Critical Study of Apoptosis and programmed cell death The WritePass Journal

Critical Study of Apoptosis and programmed cell death Introduction Critical Study of Apoptosis and programmed cell death IntroductionReferencesRelated Introduction Apoptosis in the hair follicle is programmed cell death, which occurs at a point during the cell cycle, when a sequence of programmed events causes the cells to be eliminated without the release of waste and harmful substances into the surrounding vicinity. Control of apoptosis is crucial to development of new and recycling of old cells within the body as over stimulation of apoptosis can be fatal, causing extreme tissue damage- examples of which are cancer sufferers. In this review we will discuss evidence from scientific experiments which investigate regulators of apoptosis and what really controls apoptosis in the hair follicle. Apoptosis within the hair follicle cycle is controlled by many molecular processes and elements, of which include cytokines, tumor necrosis factor receptors, bcl-2 family gene products and ICE proteases (Soma et al., 1998). Apoptosis occurs during the catagen stage of follicle cycling which can also be known as the regression stage, and begins with initiation of receptors to their binding sites. This is specifically the binding of receptors that are rich in extracellular cysteine usually needed for binding, and intracellular compartments specific for signalling (Botchkareva et al., 2006). These receptors- also known as death receptors initiate the beginning of apoptosis, signalling via the mitochondrial membrane and setting in motion adapter molecules complementary to their apoptotic receptors (APO1/Fas receptor or tumor necrosis factor receptor- TNFR). Others include tyrosine kinase receptors- such as nerve growth factor (NGF), and p75 receptor- ‘p75NTR signalling is criticall y important for apoptosis in the regressing ORS and, therefore, for its shortening during catagen’ ( Botchkarev et al.,2000). These signals are conveyed into the cell via a cascade of enzymes known as caspases, which subsequently lead to the next stages of apoptosis. Investigations into apoptosis show that ‘physiological and pathological catagen is noticeably characterised by an up-regulation of ICE expression and an apparent inversion of the Bcl-2/Bax ratio in all epithelial follicle regions that undergo involution during catagen.’(Linder et al., 1997) This refers to intracellular and extracellular molecules located around the hair follicle, which show some control of the progression of cell death, when subjected to variation. The investigation proved that apoptosis within follicular keratinocytes in a normal state or diseased state occurred after a significant reduction in the Bcl-2/Bax ratio, which in turn caused activation of ICE proteases and eventually activation of endonucleases (Linder et al., 1997). This indicates that Bcl-2 and Bax ratios to an extent control apoptosis when down regulated, and then cause a domino effect to upregulate ICE proteases known as the caspase family, to eventually cause DNA to be cleaved into small er fragments, cell shrinkage and rounding, breakdown of the cytoskeleton and membrane blebbing. Caspases are the final inducer of apoptosis from physiological or pathological stimulation, and therefore play a major role in control of apoptosis, by remaining as an inactive form when apoptosis is not required, but becoming activated by the down regulation of the Bcl-2/Bax family of receptors, when apoptosis is required to take place. Caspases are mediators of apoptosis, and are defined and separated into two groups. The first group are the ‘instigators’ and begin the cascade, the second group are the ‘terminators’ which are activated by the instigators and cause the activation of other enzymes within the cell.   The caspase family consists of caspase-8, caspase-10 and caspase-3, which act to activate the intrinsic pathway, and to link the extrinsic to the intrinsic pathway by releasing cytochrome c, a process which is primarily controlled by a family of proteins known as the Bcl-2 proteins.   These are expressed in the epithelium, surrounding mesench yme, and follicular papilla of the adult hair follicle throughout the cycle (Stenn et al., 1994). The release of cytochrome c ultimately forms a holoenzyme known as the apotosome, which is formed by the apoptosis initiator enzyme procaspase-9, and its adaptor molecule Apaf-1(Botchkareva et al., 2006). These apoptosomes then cleave and activate the procaspase into caspase-9, which subsequently turns on effector caspase-3. Caspase-3 is a major proteolytic enzyme, with the ability to defragment a wide range of molecules and substrates within the cell. The activation of caspase-3 then leads to the cell fragmentation and phagocytosis stages of hair follicle apoptosis. References nature.com/jid/journal/v126/n2/full/5700007a.html ncbi.nlm.nih.gov/pmc/articles/PMC1858357/pdf/amjpathol00024-0099.pdf http://endo.endojournals.org/cgi/content/full/146/3/1214 fasebj.org/content/14/13/1931.long fasebj.org/content/15/9/1592.full.pdf applepoly.com/studies/Analysis_of_Apoptotic_Cell_Death_in_Human_Hair_Follicles.pdf

