Vibrio Cholerae Cytolysin (VCC) Membrane Pore Formation

Vibrio Cholerae Cytolysin (VCC) Membrane Pore Formation Vibrio cholerae cytolysin (VCC) is a potent membrane pore forming protein toxin secreted by many pathogenic strain of the V.cholerae. In its membrane pore-formation mode of action, VCC belongs to the family of the ÃŽ ² barrel pore-forming toxin (ÃŽ ²-PFTs) proteins. VCC is secreted by the pathogenic bacteria V.cholerae in the form of water-soluble, monomeric, inactive precursor form of the protein, known as Pro-VCC. Proteolytic deletion of the N-terminal Pro-domain from this inactive precursor molecule generates the active, mature form of the VCC toxin. VCC induces colloid-osmotic lysis of the target eukaryotic by generating the transmembrane heptameric ÃŽ ² barrel channels/pores. The high-resolution molecular structural information is available for the water-soluble monomeric Pro-VCC form as well as for the transmembrane heptameric pore structure of the VCC. Structural analysis of the water-soluble monomeric form and the transmembrane structure suggest that the VCC follows the overa ll pattern of the archetypical ÃŽ ²-PFTs mechanism of pore-formation. However, the distinct intermediate steps leading the generation of the funcational membrane pore formation by VCC have only been characterized to a limited extent. Consistent with the generalized ÃŽ ²-PFTs mode of action, the membrane pore formation mechanism of the VCC is recommended to follow three different steps: interaction of the VCC monomeric unit towards the target cell membrane; formation of the metastable, transient prepore oligomeric intermediates on the cell membrane; and finally conversion of the prepore oligomeric assembly into the functional transmembrane oligomeric b barrel channels. Previous research work on the members of ÃŽ ²-PFTs including VCC suggest that the generation of the functional transmembrane oligomeric pore structure comprises the membrane insertion of the pore-forming stem region from each of the toxin protomer towards formation of the transmembrane ÃŽ ² barrel portions of the toxin. However, it has not been examine experimentally, in particular in the case of VCC toxin, whether the membrane insertion of the stem region could occur in the membrane-associate monomeric state of the toxin before the prepore oligomer generation or whether the prepore oligomer generation precedes the membrane insertion of the stem region of the VCC toxin. Even in the case of generalized ÃŽ ²-PFTs membrane pore-formation mechanism, such sequence of pore formation events has not been established precisely. Previous studies demonstrated that the engineered ÃŽ ²-PFTs (for example, VCC and staphylococcal LukF) not able to inserting their pore-forming stem region into the membrane lipid bilayer of the target cell membrane. Such protein variants, having their stem loop in a closed structure through the engineered disulfide linkage, are remaining trapped in their nonfunctional prepore oligomeric state. However form this observation it not clear whether the membrane oligomreization is absolutely necessary to trigger the membrane insertion or whether membrane insertion could be initiated before the prepore generation. Such perception can only be investigate by trapping the b-PFTs toxin molecule in its membrane-bound monom eric form without allowing the generation of the transmembrane oligomeric structures. In this order, a direct correlation between the membrane oligomerization and the membrane insertion has been demonstrated in Staphylococcal à ¯Ã‚ Ã‚ ¡ toxin, an archetypical member of the ÃŽ ²-PFTs family. Staphylococcal à ¯Ã‚ Ã‚ ¡ toxin containing a single point mutation has been shown to displayed defective membrane oligomerization of the membrane-bound protein and blocking the membrane insertion of the pore-forming stem loop of the toxin. This investigation suggests that, in case of Staphylococcal à ¯Ã‚ Ã‚ ¡ toxin, the membrane insertion event of the toxin depend critically on the prior membrane oligomrization step of the toxin. A similar pore-forming mechanism has been reported in the case of perfringolysin O, a prominent member of the subclass of the cholesterol-dependent cytolysin (CDC) under ÃŽ ²-PFTs family. Interestingly, streptolysin O, another prominent member in the cholesterol-de pendent cytolysin type ÃŽ ²-PFTs, follows a different mechanism of