Respond or ignore... that's the choice you have to make regarding the message you just received from a fellow member of your favorite online dating site.
It should be a relatively easy decision but which one it's going to be depends largely on how marketable your online dating profile has been. If you've been receiving a lot of attention you might just ignore the message - which has both an upside and a downside for the sender. Having a message ignored can be good if it means someone is spared an unwarranted negative remark. Then again, sometimes it's nice just to know that the other person acknowledged the effort that was put into a message, even if the interest isn't reciprocated, and a polite "thanks, good luck" response can be a really nice gesture.
Conversely, if you've been receiving a lot of attention there's a real possibility that you might get drunk off of your own ego. You might wonder why the sender thought it was okay to send you a message at all. Heck, based on the number of messages you've been receiving you qualify for outright "sexy beast" status. You might be so overwhelmed by your popularity that you question how on earth this particular person thought you were anywhere in their league. You might even get frustrated that they clogged up your inbox with their obviously misplaced message. And if you're in a really bad mood, chances are you might send a reply-message that rejects the sender so harshly that it deters them from ever wanting to respond to another online profile again.
It's true that online dating instills a certain sort of "electronic courage" in people that they might not otherwise have in person when dealing with potential suitors. It can easily be likened to the equivalent of "liquid courage" - that false bravado that guys tend to get after they've had too much alcohol to drink and are eager to entertain a fight. Same sort of concept at play when online daters are feeling their oats.
So why does online dating give people an over-inflated sense of themselves and prompt rejection? It all comes down to the filter that is the faceless internet itself. How many times have you been approached by someone in person and felt too nervous about rejecting them because you didn't know how they would react? Well, the internet provides cover that you wouldn't ordinarily enjoy in those types of situations. When someone with a profile that doesn't pass muster for you sends a message you can choose to do whatever you want with it without having to feel bad about it.
That's an interesting concept, huh? People really don't give much thought to what the person on the other side of that internet connection is going to think about a non-response or short rejection note. The internet is turning us into a very impersonal society in that regard. And the more impersonal we become the more comfortable we feel about rejecting others.
In addition, tomorrow always promises to bring a new crop of interested potentials your way so a lot of online daters choose to hedge their bets with the numbers game. The numbers game has always been a factor when it comes to dating, especially for those that don't have trouble attracting others, but the internet makes it ridiculous. There are so many members of online dating sites nowadays that even those that might not be as successful in the attraction department in person are doing relatively well on the internet. In general, when you know that you can discount someone today and still have five more potentials knocking on your door tomorrow it makes online dating a breeding ground for rejection.
The secret to success is knowing this going in. If you understand that online dating increases the likelihood of rejection for these reasons, you will fare better by playing the numbers game yourself. Okay, so the "5-Alarm Fire" hot person you emailed last week never responded. Pick your chin up off the ground and take another look at the people that have messaged you since then.
Are you sure that person you overlooked yesterday isn't Starbucks-worthy?
BlindCupids.com is an interracial dating site that features groundbreaking video profile technology and a real social network that encourages participation. A contemporary Web 2.0 experience gives members some of the greatest flexibility available for online dating. Sign up today at http://www.BlindCupids.com - where Love Doesn't Judge!
Anyone who has recently experienced an auto accident, an injury due to medical malpractice, or even a workplace injury will want to contact an attorney to help protect their rights.? However, many people are confused about what type of lawyer to contact.? Some search for general attorneys and some search for personal injury attorneys.? In order to decide which type of lawyer to pursue, it is important to understand the education, training, and experience of both types of lawyers.
General Attorneys
A general attorney has a broad scope to their practice.? They can take several different types of cases such as family law, property law, employment law, bankruptcy, financial law, and personal injury law, as well as many other areas.? They have some experience in each area that they practice, but do not have one area in which they specialize.? Such a wide range of practice can sometimes impact their performance in each area of the law.
Personal Injury Attorneys
In contrast,?personal injury lawyers are educated and licensed so that they can practice in almost any field of the law that they so choose, however, they specialize in tort law.? Personal injury attorneys have extensive training and knowledge in tort law.? Tort law is a specific area of law that covers civil wrong-doing, as well as financial and non-financial damages to a person?s property, rights, or even reputation.?? Personal injury attorneys focus on the following types of cases:
? Automobile accidents
? Motorcycle accidents
? Slip and fall accidents
? Other types of accidents
? Work Injuries
? Medical mistakes and malpractice
? Birth injuries
? Defective products
? Wrongful death
Responsibilities of Personal Injury Attorneys
Personal injury lawyers are held to a strict standard of legal ethics when it comes to representing their contracted clients.? They must protect their client?s best interest and maintain loyalty and confidentiality.? They also must keep up to date with any changes in their field by completing the required continuing legal education and keep informed of changes in their field.? By limiting themselves to personal injury law only, personal injury attorneys gain more experience in the field and can focus in on tort law.? They can also become certified in the specialty of personal injury by the American Bar Association.?
