Cationic Antimicrobial Peptides in Humans

Cationic Antimicrobial Peptides in Humans Antimicrobial peptides Introduction Cationic antimicrobial peptides (AMPs) are gene-encoded peptides of the host defence system made up of 12-50 amino acids, with at least 2 positive charges conferred by lysine and arginine residues and about 50% hydrophobic amino acids (Hancock and Scott 2000). They are produced from gene transcription and ribosomal translation and often, further proteolytically processed (Zhoa 2003). The peptides are folded so that non-polar amino acid side-chains form a hydrophobic face and polar, positively charged residues form a hydrophilic face (Robert and Hancock 1997). Expression of antimicrobial peptides can be constitutive or inducible by infectious or inflammatory stimuli like cytokines, bacteria and lipopolysaccharides (LPS) (Cunliffe and Mahida 2004). They have diverse structures to effectively kill a wide range of microbes at prone sites e. g the skin and lungs, and in secretions such as sweat and saliva (Yeaman and Yount 2004; Santamaria 2005). Many mammalian antimicrobial peptides rouse the host’s innate immune system (Jenssen et al 2006) instead of directly killing the host. Peptides which are found in living organisms from bacteria to plants, insects, fish, amphibians to mammals including humans (Kamysz 2005) are recorded in numerous existing databases e. g. AMSDb (Eukaryotic peptides) (Tossi and Sandri 2002), BAPDb (bacterial peptides), ANTIMIC (natural antimicrobial peptides) (Brahmachary et al 2004) and APPDb. Currently, 1831 peptides are hosted by the Antimicrobial peptide database with 99 antiviral, 453 antifungal, 100 anticancer and 1179 antibacterial peptides (The Antimicrobial Peptide database 2010). In humans, antimicrobial peptides are produced by granulocytes, macrophages and most epithelial and endothelial cells. They boost the immune system, have anti-neoplastic properties and help in regulating cell signalling and multiplication. Amphibian AMPs have been discovered from the skin of frogs from families ra nging from Iomedusa, Pipidae, Hyperoliidae, Ranidae, Hylidae, Discoglossidae, Agalychnis and Litoria. The structure of these peptides as unravelled by CD spectroscopy, NMR spectroscopy and molecular modeling (Suh et al 1996) have been found to be generally 10-46 amino acid residues long (Rollins-Smith et al 2005), mostly linear and simple-structured, (Conlon et al 2004) the majority being hydrophobic, cationic and possessing an amphipathic a-helix in nature. Following production, they are stored in the granular glands (poison glands) of skin dermal layer to be secreted in response to injury (Bovbjerg 1963), or as defence against pathogenic bacteria, fungi, viruses and parasites. Biologically active molecules including antimicrobial peptides are produced as large proteins harbouring a signal and an acidic propiece which get cut off to give an active peptide prior to or at secretion from the poison glands (Amiche et al 1999). Cationic peptides are also expressed in the gastric mucosa cells and in the intestinal tract (Kamysz 2005). The best-known peptides isolated from frogs are caeruleins, tachykinins, bradykinins, thyrotropin- releasing hormone (Barra and Simmaco 1995), brevinins, esculentins, magainins, ranatuerins and temporins (Conlon et al 2004). In the past, peptides were extracted using solvents like methanol or acid from the skins of amphibians after sun-drying but with concomitant dwindling of many frog species, other alternative techniques have emerged, one of which comprises stimulating the frog using mild electricity and collecting the skin secretion; 2-4 weeks after, the secretion can be re-collected after replenishment of the glands (Barra and Simmaco 1995). Large amounts of small peptides and their analogues which are resistant to protease cleavage and contain D-amino acids can be chemically synthesised while larger peptides can be expressed in a prokaryotic host from cloned cDNAs coding for a fusion protein (Piers et al 1993). An efficient means of producing therapeutic peptides in transgenic mice red blood cells has been explained by Sharma et al (1994) whereby the required peptide is collected from proteolytic cleavage from the fusion protein where the peptide is at the C-terminal end of human a-globin.

