How Material Things Contribute Towards Differences on a Street Essay Example for Free

How Material Things Contribute Towards Differences on a Street Essay Taking into consideration that ‘difference is not the same as inequality’ (Blakeley et al., 2009, p. 24), this essay intends to look at KÃâ€" and outline how the material things contribute towards differences with reference to City Road; deriving from the premise that the material assets of a street can generate either an inclusive or exclusive interaction, favouring some and not others. Kà ¶nigsalle, known by its nickname, â€Å"Kà ¶, is the most beloved upscale commercial street in Germany (Welt online, 2010). On one side of the street we have stores from the most expensive brands in the world and on the other, a mix of baroque buildings which host a different number of businesses. Being seen walking along or visiting its stores is denotative of a unique social status. Everything along the Kà ¶ is designed to be in accordance to and promote an upscale social lifestyle. The material things on City Road, while performing a more literal function, also contribute to tangible objective differences when favouring, for example, pedestrians over drivers (e.g. the red tarmac offers pedestrians an extra safety measure when crossing, while taking away space from the drivers); parking is also a critical matter, generating therefore, economic consequences for the local shops (‘Material Lives’, 2009, scene 1). Another relevant point is the fact that, City Road social appearance, along with its material assets usage, changes considerably throughout the day, making it almost a different street by nightfall (e.g. from a busy commercial street during the day to a ‘party haven’ at night, when it is taken over by young adults) (‘Making social lives on City Road’, 2009, Scene 8). Such an absolute change does not occur on the Kà ¶. On the Kà ¶, the very same material things, should not only perform the most frugal of the functions, but also be in accordance to what the street stands for, thus, being an active part of the process of creating objective tangible differences -like in City Road, as well as, subjective ones. Kà ¶ supports its image by providing the necessary visible and invisible infrastructure to sustain a busy, high-octane upscale atmosphere: The street signage is visible; there are several crossing points; clearly marked sidewalks, tarmacs and lanes favour the mobility of handicapped individuals as well as bicycles and pedestrians without deterring traffic; it is well lit; the buildings and facades are well taken care of; litter bins are everywhere and one will, for example, find plenty of parking possibilities, which as a result, allows the individual to visit the stores and restaurants and feel safe. Altogether, the material things are in perfect apparent symbiosis with its users. Separately, each material asset on the Kà ¶ objectively indicates them as being part of a regular commercial street just like City Road. When looking at them altogether, the ensemble creates a striking subjective difference. To better illustrate how the material things on both streets subjectively enforces a certain type of behaviour and attitude, take the example of an individual walking down the street wearing shorts, tank-top and flip-flops. On City Road, this individual would most likely not even be noticed. The same individual walking down the Kà ¶, would be regarded as conspicuous. The same can be applied to the type of cars circulating on the Kà ¶ or City Road, a Ferrari on the Kà ¶ would be taken for granted while on City Road it would probably stand out. Another example to consider is parking. Though there are many parking slots and options, the prices around the Kà ¶ are up to 80% more expensive than other streets in Dà ¼sseldorf (RP Online, 2011), hence, favouring the visit of the more affluent layer of the community over the lesser one. There is no sign on the Kà ¶ telling who is welcomed or not; objectively speaking everyone is welcomed, but its material things are invested with such a subjective meaning, that they set the pace and shape of the local social life, creating therefore, an alluring environment which itself dictates a whole gamut of social patterns that are absorbed and followed by the local community, consequently contributing towards differences. While City Road reveals a more inclusive image, Kà ¶ conversely manifests a more exclusive one. As we can see, each street is similar in various aspects and are designed and structured to cater and favour a specific type of person, business or activity and its material things corroborate such a process by subjectively or objectively embedding certain social patterns which will then be adopted by their users.

Cystic Fibrosis Newborn Screening

Cystic Fibrosis Newborn Screening Cystic fibrosis is a common autosomal recessive genetic disorder1. This means that to have cystic fibrosis, a person must have inherited a defective gene from each of his or her parents2. This gene is located on chromosome seven2. Absence or mutation in this particular gene results in worse performance or absence of the Cystic Fibrosis Transmembrane Conductance Regulator2. This is most commonly found in Europe, North America, and Australia1. This gene manages anion transport and mucociliary clearance in the airways1. With the failure of this function, the results are mucus retention and chronic infection in the lungs1. Nowadays, modern technology provides aid for patients with their diseases and gives them a longer and more active life. Newborn screening for cystic fibrosis is a modern technological advance which is designed to detect early signs of cystic fibrosis. Several methods under the name of the Newborn Screening are used to detect whether a newborn has cystic fibrosis or not1. These methods include immunoreactive trypsinogen (IRT) testing combined with DNA mutation analysis and the sweat chloride test1. IRT stands for Immunoreactive Trypsinogen Test. The procedure of this test is a chemical reaction. Trypsinogen is made from the pancreas, and it normally transmits to the intestines where it is activated to a form of an enzyme called trypsin. In a patient who has cystic fibrosis, the thick mucus covers the pancreatic ducts1. Therefore, trypsinogen wont reach the intestines, and the amount of trypsinogen goes up. This test runs with a blood sample, and if the results come out with a normal level of trypsinogen, then this test