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Practice Areas
Premier 100 Designation for the following years:
It is hard to imagine another employment lawyer with a comparable record both in the courtroom and at the negotiating table. Mr. Wigdor routinely tries cases to verdict – having won numerous verdicts in the millions of dollars and regularly appearing in the New York Law Journal's "Top Verdicts." Because of his employment trial verdicts and high-profile cases, Mr. Wigdor has appeared in recent profiles about his career in the New York Times, Bloomberg Businessweek, and the London Independent. Mr. Wigdor has been referred to in these and other major news publications as one of New York's most high-profile litigators.
Mr. Wigdor is known for taking on some of the most powerful people in the business and political worlds. He represented the hotel maid in the Dominique Strauss-Kahn sexual assault case, the rape victim in the Delhi Uber case that recently led to numerous executive resignations, NBA All-Star Charles Oakley in a defamation lawsuit against James Dolan and Madison Square Garden, and over 20 employees at Fox News in their claims of gender discrimination, race discrimination, retaliation and defamation against the network.
As the Founding Partner of Wigdor LLP, the Firm has been referred to as "a high-powered employment law firm known for taking on some of the biggest companies in the US." The Firm has successfully litigated discrimination, harassment and retaliation claims against virtually every large employer in New York. A former U.S. Senator for New York said of Mr. Wigdor, "it's much better to have him on our side than risk sitting across from him."
Mr. Wigdor was named as one of the Top 100 Trial Lawyers in the USA by the National Trial Lawyers and one of the Top 100 Labor and Employment Lawyers by the American Society of Legal Advocates. Two peer review studies, The Best Lawyers in America and Super Lawyers, have recognized Mr. Wigdor as one of the best Employment Trial Lawyers in America.
Mr. Wigdor's handling of numerous high-profile cases has resulted in frequent media appearances including Nightline, Good Morning America, The Today Show, CNN American Morning, Neil Cavuto as well as regular spots on CNBC, ABC News, CBS News, NY1, the BBC and NBC News. He is regularly quoted as a legal expert in newspapers and magazines including the New York Times, Wall Street Journal, New York Law Journal, London Times, Daily Telegraph, London Independent, USA Today, New York Post, and Daily News.
Mr. Wigdor has been at the forefront of challenging racial discrimination, most recently the systemic racial bias at Fox News. Mr. Wigdor currently represents thirteen clients who have alleged racial discrimination against Fox. Mr. Wigdor also represents Rod Wheeler, a Fox contributor in an "explosive" lawsuit alleging defamation in connection with a story published about murdered DNC staffer Seth Rich, Scottie Nell Hughes, a former Fox contributor in a lawsuit alleging retaliation after she complained of sexual assault by Fox Business host Charles Payne, and Lydia Curanaj, a Fox5 reporter in a lawsuit alleging gender and pregnancy discrimination against Fox News. The lawsuits join a succession of sexual harassment allegations made against Fox, and have been extensively reported on by both national and international media and referred to as a "Normandy like" legal assault. Mr. Wigdor and his clients have appeared on CNN, Good Morning America, the BBC, the Today Show and CBS This Morning, detailing the years of racial discrimination they encountered at Fox News.
Mr. Wigdor's extensive litigation experience is frequently distinguished in the media; notably, a recent sexual harassment complaint filed by Mr. Wigdor against Chief Executive Officer of data management firm Exusia was lauded by one news outlet as a "stunning piece of legal work" and a "truly spectacular complaint." The complaint was filed on behalf of Mr. Wigdor's client, a female employee at the Company. Another well-known media outlet noted that "although U.S. lawyers are known to actively seek out victims to encourage them to sue for damages, Mr. Wigdor doesn't need to chase clients".
In addition to representing clients, Mr. Wigdor is an arbitrator, serving on the American Arbitration Association Employment Panel. Mr. Wigdor is also a lecturer, editor and author of articles on employment and criminal related subjects. He is regularly invited to appear and participate in leading legal forums regarding topical employment issues. Mr. Wigdor has appeared multiple times as part of an employment mediation panel at JAMS (Judicial Arbitration & Mediation) continuing legal education events, and has also appeared as a speaker at the American Arbitration Association forum, the University of Pennsylvania and Fordham Law Schools, as well as Oxford and Cambridge Universities. Mr. Wigdor also frequently speaks and moderates other continuing legal education seminars for the American Conference Institute and Practicing Legal Institute. He is also quoted frequently in the New York Law Journal, presents lectures to various Bar Associations, and has published articles in numerous journals.
The New York Law Journal has featured Mr. Wigdor and Wigdor LLP's clients in the top New York State verdicts six times, including the number one and two employment verdicts and the number one disability discrimination verdict. Wigdor LLP has also been honored by the Litigator Awards, the highest awards in trial law. Wigdor LLP has been routinely recognized for extraordinary achievement in the categories of employee discrimination, wrongful termination, civil rights, whistle‐blower and wage and hour.
Notable Outcomes
- $23.72 million arbitration award (one of the largest single plaintiff employment arbitration verdicts) on behalf of the former Chief Financial Officer of Six Flags;
- $7.5 million verdict in a disability discrimination case against Wal‐Mart, one of the largest verdicts ever in a single plaintiff case under the Americans with Disabilities Act;
- $8 million (approx.) verdict on behalf of the former Editor‐in‐Chief of The Source Magazine, who was retaliated against after she complained of gender discrimination;
- $3.35 million verdict on behalf of a former employee of Nassau County whose due process rights were violated;
- $1.35 million verdict in a disability case where our client was terminated from his employer after disclosing he was HIV positive; and
- Arbitration award of over $700,000 on behalf of former Managing Director at Manhattan based consulting group who was terminated without basis for "Cause".
Experience and Types of Cases
Mr. Wigdor's practice focuses on litigation and counseling of individuals and companies in connection with a wide array of employment issues, criminal matters and international issues. He has represented numerous clients who have been victimized by discrimination or harassment based on pregnancy, race, gender, age, sexual orientation or disability, including, but certainly not limited to:
- Fox News contributor Rod Wheeler in an "explosive" lawsuit alleging defamation in connection with a story published about murdered DNC staffer Seth Rich, against Twenty-First Century Fox, Inc., Fox News Network LLC, Fox reporter Malia Zimmerman, and Fox contributor Ed Butowsky;
- Former Fox News contributor Scottie Nell Hughes in a lawsuit alleging retaliation after she complained of sexual assault by Fox Business host Charles Payne, against Twenty-First Century Fox, Inc., Fox News Network LLC, Dianne Brandi, Fox's General Counsel, Irena Briganti, Fox's Executive Vice President of Corporate Communications, and Fox host Charles Payne;
- Thirteen former and current employees of Fox News, including current News Anchor Kelly Wright, who have alleged race discrimination against Fox News Network LLC, Judith Slater, former Controller and Senior Vice President of Accounting at Fox, and Dianne Brandi, Fox's General Counsel;
- Current Fox5 reporter Lidia Curanaj in a lawsuit alleging gender and pregnancy discrimination against Twenty-First Century Fox, Inc., Fox Entertainment Group LLC, Fox Television Stations, LLC, and Bryon Harmon, Fox5 News Director;
- Former New York Knicks player and NBA All-Star Charles Oakley in a defamation lawsuit against The Madison Square Garden Company and its Executive Chairman, James Dolan;
- A VP in the Wealth Management Division at the large investment bank Goldman Sachs in a lawsuit alleging systematic racial discrimination against Goldman Sachs;
- Multiple individual plaintiffs in a racial profiling lawsuit against Macy's;
- Television personalities, news anchors, and other media employees and executives in discrimination, harassment and contract claims against their employers and others individually responsible;
- Employees of the New York Times in a class action lawsuit alleging age, race and gender discrimination;
- A former executive in a sexual harassment and retaliation claim against a top hedge fund that appeared on the front page of the New York Times;
- A nationwide class action against Sephora on behalf of over seven hundred and thirty Asian customers who were the victims of racial profiling and discrimination;
- A former senior VP at renowned T.V. channel Al Jazeera America, in a lawsuit alleging retaliation and discrimination against her former employer;
- The courageous victim of a heinous sex crime at the hands of an Uber cab driver in India;
- Numerous attorneys against their former employees, including prominent international law firms. The attorneys were subjected to various forms of discrimination by their employers such as gender, age and sexual orientation discrimination;
- Thousands of victims of employment discrimination, harassment, whistleblowing or retaliation against virtually every bank and thousands of other hedge funds and financial institutions;
- The former Headmaster of The Epiphany School of Global Studies, Saul Benjamin in an action against school founder and widely known novelist Nicolas Sparks;
- The Adler family, on behalf of Sol Adler, in a discrimination and wrongful termination suit against 92nd Street Y;
- A class action wage and hour suit against CitiGroup;
- Former Executive Director of the Civilian Complaint Review Board (CCRB) in a retaliation action against the police watchdog;
- Service employees in a collective and class action against Japanese ramen restaurant chain Ippudo for unlawful wage practices;
- Former service employees in a class action against celebrity chef David Bouley for failure to pay minimum wages and tips;
- Former Executive in an age discrimination action against MetLife for failure to pay retirement benefits;
- A group of women in a gender discrimination case against Citigroup;
- Numerous women in pregnancy discrimination cases against large investment financial institutions;
- Women who were paid less than similarly situated men against large financial institutions;
- Executives in sexual orientation claims against their employer;
- The former CFO of Six Flags;
- A group of people of color in a race and national origin claim against Bank of America;
- Individual women in an alleged gender discrimination class action complaint against Dresdner Kleinwort;
- The former Tour Manager of *NSYNC in a lawsuit against *NSYNC;
- Several employees in age discrimination claims against their employers;
- Employees in a large wage and hour case against CitiMortgage; and
- Several celebrity models, actors, actresses and well‐known chefs in various legal disputes.
Mr. Wigdor regularly conducts oral arguments in appellate courts, including the Second Circuit, the New York Court of Appeals, and the First Department, arguing some of the most closely watched legal issues in the employment field. Mr. Wigdor was a Federal Law Clerk to United States District Judge Arthur D. Spatt and was appointed as an Assistant District Attorney in Suffolk County, New York where he investigated, prosecuted and tried hundreds of criminal matters ranging from robberies and burglaries to complex schemes to defraud. Prior to founding Wigdor LLP, Mr. Wigdor was a senior lawyer at one of the nation's preeminent management side labor and employment firms.