Finding a Personal Injury Attorney
If someone is?searching for a personal injury attorney they can ask for references, including references from doctors, and utilize the internet and yellow pages.? It is important to keep in mind that the lawyer with the biggest yellow pages ad, or the one with the fancy daytime television commercial may not necessarily be the best or the most experienced.
Important Questions to Ask
Most personal injury attorneys offer a free consultation in order for them to find out if the victim has a case, and for the victim to?ask them questions.? Once someone has found an attorney they would like to consider for representation there are several important questions to be asked.? Such as:
? What is your?contingency fee?
? What is your experience with my type of personal injury case?
? Do you have the time to work on my case now?
? When can I expect my lawsuit to be filed?
? What is my case worth?
? What is my own role in my case?
? Will you be the attorney working on my case?
All of these questions are important so that someone with a potential personal injury case knows what to expect from time frame to finances and everything in between.? A strong attorney will be prepared for these questions and will not act annoyed or waiver in their answers.? Some of these questions may have estimations as answers, for example how long it will take for a lawsuit to be filed, but the attorney should be able to give an approximate date based on previous experiences.
Anyone needing a lawyer for a personal injury case should only consider attorneys who specialize in personal injuries.? This will increase the chances of the victim getting fair compensation for their injuries.? They should also consult with the personal injury attorney prior to hiring them and ask they appropriate questions.
Dan Thomashas worked in the legal field for many years, and knows that it is important to find a lawyer thatspecializes in your areaof need for the best results. Seeking help with the injury lawyer Atlanta firm can bring beneficial results to your case.
As the Powerball frenzy continues, people across the nation are rushing out to buy their ticket to a dream, but winning the jackpot can sometime translate to major losses. NBC's Erica Hill reports on the lottery "curse" and two September Powerball winners how their lives have changed, for better and for worse.
By NBC News staff and wire services
Updated at 1:35 p.m. ET: Someone could win $550 million in Wednesday night's Powerball drawing, the largest in the game's history.
The jackpot jumped up from half a billion dollars on Wednesday, according to the Powerball website. The new jackpot would carry a cash value of $360.2 million before taxes.
Lottery officials say they now believe there is a 75 percent chance the winning numbers will be drawn Wednesday night, The Associated Press reported. Powerball is played across 42 states, plus Washington, D.C., and the Virgin Islands.
As big as this week's Powerball jackpot is, it's not the largest lottery prize ever. That mark is held by the $656 million Mega Millions jackpot that was split by three ticket buyers earlier this year. The previous biggest Powerball prize was $365 million in 2006, shared by several ConAgra Foods workers in Lincoln, Neb.
Since the jackpot is an estimate, the prize money could be increased as the drawing nears, the AP reported.
Related: 11 things more likely to happen than winning the Powerball jackpot
There were no Powerball winners for Saturday's drawing, in which $325 million was up for grabs.?The winning numbers Saturday were 22-32-37-44-50 with Powerball 34, according to the Powerball lottery's website. There were 10 winners of $1 million and one winner of $2 million.
The huge jackpot has brought a flood of ticket sales. "It?s been crazy," said the manager of a 7-Eleven convenience store in Westminster, Colo., that sold 2,000 tickets in 11 hours on Tuesday, Reuters reported.
Ticket buyers are not only dreaming of living large, but already brewing ways in which they might quit their job.
"I was thinking maybe I should hire a marching band to help me (quit)," Joe Cooke of Illinois told Reuters, after buying $50 in Powerball tickets Wednesday morning. "Or maybe I'll just walk right into office and moon him." Cooke, 29, fields customer service calls for a financial institution, which he describes as listening to "rich, mean people" complaining all day, Reuters reported.
The Associated Press and Reuters contributed to this report.
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(Photo : (Photo:Reuters)) Steven Tyler to Nicki Minaj - 'I'm not a racist!'
During a recent interview with MTV, Aerosmith front man Steven Tyler had some rather harsh words of "advice" for "American Idol" newbie Nicki Minaj. Somehow, the rocker managed to combine "Bob Dylan," "cornfield," and "Phillip Phillips" all in one statement... and basically dissed Minaj's musical talent and taste. The "Starships" songstress didn't take the remarks lying down, and jumped into her own Twitter tirade against Tyler on Monday (Nov. 26). Now Tyler wants his fans to know that he isn't a racist and that his comments weren't meant to personally offend or disparage Minaj. Do Mstarz fans think the pop diva will accept Tyler's apology?
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Here's the remark that Tyler recently made in an interview with MTV News, which Minaj found downright racist:
"You just have to give your opinion. It wasn't hard for me, but I would imagine it's hard for some people. They need a manager to say, 'Shut the f--- up, and just give them your opinion'... These kids, they just got out of a car from the Midwest somewhere, and they're in New York City - they're scared to death! If it was Bob Dylan, Nicki Minaj would have had him sent to the cornfield! Whereas, if it was Bob Dylan with us, we would have brought the best of him out, as we did with Phillip Phillips. Just saying."