is reliable, but if there is a high level of trypsinogen, then more tests need to be run to find out whether the patient has cystic fibrosis or not. A sweat chloride test is the amount of chloride in patients sweat. In a patient that has Cystic Fibrosis, the sweat chloride test will result in significantly higher levels of chloride in sweat than a person that does not have cystic fibrosis due to the restricted movement of chloride. The gene mutation test is a DNA sequencing test to locate a defective gene in the chromosome. There are many different types of mutations that can cause a deficiency in the production of the CFTR protein. More than 2000 CFTR variants have been discovered1. About 15% of the identified gene variants are not associated with CF1. CFTR mutations can be classified into six classes according to their effects on protein function1. Classification is helpful because it relates to the molecular and cellular processes in gene translation and protein processing and has some useful clinical relations1. Class I, II, and III mutations are associated with no residual CFTR function and patients with these mutations on average have a severe phenotype, whereas individuals with class IV, V, and VI mutations have some residual function of CFTR protein and have a mild lung phenotype and pancreatic deficiency1. Today, different laboratories use a wide variety of panels depending on the patients need, like t he twenty-three panel or panel of seventy. The following is an example of a molecular CF test. Lab Corporation of America published a procedure for a Cystic Fibrosis molecular diagnostic3; The coding sequence of CFTR is amplified by polymerase chain reaction and each PCR product (amplicon) then sequenced bi-directionally, using Sanger sequencing methodology. CFTR Chr7(q31,2) Nucleotide Change Amino Acid Change Consequencing Zygosity Relation to Cystic Fibrosis c.1327G>T p.Asp443Tyr missense mutation homozygous recessive, associated 1. Prof J Stuart Elbom, Cystic Fibrosis, Lancet, 19-25 November 2016, Volume 388, Issue 10059, page 2519-2531 2. The Clinical and Functional Translation of CFTR(CFTR2) at Copyright 2011 US CF Foundation, John Hopkins University The Hospital for Sick Children; available at https://cftr2.org. 3. Corporation of America Published Documents   2014   available @ http://oneworld.labcorp.com/Billing/TestMaster/Resource Center/Sample Reports/C-4/Cystic Fibrosis (CF) CFTR 252763.pdf

Vitamin D Impact on the Liver and Kidney

Vitamin D Impact on the Liver and Kidney Revised vitamin D copy Sources and forms of vitamin D Vitamin D, also termed calciferol, is a fat-soluble secosteroid compound that is an essential regulatory factor for calcium and phosphate metabolism in humans and animals. Its biological functions involve a physiological action in bone formation and mineralization, muscle contraction, nerve signal modulation and transmission as well as many cellular metabolic effects in various organs. There are two forms of vitamin D that are metabolically important; vitamin D2 or ergocalciferol and vitamin D3 or cholecalciferol. The nutritional sources of both forms are limited to certain types of foods that naturally contain vitamin D and therefore it is added to some foods as a supplement. 1.1.1- Exogenous (Diet) Both forms of vitamin D (D2 and D3) are exogenously obtained in low quantities from some types of food in the diet. Vitamin D2 is rare as it is produced from fungal and plant sources such as mushrooms and cereals, as a result of irradiation, by ultraviolet photons, of the plant sterol ergosterol. When these foods are ingested, ergocalciferol is absorbed into the blood. Vitamin D3 , on the other hand, is available in very low amounts from animal sources including oily fish such as salmon and mackerel; other sources include meat, liver, cheese, cod liver oil, eggs and fortified foods such as margarine and milk (Holick, 2006; Engelsen et al., 2005; Nowson et al., 2004). Farmed salmon, for example, contains only 25% of the vitamin D levels present in wild salmon, however, the amount of vitamin D in canned food may affected by modern processing methods (Chen et al., 2007). 1.1.2- Endogenous In humans the principal precursor of vitamin D3 is cholesterol which is obtained from the diet. Cholesterol is initially converted to 7-dehydrocholesterol, provitamin D3, through the action of enzymes termed the mucosal dehydrogenase complex, present in the small intestine. Provitamin D3, is then incorporated within chylomicrons and transported to the skin where temperature dependent photoisomerisation processing of 7-dehydrocholesterol takes place in epidermal cells resulting in the production of D3. Within the epidermal cells, vitamin D3 undergoes photocoversion to its isomers 5,6-transvitamin D3 and suprasterol, a process which relies on the amount of ultraviolet radiation absorbed; inadequate sunlight exposure compromises this process (Holick, 2003; Iqbal, 1994). Sunlight exposure is therefore a crucial element in the regulation and enhancement of endogenous cholecalciferol production (Dusso, et al., 2005; Iqbal, 1994; Reichel, et al., 1989; Smith, 1988). Once photoconversion is completed, cholecalciferol binds to Vitamin D Binding Protein (VDBP) and transported to the liver for further metabolic processing. Vitamin D metabolism Both forms of vitamin D (D2 and D3) undergo similar metabolic activation in the liver and kidney respectively to produce the physiologically active form 1,25-dihydroxyvitamin D3. 1.2.1- Skin The skin is characterized by two layers, the outer epidermal region, consisting of several strata, and the inner dermal layer. Skin exposure to UVB rays in sunlight, characterized by a wavelength of 290 nm to 315 nm, allows the initial steps of vitamin D synthesis to occur using the substrate 7-dehydrocholesterol (7-DHC) as illustrated in step 1 of Figure 1. UVB absorption by 7-DHC is thought to occur actively in the stratum basale and stratum spinosum regions of the epidermal layer. The substrate 7-DHC is an important intermediate of cholesteryl ester biosynthesis from squalene. During the reaction, 7-DHC forms procholecalciferol through B ring opening of the steroid structure. This transition state is relatively unstable and can further undergo photocatalyzed reactions to form lumisterol and tachysterol (Wolpowitz and Gilchrest, 2006). Lumisterol and tachysterol have been shown to prevent vitamin D reaching intoxicating levels and do not have any direct vitamin D effects (Bouillon et al., 1998). In addition to this protective mechanism, previtamin D poisoning is also prevented because this is an equilibrium reaction that allows cholecalciferol to revert back to 7-DHC (Webb, 2006). Cholecalciferol (previtamin D3) is produced upon double bond rearrangement of procholecalciferol and remains in the extracellular space where it becomes bound to the ubiquitous VDBP (Holick, 2005). Figure1. Sources and steps of vitamin D synthesis in the three major sites: skin, liver and kidney (Figure obtained from Wolpowitz and Gilchrest, 2006). 