indirectly given when Akt phosphorylates TSC-2 one of the molecules of heterodimer TSC1 and TSC2, this activates the GTPase function of this heterodimer which reverses the inhibition of mTORC1, inhibiting RHEB to pass the ADP to ATP linked to this protein, by activation of cyclase function of the TSC heterodimer (8). Akt phosphorylation is important for neutralization and PRAS40, important for the activation and interactions mTOR1 and mTOR2 with their substrates (9). Thus, the mTOR pathway is also known as PI3K/Akt/mTOR. Despite the multiple substrates involved in this pathway. Additionally, Akt is not limited to this path and fulfills other functions at the cellular level. Metabolism and mTOR: Mammalian Target of Rapamycin is a serine/threonine protein kinase involved in regulation of many cellular events, such growth, survival, function, metabolism, and differentiation. It is constitutively expressed, and its regulation occurs predominantly post-translationally (7). This protein was discovery from searches about target of Rapamycin, that was originally found as a growth inhibitor which have immunosuppressive and anticancer properties (10). Additionally, due to the ability of mTOR activation to regulate metabolism, it promotes a crucial link connecting metabolic demands and cellular function (7). This link is mediated through the control of key transcriptional regulators. (11). mTOR fathers two functionally distinct signaling multi-protein complexes: mTORC1, which is composed of the scaffolding regulatory-associated protein of mTOR (RAPTOR), DEP domain containing mTOR-interacting protein (DEPTOR), Proline-Rich Akt Substrate 40 kDa (PRAS40), and mammalian Lethal with Sec13 protein 8 (mLST8); and mTORC2, which is composed of RAPTOR-independent companion of TOR (RICTOR), protein observed with RICTOR (PROTOR), mSIN1 proteins, mLST8 and DEPTOR. The connection of mTOR with these adapter proteins has functional distinct consequences (3,4). II. Metabolism and T cells differentiation Such described previously, the mTOR ability to play a role in cellular differentiation occurs through the regulation of transcription regulators. Follow, some these regulators and its role in metabolic programs regulation. HIF-1: The Hipoxia-inducible Factor is a hetrodimeric protein which regulates the expression of various genes crucial for cellular adaptation to a low-oxygen environment. This protein supports the differentiation of naà ¯ve CD4+ T cell to Th17 cell through the stabilization of the RORÃŽ ³t expression, as well as inhibits Treg differentiation through the inhibition of Foxp3, mediating its proteosomal degradation (3,5). Myc: The oncogenic transcription factor Myc regulates various metabolic pathways essentials for cellular growth and proliferation, such glycolysis, glutaminolysis, and fatty acid oxidation (14). PPARÃŽ ±: The peroxisome proliferator-activated receptor ÃŽ ± (PPARÃŽ ±) is a nuclear hormone receptor that regulates fatty acid metabolism and glucose homeostasis, playing a role as a intracellular sensor of endogenous fatty acids. This receptor induces Treg differentiation and inhibits effector differentiation (11). PPARÃŽ ³: Like its homolog PPARÃŽ ±, PPARÃŽ ³ is a nuclear hormone receptor that regulates adipogenesis, lipid metabolism and glucose homeostasis in cells. This receptor plays the same role in T cell differentiation (11). SREBP: The sterol regulatory element binding proteins (SREBP) plays a critical role in regulating cellular lipogenesis, facilitating the anabolic enzymes transcription, which is involved in cholesterol and fatty acid synthesis (11). This protein was found to associate with the IL17 promoter, where it interacts with and inhibits the activity of the aryl hydrocarbon receptor. This transcription factor is known to be important for expression of Th17-associated genes (5,7). Once the antigen is recognized, the integration of many factors from the microenvironment gives the effector fate of the naive CD4+ T cell. Until now, the T-cell subsets have been characterized only by their transcription factor expression and cytokine secretion profile. Nevertheless, it has currently proposed that each T-cell subset also hold a single metabolic profile and a corresponding set of signal requirements of mTOR complexes (11). According this metabolic classification, the T-cell would present these features: Th1 T cells phenotype exhibit a strong glycolytic phenotype and express high levels in surface of the Glut1 glucose transporter. Its development is dependent on the mTORC1 signaling complex (3,8). Th2 T cells phenotype also express high levels in surface of the Glut1 glucose transporter and exhibits a high rate of lactate production and glucose uptake following stimulation. These cells can develop in absence of mTORC1 but are dependent on the mTORC2 signaling complex (3,8). Th17 cells phenotype is the higher glycolytic T-cell subset. The IL-17-secreting CD4+ T cells development drastically decreases in T cells lacking mTOR, mTORC1 and treated with Rapamycin. Nevertheless, T cells lacking mTORC2 does not appear to have its development inhibited (3,8). Treg cells phenotype exhibits an oxidative metabolic profile which uses mitochondrial respiration and fatty acid oxidation to achieve energy. The treatment with process of glycolysis inhibitor compounds in naive CD4+ T cells importantly enhance its development, what also occurs with culture conditions that conduces to a low mTOR signaling (3,8). III. Regulation of cell B by mTORC The PI3K pathway to mTOR is required for B cell proliferation. Since the BCR is blocked by inhibition of mTOR. This was evidenced in mouse spleen cells, wherein inhibition of mTOR suppresses the proliferation and differentiation of B cells by CD40 (10,11). In humans, Rapamycin suppresses B cell proliferation when is activated in the presence of CD40L and B cell inducing cytokines. Rapamycin prevents antibody-mediated apoptosis, generating a reduction of B cells that produce IgG and IgM, also suppresses the production