Minaj then lashed out at the Rock and Roll Hall of Famer on Twitter, posting:
@NICKIMINAJ: "Steven Tyler said I would have sent Bob Dylan to a cornfield??? Steven, you haven't seen me judge one single solitary contestant yet!... I understand you really wanted to keep your job but take that up with the producers. I haven't done anything to you. That's a racist comment... You assume that I wouldn't have liked Bob Dylan??? why? black? rapper? what? go f##k yourself and worry about yourself babe... LOL lets make him a shirt that says 'No Coloreds Allowed' then escort him down 2 Barbara Walters so he can tell how he was threatened w/guns... When Steven 1st went on Idol he was ridiculed by his peers & fans alike. Called a sell out. So what does he do? Ridicule the next judge."
Woah.
Tyler then tried to save some face on Tuesday when he appeared on Canada's entertainment show "eTalk" - "I apologize if it was taken wrong, Nicki. But I am the farthest from (being a racist). I am the last thing on this planet as far as being a racist... I don't know where she got that out of me saying I'm not sure how she would've judged Bob Dylan."
Oh, the "American Idol" drama (and the season hasn't even aired yet)!
In the end, Tyler basically admitted "my bad" - "Maybe I spoke out of turn. But a racist I'm not, Nicki."
? 2012 Mstarz All rights reserved. Do not reproduce without permission.
(Reuters) - Google's biggest advertiser is neither a bank nor a retailer.
It's the for-profit University of Phoenix, which has recently been spending nearly $400,000 a day on ads, according to search analytics firm SpyFu, more than any financial firm or retailer, the traditional big spenders on online advertising.
That kind of spending may seem surprising coming from a college, but marketing has become vital for the university and its for-profit rivals as enrollments plummet and they fight back against a host of criticisms, including low job-placement rates.
Colleges such as University of Phoenix, the industry leader owned by Apollo Group Inc, will not only have to boost enrollments to reverse their fortunes, analysts say. They will also need to consider cutting tuition fees as well as continue to slash costs and take market share from rivals.
Operators of other for-profit colleges, whose ranks include the Washington Post Co's Kaplan business, DeVry Inc and ITT Educational Services Inc, are also boosting their spending on marketing and are among the 25 biggest advertisers on Google.
But no one is spending like the University of Phoenix, which doubled its spending on Google ads to about $380,000 per day on average between October 12 and November 12, compared with $170,000 a day in the previous month, according to SpyFu data - which Apollo describes as "gross speculation."
"I have witnessed several versions of this cycle but none as extreme as this," said Trace Urdan, an analyst with Wells Fargo Securities, who has been covering the U.S. for-profit education industry for about 15 years.
"We are going to see more pointed efforts at marketing and more price competition in an effort to try to capture more market share both from each other as well as from traditional schools," Urdan said.
Increased marketing alone will not be enough to fatten fast-shrinking profit margins and increase enrollments, however. Lower tuition fees and increased specialization of the type of programs offered, along with further streamlining of operations, will also be necessary, analysts say.
Industry bellwether University of Phoenix, which offers courses at about 230 campuses as well as online, announced plans last month to shut about half its locations and cut 800 jobs in order to save about $300 million a year by 2014.
New enrollments in the Apollo system are down nearly 50 percent in the past two years. As of August 31, enrollment totaled about 328,000.
Career Education Corp, which owns American InterContinental University and the Le Cordon Bleu colleges, and Lincoln Educational Services Corp have also announced closures.
LOW-COST MODEL
The $25 billion industry, which typically serves adults looking for a career change or a program to enhance job skills, is reeling after government investigations revealed fraud related to financial aid, worryingly high student debt loads and low rates of graduation and job placement.
"Many for-profit colleges make decisions that prioritize their bottom line, even when those decisions limit their students' opportunities for academic success," a U.S. Senate report said earlier this year.
Tuition fees, and therefore profits, is one area under pressure as potential students need to be convinced to take out loans in an uncertain job market.
Apollo, whose stock has lost about 65 percent of its value this year, implemented a tuition freeze earlier this year and promised students it will not increase prices through the course of their programs.
Apollo is also looking at different cost models, with a view to serving segments of the population that it cannot serve with current University of Phoenix tuition prices.
"We have certainly seen a lot more competition at the lower end of the price scale, and that's something we are focusing on," Apollo spokesman Mark Brennar said, while declining to offer specifics.
Wells Fargo's Urdan said it is likely that Apollo wants to compete in the low-cost end of the market by building a second brand, which it would likely do by acquiring another college rather than starting from scratch.
As colleges lower their revenue base by cutting tuition fees even as they spend more on marketing, lower margins could become the norm, analysts say. That has spooked investors already worried about sliding enrollments.
The S&P 1500 Education Services index has lost three-quarters of its value since April 2010, including a 50 percent decline in 2012.