1.2.2- Liver Cholecalciferol that has been transported to the liver undergoes the first step of its bioactivation, the hydroxylation of carbon 25 (Dusso, et al., 2005) by two hepatic enzymes; the microsomal and mitochomdrial 25-hydroxylases (Deluca et al., 1990). In hepatic cellular microsomes and mitochondria, vitamin D3 is hydroxylated at carbon 25 and transformed to 25-hydroxyvitamin D3 by both 25-hydroxylase enzymes. This enzyme complex requires the presence of essential catalytic cofactors including nicotinamide adenine dinucleotide phosphate (NAPDH), flavin adenine dinucleotide (FAD), ferredoxin and molecular oxygen for this reaction to proceed (Sahota and Hosking, 1999; Ohyama et al., 1997; Kumar, 1990). Recently, large numbers of hepatic cytochrome P-450 enzymes exhibiting 25-hydroxylase action have been identified in vitamin D activation pathways; these enzymes include CYP27A1, CYP3A4, CYP2D25 and CYP2R1 (Dusso, et al., 2005; Cheng et al., 2003; Sawada et al., 2000). However, CYP2R1 is b elieved to be the principal enzyme in the hepatic pathway and the presence of a genetic mutation in its gene may compromise the outcome of this process; both CYP27A1 and CYP2D25 demonstrate high capacity and low affinity features, therefore, their activity is considered insignificant in this pathway (Dusso, et al., 2005; Cheng et al., 2003; Sawada et al., 2000). This metabolic step is inefficiently regulated, i.e. the levels of 25-hydroxy vitamin D are elevated as dietary intake of vitamin D increases. Consequently, over 95% of 25-hydroxyvitamin D in serum circulates as 25-hydroxyvitamin D3 which has a half-life of approximately three weeks, and is therefore used in the assessment of vitamin D status (Dusso, et al., 2005; Reichel et al., 1989). The metabolically inert 25-hydroxyvitamin D3 is then transported to the kidney for the second step of its bioactivation. 1.2.3- Kidney The second step of vitamin D3 bioactivation takes place at the proximal convoluted tubule of the kidney. Hydroxylation occurs at C-1 of 25-hydroxyvitamin D3 whereby the highly active 25-hydroxyvitamin D3 1-ÃŽ ±-hydroxylase (CYP27B1) incorporates a hydroxyl group to Carbon-1 of the first ring to form the biologically active metabolite 1,25-dihydroxyvitamin D3 (Holick,2006; Dusso, et al., 2005; Deluca et al, 1990; Reichel, et al., 1989). The high activity of 1-ÃŽ ±-hydroxylase (CYP27B1) present in kidney is not unique to this organ and can also be found in some other organs (Bouillon, 1998). The renal hydroxylation of 25-hydroxyvitamin D3 is the rate-limiting step in the production of 1,25-dihydroxyvitamin D3 and is well regulated. An alternative pathway of hydroxylation of 25-hydroxyvitamin D3 within renal mitochondria takes place at Carbon-24 to form 24,25-dihydroxyvitamin D3 which is metabolically inert. This process is catalyzed by renal 24-ÃŽ ±-hydroxylase in response to 1-ÃŽ ±-hy droxylase suppression. However, 24-ÃŽ ±-hydroxylase not only initiates the attachment of the hydroxyl group at Carbon-24 but also enhances the dehydrogenation of 24,25-dihydroxyvitamin D3 and hydroxylation at Carbon 23 and 26 (Sahota and Hosking, 1999; Bouillon, 1998; Reichel, et al., 1989). Renal hydroxylases require the presence of catalytic cofactors that enhance their synthetic activities during this process. Figure 2 shows the details of vitamin synthesis including the enzymes and cofactors required for each step. Figure2. Enzymes, cofactor and intermediates compounds of vitamin D metabolism (Bouillon et al. 1998) 1.2.4- Regulation of vitamin D metabolism Numbers of factors have been demonstrated to be important in the regulation of vitamin D metabolism; particularly significant its regulation through renal production. The factors involved in this regulation comprise parathyroid hormone (PTH), calcitonin, dietary calcium and phosphate, insulin and insulin-like growth factor and 1,25-dihydroxyvitamin D3 itself (Holick,2006; Deluca, 2004; Sahota and Hosking, 1999). Key interactions of vitamin D with its receptor are known to initiate gene regulation. These mechanisms have been studied using vitamin D analogues which have revealed the mechanism of assembly of transcriptions factors and promotion of gene regulation by this molecule (Cheng et al., 2004; Wu et al., 2002). Figure 3 shows the effect of various regulators on vitamin D metabolism. Figure 3: Alternate pathway for vitamin D3 under different metabolic conditions of low mineral Ca and P levels, PTH concentration and secretion of GH / IGH (Figure obtained from Gomez, 2006). 1.2.4.1- Parathyroid Hormone Parathyroid hormone (PTH) is the primary regulator of renal 1,25-dihydroxyvitamin D3 formation (Holick, 2006; Dusso et al., 2005; Bouillon et al., 1998; Issa et al., 1998). PTH regulates 1,25-dihydroxyvitamin D3 production directly through enhancing 1-ÃŽ ±-hydroxylase activity within kidney cells and increasing the genetic transcription rate of renal proximal tubular 1-ÃŽ ±-hydroxylase both of which result in an increase in the renal 1,25-dihydroxyvitamin D3 production rate. High levels of 1,25-dihydroxyvitamin D3 suppress the enzyme transcription activity and PTH concentration. Thus, renal 1,25-dihydroxyvitamin D3 has a negative feedback response on PTH secretion, providing an efficient regulatory control of renal 1,25-dihydroxyvitamin D3 homeostasis (Dusso, et al., 2005; Holick,2003; Sahota and Hosking, 1999; Reichel, et al., 1989; Iqbal, 1994). 