Mr. Wigdor was named as one of the Top 100 Trial Lawyers in the USA by the National Trial Lawyers and one of the Top 100 Labor and Employment Lawyers by the American Society of Legal Advocates. Two peer review studies, The Best Lawyers in America and Super Lawyers, have recognized Mr. Wigdor as one of the best Employment Trial Lawyers in America. The American Academy of Trial Attorneys, a national organization of premier attorneys, has recognized Mr. Wigdor as one of the Premier 100 trial attorneys for New York, and he has been honored with a lifetime membership from the Top American Lawyers. Mr. Wigdor has been honored with a Fellowship of the Litigation Counsel of America, in recognition of his outstanding reputation and extensive litigation experience. Mr. Wigdor was selected as a Blue Ribbon Panelist for Super Lawyers in the employment litigation / labor and employment field after receiving one of the highest point totals in the Super Lawyers rankings. Mr. Wigdor has also received an AV rating from Martindale‐ Hubbell, indicating that his peers rank him as one of the preeminent lawyers in the labor and employment field. Avvo, a well‐respected lawyer‐rating agency, has given Mr. Wigdor its highest rating of 10.0 ("Superb"). Mr. Wigdor also served as a member of the Law360 Employment Law Editorial Advisory Board.
Mr. Wigdor received his undergraduate degree from Washington University in St. Louis, cum laude; a Master's Degree from Oxford University in England; and his Juris Doctor from Catholic University School of Law in Washington, D.C., graduating in the top of his class. Mr. Wigdor was a senior staff member on the Catholic University Law Review and an editor of the Oxford International Review. While at Oxford, Mr. Wigdor received a coveted "Full‐Blue" and was a member of the Vincent's Club.
Admitted to Practice
- U.S. Supreme Court, 2003
- Her Majesty's Courts of England & Wales, 2001
- U.S. District Court for the Eastern District of New York, 2000
- Court of Appeals, Second Circuit, 2000
- U.S. District Court for the Southern District of New York, 2000
- U.S. District Court for the Northern District of New York, 2003
- District of Columbia, 1995
- Pennsylvania, 1994
- New York, 1994
- New York State Bar Association
- Suffolk County Bar Association
- Federal Bar Council
- Association of the Bar of the City of New York
Community Involvement
Mr. Wigdor is an active and philanthropic member of the Forest Hills community, where he served on the legal committee of the Forest Hills Gardens Association, and is a proud sponsor of the New York Pops summer series at Forest Hills Stadium. Mr. Wigdor had the privilege of managing several basketball teams in the Forest Hills Little League, in addition to coaching a basketball team at the Forest Hills YMCA and Forest Hills Community House. He is a former member of the Governing Committee of the Oxonian Society, a non‐profit organization dedicated to bringing heads of state to address its members, and was also a member of both the Alexander Hamilton and Theodore Roosevelt Inns of Court, wherein he worked together with other selected lawyers and state and federal judges in the analysis of current legal issues. Mr. Wigdor travelled to Kenya with other lawyers from the Firm, to educate Kenyan Wildlife Service Officers on evidence preservation and testifying in court. Mr. Wigdor is also an active member of the Westside Tennis Club at Forest Hills and a member of the International Tennis Club of the U.S.A.
Mr. Wigdor has been awarded the Alumnus of the Year in 2007 and 2014 from St Cross College, Oxford. Due to his continued support of Oxford, St Cross College, a library has been named after Mr. Wigdor and his wife – the Douglas and Catherine Wigdor Library Garden Room. Mr. Wigdor is a member of the New York Eliot Society Membership Committee, and a volunteer for the Leading Together Campaign for Washington University. Mr. Wigdor has also endowed a scholarship for an Arts & Sciences student at Washington University and has recently endowed a cycling studio in the student Recreational Center.


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Welcome to the University of Phoenix Financial Aid Web and online financial aid process.
This is a secured site that requires the submission of a User Login Name and Password for access.
If you are a first time user, please complete the registration form to create a secure User Login Profile and begin the financial aid process! The registration process requires that you enter your Identification Record Number or IRN assigned by the school to complete the financial aid process. If you do not have your IRN number, please contact your Campus Advisor.
The U.S. Department of Education's Office of Inspector General (ED OIG) has alerted colleges and universities to the fact that ID theft and similar fraud rings are on the rise in the education community. The University of Phoenix aggressively monitors for this fraud and any student financial aid fraud, reports fraud to the ED OIG, and fully cooperates with law enforcement officials to prosecute any parties engaged in such fraud.
Scholarship Telemarketing Fraud Scheme
Reporting Scholarship Fraud

subset: commoncrawl


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Posted 5 years ago
(259 items)
I have no idea what possessed me to buy this, I guess it must have been the Deco style as well as the color. It's pretty large (1" x 2 1/4"), and a bit heavy. All the stones are there, and the design is cool. I'm thinking late 30's? There are no markings that I can find, and it appears to be Pot Metal. Still cool though!


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I had my very last exam yesterday and I couldn't be happier!! :)
The last couple of days have been pretty hectic(with exam preparation, the exam itself and celebration) and I'll be super busy the next two weeks as well so I'm not sure how much I'll be able to update.
I'm going to have a party on Saturday to celebrate and hopefully I'll have the time to post some pictures and a little update before I leave for Roskilde Festival on Sunday!
Oh, and here's a coupe of pictures from right after my exam :) Nice hat, isn't it? xD That's a traditional hat that you get when you finish "gymnasium". Most people get one like my friends'(the white and red) but mine is black because I took some extra classes, haha xD It could have just said nerd on it :P
The makeup obviously isn't too exciting, but on my lips I'm wearing MAC Blow Dry l/s with a mix of MAC Mimmy l/g and MAC Pink Lemonade l/g on top ;)
Oh, and there's a trashcan in the background... Lovely :D
Thursday, June 25, 2009
I'm done with school :D
Indsendt af Zoffe kl. 9:50 PM
Etiketter: Personal updates
7 comments:
- Ally said...
Congrats, love the lip color combo.
- June 26, 2009 at 5:53 PM
- LINEA. said...
congrats! cute dress :]
- June 26, 2009 at 5:56 PM
- Marie said...
Jag har tittat på den där klänningen på H&M själv, den är superfin!
- June 26, 2009 at 10:42 PM
- Vanessa M. said...
- June 27, 2009 at 6:03 AM
- Lilly said...
congrats! i love your dress!
- June 28, 2009 at 3:03 PM
- Ivey Scarlette said...
Congratulations! By the way the hat is awesome, I wish I got a stylish hat for completing classes.
- July 1, 2009 at 2:15 AM
- Deborah said...
that dress is gorgeous on you!!!
- July 25, 2009 at 12:51 PM
Subscribe to: Post Comments (Atom)


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While the election appears promising, much could go wrong. Democrats will make every effort to steal the election to win as they have in Cook County, Illinois and the state of Minnesota, et al. We feel that another term of Democratic socialism would collapse the nation, and we could turn into Venezuela in a heartbeat, given our $20 trillion borrowings, even though half of it is paper that would vanish in a collapse and likely ruin all the people who deserve ruination.
The traditional safe port for wealth has been gold, but on analysis it is hard to justify as is has limited use, other than in jewelry and coatings that are microscopically thin. The use of gold in high tech is limited with much of the high conductivity needs satisfied by silver, which is more abundant and cheaper. Realistically, gold has less real value than silver as that metal has so many applications.
One of the major uses of silver was in photography, as silver salts are photo-active, changing from colorless crystals to black metal deposits when struck by light. Digital photography hurt the price of silver two ways: As it was not consumed, but recycled; where there is no silver in a color print, unlike black and white pictures or films, the end of film put tons of silver back on the market reducing the price. Nothing like that foreseeable.
Trending: The NFL's Grand Illusion is Null and Void, and Pats Fans Proved It
Silver is an excellent electrical conductor, as it does not rust or corrode. The digital age has been good for silver, but it has also been subjected to much market manipulation, hoarding and dumping for trading schemes. Coinage used to consume large amounts, but that use has diminished, as has use in tableware, now mostly stainless steel. Market manipulations have pushed the price of silver below mining and smelting costs, which are about $25 per ounce and rising. On July 22, 2016 the market silver bid closing price was $19.59, with traders saying it can only go up.
In 1792 the United States set the price of silver as 1/15th that of gold. If that standard were enforced today, silver would be at $88.14 per ounce as the gold bid price close was $1322.10 on July 22, 2016. There is no chance silver will ever be legislated back to that ratio with gold, but the ratio says gold is ridiculously over-priced and could change catastrophically, as it is only supported by emotion. Silver support has basis in fact. It has more value than luster. The important point is that gold has a real downside potential while silver has an upside imperative.
If you were going to buy silver as an investment, where is the best place to plant your paper? Silver can be purchased in ingots, bars, rounds and coins. Coins are an especially good choice as there is always a chance that in a very serious downturn, or collapse, the government it apt to outlaw the owning of precious metals in an effort to legitimize their paper currencies by cutting out precious metals. Coins provide a clever way of ducking such Federal skullduggery.
Commemorative coins are legally classified as "works of art" and as such can be held by private parties regardless bans on precious metals. There are several such gold coins, but all are one ounce in weight, which is fine unless you are going to the grocery store. What will you be offered in change, but a bunch of paper of dubious value in a calamity of the kind we could have.
Inflation is the "disease de rigueur" of great national calamities so the ideal coin to have is one of intrinsic, but small value. Our choice in this class is the Columbian Exposition 1892-1893 half Dollar. If silver were to go to $88 per ounce it would still be only $44 per coin and you could buy reasonable quantities of foodstuffs and personal supplies with a few in your pocket while the less well informed struggle with pockets full of Eternal President Obama Bucks.
There is a tradition and legal precedent for the "work of art" standard to prevail in any future calamity which makes all legally minted coins, and especially any more than 100 years old, "works of art" and not just currency while they can function as either. This alone will probably double their street value in a collapse of the kind now happening in Venezuela. That nation has far less excuse for the calamity they now suffer than do we! They have the largest untapped oil reserve in the western hemisphere! There is a very real chance we will fail in the same way as the data Mr. Obama cites is all false, every last bit of it.
