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Introduction and broccoli origin, Use of Accordions in Cajun Music. By Malcolm L. Comeaux. The history of the accordion begins with the invention of the free reed in either southern China or Laos, where instruments using this reed date back to 1000 B.C. (Marcuse 1975: 730-731). Digi Background? In the broccoli origin, free reed, the tongue (lamella) fits in a frame, whereas the beating reed, so common in European instruments, fits on top of the frame. The concept of free reeds was slow to Framework for Counterterrorism Essay, arrive in Europe, and it was not until the late 1700s that they began to be used in broccoli origin, instruments there (Marcuse 1975: 734). The accordion's history begins about 1800 when Europeans began the rapid development of instruments using free reeds. The handaeoline was developed in Berlin in 1822 by C. F. L. Buschmann, and its major advance was that, rather than having a human lung force air over the reeds, it used a mechanical one (Macerollo 1980: 8-13). It had only five buttons on the treble side, but Buschmann realized it could hold more. In Vienna organ builder Cyril Demian improved on the handaeoline by placing fixed chord buttons for the left hand, and on June 6, 1829, patented his akkordion , the what in, first use of the word (Macerollo 1980: 13).

Invention of the broccoli origin, accordion thus dates back to either of these two dates. Demian's akkordion , however, was little more than a toy. A month after the akkordion was patented, Charles Wheatstone in England patented the concertina (Macerollo 1980: 13-15), at the time a much more advanced instrument than the and effects of spanish war, akkordion . This led to rapid development and evolution of the accordion, to broccoli, the point that it was soon accepted as a true musical instrument and no longer only a toy or curiosity. By 1835 there were at least six varieties of accordions available (Marcuse 1964: 2). Manufacturing of these instruments began quickly, and to avoid the question of the patent, some manufacturers who copied the akkordion called their instrument handharmonika , a word by which it now is known in some parts of the world (Marcuse 1975: 742). Many were manufactured and shipped around the world. In some way or another accordions made their way to South Louisiana and were accepted by advantages of total management the Cajuns. It will probably never be known when the first accordion came to origin, Louisiana, or when the first Cajun acquired or played one, nor does it really matter. What is important is that they did come to lipids biology, Louisiana and were accepted by musicians in broccoli origin, Southwest Louisiana.

This fact greatly changed the music of this area. The primary musical instrument used in Canada by and effects american Acadians prior to expulsion (1755) was the fiddle (or violin), and it remains the main instrument among Acadians in the Maritime Provinces (Chiasson, et. al. 1995: 699-701). Acadian refugees coming to broccoli origin, Louisiana either brought fiddles with them, or much more likely, acquired fiddles soon after their arrival (either homemade or purchased). The fiddle was widely used at house dances after Louisiana settlement, and house dances remained popular well into the twentieth century. House dances were undoubtedly crowded and noisy. Although only six to twelve couples danced at a time (Broven 1987: 12), there were many people in and around the house, and they were all talking, laughing, and in general enjoying themselves.

In order to quality management, be heard above the din, Cajun violinists developed a playing style that required them to bear down hard on bows in broccoli origin, order to play as loud as possible (Ancelet and Morgan 1984: 22). It gave this music a unique sound, but acceptance of the accordion was to bring many changes to the music. Introduction of the Accordion into South Louisiana. There is definite proof of an accordion in Louisiana in 1871 (Fig. 1). Documenting this is a picture of an old German lighthouse-keeper near the mouth of the Mississippi River playing an accordion (Keeler and Waud 1871: 524-26). This is appropriate, since accordions were probably exported from Germany to French Louisiana via the lower Mississippi River. There is what in, other evidence of accordions very early in broccoli origin, South Louisiana.

Tisserand (1998: 44-45) illustrates a copy of a daguerreotype, dated circa 1850, that is located in the Louisiana State Museum in New Orleans. A very old type of accordion, only did karl in vaguely resembling modern ones (for example, there are 12 buttons on the treble side), is held in the hands of a black musician, but there is no proof that it is truly from mid-century. Broccoli? Another early view of a black accordionist in Louisiana was in at the, 1877 when a black prisoner is broccoli origin, shown playing for fellow prisoners and guards (and another has a banjo) along the Cane River in central Louisiana ( Frank Leslie's Illustrated Newspaper 1877: 264) (Fig. 2). If a black prisoner can have an accordion, and knew how to play it, it should be assumed that accordions were rather widely available by the 1870s. Blacks, as seen above, had access to on Studies University Essays, accordions, and probably played a major role in acceptance of accordions in South Louisiana. Canray Fontenot, a black Creole fiddle player, related how he had been told that during the days of slavery some blacks learned to broccoli, play the accordions of their masters (Tisserand 1998: 44), and in a short story by Kate Chopin, published in 1897, three black musicians, two fiddlers and an accordionist, play at a dance for whites (Chopin 1969: 490). Reflection At The Essays? Canray, born in 1922, also states that his father, his mother, and his father's father all played the accordion (in Savoy 1984: 326). Thus, the accordion in Creole culture goes rather far back.

In the early twentieth century some of the most influential and innovative musicians were black Creoles (Ancelet 1989: 19). Several were accordionists, such as Amédé Ardoin and Adam Fontenot (father of Canray) (Ancelet and Morgan 1984: 23), and many older Cajun musicians mention Amédé Ardoin as having a major influence on their music. There was much cooperation between white and origin, black musicians (Ancelet, 1991: 150-51; Ancelet and Reflection at the, Morgan 1984: 74; Olivier and Sandmel 1999: 130), and many blacks played at white dances, so their influence was probably not insignificant (Ancelet 1989: 19-20; Bernard 1996: 12; Spitzer, 1986: 316-21). Although accordions were in Louisiana at an early date, their acceptance by Cajuns came later. In a book published in 1861 on a series of controversial incidents on the prairies of Southwest Louisiana, a Frenchman often mentioned fiddles (and fiddle players, although never in a positive light), as well as other instruments, such as mandolin, banjo, and guitar.

No accordion or accordion player, however, was ever mentioned (Barde 1981: passim). Twenty years later, a visitor on the prairies encountered a settlement of 150 Cajun families, and found no less than sixty fiddlers, an amazingly large number for a relatively small settlement ( Frank Leslie's Popular Monthly 1881: 566). But, again, there was no mention of accordion players. Although the accordion was introduced in the latter half of the 19th century, and was probably widely available, one scholar maintains that fiddles remained the main instrument of choice on the prairies of Southwest Louisiana until the 1920s (Sexton 1996: 157-159), and this was undoubtedly the broccoli, case. One way accordions may have been acquired was through the mail . Frank Leslie's Illustrated Newspaper (1886: 206) had an advertisement of accordions for sale in 1886. Such a magazine, however, would have been read only by local upper classes, a group that typically had disdained accordions. Accordions were also offered for sale in various early catalogs. The Montgomery Ward Company was distributing catalogs by the early 1870s, and the first Sears, Roebuck catalog was issued in 1894 (Latham 1972: 6-12; Weil 1978: 11). In a reproduction of a 1908 catalog, twenty accordion types manufactured by five companies are offered for lipids biology, sale (Sears, Roebuck 1969: 243-44). Those who accepted the accordion were the origin, largely under-educated Cajuns on the prairies of Southwest Louisiana, with many being illiterate. While it is possible for them to of spanish american, have seen such early advertisements, they probably would not have ordered them by mail, and certainly not before they had acquired some prior knowledge of accordions and broccoli, how to play them.

Accordions made by the Hohner Company were very popular, and any Hohner accordion sold through the 1908 catalog included a free carrying case (Sears, Roebuck 1969: 244). Older musicians, however, always mentioned carrying accordions in sacks, not cases. I believe that German-Jewish merchants were important in the sale of accordions. There were Jewish merchants with stores in all Cajun towns, and probably the best example was the Mervine Kahn store in Rayne, established in 1884 (Fontenot and Freeland 1997: 139, 324), only four years after the railroad arrived. Many Cajuns bought their accordions from and effects american war Mervine Kahn prior to World War II. How the first accordions arrived at broccoli origin these stores is unknown. The first ones may have been imported in a speculative fashion by Jewish merchants. More probably Cajuns began requesting accordions, and digi background, Jewish merchants found they could import and sell them for a profit. Broccoli Origin? These merchants, with close connections to Eastern firms, and possibly directly with German manufacturing companies, began importing accordions to their rural, unsophisticated, French-speaking customers. Early Acceptance of the digi background, Accordions by Cajuns.

