?Our Windows XP is at the end of its life,? said de Szendeffy. ?Support for that software will end in 2014.?
Not everything is doom and gloom in the technology department, de Szendeffy and her team have worked some miracles to keep PUSD students moving forward with technology. Photo by Andy Towle. |
Payson Unified School District (PUSD) needs between $2 million to $3 million to rebuild its technology infrastructure, Joni de Szendeffy, director of technology, told the school board at its meeting on Monday, March 25.
?If we don?t do something soon with our infrastructure, it?s not going to be of any use to anybody,? said de Szendeffy.
Most people prefer to see any money they donate to school technology go toward equipment they can see in the classroom said de Szendeffy, rather than behind-the-scenes equipment they do not see.
But if students and staff cannot get access to the Internet or move data around, all that technology is pointless, said de Szendeffy.
The district needs new software to run operating systems, servers and switches to allow increased data flow and a non-DOS based telephone system, she said.
?Our Windows XP is at the end of its life,? said de Szendeffy. ?Support for that software will end in 2014.?
Not everything is doom and gloom in the technology department, de Szendeffy and her team have worked some miracles to keep PUSD students moving forward with technology.
She found a way to replace the main router.
?I purchased the new router using some contingency capital,? said de Szendeffy. ?I felt it was too important and needed to be done ? a 20-year-old piece of equipment that critical was pretty much on borrowed time.?
The job of a router is to send and receive ?packets? of information over the Internet. Numerous desktop computers can hook into a router, which then hooks into a server that accesses the Internet. A router can also connect individual devices to a wireless network.
In fact, this year de Szendeffy and her department have expanded the wireless network, so students and staff with their own devices can access the Internet wirelessly, which lightens the load on the routers and servers.
?We have increased users in limited BYOD (bring your own device) and by adding 150 iPads to the district,? said de Szendeffy.
The incoming Common Core Standards plan focuses on both making students comfortable with technology and replacing paper and pencil tests with online exams. School districts around the country have started to allow for students to use their personal devices.
However, PUSD needs increased bandwidth and Internet speed to make those changes, said de Szendeffy. She hopes to do that next year.
The good news, de Szendeffy reported, is that the PUSD technology department, with monies from a grant written by the Mogollon Health Alliance and matching funds from the Fiesta Bowl Charities, will now have the equipment to connect to the National LambdaRail and the Internet2 through the University of Arizona.
The National LambdaRail is a high-speed network of fiber-optics available in 21 states owned by the U.S. research and education community that bypasses expensive commercial networks. The grants will allow students to access and download research, classes and information from public and private organizations, such as NASA, universities and research hospitals.
Internet2 mimics the abilities of LambdaRail. The network allows Payson students to access media libraries, scientific instruments like undersea sensors, videoconferencing for things like virtual classes, music lessons, or observations of everything from surgery to nature studies.
Yet de Szendeffy has grave doubts she will be able to keep pulling rabbits out of her hat to keep the school?s technology functioning.
?Spending money on technology needs to be a priority,? she said. ?If we get any unrestricted funds, apply them to technology.?
Richard Griffiths of "The History Boys" poses for a picture with his Tony for Best Performance by a Leading Actor in Play at the 60th Annual Tony Awards in this Sunday, June 11, 2006 file photo in New York. Griffiths, the British actor who played the boy wizard?s unsympathetic Uncle Vernon in the "Harry Potter" movies, has died. He was 65. Agent Simon Beresford announced Friday March 2013 that Griffiths died Thursday of complications following heart surgery at University Hospital of Coventry in central England. (AP Photo/Richard Drew, file)
Richard Griffiths of "The History Boys" poses for a picture with his Tony for Best Performance by a Leading Actor in Play at the 60th Annual Tony Awards in this Sunday, June 11, 2006 file photo in New York. Griffiths, the British actor who played the boy wizard?s unsympathetic Uncle Vernon in the "Harry Potter" movies, has died. He was 65. Agent Simon Beresford announced Friday March 2013 that Griffiths died Thursday of complications following heart surgery at University Hospital of Coventry in central England. (AP Photo/Richard Drew, file)
FILE - From left, actors James Corden, Clive Merrison, Richard Griffiths and Stephen Campbell Moore take the curtain call at the opening night of the play The History Boys, in this Sunday, April 23, 2006 file photo in New York. Griffiths, the British actor who played the boy wizard?s unsympathetic Uncle Vernon in the "Harry Potter" movies, has died . He was 65. (AP Photo/Dima Gavrysh, file)
Actor Richard Griffiths poses for a photograph in New York, in this Wednesday, June 18, 2008 file photo. Griffiths, the British actor who played the boy wizard?s unsympathetic Uncle Vernon in the "Harry Potter" movies, has died. He was 65. Agent Simon Beresford announced Friday March 28 2013 that Griffiths died Thursday of complications following heart surgery at University Hospital of Coventry in central England. (AP Photo/Kathy Willens, file)
File - Actor Richard Griffiths poses for a photograph in New York, in this June 18, 2008 file photo. Griffiths, the British actor who played the boy wizard's unsympathetic Uncle Vernon in the "Harry Potter" movies, has died. He was 65. (AP Photo/Kathy Willens, File)
LONDON (AP) ? Richard Griffiths was one of the great British stage actors of his generation, a heavy man with a light touch, whether in Shakespeare or Neil Simon. But for millions of movie fans, he will always be grumpy Uncle Vernon, the least magical of characters in the fantastical "Harry Potter" movies.
Griffiths died Thursday at University Hospital in Coventry, central England, from complications following heart surgery, his agent, Simon Beresford, said. He was 65.