It has never been more important for you to think clearly, plan ahead, investigate thoroughly and take a fraction of your wealth and perhaps put it into a silver parachute.


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Two Oregon educators who founded the K12Linux project seven years ago are glad that they have been able to hand that project over to Fedora, the home they always meant for K12Linux to have.
Paul Nelson and Eric Harrison met online when Nelson, a classroom teacher and technology director at a small school in Portland's Riverdale School District, went looking for Linux help. "We were doing everything on the back end with Linux, but I was spending a lot of time keeping the Windows desktops running. I thought how nice it would be to use Linux on the front end too. I posted a notice on the local user group mailing list." Harrison, then a Multnomah County IT Services support tech, befriended Nelson, and the two had an idea: make a specialized Linux Terminal Server Project (LTSP) distribution that would allow schools to use thin clients running Linux on old, inexpensive hardware.
Nelson and Harrison started K12LTSP, as it was known then, so they could show other schools how to use Linux in the classroom. Harrison met Jim McQuillan, the founder of the LTSP project, and told him about the school project. McQuillan recommended building on LTSP, so Harrison and Nelson started working on a proof of concept they could present to Red Hat.
"Our goal," says Nelson, "was to use Red Hat, and produce an installer that would install all the LTSP parts. The end result would be a working terminal server that anyone could install as easy as installing Red Hat. Part of that goal was to have Red Hat take over the work of distributing and maintaining the project. We didn't think it would take very long. It took seven years."
Harrison, who worked tirelessly as the lead developer on the project until it became a Fedora community effort, agrees. "We thought we'd do a first implementation and somebody would pick it up. But the original design of the terminal server software didn't integrate very well into a distribution. The original LTSP was an entire distribution on its own, with custom glibc, xserver, everything. So for Red Hat to take it on would double their quality assurance load." When Red Hat didn't immediately jump on board, Harrison, who was on the verge of burnout, still wasn't willing to abandon the project. "The fundamental flaw with K12LTSP is that is has mostly been me doing the grunt work," Harrison wrote on a related mailing list. He turned to the Ubuntu project for integration help.
"[Ubuntu founder Mark] Shuttleworth said he was interested but saw the same integration issues. We worked with Ubuntu and LTSP to come up with a way to make it easier to integrate LTSP into a distribution." Harrison's work led to the creation of the Edubuntu project, a parallel to K12Linux. Then he went to work "preaching to the choir," as he put it, "about how much we all have in common and how important it is that we all work together." His evangelistic approach finally brought the help he needed. "We worked together to backport this integration into Fedora," Harrison says. "We used actual packages from the distribution so that the amount of programs unique to the terminal server piece is very small. That makes it more manageable."
By early 2008, LTSP5 packages were "trickling" into the Fedora repositories, and with the release of Fedora 10, K12Linux was a full-fledged integrated piece of the distribution.
Needless to say, Harrison's workload on the project has decreased dramatically. "It's gone from 'I do all the work' to 'other people do most of the work,'" he says. "I feel great. The work that I used to do was unique. By making that investment in redesigning the core technology so that it is easier to integrate into distributions, now we have lots more development resources."
Nelson hopes that K12Linux will become a familiar name in schools all over the country. "The last great step is to be able to call up a vendor and say, 'I'd like to buy a K12Linux lab," he says. "You could do that with a reseller. Or call Dell, and they'll know what you're talking about, but you wouldn't be able to search their Web site and find the price. Hewlett-Packard too. HP produces nice thin clients for $150 or $200, but they don't market them. I don't know why they don't, but that's the next step. Whoever takes that step will start to sell way more of them."


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DemocraTEA 2016
What better way to show who you support for this year's election than with the use of DemocraTEA. You get two types with this order. Hillary ClinTEAn is Vanilla Essence Tea or Donald TEArump is Pure White Tea with Peach. This is a sure fire way to make politics a little less….angry this year.
The bags these teas come in are great! I love both of them and the tea is pretty good too. It's organic tea so no worry about pesticides here. I really like the Vanilla Essence Tea and sadly, this is not where I lie on the presidential candidates..lol. However, the Donald TEArump tea is also good. There is a light taste of the peach so it's not overbearing.
The company that puts these out is located at http://www.democratea2016.com. Right now these are the only two teas for the election, but at their website you can vote for another and if they get 25,000 votes they will make that one too. Go on! Go vote so they will put out another.
You can get your own on Amazon here .
I love the idea of these. It's a way to get the conversation going over a good cup of tea and maybe a few laughs as well.
Have a great day!
I received this item for free or at a discount for my honest review.


text:
On 30 September 2014 Labour tabled its salary demands for 2015/16. The demands are the following:
An across the board increase of 15 % with effect (w.e.f.) from 1 April 2015
Housing Allowance
- An increase in the Housing Allowance from the current R 900 p.m. to R 3 000 p.m.
- An annual adjustment (on 1 April) equal to the annual salary adjustment
Medical Subsidy
- An increase of 28, 5% in the medical subsidy, w.e.f 1 January 2015, for GEMS and open scheme members (to inter alia compensate for lack of increases in 2012/2013/2014)
- The equalisation of subsidies in respect of open medical schemes (i.e. subsidies for GEMS and open schemes to be the same)
- The annual adjustment of the subsidy based on the average medical inflation of the previous year.
- Family responsibility leave to be broadened to include assistance to immediate family and parents-in-law
- 6 (Six) months paid maternity leave
- 2 (Two) weeks paid paternity leave outside of family responsibility leave
- 10 (ten) days special leave for employees with children with special needs
Other Demands
- Levels 1 to 3 must be compressed so that level 4 becomes an entry level into the Public Service
- The State must develop a bursary scheme for Public Service employees' children
- With effect from 1 January 2016, serving employees must be allowed to exercise a once-off choice of the month in which they wish their 13th cheque to be paid (new employees to exercise the same choice upon appointment)
The Recognition of Prior Learning (RPL)
The Employer's response to the demands is awaited.
A number of matters are still outstanding from previous collective agreements. Labour and the Employer agreed to negotiate these matters in a process parallel to the salary demands. The majority of these issues do not impact on educators, e.g. review of the PMDS, review of the Resolution dealing with employees not covered by OSDs, the impact of outsourcing in the public service, a Minimum Service Level Agreement (to allow certain employees in essential services who may not strike to participate in strike action – education is not a designated essential service).
Government Employees Housing Scheme (GEHS)
One of the outstanding areas that do affect educators, however, is the envisaged Government Employees Housing Scheme (GEHS).
- The Employer's proposals on the scheme (NB: At this stage it is only proposals) were tabled in the PSCBC on 7 October 2014. In short it entails the following:
- Employees will be required to enrol with the GEHS to benefit from services offered through the Scheme (e.g. facilitating financial rehabilitation, improving access to housing finance, facilitating housing stock to buy /rent)
- A proposed increase in the housing allowance w.e.f. 1 July 2015, which for the majority of educators who qualify will be insignificant (salary 1&2 proposed to increase to R 1200 p.m., levels 3&4 to R 1050 p.m. and levels 5-10 to R 970 p.m.)
- The housing allowance to be annually increased with the average CPI of the preceding financial year
- The housing allowance will be paid for a maximum of 20 years during employment in the public service ( this is in line with the normal bond repayment period), but for levels 1-4 the allowance will only be available up to 31 March 2025 (i.e. for 10 years)
- Employees who receive the housing allowance, but whose houses have been fully paid off will forfeit the allowance on 1 April 2017
- Employees who pay off their bonds after 31 March 2017 will continue to receive the housing allowance for a maximum of two years from the date that the bond is paid off
- Employees who own and reside in houses on communal land (those who receive the housing allowance), but whose houses have been fully paid off will continue to receive the housing allowance until 31 March 2030
- Employees who rent will only receive half of the housing subsidy they qualify for, whilst the other half will be deposited in an interest-bearing and tax-efficient individual saving facility administered by the GEHS – to be used for the sole purpose of acquiring home-ownership
- If after 10 years the employee has not utilised the funds in the saving facility to acquire home-ownership or when the employee's services are terminated, the savings will be forfeited.
- Only in the case of the death of an employee (presumably before the 10 year cut-off date is reached) will the money in the savings facility be paid out - to the estate and/or the nominated beneficiaries of the deceased
Negotiations proper on the matter have not commenced – only questions of clarity from Labour have thus far been dealt with.
As the negotiations continue further reports will be placed on the webpage.


text:
Six characters go in search of meaningless pleasure over the course of one night in Brisbane. At a fast-food pizza joint called Speedie, chef Dom (Sullivan Stapleton) kicks things off by trashing the place, sticking the body of a dead cat in the oven, and behaving in a less-than-genial manner. Misha (Ryan Johnson) boasts to co-workers that he had sex with his last pizza delivery customer; when his colleagues don't believe him, he runs...more
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Expression of the T‐cell receptor (TCR):CD3 complex is tightly regulated during T‐cell development. The mechanism and physiological role of this regulation are unclear. Here, we show that the TCR:CD3 complex is constitutively ubiquitylated in immature double positive (DP) thymocytes, but not mature single positive (SP) thymocytes or splenic T cells. This steady state, tonic CD3 monoubiquitylation is mediated by the CD3ε proline‐rich sequence, Lck, c‐Cbl, and SLAP, which collectively trigger the dynamin‐dependent downmodulation, lysosomal sequestration and degradation of surface TCR:CD3 complexes. Blocking this tonic ubiquitylation by mutating all the lysines in the CD3 cytoplasmic tails significantly upregulates TCR levels on DP thymocytes. Mimicking monoubiquitylation by expression of a CD3ζ‐monoubiquitin (monoUb) fusion molecule significantly reduces TCR levels on immature thymocytes. Moreover, modulating CD3 ubiquitylation alters immunological synapse (IS) formation and Erk phosphorylation, thereby shifting the signalling threshold for positive and negative selection, and regulatory T‐cell development. Thus, tonic TCR:CD3 ubiquitylation results in precise regulation of TCR expression on immature T cells, which is required to maintain the fidelity of T‐cell development.