of cytokines that induce proliferation of B cells and IgM, as IL-2 in inflammation conditions (18). Some authors suggest that mTOR regulates IL-17, which is important in the proliferation of pro-B cells. Thus, if rapamycin in B-precursor acute lymphoblastic leukemia cell lines is evidence that IL-17 induces apoptosis in these cells is used. But when S1N1, an important element of mTORC2, is suppressed cell survival is increased possibly by the increased expression of IL-7R (20). In mature B cells, activation of TLRs and BCR induces activation of mTOR, even so, have been identified as Akt independently of mTOR regulates the BCR and this is accomplished by inactivating FoxO1 which is sequestered and degraded in cytoplasm after Akt is phosphorylated (21). When is deleted TSC1 or TSC2, is inhibited the maturation of cells B, contrary to what happened when Akt was active, in where B cells were significantly reduced in the marginal zone (MZ). But when rapamycin was fed this phenomenon was corrected, and once again the importance of mTOR is displayed in the control populations of B cells in MZ. Despite all the evidence to date is known that the PI3K pathway is a major regulatory functions and populations of B cells through regulating FoxO1. But do not have enough information to indicate the direct role of mTOR in the control and regulation of B cells, which is still under study and demonstration (22). IV. Metabolism and APCs Regulation Dendritic Cells (DC): crucial regulators of both cellular activation and tolerance in adaptive immune responses. The function which DC will perform depends on their activation and differentiation status (23). The DC activation occurs through PAMP stimulation of TLR, what leads a metabolic transition in the resting immature DC, which is characterized by a conversion from mitochondrial b-oxidation of lipid and OXPHOS to aerobic glycolysis (9,10). Once exposed to TLR agonists, in an early phase, the lacking of glucose in culture medium leads to critical faults in DC activation, such production of IL-12p40 and surface expression of CD40 and CD86. Afterwards, DCs activated by TLR signals are highly dependent on glucose for survival, becoming more sensitive to apoptosis by nutrient limitation. Thus, for full DC activation is essential initiating glycolysis at the time (9,10). Differently than OXPHOS, glycolytic pathway may be requested due to the necessity to produce substrates which will be used during DC activation. As an option, glycolytic pathway components can control protein translation and can be responsible to regulate the translation of crucial proteins for DC activation (24). Macrophagues: Macrophages can be classified into two major groups M1 (inflammatory) and M2 (anti-inflammatory). And each type of macrophage used different metabolic pathways, M1 uses energy mainly anaerobic glycolysis, mediated by HIF-1ÃŽ ±, while M2 employs FAO mediated PPARÉ ¤ and PGC-1ÃŽ ² (26). Evidencing with this, the relationship with of the metabolic function and and the population of macrophages. This regulation may be mediated by mTOR, which is an important nutrient sensor / power as processes such as protein synthesis, autophagy, glycolysis and regulation of immune response, de novo lipogenesis, among others. (27) Natural killer cells (NK cells): The NK cells rapamycin inhibits proliferation by blockade of the cell cycle in G1 phase in rat. Nevertheless, rapamycin does not affect interferon production by NK cells. When mTOR is inhibited in vitro, the death of T-cell YEC-1mediated by NK cells decreases slightly. In vivo, rapamycin reduces the number of NK cells in rat liver allografts (10). Neutrophils: Human neutrophil is inhibited the chemotaxis and chemokinesis induced by GM-CSF, when rapamycin is delivered. The same way, the response to IL-8. Rapamycin reduces polymerization of actin, important for leukocyte migration. mTORC1 is linked in activation of neutrophils and acute lung injury in association with TLR2 and TLR4 (18). V. Mitochondrial metabolism and regulation of immune response Effect Warburg: Is a termination used to describe a mechanism of some cancer cells to metabolize glucose via glycolysis, where the conversion of glucose to lactate with oxygen available to obtain energy with rapid generation but less efficient pathway for obtaining ATP (20,21). Carbon precursors necessary for the synthesis of nucleic acids, phospholipids, fatty acids, cholesterol and porphyrins can be provides by glycolysis (28). Glycolysis in normal tissues is the metabolism of 6-carbon glucose to 3-carbon pyruvate and the energy in the form of ATP occur via oxidative phosphorylation in mitochondria (30). Hexocinase-2 (HK-2) is an isoform over-expressed in many cancer cells and is located on the external mitochondrial membrane protein VDAC (voltage-dependent anion channel). HK-2 has preferential access to mitochondrial generated ATP via the mitochondrial adenine nucleotide translocator (ANT), and protection from inhibition by its product G-6-P. Cancer cells have overproduced HK-2 and making the reaction between ATP and the incoming glucose to produce G-6-P at a high rate (30). Studies suggest a link between cancer cells and Hif-1a, where high Hif-1a activity is demonstrated to mediate the Warburg effect. HIF-1a is able to produce enzymes hexokinase 2, triosephosphate isomerase, isomerase, glucose 6-phosphate, and pyruvate kinase M2 (PKM2) in glycolysis (31). HIF-1 is a transcription factor responsible for the change of gene expression during cellular response to low oxygen conditions. Amplifies HIF-1 transcription of genes encoding glucose transporters and glycolytic enzymes (32). Recent studies show Warburg effect have many mechanisms: tumor microenvironment and stabilization of HIF, oncogene activation and loss of tumor suppressor genes, mitochondrial dysfunction in cancer cells, nuclear DNA mutations, epigenetic changes, miRNA, glutamine metabolism, and post-translational modifications (28). Metabolic pathways and importance in the differentiation