membrane pore formation that may have involve distinct sequence of events. In the membrane pore formation mechanism of streptolysin O, it has been proposed that the progressive assembly of the membrane-inserted monomeric unit of the toxin may act towards the formation of the transmembrane oligomeric pore structures of different pore sizes. A similar membrane oligomeric assembly has also been reported on another cholesterol-dependent cytolysin (CDC) class of ÃŽ ²-PFTs, pneumolysin. Thus, it emerge that the ÃŽ ²-PFTs member may not necessarily follow a common generalized procedure for the membrane pore formation mechanism of the toxin. It is, therefore, important to examine the sequence of the membrane oligomreization and insertion events for each particular member of the ÃŽ ²-PFTs family to elucidate the molecular mechanistic details of their membrane pore-formation action of the toxin. Many previous studies explored the molecular mechanism(s) of the membrane oligomerization process involved with the membrane pore formation action of the member of the ÃŽ ²-PFTs family including VCC. It is generally proposed that the association of the ÃŽ ²-PFTs protein monomer with the membrane component of the target host cells work as the triggering step to initiate the following events resulting towards membrane olgiomerization, membrane insertion, and functional transmembrane ÃŽ ² barrel pore formation. In particular, lipid components of the membrane like cholesterol have been extensively involved in the regulating of membrane pore formation process. In the mode of action of VCC, the presence of cholesterol in the target membrane lipid bilayer has been reported to be an imperative requirement for the efficient oligomerization and functional membrane pore formation by the protein. Cholesterol appears to regulate the membrane pore-formation of the toxin by physically binding with the protein molecule and not by modulating the physicochemical environment of the target host cell membrane. The molecular mechanism of the membrane oligomerization in VCC has been explored only to a limited extent. In particular, the membrane interaction mechanism of the monomeric units of the VCC toxin, which probably acting to regulate the membrane oligomerization process of the VCC toxin, has not been explored so far. Structure analysis of the VCC oligomeric highlights the major interprotomer interactions between the neighboring monomer units. The most significant interactions are observed between the amino acid residues within the membrane pore forming stem loop of the toxin. More importantly, blocking the stem loop in its prestem configuration has been to abrogate the functional transmembrane oligomeric pore formation (SDS-stable oligomeric assembly) without any effect on the generation of the prepore oligomeric species (SDS-labile oligomers). It has been reported that, even i n the physically absence of the stem loop, a truncated variant of VCC can generate prepore oligomeric assembly on the membrane. These observations precisely suggest that the interprotomer interactions involved in formation of the functional transmembrane oligomeric pore assembly without playing any critical role in initiating the membrane oligomerization event of the membrane-bound protein molecules. Therefore, it appears that the additional molecular interaction between the monomer of the toxin might be playing the significant role in inducing the functional membrane oligomerization of the VCC toxin. In this part of study, to explore the details of the molecular mechanism of the membrane oligomerization process of the VCC toxin, we have mapped the key amino acid residue in the VCC molecular structure that are crucial to trigger the membrane oligomerization of the membrane-associate monomeric toxin molecules. Mutation of such key amino acid residues abrogates the membrane oligomerization step, trap the toxin in its membrane-bound monomeric state, and does not allow membrane insertion of the pore-forming stem loop form the VCC monomers. Our study, dissect the membrane interaction step from the following membrane oligomerization and insertion steps of VCC as a prototype in the b-PFTs family, This study also conclusively established that the membrane insertion critically required the functional oligomerization of the membrane-associate VCC toxin monomers on the target cell membrane.