The T‐cell receptor (TCR):CD3 complex, one of the most complicated receptor complexes on the cell membrane, is composed of a TCRαβ heterodimer, which recognizes cognate antigen, and the associated CD3 molecules (CD3δ, γ, ε, and ζ), which are required for TCR expression, signal transduction, and receptor transport (Clevers et al, 1988; Klausner et al, 1990). A hallmark of T‐cell development in the thymus is the tightly controlled cell surface expression of the TCR:CD3 complex, which is low on double positive (DP; CD4+CD8+) thymocytes and high on single positive (SP; CD4+ or CD8+) thymocytes and peripheral T cells (Bluestone et al, 1987). Subtle changes in TCR signal strength determine the fate of immature thymocytes and therefore the fine control of TCR:CD3 expression level on immature thymocytes is likely to be essential in controlling T‐cell selection (Daniels et al, 2006). However, the precise mechanism that controls TCR expression in the thymus is unclear. Initially, a posttranscriptional mechanism or instability of the nascent TCRα protein was proposed to regulate TCR:CD3 expression during T‐cell development (Bluestone et al, 1987; Klausner et al, 1990; Kearse et al, 1994, 1995). However, recent studies have suggested that ubiquitylation may contribute to this process. Ubiquitin (Ub) can be attached to proteins via free lysine (K) residues by specific E3 Ub ligases (Glickman and Ciechanover, 2002). Monoubiquitylation (the addition of a single Ub residue) has been shown to modulate protein endocytosis and intracellular transport (Haglund et al, 2003a; Marmor and Yarden, 2004). MonoUb can be further modified to generate polyUb chains via an isopeptide linkage between the C‐terminal glycine carboxyl group of the Ub being added and the ε‐amino group of a lysine on the protein‐attached Ub (Hochstrasser, 2006), which predominantly occurs at K48 and K63 (Peng et al, 2003; Xu and Peng, 2008). Whereas K48‐linked polyubiquitylation typically leads to protein degradation by 26S proteasomes (Glickman and Ciechanover, 2002; Goldberg, 2003), K63‐linked polyubiquitylation is thought to modulate a variety of events including signal transduction and receptor endocytosis (Wang et al, 2001). Two molecules that are highly expressed in the thymus, c‐Cbl (Cbl; Casitas B‐lineage lymphoma), a RING‐type E3 Ub ligase, and SLAP (Sla; Src‐like adaptor protein), a c‐Cbl adaptor protein, are thought to modulate TCR expression on DP thymocytes (Sosinowski et al, 2001; Molero et al, 2004; Myers et al, 2006). However, c‐Cbl and SLAP interact with and/or ubiquitylate multiple T‐cell signalling molecules, such as Lck and Zap70 (Tang et al, 1999; Thien and Langdon, 2001; Rao et al, 2002), and thus it is unclear which interaction is responsible for the regulation of TCR expression on immature T cells. Recently, it was suggested that LAPTM5, a lysosomal protein, negatively regulates surface TCR expression by degrading CD3ζ via its Ub‐interacting motif, suggesting a possible role for ubiquitylation in modulating TCR:CD3 complex expression (Ouchida et al, 2008). However, TCR expression on DP thymocytes was only slightly increased in Laptm5−/− mice.
In this study, we addressed the following questions using biochemical analysis, confocal microscopy, and in vivo genetic approaches: (1) Is the TCR:CD3 complex differentially ubiquitylated in thymic and splenic T cells, and if so what type of ubiquitylation occurs (e.g. monoUb, polyUb)? (2) What is the mechanism by which TCR:CD3 surface expression is regulated and what molecules participate in CD3 ubiquitylation? (3) What is the physiological role of TCR:CD3 ubiquitylation?
Tonic ubiquitylation of CD3 in DP thymocytes
To investigate the mechanism that regulates TCR surface expression on immature T cells (Supplementary Figure S1A), we first confirmed that CD3 protein expression in DP thymocytes is much lower than SP thymocytes (Supplementary Figure S1B), which is clearly due to a posttranscriptional degradative event, as mRNA levels of all four CD3 molecules were similar between DP and SP thymocytes (Supplementary Figure S1C) (Maguire et al, 1990).
As some receptors have been shown to be regulated by a Ub‐dependent endocytosis mechanism (Shih et al, 2000), and CD3ζ and δ are ubiquitylated after T‐cell activation (Cenciarelli et al, 1992), we speculated that increased ubiquitylation of CD3 may occur in immature thymic T cells. To test this possibility, we assessed whether CD3ζ was ubiquitylated in DP thymocytes. CD3ζ from resting SP thymocytes, DP thymocytes, and splenic T cells was immunoprecipitated, separated on an SDS–PAGE gel and western blots probed with a Ub monoclonal antibody (mAb). Lysate from crosslinked anti‐CD3ε‐activated splenic T cells was included as a positive control. As expected, we observed a ladder of ubiquitylated CD3ζ in activated, but not resting, splenic T cells. The size of these bands (24, 32, 40 kD, etc.) was consistent with CD3ζ modification by progressive addition of the 8‐kD Ub protein (Cenciarelli et al, 1992). Remarkably, constitutively ubiquitylated CD3ζ was observed in DP, but not SP thymocytes in the absence of TCR:CD3 crosslinking (Figure 1A). Similarly, we detected ubiquitylation of CD3ε in DP, but not SP thymocytes following immunoprecipitation with CD3ε mAbs and western blot analysis with a Ub mAb (Figure 1B). A comparable polyUb ladder was also seen by direct western blot analysis of DP thymocyte lysates with a CD3ζ mAb (Figure 1C). These data show that at any one time only a small proportion of CD3ζ is ubiquitylated suggesting a dynamic process.
Given that CD3ζ in splenic T cells is ubiquitylated following TCR ligation, it is possible that the observed ubiquitylation in DP thymocytes is derived from the fraction of thymocytes that are undergoing positive selection. Interestingly, a similar level of CD3ζ ubiquitylation was observed in CD69lo prepositive selection DP thymocytes and DP thymocytes from mice lacking MHC class I and class II [B2m−/−Abb−/−] (Figure 1D). These data suggest that CD3ζ ubiquitylation in DP thymocytes is constitutive and MHC‐ligation independent, showing that this is not restricted to cells undergoing positive selection. Hereafter, we refer to this process as 'tonic' ubiquitylation as it appears analogous to the low level, constitutive tyrosine phosphorylation of the TCR:CD3 observed in DP thymocytes (Nakayama et al, 1989). Cbl−/− DP thymocytes express high levels of TCR (Figure 1E) (Murphy et al, 1998; Naramura et al, 1998), suggesting c‐Cbl is involved in TCR downregulation. Indeed, the Cbl−/− thymocytes exhibit little CD3ζ ubiquitylation showing that c‐Cbl expression is required for ubiquitylation of CD3ζ (Figure 1F).
Given that ubiquitylation has been shown to alter protein trafficking and intracellular location (Haglund et al, 2003a; Marmor and Yarden, 2004; Mukhopadhyay and Riezman, 2007), we questioned whether the TCR:CD3 complex was differentially distributed in SP versus DP thymocytes. In wild‐type mice, CD3ζ was uniformly distributed on the cell surface of SP thymocytes (Figure 1G and H). Surprisingly, although some CD3ζ in DP thymocytes was expressed on the cell surface, most appeared to be confined to a single, defined intracellular compartment. A similar differential staining pattern was observed when thymocytes were stained with antibodies to either TCRβ or CD3ε (data not shown). Interestingly, this TCR:CD3 sequestration was not observed in Cbl−/− DP thymocytes, which instead looked essentially identical to the even surface staining pattern observed in wild‐type SP thymocytes and their Cbl−/− SP counterparts (Figure 1G and H). These data show that CD3 ubiquitylation leads to the redistribution and intracellular sequestration of the TCR:CD3 complex in DP thymocytes. We also observed a similar phenotype in Sla−/− thymocytes (Supplementary Figure S2). Taken together, these data suggest that c‐Cbl/SLAP‐dependent, MHC‐independent tonic ubiquitylation of the TCR:CD3 complex occurs on DP thymocytes, but not SP thymocytes or peripheral T cells and that this modulates TCR surface expression by orchestrating its cellular sequestration.
Lck and the CD3ε proline‐rich sequence are required for CD3 tonic ubiquitylation
To determine whether Src kinases are involved in the regulation of TCR expression in DP thymocytes, we treated neonatal thymi with Src kinase inhibitors (PP1 and PP2). Inhibition of Src kinase activity upregulated surface TCR expression on DP thymocytes, suggesting that either Lck or Fyn might be involved in the CD3 tonic ubiquitylation pathway (Figure 2A). We next analysed TCR expression on DP thymocytes from WT, Fyn−/−, and Lck−/− mice by flow cytometry. Although Fyn deficiency had no effect on TCR expression on DP thymocytes, there was a substantial increase in TCR expression on Lck−/− DP thymocytes (Figure 2B). Likewise the absence of Lck, but not Fyn altered the distribution pattern of CD3ζ in DP thymocytes, which was indistinguishable to that observed in wild‐type SP thymocytes (Figure 2C and D). To test whether Lck or Fyn mediates tonic ubiquitylation of CD3, we assessed the ubiquitylation status of CD3ζ in DP thymocytes of WT, Fyn−/−, and Lck−/− mice. Although tonic ubiquitylation of CD3ζ was observed in WT and Fyn−/− DP thymocytes, it was absent in Lck−/− DP thymocytes (Figure 2E). These data show that Lck, rather than Fyn, is required for CD3 tonic ubiquitylation and thus regulation of TCR surface expression on immature T cells.
Earlier studies have shown that the proline‐rich sequence (PRS) in CD3ε modulates TCR expression and signal transduction, suggesting that the CD3ε‐PRS may be involved in tonic ubiquitylation of CD3 in DP thymocytes (Szymczak et al, 2005; Mingueneau et al, 2008; Tailor et al, 2008). To assess this possibility, we examined CD3 expression, distribution, and ubiquitylation in DP thymocytes from mice possessing a knock‐in mutation of the CD3ε PRS (Cd3eΔPRS/ΔPRS) (Mingueneau et al, 2008). As described earlier (Mingueneau et al, 2008), TCR expression was increased on Cd3eΔPRS/ΔPRS DP thymocytes compared with their wild‐type controls (Figure 3A). As seen in DP thymocytes lacking c‐Cbl, Slap, and Lck, DP thymocytes from Cd3eΔPRS/ΔPRS mice exhibited an even TCR:CD3 surface distribution, as seen in wild‐type SP thymocytes (Figure 3B and C). Furthermore, there was a complete loss of CD3ζ tonic ubiquitylation in Cd3eΔPRS/ΔPRS DP thymocytes (Figure 3D). Taken together, these data show that the CD3ε‐PRS is required for CD3 tonic ubiquitylation and suggests that CD3ε‐PRS association with Nck may mediate TCR:CD3 complex translocation to intracellular compartments.