and function of immune cells: The response, proliferation, polarization or action of immune cells requires the supply of nutrients and high energy consumption, for this reason the contribution of ATP for these functions comes from differential form of the various metabolic pathways, from glycolysis, to pyruvate until lactate production or acyl-CoA, to enter the tricarboxylic cycle acid (TCA); or through of the fatty acids oxidation (FAO). Producing enough electrons (NADH and FADH2) to activate of the electron transport chain to fuel oxidative phosphorylation (OXPHOS) (1). It is also already considered that myeloid cells such as granulocytes, dendritic cells, macrophages, B cells and T cells mainly use glycolysis as a source of ATP via anaerobic when they present an effector or inflammatory profile (Figure XX)(1,2). This is evidenced by neutrophils that have few mitochondria and consume little oxygen (34). Under these conditions the Warburg effect is generated. Producing lactate and NADPH, an essential cofactor for the NADPH oxidase for the production of important microbicidal product H2O2 (35). Some authors suggest that eosinophils and basophils are metabolically similar to neutrophils (36) As with neutrophils, macrophages are important in the immune response and are distributed in all organs and tissues. Playing an important role in innate immunity and adopt different states of activation. Interferon-É ¤ (IFN-É ¤), in combination with TLR agonists, induces M1 (inflammatory), while IL-4 and IL-13 cytokines induces M2 (regulators) (37). M1 macrophages secrete IL-12, IFN-gamma promotes, thus inducing NK cells and T cells, addition of TNF-ÃŽ ±, that activate other immune cells, and NO. Contrary M2 macrophages, secret anti-inflammatory molecules and stimulate tissue repair. Activation of M1 and M2 is characterized by the use of different metabolic pathways (38). M1 using arginine as a substrate to produce iNOS occurs only in the M1, and not in M2. M2 using arginine as a substrate for Arginase1 expressed only in the M2, and not in M1(37). The M1 macrophages possess a glycolytic metabolism. Similar to the different types of activated cells such as dendritic cells and granulocytes. (Figure XX). The Macrophage M1 has higher basal mitochondrial oxygen consumption, the other macrophages. M2 macrophages inducing the mitochondrial OXPHOS through of IL-4 and FAO. in such a way, metabolism M2 is strongly biased towards the use of FAO and mitochondrial respiration to meet their energy needs (Figure XX) (39). DCs derived from cultured bone marrow stimulated with colony-stimulating factor granulocyte-macrophage, are a model of production of TNF-ÃŽ ± and inducible nitric oxide synthase (iNOS). At rest, the DCs oxidize glucose in the mitochondria, by OXPHOS, with little lactate production. But, once stimulated with TLR agonists, become dependent on Warburg metabolism to subsistence (40). PI3K and Akt are important in the activation of glycolytic metabolism (41); play an important role in the duration of glycolysis in DCs activated. As evidenced by DCs activated by more than 12 hours which increases glucose consumption and TCA and mitochondrial oxygen consumption cease (40), increasing lactate production, and the cells survive only by aerobic glycolysis (Fig. XX). The high production NO gas by iNOS from arginine, inactive mitochondrial respiration in these cells. So the activation of glycolytic metabolism in activated DCs induces the expression of iNOS and production of NO thus inhibits OXPHO S. This subsistence mechanism is vital for the rapid production of ATP in the absence of machinery for the production of mitochondrial ATP (42). As the cells of the innate immune system, the T and B cells activated Warburg metabolism used at the time of the proliferation. In contrast to most of innate cells, which use Warburg metabolism after activation but not proliferate (1). Contrary to activated effector T cells, memory T and B cells do not use aerobic glycolysis but if they use mitochondrial FAO for their development and persistence, maintain or adopt a catabolic metabolism (Figure XX) (43). Once an antigen recognized by naive T cells and with adequate costimulation, this growth rapid, proliferation, and acquisition of specialized effector functions is initiated. This requires of the T cell a metabolic reprogramming and energetic. This pass of a catabolic metabolism to an anabolic metabolism, changes the cell is not in a state of maintenance and homeostasis (1). Some molecules such P13K, Akt, Myc, and HIF are associated with immune and metabolic signals for the activation, function, development and upkeep of T cells. So the metabolic pathways induce a T helper subsets (1). As was evidenced in Treg cells mainly use mitochondrial OXPHOS and FAO for their development and subsistence (17) or in Th17 cells where glycolysis is primarily required (44). In activated T cells the IL-12 induce an increase in the glucose transporter and glycolytic metabolism. Besides glycolysis in maintaining the activity of active effector T cells, exist other pathways involved, as via the pentose phosphate and glutaminolysis as well as the use of key molecules such as citrate and malate (Figure XX) (1).It is important to consider the available nutrients, substrates, or other resources that can create an imbalance in the environment of immune cells, affecting the metabolism of cell function and fate of immune cells. Mitochondria in the production of iNOS and inflammation: All metabolic process to generate ATP by OXPHOS generates ROS, which are involved in oxidative stress of the mitochondria. Production of O2- in excess, induces activation of factors of redox-sensitive transcription, such as NF-kB, and thus an increase of cytokines, chemokines, inducible nitric oxide synthase (iNOS), eicosanoids, and adhesion molecules (45). Some of these superoxide anions combine with nitric oxide (NO) to produce peroxynitrite (ONOO-), a powerful oxidant. These ROS oxidize proteins, membrane lipid and mtDNA; damaging mitochondrial integrity (46). Being mitochondria, the inducer of the pro-inflammatory action by the action of innate immunity using redox sensitive or direct inflammasome activation molecules. Progression that result in the immediate activation of caspase-1, and subsequent activation of the inactive precursor of IL-1ÃŽ ² and IL-18 (47). DAMPs activate the same receptors that detect PAMPs, such as TLRs and cytoplasmic NOD and NLRs (46). Once activated, NLRP3 this is depolymerized and induces the recruitment of the adapter protein ASC and caspase-1 (and her cleavage), and other cytoskeletal proteins, glycolytic enzymes and caspase-7. This group of proteins called inflammasome. This complex induces pro-inflammatory, such as IL-1ÃŽ ² and IL-18.