We will never know the name of the first person to bring an accordion into South Louisiana. Since the accordion evolved in German-speaking lands, it is usually assumed that it was a person from this region who first brought an accordion to South Louisiana. Germans were constantly filtering into New Orleans and from there into Southwest Louisiana. The only organized settlement of Germans in Southwest Louisiana, in origin, Roberts Cove, did not occur until 1881, well after the accordion was in Louisiana (McCord 1969: 70). Also, German-Americans from this community were never noted for lipids biology, playing accordions, so they played no role in acceptance of the accordion. German-American wheat farmers from the origin, Midwest came to Cajun country to become involved in the rice industry soon after 1880, and one researcher states it is probable that one of these introduced the instrument (Blanchet 1970: 72). Another source states that the accordion entered South Louisiana by on Studies University Essays way of Texas and broccoli, German settlers (Ancelet and Morgan 1984: 22). There is simply no proof for any of of total quality management, these theories at broccoli this time. It must further be noted that accordions were manufactured in places other than Germany, such as in France, and advantages quality, accordions were exported around the world at a very early date. Broccoli? The first accordion could have arrived here in any number of ways, and by whom, when, and how is not important. What is important is of total, that it came, was accepted, and made a major impact on Cajun music.

It will probably never be known when the broccoli, first Cajun began to what did karl marx, play the origin, accordion or who this person was, but it seems that the Reflection on Studies at the University Essays, first individual to bring an accordion to South Louisiana did not teach Cajuns or black Creoles to play it. People on the prairie of Southwest Louisiana developed a style of playing that was not smooth and easy, as was done in Europe, but rather they began playing with fast choppy rhythms in a syncopated style that had many fast runs. It evolved into a style not found elsewhere in the world, and based on the style, probably first developed by black Creoles and then taught to Cajuns. The first Creoles to develop accordion skills were probably descendants of small independent black farmers who lived on the prairie west of Opelousas. Origin? This is the only large settlement of small independent black farmers on the prairie, and it is in Framework for Counterterrorism, this area where many of the early black accordionists originated, and where many, especially those using the old diatonic accordion, are now found. Broccoli? This region has always been a hotbed of and effects american, accordion players, both white and black.

Although there were undoubtedly accordions in South Louisiana at an early date, they at first did not make an impression on Cajun musicians. One reason is that the first ones imported were in the keys of A and F (Comeaux 1978: 118; Savoy 1984: 13). The fiddles could not be tuned to those keys (the strings would have to be strung too tight, and thus tended to origin, break), so the accordion had to be played as a solo instrument. It did not receive much local attention. A New For Counterterrorism? Good quality accordions, made with excellent reeds and good quality bellows, began to be imported in the early 1900s. The first of these was the Monarch brand, and later the Sterling and Eagle were introduced, and they were widely accepted by Cajuns. These were called les tit noirs (the little blacks) by their users because of their color, and broccoli, they became the A New, basic model for broccoli, all Cajun accordions after this time (except for the color). It was in the 1920s that accordions in the keys of C and D began to be imported (Savoy 1984: 13). Digi Background? These could be played with the fiddle, and now the accordion, already well known and origin, widely used, exploded in popularity. Accordions lost popularity in the 1930s, and when they again came in vogue in the 1940s, none were to be had from Germany. No accordions were imported during World War II, and few were imported for many years after the war because German factories were devastated, and some accordion factories were located in the Russian sphere of influence.

Since no new accordions could be purchased for a considerable time, local Cajuns began repairing and refurbishing old accordions, and soon began making accordions (Comeaux 1978). The quality of these first accordions was not particularly good (because the reeds and bellows were often taken from Hohner accordions, or from very old accordions). Quality, however, has improved greatly since 1980, and now the A New for Counterterrorism Essay, accordions are made by true craftsmen using the finest of imported bellows, reeds (both from Italy), and woods. They cannot be called truly homemade (Fig. 3). There are at present 29 persons in Southwest Louisiana making accordions (and one in Texas and another in broccoli, New Orleans), and digi background, their accordions are sold around the world. Unfortunately, Cajun music was often derogatorily called chank-a-chank, and throughout the first half of the twentieth century (at least until the mid-1960s) this music was not valued by the local intelligentsia. It was considered the broccoli origin, music of unsophisticated, rural, under-educated whites.

Anyone who played it, or listened to it, received ridicule by the educated and the press. It was not until this music was accepted on the national level, particularly at national folk festivals, that the educated in did karl, Louisiana realized that it was a unique music style and broccoli, worthy of respect. This national recognition also gave local Cajun musicians respect and pride in their music and their skills, and acceptance grew rapidly among all people in South Louisiana. Some black Creoles from Southwest Louisiana, steeped in French culture and tradition, also accepted the accordion, but took the music along different lines. This Creole music was first called la-la , but now it is universally known as zydeco. Many of the did karl in, black zydeco musicians use large piano accordions or triple-row button accordions (especially those living along Bayou Teche), but the small diatonic accordion was always popular with black Creoles on the prairies, and origin, several of these folks in recent years have received recognition in the zydeco community. Zydeco music is A New for Counterterrorism, thus played on all types of origin, accordions, but small diatonic accordions, similar to the ones made and used by Cajuns, seem to be gaining in popularity in zydeco music. Although accordions were dependable and did not tend to get out of tune, probably the main reason they were accepted by of spanish american war Cajuns and Creoles was the fact that they were loud instrumentsin fact very loud when compared to origin, other folk instruments. Even when fiddlers bore down hard on their bows, they could not make it play loud enough to be heard over what did karl in a large crowd. Fiddles were acceptable in a confined place, such as a room at a house dance, but when dance halls began to gain acceptance in the late 1800s, dancers could only hear music from the fiddle when they were immediately in front of the band (they went in a counter-clockwise fashion on the dance floor).

Electric amplification of music began in the early 1930s (Savoy 1984: 115-16, 118; Post 1970: 46ff). At that time fiddle players began to change their style to origin, a lighter one, but by then the accordion was firmly entrenched, and fiddles (although quite loud with amplification) had taken a back seat to accordions in Cajun and Creole music in Southwest Louisiana. Other instruments were added to Cajun bands, and today it is common to hear drums, guitars, steel guitars, a small triangle, and the like, but accordions remain the main instrument that defines a Cajun band. The accordion goes back to for Counterterrorism, the latter half of the 19th century in South Louisiana. How, when, and by whom it was first introduced is unknown, but the influence of black musicians cannot be discounted. The accordion was accepted on a limited scale by Cajuns sometime at the end of the 19th century, and broccoli origin, became very popular by the 1920s when accordions were imported in keys that were compatible with fiddles. It is the instrument by digi background which most Cajun music is origin, identified, especially that from the prairies of Southwest Louisiana, and this music has had an impact on the national scene.

Limited in on Studies at the University Essays, keys and notes, the broccoli, diatonic accordion's acceptance greatly simplified old Cajun songs, and those songs it could not play were abandoned (Ancelet and Morgan 1984: 23; Savoy 1984: 13). Cajun music lost much, but gained in other ways, as it continued to Framework, grow and evolve. There was a brief time in the 1930s when the broccoli origin, accordion, and Cajun music in general, began to lose favor, but it was revived in A New Essay, the 1940s, and today is growing in popularity and recognition, not only in broccoli origin, South Louisiana, but around the A New for Counterterrorism, country, and indeed around the world. It is no longer considered chank-a-chank music, and rarely is this derogatory term used today. Many very young musicians are learning to broccoli, play the accordion, and bands now are having a hard time finding fiddle players. Many Cajuns now play the accordion as if to make a political statementI am a Cajun. Older Cajun tunes are still being played, and new sounds are constantly evolving. Excellent quality accordions are being hand-made by local artisans (and inferior copies are made and sold by German manufacturing firms), and many youngsters are learning to play it. The future of the Reflection on Studies University Essays, accordion in South Louisiana, and in Cajun music, is firm. Ancelet, Barry Jean. 1989.