Of all the lies out there, the one that corporate executives pay is Essay

Of all the lies out there, the one that corporate executives pay is linked to the performance of their companies takes the prize. Discuss this in relation to - Essay Example For the business to be viable, it has to turn out products or services that are profitably sold to meet the needs of customers. The principals in turn may (or may not) hire managers to run the business and generate the expected profits. These hired managers (agents or executives as they are now called because they carry out or execute the plans of principals) have their own interests, the main of which is to receive adequate levels of compensation or pay to convince them to work for the principal and in such a work environment. Principals and agents therefore each have their own interests. While principals want the highest return for funds invested, agents want the highest pay they can get for their work. Their interests converge in a common desire to keep the business viable so that both continue to enjoy the rewards of their work. It is therefore to their advantage to align their respective self-interests and desires. In practice, however, this has not always been the case, as shown by events in early 20th century America when agents (managers) of railroad companies got paid well even as they mismanaged their companies, resulting in principals suffering heavy losses on their investments. Recent examples (Enron and WorldCom) show this to be still a problem. The study of thThe study of the relationship between principals (owners represented by the board of directors) and agents (managers or executives) was pioneered by Berle and Means (1932), who pointed out that the interests of the owner and the manager may diverge because of the separation of ownership and control and the absence of a system of checks and balances in the exercise of power within the organization. Unlike in a business where the owner is also the manager who works to earn the maximum profit under acceptable levels of risk, Berle and Means concluded that hired managers if these are not the same as owners tend to work with the limited aim of running the company only for their (the agent's) own profit. The experiences of modern business corporations in the last century contain numerous examples of divergence between the interests of agents and principals, with disastrous results (mainly to the principals). This led to debates by economics and finance academics as to whether an ideal ownership structure exists that would prevent the failure of a business. This issue touches the core of why businesses exist in the first place, which is to maximize profits for its owners' investments, and attempts to explain a related set of problems: why and how firms previously managed successfully by their owners eventually fail when under hired managers. Economists used to assume without question that everyone - owners, managers, employees, and lenders - act together for the good of the firm because "each one is bound by formal and informal contracts to ensure that shareholder value is maximized" (Brealey and Myers 991). After all, biting the hand that feeds them would seem unwise and against common sense for intelligent managers to do, but through the years this continued to happen as well-paid managers continue to

Hydraulic Machines Essay Example | Topics and Well Written Essays - 1000 words - 1

Hydraulic Machines - Essay Example The former types of machines are called turbines and the latter, pumps. A combination of both pump and turbine is used in fluid couplings and torque converters for the transmission of power smoothly through a fluid medium. The analysis of impact of fluid jets on vanes is typically involved in the design of an efficient turbo-machine. When a vane moves away from the jet as shown in the below figure, the mass flow arriving at the vane is considerably reduced because some of the mass leaving the nozzle results in a growing column of fluid between the jet and the nozzle. This is what happens in turbines where the vanes are part of a revolving wheel. We need only consider the simplest case of movement in a straight line in the direction of the jet. Assuming the velocity of the jet is v and the velocity of the vane is u as shown above, the velocity of the fluid arriving would be v - u. This is the relative velocity, that is, relative to the plate. The mass flow rate arriving on the plate is then calculated as The true velocity of the fluid leaving the nozzle is v1 and velocity of the vane is u. The fluid arrives on the vane with relative velocity v1-u as before, which is shown in the above figure. This is a relative velocity with respect to someone moving with the vane. In the absence of friction, the velocity of the fluid over the surface of the vane will be v1-u at all points. At the tip where the fluid leaves the vane, it will have two velocities. The fluid will be flowing at v1-u over the vane but also at velocity u in the forward direction. The true velocity v2 at the exit as shown above must be the vector sum of these two. The vector diagram is illustrated below: If only the force acting on the vane in the direction of movement is required, then the horizontal component of v2 must be determined. Because this direction is the direction in which the vane is whirling around the centre of the wheel, it is