(47). Elevated levels of ROS generated by the mitochondria activate NLRP3 inflammasome. Interestingly, the humidity and the myth-AMPS can activate APCs, as well as other non-immune cells including mesenchymal stem cells and astrocytes. Additionally, IL-1ÃŽ ² pro-inflammatory IL-6, MCP-1 and TNF is induced by degradation of mtDNA in mouse primary astrocytes. (48). This activation of the inflammasome can activate NF-kB, increasing even more pro-inflammatory cytokines duration of the inflammatory response. This summation of events can be a clear explanation to the high deterioration of mitochondria (46). Biogenesis of mitochondria: The availability of nutrients and oxygen can determine the function of a time cell proliferate and differentiate. Under normal conditions the cell has high level out of ATP/ADP/AMP. Thus, an increase in AMP activates AMPK, activating ATP production by activating TSC 1 and 2 which blocks mTOR (7). After ATP levels are increased activated Akt/PKB promotes mitochondrial biogenesis by phosphorylation and nuclear translocation of NRF-1 and nuclear translocation with increased mitochondrial hexokinase (HK), using glycolysis coupled to OXPHOS with uptake mitochondrial ATP, especially in order to allow cell survival and maintenance of cell functions (49). An important protein in the biogenesis of mitochondria is BAD, which is involved in the initiation of a protein complex that catalyzes the first step of glycolysis by deHK-4 activation. But absent BAD gives a restriction of respiration in the presence of glucose and in the absence of glucose dephosphorylated BAD and induces apoptosis(50). This interaction between energy metabolism and the regulation of apoptosis, is important in mitochondrial biogenesis, and any imbalance can lead to mitochondrial failure and loss problems inducing pathological cell survival (51). Thus, the whole process of inflammation, oxidation and apoptosis, requires a high rate of mitochondrial replacement to allow the restoration of damaged mitochondria continuously and cell survival, which may serve as a signal that stimulates the production of mediators anti-inflammatories such as the IL-10. 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Indian Film Industry Bollywood Essay

The entertainment industry in India has outperformed the economy and is one of the fastest growing sectors in India. However, it registered a moderate growth of over 6 per cent in 200.The industry is expected to grow from Rs. 166 billion (U.S. $ 3.45 billion) to Rs. 419 billion(U.S. $ 8.72 billion) by the year 2007. Film entertainment is the most popular form of entertainment and it is this undiminished passion through the decades that has driven India to become the largest producer of films in the world. Since 1931, when talkies were introduced in the country, the film industry has produced more than 67,000 films in more than 30 different languages and dialects. The film industry recorded a loss of Rs. 3 billion (U.S. $ 62.5 million) in gross revenues of Rs 39 billion (U.S. $ 812.5 million) in 2002. But, it is expected to grow annually by 19 per cent to reach Rs. 93 billion (U.S. $ 1.93 billion) by 2007. The industry produced 1200 films in 2002, and 1,013 films in 2001, up from 855 films in 2000. While Hindi films continued to be the largest segment in 2001 (23 per cent share), south Indian language films (Telegu, Tamil and Malyalam) have seen growth in their shares. India’s movie industry is a great sector for foreign investment by corporatized entertainment companies. Though risks are high on a per-movie basis, the risk spreads out across a number of films. However, the domestic filmmaking industry, despite its profligacy, is yet to acquire the character of professionalism on a large scale. BRIEF HISTORY OF INDIAN MOVIE INDUSTRY When the Lumiere Brothers’ first films were shown at Bombay’s Watson’s Hotel in 1895 or when Dadasaheb Phalke released his epochal feature film Raja Harischandra in 1913, it is unlikely that either the exhibitors or the pioneer film maker realised they were unleashing a mass entertainment medium that would hold millions in sway for the next hundred years; that they were spawning an industry that in years to come would overtake the rest of the  world in film production! For most Indians, cinema is integral to their lives; it is not a distant, two to three hour distraction, but a vicarious lifestyle for them. The large screen provides an alternative, an escape from the realities of day-to-day life. The protagonists are totally identified with, the hero is applauded, the virtuous is worshipped and the villain is condemned. The actors and actresses are household names; there is no escaping their omnipresence, from the Paanwala (betel vendor) to the most revered Indian painter – they are all caught up with the magnetism of screen personalities. A study of the vicissitudes of Indian cinema would throw light on the progress of technology, especially cinematography, and the changing political scene and social mores and attitudes. The silent films launched by Phalke, which had titles in English, Gujarati, Hindi and Urdu, by and large related to myths and legends. The stories were familiar to the audience and required minimum commentary. Historicals also proved very