All About Americas Gilded Age

All About Americas Gilded Age The Gilded Age. The name, popularized by American author Mark Twain, conjures images of gold and jewels, lavish palaces, and wealth beyond imagination. And indeed, during the period we know as the Gilded Age - the late 1800s to the 1920s - American business leaders amassed huge fortunes, creating a suddenly-rich baron class with a fondness for ostentatious displays of newfound wealth. Millionaires built palatial and often gaudy homes in New York City and summer cottages on Long Island and in Newport, Rhode Island. Before long, even refined families like the Astors, who had been wealthy for generations, joined in the whirlwind of architectural excesses. In large cities and then in upscale resort communities, noted established architects like Stanford White and Richard Morris Hunt were designing enormous homes and elegant hotels that mimicked the castles and palaces of Europe. Renaissance, Romanesque, and Rococo styles merged with the opulent European style known as Beaux Arts. The Gilded Age of architecture usually refers to the opulent mansions of the super-wealthy in the United States. The well-to-do built elaborate second homes in the suburbs or in rural settings while at the same time many more people were living in urban tenements and the decaying farmlands of America. Twain was being ironic and satiric in naming this period of American history. Americas Gilded Age The Gilded Age is a time period, an era in history with no specific beginning or end. Families had accumulated wealth from generation to generation - profits from the Industrial Revolution, the building of the railroads, urbanization, the rise of Wall Street and the banking industry, financial gains from the Civil War and Reconstruction, the manufacturing of steel, and the discovery of American crude oil. The names of these families, such as  John Jacob Astor, live on even today. By the time the book The Gilded Age, A Tale of Today was published in 1873, authors Mark Twain and Charles Dudley Warner could easily describe what  was behind the ostentation of wealth in post-Civil War America. There is no country in the world, sir, that pursues corruption as inveterately as we do, says one character in the book. Now here you are with your railroad complete, and showing its continuation to Hallelujah and thence to Corruptionville. For some observers, the Gilded Age was a time of immorality, dishonesty, and graft. Money is said to have been made off the backs of an expanding immigrant population who found ready employment with men of industry. Men such as John D. Rockefeller and Andrew Carnegie are often considered robber barons. Politcal corruption was so pervasive that Twains 19th century book continues to be used as a reference for the 21st century U.S. Senate. In European history this same time period is called the Belle Époque or the Beautiful Age. Architects, too, jumped on the bandwagon of what is often called conspicuous consumption.  Richard Morris Hunt (1827-1895) and Henry Hobson Richardson (1838-1886) were professionally trained in Europe, leading the way to making architecture a valued American profession. Architects the like of Charles Follen McKim (1847-1909) and Stanford White (1853-1906) learned opulence and elegance by working under the leadership of Richardson. Philadelphian Frank Furness (1839-1912) studied under Hunt. The sinking of the Titanic in 1912 put a damper on the boundless optimism and excessive spending of the era. Historians often mark the end of the Gilded Age with the stock market crash of 1929. The grand homes of the Gilded Age now stand as monuments to this time in American history. Many of them are open for tours, and a few have been converted to luxury inns. The 21st Century Gilded Age The great divide between the wealthy few and the poverty of many is not relegated to the end of the 19th century. In reviewing Thomas Pikettys book Capital in the Twenty-First Century, economist Paul Krugman reminds us that It has become a commonplace to say that we are living in a second Gilded Age - or, as Piketty likes to put it, a second Belle Époque - defined by the incredible rise of the one percent. So, where is the equivalent architecture? The Dakota was the first luxury apartment building in New York City during the first Gilded Age. Todays luxury apartments are being designed all over New York City by the likes of Christian de Portzamparc, Frank Gehry, Zaha Hadid, Jean Nouvel, Herzog de Meuron, Annabelle Selldorf, Richard Meier, and Rafael Vià ±oly - they are todays Gilded Age architects. Gilding the Lilly Gilded Age architecture is not so much a type or style of architecture as it describes an extravagance that is not representative of the American population. It falsely characterizes the architecture of the time. To gild is to cover something with a thin layer of gold - to make something appear more worthy than it is or to attempt to improve that which needs no improvement, to overdo, like gilding a lilly. Three centuries earlier than the Gilded Age, even British playwright William Shakespeare used the metaphor in several of his dramas: To gild refined gold, to paint the lily,To throw a perfume on the violet,To smooth the ice, or add another hueUnto the rainbow, or with taper-lightTo seek the beauteous eye of heaven to garnish,Is wasteful and ridiculous excess.- King John, Act 4, Scene 2 All that glitters is not gold;Often have you heard that told:Many a man his life hath soldBut my outside to behold:Gilded tombs do worms enfold.- The Merchant of Venice, Act 2, Scene 7 Architecture of the Gilded Age: Visual Elements Many of the Gilded Age mansions have been taken over by historic societies or transformed by the hospitality industry. The Breakers Mansion is the largest and most elaborate of Newports Gilded Age cottages. It was commissioned by Cornelius Vanderbilt II, designed by architect Richard Morris Hunt, and built oceanside between 1892 and 1895. Across the waters from the Breakers you can live like a millionaire at  Oheka Castle on Long Island in New York State. Built in 1919, the Chà ¢teauesque summer home was built by financier Otto Hermann Kahn. Biltmore Estate and Inn is another Gilded Age mansion that is both a tourist attraction and a place to rest your head in elegance. Constructed for George Washington Vanderbilt at the end of 19th century, Biltmore Estate in Asheville, North Carolina took hundreds of workers five years to complete. Architect Richard Morris Hunt modeled the house after a French Renaissance chateau. Vanderbilt Marble House: Railroad baron William K. Vanderbilt spared no expense when he built a house for his wifes birthday. Designed by Richard Morris Hunt, Vanderbilts grand Marble House,  built between 1888 and 1892, cost $11 million, $7 million of which paid for 500,000 cubic feet of white marble. Much of the interior is gilt with gold. The Vanderbilt Mansion on the Hudson River was designed for Frederick and Louise Vanderbilt. Designed by Charles Follen McKim of McKim, Mead White, the  Neoclassical Beaux-Arts Gilded Age architecture is uniquely set in Hyde Park, New York. Rosecliff Mansion was built for Nevada silver heiress Theresa Fair Oelrichs - not a household American name like the Vanderbilts. Nevertheless, Stanford White of McKim, Mead White designed and constructed the Newport, Rhode Island cottage between 1898 and 1902. Sources Why We’re in a New Gilded Age by Paul Krugman, The New York Review of Books, May 8, 2014 [accessed Jun 19, 2016]Getty Images include Rosecliff Mansion by Mark Sullivan; Biltmore Estate by George Rose; Gold Room of Marble House by Nathan Benn/Corbis; and Vanderbilt Mansion on the Hudson by Ted Spiegel/Corbis