Similarities Between Judaism And Christianity Religion Essay

Similarities Between Judaism And Christianity Religion Essay The creation of the universe still remains a mystery to many of us. Almost all mankind is obsessed with trying to discover how the creation of everything that exists came about. Some are convinced about the divine existence of God while others are atheist. The religious people are also faced with many differences and disagreement about the existence and the nature of the real God. The purpose of this paper is to compare and contrast two specific characteristics that are evident in Christianity and Judaism. As much as there are differences between the two religious groupings, there are also similarities between them. This is because, Christianity emerged and protested from Judaism, but it is not a continuation of Judaism as some people would suppose it to .Therefore, there are various characteristics that makes the two different. The first characteristic is how they define sin and the second is how they define atonement and religious human intercession. Similarities Between Judaism and Christianity Both religions define sin as rebellion, and God has made his will to be known to all people through His word. Acting contrary to this set will against God is a sin. Although Wyschogrod states that Judaism doesnt take the consequences of sin seriously, Plantinga feels Christians should go back to their original religion so that they can understand the consequences of sin. Therefore, both believe that sin has its consequences. God is all powerful and supreme, the only thing he can do is to allow people to sin but he limits the freedom. One of the reasons for allowing the people to sin is so as He can demonstrate his will and achieve his objectives; which could be to demonstrate his love since his lover supersedes his hatred. Therefore both religions believe that God is a God of mercy. God has provided atonement in order to reconcile all his people with him. This shows that whenever people are engaged in sin and have a deep repentance for it, there is a way out for both religions. This cleanses and erases all the sins and the makes man right with God. They both believe that in order to be forgiven, faith must be incorporated with the atonement. Since there is a continuous behavior of rebellion, both religions believe that they live under two principles which include being loyal to God and being rebellious. Therefore, sin is a continuous process and cannot be avoided by any human being.Because of this repentance must be done regularly. Differences in Judaism and Christianity In regard to Sin, Christianitys center of attention is found on The Original Sin which is the sin that committed by Adam and Eve while they were in the Garden of Eden and continues on from that generation to this generation we are living today .While Judaisms center of attention on Sin which means the continuous sins committed after a person is born, thus proving that at birth a person is with no sin. Therefore, according to Judaism, repentance is done for disobedience done either intentionally or unintentionally after the person is born while for Christianity, repentance is done for an entire persons life since his birth even to the extend of repenting the sins of a former generation. While reviewing the Holy Bible in Genesis chapter 3, the two religions interpret this differently. According to the Christian perspective, when Adam and Eve sinned, the glory of God in them was taken away, thus making the whole creation perverted. While in Judaism, when Adam and Eve sinned, God made them to suffer the consequences by only chasing them out of the Garden of Eden but never meant that sin will follow their forthcoming generation. Christianitys element of redemption that is meant to return the glory of God which was lost after Adam and Eve sinned in the garden of Eden is only through Jesus Christ who is claimed to be God in the flesh and a part of the Holy trinity, cleanses the sins of the whole world for those who accept this redemption. The Judaism element of redemption is done through is through prayer which cleanses the sin impartially, and full cleansing is done after they ask for forgiveness from the people. According to Judaism Jesus was just a good man and was not reincarnation of God into mankind, he has no powers to save souls as Christianity perceives and believes it to be, and he never resurrected from the dead. Since piece has never reigned in this world. Judaism has never approved Jesus as the Prince of Peace and the Messiah. They claim that the Prince of Peace shall rule the world later and peace shall dominate this whole world. But Christianity believes Jesus as the Prince of peace and the promised Messiah and all them that accept this divinity have peace in their minds and souls. Furthermore, Judaism continues to state that God is one. God cannot be made of three parts which are termed as the Holy trinity, even though Christianity claims it to be a mystery. They claim that this can be compared to pagans who worship many god and that the capacity of claiming that God is in three parts diminishes the preeminence of his power. Therefore, it has no room for Jesus having a position of being God the Son. This is opposed by Christianity since according to the Bible in the Book of John 1:1, 14 which claims that In the beginning there was the word, and the word was with God and the word was God. The word became flesh and dwelt among us in this world. As much as there are differences and similarities, only time can tell since Christianity is based on faith. There is no religion that can be placed above the other. Its hard for worshipers also to judge themselves since they can not identify and accept easily their shortcomings since it may be to their disadvantage. Therefore, judgment is left to God alone.

