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A new study involving researchers at The University of Nottingham has revealed how children with an aggressive cancer predisposition syndrome experience a never before seen flood of mutations in their disease in just six months.

The syndrome, called 'biallelic mismatch repair deficiency' (bMMRD) causes multiple brain tumours, lymphomas and gastrointestinal cancers by the age of 10. As a result these children rarely survive into adulthood.

While most cancers grow progressively, developing genetic mutations over many years, researchers at The Hospital for Sick Kids in Toronto, Canada, the Wellcome Trust Sanger Institute and the Children's Brain Tumour Research Centre in Nottingham, were shocked to find that children with this syndrome develop more mutations than any human cancers by far -- as many as 20,000 mutations in as little as six months.

The new paper, published online in Nature Genetics, suggests a previously undiscovered mechanism for cancer progression which could lead to more targeted treatment for these patients and indeed for more common cancers.

Children with biallelic mismatch repair deficiency, or bMMRD, have mutations in the genes responsible for mismatch repair and therefore cannot fix mistakes in DNA while the cell is dividing (or replicating). This study identifies a secondary mutation which occurs only in tumour cells in an enzyme called polymerase, which is a second safeguard that helps to effectively repair mutations while the DNA replicates. The combination of these two mutations leaves patients with no ability to repair mistakes that may occur while DNA is replicating, and causes a rapid wave of cancer that the investigators have dubbed the "great flood."

Professor Richard Grundy from the University's Children's Brain Tumour Research Centre said: "This study provides a major step forwards in understanding why certain children are more susceptible to developing multiple cancers and can screen for this eventuality. In turn, this study allows us to begin to understand the steps that lead to cancer developing. Ultimately, we hope this leads to treatments to avoid the presently inevitable consequences of this predisposition syndrome"

Dr Uri Tabori, co-principal investigator of the study from Genetics & Genome Biology at SickKids, Toronto said: "In other cancer predisposition syndromes like BRCA1 and Li Fraumeni syndrome, we know that there is a genetic mutation that predisposes the individual to cancer, but we do not know the secondary mutation, or genetic driver that actually causes the cancer to occur. Our findings indicate the genetic driver that causes this 'great flood' of cancer mutations in patients with bMMRD. The secondary mutation in the enzyme polymerase causes a unique signature of mutations that is present in 100 per cent of the cases. This has important implications for both diagnosis and targeted treatment of this devastating disease."

The Children's Brain Tumour Research Centre in Nottingham is part of an international consortium run by SickKids, Toronto, that offers free genetic testing, genetic counseling and surveillance of cancers in children and family members with bMMRD. Using genetic and clinical information and tumour samples gathered from each patient, the research team was able to take a deeper look at this cancer predisposition syndrome and for the first time they are able to tell the story of how this cancer develops.

"We were able to describe how many mutations develop, how fast they occur, how many mutations the tumour can sustain, and the type of mutation that occurs, which we found is unique to bMMRD cancers," says Dr Adam Shlien, lead author of the study and Associate Director of Translational Genetics and Scientist in Genetics & Genome Biology at SickKids.

"Additionally, by studying a rare cancer syndrome we were able to have an unobstructed view on how cancer develops and learn not only about how we can help these patients, but also about cancer progression in general."

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Study sheds new light on aggressive cancer in children

Date:

February 3, 2015

Source:

Max Planck Florida Institute for Neuroscience

Summary:

Using multiphoton imaging, researchers are now able to move beyond characterizing the properties of individual cells to investigate how communication among neurons changes over the course of development. In a new paper, researchers report substantial developmental changes in communication among cells that significantly improve the information processing capabilities of the brain.

Previous work, including studies performed in the Fitzpatrick Lab at MPFI, has shown that individual brain cells refine their responses to stimuli with experience so they can better discriminate between similar features in their environments. However, the signals of individual brain cells can be noisy and imprecise which means our brains cannot rely solely on the activity of single neurons to make accurate decisions about our world. Instead, we combine the activity of thousands to millions of neurons to ensure a more accurate message, which makes effective communication amongst large populations of neurons a central feature of the brain.

This study demonstrates that, over development, neural circuits reorganize themselves to decrease noise and improve the fidelity of communication amongst each other. The critical role these changes play in brain development highlights the importance and urgency in understanding neural circuits in more detail and suggests new avenues for investigating the underlying causes of developmental disorders such as autism.

The authors of the study said the key question moving forward is to understand what specific changes in brain circuitry give rise to the effects observed in this study. Where do these changes manifest themselves within the circuit and what molecular processes do they utilize? We know that a number of structural changes also occur during this developmental period, and we now can attempt to link those changes to the changes in circuit function.

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New research sheds light on neural circuit development

Bought by Columbus Nova, Sony Online Entertainment becomes an independent game development studio

Sony has sold Sony Online Entertainment, an Internet games company it established in the 1990s, to investment firm Columbus Nova.

SOE has been renamed Daybreak Game Company and will operate as an independent game development studio producing titles for the PlayStation and Xbox, according to a statement on its forum.