1.2.4.2- Calcium Dietary calcium exhibits a direct regulatory influence on renal 1-ÃŽ ±-hydroxylase activity via fluctuating serum calcium concentration and indirectly via its effect on serum PTH concentration. Calcium exerts its effect through calcium-sensing receptor (CaR) activation within the parathyroid gland and renal proximal tubules cells in response to low calcium concentration. Thus, the low intracellular calcium levels lead to increased production of 1,25-dihydroxyvitamin D3 within renal cells (Ramasamy, 2006; Bland et al., 1999; Chattopadhyay et al., 1996). On the other hand, it has been shown that high calcium concentrations markedly impair renal 1,25-dihydroxyvitamin D3 formation in human nephrotic cell cultures and in parathyroidectomised animals (Bland et al., 1999; Chattopadhyay et al., 1996). An increase in extracellular calcium indirectly suppresses 1,25-dihydroxyvitamin D3 production at the proximal convoluted tubule by inhibiting PTH release (Deluca, 2004; Carpenter, 1990). Howev er, the detailed mechanism of calcium-sensing receptors (CaR) activation is not yet fully understood (Dusso, et al., 2005; Hewison, et al., 2000). 1.2.4.3- Phosphate Dietary phosphate intake and serum phosphate concentrations exhibit regulatory effects on 1,25-dihydroxyvitamin D3 production in proximal renal tubules. This effect has been demonstrated in several studies which showed that a decrease in dietary phosphate accelerated renal formation of 1,25-dihydroxyvitamin D3, but did not directly affect 1, 25-dihydroxyvitamin D3 catabolism. Conversely, elevated serum phosphate and increased phosphate intake led to decreased production of 1, 25-dihydroxyvitamin D3 (Carpenter, 1989; Reichel et al., 1989). Several studies have shown that inorganic phosphate levels have no significant direct effect on mitochondrial 1-ÃŽ ±-hydroxylase activity in cultured renal cells in the short term, suggesting that the action of inorganic phosphate is not mediated via changes in PTH and Calcium concentrations and is possibly inducted by other hormones such as growth hormone, insulin and insulin-like growth factor (Khanal et al., 2006; Dusso et al., 2005; Carpenter, 1 989). In recent studies, fibroblast growth factor 23 (FGF-23), frizzled-related protein 4 (FRP-4) and matrix extracellular phosphoglycoprotein (MEPE) have all been identified as potent and key regulatory factors of 1-ÃŽ ±-hydroxylase activity in renal cells. These factors act through a biphasic mechanism on renal phosphate homeostasis and modulate the circulating levels of 1, 25-dihydroxyvitamin D3 produced by proximal renal tubules (Dusso et al., 2005; Inoue et al., 2005; Mirams et al., 2004). 1.2.4.4- Calcitonin Calcitonin belongs to a family of calcium regulating hormones that is produced in the parafollicular cells of the thyroid gland, also known as C cells. It is a short and linear polypeptide with a molecular weight of only 3.7 kD. It is characterized by 32 amino acids and a disulfide bridge in the N terminal portion of the peptide. Calcitonin is secreted in response to increased free Ca2+ in blood and acts on osteoclasts, the bone resorbing cells, as a suppressor of bone dissolution. Although calcitonin decreases Ca+2 and inorganic phosphate in blood, it also has the ability to recruit phosphorus into other cells. In addition to these metabolic functions, it is also involved in the upregualtion of CYP27B hydroxylase through the protein kinase C pathway (Yoshida et al., 1999) via a phosphorylation cascade that activates cAMP and induces the expression of hydroxylase thereby activating the transformation of 25(OH) D3 to 1,25(OH)2 D3. In addition to the significant role as a calcium regulating hormone, calcitonin is also known to stimulate the production of vitamin D in tandem with PTH (Yoshida et al., 1999; Wongsurawat and Armbrecht, 1991). Previous studies revealed that 1-ÃŽ ±-hydroxylase mRNA expression, 1-ÃŽ ±-hydroxylase activity and the production of 25(OH)D and 1,25(OH)2D3 all increased in rat kidney cells following the administration of calcitonin (Yoshida et al., 1999; Galante et al., 1972; Rasmussent et al., 1972). However, in cases of diabetes, it is postulated that the kidney becomes immune to the effect of this hormone in diabetic rats which lead to increase vitamin D production (Wongsurawat and Ambrecht, 1991). 1.2.4.5- Growth hormone, Insulin and Insulin-like growth factor-1 Growth hormone (GH) has many regulatory actions in various metabolic processes in humans and mammals and its effect on mineral homeostasis in target organs such as bone and renal cells is well documented. While the regulatory effects of GH on dietary calcium and phosphate metabolism in different tissues have been established, its effect on vitamin D metabolism remains controversial. However, many studies have shown that GH increases the expression of 1-ÃŽ ±-hydroxylase and 1, 25-dihydroxyvitamin D3 in cultured cells and experimental animals (Gomez, 2006). Wu and colleagues reported that serum1, 25-dihydroxyvitamin D3 increases after GH administration in hypophysectomized rats fed with a phosphate depleted diet. Short-term studies in healthy humans have shown that GH raises 1-ÃŽ ±-hydroxylase enzyme activity and promotes 1, 25-dihydroxyvitamin D3 synthesis without changes in PTH, calcium and phosphate concentrations, suggesting that the increasing circulating levels of 1, 25-dihydroxy vitamin D3 following GH administration is not mediated by PTH action (Wu et al., 1997; Bianda et al., 1997; Wright et al., 1996). GH has also been shown to lead to increased production and serum concentration of 1, 25-dihydroxyvitamin D3 in pigs and in renal impaired prepubescent children. These are thought to be a result of the direct and indirect effects of GH on 1-ÃŽ ±-hydroxylase expression, and on calcium and inorganic phosphate homeostasis in renal tubules cells (Strife and Hug, 1996; Denis et al., 1995). However, the action of GH on vitamin D metabolism in vitro remains uncertain and may involve other regulatory factors such as PTH and Insulin-like growth factor-1 (IGF-1). It has been shown that GH does not raise 1, 25-dihydroxyvitamin D3 levels directly in cultured cells obtained from aged-rats; yet it stimulates calcium absorption and the expression of calcium binding proteins in vitro indicating that the effect of GH is mediated through the action of other factors such as IGF-1 (Fleet et al., 1991). Insulin is another key factor with a role in vitamin D homeostasis. Insulin significantly decreases renal hydroxylase activity and renal synthetic capacity of 1, 25-dihydroxyvitamin D3 in insulin deficient patients or those receiving insulin therapy (Armbrecht et al., 1996). However, a study of different routes of therapeutic insulin administration in human diabetic subjects concluded that insulin induces the hepatic hydroxylation of 25-hydroxyvitamin D3. This effect is related to the fact that insulin is a potent inducer of the vast majority of liver hydroxylases enzymes (Colette et al., 1989). This study also showed that there was no significant difference in circulating levels of 1,25-dihydroxyvitamin D3 between different methods of insulin administration. Serum 1,25-dihydroxyvitamin D3 is maintained at normal concentrations in those subjects on long term insulin therapy; however, continuous intraperitioneal infusion procedure (CPII) may augment hepatic 25-hydroxlase activity (Col ette et al., 1989). Similarly insulin has shown a significant effect on stimulating 1,25-dihydroxyvitamin D3 production through 1,25-dihydroxyvitamin D3 and PTH stimulation with no concomitant action on 24-hydroxylase expression in rat osteoblast cells when these cells were cultured with known concentrations of 1,25-dihydroxyvitamin D3 and PTH (Armbrecht et al., 1996). Insulin-like growth factor-1 (IGF-1) is a relatively small peptide that is primarily expressed in hepatic cells and to a lesser extent in some other cells and tissues. It has been identified as one of the potent regulatory components of mineral metabolism in humans and mammals. Recent studies on the metabolic effect of IGF-1 revealed that the administration of IGF-1 to aged laboratory animals, fed on a calcium- and phosphate- deficient diet, can restore 1-ÃŽ ±-hydroxylase activity and enhance the production of 1,25-dihydroxyvitamin D3. In contrast, there was no significant effect of IGF-1 on enzyme activity and 1,25-dihydroxyvitamin D3 levels in adolescent or elderly rats fed on a calcium and phosphate fortified diet concluding that the expression of IGF-1 is not age related but related to the dietary calcium and phosphorus status. (Gomez, 2006; Wong et al., 1997; Wu et al., 1997). In healthy human subjects, a significant effect of IGF-1 on renal 1,25-dihydroxyvitamin D3 synthesis wa s observed after short term infusion with IGF-1. There was no noticeable alteration of the levels of circulating calcium, phosphate and PTH highlighting the role of IGF-1 in stimulating renal expression of 1-ÃŽ ±-hydroxylase and 1,25-dihydroxyvitamin D3 formation in conjunction with GH, independently from PTH (Bianda et al., 1997). In vitro studies have shown that IGF-1 influences the expression of 1-ÃŽ ±-hydroxylase and 1,25-dihydroxyvitamin D3 synthesis in cells cultured from non renal human tissues. Halhali and colleagues demonstrated that IGF-1 noticeably elevates both the enzyme activity and 1,25-dihydroxyvitamin D3 levels when added into cultured syncytiotrophoblast cells obtained from human placental sources. This study demonstrated that IGF-1 strongly enhances the ability of non renal cells to produce 1,25-dihydroxyvitamin D3 without involvement of GH and PTH (Halhali et al., 1997). 1.2.4.6- 1, 25-dihyroxy vitamin D3 The circulating levels of 1,25-dihydroxyvitamin D3 modulate its production by renal cells through an indirect negative feedback mechanism. This mechanism appears to reduce the likelihood of vitamin D toxicity by inhibiting 1,25-dihydroxyvitamin D3 synthesis by an indirect mechanism that controls the 1-ÃŽ ±-hydroxylase gene expression at the molecular level rather than inhibiting 1,25-dihydroxyvitamin D3 synthesis directly. However, the exact mechanism is not yet fully understood (Dusso et al., 2005; Deluca et al., 1990). A recent study examined the effect of 1,25-dihydroxyvitamin D3 on 1-ÃŽ ±-hydroxylase production by cultured human keratinocytes. Keratinocytes were cultured with labeled 25-hydroxyvitamin D3 and different concentrations of 1-ÃŽ ±-hydroxylase mRNA and 24-hydroxylase- suppressed proteins. The 1,25-dihydroxyvitamin D3 did not suppress either the 1-ÃŽ ±-hydroxylase activity or the rate of gene transcription. The study implied that metabolic regulation of 1,25-dihydroxyvi tamin D3 is related to the molecules biodegradation in response to augmented 24-hydroxylase activity rather than 1,25-dihydroxyvitamin D3 formation by 1-ÃŽ ±-hydroxylase (Xie et al., 2002). In addition, Wu and colleagues demonstrated a possible alternative mechanism of 1,25-dihydroxyvitamin D3 synthesis linked to the fact that both 24-hydroxylase and 1-ÃŽ ±-hydroxylase enzymes share equivalent metabolic capability and they proposed the possibility of protein- protein interaction between intracellular vitamin D binding protein and 1-ÃŽ ±-hydroxylase (Wu et al., 2002). 1.2.5- Vitamin D Transport, receptors and mechanism of action Vitamin D receptor (VDR), also known as calcitriol receptor, is a member of the steroid family and belongs to the nuclear receptor superfamily (NHR). Human VDR until recently was thought to comprises four functional units with a total of 427 amino acids residues with an estimated molecular weight of about 48 kDa. These units are the DNA binding domain (DBD) or C domain, the D domain and the ligand binding domain (LBD) or E domain. More recently, a carboxy-group with undefined function, known as the F region has been identified (Christakos et al., 2003; Aranda and Pascual, 2001; Rastinejad et al., 2000). These units as, shown in figure 4, are also known as A/B domain. The A/B region of VDR contains a low number of amino acids that participates in essential ligand-independent receptor stimulation (Aranda and Pascual, 2001; Issa et al., 1998). It is not yet clear if the deletion of A/B domain from VDR will compromise ligand binding, DNA binding or its transactivation features (Issa et a l., 1998). In contrast, the structure of the DNA binding domain or C region among NHRs comprises 40% unique amino acids sequences and a domain of more than 67 resemble amino acids residues (Rastinejad et al., 2000). Moreover, the core structure of DBD comprises between 22 and 114 amino acid residues, nine of them are cysteines. Eight of cysteine residues orchestrate with zinc atoms in tetrahedral fashion to form a dual â€Å"zinc-like finger† DNA binding configurations containing approximately 70 amino acids with a carboxy-terminal extension (CTE). This encloses T and A boxes in a dual helix molecule in which one helix is essential for definitive interaction with the main domain on DNA while the second helix takes a part in receptors structural properties (i.e. receptor dimerization) (Aranda and Pascual, 2001; Issa et al., 1998). However, the integration of the structural amino acids of the DBD ÃŽ ±-helix one, at the site of the first zinc atom, determines the selectivity and specificity of recognition of DBD and forms an area known as the â€Å"P Box†. Similarly; the integration of amino acids at the position of the second zinc atom modulates