Cardiac Muscle Structure and Function

Cardiac Muscle Structure and Function The structure of cardiac muscle The capacity for cells to utilize biochemical energy to generate both mechanical force and movement of the human body is a dominant feature found in muscle cells. There exist three distinct categories of muscle tissue, each differing by specific structural and functional properties. These categories include smooth muscles, skeletal muscles and cardiac muscles. Smooth muscles are involuntarily contracting, non-striated muscles that surround the inside walls of hollow organs such as the urinary bladder, reproductive organs, and both the gastrointestinal and respiratory tracts. Its contraction enables and regulates the progression of liquid content, such as food, urine and blood, along the internal passageways. Skeletal muscles are voluntarily contracting, striated muscles that attach to bones of the skeleton. The contraction of skeletal muscle is primarily responsible for the movement of the skeleton, but also has roles in heat production and protection of internal organs. Cardiac musc les are an involuntarily contracting, striated muscle found exclusively in the walls of the heart, more specifically in the myocardium. Contraction of cardiac muscles propel oxygenated blood into the circulatory system to deliver oxygen to the body, as well as regulates blood pressure (Martini et al., 2009). Cardiac muscle tissue is composed of a network of individual cardiac muscle cells, called cardiomyocytes. Cardiomyocytes are small in size, averaging 10-20ÃŽ ¼m in diameter and 50-100ÃŽ ¼m in length, have a single centrally positioned nucleus and connect to adjacent cells in a branched manner through specialized sites known as intercalated discs (Martini et al., 2009). Two structures that are found within the intercalated discs are  desmosomes and gap junctions. Desmosomes are specialized structures involved in cell-to-cell adhesion and gap junctions are intercellular channels that connect the cytoplasm of adjacent cells, allowing the free passage of molecules, ions and electrical signals. Within the cytoplasm of striated muscle cells are long, cylindrical organelles termed myofibrils. With a diameter of 1 to 2ÃŽ ¼m and numbering between hundreds to thousands in a cell, myofibrils are enveloped and grouped together by connective tissue called the fasciculus, which forms bundles of myofibrils that spans the length of the cell (Widmaier et al., 2006). Individual myofibrils can be further divided into two types of contractile filaments: thin filaments and thick filaments. These filaments are composed primarily of actin and myosin proteins, respectfully. The thin and thick filaments are aligned in a manner where they form repeating structural units along the length of the myofibril. Among these structures is the sarcomere, which is a Ca2+-dependent contractile unit responsible for muscle contraction and relaxation (Widmaier et al., 2006). An increase in cytoplasmic Ca2+ influx causes the thin and thick filaments to overlap each other, causing a shortening of the sarcomere, leading to a muscle contraction. Alternatively, a decrease in cytoplasmic Ca2+ levels causes the thin and thick filaments to pull away from each other, leading to relaxation of the myofilaments. The specific arrangement of the thin and thick myofilaments is responsible for the striated appearance of both skeletal and cardiac muscle tissue. Electrical stimuli, called action potentials, are required for striated muscle cell contraction. In skeletal muscles, action potentials are derived from neurons in the brain and spinal cord that transmits the signal through the nervous system and innervates muscle fibers, causing contraction. However, unlike skeletal muscles, the contraction of cardiac muscles occurs without neural stimulation, a property called automaticity (Martini et al., 2009). This is because the heart contains pacemaker cells, which are specialized cells that have no contractile function; rather having the ability to initiate and conduct action potentials to neighboring cardiomyocytes. The cardiac action potential propagates across cardiomyocytes through gap junctions, allowing the cells to contract in tandem, which enables the heart to contract as one muscle. Cells which have pacemaker activity constitute 1% of cardiac muscle cells, whereas the other 99% are contractile cells (Sherwood, 2006). The conversion of an electrical stimulus into a mechanical response is performed through a physiological process known as the excitation-contracting coupling or the ECC. This phenomenon has a critical role in muscle cells as it allows a propagating action potential to cause shortening of the sarcomere, leading to muscle cell contraction. When action potentials are produced by pacemaker cells, they conduct across the heart by traveling along the length of the myofibril on the muscle sarcolemma. An action potential will transmit on the sarcolemma until it reaches a transverse-tubule (T-tubule). T-tubules are defined as deep invaginations into the sarcolemma that contact the cisternae of the sarcoplasmic reticulum (SR), an organelle that functions as a Ca2+ storing body. Upon penetrating the T-tubules, the action potential will cause a depolarization of the membrane voltage potential, leading to an increased influx of Ca2+ into the cytoplasm. Resting within the T-tubules are many ion tr ansporters such voltage-gated L-type Ca2+ channels and Na+ / Ca2+ exchangers (D. Bers, 2002). These Ca2+-transporters are opened/activated when stimulated by action potentials, prompting the entry of extracellular Ca2+ into specific microdomains in the cytosol (Berridge, 2006). An elevation of cytoplasmic Ca2+ levels will trigger the opening of ryanodine receptors (RyR), which are intracellular Ca2+ channels present on the membrane of the SR, allowing stored Ca2+ to exit the SR and enter the cytosol. The mechanism of how Ca2+ ions triggers Ca2+ release from the SR was identified by several groups in the 1960s, and appropriately termed Ca2+-induced- Ca2+-release (Endo et al., 1968; Ford et al., 1968). An overall increase in intracellular Ca2+ level causes Ca2+ to bind and cause a conformational change in Troponin C, a protein present on actin filaments. This conformational change causes a displacement of Tropomyosin, which prevents the interaction of myosin protein with actin filaments, thereby allowing myosin to contact actin, which promotes sarcomeric contraction. Alternatively, Ca2+ sequestration from myofilaments and cytoplasmic depletion prompts a relaxation of the sarcomere. Such a decrease of cytoplasmic Ca2+ occurs by either by re-entering the lumen of organelles, such as the SR and mitochondria, or cellular export by Ca2+ pumps and Na+/ Ca2+ exchangers on the sarcolemma (D. Bers, 2002). The efficiency of muscle contraction is partly depicted by the type of myosin heavy chain (MyHC) that