"All of our games are still here and will continue to be," Daybreak president John Smedley wrote in a message on Twitter, adding that the company is still working on EverQuest Next, the latest sequel to 1999's EverQuest, a massively multiplayer online role-playing game (MMORPG).

With an emphasis on PC games, the company had been in the shadow of Sony's more popular video game hardware business including the hit PlayStation 4 console, as well as the recent rise of games for mobile platforms.

"We determined it was in the best interest of both entities to allow the studio to realize its full potential as a multi-platform online gaming company," Sousuke Kamei, a spokesman at Sony's Tokyo headquarters, said via email.

"The environment surrounding the game industry is always challenging, and we are doing a review of our business on a regular basis. As part of it, we decided to sell SOE for strengthening the overall business quality in order to increase higher profitability," Kamei said.

SOE is the latest business to be shed by the struggling manufacturer, which sold its Vaio PC business and pulled out of e-readers last year.

Tim Hornyak covers Japan and emerging technologies for The IDG News Service. Follow Tim on Twitter at @robotopia.

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Sony sheds online game unit known for EverQuest

Contributed Photos

This curved tunnel beneath Homestead Avenue, in Hartford's North End, is part of The Metropolitan District Commission's Clean Water Project for separating its storm drains and septic-sewer channels. The project will improve the quality of treated wastewater before it winds up in Connecticut's inland waterways and Long Island Sound.

The State Bond Commission on Friday approved $480 million in grants and loans to wastewater projects in Hartford, Bristol, Norwich, and more statewide.

The Metropolitan District Commission received $80 million in grants and $178 million in loans for a 20-year investment in Greater Hartford to separate the flow of stormwater from sanitary sewers.

The Bristol Wastewater Treatment plant received $9.5 million in grants and $9.5 million in loans for various upgrades, including removing phosphorous from wastewater in order to protect the Pequabuck River.

The Norwich Wastewater Treatment Plants received $20 million in grants and $80 million in loans to upgrade its infrastructure and nitrogen removal.

The remaining $103 million will be used for a variety of projects across the state, including planning studies, engineering designs, and green infrastructure projects, including compensating for sea level rise.

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CT approves $480M for wastewater projects

14 Suffolk Street, Pembroke, MA
Meticulously maintained Gambrel Cape w/large family room addition with vaulted ceiling, skylights, and wood ceiling. Sliders to large 3 season room w/hot tub, ceramic tile floor and sliders...

By: Larry Meredith Hunt, The Hunt Team

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14 Suffolk Street, Pembroke, MA - Video

Niceville residents J.V.O. and Sharon Weaver stroll down the boardwalk at Turkey Creek Nature Trail on Monday. The boardwalk follows the creek from a pavilion next to John Sims Park-way 3/4 of a mile north.

NICEVILLE Fans of the Turkey Creek Nature Trail boardwalk will soon have even more room to roam.

Beginning in late February/early March, construction will begin on an addition that will connect two separate sections of walkway.

Currently, the section of the park with its entrance on John Sims Parkway has approximately of a mile of boardwalk that is enjoyed by walkers, joggers and swimmers headed for a dip in the creek. The other section of the park, whose entrance is located off of College Boulevard, includes approximately 900 feet of boardwalk. Both sections feature pavilions and picnic tables.

It will take about 320 feet of new boardwalk to connect the two sections, giving park visitors nearly a full mile of walking and jogging space. The addition is expected to take about three months.

If all goes well, we hope to get started soon, and have the addition finished by summer, said Willie Hines, the citys repair and maintenance foreman.

Visitors to the park on Monday were happy to hear that work on the addition will begin soon.

I think its wonderful, said Niceville resident Michelle Tew, who walks the length of the boardwalk and back at least once a day and sometimes twice. This is such a beautiful place to walk, and Ive been looking forward to the new section.

Crestview residents Debbie and Burl Olson are also frequent visitors.

Im happy to hear that, Burl said. We try to walk about two miles a day, so the addition will put the length right in our wheelhouse.

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Turkey Creek to see improvements

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Katy Perry's Super Bowl Halftime Show Was the Most-Watched in U.S. History

The Jacka Dies in Oakland Shooting

Following "Coyotes" and "Lampshades on Fire," Modest Mouse have a new track out titled "The Best Room." Showcasing Isaac Brock's signature choppy vocals, the penultimate track on the forthcoming Strangers to Ourselves decries the deteriorating state of Western civilization, crowing, "The lessons unlearned, oh this meeting it's adjourned! / These western concerns, 'Hold my place in line while I take your turn.'"

In addition to the new song, the guys announced plans to push the release of their album back to March 17, which is a bummer, but to help make up for things they released the album's track list, which you can see below. Hear "The Best Room" above.