Some for-profit colleges already differentiate themselves in the crowded higher-education market by offering programs in a particular field or by targeting students of a particular background, and that trend could accelerate.
American Public Education, for example, is known for enrolling those who work in the military and public services, while Universal Technical Institute offers programs related to the automotive industry.
For-profit colleges play up their links to employers to attract students who may otherwise opt for traditional or community colleges, said Rob Lytle, head of the education practice at advisory firm Parthenon Group.
"They are about getting people workforce employability skills, and I think they are going to be focusing tighter on that," said Lytle.
(Reporting by A. Ananthalakshmi in Bangalore; Editing by Ted Kerr)
The Sundance Film Festival has an apparent record lineup of female directors competing for its top honor this January.
Half the entries - eight of the 16 films - announced Wednesday in the festival's U.S. dramatic competition were directed by women for the next installment of Robert Redford's independent-cinema showcase, which runs Jan. 17-27 in Park City, Utah.
Going back to 1992, the best showing previously for female filmmakers was in 2000, when six of the 16 U.S. dramatic contenders were directed by women.
Sundance organizers were still trolling back to the early years of the festival's 33-year history, but this January's eight competition films appears to be most ever from women and the first time the entries have been evenly split between female and male directors.
Among the competition films from female filmmakers are Francesca Gregorini's "Emanuel and the Truth About Fishes," whose cast includes Jessica Biel and Frances O'Connor in the story of a troubled girl fixated on a mysterious neighbor; Lynn Shelton's "Touchy Feely," featuring Rosemarie DeWitt, Allison Janney and Ellen Page in a tale of a massage therapist who develops a distaste for bodily contact; and Liz W. Garcia's "The Lifeguard," with Kristen Bell as a reporter who moves home to Connecticut and takes a job as a lifeguard.
The festival's U.S. dramatic lineup also features the first Sundance entry for "Harry Potter" star Daniel Radcliffe, who stars as Allen Ginsberg in director John Krokidas' "Kill Your Darlings."
Male directors still dominate the big-screen, but the low-budget indie world has been narrowing the gender gap. Sundance director John Cooper said some Sundance film categories have had a nearly even split between male and female directors in the past, a sign that more and more women are breaking into filmmaking.
"I think that's absolutely it," Cooper said. "Also, what we've found is that through our short-film programs, they've been coming close to 50-50 in certain years or at least a high level of women directors. So it's more of a coming-up-through-the-ranks situation" as female directors graduate from short films to feature-length stories.
Sundance has scheduled 113 feature-length films, chosen out of 4,044 titles submitted.
The festival will feature four opening-night films, one each from its U.S. drama and documentary and world-cinema drama and documentary categories. Among the opening films is director Cherien Dabis' U.S. drama contender "May in the Summer," in which she stars as a woman in conflict with her family after returns home to Jordan as her wedding nears.
Other films in the U.S. dramatic lineup include "Napoleon Dynamite" co-writer Jerusha Hess' directing debut, "Austenland," starring Keri Russell and Jennifer Coolidge in a romance about a "Pride and Prejudice"-obsessed woman searching for love at a Jane Austen theme resort; "In a World ...", the directing debut of actress Lake Bell, who stars in the story of a woman trying to follow her father's footsteps to become a voice-over star; Jill Soloway's "Afternoon Delight," with Kathryn Hahn and Juno Temple in the tale of a Los Angeles housewife who takes in a stripper as a live-in nanny; and David Lowery's "Ain't Them Bodies Saints," featuring Rooney Mara and Casey Affleck in a drama about an escaped prisoner crossing the Texas hills to reunite with his family.
The U.S. documentary competition also has an even gender split, with eight of the 16 films directed or co-directed by women. That's not a record, though, as women have made stronger in-roads into documentary filmmaking and have accounted for more than half of the entries in Sundance's non-fiction lineup in the past.
Among films in the U.S. documentary program are Audrey Ewell, Aaron Aites, Lucian Read and Nina Kristic's "99%: The Occupy Wall Street Collaborative Film," which examines the 2011 protests over economic inequality; Martha Shane and Lana Wilson's "After Tiller," profiling doctors providing late-term abortions after the murder of a colleague by an abortion opponent; and Gabriela Cowperthwaite's "Blackfish," which explores the consequences of captivity for killer whales, one of which was involved in the deaths of three people.
The opening-night film for the U.S. documentary lineup is Morgan Neville's "Twenty Feet From Stardom," a portrait of pop music's generally anonymous backup singers. On the world-cinema front, the opening-night dramatic entry is Chilean director Sebastian Silva's "Crystal Fairy," with Michael Cera and Gabby Hoffmann in a South American road trip adventure, while the opening documentary is British filmmaker Marc Silver's "Who Is Dayani Cristal?," chronicling the search for the identity of an anonymous body found in the Arizona desert.
Sundance announces its lineup of premieres featuring bigger-name stars and filmmakers on Monday.