Leading at a Higher Level

IntroductionThe book under consideration is named â€Å"Leading at a Higher Level† and this extraordinary book was written by Ken Blanchard. The author has previously written numerous books namely The One Minute Manager, Raving Fans and now this book. The books written by the aforementioned author have turned out to be helpful for a number of people in perfecting their own leadership skills and expand the prospective of those around them.Now, in Leading at a Higher Level, Ken Blanchard discloses the answers to superlative leadership. Anyone and everyone can profit from the recommendations in this book that have previously helped thousands of leaders and business’ become more oriented around its people, centered on the satisfaction of its customers and performance-driven. The author introduces the readers to innumerable concepts such as the â€Å"triple bottom line† and how to use it to generate effectual objectives and visions.The book provides the readers with t he ways to determine ways to turn customers into what the author calls â€Å"raving fans† and build up a proper â€Å"customer mania.† Any of the higher authorities of an organization can use the techniques presented by the author in his book their own guidance, for leading teams as well as complete organizations. It can also help one in finding their own individual â€Å"leadership point of view†, which is a skill that all really great leaders have power over and it is also helpful in finding out how to relate it all the way through your entire life. By the use of this book, regardless of who or what place you are at, one can produce high-performing business; that can ease out life for everyone. Hoist your game, improve your presentation and make sure that you are foremost at a higher level.ReviewAs said, â€Å"Leaders in any realm of life can become self-serving when the driving reason for being in business is based solely on profit. While profit is a legitim ate goal, neglecting to see leadership as part of a higher calling diminishes the capacity to influence others and impact the greater good† (William, p.1). Leading at a Higher Level scrutinizes the notion of leading with a higher rationale, which necessitates a persuasive visualization and a way of life that the expansion of people is in the same way important to that of presentation. Author Ken Blanchard dares readers to show the way by asking themselves about their own realities, what they position for, and how they can take the inventiveness even if they do not have authoritative power.In the aforementioned book, the author along with a number of his colleagues has made the efforts to put forward their own understanding of top-notch leadership. By reading the book one can learn just how to create aims and objectives for the organization and the ways by which you can make your existence known as well as where your company is moving.Blanchard expands his step forward work on conveying well-known customer service and creating what he calls â€Å"raving fans.† In the book one will find the state-of-the-art dialogue of the well-known Situational Leadership II techniques for leading yourself, persons, teams, and complete businesses. Most significantly, Leading at a Higher Level the book is a big help if one wishes to take a good look at himself, determine the private â€Å"leadership point of view† and then use it for the rest of his or her life.  In the words of the author, â€Å"those who want to lead at a higher level need to understand what a high performing organization looks like and what is necessary to create one. They need to aim for the right target. Profit is the applause you get for taking care of your customers and creating a motivating environment for your people† (Blanchard, p.4).The author believes that anyone who wishes to become a better leader in any company, any organization, and any area of life needs to have a fi xed aim, follow the right idea, focus on the â€Å"bottom lines† that really matter at the same time as providing the customers with good support and deliver your ideal customer experience, and create â€Å"raving fans†. But most of all what he wants to deliver is that leaders should, â€Å"Listen, praise, support, guide, and help your people win† (Blanchard, p.5).The book is extremely informative when it comes to learning how to lead your people to enormity as you create elevated performing organizations that make life better for everyone. This book will direct you, motivate you, incite you, and be your criterion. Ken Blanchard along with a vast number of his colleagues are people that have spent a number of years in serving good leaders and organizations become grand, and as well as stay that way. In this book, they have made an effort to bring together everything they have learnt in the years gone by. By this book one can discover how to, â€Å"Go beyond the short term and zero in on the right target and vision, deliver legendary, maniacal customer service, and earn raving fans, truly empower your people and unleash their incredible potential, ground your leadership in humility and focus on the greater good† (Blanchard, p.10). Since a very long time, a vast number of people have benefited from the insight, understanding, and convenient procedures.From my personal point of view, the book is excellently written providing examples from the lives of real leaders. The book has been written in a very exciting manner and one can not get bored while reading it. Speaking for myself, I have not found anything negative about the book.ConclusionIn the light of the above discussion we can hereby culminate that the book that has been mentioned above namely Leading at a Higher Level was written by Ken Blanchard and the book is related to the ways in which leaders can understand themselves and then lead themselves, their teams and the entire org anizations on the way to success.Works CitedBlanchard, Ken. Leading at a Higher Level: Blanchard on Leadership and Creating High Performing Organizations.   United States of America. FT Press. 2006 Pp. 4,5,10.Williams, Susan. Leading at a Higher. Financial Times. 2007. Pp.1.