TCR:CD3 monoubiquitylation mediates its dynamin‐dependent internalization and targeting to lysosomes for degradation
The intracellular TCR:CD3 sequestration observed in DP thymocytes suggested that there might be an active downregulation process mediated by tonic CD3 ubiquitylation. Dynamin is a guanosine triphosphatase that is required for the fission of membrane and endocytic vesicles (Praefcke and McMahon, 2004). To determine whether dynamin contributes to TCR internalization in DP thymocytes, we treated neonatal thymi with a dynamin inhibitor (MiTMAB) (Figure 4A and B). There was a substantial increase of surface TCR on DP, but not SP thymocytes, suggesting that ubiquitylation may mediate enhanced, dynamin‐dependent TCR:CD3 internalization and downregulation in immature DP but not mature SP thymocytes. However, additional studies will be required to fully elucidate the contribution of dynamin in these events.
The reduced CD3 protein levels in DP versus SP thymocytes, despite comparable mRNA levels (Supplementary Figure S1), suggested that the TCR:CD3 complex was being degraded in DP thymocytes. We reasoned that this Ub modification might mediate the internalization and trafficking of the TCR complex in DP thymocytes to sites of degradation; lysosomes or proteasomes. Thus, we next determined the fate of tonic ubiquitylated TCR:CD3 complexes on DP thymocytes in neonatal thymic organ culture experiments using inhibitors of lysosomal (NH4Cl and Concanamycin A) and proteasomal degradation (MG132 and lactacystin). Consistent with earlier studies (Kosugi et al, 1992; Lacorazza and Nikolich‐Zugich, 2004), our data suggest that the TCR:CD3 complexes in DP thymocytes are degraded in lysosomes, and not by proteasomes (Figure 4C). A recent study reported that a lysosomal protein, LAPTM5, controls the degradation of CD3ζ in DP thymocytes and activated T cells, a process that requires the LAPTM5 Ub‐interacting motif (Ouchida et al, 2008). Consistent with these data, we observed that CD3ζ colocalized with LAPTM5 in DP but not SP thymocytes (Supplementary Figure S3). Taken together, these data suggest that ubiquitylated TCR:CD3 complexes are degraded in lysosomes. However, additional analysis will be required to fully define the intracellular trafficking and degradation pathway of TCR:CD3 complexes in DP thymocytes.
Two types of Ub modification have been linked with protein internalization and trafficking to lysosomes; monoubiquitylation (Haglund et al, 2003a; Marmor and Yarden, 2004) and K63‐linked polyubiquitylation (Mukhopadhyay and Riezman, 2007). To distinguish between these two forms of Ub modification, we used a mAb specific for all forms of poly‐, but not mono‐, ubiquitylated proteins (polyUb, clone FK1) (Haglund et al, 2003b; Fujimuro and Yokosawa, 2005) and a highly specific and sensitive K63‐linked polyUb‐specific mAb (K63Ub, clone HWA4C4) that we recently developed (Wang et al, 2008). Western blot analysis of CD3ζ in DP thymocytes clearly indicated that tonic Ub modification was detected with an mAb specific for Ub but not polyUb mAb or K63Ub mAb (Supplementary Figure S4). Taken together, these data are consistent with a model in which tonic monoubiquitylated TCR:CD3 complexes are internalized in a dynamin‐dependent manner and transported to lysosomes for degradation, thus maintaining the characteristic low surface TCR expression seen on DP thymocytes. However, we cannot completely rule out the possibility that CD3 polyubiquitylation occurs, albeit to an extent that could not be detected with the approaches used here.
Tonic ubiquitylation regulates TCR surface expression on immature T cells
We next directly assessed whether this tonic ubiquitylation was required and sufficient for the regulation of TCR surface expression on DP thymocytes by generating mutant mice in which CD3 ubiquitylation was blocked. Of the known target residues for ubiquitylation (Cadwell and Coscoy, 2005), there are 37 lysines and no cysteines in the CD3 cytoplasmic domains (Figure 5A). Furthermore, it has been shown previously that the intracellular lysines of CD3ζ are required for CD3ζ ubiquitylation (Hou et al, 1994). To block CD3 tonic ubiquitylation, we generated mice expressing CD3 mutant molecules (CD3KR), in which all cytoplasmic lysines were mutated to arginines, using retroviral‐mediated stem cell gene transfer and multicistronic 2A peptide‐linked retroviral vectors (Supplementary Figure S5) (Holst et al, 2006a, 2006b) [referred to as retrogenic mice]. CD3‐deficient bone marrow donors (referred to herein as CD3εζ−/− mice) were generated by crossing Cd247−/− (CD3ζ) and Cd3eΔp/Δp (CD3ε) mice. The latter possess a PGK‐neo cassette inserted into Cd3e gene that results in the complete silencing of the adjacent Cd3g (CD3γ) and Cd3d (CD3δ) genes (Wang et al, 1999; Holst et al, 2008). Rag1−/− mice, which lack T and B cells, were used as recipients. Western blot analysis confirmed that CD3ζ was no longer ubiquitylated following activation of T cells from CD3KR retrogenic mice (Figure 5B). Interestingly, TCR expression on CD3KR DP thymocytes was upregulated more than three‐fold compared with wild‐type (CD3WT) mice (Figure 5C). The upregulation of TCR on DP thymocytes from CD3KR mice was not due to CD3 overexpression as the level of the green florescent protein (GFP) reporter contained within these retroviral vectors (an internal ribosome entry site‐GFP) was comparable between the CD3WT and CD3KR retrogenic mice (Supplementary Figure S5C). In contrast to DP thymocytes, a 40% reduction in TCR expression was observed on SP thymocytes from CD3KR mice compared with the CD3WT mice, which is also observed in Cbl−/− and Cbl loss‐of‐function mutant mice (Thien et al, 2003). These data suggest that tonic CD3 ubiquitylation is required to control TCR expression on immature DP thymocytes.
Functional redundancy in the usage of ubiquitylated CD3 cytoplasmic lysines
All four CD3 cytoplasmic domains possess lysine residues (four in CD3γ, three in CD3δ, six in CD3ε, and nine in CD3ζ; Figure 5A). To determine which CD3 subunits contain functional ubiquitylation sites that are sufficient to limit TCR:CD3 expression on DP thymocytes, we generated four additional groups of retrogenic mice expressing combinations of one CD3 wild‐type subunit with the remainder CD3KR mutant (e.g. CD3ζWTδγεKR encodes wild‐type CD3ζ and lysine‐mutated CD3δ, CD3γ, and CD3ε). TCR expression on DP thymocytes in the CD3δWTγεζKR, CD3εWTδγζKR, and CD3ζWTδγεKR mice was restored to wild‐type levels (Figure 5D). However, the CD3γWTδεζKR mice had higher TCR expression on DP thymocytes, indicating that the lysines in the CD3γ chain are insufficient for tonic ubiquitylation‐meditated regulation of TCR expression on immature T cells. Therefore, there is functional redundancy in the usage of ubiquitylated CD3 cytoplasmic lysines and that very few lysines (3 lysines in CD3δ chain versus 37 in all the CD3 cytoplasmic domains) are sufficient to control TCR:CD3 expression.
CD3ζ monoubiquitylation is sufficient to mediate low TCR expression on DP thymocytes
Lysine residues can also be the target of other modifications, such as sumoylation, neddylation, and methylation, which may occur on CD3 molecules. None of these modifications were detectable on CD3ζ in either mature or immature T cells (Supplementary Figure S6), although we cannot exclude the possibility that increased TCR on DP thymocytes in CD3KR mice is mediated by subtle or alternate CD3ζ modifications. Furthermore, we cannot completely rule out the possibility that these mutations may affect the structure of the CD3 cytoplasmic tails, although they appear relatively unstructured except for the ITAMs (Aivazian and Stern, 2000; Sigalov et al, 2006; Xu et al, 2008). They do appear to associate with the inner leaflet of the plasma membrane via electrostatic interactions between basic CD3 residues and acidic phospholipids, which one might predict would be retained with conservative Lys:Arg substitutions.
To address these issues directly, we investigated whether attaching Ub to the carboxy‐terminal end of CD3ζ was able to restore control of TCR expression. We attached a monoUb to the COOH‐terminus of CD3KR (CD3KR‐monoUb) to mimic the monoubiquitylated form of the TCR:CD3 complex. Two modifications were made to ensure that this Ub moiety was not further modified. First, all seven Ub lysines were mutated to arginine (K6/11/27/29/33/48/63R) to prevent polyubiquitylation (Shih et al, 2000). Second, the two C‐terminal glycine residues (G75/76) were removed to prevent conjugation to endogenous Ub or another protein. We assessed TCR:CD3 complex expression on HEK‐293T cells using CD3ζKR, CD3ζKR‐monoUb, or an unmodified Ub attached to the CD3ζKR COOH‐terminus as a control (CD3ζKR‐Ub). Attaching either form of Ub to CD3ζ substantially reduced TCR expression (Supplementary Figure S7A).
As the internalization of ubiquitylated TCR:CD3 appeared to be dynamin‐dependent (Figure 4A and B), and enzymatically inactive forms of dynamin act as dominant negatives and block endocytosis (Praefcke and McMahon, 2004), we reasoned that such mutants should block the internalization of an appropriately modified CD3‐Ub chimera. Dominant negative dynamin had no effect on TCR expression on the CD3ζKR‐Ub transfectants, suggesting that attachment of wild‐type Ub to CD3ζKR led to intracellular TCR:CD3 complex retention and/or degradation (Supplementary Figure S7B). In contrast, normal expression of TCR complexes containing CD3ζKR‐monoUb was completely restored by dominant negative dynamin, consistent with our observations using the dynamin inhibitor MiTMAB with DP thymocytes. Collectively, these data suggested that CD3 monoubiquitylation triggered rapid dynamin‐dependent TCR internalization and lysosomal sequestration.