What keeps a cell's energy source goingPublic release date: 27-Nov-2012 [ | E-mail | Share ]
Contact: Karen Kreeger karen.kreeger@uphs.upenn.edu 215-349-5658 University of Pennsylvania School of Medicine
PHILADELPHIA Most healthy cells rely on a complicated process to produce the fuel ATP. Knowing how ATP is produced by the cell's energy storehouse the mitochondria -- is important for understanding a cell's normal state, as well as what happens when things go wrong, for example in cancer, cardiovascular disease, neurodegeneration, and many rare disorders of the mitochondria.
Two years ago, Kevin Foskett, PhD, professor of Physiology at the Perelman School of Medicine, University of Pennsylvania, and colleagues discovered that fundamental control of ATP production is an ongoing shuttle of calcium to the mitochondria from another cell compartment. They found that mitochondria rely on this transfer to make enough ATP to support normal cell metabolism.
Foskett's lab and the lab of colleague Muniswamy Madesh, PhD, at Temple University, discovered last month an essential mechanism that regulates the flow of calcium into mitochondria, described in the October 26 issue of Cell. They found that the mitochondrial protein MICU1 is required to establish the proper level of calcium uptake under normal conditions.
In a new paper out this week in Nature Cell Biology, the same Penn-Temple team describe a new protein and its function. Like MICU1, this new protein, MCUR1, interacts physically with MCU, the uniporter calcium ion channel within the mitochondria. Calcium uptake is driven by a voltage across the inner mitochondrial membrane and mediated by the calcium-selective ion channel called the uniporter.
"But this newly described protein, MCUR1, has the opposite role as MICU1," notes Foskett. "It seems to be a subunit that, together with MCU, is required for a functional uniporter calcium channel."
Many cell plasma membrane ion channels also have subunits that are required for those channels to work. Before this paper, there was no realization that this mitochondrial channel, MCU, did as well.
Maintaining the correct levels of calcium in the mitochondria plays an important role in cellular physiology: Calcium flux across the inner mitochondrial membrane regulates cell energy production and activation of cell-death pathways, for example. In MICU1's absence mitochondria become overloaded with calcium, generating excessive amounts of reactive oxygen molecules and eventually cell death. In contrast, in the absence of MCUR1, mitochondria cannot take up enough calcium. This also has detrimental effects: the cells cannot make enough ATP and they activate autophagy, a mechanism in which cells "eat themselves" to provide sufficient nutrients for survival
Both papers deal with the function of the uniporter, the calcium channel in the inner membrane of mitochondria that lets calcium get into the mitochondrial matrix where it can do good things like promote ATP synthesis and healthy bioenergetics, or bad things, like mitochondrial-mediated cell death, apoptosis and necrosis.
Because of these two papers, the uniporter is now recognized as a channel complex, containing -- at least -- MCU, MCUR1 and MICU1. Since the uniporter can be a therapeutic target is reperfusion injury, ischemic injury, and programmed cell death, MCUR1 and its interaction with MCU are now targets for drug development.
###
Other investigators contributing to the work include Cesar Cardenas, Jun Yang, Marioly Muller, Russell Miller, Jill E. Kolesar, Brett Kaufman, all from Penn; first author Karthik Mallilankaraman, Patrick Doonan, Harish C. Chandramoorthy, Krishna M. Irrinki, and Priyanka Madireddi, all from Temple; Tunde Golenar, Gyorgy Csordas, Gyorgy Hajnoczky, all from Thomas Jefferson University; and Jordi Molgo, Institute de Neurobiologie Alfred Fessard, Laboratoire de Neurobiolgie Cellulaire et Dveloppement, France.
Penn Medicine is one of the world's leading academic medical centers, dedicated to the related missions of medical education, biomedical research, and excellence in patient care. Penn Medicine consists of the Raymond and Ruth Perelman School of Medicine at the University of Pennsylvania (founded in 1765 as the nation's first medical school) and the University of Pennsylvania Health System, which together form a $4.3 billion enterprise.
The Perelman School of Medicine is currently ranked #2 in U.S. News & World Report's survey of research-oriented medical schools. The School is consistently among the nation's top recipients of funding from the National Institutes of Health, with $479.3 million awarded in the 2011 fiscal year.
The University of Pennsylvania Health System's patient care facilities include: The Hospital of the University of Pennsylvania -- recognized as one of the nation's top "Honor Roll" hospitals by U.S. News & World Report; Penn Presbyterian Medical Center; and Pennsylvania Hospital the nation's first hospital, founded in 1751. Penn Medicine also includes additional patient care facilities and services throughout the Philadelphia region.
Penn Medicine is committed to improving lives and health through a variety of community-based programs and activities. In fiscal year 2011, Penn Medicine provided $854 million to benefit our community.
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AAAS and EurekAlert! are not responsible for the accuracy of news releases posted to EurekAlert! by contributing institutions or for the use of any information through the EurekAlert! system.