Beowulf and Hercules

Beowulf and Hercules Beowulf and Hercules are both extremely heroic characters with tons of characteristics that make them that seem that way. Both Hercules and Beowulf are very well known heroes that have had stories told about them for hundreds and hundreds of years. They both have similarities and differences but the similarities definitely outweigh the differences.Beowulf and Hercules similarities are so much alike they are pretty much the same character in different stories. Both Beowulf and Hercules are great warriors that wanted nothing more than to help and protect the people they knew, one example that shows this is how Beowulf was called â€Å"the mighty protector of men† (Part one, section two). They both killed the same type of mythical creatures in their stories. â€Å"I give thanks that I behold all of this treasure in front of me. (Part two, section nine)- This shows how generous of a person the character is and Hercules is just the same. â€Å"A word so massi ve no ordinary man could lift, he drew it from its scabbard† (Part one, section two) shows the similarities between both Hercules and Beowulf in that they used the same basic weapon and not anything fancy, just their hands and sword. There are very few differences between these characters. One is that Hercules is known as a God and Beowulf is only just a king.Another difference between the two is that Beowulf is a mortal that can possibly die in battle and Hercules is an immortal that is pretty much impossible to kill. As you can see both Hercules and Beowulf are two great heroes that are very protective over the people. They are so powerful they can kill magnificent creatures with just their bare hand or a sword. To are both two of the greatest heroes known to literature today.

Kyoto Accord essays

Kyoto Accord essays No matter how bright a solution may seem, it may only be drawing near the eye of the storm. A problem cannot be completely resolved without creating more. Such is the effect of the Kyoto accord. At this point in time, the Kyoto treaty should not come to pass because of its overwhelming negative effects. Among the many reasons why it should not be signed, are that jobs will dramatically be decreased in the energy industry, global warming occurs periodically without human induced factors, and the unknown cost of this project could prove fatal to the Canadian economy. Even though the greenhouse gases produced by the energy industries play a role in such global warming effects as cataclysmic storms, floods, and drought worldwide, these disasters would occur naturally anyway and it is still not quite certain as to how much it contributes to them. Without a certain amount of warming, all life on the planet would cease to exist. Furthermore, a reasonable increase in present global temperatures could be beneficial as warming could result in greater precipitation, which would aid in the production of agricultural. The idea that an increase in the climate would cause more violent storms worldwide is untrue also as storms are more closely associated with cold weather than warm weather. Only two of the top twenty deadliest storms occurred during extreme heat conditions. As for the decrease in the emissions to cool down the planet, this is merely a speculation since forty million years ago the concentration of carbon dioxide in the atmosphere was ten times greater than today yet the temperature was substantially cooler. Too many facts are still unknown about the overall effect of the Kyoto project for it to come to pass. Although gas emissions would be reduced considerably, many jobs would be lost in the process. Hundreds of thousands of workers jobs would be put at stake just for the slight chance of a decrease in the climate, whi ...