Cajun Music: Its Origins and Development . Broccoli Origin? Louisiana Life Series, No. 2. Lafayette: Center for Louisiana Studies, University of Southwestern Louisiana. Ancelet, Barry Jean, Jay Edwards, and Glen Pitre. A New Framework Essay? 1991. Cajun Country . Origin? Jackson: University Press of Mississippi. Ancelet, Barry Jean, and Elmore Morgan, Jr. 1984. The Makers of Cajun Music /Musiciens cadiens et créoles.

Austin: University of Texas Press; and Québec: Presses de l'Université du Québec. Barde, Alexandre. 1981. Digi Background? The Vigilante Committees of the Attakapas . ed. by origin David Edmonds and Dennis Gibson, tran. by Henrietta Guilbeau Rogers. Lafayette, La.: Acadiana Press. Bernard, Shane K. 1996. Swamp Pop: Cajun and Creole Rhythm Blues . Jackson: University Press of Mississippi. Blanchet, Catherine. 1970. Acadian Instrumental Music.

Louisiana Folklore Miscellany 3 (1): 70-75. Broven, John. 1987. South to Louisiana: The Music of the Cajun Bayous . Gretna, La.: Pelican Publishing. Chiasson, Anselme, Charlotte Cormier, Donald Deschenes, and Ronald LaBelle. 1995. Le Folklore Acadien. In L'Acadie des Maritimes, ed. Framework For Counterterrorism? Jean Daigle, pp. 649-705. Moncton, N.B.: Chair d'etudes acadiennes, Universite de Moncton.

Chopin, Kate. Broccoli Origin? 1969. The Complete Works of Kate Chopin (2 Vols), ed. Per Seyersted. Baton Rouge: Louisiana State University Press. Comeaux, Malcolm L. University? 1978. The Cajun Accordion. Louisiana Review 7: 117-28. Fontenot, Mary Alice, and Paul B. Broccoli Origin? Freeland.

1997. Acadia Parish, Louisiana: A History to 1900 , Vol. Of Total Quality Management? 1. Lafayette: Center for Louisiana Studies, University of broccoli origin, Southwestern Louisiana. Frank Leslie's Illustrated Newspaper . 1877. Dec. 22, 264: 1886, May 15, 206. Frank Leslie's Popular Monthly .1881. Framework For Counterterrorism? 12: 566. Keeler, Ralph, and broccoli origin, Frank Waud.

1871. On the Mississippi. Every Saturday . June 3, 524-26. Latham, Frank Brown. Reflection On Studies? 1972. 1872-1972, A Century of Serving Consumers: The Story of Montgomery Ward . Origin? Chicago: Montgomery Ward. Macerollo, Joseph.

1980. Accordion Resource Manual . n.p.: Avondale Press. Marcuse, Sibyl. 1964. Musical Instruments: A Comprehensive Dictionary . Garden City, N.Y.: Doubleday. _____. 1975. A Survey of Musical Instruments . New York: Harper and Row. McCord, Stanley Joe. Did Karl? 1969.

A Historical and Linguistic Study of the origin, German Settlement at Roberts Cove, Louisiana. What Did Karl Marx Believe In? Ph.D. dissertation. Louisiana State University. Olivier, Rick, and broccoli, Ben Sandmel. 1999.

Zydeco . Jackson: University Press of Mississippi. Post, Lauren C. 1970. Joseph C. Falcon, Accordion Player and Singer. Louisiana History , 11: 63-79. Savoy, Ann Allen. Digi Background? 1984. Broccoli Origin? Cajun Music: A Reflection of a People, (Vol. 1). Eunice, La.: Bluebird Press. Sears, Roebuck and digi background, Company.

1969,. The Great Price Maker, Catalog Number 117, 1908 , ed. Joseph J. Schroeder, Jr. Chicago: Follett. Sexton, Rocky. Origin? 1996. Cajuns, Germans, and A New Framework, Les Americans: A Historical Anthropology of Cultural Demographic Transformations. Ph.D. dissertation, University of origin, Iowa. Spitzer, Nicholas. 1986.

Zydeco and Mardi Gras: Creole Identity and for Counterterrorism, Performance Genres in Rural French Louisiana. Ph.D. Dissertation, University of broccoli, Texas. Tisserand, Michael. 1998, The Kingdom of Zydeco . New York: Arcade. Weil, Gordon Lee. A New Framework Essay? 1978. Sears, Roebuck, U.S.A.: The Great American Catalog Store and How it Grew . Briarcliff Manor, N.Y.: Stein and Day. There is no proof or evidence that this photo was taken at mid-century. It could have been taken much later, with a musician holding an old instrument.

Also, if it was taken in Louisiana (and it probably was), it was probably taken in New Orleans, and not in Southwest Louisiana. 2. Broccoli? Tisserand (1998: 44) reported on a WPA interview where an accordion was mentioned long ago, but it stretches credulity in some respects. Lipids Biology? It was from a woman reportedly born in 1827, who as a young girl went to dances where an accordion was played by a black musician. It would thus have probably been prior to broccoli, 1847. But, if the lipids biology, interviewee was truly born in 1827, that would have meant that she was well over 100 at broccoli origin the time of a WPA interview, and and effects american, 1847 is terribly early to origin, find the accordion in South Louisiana.

This was reported for and effects american, the lower Teche, an area today not noted for accordion players. 3. Accordionists in broccoli origin, Black Africa also play in a highly syncopated style, and while not identical to that found in Cajun music, it is rather close. 4. According to Larry Miller, an digi background, accordion maker from origin Iota, it was Mr. John J. Mrnustik, an lipids biology, owner of a music store in Houston and broccoli, an immigrant from digi background Eastern Europe, who first began making accordions sometime in the 1950s. Origin? He would only make them when he had an order for five or more, and he sold them locally and to Cajuns in causes and effects of spanish american war, Southwest Louisiana. His widow told Mr. Miller that he made over ten accordions. Mr. Sidney Brown, of Lake Charles, is the person recognized as making the first accordions in Louisiana. He had been repairing accordions, and may have picked up the idea of making accordions from Mr. Mrnustik.

5. The best studies of zydeco are by Tisserand (1998) and Spitzer (1986: 300-410). This article was first published in the 1999 issue of the Louisiana Folklore Miscellany and broccoli, is reprinted here with permission. Dr. Malcolm Comeaux is a cultural geographer at A New for Counterterrorism Essay Arizona State University in broccoli, Tempe, Arizona. Louisiana Folklife Program, PO Box 44247, Baton Rouge, LA 70804, tel 225-342-8180.

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43 Resume Tips That Will Help You Get Hired. Broccoli! When you havent updated your resume in advantages of total quality, a while, it can be hard to know where to start. What experiences and broccoli accomplishments should you include for the jobs youve got your eye on? What new resume rules and trends should you be following? And seriously, one page or two? Well, search no more: Weve compiled all the A New Framework for Counterterrorism Essay, resume advice you need into one place. Read on for tips and tricks thatll make sure you craft a winning resumeand help you land a job.

Your resume should not have every work experience youve ever had listed on it. Think of broccoli origin your resume not as a comprehensive list of your career history, but as a marketing document selling you as the for Counterterrorism, perfect person for the job. For each resume you send out, youll want to highlight only the broccoli origin, accomplishments and skills that are most relevant to the job at hand (even if that means you dont include all of advantages of total quality your experience). Job search expert Lily Zhang explains more about what it means to tailor your resume here . 2. But Keep a Master List of All Jobs. Since youll want to be swapping different information in and out depending on the job youre applying to, keep a resume master list on your computer where you keep any information youve ever included on a resume: old positions, bullet points tailored for different applications, special projects that only sometimes make sense to include. Then, when youre crafting each resume, its just a matter of cutting and pasting relevant information together. Think of this as your brag file . 3. Put the Best Stuff Above the Fold In marketing speak, above the fold refers to what you see on the front half of a folded newspaper (or, in the digital age, before you scroll down on a website), but basically its your first impression of a document. In resume speak, it means you should make sure your best experiences and accomplishments are visible on origin, the top third of your resume. Framework For Counterterrorism! This top section is what the hiring manager is going to see firstand what will serve as a hook for someone to keep on reading.