What keeps a cell's energy source goingPublic release date: 27-Nov-2012 [ | E-mail | Share ]
Contact: Karen Kreeger karen.kreeger@uphs.upenn.edu 215-349-5658 University of Pennsylvania School of Medicine
PHILADELPHIA Most healthy cells rely on a complicated process to produce the fuel ATP. Knowing how ATP is produced by the cell's energy storehouse the mitochondria -- is important for understanding a cell's normal state, as well as what happens when things go wrong, for example in cancer, cardiovascular disease, neurodegeneration, and many rare disorders of the mitochondria.
Two years ago, Kevin Foskett, PhD, professor of Physiology at the Perelman School of Medicine, University of Pennsylvania, and colleagues discovered that fundamental control of ATP production is an ongoing shuttle of calcium to the mitochondria from another cell compartment. They found that mitochondria rely on this transfer to make enough ATP to support normal cell metabolism.
Foskett's lab and the lab of colleague Muniswamy Madesh, PhD, at Temple University, discovered last month an essential mechanism that regulates the flow of calcium into mitochondria, described in the October 26 issue of Cell. They found that the mitochondrial protein MICU1 is required to establish the proper level of calcium uptake under normal conditions.
In a new paper out this week in Nature Cell Biology, the same Penn-Temple team describe a new protein and its function. Like MICU1, this new protein, MCUR1, interacts physically with MCU, the uniporter calcium ion channel within the mitochondria. Calcium uptake is driven by a voltage across the inner mitochondrial membrane and mediated by the calcium-selective ion channel called the uniporter.
"But this newly described protein, MCUR1, has the opposite role as MICU1," notes Foskett. "It seems to be a subunit that, together with MCU, is required for a functional uniporter calcium channel."
Many cell plasma membrane ion channels also have subunits that are required for those channels to work. Before this paper, there was no realization that this mitochondrial channel, MCU, did as well.
Maintaining the correct levels of calcium in the mitochondria plays an important role in cellular physiology: Calcium flux across the inner mitochondrial membrane regulates cell energy production and activation of cell-death pathways, for example. In MICU1's absence mitochondria become overloaded with calcium, generating excessive amounts of reactive oxygen molecules and eventually cell death. In contrast, in the absence of MCUR1, mitochondria cannot take up enough calcium. This also has detrimental effects: the cells cannot make enough ATP and they activate autophagy, a mechanism in which cells "eat themselves" to provide sufficient nutrients for survival
Both papers deal with the function of the uniporter, the calcium channel in the inner membrane of mitochondria that lets calcium get into the mitochondrial matrix where it can do good things like promote ATP synthesis and healthy bioenergetics, or bad things, like mitochondrial-mediated cell death, apoptosis and necrosis.
Because of these two papers, the uniporter is now recognized as a channel complex, containing -- at least -- MCU, MCUR1 and MICU1. Since the uniporter can be a therapeutic target is reperfusion injury, ischemic injury, and programmed cell death, MCUR1 and its interaction with MCU are now targets for drug development.
###
Other investigators contributing to the work include Cesar Cardenas, Jun Yang, Marioly Muller, Russell Miller, Jill E. Kolesar, Brett Kaufman, all from Penn; first author Karthik Mallilankaraman, Patrick Doonan, Harish C. Chandramoorthy, Krishna M. Irrinki, and Priyanka Madireddi, all from Temple; Tunde Golenar, Gyorgy Csordas, Gyorgy Hajnoczky, all from Thomas Jefferson University; and Jordi Molgo, Institute de Neurobiologie Alfred Fessard, Laboratoire de Neurobiolgie Cellulaire et Dveloppement, France.
Penn Medicine is one of the world's leading academic medical centers, dedicated to the related missions of medical education, biomedical research, and excellence in patient care. Penn Medicine consists of the Raymond and Ruth Perelman School of Medicine at the University of Pennsylvania (founded in 1765 as the nation's first medical school) and the University of Pennsylvania Health System, which together form a $4.3 billion enterprise.
The Perelman School of Medicine is currently ranked #2 in U.S. News & World Report's survey of research-oriented medical schools. The School is consistently among the nation's top recipients of funding from the National Institutes of Health, with $479.3 million awarded in the 2011 fiscal year.
The University of Pennsylvania Health System's patient care facilities include: The Hospital of the University of Pennsylvania -- recognized as one of the nation's top "Honor Roll" hospitals by U.S. News & World Report; Penn Presbyterian Medical Center; and Pennsylvania Hospital the nation's first hospital, founded in 1751. Penn Medicine also includes additional patient care facilities and services throughout the Philadelphia region.
Penn Medicine is committed to improving lives and health through a variety of community-based programs and activities. In fiscal year 2011, Penn Medicine provided $854 million to benefit our community.
[ | E-mail | Share ]
?
AAAS and EurekAlert! are not responsible for the accuracy of news releases posted to EurekAlert! by contributing institutions or for the use of any information through the EurekAlert! system.