the formation of a configuration termed the â€Å"D Box† which forms a dimerization interface zone (Aranda and Pascual, 2001; Rastinejad et al., 2000; Issa et al., 1998). Furthermore the vast majority of DBD amino acid units are basic amino acids which enhance the non-covalent binding of the DNA helix at the negatively charged phosphate group (Issa et al., 1998). The ligand binding domain (LBD) or E domain has a spherical configuration with many functional regions composed of 12 cohered helix anchors defined as H1 to H12. LBD itself comprises a net of 427 amino acids which contribute to homodimerization and heterodimerization and the interaction of hormones and costimulaotors by a crucial transactivational mechanism (Aranda and Pascual, 2001; Weatherman et al., 2000; Issa et al., 1998). Crystallograp hic studies show that LBD have two cohered and integrated domains, the Ti or â€Å"signature motif† and the carboxy or C terminal AF-2 providing the self-ligand transcriptional properties; hence a higher degree of attraction of 1,25 dihydroxyvitamin D3 binding is observed at 382 to 402 of LBD amino acid sequence and any genetic aberration at this particular amino acids sequence will diminish the interaction capability of LBD (Aranda and Pascual, 2001; Issa et al., 1998). Figure 4: The primary structure of the vitamin D receptor (VDR) and the binding of retinoid X receptor (RXR)-VDR heterodimers to vitamin D response elements (VDREs) in the form of DR3 and ER6 motifs. (Figure from Lin and White, 2003) 1,25-dihydroxyvitamin D3, has been identified as steroid hormone with a mechanism of action similar to other steroid hormones, causing new protein expression in various target organs. Based on the nuclear receptors structural studies, calcitriol is known to exert its biological action through binding with VDR in the cell nucleus to mediate a cascade of transcriptional and translational processes resulting in either the regulation or inhibition of new protein expression in target tissues or the binding to plasma membrane receptors without stimulating new protein synthesis (Nezbedova and Brtko, 2004; Reichel and Norman, 1989). Two different receptors for 1,25-dihydroxyvitamin D3 have been recognized in different target cells; identified as genomic VDRnuc and typical VDRmem .These receptors provide the best dynamical conformational forms for calcitriol interaction and to evoke its genomic and non-genomic effects (Norman et al., 2002). The binding of 1,25-dihydroxyvitamin D3 to VDRnuc e nhances the interaction with an undistinguished protein known as the nuclear accessory factor (NAF) and to the caroxy-terminal of VDR. This interaction leads to a structural conversion pattern of the C-terminal of VDR allowing the AF-2 domain to attach with other transcriptional elements such as SCR-1, calcium binding protein (CBP) and P300. This promotes the binding of the heterodimer molecule with DNA at the vitamin D response sites (VDRE) and directs its transcriptional gene activity (Jones et al., 1998; Iqbal, 1994). In addition, these coactivators play a role in DNA configurational changes through histone acetyl transferase activation pathway of the core components of histones. This results in mechanical instability of the DNA structure and enhances the net binding capacity of the coactivators with their corresponding receptors at nucleosomal histone level and leads to the upregulation of these transcriptional coactivators which in trun, accelerate the net gene transcriptional rate to promote the synthesis of the analogous protein (Lipkin and Lamprech, 2006; Jones et al., 1998). Conversely, the non-genomic or classical effect of 1,25-dihydroxyvitamin D3 is modulated through its binding with the surface cellular membrane receptor known as mVDR which initiates an immediate response in various target tissues with no genomic transcriptional activity. Many studies demonstrate the rapid effect of calcitriol in rapidly increasing both the level of circulating calcium and its absorption rate in animal intestines, evoking phosphoinoisitide bioactivation, cyclic guanosine monophosphate (cGMP) elevation, activation of protein kinase C and triggering the mitogen activated protein kinase pathways and involving the chloride gates action potential in different organs (Dusso et al., 2005; Nezbedova and Brtko, 2004; Boyan and Schwartz, 2004; Norman et al., 2002). The entire mechanism, as shown in figure 5, for the rapid effect of calcitriol remains doubtful, however; the proposed mechanism is mediated through the interaction with mVDR leading to a series of intracellular sig naling events. Signaling is orchestrated by the activation of various metabolic pathways involving different transportation mechanisms of certain mineral components of target organs. (Pedrozo et al., 1999; Norman et al., 1999; Revelli et al., 1998). However, other studies reveal that the genomic effect of 1,25-dihydroxyvitamin D3 is independent of its non-genomic mechanism (Dusso et al., 2005). Figure 5: Cellular mechanism of action of 1,25(OH)2D3 (Figure from Horst et al., 1997) 1.3- Biological actions of Vitamin D on target tissues and Systems The active form of vitamin D, 1,25-dihydroxyvitamin D3 is well recognized as a member of steroid hormones that mediates several metabolic and non-metabolic processes in various organs in human and animals as shown in figure 6. 1.3.1- Intestine Mineral absorption in the intestines is increased in the presence of the hormone 1,25(OH) vitamin D. However without this, only 10 to 15% of dietary calcium and 60% of phosphorus is absorbed from the diet (De Luca, 2004). Ca2+ and HPO42- are also absorbed when intestinal cells interact with the vitamin D- VDR- RXR complex. The latter enhances the expression of the epithelial calcium channel and calcium-binding protein which recruits calcium and phosphorus (Holick, 2007). Knock out mice experiments studying the effect of VDR gene deletions also show that the size of the small intestines is related to the levels of calcitriol and dietary calcium availability. Vitamin D deficient mice fed with diets low in calcium exhibited the largest small intestine to large intestine ratio (Cantorna et al., 2004). VDR knock-out mice experiments also aid in the discovery of calcium channels, the route for Ca absorption, in the intestine (Peng et al., 1999). Calbindin is a potent calcium transporter in mammals which characterized by a high affinity for calcium ions. Therefore, the binding of vitamin D to VDR and RXR signals an increased production of calbindin which facilitates systemic Ca2+ ions transportation and prevent the occurrence of calcium toxicity in the intestines. Figure 6: Schematic diagram of the effects of Vitamin D on different tissues and organs (Figure from Holick, 2007). 