popular; Harsh, Chandragupta, Ashoka and the Mughal and Maratha kings strode the silver screen amidst cardboard pillars and in tinsel costumes. Strangely enough, while in the nineties we are still arguing over whether or not ‘kissing’ should be shown on screen, in the first decade of Indian cinema, with the British paying scant attention to censorship except when the Establishment was attacked in any way; leading heroines of the day kissed their leading men without inhibitions, like Lalita Pawar in Pati Bhakti (1922)! With the advent of Gandhiji came the plea for according a better status to women, the removal of untouchability and a cry for religious harmony. The silent era of Hiralal Sen, Baburao Painter and R. Nataraja Mudaliar came to an end when Adershir M. Irani produced his first talkie, Alam Ara in 1931. If Phalke was the father of Indian cinema, Irani was the father of the talkie. The classic Hollywood musical Singing in the Rain exemplifies the cynicism with which people first regarded the talking movie and this holds good for India too. There were too many gargantuan problems to be tackled; there were no dialogue writers, no lyricists; songs had to be sung during the filming as prerecording facilities were yet unknown. Minimum instruments  were used as the instrumentalists had to be camouflaged behind the singer. A quaint story goes that during the filming of a song the actress was getting agitated as the tabla beat was too fast. Finally the shooting had to be stopped and a hapless tabla player was pulled out of the pool where he had been hidden. â€Å"What can I do,† he cried, â€Å"a fish got into my dhoti (loin cloth)†. But the talking film had come to stay. Considering that even the silent film had a preponderance of songs, the talkie came to be more of a single; the heroes and heroines sang their way through the three-four hour movie. Histrionics and appearances counted less; a singing talent was all that mattered. To this day the Indian film song has a unique thrall. The music director, the song writer and the playback singers have an unparalleled status in India’s cinema. If Bombay was the hub of early cinema the other centres were not far behind; Calcutta and Madras with their own patriarchs were also making path-breaking films. Chandidas a film glorifying the Bhakti movement and castigating casteism, directed by Debaki Bose in 1932 for New Theatres, was lauded for its use of background music and dramatic narrative. K. Subrahmanyam’s Thyaga Bhoomi (1939) and Seva Sadan both advocated women’s rights and self-dependence. Seva Sadan also introduced to the world through the silver screen, the great singer M.S. Subbalakshmi, who came to be immortalised for her role in and as the poet-saint Meera both in Hindi and Tamil. While it is almost impossible to even list all the luminaries of Indian cinema over ten decades, the Wadia Brothers deserve special mention, before going into the different genres. JBH and Homi Wadia were the forerunners of the stunt film – the thirties was a period in Indian cinema when ‘Wadia’ and ‘Nadia’ were synonymous. Australian by birth, Mary Evans came to India with a dance troupe. She was asked to do a number for JBH’s Noor-e-Yman; she changed her name to Nadia. â€Å"Besides being a lucky name, it rhymes with Wadia†, she is reported to have said, and through various circumstances she became stunt actress for the Wadias, earning the sobriquet â€Å"Fearless Nadia†. The Wadias had a fixation for trains and made a number of films titled,  Toofan Mail, Flying Ranee, Punjab Mail and so on. Nadia got so used to sitting on roof top of trains for her stunts that she became reluctant to step off and even demanded her lunch be sent up! The true stunt woman, she grappled with a lion, did the trapeze, carried a calf and a man over running trains – it is unlikely there could ever be another actress like Nadia. She married Homi in 1960, and breathed her last recently. The forties was a tumultuous decade; the first half was ravaged by war and the second saw drastic political changes all over the world. Film-makers delved into contemporary themes. V. Shantaram, the doyen of lyrical films, made Dr. Kotnis Ki Amar Kahani – a tribute to Dr. Dwaraknath Kotnis who went out with a medical team to China and died there. Shantaram’s other films were reformist but visually appealing, like, Do Aankhen Barah Haath, Pinjra, Chaani. But there were films where pure artistic merit supersedes social message as in Jhanak Jhanak Payal Baaje and Geet Gaya Pattharon Ne. South Indian films also gained great footing. AVM and Gemini were two of the most prolific producers turning out social drama in the South Indian languages as well as in Hindi. While the thespian actor Shivaji Ganesan delivered mind boggling soliloquies on screen, many of the politically inclined writers and actors of the south Indian screen began to use the medium for reaching out to people. The DMK stalwarts, Annadurai, Karunanidhi and MG Ramachandran did not even resort to subtlety. â€Å"Naan anaittal adu nadandu vital†¦Ã¢â‚¬  sang MGR, (if I could be the decision maker, the poor of this world will not suffer†¦.