Becoming an electrician starts with getting the right schooling. One can start quite early, even in High School. Many vocational programs in secondary schools have an electrical program. Following High School graduation, one can enter a program at a college to further their learning. Community colleges often have excellent trades program, including electrical. In addition to their typical general education courses like math and English, students will take practical courses where they learn both the science behind the trade and also get to apply and learn new skills in hands-on work. If one desires to learn more about the scientific end of things, they can attend a four year college that offers advanced programs like electrical engineering or similar majors. Community colleges are great because they offer students practical experience.
One can also do some extra work on their own to increase their skills and education. It is a great idea to find an experienced individual who works in the field and get close to them. An experienced worker can offer electrician training in the form of an apprenticeship or might be able to hire a student to work for them. They can also share the pros and cons of the industry, as well as stories from on the job. This will give the young student a better idea of what daily life is like as an electrical worker, and help them decide if this is really the field that they want to devote their life to. Working with a professional can help one meet others in the field and perhaps potential future customers. The pro may also have some suggestions for training programs or courses that the aspiring electrician can take advantage of. They can serve as a reference for the student's resume.
Before one can be successful in industry, they must have to proper education and training. Fortunately, budding electrical workers have many options to help them reach their goals and better themselves.
For years they have lived as orphans and outliers, a colony of misfit characters on their own island: the bizarre one and the needy one, the untrusting and the crooked, the grandiose and the cowardly.
Their customs and rituals are as captivating as any tribe?s, and at least as mystifying. Every mental anthropologist who has visited their world seems to walk away with a different story, a new model to explain those strange behaviors.
This weekend the Board of Trustees of the American Psychiatric Association will vote on whether to adopt a new diagnostic system for some of the most serious, and striking, syndromes in medicine: personality disorders.
Personality disorders occupy a troublesome niche in psychiatry. The 10 recognized syndromes are fairly well represented on the self-help shelves of bookstores and include such well-known types as narcissistic personality disorder, avoidant personality disorder, as well as dependent and histrionic personalities.
But when full-blown, the disorders are difficult to characterize and treat, and doctors seldom do careful evaluations, missing or downplaying behavior patterns that underlie problems like depression and anxiety in millions of people.
The new proposal ? part of the psychiatric association?s effort of many years to update its influential diagnostic manual ? is intended to clarify these diagnoses and better integrate them into clinical practice, to extend and improve treatment. But the effort has run into so much opposition that it will probably be relegated to the back of the manual, if it?s allowed in at all.
Dr. David J. Kupfer, a professor of psychiatry at the University of Pittsburgh and chairman of the task force updating the manual, would not speculate on which way the vote might go: ?All I can say is that personality disorders were one of the first things we tackled, but that doesn?t make it the easiest.?
The entire exercise has forced psychiatrists to confront one of the field?s most elementary, yet still unresolved, questions: What, exactly, is a personality problem?
Habits of Thought
It wasn?t supposed to be this difficult.
Personality problems aren?t exactly new or hidden. They play out in Greek mythology, from Narcissus to the sadistic Ares. They percolate through biblical stories of madmen, compulsives and charismatics. They are writ large across the 20th century, with its rogues? gallery of vainglorious, murderous dictators.
Yet it turns out that producing precise, lasting definitions of extreme behavior patterns is exhausting work. It took more than a decade of observing patients before the German psychiatrist Emil Kraepelin could draw a clear line between psychotic disorders, like schizophrenia, and mood problems, like depression or bipolar disorder.
Likewise, Freud spent years formulating his theories on the origins of neurotic syndromes. And Freudian analysts were largely the ones who, in the early decades of the last century, described people with the sort of ?confounded identities? that are now considered personality disorders.
Their problems were not periodic symptoms, like moodiness or panic attacks, but issues rooted in longstanding habits of thought and feeling ? in who they were.
?These therapists saw people coming into treatment who looked well put-together on the surface but on the couch became very disorganized, very impaired,? said Mark F. Lenzenweger, a professor of psychology at the State University of New York at Binghamton. ?They had problems that were neither psychotic nor neurotic. They represented something else altogether.?
Several prototypes soon began to emerge. ?A pedantic sense of order is typical of the compulsive character,? wrote the Freudian analyst Wilhelm Reich in his 1933 book, ?Character Analysis,? a groundbreaking text. ?In both big and small things, he lives his life according to a preconceived, irrevocable pattern.?
Others coalesced too, most recognizable as extreme forms of everyday types: the narcissist, with his fragile, grandiose self-approval; the dependent, with her smothering clinginess; the histrionic, always in the thick of some drama, desperate to be the center of attention.
In the late 1970s, Ted Millon, scientific director of the Institute for Advanced Studies in Personology and Psychopathology, pulled together the bulk of the work on personality disorders, most of it descriptive, and turned it into a set of 10 standardized types for the American Psychiatric Association?s third diagnostic manual. Published in 1980, it is a best seller among mental health workers worldwide.