"Harry Potter" star Daniel Radcliffe paid tribute to the actor Friday, saying that "any room he walked into was made twice as funny and twice as clever just by his presence."
"I am proud to say I knew him," Radcliffe said.
Griffiths won a Tony Award for "The History Boys" and appeared in dozens of movies and TV shows. But he will be most widely remembered as a pair of contrasting uncles ? Harry Potter's Uncle Vernon Dursley and Uncle Monty in cult film "Withnail and I."
Griffiths was among a huge roster of British acting talent to appear in the "Harry Potter" series of films released between 2001 and 2011.
His role, as the grudging, magic-fearing guardian of orphaned wizard Harry, was small but pivotal. Griffiths once said he liked playing Uncle Vernon "because that gives me a license to be horrible to kids."
But Radcliffe recalled Griffiths' kindness to the young star.
"Richard was by my side during two of the most important moments of my career," said Radcliffe, who in 2007 starred with Griffiths in a London and Broadway production of "Equus."
"In August 2000, before official production had even begun on 'Potter,' we filmed a shot outside the Dursleys', which was my first ever shot as Harry. I was nervous, and he made me feel at ease.
"Seven years later, we embarked on 'Equus' together. It was my first time doing a play, but, terrified as I was, his encouragement, tutelage and humor made it a joy."
Earlier, Griffiths was the louche, lecherous Uncle Monty to Richard E. Grant's character Withnail in "Withnail and I," a low-budget British comedy about two out-of-work actors that has become a cult classic. Years after its 1987 release, Griffiths said people would regularly shout Monty's most famous lines at him in the street.
"My beloved 'Uncle Monty' Richard Griffiths died last night," Grant tweeted Friday. "Chin-Chin my dear friend."
A huge stage presence with a grace rendered all the more striking by his physical bulk, Griffiths created roles including the charismatic teacher Hector at the emotional heart of Alan Bennett's school drama "The History Boys." He won an Olivier Award for the part in London and a Tony for the Broadway run, and repeated his performance in the 2006 film adaptation.
National Theatre artistic director Nicholas Hytner, who directed "The History Boys," called Griffiths' performance in that play "a masterpiece of wit, delicacy, mischief and desolation, often simultaneously."
Griffiths also played poet W.H. Auden in Bennett's "The Habit of Art," a hugely persuasive performance despite the lack of physical resemblance between the two men.
Griffiths was born in northeast England's Thormaby-on-Tees in 1947 to parents who were deaf and mute ? an experience he and his directors felt contributed to his exceptional ability to listen and to communicate physically.
"The first language he learned was sign. And therefore his ability to listen to people with his eyes as well as his ears is incredible," Thea Sharrock, who directed "Equus," told The Associated Press in 2008.
Griffiths left school at 15 but later studied drama and spent a decade with the Royal Shakespeare Company, making a specialty of comic parts such as the buffoonish knight Falstaff.
On television, he played a crime-solving chef in 1990s' British TV series "Pie in the Sky," and he had parts in movies ranging from historical dramas "Chariots of Fire" and "Gandhi" to slapstick farce "The Naked Gun 2 ?."
Known for his sense of humor, large store of rambling theatrical anecdotes and occasional bursts of temper, Griffiths was renowned for shaming audience members whose cell phones rang during plays by stopping the performance and ordering the offender to leave.
Griffiths' last major stage role was in a West End production of Neil Simon's comedy "The Sunshine Boys" last year opposite Danny DeVito. The pair had been due to reprise their roles in Los Angeles later this year.
Theater director Trevor Nunn, who as head of the Royal Shakespeare Company was one of the first to spot Griffiths' talent, said he was "an actor of rare emotional and indeed tragic power."
"Richard inspired great love and spread much happiness, and as the Shakespeare he loved put it, 'There's a great spirit gone,'" Nunn said.
Griffiths is survived by his wife, Heather Gibson.
___
Jill Lawless can be reached at http://Twitter.com/JillLawless
Miami Beach Fire Dispatcher Put On Leave With Pay After Response Delay
NBC6:
An emergency dispatcher has been placed on leave with pay after a man died when it took a Miami Beach Fire Rescue team 31 minutes to get to his home, authorities said Friday.
FILE - In this May 17, 2012 file photo, Sen. Charles Schumer, D-N.Y. gestures during a news conference on Capitol Hill in Washington. Big business and major labor unions appeared ready Friday, March 29, 2013 to end a fight over a new low-skilled worker program that had threatened to upend negotiations on a sweeping immigration bill in the Senate providing a pathway to citizenship for 11 million immigrants already in the U.S. Schumer, who's been brokering talks between the AFL-CIO and the Chamber of Commerce, said in a statement that negotiators are "very close, closer than we have ever been, and we are very optimistic." He said there were still a few issues remaining. (AP Photo/Susan Walsh, File)
FILE - In this May 17, 2012 file photo, Sen. Charles Schumer, D-N.Y. gestures during a news conference on Capitol Hill in Washington. Big business and major labor unions appeared ready Friday, March 29, 2013 to end a fight over a new low-skilled worker program that had threatened to upend negotiations on a sweeping immigration bill in the Senate providing a pathway to citizenship for 11 million immigrants already in the U.S. Schumer, who's been brokering talks between the AFL-CIO and the Chamber of Commerce, said in a statement that negotiators are "very close, closer than we have ever been, and we are very optimistic." He said there were still a few issues remaining. (AP Photo/Susan Walsh, File)
Several southwest Michigan pastors along with immigrant families and members of the general public take part in a pray-in for immigration reform event outside of Representative Fred Upton's office in downtown Kalamazoo on Friday, March 29, 2013. (AP Photo/Kalamazoo Gazette-MLive Media Group, Matt Gade ) ALL LOCAL TV OUT; LOCAL TV INTERNET OUT
Several southwest Michigan pastors along with immigrant families and members of the general public take part in a pray-in for immigration reform event outside of Representative Fred Upton's office in downtown Kalamazoo on Friday, March 29, 2013. (AP Photo/Kalamazoo Gazette-MLive Media Group, Matt Gade ) ALL LOCAL TV OUT; LOCAL TV INTERNET OUT
WASHINGTON (AP) ? Big business and labor have struck a deal on a new low-skilled worker program, removing the biggest hurdle to completion of sweeping immigration legislation allowing 11 million illegal immigrants eventual U.S. citizenship, a person with knowledge of the talks said Saturday.