the cell expresses. MyHC are enzymes, found on the head of myosin proteins, which catalyze the hydrolysis of ATP. The rate at which MyHC can hydrolyze ATP ultimately depicts the speed at which the myofilaments contract, as well as the overall energy efficiency of that cell. In cardiomyocytes, two types of MyHC proteins are expressed: ÃŽ ±-MyHC and ÃŽ ²-MyHC. The following table represents the distinguishing features of the cells that express either ÃŽ ±-MyHC or ÃŽ ²-MyHC: Similar to skeletal muscles, cardiomyocytes are categorized into two distinct classes, based on the type of myosin heavy chain (MyHC) that is expressed. Those who predominantly express ÃŽ ±-MyHC are found in adult hearts, contract in a more energy inefficient manner and are quicker to fatigue. In contrast, cardiomyocytes that express more ÃŽ ²-MyHC are present in developing hearts, have a more energy efficient contraction and are more resistant to fatigue. Cardiovascular diseases and pathological cardiac hypertrophy Cardiovascular diseases are disorders that prevent the proper function of the heart and blood vessels, causing abnormalities of the cardiovascular system, which lead to defects in the brain, kidneys, lungs and other parts of the body (Public Health Agency of Canada, 2009). According to the World Health Organization, cardiovascular diseases accounted for 29% of global deaths in 2004, making it the leading cause of death in the world (World Health Organization, 2009). Furthermore, with an aging population, the number of patients diagnosed with heart disease in America is expected to double within the next 30 years, from 5 million to 10 million (Hobbs, 2004). In Canada, this disease was responsible for 31% (or >70,000) of total deaths in 2005 (Statistics Canada, 2009). Amongst the numerous categories of cardiovascular diseases, heart failure is the most prevalent, with the fastest spreading rate and the highest mortality rate over the past decade (Heineke et al., 2006). Heart failure is defined by defects in cardiomyocyte structure, function, rhythm or conduction, which prevents the heart to pump adequate amounts of oxygenated blood and nutrients to meet the bodys demands (McMurray et al., 2005). Individuals living with a failing heart suffer from severe coughing, shortness of breath and edema, leading to a decreased tolerance to exercise and an overall diminishment in physical and mental health. As the disease progresses, patients may develop further pathophysiologies due to detrimental effects on the function of vital organs, ultimately resulting in death. A common abnormality that precedes heart failure is the pathological enlargement of the heart, a condition known as cardiac hypertrophy. Cardiac hypertrophy is induced by the release of hormones, cytokines, chemokines and peptide growth factors, which act on cardiomyocytes in an endocrine, paracrine and autocrine manner (Heineke et al., 2006). The release of these factors occurs in response to increased cardiac workload, myocardial injury or defects in the contractibility of cardiomyocytes (J. Molkentin, 2000). The initial stage leading to cardiac hypertrophy is increased size and cell volume of cardiomyocytes in order to sustain the increased cardiac output demanded by the hypertrophied heart. Such a process is referred to as compensatory hypertrophy. At later stages of cardiac hypertrophy, the hypertrophied heart can no longer keep up with the increased workload, which subjects patients to heart failure, cardiac arrhythmias and sudden death (Berenji et al., 2005). It should be noted physiological cardiac hypertrophy, which occurs during pregnancy, adolescence growth and aerobic training, does not share the same detrimental consequences on cardiomyocytes as pathophysiological heart growth (Oakley, 2001). A characteristic of pathologically hypertrophied hearts is cardiomyocyte disarray, which is a disorder of heart cells. Misaligned cardiomyocytes prompts a disruption in the conduction of action potentials across cells, leading to compromised intracellular Ca2+ kinetics and decreased shortening of the sarcomere, which ultimately compromises the contractions of the heart. The molecular signaling pathways, responsible for cardiac hypertrophy, are being extensively studied by researchers with the hopes of developing therapies to treat cardiac hypertrophy. Calcineurin-NFAT signaling pathway The availability of intracellular calcium (Ca2+) in mammalian cells is critical for their existence and proper function. In addition to its role in muscle cell electrophysiology and contraction, Ca2+ acts as a secondary messenger in many signal transduction pathways, involved in physiological processes such as fertilization, memory, apoptosis, membrane trafficking and cell division (D. M. Bers, 2008). Furthermore, at the molecular level, Ca2+ has been implicated in regulation of gene transcription, DNA replication, DNA repair and both protein synthesis and degradation. A common question in muscle cell biology is that, with its numerous downstream targets, how does Ca2+ specify and activate a particular signaling pathway. It is generally understood that Ca2+ influxes into the cytoplasm through Ca2+ transporters on the sarcolemma as waves of Ca2+. In the 1990s, researchers have identified that depending on the amplitude and frequency at which Ca2+ waves penetrate the cell, different Ca2+-dependent signaling pathways are activated, which also affects gene expression and cell differentiation (Berridge, 1997; Dolmetsch et al., 1997; Dolmetsch et al., 1998). However, the exact molecular mechanisms in which specific Ca2+-dependent pathways in contracting cardiomyocytes are regulated remains disputed due to the highly specialized rhythmic cycling of Ca2+ involved in the hearts ECC. Molkentins group have postulated the existence of Ca2+ microdomains in the cytoplasm, which are relatively independent of the Ca2+ involved in the ECC. Within these microdomains , Ca2+ is locally regulated and can activate protein signaling pathways in that particular region (Houser et al., 2008). Many proteins that require Ca2+ to be active cannot readily bind Ca2+, thus use Calmodulin (CaM), a high affinity Ca2+-binding protein, as a Ca2+ sensor and signal transducer. Expressed in all eukaryotic cells, CaM is a 17kDa protein composed of four EF-hand motifs, each capable of binding a single Ca2+ ion. The affinity to which Ca2+ binds CaM depends on changes in intracellular Ca2+ concentrations. When cytoplasmic Ca2+ level are low, CaM exists in a closed conformation, where the EF-hand motifs are packed together, hiding the Ca2+ binding sites. Alternatively, when intracellular Ca2+ level are high, Ca2+ ions bind to the EF hand motifs on CaM, causing a conformational change that allow Ca2+ to bind more readily to the other motifs, allowing CaM to attain an open configuration (Chin et al., 2000). Because CaM is a small, flexible molecule with