Definition and Examples of Context Clues

Definition and Examples of Context Clues In reading  and listening, a context clue is information (such as a definition, synonym, antonym, or example) that appears near a word or phrase and offers direct or indirect suggestions about its meaning. Context clues are more commonly found in nonfiction texts than in fiction, though they are found in childrens literature, often with the goal of building readers vocabulary. Words can have multiple meanings, so being able to infer the correct meaning from context is a valuable reading comprehension skill. Types of Context Clues You learn new words through context of the words around them, inferring their meaning through whats going on in the story or what has already been explained in the article. Clues to deciphering a words meaning can be subtle hints or straight-out explanations or illustrations of meaning.   Context clues can be synonyms, antonyms, definitions, explanations, word-structure clues, comparisons (such as metaphors and similes), and contrasts. For example: Synonym context clues will have words nearby that mean the same thing: Synonym: The annual fete is scheduled for the last day of school. Its always a great party.Synonym:   That charlatan! he cried. That absolute fake! Antonym context clues will have words nearby that mean the opposite. Antonym: You look pretty content about it, not like youre all languishing in worry, he said.Antonym:  No, no, that didnt literally happen, she said. I was just  speaking figuratively. Definition context clues just spell out the meaning in a straightforward manner: Definition: In Britain they call a cars trunk its boot.Definition: The department  super, as we call them, she explained to the new hire, is Jerry, the utilities  superintendent.   An explanation or illustration can also show the context of the word: Explanation:  She looked at the  random stuff  that had been thrown in the packing box at the last minute, from toothpaste and razors to spatulas and sticky notes. Well, thats quite the  melange, isnt it? she thought.Explanation:  No, no, thats just a  crane fly, not a  gigantic mosquito, he explained. Word-structure clues come from a reader or listener understanding, for example, a base word and a prefix and inferring meaning of their combination, such as knowing anti- means against or knowing one word when hearing something very similar, such as understanding that a memorial is for someone whos died: Word-structure: Im absolutely anti-establishment, the candidate declared.Word-structure: The book was listed in memoriam of his father. Comparison context clues will show the meaning of a word through similarities to other items or elements, similies or metaphors: Comparison: He looked absolutely  flummoxed, like a toddler staring down at his feet on the floor and who just isnt sure about this whole walking thing.Comparison:  No, she said, Im as carefree about it as a bird floating among the clouds. Contrast context clues show meaning through dissimilar elements: Contrast:  It isnt exactly the melee that I expected by your description, he said. The kids are just roughhousing a little. I expected them to be bruised and bleeding.Contrast: I know she said she could  reconstitute  the dried fruit, but a wet raisin just isnt a grape any longer. Limitations of Context Clues Learning new words this way has its limitations, as contexts arent always informative; theyll likely give a reader only a general idea of a word, not a full meaning. If the sentences in which the new word appear dont clearly spell out the definition of the word, the meaning may not be retained by the readers memory for long. For long-term retention, a reader needs to see a word multiple times, and having some instances include a definition will increase the likelihood of a person remembering the word.   Michael Graves wrote in The Vocabulary Book: Learning and Instruction, All in all, the descriptive research on learning from context shows that context can produce learning of word meanings and that although the probability of learning a word from a single occurrence is low, the probability of learning a word from context increases substantially with additional occurrences of the word. That is how we typically learn from context. We learn a little from the first encounter with a word and then more and more about a words meaning as we meet it in new and different contexts.