The agreement was reached in a phone call late Friday night with AFL-CIO President Richard Trumka, U.S. Chamber of Commerce head Tom Donohue, and Democratic Sen. Chuck Schumer of New York, who's been mediating the dispute.
The person, who spoke on condition of anonymity ahead of a formal announcement, said the deal resolves disagreements over wages for the new workers and which industries would be included. Those disputes had led talks to break down a week ago, throwing into doubt whether Schumer and seven other senators crafting a comprehensive bipartisan immigration bill would be able to complete their work as planned.
The deal must still be signed off on by the other senators working with Schumer, including Republicans John McCain of Arizona and Marco Rubio of Florida, but that's expected to happen. With the agreement in place, the senators are expected to unveil their legislation the week of April 8. Their measure would secure the border, crack down on employers, improve legal immigration and create a 13-year pathway to citizenship for the millions of illegal immigrants already here.
It's a major second-term priority of President Barack Obama's and would usher in the most dramatic changes to the nation's faltering immigration system in more than two decades.
The AFL-CIO and the Chamber of Commerce, longtime antagonists over temporary worker programs, had been fighting over wages for tens of thousands of low-skilled workers who would be brought in under the new program to fill jobs in construction, hotels and resorts, nursing homes and restaurants, and other industries.
Under the agreement, a new "W'' visa program would go into effect beginning April 1, 2015, according to another official involved with the talks who also spoke on condition of anonymity ahead of a formal announcement.
In year one of the program, 20,000 workers would be allowed in; in year two, 35,000; in year three, 55,000; and in year four, 75,000. Ultimately the program would be capped at 200,000 workers a year, but the number of visas would fluctuate, depending on unemployment rates, job openings, employer demand and data collected by a new federal bureau pushed by the labor movement as an objective monitor of the market.
A "safety valve" would allow employers to exceed the cap if they can show need and pay premium wages, but any additional workers brought in would be subtracted from the following year's cap, the official said.
The workers could move from employer to employer and would be able to petition for permanent residency and ultimately seek U.S. citizenship. Neither is possible for temporary workers now.
The new program would fill needs employers say they have that are not currently met by U.S. immigration programs. Most industries don't have a good way to hire a steady supply of foreign workers because there's one temporary visa program for low-wage nonagricultural workers but it's capped at 66,000 visas per year and is only supposed to be used for seasonal or temporary jobs.
Business has sought temporary worker programs in a quest for a cheaper workforce, but labor has opposed the programs because of concerns over working conditions and the effect on jobs and wages for U.S. workers. The issue helped sink the last major attempt at immigration overhaul in 2007, which the AFL-CIO opposed partly because of temporary worker provisions, and the flare-up earlier this month sparked concerns that the same thing would happen this time around. Agreement between the two traditional foes is one of many indications that immigration reform has its best chance in decades in Congress this year.
After apparent miscommunications earlier this month between the AFL-CIO and the Chamber of Commerce on the wage issue, the deal resolves it in a way both sides are comfortable with, officials said.
Workers would earn actual wages paid to American workers or the prevailing wages for the industry they're working in, whichever is higher. The Labor Department would determine prevailing wage based on customary rates in specific localities, so that it would vary from city to city.
There also had been disagreement on how to handle the construction industry, which unions argue is different from other industries in the new program because it can be more seasonal in nature and includes a number of higher-skilled trades. The official said the resolution will cap at 15,000 a year the number of visas that can be sought by the construction industry.
Schumer called White House chief of staff Denis McDonough on Saturday to inform him of the deal, the person with knowledge of the talks said. The three principals in the talks ? Trumka, Donohue and Schumer ? agreed they should meet for dinner soon to celebrate, the person said.
Separately, the new immigration bill also is expected to offer many more visas for high-tech workers, new visas for agriculture workers, and provisions allowing some agriculture workers already in the U.S. a speedier path to citizenship than that provided to other illegal immigrants, in an effort to create a stable agricultural workforce.
___
Follow Erica Werner on Twitter: https://twitter.com/ericawerner
WASHINGTON (AP) ? In a story March 27 about a new multiple sclerosis drug, The Associated Press reported erroneously that Novartis' drug Gilenya was launched in March 2011. The drug was launched in October 2010.
A corrected version of the story is below:
FDA approves new multiple sclerosis capsules
FDA approves pill-based Biogen Idec drug for multiple sclerosis symptoms
By MATTHEW PERRONE
AP Health Writer
WASHINGTON (AP) ? The Food and Drug Administration said Wednesday it approved a new drug from Biogen Idec to control multiple sclerosis in adults with hard-to-treat forms of the disease.
The twice-a-day capsules, called Tecfidera, offer a new option for multiple sclerosis, a debilitating disease in which the body attacks its own nervous system. Cambridge, Mass.-based Biogen Idec already sells two other drugs for the disease, but both require injections.