Retrogenic mice expressing CD3KR‐monoUb showed a 50% reduction in TCR:CD3 complex expression on DP thymocytes compared with CD3WT levels, showing that 'increased' ubiquitylation of CD3ζ on DP thymocytes leads to reduced surface TCR expression (Figure 7A). Collectively, these data are consistent with a model in which highly controlled, tonic ubiquitylation is required for fine tuning TCR:CD3 complex expression on immature DP thymocytes.
Tonic ubiquitylation controls TCR signalling in DP thymocytes and regulates T‐cell development
To test whether altered tonic ubiquitylation of the TCR:CD3 complex affects TCR signalling in DP thymocytes, we measured immunological synapse (IS) formation and ERK phosphorylation status in activated CD3WT and CD3KR DP thymocytes. Earlier studies have suggested that DP thymocytes form multifocal synapses, whereas mature peripheral T cells form compact IS (Hailman et al, 2002). Thus, we used total internal reflection fluorescent microscopy with synthetic planar lipid bilayer containing unlabelled His‐tagged ICAM‐1 and fluorescently labelled streptavidin conjugated to biotinylated TCRβ mAbs to assess the effect of abrogated CD3 ubiquitylation on IS formation in DP thymocytes. Significant differences were observed between the pattern of IS formed by CD3WT versus CD3KR DP thymocytes 15 min poststimulation on lipid bilayers. First, the TCR contact area was significantly reduced with CD3KR DP thymocytes (Figure 6A). Second, the percentage of compact IS relative to multifocal and diffuse IS was significantly increased with CD3KR versus CD3WT DP thymocytes (Figure 6B and C). These data suggest that preventing CD3 ubiquitylation leads to IS formation that is more reminiscent of mature peripheral T cells.
We also assessed ERK phosphorylation following TCR stimulation of DP thymocytes by flow cytometry. A significantly increased percentage of CD3KR versus CD3WT DP thymocytes expressed pERK (Figure 6D and E). Similar observations were also made with Sla−/− DP thymocytes (Supplementary Figure S8). The specificity of these observations was confirmed by the use of the MEK inhibitor U0126. Interestingly, increased pERK was more prolonged in CD3KR DP thymocytes compared with Sla−/− thymocytes (Figure 6D; Supplementary Figure S8A). Taken together, these data suggest that blocking CD3 tonic ubiquitylation increases TCR signalling strength in immature T cells.
To determine whether tonic ubiquitylation of the TCR:CD3 complex regulates T‐cell development, we analysed the distribution of DN, DP, and SP thymocytes and total thymocyte number in CD3WT, CD3KR, and CD3KR‐monoUb retrogenic mice. CD3KR mice had twice as many thymocytes as CD3WT mice, whereas CD3KR‐monoUb mice had substantially reduced thymic cellularity that was ∼1/10th of CD3WT mice (Figure 7B). The distribution of DN, DP, and SP thymocytes in CD3KR versus CD3WT mice was unchanged (Figure 7C and D; Supplementary Figure S9A). In contrast, CD3KR‐monoUb mice had an increased percentage of DN thymocytes (Figure 7C and D). Furthermore, the number and percentage of natural regulatory T cells (Tregs) in the thymus and spleen was substantially reduced in CD3KR‐monoUb mice (Figure 7E–G). Interestingly, the CD3KR‐monoUb mice became sick and died 8–12 weeks post bone marrow transfer, with moderate inflammation, multifocal crypt necrosis, and enterocyte apoptosis in the small and large intestines, and vasculitis in the liver (Supplementary Figure S10 and Supplementary Table S1). Whether this disease is due to a breakdown of central tolerance as described in other mouse models with TCR hyporesponsiveness (Aguado et al, 2002; Sommers et al, 2002; Holst et al, 2008) and/or limited generation of natural Tregs in the periphery is unclear and would require further analysis. To rule out the possibility that hypo‐ or hyper‐ubiquitylation promotes the generation of DP thymocytes in the absence of TCR, we generated retrogenic mice using CD3WT, CD3KR, and CD3KR‐monoUb transduced CD3εζ−/− Rag1−/− bone marrow (Supplementary Figure S11). In the absence of TCR, we found little, if any, DP thymocytes in CD3WT, CD3KR, or CD3KR‐monoUb retrogenic mice. Collectively, these results suggest that the altered TCR:CD3 ubiquitylation in thymocytes affects T‐cell development.
Finally, to assess whether positive and negative selection were altered by the extent of TCR:CD3 ubiquitylation, we generated retrogenic mice co‐expressing either CD3WT, CD3KR, or CD3KR‐monoUb with the MataHari TCR, a H‐2Kb‐restricted Vβ8.3+ TCR specific for the male antigen Uty (Valujskikh et al, 2002; Holst et al, 2006b). Bone marrow from male or female CD3εζ−/−Rag1−/− mice was transduced with retrovirus encoding the MataHari TCR and the different versions of CD3, and transplanted into irradiated Rag1−/− mice of the same sex. In female mice, where MataHari T cells are normally positive selected, we observed a uniform population of CD8+Vβ8.3+ T cells in the periphery in mice expressing CD3WT molecules (Figure 8A). However, CD3KR female mice have ∼3 times more thymocytes than CD3WT female mice, a higher CD8 SP to TCR+ DP thymocyte ratio, and a higher percentage of CD8+Vβ8.3+ T cells in the periphery (Figure 8A and B; Supplementary Figure S9B), suggesting that positive selection was enhanced when CD3 tonic ubiquitylation was blocked. Interestingly, T‐cell development was blocked at the DP stage in MataHari CD3KR‐monoUb female mice with very low CD5 expression on DP thymocytes, normally upregulated on positive selection (Jameson et al, 1995; Tarakhovsky et al, 1995), and no T cells found in the periphery, despite substantial thymocyte cellularity (Figure 8A–C; Supplementary Figure S12). These data suggest that the signal that normally mediates positive selection in MataHari mice may be converted into one that mediates neglect in CD3KR‐monoUb MataHari female mice (Supplementary Figure S13).
In male mice, CD3WT and CD3KR MataHari T cells were deleted normally, as expected, with thymic cellularity significantly reduced compared with MataHari female mice (Figure 8A–C; Supplementary Figure S12). As shown earlier, some T cells escaped negative selection in the thymus by downregulation of CD8 and/or TCR expression and appear in the periphery (Figure 8A) (Valujskikh et al, 2002). It is noteworthy that in both male and female CD3KR MataHari mice, there are significantly less CD8−Vβ8.3+ T cells in the periphery (Figure 8A), again suggesting that altered CD3 ubiquitylation can alter T‐cell tolerance mechanisms. In contrast, there appeared to be no deletion in male CD3KR‐monoUb MataHari mice as thymus size and cellularity, and CD5 expression on DP thymocytes were comparable to CD3WT female mice (Figure 8B and C; Supplementary Figure S12), and a uniform population of GFP+CD8+ T cells was found in the blood (Figure 8A) [note that consistent with CD3KR‐monoUb mice, TCR surface expression is also low in the MataHari CD3KR‐monoUb mice]. These data suggest that negative selection may be converted into positive selection in CD3KR‐monoUb MataHari male mice (Supplementary Figure S13). Collectively, these findings suggest that the signalling threshold for positive and negative selection is directly regulated by tonic ubiquitylation of the TCR:CD3 complex.
Our results show that c‐Cbl‐dependent, MHC‐independent constitutive, tonic ubiquitylation of the TCR:CD3 complex occurs in, and is restricted to, DP thymocytes. Earlier studies had suggested that TCR:CD3 ubiquitylation was restricted to activated mature T cells (Cenciarelli et al, 1992). CD3 tonic ubiquitylation is mediated by Lck and the CD3ε‐PRS, which may cooperatively recruit a c‐Cbl:SLAP complex that subsequently mediates CD3 ubiquitylation. We further show that CD3 tonic ubiquitylation is required and sufficient for the downregulation of surface TCR expression, a hallmark of T‐cell development. Our data are consistent with a model in which there is a moderate level of constitutive Lck activity, perhaps facilitated by the miR181a‐mediated depletion of Src‐inactivating phosphatases (Li et al, 2007b), which phosphorylates CD3 and the c‐Cbl:SLAP complex that is subsequently recruited to the CD3ε‐PRS, perhaps via Nck. Collectively, these molecular events mediate the tonic ubiquitylation of the TCR:CD3 complex in the absence of any TCR:MHC ligation. The ubiquitylated TCR:CD3 complex is internalized in a dynamin‐dependent manner and transported to lysosomes for degradation mediated by LAPTM5. Clearly, there are steps in this model that require further examination. First, whether there is a direct connection between miR181a and tonic ubiquitylation remains to be determined. Second, whether Lck is directly or indirectly recruited to the CD3ε PRS by Nck remains to be determined. Indeed, the precise role of the CD3ε PRS in mediating tonic ubiquitylation remains obscure. Third, the precise fate and pathway followed by tonic ubiquitylated TCR:CD3 complexes remains to be more fully defined.
Why might tonic ubiquitylation only occur in DP thymocytes? First, the E3 ligase machinery that drives tonic ubiquitylation (c‐Cbl+Slap) is predominantly expressed in immature T cells (Sosinowski et al, 2001; Molero et al, 2004; Myers et al, 2006). Although c‐Cbl is expressed at higher amounts in thymocytes, compared with splenic T cells, SLAP expression is essentially restricted to DP thymocytes, which may serve to mitigate c‐Cbl activity. Second, a recent study has shown that high expression of miR181a in DP thymocytes represses multiple phosphatases, which leads to increased tyrosine kinase activity and target phosphorylation (Li et al, 2007b). This may in turn lead to enhanced activation of the c‐Cbl:SLAP complex.