So focus on putting your best, most relevant experiences firstand then check out these five other marketing tricks to broccoli origin get your resume noticed . Lipids Biology! According to broccoli Zhang , the only occasion when an objective section makes sense is when youre making a huge career change and digi background need to explain from the get-go why your experience doesnt match up with the position youre applying to. In every other case? Consider whether a summary statement would be right for origin you or just nix it altogether to save space and focus on making the rest of your resume stellar. There are lots of digi background different ways to organize the information on your resume, but the good old reverse chronological (where your most recent experience is broccoli origin listed first) is at the University still your best bet. Unless its absolutely necessary in your situation, skip the broccoli origin, skills-based resumehiring managers might wonder what youre hiding. The two- (or more!) page resume is a hotly debated topic , but the bottom line is thisyou want the information here to be concise, and making yourself keep it to digi background one page is a good way to force yourself to do this.

If you truly have enough relevant and important experience, training, and origin credentials to showcase on more than one page of digi background your resume, then go for it. But if you can tell the same story in less space? Do. If youre struggling, check out these tips for cutting your content down , or work with a designer to broccoli origin see how you can organize your resume to fit more in less space. Cant figure out quality, how to broccoli origin tell your whole story on one page, or want to be able to lipids biology include some visual examples of your work? Instead of broccoli origin trying to have your resume cover everything, cover the most important details on that document, and then include a link to your personal website , where you can dive more into what makes you the advantages of total quality, ideal candidate. Well talk about getting creative in broccoli, order to stand out in lipids biology, a minute. But the most basic principle of good resume formatting and design? Keep it simple.

Use a basic but modern font, like Helvetica, Arial, or Century Gothic. Make your resume easy on origin, hiring managers eyes by using a font size between 10 and 12 and leaving a healthy amount of white space on lipids biology, the page. Origin! You can use a different font or typeface for your name, your resume headers, and the companies for which youve worked, but keep it simple and keep it consistent. Your main focus here should be on readability for Framework the hiring manager. That being said, you should feel free to Really want your resume stand out broccoli origin, from the sea of digi background Times New Roman? Yes, creative resumeslike infographics, videos, or presentationsor resumes with icons or graphics can set you apart, but you should use them thoughtfully. If youre applying through an ATS, keep to the standard formatting without any bells and whistles so the computer can read it effectively. If youre applying to a more traditional company, dont get too crazy, but feel free to add some tasteful design elements or a little color to broccoli make it pop. No matter what, dont do it unless youre willing to put in A New for Counterterrorism, the time, creativity, and design work to make it awesome.

10. Make Your Contact Info Prominent. You dont need to broccoli include your address on your resume anymore (really!), but you do need to make sure to include a phone number and professional email address (not your work address!) as well as other places the hiring manager can find you on the web, like your LinkedIn profile and Twitter handle. (Implicit in this is causes and effects that you keep these social media profiles suitable for prospective employers.) Youve heard before that hiring managers dont spend a lot of time on each individual resume. So help them get as much information as possible, in as little time as possible. These 12 small formatting changes will make a huge difference. Know that design skills arent your strong suit but want your resume to look stunning? Theres no shame in getting help, so consider working with a professional resume designer. Broccoli! This is arguably the most important document of your job search, so its worth getting it exactly right!

13. Digi Background! Keep it Recent, Keep it Relevant. As a rule, you should only show the most recent 10-15 years of your career history and only include the experience relevant to broccoli origin the positions to which you are applying. And remember to allocate real estate on your resume according to importance. If theres a choice between including one more college internship or going into more detail about your current role, always choose the latter (unless a previous job was more relevant to the one youre applying to). 14. No Relevant Experience? No Worries! Dont panic if you dont have any experience that fits the bill. Instead, Zhang explains , focus your resume on your relevant and advantages of total quality management transferrable skills along with any related side or academic projects, and then make sure to broccoli origin pair it with a strong cover letter telling the Framework for Counterterrorism Essay, narrative of why youre ideal for the job.

No matter how long youve been in a job, or how much youve accomplished there, you shouldnt have more than five or six bullets in origin, a given section. No matter how good your bullets are, the recruiter just isnt going to get through them. Check out these tips for digi background writing impressive bullet points . You may be tempted to throw in tons of industry jargon so you sound like you know what youre talking about, but ultimately you want your resume to be understandable to the average person. Remember that the first person who sees your resume might be a recruiter, an assistant, or even a high-level executiveand you want to be sure that it is readable, relevant, and interesting to broccoli origin all of them. Use as many facts, figures, and numbers as you can in your bullet points. How many people were impacted by your work? By what percentage did you exceed your goals? By quantifying your accomplishments, you really allow the hiring manager to advantages management picture the level of work or responsibility you needed to broccoli achieve them. Even if you dont actually work with numbers, here are some secrets to adding more to your resume . People hire performers, so you want to show that you didnt just do stuff, but that you got stuff done! As you look at your bullet points, think about how you can take each statement one step further and advantages quality management add in broccoli, what the benefit was to your boss or your company.

By doing this, you clearly communicate not only what youre capable of, but also the lipids biology, direct benefit the employer will receive by origin, hiring you. If youre not sure how to explain your impact, check out these tips for turning your duties into accomplishments . Describing soft skills on a resume often starts to sound like a list of meaningless buzzwords, fast. But being a strong leader or an effective communicator are important characteristics you want to get across. Digi Background! Think about broccoli how you can demonstrate these attributes in your bullet points without actually saying them. Zhang demonstrates here how you can show five different qualities with the same bullet pointtry it yourself until you get the result youre going for! 20. Framework Essay! Dont Neglect Non-Traditional Work. Theres no law that says you can only put full-time or paid work on your resume. So, if youve participated in a major volunteer role, worked part-time, were hired as a temporary or contract worker , freelanced, or blogged? Absolutely list these things as their own jobs within your career chronology.

If every bullet in your resume starts with Responsible for, readers will get bored very quickly. Broccoli! Use our handy list of better verbs to mix it up ! Use keywords in your resume: Scan the and effects of spanish, job description, see what words are used most often, and make sure youve included them in your bullet points. Not only is broccoli this a self-check that youre targeting your resume to the job, itll make sure you get noticed in digi background, applicant tracking systems. Stuck on which words to include? Dump the job description into origin a tool like TagCrowd , which will analyze and spit out the most used keywords. What words shouldnt you include? Detail-oriented, team player, and hard workeramong other vague terms that recruiters say are chronically overused . We bet theres a better way to describe how awesome you are. 24. A New Essay! Experience First, Education Second. Unless youre a recent graduate, put your education after your experience. Origin! Chances are, your last couple of jobs are more important and relevant to you getting the job than where you went to college.

25. Also Keep it Reverse Chronological. Usually, you should lay down your educational background by advantages, listing the most recent or advanced degree first, working in reverse chronological order. But if older coursework is more specific to the job, list that first to grab the reviewers attention. Dont list your graduation dates. The reviewer cares more about whether or not you have the degree than when you earned it.

If you graduated from college with high honors, absolutely make note of it. Broccoli Origin! While you dont need to Reflection on Studies list your GPA, dont be afraid to broccoli origin showcase that summa cum laude status or the fact that you were in the honors college at your university. 28. Include Continuing or Online Education. Dont be afraid to lipids biology include continuing education, professional development coursework, or online courses in your education section, especially if it feels a little light. Kelli Orrela explains , Online courses are a more-than-accepted norm nowadays, and your participation in them can actually show your determination and motivation to get the skills you need for your career. Be sure to broccoli origin add a section that lists out all the relevant skills you have for a position, including tech skills like HTML and Adobe Creative Suite and any industry-related certifications.

Just make sure to skip including skills that everyone is expected to have, like using email or Microsoft Word. Doing so will actually make you seem less technologically savvy. Lipids Biology! If you have lots of skills related to a positionsay, foreign language, software, and leadership skillstry breaking out one of those sections and origin listing it on its own. Below your Skills section, add another section titled Language Skills or Software Skills, and detail your experience there. Againwere going for digi background skimmability here, folks!

Feel free to include an Interests section on your resume, but only add those that are relevant to the job. Are you a guitar player with your eye on a music company? Definitely include it. But including your scrapbooking hobby for origin a tech job at lipids biology, a healthcare company? Dont even think about it. 32. Beware of Interests That Could Be Controversial. Maybe you help raise money for your church on the reg. Origin! Or perhaps you have a penchant for canvassing during political campaigns.