There is no cure for multiple sclerosis and most patients experience relapses of symptoms, including loss of balance, weakness in arms and legs, and blurred vision. Over time patients usually become weaker and less coordinated. More than 2 million people worldwide have the disease, with about 400,000 of them in the U.S., according to Biogen.
The FDA said it approved Tecfidera based on two studies showing patients taking the drug had fewer relapses than patients taking a dummy pill.
The approval gives Biogen a new product in an increasingly crowded field of multiple sclerosis drugs.
The biotech drugmaker already sells the once-a-week multiple sclerosis injection Avonex. It also markets the once-a-month injection Tysabri through a partnership with Elan Corp. PLC of Ireland. However, Tysabri's severe side effects have curtailed its use.
Tecfidera is designed to be taken orally, which could make it a preferred option for patients and doctors.
A Biogen executive said Wednesday that its three drugs would be used to treat different groups of patients.
"Multiple sclerosis is a reasonably complex disease and we think there are a lot of needs out there," said Tony Kingsely, a vice president at Biogen. "By having three drugs out there I think we can address a lot of those needs."
Kinglsey said the company will announce the pricing of the drug when it begins shipping in the next week.
Novartis launched the first pill-based multiple sclerosis drug, Gilenya, in October 2010. Sanofi won FDA approval for a second pill, its drug Aubagio, last September.
The top-selling drug for the disease worldwide is Copaxone, which is made by Teva Pharmaceutical Industries. That injection had sales of nearly $4 billion last year, according to Teva's latest financial report.
Avonex and Tysabri had annual sales of $2.7 billion and $1.5 billion in 2011, the most recent year for which Biogen has reported annual sales.
Biogen Idec Inc. shares rose $5.59, or 3.2 percent, to close Wednesday at $182.68.
We've all seen our share of quadruple rainbows and rainbows from space, but it's not to often you catch on lying down one the job. A particularly lazy refraction showed up in Paris the other day, but it's not quite as it seems. More »
NASA confirms that a fireball, as bright as a full moon, was seen from Florida to New England. The Friday night meteor was probably a small "boulder" that entered the Earth's atmosphere.
By Staff,?Associated Press / March 23, 2013
Reports of a flash of light that streaked across the sky over the U.S. East Coast appeared to be a "single meteor event," the U.S. space agency said. Residents from New York City to Washington and beyond lit up social media with surprise.
Click Here for your FREE 30 DAYS of The Christian Science Monitor Weekly Digital Edition
"Judging from the brightness, we're dealing with something as bright as the full moon," Bill Cooke of NASA's Meteoroid Environmental Office said Friday. "We basically have (had) a boulder enter the atmosphere over the northeast."
Cooke said the meteor was widely seen, with more than 350 reports on the website of the American Meteor Society alone.
Robert Lunsford of the society told USA Today "it basically looked like a super bright shooting star."
The sky flash was spotted as far south as Florida and as far north as New England, the newspaper reported.
Matt Moore, a news editor with The Associated Press, said he was standing in line for a concert in Philadelphia around dusk when he saw "a brilliant flash moving across the sky at a very brisk pace... and utterly silent."
"It was clearly high up in the atmosphere," he said. "But from the way it appeared, it looked like a plane preparing to land at the airport."
Moore said the flash was visible to him for about two to three seconds, and then it was gone. He described it as having a "spherical shape and yellowish and you could tell it was burning, with the trail that it left behind."
Derrick Pitts, chief astronomer at Philadelphia's Franklin Institute, agreed that the sightings had all the hallmarks of a "fireball."
Pitts said this one got more attention because it happened on a Friday evening ? and because Twitter has provided a way for people to share information on sightings.
He said what people likely saw was one meteor ? or "space rock" ? that may have been the size of a volleyball and fell fairly far down into the Earth's atmosphere. He likened it to a stone skipping across the water ? getting "a nice long burn out of it."
Pitts said experts "can't be 100 percent certain of what it was, unless it actually fell to the ground and we could actually track the trajectory."
But he said the descriptions by so many people are "absolutely consistent" with those of a meteor.
A disgruntled customer says that Lululemon employees made her bend over to prove her pants were see-through.?
The yoga retailer announced it was recalling 17 percent of its pants last week because many were too sheer.?
The Consumerist first reported about the woman's complaint, made on the Lululemon Facebook page.?
"I went into my local store to return my Astro pants and Invert crops, both purchased this month. I was asked to BEND OVER in order to determine sheerness. The sales associate then perused my butt in the dim lighting of the change room and deemed them ?not sheer?. I felt degraded that this is how the recall is being handled. I called the GEC to confirm this is their protocol, and they verified that yes, the ?educators? will verify sheerness by asking the customer to bend over.
Please explain as to how this is gratifying customer service? If I think my black Luon pants are sheer and there is a mass recall happening, am I not entitled to go in without having to BEND OVER and obtain a refund?"
But Lululemon's Facebook administrator quickly worked to address the woman's complaint, offering to contact her local store.
?
The company also posted this on Facebook:?
"?We don?t need to see our guests in the garments to deem them sheer. We want our guests to be comfortable in their products and will make it right for them if they feel their black bottoms are sheer."?
Carolyn?Beauchesne, author of?the blog Lululemon Addict,?also reported about women who said they had to bend over in stores to prove sheerness.?
"Lululemon has been pretty?tone-deaf in handling quality issues before?but this really takes the cake," Beauchesne wrote.?
Beauchesne also suggested a solution for the controversy.?
"Publishing a list of items that have been recalled would help clear up a lot of confusion," she wrote. "No list has been released?as of yet."