The requirement for a c‐Cbl:SLAP complex as the primary, if not sole mediator of TCR:CD3 tonic ubiquitylation, is consistent with earlier studies showing that Cbl−/− and Sla−/− mice have upregulated TCR expression on DP thymocytes and increased positive selection in DO11.10 TCR transgenic mice (Naramura et al, 1998; Sosinowski et al, 2001; Myers et al, 2006). Importantly, we also show that the modulation of TCR:CD3 ubiquitylation has a substantial effect on thymocyte cellularity, positive and negative selection, and ultimately the establishment of a peripheral T‐cell pool. We propose that tonic ubiquitylation of the TCR:CD3 complex on immature thymocytes tightly regulates surface TCR expression and may help to maintain the fidelity of T‐cell development.
How might the CD3ε‐PRS be involved in mediating CD3 tonic ubiquitylation in DP thymocytes? Our data have shown that Lck is required for tonic ubiquitylation of CD3 in immature T cells. A recent study proposed that recruitment of Lck in immature T cells is mediated by the CD3ε‐PRS in DP thymocytes (Mingueneau et al, 2008). The CD3ε‐PRS seems to be constitutively exposed and interacts with Nck (Gil et al, 2002; Mingueneau et al, 2008; Brodeur et al, 2009; Wang et al, 2009). As ∼50% of Lck in DP thymocytes is not associated with CD4 or CD8, this free Lck may be recruited to the TCR:CD3 complex by interacting with the Nck‐SH3 domain, resulting in tonic phosphorylation of CD3 chains, c‐Cbl and SLAP, which in turn triggers the tonic CD3 ubiquitylation pathway. Consistent with this model, our data showed that tonic CD3 ubiquitylation is blocked and the distribution of the TCR:CD3 is altered in DP thymocytes from mice lacking CD3ε‐PRS, Lck, c‐Cbl, or SLAP.
In addition to observing increased TCR on DP thymocytes in CD3KR mice, counterintuitively, we also saw a reduction in TCR expression on SP thymocytes and peripheral T cells (Figure 5C). Interestingly, similar observations were made with the Cbl−/− or Cbl loss‐of‐function mutant mice (Thien et al, 2003). This phenotype may be cell extrinsic and caused by increased TCR signalling strength due to higher TCR expression on DP thymocytes (Figure 6; Supplementary Figure S8), which may lead to increased negative selection. Thus, some thymocytes, which have lower TCR expression, may successfully escape negative selection. Alternatively, lowered TCR on SP and peripheral T cells, may be cell intrinsic with ubiquitylation performing a protective role in the regulation of TCR expression in mature T cells, perhaps by limiting AP1‐mediated internalization (Liu et al, 2000; Szymczak and Vignali, 2005).
Several lines of evidence suggest that the primary role of CD3 ubiquitylation in DP thymocytes is to target the TCR:CD3 complex to lysosomes for degradation thereby reducing surface TCR expression. First, earlier studies have shown that receptor monoubiquitylation mediates their internalization and lysosomal degradation (Shih et al, 2000; Haglund et al, 2003b). Our data suggest that the TCR:CD3 complex in DP thymocytes is constitutively subjected to multiple monoUb additions to multiple lysine residues throughout the CD3 cytoplasmic domains. Second, we have also shown that mimicking monoubiquitylation by expression of a CD3ζ‐monoUb chimeric molecule reduces surface TCR expression on thymocytes. Third, blocking internalization with dynamin inhibitors (MiTMAB) or blocking lysosomal degradation with acidification inhibitors (NH4Cl or Concanamycin A) resulted in increased surface TCR expression on DP thymocytes. Fourth, a recent study showed that LAPTM5 mediates CD3 degradation in both thymocytes and activated T cells (Ouchida et al, 2008). Interestingly, the Ub‐interacting motif of LAPTM5 is required for CD3 degradation. Our data showed that LAPTM5 and CD3 colocalize in immature DP thymocytes, which is consistent with a model in which LAPTM5 may selectively interact with ubiquitylated CD3 via its Ub interacting motif to induce CD3 lysosomal degradation. At odds with this model is the observation that TCR expression on DP thymocytes was only slightly increased in Laptm5−/− mice, in contrast to the significant increases seen with Cbl−/−, Sla−/−, Lck−/−, and Cd3eΔPRS/ΔPRS mice (Figures 1G, 2C, and 3B; Supplementary Figure S2B) (Molina et al, 1992; Sosinowski et al, 2001; Molero et al, 2004; Mingueneau et al, 2008; Ouchida et al, 2008). However, it is possible that other Ub‐binding, lysosomal resident proteins cooperate with LAPTM5 to mediate TCR:CD3 sequestration and degradation.
Why might tonic CD3 ubiquitylation in DP thymocytes be important? Clearly, a key consequence of abrogating tonic CD3 ubiquitylation is increased TCR. Our data suggest that this leads to altered IS formation and contraction, and increased Erk phosphorylation, thereby shifting the signalling threshold for positive and negative selection, and regulatory T‐cell development. Earlier studies have suggested that the type of synapse that forms between DP thymocytes and thymic epithelial cells (TECs) alters their selection fate (Hailman et al, 2002; Richie et al, 2002; Ebert et al, 2008). Thus, tonic ubiquitylation may help to ensure that the appropriate DP:TEC interactions are maintained for optimal positive and negative selection. What remains unclear is whether modulated IS formation and signalling are a direct consequence of increased TCR or are independently regulated by tonic CD3 ubiquitylation.
Understanding the role of CD3 tonic ubiquitylation in immature T cells may also provide insight into the role/contribution of CD3 ubiquitylation in activated T cells, whether this is mediated by the same, related or distinct molecules, and if the fate of ubiquitylated CD3 following TCR ligation is the same or different. Our results suggest that disruption of TCR expression control in DP thymocytes can lead to increased TCR signalling, altered positive and negative selection, and reduced Treg development. Although profound autoimmunity was not observed in CD3KR mice, it is possible that more chronic conditions may develop with time as has been observed in mice possessing mutations that disrupt TCR expression (Naramura et al, 2002). Clearly, this is a topic that will require further study.
Materials and methods
Rag1−/− (recombination activating gene 1) and C57BL/6J mice were obtained from Jackson Laboratories. B2m−/−Abb−/− mice (β‐2 microglobulin and MHC class II H‐2A β chain, respectively) were purchased from Taconic Farms. Thymi from Cbl−/− (c‐Cbl—Casitas B‐lineage lymphoma) mice were provided by M Naramura and H Band. Thymi from CD3eΔPRS/ΔPRS mice were provided by B Malissen. Thymi from Lck−/− and Fyn−/− mice were provided by S Hayes. Thymi from Slap−/− mice were provided by L Dragone. CD3εζ‐KO mice lacking all four CD3 chains were generated by crossing CD3eΔP/ΔP mice with CD3ζ−/− mice as described earlier (Wang et al, 1999; Szymczak et al, 2004; Holst et al, 2008). All animal experiments were performed in an AAALAC‐accredited, Helicobacter‐free, specific pathogen‐free facility following national, state, and institutional guidelines. Animal protocols were approved by St Jude Institutional Animal Care and Use Committee.
Generation of CD3 multicistronic vectors
See Supplementary data.
Generation of retroviral producer cells
See Supplementary data.
Retroviral‐mediated stem cell gene transfer
Retroviral transduction of murine bone marrow cells was performed as described earlier (Holst et al, 2006a, 2006b, 2008). Briefly, we harvested bone marrow from 8‐ to 10‐week‐old donor mice 48 h after treatment with 150 mg/kg 5‐fluoruracil (Pharmacia & UpJohn). Bone marrow cells were single cell suspended and cultured in complete DMEM with 20% fetal bovine serum (FBS), murine IL‐3 (20 ng/ml), human IL‐6 (50 ng/ml), and murine SCF (50 ng/ml) (Biosource‐Invitrogen) for 48 h. Cells were subsequently co‐cultured for a further 48 h with irradiated (1200 rads) retroviral producer cell lines plus polybrene (6 μg/ml) and cytokines as detailed above. Transduced bone marrow cells were collected, washed, and cells resuspended in phosphate‐buffered saline (PBS) containing 2% FBS with heparin (20 U/ml). Bone marrow cells (4 × 106 per mouse) were injected via the tail vein into irradiated (450 rads) Rag1−/− recipient mice. Retrogenic mice were analysed 6–12 weeks after bone marrow transplant.
Flow cytometric analysis, intracellular staining, and cell sorting
See Supplementary data.
CD3ε crosslinking and intracellular staining
See Supplementary data.
Confocal microscopy
Thymocytes purified by fluorescence‐activated cell sorting (FACS) were fixed with 4% formaldehyde and permeabilized with 0.2% Triton X‐100. These fixed cells were plated to the chamber of the glass slide (Nunc), which was pretreated with 0.1% Polyethyleneimine solution (Sigma). After 1 h incubation at room temperature, the chamber slide was washed twice with PBS and then treated with Image‐iT FX signal enhancer (Invitrogen) for 30 min. Primary Abs in 2% milk solution were added into the chamber and the slide was kept at 4°C over night. The slide was washed extensively with PBS, and fluorchrome labelled secondary Abs diluted in 2% milk solution were added into the chamber and kept at room temperature for 1 h. After washing the chamber four times with PBS, the stained cells were mounted using Prolong Gold antifade reagent with DAPI (Invitrogen). All images were taken using a Zeiss LSM 510 NLO META confocal microscope. CD3ζ (H146) mAb was conjugated with Alexa‐647 using an Alexa Fluor labelling kit (Invitrogen) following the manufacturer's instructions. LAPTM5 mAb was provided from Ji‐yang Wang, RIKEN, Yokohama, Japan. An Alexa‐488‐conjugated mAb against rabbit IgG was purchased from Invitrogen.
Lipid bilayers and microscopic analyses
See Supplementary data.
RNA, cDNA, and quantitative real‐time PCR
See Supplementary data.