numerous targets, such conformational changes are required to expose specific hydrophobic regions on each domain, which allow the Ca2+-CaM c omplex to bind and activate specific proteins (Al-Shanti et al., 2009). One of the most recognized signaling pathways that require the Ca2+-CaM complex to be activated is the Calcineurin Nuclear Factor of Activated T-Cells cascade. Calcineurin (Cn), also referred to as protein phosphatase 2B (PP2B), is a Ca2+-dependent serine/threonine phosphatase that was first discovered in 1979 as a CaM binding protein in brain extracts (Klee et al., 1979). Further research by Schreibers group identified that Cn played a prominent role in the immune system, where the addition of immunosuppressive drugs, cyclosporine A (CsA) and FK506, decreased Cns activity (Liu et al., 1991). Cn is ubiquitously expressed in all cells and the gene that encodes the Cn protein is conserved from yeast to mammals, suggesting a common mode of regulation (Al-Shanti et al., 2009; Rusnak et al., 2000). Once active, Cn can de-phosphorylate a number of transcription factors such as myocyte enhancer factor 2 (MEF2), nuclear factor kappa-light-chain-enhancer of activated B cells (NFÃŽ ºB) and nuclear factor of activated T-cells (NFAT) (Alzuherri et al., 2003; Blaeser et al., 2000; Jain et al., 1993; Michel et al., 2004). In addition to transcription factors, Cn has been identified as a direct regulator of the pro-apoptotic factor, Bcl-2 (Wang et al., 1999). The most characterized downstream target of Cn is the family of NFAT transcription factors. In the heart, the role of the Cn-NFAT signaling pathway in mediating pathological cardiac hypertrophy in vitro and in vivo has been extensively studied (Bueno et al., 2002; De Windt et al., 2001; Hill et al., 2002; Molkentin et al., 1998; Sussman et al., 1998; Zou et al., 2001). Once de-phosphorylated, NFAT transcription factors translocate to the nucleus and dimerize with other transcription factors to re-activate cardiac fetal genes, leadin g to hypertrophy of the adult heart. The structure of Calcineurin Human Cn was first crystallized in 1995 by the Villafranca group (Kissinger et al., 1995). Although it shares similar sequence homology to other serine/threonine protein phosphatases, PP1 and PP2A, the structure of Cn was found to be unque due to its dependence on Ca2+ for optimal activity (Griffith et al., 1995; Kincaid et al., 1988; Klee et al., 1988). From its structure, it was discovered that Cn exists as a heterodimeric protein, consisting of two subunits: the 59kDa catalytic subunit, calcineurin A (CnA), and the 19kDa regulatory subunit, calcineurin B (CnB) (Kissinger et al., 1995). The structure of CnA consists of two domains: a catalytic region which is found on the N-terminal and the regulatory domain which is present on the C-terminal region (Al-Shanti et al., 2009). The regulatory domain of CnA consists of three sub-domains: a CnB binding domain), a CaM binding domain) and an autoinhibitory domain (AI) as depicted in Figure 1.4 (Ke et al., 2003; Klee et al., 1998). Alternatively, the structure of CnB shares a 35% sequence identity to CaM and contains four EF-hand motifs, allowing it to bind Ca2+ ions in a similar mechanism as CaM (Klee et al., 1988; Kretsinger et al., 1973). In non-stimulated muscle cells, Cn is present in its inactive conformation, in the cytoplasm, where the autoinhibitory domain sterically blocks CnAs catalytic domain, rendering the phosphatase inactive. Upon stimulation, cytoplasmic Ca2+ will bind CnB, causing a conformational change, which exposes the CaM binding domain on CnA. Once the Ca2+-CaM complex docks onto its respective binding domain, another conformation change occurs which displaces the autoinhibitory domain from the catalytic domain, enabling the enzyme to be active. The crystal structure of full length human Cn was solved with a resolution of 2.1Ç º. The globular structure of CnA consists of 521 residues, where residues 14-342 form the catalytic domain and residues 343-373 form the CnB binding helical domain (Kissinger et al., 1995). Residues 374-468 and 487-521 are not visible in the crystal structure because they are presumed to exist in a random conformation(Ke et al., 2003). The AI domain is represented by a segment of 18 residues (Ser469-Arg486) that lie over the substrate-binding cleft on the C-terminus of CnA. The AI domain consists of two conserved short ÃŽ ±-helical domains, with five additional residues in its extended form. The residues of the AI domain that have the strongest interactions with the substrate-binding cleft of CnA were identified as Glu481-Arg-Met-Pro484, where Glu481 hydrogen-bonds with water molecules bound to the dimetal site in Cns active site (Kissinger et al., 1995). Residues 343-373 form an extended amphipathic ÃŽ ±-helical region that interacts with hydrophobic residues within the CnB binding cleft. In mammals, CnA is encoded by three genes (CnAÃŽ ±, CnAÃŽ ², CnAÃŽ ³) and CnB by two genes (CnB1, CnB2). Yet in the heart, only CnAÃŽ ±, CnAÃŽ ² and CnB1 are expressed (J. Molkentin, 2000). NFAT proteins NFAT transcription factors were first identified by the Crabtree group where, similar to Cn, NFAT played an important role in the regulation of early T-cell activation genes (Shaw et al., 1988). Since its discovery, researchers have provided evidence that the role of NFAT proteins was not restricted to T-cells, having been implicated in the central nervous system, blood vessels, heart, kidney, bone, skeletal muscle and haematopoietic stem cells (Crabtree et al., 2002; Graef et al., 2001; Hogan et al., 2003; Kiani et al., 2004; Macian, 2005). NFAT proteins are part of the Rel-family of transcription factors. The molecular mass of NFAT ranges from 70-200kDa, which is due to alternative splicing of genes resulting in varying protein sizes and differential phosphorylation states (van Rooij et al., 2002). The primary structure of NFAT consists of a moderately conserved N-homology region (NHR), a conserved Rel-homology region (RHR) and a non-conserved C-terminal domain (CTD). Firstly, the NHR (residues 1-407) contains a transactivation domain (TAD), a Cn docking site, a nuclear localization signal (NLS), a nuclear export signal (NES), serine-rich regions (SRR) and Ser-Pro-X-X-repeating motifs (SP), where X denotes any amino acid. The TAD is required for NFAT to bind the promoter region of genes to initiate transcriptional events. The Cn docking domain contains a SPRIEIT sequence, a variant of PxIxIT, which allows Cn to bind to NFAT and de-phosphorylate serine residues, mediating the nuclear shuttling of NFAT. Secondly, the RHR (residues 408-677), which is conserved among all Rel proteins, confers to a shared DNA binding specificity (L. Chen et al., 1998). The C-terminus of the RHR contains a DNA binding motif, which permit Rel-proteins to bind the 5-GGAAA-3 consensus sequence (Rao, 1994). The N-terminus of the RHR