1.3.2- Bone Takeda et al. (1999) studied the role of vitamin D and VDR in bone cells using knock out mice experiments. Their results showed that bone cells formation triggering mechanisms such as cell to cell interaction between osteoblast and osteoclast progenitors and stromal cells induced by 1,25(OH)2 vitamin D3 and provoke the formation of osteoclasts. In their capacity as bone resorbing cells, osteoclasts can be triggered by low serum calcium levels, to break down bone and free calcium back in to the blood thus redistributing calcium throughout the body. However, this does not occur without the expression of VDR and without vitamin D complexing with its receptor. This study emphasizes the important role of recognition sites on the VDR and the structural implications that the receptor-ligand binding has on VDREs and transcription initiation. Although the effects of PTH

My Friend Essay -- Friendship Essay Personal Narrative

Have you ever wondered why your best friend is actually your best friend? Is it just because you have known them all of your life? Or is it simply because you just like to hang out with them? My best friend is as unique as they come. I have watched and admired his way of life over the past eight years. My friends' name is Mike Linn. Mike and I met in the sixth grade. He immediately stood out to me. There was just something about him that caught my eye. He had short messy brown hair as if he had just rolled out of bed and he was wearing a yellow Nautica t-shirt that glared at you as if you were looking directly into the sun. He had on a pair of cream colored cargo shorts and a pair of sneakers from Wal-Mart. He was the typical sixth grader everyone could imagine. From that moment on we have had many great and memorable times. Today Mike’s look is very unique. Over the years he has changed it dramatically. He has realized that the way he looked was not the way he wanted to look. It was the way his parents and friends wanted him to look. In middle school he was always wearing bright polo’s, cargo sorts, and K-Swiss sneakers. He had short dirty blonde hair that he always spiked. Today you will see him wearing all black pretty much. Most people would say he’s gothic or emo. There totally wrong. He is nowhere near gothic or emo. He is always wearing black t-shirts that have some sort of design on them. His pants are usually black and for some odd reason he loves to wear black cargo pants, not those skinny jeans or denim jeans; but black cargo pants. He has an obsession with love so occasionally he wears weird pants with hearts all over them just to catch peoples attention. Most people call him gay but he has had the same girlfriend f... ... her and how much I truly missed being with her. Mike’s right, love isn’t a game. It’s a gift, a privilege, an honor. His friendship and passion for others make me a better person everyday. I have learned so much from him by watching and observing his actions over the years. He has helped me in so many ways. He helped me learn the value of life; and he helped me put my relationship with the love of my life back together. So many teenagers today are too busy trying to fit in; worrying about what people think of them. He doesn’t care what people think. He just wants to be him, he wants to be different, and he wants people to acknowledge him BECAUSE he is different. Like I’ve said before, he really has made a positive impact and influence on not only my life, but our friendship as well, and I will always appreciate him for who he is and everything he has done for me!

A destructive love Essay --

A destructive love Othello is such a character who is portrayed as a tragic hero through his high ranking in army, jealousy caused by racial inferiority, and credulousness for the villain Iago. In Shakespeare’s play, The Moor of Venice, jealousy is the major component constructed though out the entire play and eventually leads to Othello’s downfall and ultimately destroys his marriage with Desdemona. The play is a story of a black hero in the white community at an era of alteration from racist past to a less biased future. During this social transform period, a black Moor is able to be promoted over other white men and therefore Othello is in a higher ranking than most of white people in Venetian society. However, during this period of alteration, many social disciplines and social understanding are arbitrary. On one side, the society promotes a certain degree of racial equality by having black Moor appointed as general. On other side, Othello is alienated in Venetian society because most Venetians see him as an outsider whom is protecting their country. Therefore, Othello only gains respect for his bravery in fighting the war and his reputation for being a skilled general in the army and nothing else like his lieutenant, Cassio is, who comes from an upper class and white race family and has strong social skill. Othello is clearly aware the fact that he is not being recognized as part of Venetian society, yet he cannot do anything to the existing class prejudices. But not only that he is fully aware of presented racial prejudices, this racism has somewhat made him feel racially inferior to other light skinned people around him. Othello’s racial inferiority is intensified when he is being compared to Cassio ... ...,† his jealousy of honor has blinded his mind and he wrestled with a rising feeling of impotence, self-pity and vengeance. Yet, this jealousy also blinds his mind when Desdemona tries to defend herself before Othello smothers her. Othello firmly believes his wife has cheated on him, and he confirms his deed by telling himself that he is defending his honor. Therefore, I believe that right before Othello kills Desdemona, he himself is too afraid that he is wrong about Desdemona because he firmly confirms himself the purpose of this monstrous murder with an apparently upright reason. However, his self-affirmation is crushed as Emilia reveals the truth about the handkerchief and the fact that Iago has plotted all these traces to mislead Othello. Othello’s loss of his one true love is like â€Å"the base Judean, threw a pearl away/ Richer than all his tribe† (5.2.352-353).