Immunoprecipitation and western blotting
Immunoprecipitation and immunoblotting were performed as described earlier (Li et al, 2007a). Briefly, cells were lysed with lysis buffer containing 1% Triton X‐100, 50 mM Tris–HCl (pH 7.6), 300 mM NaCl, 2 mM Pefabloc, 10 μg/ml Aprotinin, 10 μg/ml Leupeptin, 1 μg/ml Pepstatin (Roche), and 10 mM N‐ethylmaleimide (Sigma) on ice for 30 min, followed by centrifugation at 15 000 g for 15 min. For protein analysis, 20 μl of lysate was collected, gel separated, and immunoblotted with indicated antibodies. Antibodies against the following proteins were used: CD3ε (HMT3.1 mAb) (Szymczak et al, 2004), CD3ζ (H146‐968 mAb, gift from Ralph Kubo, Cytel Corp., San Diego, CA) (Liu et al, 2000), α‐Tubulin (Sigma), CD3δ and CD3γ (two rabbit polyclonal antisera that were generated in our laboratory) (Holst et al, 2008). For immunoprecipitation, 1 ml lysate was precleared with protein G‐sepharose beads and further immunoprecipitated with a polyclonal antisera against CD3ζ (551‐ζ, gift from David Wiest, Fox Chase Cancer Center, Philadelphia, PA) conjugated Protein G‐sepharose beads. Immunoprecipitates were resolved by SDS–PAGE (Invitrogen Life Technologies), and blots were probed with mAbs against Ub (P4D1; Santa Cruz), polyUb (FK1, Millipore), K63Ub (HWA4C4; Wang H, submitted for publication), Sumo‐1 (ZYMED), Nedd8 (gift from Brenda Schulman, SJCRH, Memphis, TN), or pan methyl lysine (Abcam). Blots were developed using enhanced chemiluminescence (Amersham Biosciences) and autoradiography. Membranes were stripped and blots re‐probed with CD3ζ mAb (H146‐968).
Transient transfection of HEK‐293T cells
See Supplementary data.
Thymic organ culture
See Supplementary data.
Histological examination
See Supplementary data.
Supplementary data
Supplementary data are available at The EMBO Journal Online (http://www.embojournal.org).
Conflict of Interest
The authors declare that they have no conflict of interest.
Supplementary Information
Supplementary data [emboj201010-sup-0001.pdf]
We are very grateful to Mark Davis and Johannes Huppa for assistance and advice with establishing the lipid bilayer/spinning disk confocal microscopy system; Doug Green for helpful comments on the manuscript; Dave Wiest, Brenda Schulman, and Ralph Kubo for reagents; Kelli Boyd (Animal Resource Center, St Jude Children's Research Hospital) for histological analysis; Karen Forbes for animal colony management; R Cross, G Lennon, S Morgan, J Rogers, and Y He for FACS; Z Liu for providing neonatal thymi; and the Vignali laboratory for assistance with bone marrow harvesting. This work was largely supported by the National Institutes of Health (NIH) (AI52199), a Cancer Center Support CORE grant (CA21765) and the American Lebanese Syrian Associated Charities (ALSAC) to DAAV. HB was supported by the NIH (CA087986, CA99163).
- Copyright © 2010 European Molecular Biology Organization


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The Atrium at the Curtis Center is one of the Philadelphia's most beautiful and sophisticated wedding venues. I must say it is one of a kind. It is grand, majestic and absolutely stunning. It is always a treat to photograph wedding events there. Any angle you take will look wonderful.
This photograph was taken during a greek wedding reception that took place at the Curtis Center.
The bridal party just made their entrance into the grand ballroom and the bride and groom went into their first dance as husband and wife. It was truly a precious moment to document. We were able to take a whole variety of different angles, but this frame might be one of my favorite. I love how softly the bride's head rest on the grooms shoulder, how gently the groom hold his bride, how the light touches them and bring the viewer's eyes to the couple, and at the same time it creates a distinct separation from the guests standing behind. The tulle ceiling, that is probably one of the key decor elements at the Atrium at the Curtis Center, served perfectly as the leading lines and is simply a great compositional element. The soft purple uplighting is well combined with yellowish light coming from the chandeliers, which worked perfectly to creating a nice ambience for the entire wedding reception.
There was one off camera flash to camera's right used to lit the scene.
Canon 5D mark III; ISO 800; f/3.2; 1/100 sec
Location: 601 Walnut St, Philadelphia, PA 19106.


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Career Opportunity
Associate Quality Engineer
|Full Time
|Gomez Palacio, Durango Mexico
Hightlight of the Position
Henniges Automotive has an opportunity in Gomez Palacio I location for an Associate Quality Engineer. Leads the Quality initiative in assigned business areas (programs and/or physical areas or functions) to ensure conformance, maintenance and improvement to engineering specifications, Quality System requirements, and continual improvement criteria.
Essential Duties and Responsibilities
- Act as LiaisonAct as Liaison between the customer and the Company on current production/service products regarding quality of material relating to print conformance; Fit, Form, or Function; identification of materials.
- Lead problem solving teams both in a formal and informal environment using disciplined techniques to identify root cause and develop corrective and preventative actions.
- Review on-going Quality data for opportunities of improvement and the identification of deteriorating performance and recommend correction/improvement.
- Establish controls to maintain/improve Quality performance, external complaints, external PPM, and scrap percentage.
- Perform audits on a regular basis to identify potential system/product issues.
- Maintain all APQP/TS 16949 documentation as required on assigned areas.
- Prepare PPAPs as required on assigned products.
- Initiate Containment on identified nonconformance issues, identify root causes and ensure
- corrective/preventative actions are implemented, effective and maintained.
- Coordinate and/or perform any assigned quality functions such as lab management, calibration and/or supplier quality.
- Assist in the development of new program APQP when required.
- Other duties as assigned.
- May lead projects and/or project teams (including assigning work, reviewing progress and evaluating results), mentor, provide guidance and technical direction to less experienced engineering and technical
- staff, including the provision of input in performance evaluations, but does not supervise.
- Well-developed active listening and negotiation skills.
- Proficient verbal, written and presentation skills; communicates clearly, with credibility and confidence.
- Communicates effectively (verbally and in writing) with individuals at all levels, inside and outside the company.
- Consulting and influencing skills consistent with the ability to build relationships and influence parties; may include getting parties to embrace changing expectations and initiatives.
- Written and verbal communication & advocacy skills consistent with the ability to present results of projects and research and to engage in persuasive written and verbal interaction with senior- and executive-level management.
- Intermediate-to-advanced analytical and project management skills.
- Develops challenging short- and long-term group plans and objectives aligned with those of the department and/or company; solicits staff input in the developmental process.
- Ability to develop / coordinate cross-functional work groups and projects, yielding optimal outcomes.
- Working knowledge of automotive manufacturing processes, practices, and challenges.
- Well-developed organization and planning skills.
- Ability to apply project planning, implementation, and/or continuous improvement principles to affect tangible, positive outcomes.
- Competent in multi-tasking (i.e. the ability to prioritize and manage multiple tasks, issues or projects that may include high-visibility initiatives and require innovation, teamwork and planning).
- Proficiency in the following software applications: Microsoft Office including Word, Excel, Outlook and PowerPoint; and Quality based systems sufficient to apply and /or support the application with minimal instruction or guidance; this level of proficiency is typically attainable through 3-plus year(s) of substantive experience with the applications.
- Promotes an atmosphere conducive to the open exchange of new ideas, and alternatives to orthodox approaches.
- Deals effectively with resistance; takes positive steps to avoid the recurrence of errors through constructive critique.
- Ability to work in a team and/or matrixed structure, supporting multiple clients.
- Ability to conduct effective/efficient meetings and manage the meeting process with optimal results.
- Flexibility and the ability to work with shifting priorities; embrace new/evolving responsibilities. Balances multiple demands from superiors, subordinates, and/or peers in a positive and even-handed fashion; displays a calm demeanor under pressure.
- Initiates new ideas and approaches; challenges prevailing practices and approaches with reasonably sound alternatives.


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Elvira Dyangani Ose has been named curator for the next edition of the Gothenburg International Biennial for Contemporary Art (GIBCA), to take place from 12 September to 22 November 2015 in Sweden.
Elvira Dyangani Ose is currently curator of International Art at Tate Modern. She joined the British institution in 2011 and plays a leading role in the development of acquisitions and projects related to African art and its diaspora. She works in strong collaboration with the acquisitions committee dedicated to the continent.


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What Is Avian Influenza (AI)?
AI viruses can infect chickens, turkeys, pheasants, quail, ducks, geese and guinea fowl, as well as a wide variety of other birds. Migratory waterfowl have proved to be a natural reservoir for the less infectious strains of the disease known as low pathogenicity avian influenza. AI viruses can be classified into low pathogenicity (LPAI) and high pathogenicity (HPAI) based on the severity of the illness they cause. HPAI is an extremely infectious and fatal form of the disease that, once established, can spread rapidly from flock to flock. However, some LPAI virus strains are capable of mutating under field conditions into HPAI viruses.
Signs of Avian Influenza
How Is AI Spread?
The disease can be spread to birds from contact with infected wild birds and their droppings, or from bird to bird by direct contact. AI viruses can also be spread by manure, equipment, vehicles, egg flats, crates, and people whose clothing or shoes have come in contact with the virus. AI viruses can remain viable at moderate temperatures for long periods in the environment and can survive indefinitely in frozen material.
For more information, visit APHIS' avian influenza page.
What is Exotic Newcastle Disease (END)?
END, also known as virulent Newcastle Disease (vND), is a contagious and fatal viral disease affecting all species of birds. END is one of the most infectious diseases of poultry in the world and is so deadly that many birds die without showing any signs of disease. A death rate of almost 100 percent can occur in unvaccinated poultry flocks. It can infect and cause death even in vaccinated birds.
What Are the Signs?
END is a deadly viral disease that can affect all species of birds. END spreads quickly and can infect and cause death even in vaccinated poultry. An infected bird may show the following signs:
How Does END Spread?
END is spread mainly through direct contact between healthy birds and the bodily discharges of infected birds. The disease is transmitted through infected birds' droppings and secretions from the nose, mouth, and eyes. END spreads rapidly among birds kept in confinement, such as commercially raised chickens.
Virus-bearing material can be picked up on shoes and clothing and carried from an infected flock to a healthy one. The disease is often spread by vaccination and debeaking crews, manure haulers, rendering truck drivers, feed delivery personnel, poultry buyers, egg service people, and poultry farm owners and employees.
The END virus can survive for several weeks in a warm and humid environment on birds' feathers, manure, and other materials. It can survive indefinitely in frozen material. However, the virus is destroyed rapidly by dehydration and by the ultraviolet rays in sunlight.