contains a domain that allows NFAT to interact with other transcription factors in the nucleus. Such molecular partners include the leucine zipper protein activator protein-1 (Fos, Jun), the Zn-finger protein GATA-4, the MADS box protein MEF2 and many others (L. Chen et al., 1998; Crabtree et al., 2002; Hogan et al., 2003; Molkentin et al., 1998). Lastly, although the exact role of the CTD (residues 678-928) remains ill defined, due to the differences in the length of the CTD between NFAT isoforms, it is possible that the CTD is responsible for the different transcriptional activity of the NFAT isoforms, as shown by several groups (Calabria et al., 2009; Rinne et al., 2010). NFAT transcription factors are ubiquitously expressed and consists of five isoforms: NFATc1, NFATc2, NFATc3, NFATc4 and NFAT5 (also known as tonicity-responsive enhancer-binding protein or TonEBP) (Mancini et al., 2009). Of the five NFAT proteins, only NFATc1, NFATc2, NFATc3 and NFATc4 are regulated by Ca2+-Cn signaling and are have known roles in skeletal and cardiac muscles (Calabria et al., 2009; van Rooij et al., 2002). NFAT5 cannot interact with Cn due to the absence of a SPRIEIT domain and is therefore insensitive to Ca2+-Cn signaling (Lopez-Rodriguez et al., 1999). Rather, NFAT5 is regulated by osmotic stress and is known to control the expression of cytokines, such as tumor-necrosis factor (TNF) and lymphotoxin-ÃŽ ², in lymphocytes (Lopez-Rodriguez et al., 2001; Macian, 2005). Due to its insensitivity of Cn and unclear roles in muscle cells, for the remainder of this thesis, the focus will be on the Ca2+-Cn regulated NFAT isoforms: NFATc1, NFATc2, NFATc3 and NFATc4. The cellular localization of NFAT proteins depend on the phosphorylation state of approximately 14 serine residues on the NHR. Okamura et al. identified that of these residues, 13 phosphoserines are targeted by Cn and are located in motifs SRR1, SP2 and SP3 (Macian, 2005; Okamura et al., 2000). Upon de-phosphorylation, the NLS sequence of NFAT is exposed and the NES is masked, prompting nuclear entry. NFAT kinases are regulators of NFAT transcription factors, which can interact with NFAT and reversibly phosphorylate the same serine residues that are targeted by Cn. Known NFAT kinases include casein kinase-1 (CK-1), glycogen-synthase 3ÃŽ ² (GSK3-ÃŽ ²), p38 and JUN-N-terminal kinase (JNK) (Beals, Sheridan et al., 1997; Chow et al., 1997; Gomez del Arco et al., 2000; Zhu et al., 1998). Upon re-phosphorylation, the NES sequence is re-exposed whereas the NLS sequence is hidden, prompting cytoplasmic retention of NFAT (Okamura et al., 2000). These kinases can either be classified as mainte nance kinases, which phosphorylate NFAT in the cytosol to prevent nuclear import or export kinases, which target NFAT in the nucleus to promote nuclear export. Each kinase can phosphorylates serine residues on specific motifs. CK-1 acts as both an export and maintenance kinase on SRR1 of NFATc2 (Okamura et al., 2004). GSK3-ÃŽ ² functions as an export kinase on both SP2 and SP3 of NFATc1 and SP2 on NFATc2 (Beals, Clipstone et al., 1997; Macian, 2005). The mitogen activated protein kinase (MAPK) family consists of p38, JNK and extracellular-regulate-signal kinases (ERK) and can phosphorylate the first serine of SRR1 on different NFAT isoforms. JNK phosphorylates NFATc1, whereas p38 targets NFATc2 (Chow et al., 1997; Gomez del Arco et al., 2000). CK1 may be responsible for phosphorylating the remaining serines on SRR1 (Macian, 2005). Although a cell may have the potential to translate different NFAT isoforms, depending on which NFAT kinase is expressed, only certain NFATs may be nuclea r localized. Cn-NFAT signaling in cardiac hypertrophy Cn-NFAT signaling is described as a multifunctional regulator, where its function depends on the cell type in which this pathway is active. In the brain, Cn-NFAT signaling mediates numerous processes, which include memory, brain strokes, ischemic injury, Parkinson and Alzheimers disease and the regulation of the cAMP-response-element binding protein (CREB) (Shibasaki et al., 2002). In the lungs, Cn-NFAT signaling has been implicated in the perinatal lung maturation and function, and regulating genes involved in the homeostasis of pulmonary surfactant, which is required for proper breathing (Dave et al., 2006). In skeletal muscles, this pathway is required for functional-overload induced skeletal muscle hypertrophy and for mediating skeletal muscle-fiber type conversions from fast muscle fiber type to slow muscle fiber type (Dunn et al., 1999; Michel et al., 2004). In the cardiovascular system, Cn is required for the early development of the heart, specifically the cardiac septum and valves (de la Pompa et al., 1998; Ranger et al., 1998). During heart disease, Cn-NFAT signaling promotes the reactivation of cardiac fetal genes, which are responsible for cardiac growth during development. The reactivation of these genes in the adult heart is responsible for the pathological growth of the heart, and not physiological growth (Wilkins et al., 2004). In 1998, Molkentin et al. first reported the novel role that Cn-NFAT signaling played in mediating pathological cardiac hypertrophy (Molkentin et al., 1998). Among the major findings of this report was that Cn-induced the de-phosphorylation of NFATc4, prompting its nuclear entry and allowed NFATc4 to interact with the GATA-4 transcription factor, leading to cardiac hypertrophy. In addition, cultured cardiomyocytes, treated with Cn inhibitors CsA and FK-506 immunosuppressive drugs, blocked chemical-induced cardiac hypertrophy. To support their in vitro findings, transgenic mice that expressed a cardiac-specific constitutively active form of CnA were generated. The hearts of CnA overexpressing transgenic mice, compared to the hearts of wild-type counterparts, displayed a 2-to-3 fold increase in heart weight-to-body weight ratio, a thickening of the left ventricular wall and intraventicular septum, a 2-fold increase in cross-sectional area of cardiomyocytes and extensive fibrosis. Furth ermore, CnA overexpressing mice had a greater increased susceptibility to sudden death, mimicking the effects of heart failure in humans. Upon treatment with the Cn inhibitor, CsA, the hearts of CnA transgenic mice returned to normal size. Many genes and proteins that are re-employed in response to heart disease have prominent functions in embryonic and fetal heart development. For example, cardiac fetal genes are active during the physiological growth in developing hearts. This family of genes consists of atrial natriuretic factor (ANF), b-type natriuretic peptide (BNP), ÃŽ ±-myosin heavy chain (ÃŽ ±-MHC), ÃŽ ²-myosin heavy chain (ÃŽ ²-MHC), and many others (Oka et al., 2007). When the heart has fully matured into an adult heart, the expression of these genes becomes dormant. During heart disease, hypertrophic stimuli re-activate the expression of these