Yes, these experiences show a good amount of work ethicbut they could also be discriminated against by someone who disagrees with the cause. Zhang explains here how to weigh the decision of whether to include them or not. Do include awards and accolades youve received, even if theyre company-specific awards. Just state what you earned them for, e.g., Earned Gold Award for having the companys top sales record four quarters in did karl marx, a row. What about personal achievementslike running a marathonthat arent totally relevant but show youre a driven, hard worker? Zhang shares the broccoli origin, proper ways to include them. On Studies University! Gaps and Other Sticky Resume Situations. If you stayed at a (non-temporary) job for only a matter of months, consider eliminating it from your resume. According to The New York Times career coach , leaving a particularly short-lived job or two off your work history shouldnt hurt, as long as youre honest about your experience if asked in broccoli origin, an interview.

If you have gaps of a few months in your work history, dont list the usual start and Reflection on Studies at the end dates for broccoli each position. Lipids Biology! Use years only (2010-2012), or just the number of years or months you worked at your earlier positions. If youve job-hopped frequently, include a reason for leaving next to each position, with a succinct explanation like company closed, layoff due to downsizing, or relocated to new city. By addressing the broccoli, gaps, youll proactively illustrate the reason for your sporadic job movement and make it less of an issue. Re-entering the workforce after a long hiatus? This is the perfect opportunity for a summary statement at A New Framework Essay, the top, outlining your best skills and accomplishments. Then, get into broccoli your career chronology, without hesitating to what did karl marx believe include part-time or volunteer work. See more tips from Jenny Foss for killing it on your comeback resume. Dont try to creatively fill in origin, gaps on Framework for Counterterrorism, your resume. Broccoli Origin! For example, if you took time out of the what marx, workforce to raise kids, dont list your parenting experience on your resume, a la adeptly managed the broccoli origin, growing pile of laundry (weve seen it). While parenting is digi background as demanding and intense a job as any out there, most corporate decision makers arent going to take this section of your resume seriously. 39.

Ditch References Available Upon Request If a hiring manager is interested in origin, you, he or she will ask you for referencesand will assume that you have them. Theres no need to address the Reflection on Studies at the University, obvious (and doing so might even make you look a little presumptuous!). It should go without saying, but make sure your resume is broccoli origin free and clear of typos. And dont rely on spell check and grammar check aloneask family or friends to digi background take a look at it for you (or get some tips from an broccoli origin, editor on what did karl in, how to origin perfect your own work ). If emailing your resume, make sure to causes and effects war always send a PDF rather than a .doc. That way all of your careful formatting wont accidentally get messed up when the hiring manager opens it on origin, his or her computer.

To make sure it wont look wonky when you send it off, Googles head of HR Laszlo Bock suggests, Look at it in and effects war, both Google Docs and origin Word, and then attach it to an email and advantages of total management open it as a preview. Ready to save your resume and send it off? Save it as Jane Smith Resume instead of Resume. Its one less step the broccoli, hiring manager has to take. Carve out some time every quarter or so to pull up your resume and make some updates. Have you taken on at the, new responsibilities? Learned new skills? Add them in. When your resume is updated on broccoli, a regular basis, youre ready to did karl marx believe in pounce when opportunity presents itself. Broccoli! And, even if youre not job searching, there are plenty of good reasons to keep this document in tip-top shape. Photo courtesy of Hero Images / Getty Images . Erin Greenawald is a freelance writer, editor, and content strategist who is passionate about elevating the standard of writing on A New Framework for Counterterrorism Essay, the web. Erin previously helped build The Muses beloved daily publication and led the companys branded content team.

If youre an individual or company looking for help making your content betteror you just want to origin go out to teaget in touch at Hmmm, seems you#39;ve already signed up for this class. While you#39;re here, you may as well check out Framework for Counterterrorism, all the amazing companies that are hiring like crazy right now.

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Cellular and molecular pathogenesis of systemic lupus erythematosus: lessons from animal models. BioMed Central Ltd 2011. Published: 30 September 2011. Systemic lupus erythematosus (SLE) is a complex disease characterized by the appearance of autoantibodies against nuclear antigens and the involvement of multiple organ systems, including the kidneys. The precise immunological events that trigger the onset of clinical manifestations of broccoli origin SLE are not yet well understood. However, research using various mouse strains of spontaneous and inducible lupus in and effects the last two decades has provided insights into the role of the immune system in broccoli origin the pathogenesis of this disease. According to our present understanding, the immunological defects resulting in digi background the development of origin SLE can be categorized into two phases: (a) systemic autoimmunity resulting in on Studies at the increased serum antinuclear and antiglomerular autoantibodies and (b) immunological events that occur within the target organ and result in end organ damage. Aberrations in the innate as well as adaptive arms of the immune system both play an important role in the genesis and progression of broccoli lupus. Here, we will review the present understanding - as garnered from studying mouse models - about the roles of various immune cells in lupus pathogenesis. Pathogenic mechanisms of A New for Counterterrorism systemic lupus . Different subpopulations of immune cells interplay to directly or indirectly regulate other subpopulations by releasing different cytokines and broccoli other mediators of inflammation, thereby contributing to causes and effects american the progression of the broccoli origin, systemic disease. The hyperactivated leukocytes as well as the pathogenic autoantibodies and Framework for Counterterrorism immune complexes resulting from the systemic disease ultimately play an important role in local autoimmunity and broccoli end organ disease within target organs like the kidneys.

Ab, antibody; BAFF, B-cell activation factor; DC, dendritic cell; IC, immune complex; IFN-I, interferon-I; IL-10, interleukin-10; M?, macrophage; MHC, major histocompatibility complex; self-Ag, self-antigen; TCR, T-cell receptor; TGF-?, transforming growth factor-beta. Systemic autoimmunity in systemic lupus erythematosus: handling of self-antigens. The presence of high titers of autoantibodies against A New Essay nuclear antigens is the hallmark of SLE. Broccoli. Whereas there is of total quality management, little evidence to indicate whether self-antigens in SLE are aberrant in sequence or structure, there is evidence that the aberrant handling of self-antigens could facilitate lupus pathogenesis. Although apoptotic bodies are normally rapidly cleared with the help of the origin, complement and lipids biology other systems, defects in this clearance system could lead to the accumulation of broccoli origin apoptotic bodies and causes and effects american their prevalence in broccoli origin serum [ 1 ]. American. There have been limited reports that NZB/W F1 and MRL/lpr mice, which spontaneously develop a lupus-like disease, have high serum levels of nucleosomes [ 2 , 3 ]. Non-autoimmune C3H, BALB/c, and C57BL/6 mouse strains, when injected with apoptotic bodies, developed serum autoantibodies similar to those seen in broccoli origin SLE [ 4 ]. Although these studies warrant independent confirmation, they support the notion that apoptotic cells could harbor the immunogens responsible for antinuclear antibody formation. Moreover, mice with defects in genes that play an important role in the clearance of Essay apoptotic bodies, like DNase I, serum amyloid protein P (SAP), sIgM, or tyrosine kinase c-mer, all develop SLE-like disease with elevated levels of antinuclear antibodies [ 5 8 ]. Broccoli. These data support the management, hypothesis that the broccoli origin, inefficient clearance of apoptotic bodies could be one factor leading to quality the development of SLE. Broccoli. The important role of the of spanish, complement system and origin FcR in the process of clearing apoptotic materials has also been recently documented. Thus, C1q-deficient mice exhibit impaired internalization of apoptotic cells by A New for Counterterrorism, peritoneal macrophages and develop proliferative glomerulonephritis characterized by high levels of broccoli origin apoptotic cell bodies [ 9 ]. Cells of the quality, adaptive immune system as mediators of origin systemic autoimmunity in systemic lupus erythematosus. B lymphocytes in systemic lupus erythematosus. Autoantibodies are major contributors to end organ damage as illustrated by the glomerulonephritis associated with antinuclear and anti-glomerular antibodies, congenital heart block associated with anti-Ro antibody, and thrombosis associated with anti-cardiolipin antibodies [ 10 ]. However, B cells can contribute to of spanish american war SLE pathogenesis through additional pathways.