Protective prion keeps yeast cells from going it alonePublic release date: 28-Mar-2013 [ | E-mail | Share ]
Contact: Matt Fearer fearer@wi.mit.edu 617-452-4630 Whitehead Institute for Biomedical Research
CAMBRIDGE, Mass. (March 28, 2013) Most commonly associated with such maladies as "mad cow disease" and Creutzfeldt-Jakob disease, prions are increasingly recognized for their ability to induce potentially beneficial traits in a variety of organisms, yeast chief among them.
Now a team of scientists has added markedly to the job description of prions as agents of change, identifying a prion capable of triggering a transition in yeast from its conventional single-celled form to a cooperative, multicellular structure. This change, which appears to improve yeast's chances for survival in the face of hostile environmental conditions, is an epigenetic phenomenona heritable alteration brought about without any change to the organism's underlying genome.
This latest finding, reported in the March 28 issue of the journal Cell, has its origins in work begun several years ago in the lab of Whitehead Institute Member Susan Lindquist. In 2009, Randal Halfmann, then a graduate student in Lindquist's lab, identified dozens of proteins in yeast that have the ability to form prions. That research greatly expanded the known universe of prion elements in yeast, but it failed to answer a key question: What function, if any, do these prions actually have?
In search of an answer, Halfmann, now a fellow the University of Texas Southwestern Medical Center, and colleagues in the Lindquist lab attempted to exploit the fact that several of the prion-forming proteins they had identified acted to modify transcription of yeast genes. It stood to reason that if they could identify which genes were being regulated, they might be able to determine the prions' function.
"We looked at the five transcriptional regulators that are known to be prions in yeast, and we found that in fact, only one gene in the entire yeast genome was regulated by all five transcription factors," says Halfmann.
That gene, as it turns out, was FLO11, a key player in multicellularity in yeast. Indeed changes in FLO11 expression have been shown to act as a toggle, switching yeast from spherical to filamentous form. Halfmann notes that FLO11, which has been shown to be regulated by epigenetic elements, is also highly responsive to environmental stress. Knowing that the prion form of a protein is essentially a misfolded form of that protein, and that stressful conditions increase the frequency of protein misfolding and prion formation, the scientists began to consider the possibility that the prions themselves might be among the epigenetic switches influencing the activity of FLO11.
The group focused on one transcription factor known as mot3, finding that yeast cells containing the prion form of this factor, [MOT3+], acquired a variety of multicellular growth forms known to require FLO11 expression. This was a clear indication that prion formation was causing the differentiation of the cells and their subsequent cooperation. But what about the stress aspect of the hypothesis?
By testing yeast cells against a variety of stressors, the scientists discovered that exposure to a concentration of ethanol akin to that occurring naturally during fermentation increased [MOT3+] formation by a factor of 10.They also found that as the cells exposed to ethanol shifted their metabolism to burn surrounding oxygen through respiration, the prions reverted to their non-prion conformation, [mot3-], and the yeast returned to the unicellular state. In essence, prion formation drove a shift to multicellularity, helping the yeast to ride out the ethanol storm.
"What we have in the end is two sequential environmental changes that are turning on a heritable epigenetic element and then turning it off," says Halfmann. "And between those two changes, the prion is causing the cells to acquire a multicellular growth form that we think is actually important for their survival."
Lindquist, who is also a Howard Hughes Medical Institute investigator, has long argued that prions have played a vital role in yeast evolution and has amassed a body of strong supporting evidence.
"We see them as part of a bet-hedging strategy that allows the yeast to alter their biological properties quickly when their environments turn unfavorable," Lindquist says. She also theorizes that prions may play such roles beyond yeast, and her lab intends to take similar approaches in the hunt for prions and prion-like mechanisms that are potentially beneficial in other organisms.
For Lindquist lab postdoctoral scientist Alex Lancaster, who is also an author of the new Cell paper, these latest findings hint at a potentially novel approach to understanding basic mechanisms underlying the complexities of human diseases, including cancer, whose hallmarks include protein misfolding, epigenetic alterations, metabolic aberrations, and myriad changes in cell state, type, and function. Lancaster likens the opportunity to that of opening a black box.
"It's exciting to think that this could become another tool in the toolbox in the study of multicellularity," Lancaster says. "We know that some tumors are a heterogeneous population of cells and we know that tumor cells can evolve within in their environments to help ensure their own survival. This system could help us further understand the role of epigenetic inheritance within tumors and how it might be influencing cell-cell interactions and even affecting the effectiveness of drug therapies."
###
This work was supported by grants from the National Institutes of Health, the G. Harold and Leila Y. Mathers Foundation and Howard Hughes Medical Institute.
Written by Matt Fearer
Full Citation:
"Heritable Remodeling of Yeast Multicellularity by an Environmentally Responsive Prion"
Cell, March 28, 2013
Daniel L. Holmes (1), Alex K. Lancaster (2), Susan Lindquist (2,3,4) and Randal Halfmann (1)
1. Department of Biochemistry, University of Texas Southwestern Medical Center, Dallas, TX 75390-9038
2. Whitehead Institute for Biomedical Research, 9 Cambridge Center, Cambridge, MA 02142
3. Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139
4. Howard Hughes Medical Institute Massachusetts Institute of Technology, Cambridge, MA 02139
[ | E-mail | Share ]
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Protective prion keeps yeast cells from going it alonePublic release date: 28-Mar-2013 [ | E-mail | Share ]
Contact: Matt Fearer fearer@wi.mit.edu 617-452-4630 Whitehead Institute for Biomedical Research
CAMBRIDGE, Mass. (March 28, 2013) Most commonly associated with such maladies as "mad cow disease" and Creutzfeldt-Jakob disease, prions are increasingly recognized for their ability to induce potentially beneficial traits in a variety of organisms, yeast chief among them.