genes in the adult heart, which enables the heart to grow to a pathological state. One of the most studied transcription factor that interacts with NFAT to initiate cardiac hypertrophy are GATA proteins. GATA transcription factors consist of two conserved zinc fingers that are required to bind to the consensus DNA sequence 5-(A/T)GATA(A/G)-3, as well as domains that allow GATA to interact with transcriptional cofactors (Ko et al., 1993; Merika et al., 1993; Oka et al., 2007). Of the six members of the GATA family (GATA-1 to GATA-6), GATA-4, GATA-5 and GATA-6 are expressed in the heart (J. D. Molkentin, 2000). Among the GATA proteins expressed in the heart, GATA-4 has been associated with embryonic cardiogenesis, such as heart tube formation, and pathological growth of the adult heart (Molkentin et al., 1997; Pikkarainen et al., 2004). In addition, GATA-4 is a known regulator of the expression of cardiac structural genes during development. GATA-4 gene targeted mice were embryonic lethal at E7-9.5 due to structural and functional defects of the heart (Molkentin et al., 1997). Alternatively, cultured cardiomyocytes overexpression of GATA-4 caused a 2-fold increase in cell surface area, whereas GATA-4 overexpressing transgenic mice lead to increased heart-weight-to-body weight ratio, cardiomyopathy features of the cells and upregulation in the expression of cardiac fetal genes (Liang, De Windt et al., 2001). The regulation of GATA-4 occurs post-translationally, where such modifications affect its DNA binding ability, transcriptional activity and cellular localization. A number of chemical stimuli that induce cardiac hypertrophy have been associated with the phosphorylation of GATA-4, which increases both its DNA binding and transcriptional activity (Oka et al., 2007; Pikkarainen et al., 2004). Molkentins group identified that phosphorylation of Ser105 on GATA-4 by the ERK1/2 and p38 MAPK was responsible for GATA-4 increased DNA binding affinity and transactivation during heart failure (Charron et al., 2001; Liang, Wiese et al., 2001). Another kinase that targets GATA-4 is GSK3-ÃŽ ², a known negative regulator of cardiac hypertrophy (Haq et al., 2000). GSK3-ÃŽ ²-mediated phosphorylation of GATA-4 prompts its export from the nucleus, rescuing Cn-mediated cardiac hypertrophy (Morisco et al., 2001). A second family of transcription factor that is re-activated during heart disease is the myocyte enhancer factor 2 (MEF2). There are four members of the MEF2 family expressed in vertebrates: MEF2A, MEF2B, MEF2C and MEF2D. MEF2 proteins can either homodimerize or heterodimerize with other transcription factors such as NFAT and GATA, which can then bind to the DNA sequence 5-CTA(A/T)4TAG-3 to carry out transcriptional events (Blaeser et al., 2000; McKinsey et al., 2002; Morin et al., 2000; Oka et al., 2007). Although the MEF2 proteins are expressed in most cell types, their transcriptional activity is restricted to the immune system, neurons and contractile muscle cells (Akazawa et al., 2003). In the heart, MEF2 have critical roles in cardiac differentiation. MEF2C null mice were embryonic lethal, due to cardiac looping defects, an absence of a right ventricle and a downregulation of cardiac structural genes (Bi et al., 1999; Lin et al., 1997; Oka et al., 2007). The majority of MEF2A null mice died 2-10 days after birth because of defects in conduction and architecture of the heart. Surviving MEF2A null mice displayed reduced mitochondrial content and a less efficient conductive system. (Naya et al., 2002). In addition, transgenic mice that express a dominant negative MEF2 died shortly after birth because of cardiomyocyte hypoplasia, thinning of the ventricular walls and heart chamber dilation (Kolodziejczyk et al., 1999; Oka et al., 2007). A greater workload imposed on the heart, a phenotype of cardiac hypertrophy, has been associated with increased MEF2-DNA binding (Molkentin et al., 1993; Nadruz et al., 2003). In cultured cardiomyocytes, adenoviral-mediated overexpression of MEF2A or MEF2C caused sarcomeric degeneration and cell elongation, both of which indicate cardiac dilatation. The hearts of transgenic mice overexpressing MEF2A or MEF2C were subject to contractile defects, ventricular dilation and were more readily hypertrophied when pressure overload stimulation was induced. However, when cells of the transgenic hearts were isolated, rather than having a greater cross-sectional area, the cardiomyocytes were more elliptical in shape, suggesting that MEF2 did not d

Shakespeare Finds Love On A Midsummer Night :: essays research papers

The forest outside Athens is filled with changelings, magic, and ancient myth: in other words, the stage is set. The night is silent and still as four mortals alternately hate and love, monarchs of the faerie world clash wills, and the mischief of one irrepressible woodland sprite weaves a spell over all. The breath of the darkness is lit with the glow of foxfire; hearts are broken and mended within the span of short hours. In the bower of the Faerie Queen a man transformed by magic slumbers peacefully. The pen of William Shakespeare has captured the imagination and hearts of audiences and readers alike across the world and through the decades, but his classic romantic comedy, A Midsummer Night’s Dream, offers something much more profound. Shakespeare has found insight into the heart, and, through his verse, best exemplifies the complicated and capricious emotions found there. The play, much like reality, is sprinkled throughout with gems of humor, and it will continue to fasc inate as long as there is love. Shakespeare’s characters are certainly the most important part of A Midsummer Night’s Dream. All action must be carried out through them; all ideas must be transported to the audience through their moves and dialogue. The first and most obvious characters are the four mortal lovers. The women, Helena and Hermia, are respectively tall and fair, short and dark; there are no other notable differences between them. The men, Lysander and Demetrius, have no differences in personality that are remarked upon in the text of the play. Outside the walls of Athens, inside the enchanted forest, the courts of Oberon, king of the faeries, and Titania, his queen, hold sway. The two magistrates quarrel often, but know they are meant for each other, no matter how they scowl. Their adventures include Bottom, a town actor turned into an ass by Oberon to seek revenge on Titania. The last major role in Dream is Robin Goodfellow, more commonly known as Puck. He is mischievous and playful; his role in the faerie court is to entertain Oberon and run his errands, as he tells the faeries in Act 2 when he is introduced. In human nature and all its facets, there is a certain amount of inherent mirth, including sarcasm, and Shakespeare does not neglect this mirth in his writing. First, humor is used as a sort of release valve.