Corporate Reporting Essay Example | Topics and Well Written Essays - 1500 words

Corporate Reporting - Essay Example "Usually mergers occur in a consensual setting where executives from the target Company help those from the purchaser in a due diligence process to ensure that the deal is beneficial to both parties." (Wikipedia) Goodwill is defined as the present value of future earnings in excess of the normal return on net identifiable assets. According to the acquisition events it's defined as the excess of the cost of acquisition over a group's interest in the fair value of the identifiable assets and liabilities of a subsidiary, associate or jointly controlled entity at the date of acquisition. Goodwill is treated as an asset in the balance sheet of a company. The reduction in the goodwill needs to be calculated at annual basis and the decrease should be written off in the profit and loss account. Due to the replacement of IAS22 by the IFRS3 the treatment of goodwill changed to the defacement-only practice in January 2005. The US GAAP has the same treatment of Goodwill and defines it as the surplus acquisition price paid in addition to the fair value of the net identifiable assets. The change in treatment was first undertaken after the imposition of the SFAS142 which transformed the goodwill accounting from changed accounting for goodwill from a paying-off method to defacement-only method in July 1, 2001. As the standard was affecting international groups many of them preferred using US GAAP standards which could minimize the adverse effects of goodwill amortization and was beneficial for the groups The acquiring company should make sure that the value in excess to the fair value of the net assets should not be reduced and hence this difference should be treated as an asset that's not really identifiable. The standard addresses all the issues regarding the disclosure of the information regarding the acquisition and the management can play an important role in making the most of this information. It suggests that an effective business report must have More forward looking information Have more coverage of non-financial value creating information. Should align internal and external information. The model includes different components of business reporting, which are: 1) financial and non financial data regarding the acquisition 2) Management's analysis of financial and non-financial data. 3) Future forecasting information regarding the goodwill. 4) Shareholders and management related information. 5) Background information. 6) Proper disclosure of information 7) Proper information regarding each business segment. The model provides the shareholders and investors with the case of proper information regarding the securities in order to save them from being misallocated. IFRS3 puts more emphasis on stakeholders' relationship rather than on financial measures. Heavy reliance on financial measures has damaged most of the company's reputation. The financial performance does not represent the overall performance of the business. The position of the company in the market and the performance cannot be judge by only addressing the financial measures. The standard recommends that the role of the intangible assets is growing in determining the future performance of a company. The standard provides the solution in shape of focusing more on qualitative measures rather than

Industrial and biotechnology Essay Example | Topics and Well Written Essays - 2000 words

Industrial and biotechnology - Essay Example Its revolution rides on a series of concurrently related advances in three areas: genomics, proteomics, and bioinformatics. It is now possible to manipulate genetic information and design products, or to even tweak gene expression and genetic information can be transferred between markedly different groups of organisms. Recombinant DNA technology and molecular manipulations have been exploited to improve the production by increasing titers and yields of microbial processes. Introduction Industrial biotechnology is the application of biotechnology for production and processing of chemicals, materials, pharmaceuticals, and bio-energy with less energy consumption, reduced greenhouse gas emissions, higher yields and reduced waste. It uses enzymes and micro-organisms to environmentally friendly manufacturing of products by maximizing and optimizing already established and utilized biochemical pathways. Industrial biotechnology, also known as white biotechnology, has developed rapidly in t he last several decades and has enormous potential and versatility in manufacturing with higher yield and titer. The industry’s economy i.e. Bioeconomy has made a substantial impact in the world economy, is growing at rate without historical precedence. It has no doubt, revolutionized almost every sector of economy whether, it is agriculture or healthcare or petroleum industry. Today, biotechnology is a major participant in global economy and promise to be a major player in next a couple of decades. According to Steve Burrill, President and CEO of Burrill & Co at BIO (Biotechnology industry organization) conference, May 2010 in Chicago, USA said with his trade mark optimism that â€Å"those in the industry were fortunate to be alive at this time, when all current world problems -- climate change, sustainability, energy security, food production and security, and healthcare reform could be tackled if not solved by biotechnology†. To-day’s world’s economy i s facing a range of environmental, social, and economic challenges, development and deployment of biotechnology tools can provide opportunities for renewed economic growth. No doubt, it has already successfully established in some sectors, is still in its infancy. It is a market reality and has consumer demand, from new innovative approaches with huge promise to lower the carbon footprint. Major Products of Industrial Biotechnology Industrial biotechnology has provided products that have impacted our lives. These products have profoundly changed our lives, environment, and economy. They include industrial and agricultural products, food additives, healthcare products, and biofuels. The development of penicillin fermentation in the 1940s marked the beginning of industrial biotechnology. This resulted in production of a large number of metabolites of commercial importance by fermentation. Primary metabolism inside a living organism involves a cascade of enzyme mediated catabolic, and anabolic reactions which provide biosynthetic intermediates and energy, and convert biosynthetic precursors into essential macromolecules such as DNA, RNA, proteins, lipids, and polysaccharides. It is finely balanced and intermediates are rarely accumulated. By deregulating primary metabolism, overproduction of many primary metabolites has been achieved in the fermentation industry. There is enormous use of biotechnological processes in production of primary and secondary