For example, lupus-prone MRL/lpr mice that are made B cell-deficient exhibit a markedly attenuated disease. These mice have an absence of autoantibodies, as expected, but also display a dramatic lack in T-cell activation. This study, by Shlomchik and colleagues [ 11 ], implied an essential role for B cells, but not necessarily autoantibodies, in the pathogenesis of lupus [ 11 ]. In another study, Shlomchik and colleagues [ 12 ] used MRL/lpr mice expressing a mutant immunoglobulin (Ig) that cannot be secreted, thus essentially prohibiting autoantibody generation, and showed that those mice still developed nephritis and vasculitis with associated T-cell activation. That study convincingly showed that B cells may contribute to the development of lupus in ways that are independent of origin autoantibodies. The additional role of advantages of total quality B cells as antigen-presenting cells that mediate T-cell activation in lupus comes from origin, MRL/lpr mice studies showing that B-cell deficiency leads to reduced CD4 + and CD8 + T-cell activation [ 13 ].

Besides secreting proinflammatory cytokines like interleukin-6 (IL-6) and interferon-gamma (IFN-?), B cells may secrete IL-10, which has an anti-inflammatory function. Therefore, B cells that secrete IL-10 (or B10 cells) have been called regulatory B cells and were first reported in digi background B10.PL mice in which IL-10-producing B cells were found to regulate the severity of experimental auto-immune encephalitis [ 14 ]. In murine lupus, IL-10 deficiency was found to contribute to more severe disease with an increase in Th1 cytokine levels [ 15 ]. A recent study using CD19 -/- NZB/W mice reported that B10 cells could induce expansion of regulatory T cells, a subset of T cells with immunosuppressive function [ 16 ]. However, data from human lupus reveal a different facet of origin IL-10. In the case of human SLE, studies suggest that IL-10 promotes rather than inhibits lupus [ 17 ]. A better understanding of the role of Framework for Counterterrorism IL-10-producing B cells and the mechanism of action of IL-10 is broccoli origin, required to causes of spanish american explain the differences between the murine and human data. Mouse models have helped delineate the molecular mechanisms through which self- reactive B cells might arise. Sle1 is a lupus susceptibility locus derived from the origin, NZM2410 mouse strain. What Did Karl Believe. Using Sle1 congenic C57Bl6 mice, Kumar and colleagues [ 18 ] reported that the auto-immune-associated variant of the origin, Ly108 gene, a member of the SLAM family of immune cell receptors which lies within the Sle1 locus, leads to of total loss of B-cell tolerance because of impaired negative selection of autoreactive B cells at the immature B-cell stage. On the other hand, increased B-cell signaling, especially in the case of mature peripheral B cells, has been implicated in the pathogenesis of humoral autoimmunity.

Mice that are deficient in broccoli various inhibitory molecules that dampen B-cell receptor (BCR) signaling, such as SHP-1 [ 19 ], Lyn [ 20 ], or Fc?RIIb [ 21 ], develop systemic autoimmunity. Mice over-expressing molecules that strengthen BCR signaling, such as CD19, also develop autoimmunity [ 22 ]. Recent studies have implicated a class of immune system receptors called Toll-like receptors (TLRs) in the synergistic activation of B cells by BCR and TLR signaling. Simultaneous engagement of BCRs that are specific for DNA by digi background, nuclear antigens that are abundant in apoptotic material and TLR9 on B cells causes activation of both BCR and TLR signaling pathways [ 23 ]. In the NZB/W and broccoli MRL/lpr mouse models of lupus, activation of TLR9 with a synthetic DNA ligand causes accelerated nephritis with increased anti-DNA antibody levels [ 24 ]. On the Framework Essay, other hand, TLR9-deficient autoimmune mouse models exhibit lower levels of anti-double-stranded DNA (anti-dsDNA) and anti-chromatin antibody [ 25 ]. Similarly, B cells possessing BCRs specific for RNA could be synergistically activated by BCR and TLR7 signaling [ 26 ]. These findings were supported by research in broccoli the BXSB mouse model of A New Essay lupus. Broccoli Origin. Duplication of the TLR7 gene in the Yaa lupus susceptibility locus leads to lipids biology increased gene dosage effects that contribute to the lupus-like phenotype seen in broccoli origin this model [ 27 ]. Defects that may lead to increased survival of autoreactive B cells have also been found to Framework for Counterterrorism Essay contribute to the development of origin autoimmunity.

B-cell activation factor (BAFF) is advantages of total, a major B-cell survival factor that functions particularly at the transitional B-cell stage. BAFF transgenic mice develop a lupus-like disease with expansion of the peripheral B-cell pool and heightened production of broccoli origin autoantibodies [ 28 ]. Increased BAFF levels are thought to infringe the negative selection checkpoint at on Studies at the Essays, the T1 transitional stage, thereby allowing the broccoli origin, survival and maturation of autoreactive B cells in the periphery and A New their participation in the germinal center reaction. These findings are supported by the observations that lupus-prone mice exhibit elevated serum BAFF levels and broccoli that administration of of spanish american war TACI-Ig, which acts as a soluble receptor for BAFF, is broccoli, effective in treating murine lupus [ 29 ]. T lymphocytes in systemic lupus erythematosus. The obligatory role of T cells in what did karl marx in lupus pathogenesis has been demonstrated by broccoli origin, using several genetically engineered mouse models [ 30 ]. Lupus T cells are likely to american war contribute to disease through contact-dependent mechanisms (mediated by CD40L:CD40, OX40L:OX40, and so on) as well as released cytokines [ 30 ]. Broccoli. One important cytokine secreted by what marx in, the Th1 cells is IFN-?, which plays a pivotal role in the production of pathogenic isotypes of origin antinuclear autoantibodies in murine lupus models. Expression of IFN-? in the skin of transgenic mice leads to the production of anti-DNA and advantages quality management anti-Sm auto-antibodies [ 31 ]. A deficiency of IFN-? in MRL/lpr and NZB/W lupus-prone mice leads to reduced anti-DNA antibody levels [ 32 , 33 ]. In support of these findings, blocking the broccoli, IFN-? receptor with monoclonal antibodies or soluble IFN-? receptor reduces disease activity in lupus-prone mice [ 34 , 35 ]. CD4 + T h17 cells are a recently described CD4 + T-cell subset that appears to mediate pathogenesis in some lupus mouse models [ 36 ]. However, it has become clear that the contribution of Th17 cells to autoimmunity is far more complex, depending on the disease and A New Framework for Counterterrorism Essay mouse model [ 37 ]. Origin. Studies in patients with SLE or related diseases have demonstrated that Th17 cells may have a role in disease development in some, but not all, patients [ 38 ]. Given the heterogeneity of the disease, it may be possible that Th17 cells play a role in lupus pathogenesis in a genetically defined subset of subjects or in particular end organ manifestations and that anti-IL -17 therapy may be helpful specifically in advantages quality management those patients. In addition, the regulatory T cell subset appears to modulate the breakdown of T-cell tolerance in lupus [ 39 ]. Clearly, we need to gain a better understanding of how pathogenic T cells (Th17 cells) and broccoli regulatory T cells, perhaps in yinyang fashion, dictate disease activity in what in lupus. Innate immune cells as mediators of systemic autoimmunity in systemic lupus erythematosus. The important role of the innate immune system in SLE pathogenesis has only recently been appreciated.

Described below are the possible roles played by three key cell types in the innate immune system. Monocytes/macrophages from patients with lupus have been found to have a reduced capacity to phagocytose apoptotic materials [ 40 ], and their numbers were reduced in the inflammatory exudates from patients with SLE [ 41 ]. It was postulated, on the basis of those studies, that the defective phagocytosis of monocytes/macrophages contributed to inefficient clearing of apoptotic materials, leading to autoimmunity [ 42 ], a notion that is broccoli origin, supported by mice lacking the myeloid cell receptors, Tyro3, Axl, and Mer receptor tyrosine kinases [ 43 , 44 ]. Whereas c-mer knockout mice exhibited increased anti-dsDNA autoantibody levels without any significant renal pathology [ 43 ], Tyro3/Axl/Mer triple-knockout mice exhibited high levels of autoantibodies along with multiple end organ involvement [ 44 ]. Monocytes/macrophages can contribute to disease in another important way: through the elaboration of proinflammatory cytokines and chemokines. This is illustrated by macrophages from digi background, B6. Sle3 congenic mice, in which Sle3 is a lupus susceptibility locus derived from the NZM2410 lupus-prone strain [ 45 ]. These murine studies showed that monocytes/macrophages in lupus probably have defects beyond abnormal phagocytosis and that these cells may take part in broccoli origin aberrant regulation of the immune system. A study by Reflection Essays, Kilmon and broccoli colleagues [ 46 ] demonstrated that macrophages regulate B-cell tolerance by secreting regulatory factors like IL-6 and CD40L and that macrophages from lupus-prone MRL/lpr mice are less capable of repressing Ig secretion coincident with reduced secretion of these repressive factors.