†). The very titles of the films were chosen with care; Rickshakaran (Rickshaw Driver), Muttukara Velan (cowherd Velan) and En Kadamai (my duty) to convey his identification with the masses. No wonder he was hailed Makkal Thilagam (gem amongst people). Just how effective was the use of the medium was amply proved with the party coming to power and MGR getting voted Chief Minister of the state. The other star who used the screen image to great advantage was N.T. Rama Rao of Andhra Pradesh. The veritable screen god, NTR played the role so often that he began believing in his divinity. Apparently so did a lot of other people in Andhra, which is why we had a second screen hero from south as Chief Minister. While the south was busy wooing the public for votes, Bombay was either turning out escapist fare, light, happy, musical films with Dilip Kumar, Raj Kapoor, Dev Anand, Shammi Kapoor, Kishore Kumar, Nargis, Madhubala, Nutan, Geeta Bali, Mala Sinha and others or gave the audience absolute tear jerkers with social melodrama. This was the golden era of music. Shankar- Jaikishan, O.P. Nayyar, Madan Mohan, C. Ramchandra, Salil Chaudhury, Naushad, S.D. Burman – all had their distinctive sway. Each vied with the other to produce some of the most unforgettable melodies India has ever known. This was also the age of innocence; the screen was black and white, the vamp and the heroine did not merge, they had their domains, there were no shades to the hero, a man was all good or rotten to the core. No double entendres were woven into the songs and even the vamp was decently attired on the screen. This was the era of Raj Kapoor, of Shree 420, Awara, Boot Polish, Jagte Raho, Chori Chori and of course his magnum opus Mera Naam Joker – he was still making and acting in enduring films, the tramp who is not able to cope with the pace of the world. He caught up with times and his films changed with Sangam, Jis Desh Mein Ganga Behti Hai, Satyam Shivam Sundaram and Ram Teri Ganga Maili. Dilip Kumar and Guru Dutt were excellent foils to the chocolate-faced heroes as tragedy kings. So were Meena Kumari and Bina Rai amongst the heroines. But such was their versatility that they could also carry off comedy effectively. Two outstanding Hindi films of the fifties that deserve mention are K. Asif’s Mughal-e-Azam (took 14 years to make and is one of the most lavishly produced historical of Indian cinema) and Mehboob Khan’s Mother India, which is said to have gained the status of Gone With the Wind. In the meantime in Bengal, the man who was to take Indian cinema to the international arena and win accolades from the greatest film- makers, Satyajit Ray, released his first film, Pather Panchali (1955). After his trilogy there was no looking back for him or for cinema from Bengal. Mrinal Sen conveyed his quiet commitment to socialism through films like Calcutta, Oka Orie Katha (Telugu) and Bhuvan Shome. Director Ritwik Ghatak gave us memorable films Meghe Dhaka Tara and Subarnarekha. Although Bengal also came up with films that asked for a willing suspension of disbelief, these were  exceptions rather than the rule as in Bombay films, where the Mukherjis, Sippys, Chopras, Chakraborty and Manmohan Desai produced one bonanza after another for the masses and laughed all the way to their banks. There was no market for serious films, it was felt, and the classics that failed to break even like Guru Dutt’s Kagaz ke Phool and Raj Kapoor’s Mera Naam Joker, only strengthened the conviction. The former committed suicide and the latter resorted to the populist fare with Bobby. It was only after the government set up the Film Finance Corporation (FFC, which in 1980 came to be known as NFDC i.e. National Film Development Corporation) that several small but serious film makers got the wherewithal to make films, notable among them being Mani Kaul, Kumar Shahani and GV Iyer (with his maiden venture in Sanskrit, Adi Sankaracharya). The Corporation also partnered the making of Attenborough’s Gandhi and financed Satyajit Ray’s Ghare Baire which was to be one of the last films of the master. Like cinema in Bengal, Malayalam cinema too was meaningful but it took a longer time to get noticed. In fact it was Ramu Kariat’s melodious tragedy Chemmeen winning the President’s gold medal in 1965 that drew attention to Malayalam cinema. Adoor Gopalakrishnan (Swayamvaram) and others all gained similar recognition in the years to come. With actor Prem Nazir doing stellar roles in a record breaking 600 films, Malayalam films have come to be characterised by simple narration of powerful stories, authentic locales and low cost production. The Karanth (BV) – Karnad (Girish) combine have produced two milestone Kannada films Vamsa Vriksha and Samskara, both essentially iconoclast in treatment. Though much talked about, the critique of caste brahmins, the theme of both films was later seen to be rather extreme. In this context it is worthwhile to mention two films made in Tamil on the same subject. Vedam Pudithu directed by P. Bharatiraja and Ore Oru Gramathile by K. Jyothi Pandyan. Both carried strong indictments against caste hierarchy and the common man’s struggle to overcome it, but retained a balance – rather unusual for Tamil films. With government funds available for making films, the seventies saw an unhealthy divide between the existing commercial or mainstream cinema and the new parallel cinema or art films. The former was condemned unequivocally by the critics but continued to fill the coffers while the latter got rave reviews, bewildered the masses and created deep dents in government resources. Fortunately this situation did not last long, for soon there came a crop of film makers who realised that meaningful films need not necessarily incur heavy losses. Shyam Benegal, (Ankur, Nishant, Manthan) proved that there was an audience for films without frills but with a strong story and interesting narration. Govind Nihalani, Jabbar Patel, Mahesh Bhatt, K. Balachander, Bharati Raja, Adoor Gopalakrishnan, all fell into this category. Around this time, the singular phenomenon, the angry young man with his dark looks, smouldering eyes and mesmerising voice, Amitabh Bachchan, began to stride the scene like a colossus. He introduced to cinema for the first time as a cult, the negative or the anti-hero. Special screen plays were written for this hero seeking vengeance and taking on single-handed an unsympathetic establishment and inadequate legal system. The eighties saw the advent of women film makers, Vijaya Mehta (Rao Sabeb), Aparna Sen (36, Chowringhee Lane, Paroma), Sai Paranjpye (Chashme Baddoor, Katha, Sparsh), Kalpana Lajmi (Ek Pal and, later the much acclaimed Rudali), Prema Karanth (Phaniamma) and Meera Nair (Salaam Bombay). The most commendable thing about these directors is their individuality. Their films have strong content and are told with passion, (only Sai has tackled light