Now a team of scientists has added markedly to the job description of prions as agents of change, identifying a prion capable of triggering a transition in yeast from its conventional single-celled form to a cooperative, multicellular structure. This change, which appears to improve yeast's chances for survival in the face of hostile environmental conditions, is an epigenetic phenomenona heritable alteration brought about without any change to the organism's underlying genome.
This latest finding, reported in the March 28 issue of the journal Cell, has its origins in work begun several years ago in the lab of Whitehead Institute Member Susan Lindquist. In 2009, Randal Halfmann, then a graduate student in Lindquist's lab, identified dozens of proteins in yeast that have the ability to form prions. That research greatly expanded the known universe of prion elements in yeast, but it failed to answer a key question: What function, if any, do these prions actually have?
In search of an answer, Halfmann, now a fellow the University of Texas Southwestern Medical Center, and colleagues in the Lindquist lab attempted to exploit the fact that several of the prion-forming proteins they had identified acted to modify transcription of yeast genes. It stood to reason that if they could identify which genes were being regulated, they might be able to determine the prions' function.
"We looked at the five transcriptional regulators that are known to be prions in yeast, and we found that in fact, only one gene in the entire yeast genome was regulated by all five transcription factors," says Halfmann.
That gene, as it turns out, was FLO11, a key player in multicellularity in yeast. Indeed changes in FLO11 expression have been shown to act as a toggle, switching yeast from spherical to filamentous form. Halfmann notes that FLO11, which has been shown to be regulated by epigenetic elements, is also highly responsive to environmental stress. Knowing that the prion form of a protein is essentially a misfolded form of that protein, and that stressful conditions increase the frequency of protein misfolding and prion formation, the scientists began to consider the possibility that the prions themselves might be among the epigenetic switches influencing the activity of FLO11.
The group focused on one transcription factor known as mot3, finding that yeast cells containing the prion form of this factor, [MOT3+], acquired a variety of multicellular growth forms known to require FLO11 expression. This was a clear indication that prion formation was causing the differentiation of the cells and their subsequent cooperation. But what about the stress aspect of the hypothesis?
By testing yeast cells against a variety of stressors, the scientists discovered that exposure to a concentration of ethanol akin to that occurring naturally during fermentation increased [MOT3+] formation by a factor of 10.They also found that as the cells exposed to ethanol shifted their metabolism to burn surrounding oxygen through respiration, the prions reverted to their non-prion conformation, [mot3-], and the yeast returned to the unicellular state. In essence, prion formation drove a shift to multicellularity, helping the yeast to ride out the ethanol storm.
"What we have in the end is two sequential environmental changes that are turning on a heritable epigenetic element and then turning it off," says Halfmann. "And between those two changes, the prion is causing the cells to acquire a multicellular growth form that we think is actually important for their survival."
Lindquist, who is also a Howard Hughes Medical Institute investigator, has long argued that prions have played a vital role in yeast evolution and has amassed a body of strong supporting evidence.
"We see them as part of a bet-hedging strategy that allows the yeast to alter their biological properties quickly when their environments turn unfavorable," Lindquist says. She also theorizes that prions may play such roles beyond yeast, and her lab intends to take similar approaches in the hunt for prions and prion-like mechanisms that are potentially beneficial in other organisms.
For Lindquist lab postdoctoral scientist Alex Lancaster, who is also an author of the new Cell paper, these latest findings hint at a potentially novel approach to understanding basic mechanisms underlying the complexities of human diseases, including cancer, whose hallmarks include protein misfolding, epigenetic alterations, metabolic aberrations, and myriad changes in cell state, type, and function. Lancaster likens the opportunity to that of opening a black box.
"It's exciting to think that this could become another tool in the toolbox in the study of multicellularity," Lancaster says. "We know that some tumors are a heterogeneous population of cells and we know that tumor cells can evolve within in their environments to help ensure their own survival. This system could help us further understand the role of epigenetic inheritance within tumors and how it might be influencing cell-cell interactions and even affecting the effectiveness of drug therapies."
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This work was supported by grants from the National Institutes of Health, the G. Harold and Leila Y. Mathers Foundation and Howard Hughes Medical Institute.
Written by Matt Fearer
Full Citation:
"Heritable Remodeling of Yeast Multicellularity by an Environmentally Responsive Prion"
Cell, March 28, 2013
Daniel L. Holmes (1), Alex K. Lancaster (2), Susan Lindquist (2,3,4) and Randal Halfmann (1)
1. Department of Biochemistry, University of Texas Southwestern Medical Center, Dallas, TX 75390-9038
2. Whitehead Institute for Biomedical Research, 9 Cambridge Center, Cambridge, MA 02142
3. Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139
4. Howard Hughes Medical Institute Massachusetts Institute of Technology, Cambridge, MA 02139
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Mar. 27, 2013 ? On March 27thJoVE (Journal of Visualized Experiments) will publish a new video article by Dr. Lotfi Merabet showing how researchers in the Department of Ophthalmology at Massachusetts Eye and Ear Infirmary and Harvard Medical School have developed a virtual gaming environment to help blind individuals improve navigation skills and develop a cognitive spatial map of unfamiliar buildings and public locations.
"For the blind, finding your way or navigating in a place that is unfamiliar presents a real challenge," Dr. Merabet explains. "As people with sight, we can capture sensory information through our eyes about our surroundings. For the blind that is a real challenge? the blind will typically use auditory and tactile cues."