Air Traffic Controller

Air Traffic Controller Essay Air Traffic Controller is an occupation were you work with pilots and guide them safely from the time they push back to when they park at the gate. Being an Air Traffic Controller is a difficult job, they have a big responsibility which is to keep everyone safe in the skies. They are responsible for the safety, separation and sequencing of aircraft. I was told that in the tower that this is a job where you have to be alert to all of the surroundings, weather and pilots doing what they are supposed to be doing. This job is not like some people say it is.It’s not easy; this job takes a lot of training and a lot of patience with the pilots. In ATC you have three positions: the first is â€Å"Clearance Delivery† is when the pilot calls the tower to request his clearance to their destination. The pilot calls clearance and he’d say the type of aircraft they are flying, were his parked at and their destination. For example: â€Å"Vieques 89 2 requesting clearance to Boriquen† then the controller tells the pilot: â€Å"Vieques 892 you are cleared to Boriquen via the assigned route and gives them an assigned transponder code. The Boriquen airport is the name for Aguadilla airport or in the aviation language BQN is the three letter identifier. In Luis Munoz Marin international airport the larger companies like Delta, JetBlue, United and others have a service they pay for. It’s a third party company that gives them the clearance information in a short computer message that is sent to the aircraft when the pilot requests a clearance without ever having to talk to the clearance controller. After this happens the pilots contact ground control. Ground control is one of the most difficult positions in this type of work.Ground control is the controller the pilot calls to ask for their clearance for pushback and taxi. The pilot does this â€Å"Delta 422 requesting clearance to pushback and the gate number they are parked at†, and then the controller tells the pilot â€Å"Delta 422 cleared to push (the direction he is going) and to call when ready to taxi†. Once they are call that they are ready the ground controller will issue instructions on how to get to the runway. Ex â€Å"Taxi to runway 10 via Hotel 6 right turn on Hotel and hold short of runway 10†.Also the controller has the responsibility of sequencing aircraft correctly and all other movements in the FAA controlled areas. Also the controller is responsible for issuing taxi instructions to arriving aircraft as well. For example the pilot calls ground and says: â€Å"Delta 597on H9 Requesting taxi to the gate†, The Ground Controller responds â€Å"Delta 597 take N3 and right on to N to the assigned gate†. Ground control is not an easy job and is not an easy position to train on, this position when you train on it could get a little difficult and busy.But is a process that every controller has to go thr ough because an Air Traffic Controller has to work any of the assigned positions when they receive their certificate, and the next position is Local Tower. Local Tower is when and a pilot calls and request clearance for landing or for takeoff. When they are going to takeoff they call the tower and say: â€Å"Delta 422 holding short of runway 10 ready for takeoff† and then the controller working the tower position will tell the pilot if he is cleared to takeoff â€Å"Delta 422 you are cleared for takeoff† or the controller might say â€Å"Delta 422 line up and wait†.Then when the airplane is out and climbing the tower calls the aircraft and says: â€Å"Delta 422 contact departure†. Tower has the responsibility of every airplane coming in and going out of the airport. Tower has the responsibility of all of the airplanes in their airspace and it’s their responsibility of any aircraft flying around or inside the controlled airspace. This line of work i s not for everybody and the people that currently work them are sometimes stressed and tired.I like this profession because I enjoy working with pilots and the aviation community as a whole. My favorite position is Tower, because I can work with airplanes. I like this position because at times it can get a busy and you have to be on top of everything that is going on. In conclusion all of the positions are good as long as you can do something you love and truly have passion for. The only thing I have to say is I can’t wait to work in ATC.

Social Work: Components of Working in the Substance Abuse Field

1) The critical components of professional practice while working in the substance abuse field: I. Engagement: – This process continues throughout all of the stages, or components. Engagement involves building rapport with the client but because people with substance abuse problems are often scared, emotional, defensive and unable to trust this can be difficult. Preparing prior to the initial interview is very important as well as limiting any interruptions while meeting with your client. II. Assessment: Assessment of a person with a possible substance abuse problem can be very complicated. First step is to find out if the client is suffering from substance abuse or substance dependency. The various dimensions of an assessment are biological, psychological and social. – The biological assessment can be done by reviewing their medical history and current health and can provide clues to any medical treatment needed. – The psychological dimension involves reviewing the clients mental health history to determine if there may be any underlying mental disorder.Questions about anxiety levels, depression, unresolved trauma or grief are asked then shifts to the reasons for starting, stopping and continuing the behavior. – The social dimension involves engaging the client in review the various people in their life: family, friends, co-workers and other social networks. Who supports them, where is there tension and stress, what relationships have been affected by the behavior, etc†¦ – Strength based assessments focuses on what the client wants in their life and tends to me more motivating.Exploring the strengths in addition to the negative provides a better balance and is respectful. – Once the assessment has been made, the next step is to develop an intervention plan that is unique to the situation and the client. III. Intervention: Interventions focus on work at many different systems levels, from individuals and families t o organizations and communities. In addition, include inpatient detoxification to help with the initial withdrawal and pre-existing medical problems. There is behavioral approach that involves changing behavior by using positive and negative reinforcement.Family interventions, which help to identify relationships and communications that encourage or excuse substance abuse behavior. There are also options to join self-help groups or group therapy, which focus on the why's. In some cases medication may need to be prescribed or moving to a therapeutic community is necessary. The social worker decides which approach to take or what strategy to use and client based on what the client needs, their culture, and specific goals. 2) Most older adults want to maintain independence as long as possible; how has this led to the development of a continuum of care for older people? The continuum of care is based on the principle of least restrictive which involves helping the older adult remain in their own home for as long as possible. Some of the services apart of the continuum that are least restrictive include monitoring services like life alert, homemaker services that involve someone assisting around the house (cleaning, laundry, shopping, or personal care such as, bathing and dressing etc) or even in home health care. 3) Social workers involved in low enforcement†¦Social workers are involved in cases regarding traffic accidents and fatalities, child abuse, suicide, alcohol and substance abuse, mental health emergencies and family disputes. Social workers provide crisis intervention, brief individual or family counseling, referrals, victim assistance as well as community crime prevention efforts. Home visits, crime scene crisis work, and increasingly involved in crime prevention work in the community by leading action efforts related to the development of youth services, drug courts and even in the reform of mental commitment laws.