hearted subjects). In the nineties, Indian cinema faces tough competition from television; the cable network gives viewers any number of channels and though the most popular channels continue to be the film-based ones, the cinema halls have taken a beating. Nevertheless, films like Aditya Chopra’s maiden effort, Dilwale Dulhaniya Le Jayenge and Suraj Barjatya’s Hum Aapke Hain Kaun have broken all records, because they recall the innocence of the fifties, a novelty in this age of sex and violence. This gives hope. Cinema in India can never cease, it has gone too deep into our psyche. It may undergo several reverses in fortune. With other mediums opening up, there will be a smaller market for films. Living as we are in a global village today, we are becoming a more discerning audience. No longer are we going to lap up every mediocre fare dished out by the moghuls of cinema; only the best will survive. And this is just as well.

Provide Reception Services Essay

1.1 There are many purposes to a receptionist role especially being the first point of call between the company and the client/supplier. Being the first point of call is an important role because it helps the whole company. When a customer/supplier comes in a receptionist can get the correct member of staff for the person. Also it ensures that somebody knows who is in the building and has got them to sign in so the company had a record and it’s easier for people to be accounted for in cases of emergency. In some businesses the receptionists make appointments for the other staff for customers/suppliers to come in. They also take the call and pass it to the right person. Being a smaller company we do not have somebody that has been employed as a receptionist but because of where my desk is placed I have adopted the role. In this role I have to welcome people into the building, make sure that they sign in and offer them a drink. I also find out who they are here to see or do. If they want to collect goods I can pass them on if the girls in sales are busy but if they are here for a meeting or chat I let the member of staff know. 1.2 When doing a receptionist role you have to present a positive image of yourself and of the company. When someone enters the building and a positive image is being portrayed it makes them feel more comfortable and that the company is a good business to work with or use. If the staff a positive it shows the customer/supplier that they are going to get things done and enjoy what you do so you are going to do the best you can for them. 1.3 It doesn’t take a lot to show a positive image of yourself and the company. For starters just having a smile on your face helps massively because people can tell. Offering a drink when people walk in also presents a good image because it shows that you will do anything to make them feel comfortable. Keeping yourself and you work space clean, organised and smart shows that you care about yourself and what you are doing and also shows that you are a person that is ready to do things. 2.1In any business there are many lines of communication fro m the reception. For example if somebody came into the office with a complaint the receptionist would have to take down details and pass them on. If the complaint is about a product that would be passed on to their account manager, if the complaint was about employee –depending on the size of the  company- you would go to the supervisor or managing director. If someone came into Othello Martin James and could be a potential new customer I would take down some details and pass it on to the best person depending on who was free or where the person was based for example if they are based in Swadlincote or the surrounding areas I would pass it on to Tanya. But is she wasn’t available I would pass it to whoever was free and able to talk. If someone came in with questions about new products or a new order I would find out who the account manager was. 2.2In larger companies both employee’s and the public have to make appointments to see supervisors or the managing director. This all g oes through the reception as they can arrange the appointments and mange diaries. But at Othello Martin James we are a smaller office and less formal than big businesses. We don’t need to make an appointment to see our supervisors or managing director we are all in the same office and can just ask for two minutes if we need to have a chat. 2.3In every business there are many procedures for people coming into the office. For example entry and departure, security and confidentiality and finally health and safety, all of these procedures are made to difference business standards depending on the company. For example with entry and departure some high security companies might have to so more checks on people than say an office like ours. For example in any business visitors will have to sign in so the company has a record of who has visited and also in cases of emergency there is a record of who is in the building. This is very important so there are records because if there isn’t and an emergency does happen somebody could be in the building but you wou ldn’t know because you have no records. Security and confidentiality are important to any business because there are some many documents that need to be covered under the data protection act. In a reception a lot of documents are held for example in a doctors surgery they have all the patient records for the people that are going in that day, in an office there are details of the employees and the business. If people could just walk in they can easily get these records. If somebody is on reception all the time while the office is open this stops the security and confidentiality risk. 2.4Like I have mentioned earlier in our office we do not have somebody that is employed as a receptionist but because of where my desk is placed I have adopted the role. The way our office is designed there are four desks in our reception  area which is also the accounts department. There is also somebody in this part of the office so people can’t just walk into our office without somebody knowing. We ask visitors to sign into our sign-in book so we have a record. Also when someone is always in that office people can’t just walk in and access information that isn’t to b e viewed by them. Also our office is in a business park which has security fencing around the units, when people arrive they have to press the buzzer to be let in. For example is somebody is coming round for a meeting the have to press our buzzer and I have to pick up the phone find out who they are and let them in through the gates. 