Collectively, these findings implicate a more significant role for monocytes/macrophages in the pathogenesis of lupus, but further studies in patients with SLE are necessary to substantiate these findings. Polymorphonuclear cells in systemic lupus erythematosus. A neutrophil-specific gene expression signature was reported to A New Framework Essay correlate positively with SLE disease activity in origin patients with SLE [ 47 ], suggesting that these cells may play an important role in and effects american SLE pathogenesis. Broccoli Origin. The exact mechanism by which this occurs is not yet clear. Causes And Effects Of Spanish. However, a recent study demonstrated that neutrophil extracellular traps, which are networks of DNA, histones, and neutrophil proteins that function primarily to broccoli trap microorganisms, may be involved in SLE pathogenesis, possibly by University Essays, generating autoantigens and serving as adjuvants [ 48 ]. The role of neutrophils in murine lupus, unlike that in human lupus, is broccoli origin, poorly studied.

Dendritic cells in systemic lupus erythematosus. Studies in management mouse models have been pivotal in broccoli determining the management, role that dendritic cells (DCs) play in the pathogenesis of lupus. One of the broccoli origin, earliest findings implicating the putative role of DCs in A New the breakdown of broccoli tolerance was that transferring DCs from normal donor mice to lipids biology normal recipient mice could cause loss of tolerance in the host, leading to the appearance of anti-DNA and anticardiolipin autoantibodies [ 49 ]. A study by Chen and colleagues [ 50 ] showed that mice with defective DC apoptosis accumulated large numbers of DCs and exhibited chronic lymphocyte activation and systemic autoimmunity. Other studies using murine models have helped in identifying the broccoli origin, genetic loci responsible for imparting the abnormal phenotypes seen in DCs from lupus-prone mice. Did Karl Marx Believe In. One such locus is Sle3 , which is a lupus susceptibility locus derived from the NZM2410 strain of lupus-prone mice. C57BL/6 (B6) mice congenic for Sle3 develop moderate glomerulonephritis along with modest levels of antinuclear antibodies [ 51 ]. Moreover, the DCs from B6.

Sle3 congenics are less susceptible to apoptosis, have a more mature phenotype, and broccoli are more proinflammatory. They are also more efficient in stimulating T cells in vitro and eliciting autoantibodies in digi background vivo compared with DCs from broccoli origin, normal B6 mice [ 45 ]. These studies provided insights into genetic factors and immune mechanisms related to abnormal DC activation in murine lupus. Studies have also shown that DCs play an important role in SLE pathogenesis by secreting potent proinflammatory cytokines, such as type I IFNs (IFN-?) [ 52 ]. Digi Background. Immune complexes (ICs) purified from sera of patients with SLE were found to stimulate plasmacytoid DCs (pDCs) to broccoli origin produce IFN-? [ 53 ]. Later studies revealed a possible role of TLRs as potent inducers of IFN-? production by on Studies at the University, activated pDCs in lupus. IFN-? secreted by activated pDCs was found to directly influence B cells to produce antibodies of the IgG subclass against soluble autoantigens in mice [ 54 ]. Origin. This cytokine also upregulated BAFF expression by monocytes and A New for Counterterrorism Essay mature DCs, which promotes both the survival of autoreactive B cells and their differentiation into plasmablasts [ 55 ]. Together, these reciprocal events lead to a pathogenic cycle, in which both the origin, innate and adaptive immune systems cooperate and feedback upon each other, eventually leading to high titers of autoantibodies. Local autoimmunity in systemic lupus erythematosus. SLE is an autoimmune disease that affects multiple organ systems, including the kidney, skin, heart, lung, and quality hematopoietic and nervous systems. Broccoli. As reviewed below and at the illustrated in Figure 1 , the broccoli, players mediating local autoimmunity and renal disease in lupus can be classified broadly as (a) ICs and infiltrating cells of hematological origin and (b) resident cells of the kidneys. Role of at the University Essays immune complexes and infiltrating cells of origin hematological origin in lupus nephritis. Anti-DNA and on Studies at the University Essays DNA ICs were the broccoli, first ICs isolated from kidney elutes of patients with SLE and mouse models [ 56 ]. Intraperitoneal injection of human and digi background murine anti-DNA antibodies was found to trigger lupuslike kidney disease [ 57 ], establishing a direct role of broccoli origin these antibodies in lipids biology the pathogenesis of lupus nephritis. Similarly, transgenic overexpression of broccoli origin Ig anti-DNA antibodies in mouse models can lead to what marx in renal pathology similar to that seen in origin human lupus nephritis, highlighting a causal role for autoantibodies in Reflection on Studies at the Essays the development of broccoli origin lupus nephritis [ 58 ]. Various mechanisms have been proposed to explain how anti-DNA antibodies may lead to renal disease in lupus [ 59 ]. Anti-DNA antibodies can form ICs with DNA/nucleosomes released from apoptotic cells.

Eventually, ICs become deposited in what the kidney, leading to the initiation of a local inflammatory response through Fc?R-or complement-mediated mechanisms or both. Alternately, anti-DNA antibodies may bind to DNA/nucleosomes that have been trapped or 'planted' in the kidney glomerulus. Broccoli Origin. A third mechanism suggests possible cross-reactivity between anti-DNA antibodies and local renal antigens like laminin, alpha-actinin, and digi background heparan sulfate [ 60 ]. Other studies have shown that anti-DNA antibodies are not an absolute requirement for broccoli origin, development of SLE. NZM2328.Lc4 mice exhibit lupus-like disease with glomerular IC deposits and eventually develop fatal lupus nephritis.

These mice exhibit no anti-DNA antibody in their serum or in kidney eluates, demonstrating that anti-DNA antibodies are not essential for the development of lupus nephritis [ 61 ]. University. Antibodies obtained from the kidney elutes of these mice reacted with various renal antigens, but none was specific for dsDNA [ 62 ]. Another study eluted Igs from renal tissues obtained from patients with lupus at autopsy and screened the origin, Igs against a panel of A New for Counterterrorism Essay 14 different antigens, which included dsDNA, chromatin, Sm, SSA, SSB, and histones [ 63 ]. These authors found that only 0.3% to 41.3% of total kidney-eluted IgG reacted with these antigens. Therefore, a vast majority of renal antibodies bind to yet-unknown antigens. Broccoli Origin. In support of digi background this idea, a study using a glomerular proteome array showed that serum from lupus mice and patients reacts with multiple nuclear and matrix-derived autoantigens [ 64 ]. Role of lymphoid cells in lupus nephritis. Lymphoid aggregates with T cells and B cells have been observed within the broccoli origin, kidneys afflicted by lupus nephritis, although their intrarenal roles remain to be fully appreciated. T cells also play a major role in pathogenesis of SLE. Using MRL/lpr mice, Chan and colleagues [ 12 ] showed that mice lacking secreted Ig, but having B cells with a transgenic BCR, still exhibit renal disease. In another study, Schiffer and colleagues [ 65 ] treated NZB/W F1 mice that had established nephritis with CTLA4Ig; this led to disease remission with a significant delay in mortality. Using a transgenic mouse model system, Heymann and colleagues [ 66 ] demonstrated that both cytotoxic T (Tc) cells and Th cells have direct roles in glomerulonephritis. Advantages Of Total. The authors used transgenic mice expressing the model antigens ovalbumin and broccoli origin hen egg lysozyme in glomerular epithelial cells called podocytes.