The technique utilizes computer generated layouts of public buildings and spatial sensory feedback to synthesize a virtual world that mimics a real world navigation task. In the game, participants must find jewels and carry them out of the building, without being intercepted by roaming monsters that steal the jewels and hide them elsewhere.
Participants interface with the virtual building by using a keyboard and wearing headphones that play auditory cues that help spatially orient them to the world around them. This interaction helps users generate an accurate mental layout of the mimicked building. Dr. Merabet and his colleagues are also exploring applications of this technology with other user interfaces, like a Wii Remote or joystick.
"We have developed software called ABES, the Audio Based Environment Simulator that represents the actual physical environment of the Carol Center for the Blind in Newton Massachusetts. The participants will use the game metaphor to get a sense of the whole building through open discovery, allowing people to learn room layouts more naturally than if they were just following directions."
The technology will invariably be useful for the 285 million blind people world-wide, 6 million of which live in the United States. It will also have applications beyond the blind community for individuals with other visual impairments, cognitive deficits, or those recovering from brain injuries.
Dr. Merabet considers publication in JoVE's video format especially helpful. "It is conceptually difficult for a sighted person to understand 'a video game for blind people.' What JoVE allows us to do is break down layouts of the game and strategy, show how the auditory cues can be used and how we quantify performance going from the virtual game to the physical world."
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The above story is reprinted from materials provided by Journal of Visualized Experiments.
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Journal Reference:
Erin C. Connors, Lindsay A. Yazzolino, Jaime S?nchez, Lotfi B. Merabet. Development of an Audio-based Virtual Gaming Environment to Assist with Navigation Skills in the Blind. Journal of Visualized Experiments, 2013; (73) DOI: 10.3791/50272
Note: If no author is given, the source is cited instead.
Disclaimer: This article is not intended to provide medical advice, diagnosis or treatment. Views expressed here do not necessarily reflect those of ScienceDaily or its staff.
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DUKU, Thailand (Reuters) - Rusnee Maeloh slept through the 30-minute gunfight that killed her husband, but her neighbors in the notoriously violent Bacho district of southern Thailand heard distant explosions and feared the worst.
Mahrosu Jantarawadee, 31, was Rusnee's childhood sweetheart, the father of their two children, and part of a secretive Islamic insurgency fighting a brutal nine-year war with the Thai government that has killed more than 5,300 people.
Mahrosu died with 15 other militants while attacking a nearby military base in Bacho district on February 13. Acting on a tip-off, Thai marines repelled the attack with rifle fire and anti-personnel mines. "He died a martyr," said Rusnee, 25, dabbing her eyes with a black headscarf.
Just over two weeks later, the Thai government agreed on peace talks in neighboring Malaysia with the insurgent group Barisan Revolusi Nasional (National Revolutionary Front, or BRN). Although the first round is set for Thursday, there has been no halt in the fighting and people in the region see no early end to one of Southeast Asia's bloodiest conflicts.
In a rare interview, an operative for BRN-Coordinate, a faction blamed for most of the southern violence, told Reuters the talks were "meaningless" and "tens of thousands" of Malay-Muslims would fight on.
An older generation of insurgent leaders has struggled to control young jihadis like Mahrosu, said the operative, nicknamed Abdulloh. This raises doubts over the BRN's ability to meet the Thai government's key initial demand at the talks: stop the escalating bloodshed.
Thailand is dominated by Thai-speaking Buddhists, but its three southernmost provinces are home to mostly Malay-speaking Muslims. They have chafed under the rule of faraway Bangkok since Thailand annexed the Islamic sultanate of Patani a century ago. The latest and most serious violence erupted in the early 2000s.
"This round of talks will not result in any formal deals," said Paradorn Pattanathabutr, secretary-general of the National Security Council (NSC), Thailand's lead agency in the process. "We will ask them to reduce violence towards certain groups and soft targets."
More insurgents were killed during the Bacho raid than in any other single clash since April 2004. But even this rare defeat revealed their growing military sophistication, the depth of local support they enjoy, and their links to Malaysia - long an insurgent safe haven and source of bomb-making materials and other supplies, say security analysts.
POORLY UNDERSTOOD
Thailand's southern provinces are only a few hundred miles from Phuket and other tourist destinations, but the insurgency is poorly understood, partly because it doesn't fit the pattern. Long-running sub-national conflicts are usually found in weak or failing states, not along the border of two prospering allies in a fast-developing region.
Thailand's homegrown jihad also rarely blips on the global security radar. That's because the militants have no proven operational link to Al Qaeda or regional terror groups such as the Indonesia-based Jemaah Islamiya, although they do boast a secretive, cell-like structure and are partly driven by post-9/11 jihadi zeal.
The militants, who number in the low thousands, are ranged against 66,000 soldiers, police and paramilitary forces spread across a conflict area half the size of Israel. Like their U.S. counterparts in Afghanistan, Thai soldiers face a ruthless enemy sheltering amid a largely hostile Muslim population.
Their pitiless response has further fueled the insurgency. The dispersal by soldiers and armed police of a protest at Tak Bai town in 2004 led to deaths of 85 Muslim men and boys, mostly by suffocation, after they were stacked four or five deep in army trucks.
Mahrosu Jantarawadee symbolizes the divide between Muslims and Buddhists in southern Thailand - a martyr to some, a murderer to others. He was born, killed and buried in Bacho, an area of rice fields and rubber plantations the Thai military calls a "red zone" of insurgent activity.
Hundreds of mourners cried "God is great!" at his funeral in Duku village. Mahrosu's family and neighbors believe he died while fighting a holy war against a Thai government whose harsh assimilation policies have suppressed their religion, language and culture.