These diagnostic criteria held up well for years and led to improved treatments for some people, like those with borderline personality disorder. Borderline is characterized by an extreme neediness and urges to harm oneself, often including thoughts of suicide. Many who seek help for depression also turn out to have borderline patterns, making their mood problems resistant to the usual therapies, like antidepressant drugs.
Today there are several approaches that can relieve borderline symptoms and one that, in numerous studies, has reduced hospitalizations and helped aid recovery: dialectical behavior therapy.
This progress notwithstanding, many in the field began to argue that the diagnostic catalog needed a rewrite. For one thing, some of the categories overlapped, and troubled people often got two or more personality diagnoses. ?Personality Disorder-Not Otherwise Specified,? a catchall label meaning little more than ?this person has problems? became the most common of the diagnoses.
It?s a murky area, and in recent years many therapists didn?t have the time or training to evaluate personality on top of everything else. The assessment interviews can last hours, and treatments for most of the disorders involve longer-term, specialized talk therapy.
Psychiatry was failing the sort of patients that no other field could possibly help, many experts said.
?The diagnoses simply weren?t being used very much, and there was a real need to make the whole system much more accessible,? Dr. Lenzenweger said.
Resisting Simplification?
It was easier said than done.
The most central, memorable, and knowable element of any person ? personality ? still defies any consensus.
A team of experts appointed by the psychiatric association has worked for more than five years to find some unifying system of diagnosis for personality problems.
The panel proposed a system based in part on a failure to ?develop a coherent sense of self or identity.? Not good enough, some psychiatric theorists said.
Later, the experts tied elements of the disorders to distortions in basic traits.
NEW YORK (AP) ? Radio talk show host Laura Ingraham is off the air ? at least temporarily.
She said Tuesday that she's leaving her distributor, Talk Radio Network, after more than nine years because her contract is up. Ingraham said she is in discussions with other distributors about her show, which currently airs on 325 stations nationally.
Talkers magazine says the conservative Ingraham is the most-listened to woman on radio, with an estimated 5.75 million listeners a week. Talkers said that ranks her among the top eight radio hosts overall.
In the meantime, she said she'll keep her opinions flowing on her website, on Twitter and during Fox News Channel appearances.
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Before rebels known as M23 split up Congo any further, the United Nations must help this giant African nation find a unifying identity. The same goes for Rwanda.
By the Monitor's Editorial Board / November 25, 2012
People flee a town near Goma in the Democratic Republic of Congo after rebels known as M23 took over parts of eastern Congo last week.
AP
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Some countries that split apart should trouble the world?s conscience more than others. Congo, as one of the largest and most violence-prone in Africa, is one of them.
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Last week, a few thousand armed rebels known as M23 took over Goma, the most important city in the eastern part of the Democratic Republic of Congo. Given that more than five million people have died in fighting there since 1997, the United Nations is rightly alarmed.
It is one thing if Spain?s Catalonia or Britain?s Scotland should split off. Separatism by voting, whether caused by ethnic or religion differences, doesn?t usually entail violence. Europe knows by experience not to change borders by war. But a fracturing of Congo by arms might be akin to the current civil war in Syria, where Alawites and Kurds could splinter that country at the heart of the Middle East.
Congo lies at the heart of Africa and has long been burdened by killing over its vast mineral wealth, tribal hostilities, and interventions by troubled neighbors. Mass rape has become a favored tactic of armed groups. And UN peacekeepers in the eastern provinces, known by their acronym Monusco, have too often stood by as massacres took place.
UN passivity in Congo is in contrast to the NATO and UN action in the 1990s to defend Kosovo from Serbia and later help it become independent. With so many nations now troubled by secession movements ? from Burma to Belgium to Mali and even in the United States ? the world needs a consistent, nonviolent response to such tensions over national identity.
Congo, like many former colonies, has yet to develop a unifying identity based on shared values and interests. It held its first democratic elections only in 2006. The government of President Joseph Kabila is weak, causing a corrupt Army to falter in defending the nation?s territory.
The size of western Europe, Congro can barely stand up to tiny Rwanda, which backs the M23 rebels, according to the UN. The rebels are part of a proxy fight between Rwanda?s ruling Tutsis and the Hutus who were behind the country?s 1994 genocide. Carving out a new country in eastern Congo under Tutsi control would serve the interests of Rwanda?s ruling (and minority) Tutsis.
Western pressure on Rwanda to end its meddling in Congo can only be effective if it also address the fears of Tutsis. The UN also needs to bolster Congo unity and nationalism through better peacekeeping and massive development. Land disputes in the eastern provinces are a big driver of violence.
The world has one recent example in how to help a fractured nation. The UN, led by the US, assisted southern Sudan and its largely nonMuslim population in splitting off from the Arab-dominated north. Now the UN must focus as intently on Congo, where some 60,000 people have already been displaced by last week?s rebel action. The world needs to set up more models of nations that overcome their internal differences peacefully.
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Public release date: 27-Nov-2012
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