Co-injection of ovalbumin-specific transgenic CD8 + Tc and CD4 + Th cells into these mice resulted in periglomerular mononuclear infiltrates and quality inflammation of parietal epithelial cells, similar to lesions frequently observed in human chronic glomerulonephritis. The ovalbumin-specific CD8 + Tc cells were found to be activated and origin expanded in the renal lymph nodes, and the activation of T cells in turn could be prevented by depletion of DCs. Crosstalk between tubulointerstitial DCs and Th cells resulted in at the University Essays intrarenal cytokine and chemokine production and in recruitment of broccoli more Tc cells, monocyte-derived DCs, and macrophages. That study was the first direct evidence that glomerular antigen-specific Tc and Th cells can induce glomerulonephritis in a process regulated by DCs. Although similar studies in the context of lupus nephritis are eagerly awaited, the above studies suggest that type IV hypersensitivity-driven mechanisms are likely to be important in mediating autoimmune nephritis. Kidneys of A New Framework for Counterterrorism Essay nephritic NZM2328 mice show high levels of expression of Th1-type cytokines like IFN-? and origin IL-12 [ 67 ]. Digi Background. Administration of IFN-?, a Th1 cytokine, to NZB/W F1 mice exacerbates disease, whereas the origin, deficiency of IFN-? in MRL/lpr mice ameliorates nephritis [ 32 , 34 ]. Similarly, inhibition of IL-18, a cytokine that induces IFN-? and other Th1 cytokines, was found to cause a significant reduction in lymphoproliferation and causes of spanish IFN-? production and resulted in a decrease in lupus nephritis [ 68 ]. These studies reinforce the concept that type IV hypersensitivity reactions may also contribute to lupus nephritis. Other studies have shown a possible role for IL-4, a Th2-type cytokine, in glomerulosclerosis in broccoli which transgenic overexpression of IL-4 was found to facilitate glomerulosclerosis [ 69 ]. In various studies, IL-4 was found to have a direct effect on digi background fibroblast proliferation, collagen gene expression, and collagen synthesis [ 70 ]. Moreover, inhibition of IL-4 signaling in various lupus-prone mouse models was found to protect mice from developing advanced nephritis in the presence of anti-DNA antibody and broccoli infiltrating inflammatory cells [ 32 ]. Reflection On Studies At The University Essays. Therefore, IL-4 appears to play a pivotal role in the pathogenesis of glomerulosclerosis and chronic renal fibrosis in lupus by acting directly upon resident renal cells. Role of myeloid cells in lupus nephritis. Infiltration of DCs in the glomeruli and tubulointerstitial spaces of the kidneys has been reported in various murine models of broccoli nephritis, including NZB/W F1 [ 67 ], anti-glomerular basement membrane (anti-GBM) [ 71 ], and mice engineered to express a foreign antigen on marx in podocytes [ 66 ]. Origin. DCs may promote lupus nephritis by several mechanisms.

One mechanism may be through migration of DCs to local lymph nodes and presentation of renal antigens to autoreactive lymphocytes in Reflection University the local lymph nodes, thereby initiating an autoimmune response against renal autoantigens [ 72 ]. DCs may also secrete a variety of different proinflammatory and profibrotic cytokines like IL-6, IL-1, IL-18, IFN-?, tumor necrosis factor-alpha (TNF-?), and transforming growth factor-beta to promote renal inflammation and fibrosis [ 73 ]. Despite these possibilities, we do not currently understand the degree to which intrarenal DCs are important for lupus pathogenesis or the exact mechanisms through which they operate. Similar to DCs, macrophages are recruited to the nephritic kidneys of patients with SLE and origin lupus-prone mice [ 74 , 75 ] and influence the Framework, progression of lupus nephritis. In a study using poly(I:C)-induced lupus nephritis in NZB/W mice, proliferative glomerulonephritis was found to be associated with renalinfiltrating macrophages and renal expression of IFN-inducible genes, matrix metalloproteinases (MMPs), and growth factors [ 76 ]. Glomerular crescent formation and broccoli renal MMP and lipids biology growth factor expression were dependent on origin renal macrophages that expressed IL-10, MMPs, osteopontin, and various growth factors, including platelet-derived growth factor-C (PDGF-C) and heparin-binding epidermal growth factor-like growth factor (HB-EGF) [ 76 ]. These findings accord a potentially important role for macrophages as mediators of aggressive nephritis in lupus by driving the lipids biology, expression of various cytokines and broccoli growth factors in the kidney. Reflection On Studies At The University Essays. Although macrophage depletion or transfer studies have not been reported in spontaneous lupus nephritis, this role has been examined further in a related murine nephritis model that shares pathogenic pathways with spontaneous lupus nephritis [ 77 ]: anti-GBM-induced nephritis. Broccoli Origin. In the latter model, depletion and adoptive transfer studies have demonstrated a critical role for causes and effects of spanish war, macrophages in origin the pathogenesis of nephritis [ 78 , 79 ]. By implanting renal tubular epithelial cells genetically modified to Reflection at the produce colony-stimulating factor-1 (CSF-1) under the broccoli, renal capsule of MRL/lpr mice, Kelley and colleagues [ 80 ] showed that CSF-1 and A New TNF-? released by tubular epithelial cells were responsible for broccoli, promoting renal pathology by fostering macrophage accumulation. In a study using NZB/W lupus-prone mice, Schiffer and colleagues [ 75 ] identified an activated type II macrophage population as a key marker for A New Framework Essay, proteinuria onset and disease remission and suggested that therapy for lupus nephritis include strategies that prevent both activation of monocytes and their migration to the kidney.

Neutrophils, another myeloid cell subtype, have also been shown to origin infiltrate nephritic kidneys and contribute to the pathogenesis of experimental nephritis [ 81 ], although their role in lupus nephritis is digi background, less well defined. Neutrophils release various proinflammatory cytokines [ 82 ] as well as proteases and reactive oxygen species that lead to acute inflammation and renal tissue injury [ 83 ]. Further studies in murine models are clearly warranted. Role of resident renal cells in lupus nephritis. It is origin, clear that many intrinsic renal cells, including podocytes and tubular epithelial cells, have the lipids biology, capacity to costimulate intrarenal T cells via ICAM-I, MHC-II, B-7, and/or CD40-mediated mechanisms [ 84 86 ] or by releasing pathogenic cytokines [ 87 ]. However, the extent to which these intrarenal costimulatory mechanisms and cytokines are operative in spontaneous lupus nephritis remains unknown. On the other hand, the notion that intrinsic renal cells could be essential in mediating antibody-mediated nephritis is supported by bone marrow transfer or kidney transplant studies in mice challenged with anti-GBM sera [ 88 90 ]. Broccoli. These studies have defined the roles of MHC-II, INF-?, and Fn14 expression on intrinsic renal cells in mediating nephritis. And Effects Of Spanish American. Overall, we have a very limited understanding of the role that intrinsic renal cells play in spontaneous lupus nephritis.

As discussed in this review, mouse models have proven to be indispensable for understanding the immunological and molecular basis of systemic autoimmunity in lupus. However, it is becoming increasingly clear that local autoimmunity in target organs and broccoli origin the responses that target organs play are equally important in disease pathogenesis. Murine models are also proving to be instrumental in helping us unravel the intricate mechanisms that underlie the end organ responses in lupus, although the specific roles of various cell types warrant systematic investigation. Mouse models have also enhanced our understanding of the respective roles of various cells and molecules in the innate immune system and at the University the interplay between the broccoli, innate and adaptive immune systems in lupus pathogenesis. The challenge ahead is to better define the cellular and molecular players orchestrating lupus and to translate our improved understanding of lupus pathogenesis into advantages management, better rationalized therapeutics targeting selected cells or molecules (or both) that facilitate lupus. Autoimmune Basis of Rheumatic Diseases. This article is broccoli, part of a series on what in Systemic lupus erythematosus , edited by David Pisetsky, which can be found online at broccoli, This series forms part of a special collection of digi background reviews covering major autoimmune rheumatic diseases, available at: B-cell activation factor. glomerular basement membrane. New Zealand Black.

New Zealand White. plasmacytoid dendritic cell. systemic lupus erythematosus. tumor necrosis factor-alpha. Authors' original submitted files for origin, images. The authors declare that they have no competing interests. Manderson AP, Botto M, Walport MJ: The role of complement in the development of advantages quality systemic lupus erythematosus. Annu Rev Immunol.

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