2.5/6The purpose of having health and safety procedures is to make sure that everyone safe and protected. This includes procedures such as signing in. It is my responsibility to make sure that everyone that comes into the office sign in and also know where the assembly point is in case of emergency. When visitors come in to the building I just ask them to fill in the book before I ask who they are here to see or if they want a drink. 2.7There are many emergency procedures in businesses from fire exits to if somebody becomes ill. In our office if a fire happens first the fire alarm will go office then we all have to get up and leave in a calm manner via the fire exits that are lit up and meet at the assembly point that is across the car park. My role is just to make sure that I can get out without causing a fuss als o when we are at the assembly point I should know if someone is missing because I see everyone that walks through the door. But being a small business the majority of us are in the same office on the same floor the rest will be our delivery drivers which could be in the warehouse or on the road. The sales office knows when drivers come back so will know if somebody is in the warehouse. If somebody falls ill or has an accident first we find out how urgent it is for example can we phone their emergency contact or do they need to go to hospital. I don’t have much of a role in this as I am not the first aider. But if I needed to help I will also my desk is closest to the kitchen where the first aid kit and emergency numbers are kept so I may have to run in and get them. 2.8/9In our office we don’t tend to get visitors that come in showing aggression and causing conflict because everyone comes in for a reason. But we sometimes receive conflict/aggression on the telephone and have to act in the same way – also sometimes our delivery drivers receive face to face conflict and aggression  wh ile out on the road. When this does happen we have to remain calm and take details of what the person is being aggressive about. If the person starts being aggressive we can ask them to leave or put the phone as we don’t have to tolerate that behaviour. Depending on what the person was being aggressive about depends on who I would refer it to. But in all cases I would tell my managing director and supervisor. 3.1/4.8In any office there are many reasons/purposes for suggesting ideas for improving the reception area. A reception area should have a desk for the receptionist where they can see the door, a telephone, a computer for the work of the receptionist and basic office equipment. If the building has security gates the buzzer should be behind the receptionist desk. For the visitors it should have a seating area and a signing in book. Some businesses have a water dispenser and magazine racks. The receptionist is best for suggesting ideas for the reception area because they are in there all the time and can see how it works for the visitors. Also the reception area should be a clean and welcoming environment. When suggesting ideas it helps keep the reception area modern and in best working order for you – the receptionist and the visitor. 3.2In any office there is always going to be quite times when all your jobs have been completed. At this point you can ask other members of staff if they need a hand with anything just to help with their work load. As previously mentioned about me adopting the role I work in the accounts department so I have many roles to duties to do but we can still have quite times where I go and ask if anybody needs a hand. Just before we finished for Christmas 2014 we had a couple of issues with our account program Sage. While this was being sorted I went in to the sales office and asked if they wanted a hand to finish the jobs for the year so I helped file the scanned delivery notes on the computer.

Part of our Neorons, Dopamine Controls Pleasure - 547 Words

The parts of the brain are what make us function in our day to day lives, if one thing were to go wrong it could throw our whole system off. Dopamine is a part of our neurons that control how we feel pleasure and basically what actually makes us feel good. This neuron controls our emotions as well as our movements. Dopamine causes the human being to stay close to the good feeling we have had and makes us move towards them. This part of our neuron can lead us to addictions of these pleasures. Drugs that are used today ignite these receptors of dopamine and continually leads us back to this feeling again and again, this is an addiction. Many people have addictions to drugs, one in particular cocaine. This drug sets off our neurons and reward us for something that actually hurts us and is not good for us. In the article we read of an experiment with mice and rats. The experiment entails targeting the dopamine receptors in these animals by incentives of the electrical sort. The rats feel rewarded for â€Å"VTA microinjections†, which they say â€Å"can also establish condition-placed preference†. The VTA is very high with the electric stimulations, when eating, drinking, and the use of cocaine. The need for cocaine is increased as the use becomes abuse. They study the effects of this on the system and see how they affect the cholinergic cells. The loss of these cells did not affect the use of cocaine, and was not a factor. They also did this study with heroine and yielded the same