Philosophical Pluralism in the Service of Humane Governance :: Philosophy Philosophical Essays

Philosophical Pluralism in the Service of Humane Governance ABSTRACT: In recent times, the American Philosophical Association has been exposed in a serious way to the issue of pluralism in philosophy curriculums in the departments of philosophy of American universities and colleges. This conversation brings to the fore the fact that what is at issue in the prospect of pluralizing American philosophy departments is not merely the matter of deciding the discipline's boundaries of intellectual formation relative to the current generation of students, but the unforeseeen consequences of pluralism which challenge both 'the American canon' and the profession's self-understanding vis-Ã  -vis a 'Western' intellectual heritage that distinguishes the 'essential' from the 'marginal' by privileging essential figures, problems, and time-honored methodological commitments. Yet, to the degree that there is a quest for relation of differences, this need not presuppose the universality of philosophical discourse, comparative philosophy moving inevitably with in a logic of opposition rather than a logic of mutuality. Our thinking is surely problematic if at this World Congress we find an occasion for a confrontation between 'the West' and 'the margin,' the latter construed negatively as a 'mute, growing and menacing pressure.' In recent time the American Philosophical Association has been exposed in a serious way to the issue of pluralizing the philosophy curriculum in the departments of philosophy of American universities and colleges. John Lachs, Philip Quinn, John Stuhr, and Kathleen Wright each contributed thoughtful discussions to the "issues in the profession" section of the November 1996 Proceedings and Addresses. (1) As Lachs observed, there are those who conceive pluralism to mean "due representation of the analytic, Continental, and American philosophical traditions". Others who have explicit concern with the developing "sub-discipline" of comparative philosophy conceive pluralism to include "work in the complex traditions of Chinese, Indian, African, Latin American, Islamic, Jewish, feminist, and Native American thought, as well". Quinn perhaps speaks for a majority of philosophers when he suggests that hardly anyone would deny that "it is a good thing to expose students to the many ways in which philosophy has been done in various places and at different times", that "it is a good thing to carry forward philosophical inquiry in the many traditions that have proved to be of enduring value". Thus Quinn favors a more inclusive pluralism, one which "would consist of a conversation that contains many more non-Western philosophical voices". Notwithstanding Quinn's hopeful remarks, Stuhr noted that today pluralism is not widely endorsed.

The Complex Process of Selecting a Pair of Shoes Essay -- Research Ess

The Complex Process of Selecting a Pair of Shoes I plan to prove that the majority of people that invest money into footwear do so because of style. People usually don’t choose a pair of shoes because of comfort, color, or any other means at all. They usually base their decision of purchasing a pair of shoes on style. There are three tools that I will use during this experiment that will help me out. These tools will be comprised of surveys, interviews, and observations. Through survey’s I will have a sheet of paper with approximately eight questions on it. These questions range from the subjects personal preference when it comes to purchasing a pair of shoes. Whether they do it for comfort, style, color, work related, price, or even none of the above at all, to how many pairs of shoes that these individuals currently own. This will give me a general idea of what goes through peoples minds when they purchase a pair of shoes. Then I will use my observation skills. I plan to sit in the mall since it’s t he best public place for this experiment, and observe what brand, color, and style of footwear the general public wear. I will more than likely sit in front of Finish Line since they are one of the major footwear sales stores in the country. This will show me exactly what people choose to wear, but won’t tell me why. Since I wouldn’t know why they wear them I plan to interview a couple of volunteers to get their opinion. This plus the rest of my research will give me a good idea of what people choose to wear, and why. I’m going to pick a few individuals from the public that seem to keep â€Å"shoes† an important part of their lives. I will ask them the same questions that are on my survey plus a few more that will go int... ... and style go hand in hand. He said people prefer one brand name against another because of the way they look. On the other hand I interviewed a girl who said that she would buy any pair of shoes as long as it was cheap and looked nice. She said she had no real preference, and owned a lot of shoes. Price was her deciding factor and no matter how it looked, what the brand name was, or even the color, she wouldn’t purchase it unless the price wasn’t very high, or if it was on sale. I think my observations, surveys, and interviews prove my thesis to be correct. Even though not everybody uses style for their deciding factor, the majority of people that participated in my survey, and my interview with Rob the shoe salesman concludes that style usually is the number one factor in one way or another when a person purchases a pair of shoes.

Rhetorical Analysis on Lux Toilet Soap Ad Essay

Lux Toilet Soap Susan Sanders Devry University Lux Toilet Soap A 1954 ad for Lux Toilet Soap states, â€Å"Luscious is the word for Greer Garson’s complexion and she keeps it that way with Lux Toilet Soap. †This statement is an example of how emotional appeal is used in the ad to grab the reader’s attention. The advertiser uses character appeal by including information about Garson’s success in the ad to make the reader want to use the product. Logical appeal is used when a refund is offered to leave the reader with no objections to trying the product. The Greer Garson Lux Toilet Soap ad was effective in raising product awareness and profits due to its usage of these appeals. Garson is pictured against a white background with a vine of grapes in hand in the ad. Purple is the color theme here, as Garson’s eye makeup, necklace and grapes are of this color. This gives the ad a sense of sophistication, warmth, luxury and even a little mystery. This grabs the reader’s attention and makes her want to read the ad. The reader’s attention is then drawn to a sentence below Garson in which the first word, â€Å"Luscious,† is of a larger font size than the rest of the text. The color pink draws the reader to look in the bottom right corner of the ad, where a Lux Toilet Soap wrapper reveals the bar of soap. This completes the attraction, femininity, and smooth texture of the ad. The image and larger-sized text are present in the advertisement to appeal to the reader’s emotion of craving for Garson’s flawless skin. Women of this time were open to ideas on how to look as beautiful as possible. This could have been to succeed in their careers or simply to please a man. Looks play a large role in any aspiring actresses success because she is trying to talk people into casting her for roles. In addition, having and taking care of a family was a very important part of women’s lives. They had to look their best in the hopes of getting a husband. This advertisement had their solution and informed the readers to use Lux Toilet Soap to get that desired look. If the picture of Garson wasn’t enough to get the reader to find character appeal in the advertisement, there is also smaller blue text at the bottom of the ad informing them of her credentials. The ad states, â€Å"Besides being beautiful, Greer Garson is intelligent (she’s lectured Shakespeare), talented (probably won more awards than any other film actress)†¦ † There is also a statement at the top of the ad promoting a movie Garson most recently starred in, â€Å"Her Twelve Men. † The ad then goes on to state her insistence on the use of Lux Toilet Soap in her home and dressing room, as well as the statistic â€Å"Greer’s used Lux for years now-she believes in it, like 9 out of 10 Hollywood stars do.This information about Garson’s career leads readers to trust in her belief of the soap’s effectiveness. It suggests that the reader should want to use the Lux soap because successful and beautiful people like Garson do. If it plays some part in Garson’s success, then the reader might have that same luck with life as well, after using Lux soap. As the reader continues through the text, the final appeal is utilized, logic. The ad states that â€Å"Miss Garson’s luscious complexion is as good a recommendation as we know of for using Lux Toilet Soap. If you find Lux isn’t everything a good soap can be, we’ll return what you paid for it. Fair enough? † After being presented this offer, the reader runs out of objections to trying the product. Reasoning tells them to buy it, try it, if it isn’t satisfactory, get a refund, and no loss would be incurred. The offer leaves the reader with a feeling of obligation to buying the product. It is important that the ad achieves this because it ultimately leads to higher sales profit. Lux Toilet Soap was not the only solution to uneven or imperfect complexion.