Mahrosu is no hero to the authorities or to the relatives of his alleged victims. The Thai military links him to an eight-year streak of gun and bomb attacks that killed at least 25 people. Sometimes, said the military, he shot his victims and then set their bodies alight. His mug shot appears on posters at heavily fortified police stations across the region.
One of his alleged victims was teacher Cholatee Jarenchol, 51, shot twice in the head in front of hundreds of children at a Bacho school on January 23. The children included Cholatee's seven-year-old daughter. "She's scared she'll be killed next," her mother Fauziah, 47, said.
Cholatee was one of at least 157 teachers killed by suspected insurgents since 2004, ostensibly for being government employees.
STUBBORN
Mahrosu was advised not to attack the Bacho military base, said Abdulloh, the BRN-C operative. A wiry man in his sixties dressed in a tracksuit and sneakers, Abdulloh met Reuters in a teashop in Yala, the capital of Yala province, in a shabby neighborhood known locally as "the West Bank".
Like many militants, Abdulloh hides in plain sight in the towns of the region, although he kept the meeting brief and clutched a bag that he said concealed a pistol.
"He wouldn't listen to the elders," Abdulloh said, referring to Mahrosu. "They told him it was too risky to have so many fighters in one place. But he was stubborn and went ahead."
It was Abdulloh's task to monitor the movement of soldiers and police, and to liaise between militant cells and what he called "the elders". He said nine of the 16 dead, including Mahrosu, were "commandos" - well-equipped veterans who join forces with villagers to form platoon-strength units for big attacks.
The Bacho operation illustrated an insurgent attempt to "shift military operations to a higher level", said Anthony Davis, a Thai-based analyst at security consulting firm IHS-Janes. There are relatively fewer attacks than in previous years, but they are often better planned and more lethal, reflecting a "growing professionalization within insurgent ranks", Davis said.
The insurgents are also making more - and bigger - bombs. On March 15, just two weeks after the Malaysia talks were announced, a 100-kg device exploded beneath a pick-up truck carrying three policemen through Narathiwat province, flipping the vehicle and scattering body parts across the road. All three died on the spot.
In towns and villages, insurgents move about with surprising ease, considering the massive deployment of security forces, and pay discreet but regular visits to their families.
"He usually stayed for less than an hour," Rusnee said of Mahrosu. He was already on the run when they married in 2006. Many insurgents manage to raise families. Mahrosu and Rusnee have a six-year-old daughter and a 17-month-old son.
The ability to blend with the population also makes the militants a formidable enemy. Bacho-style insurgent attacks are logistically complex, said Thamanoon Wanna, commander of a Thai marine task force responsible for Bacho.
Weapons, ammunition and uniforms must be retrieved from multiple hiding places, then delivered to commandos arriving from all three war-torn provinces. "They have supporters in the village but right now we don't know who they are," Thamanoon said.
These militant cells have become "self-managed violence franchises", said Duncan McCargo, a British scholar of Thailand and the author of Tearing Apart the Land, a book on the southern conflict. How to rein them in will top the Thai government's agenda at this week's talks in Kuala Lumpur.
LINKS ACROSS BORDER
Malaysia established its role as a regional peacemaker after helping broker a deal between the Philippine government and Muslim rebels in October. Doing the same in southern Thailand is complicated by the fact that insurgents often seek refuge across a porous border in Malaysia. Those suspected links, which the Malaysian government denies, have periodically strained ties with Thailand.
Yet, bringing peace to southern Thailand without Malaysian help would be like ending Northern Ireland's "troubles" without the Republic of Ireland. "The Thais have got to stop demonizing Malaysia and be ready to work with them," McCargo said.
The BRN-C operative Abdulloh was pessimistic about the talks. The main insurgent delegate, Hassan Taib, who has identified himself as "chief of the BRN liaison office in Malaysia", has no control over the fighters, he said.
McCargo also questioned Hassan's credentials, saying: "The question is whether he can bring other people to the table." Historically, Thai governments have used dialogue to identify the movement's leaders and "then buy them off or get rid of them," said McCargo. "So you can understand why the militants are so suspicious."
Thailand's powerful military also has reservations. It has been lukewarm about the talks that confer legitimacy on an armed movement Thai generals have dismissed as more criminal than political.
The talks could encourage ethnic Malay Muslims in southern Thailand to express political aspirations Bangkok has long viewed as disloyal. Thailand's militants are often described as "separatists". But many southerners acknowledge that creating a tiny new Islamic republic sandwiched between Thailand and Malaysia is, as McCargo put it, "a fantasy".
Abdulloh, who is bullet-scarred from a decades-old gunfight with Thai troops, seemed to be one of them. He wanted the Thai government to apologize for past human rights abuses and recognize a "Malay homeland", but stopped short of demanding a separate state.
Even so, any solution will likely have to include greater autonomy for Pattani, Yala and Narathiwat. Thailand is highly centralized, with the governors of its 76 provinces appointed by Bangkok. The three southern border provinces were traditionally a dumping ground for venal or inept officials.
It's unclear whether Thailand will offer greater self-rule, or anything else that will make the process any more successful than a string of semi-secret dialogues since 2005.
Winning over locals in the hardest-hit areas could be the greatest challenge.
"Of course we welcome a peace agreement, if the Thais are sincere," said Zakaria bin Adbulrasid, whose 28-year-old son Barkih Nikming was also killed during the Bacho raid and given a martyr's burial in the nearby village of Cuwo. "But their promises of peace and justice are all lies."
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Public release date: 28-Mar-2013
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Let us take you now into the real thing why you?re here; Love text messages for girlfriend or boyfriend