Industrialization of the United States Essay

The history of the United States of America had always been one of progress. Though the socio-political realm of the history of the nation is partially enshrouded by black veil of struggles, conflicts, and eventual changes, the economic sphere of the American history still conveys about the significant progresses the country has been making since the inception of the process of industrialization. It is noteworthy that industrialization in the United States of America opened new arenas for economic opportunity even though it was ingrained with several sociological drawbacks that included the encroachment of capitalist exploitations and resulting militant labor unionism. The industrial growth that the United States still boasts on had its inception in the early 1800’s and the progress went through the post-Civil War era. It must be noted that after the Civil War a dramatic change occurred in the realm of American industry. Machines started replacing the conventional hand labor w hich was once considered the primary means of manufacturing, and this mechanization gradually started increasing production capacity of the American industries in a tremendous manner (‘History of the United States: Industrialization and reform (1870-1916)’ n.d.). Moreover, the development of railways did fuel the process of industrialization greatly as distribution of goods to different corners of the nation far and wide became possible (â€Å"History of the United States: Industrialization and reform (1870-1916)†, n.d.). Also, it must be noted that â€Å"Inventors developed new products that the public wanted, and businesses produced the products in large quantities. Investors and bankers supplied the huge amounts of money that business leaders needed to expand their operations† (‘History of the United States: Industrialization and reform (1870-1916)’ n.d.). And all these ensured that the United States is on the right track of industrialization and economic progress. For the emergence of the process of industrialization in the United States and for its sustainability, as noticed in the history of the industrialization of other nations, iron and steel played a significant role. Iron and steel became the cornerstone of American industrialization since the Scottish immigrant, Andrew Carnegie, did build the steel industry with a mill that was responsible for integrating all stages of the iron refinement process  starting from ore to finished rails (‘American Industrialization’ n.d.). Moreover, it was due to the establishment of the iron and steel industry that it was possible for the nation to witness the development of railways, another factor which instigated American industrialization in a faster pace. In this respect it must be said that over 100,000 miles of railway track were laid between 1877 and 1893 and this process included the standardization of gauge which again initiated more developments and among the developments were the time zone adoption allowing the coordination of systems and the adoption of steel rails that were capable of bearing heavier loads (‘American Industrialization’ n.d.). The process of industrialization of America that carried on between 1870 and 1920 also paved the way for the United States to be the primary nation of choice for innumerable immigrants. It is noteworthy that in the course of American industrialization (between 1870 and 1920) â€Å"approximately 26.5 million immigrants from Asia, Latin America, and Euro pe entered all regions of the United States, with the majority settling in the Northeast and Midwest† (‘Industrializing America: Theme 2’ n.d.). Some of these migrants came to the United States to avoid political and religious persecution while some others reached the land forsaking their motherland for the sake of economic opportunity and financial prosperity (‘Industrializing America: Theme 2’ n.d.). In this relation it must be noted that, the more the immigrants gathered in the United States the more the nation’s workforce was strengthened and this strengthening also contributed significantly to the process of industrialization of the United States. And this is evident in the fact that â€Å"Using transcontinental railroads ad river boats, immigrants fanned out across the country to look for jobs: the Japanese in California’s fruit orchards, Mexicans in Colorado’s mines and beet fields, Scandinavians in western mines, Italians in iron mining camps in Missouri, and the Irish in New York factories† (â€Å"Industrializing America: Theme 2†, n.d.). But with every boon comes a ban e and this was also the case with American industrialization. The more the industries started growing the more was the degree of ill-treatment of the factory owners toward the labor class. To protect the interests of the labors different labor unions started to crop up. But despite of unionism the relation between labors and capitalists could not be improved considerably. As a result labor strife arose in the  1870s and frequent strikes started following and the unrests also encompassed tragic events like Haymarket Massacre which occurred in 1886 in Chicago when a bomb killed seven people and wounded seventy, and such incidents became frequent in the form of events like Homestead Strike in Pennsylvania in 1892 that claimed seven deaths (‘American Industrialization’, n.d.). And the tensions that were generated through these events reshaped the sociological concepts of class struggle in the United States – a concept which is still plaguing the U.S. society extensively. In conclusion, industrialization of the United States was the culmination of different factors that were combined together and functioned collaboratively. And these factors were correlated. As a matter of fact, industrialization of the United States of America opened new arenas for economic opportunity even though it was ingrained with several sociological drawbacks that included the encroachment of capitalist exploitations and resulting militant labor unionism. Bibliography ‘American Industrialization’. n.d.. Accessed October 11. http://home.earthlink.net/~gfeldmeth/lec.indust.html. ‘History Of The United States: Industrialization And Reform (1870-1916)’. n.d.. Accessed October 11. http://www.theusaonline.com/history/industrialization.html. ‘Industrializing America: Theme 2’. n.d.. http://www.learner.org/courses/amerhistory/units/14/themes/2.html.