Modest Mouse, Strangers to Ourselves track list: 1. "Strangers To Ourselves" 2. "Lampshades On Fire" 3. "Shit In Your Cut" 4. "Pistol (A. Cunanan, Miami, FL. 1996)" 5. "Ansel" 6. "The Ground Walks, With Time In A Box" 7. "Coyotes" 8. "Pups To Dust" 9. "Sugar Boat" 10. "Wicked Campaign" 11. "Be Brave" 12. "God Is An Indian And Youre An Asshole" 13. "The Tortoise And The Tourist" 14. "The Best Room" 15. "Of Course We Know"

spin

The Lists The Top 100 Alternative Albums of the 1960s

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Stream Modest Mouse's Political New Track, 'The Best Room'

Kevin C. Cox/Getty Images Robert Griffin III reportedly has some personal issues with his teammates.

By Larry Brown

The NFL season has finally ended, which means its time for NFL writers to do what they do best: criticize easy targets. Its no surprise that the columns about Robert Griffin III have already started.

The Washington Posts Jason Reidchecked in with a column Mondayabout RG3s personality. The crux is that the quarterback isnt one of the boys and that hurts his ability to be a leader.

Heres what Reid wrote:

(Tim) Brown said publicly what some of Washingtons coaches and players have shared with me privately: Griffins aloofness has been an issue in the locker room. Combine that with Griffins poor performance the past two seasons and a Super Bowl-sized ego that tripped him up after his magical rookie year, and its clear Griffin isnt close to becoming the player the Redskins need him to be.

Reids writing was inspired mostly by comments Tim Brown, who was on the radio Thursday to promote his Hall of Fame candidacy.

Brown has interacted with Griffin during Heisman Trophy gatherings andshared some insight on Griffins character.

But I know RGIII well enough to know that hes a little different, Brown said on ESPN 980 last week. I mean, I know he is maybe not the brother that youre gonna be hanging out in the locker room with. And from that standpoint, thats something that he has to work on. If hes going to be a leader, he has to be a leader of everybody in the locker room, and not just one or two guys in the locker room.

Brown also said that Griffin has a hard time joking around with the other Heisman winners, which leads him to be an outcast. Brown suggests Griffin should loosen up in order to relate better to his teammates.

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RG3's 'aloofness' in locker room an issue for Redskins?

Leo Krizan, Bell Captain, at The Oxford Hotel, waits for guest to arrives, February 02, 2015. Colorado's hotel sector is improving fast since its dip during the recession. Room rates and occupancy levels are at record highs. (RJ Sangosti, The Denver Post)

There's still room at the inn, but less of it than ever before in Colorado's hotels.

A resurgent economy brought a record number of guests to the state's hotels in 2014. Along with healthy occupancy levels came the highest room rates ever recorded in Colorado.

Analysts say the industry is hitting on each of its three main cylinders: business travel, convention bookings and vacationing visitors.

2014 marked the fifth consecutive year of improvement for hotel operators since the market faltered during the recession of 2008-09.

Rising fundamentals also are helping bring the industry out of years of dormancy in which few new hotels were built. An estimated 1,700 rooms will be added in metro Denver in 2015. That 3.8 percent gain in inventory is the fastest growth spurt in 15 years.

"The market is strong and I think we'll continue to see demand (for rooms) continue to increase in 2015," said Bob Benton of Robert S. Benton & Associates, co-author of the Rocky Mountain Lodging Report.

Colorado hotels reached an average occupancy rate in 2014 of 68.3 percent, according to the lodging report. The statewide average room rate was $135, an increase of 6 percent from 2013.

Metro Denver's room rates grew even faster, rising 8 percent to an average of $124.

The metro average rate belies an extremely healthy luxury hotel market in downtown Denver where it's not unusual to see rates as high as $400 a night during peak weekday business travel periods.

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Demand fuels record room rates, occupancies in Denver and Colorado hotels

Fort Lauderdale, FL (PRWEB) February 03, 2015

Jafrejo Holdings & the Florida Restaurant Franchise Group are bringing Twin Peaks to South Florida. What has been called the Fastest Growing Restaurant Chain in America by both Businessweek and Forbes magazines, the booming restaurant chain already has Florida locations in Orlando and Pensacola and the company is expected to open the brands 1st South Florida location in early May with another 4 locations scheduled to open throughout the a area over the next 12 months.

The 11,000-square-foot restaurant is currently under construction and will be located in the Tower Shoppes (at the corner of University Drive and I-595) in Davie, FL. We're building the Ultimate Man Cave with the coldest beer in town and made from scratch food said Joe Sloboda, Vice President of Operations for Jafrejo Holdings. The Davie location will have 32 beers on tap and more than 70 large screen hi-def televisions with for every sports fans viewing pleasure.

Twin Peaks is mountain-lodge themed sports bar, known for its rugged feel and man cave setting, with 29 degree beer and made from scratch food served by beautiful Twin Peaks Girls. The Texas based franchise has been taking the country by storm and currently has 65 locations across the United States and is expected to have more than 100 stores opened by the end of the year. We are coming into South Florida in a big way and will be opening stores in West Palm Beach, Ft. Myers, Pembroke Pines and Fort Lauderdale over the next 12 months, added Sloboda.

About Jafrejo Holdings, LLC and the Florida Restaurant Franchise Group Based in Weston, FL, Jafrejo Holdings, LLC and their subsidiary, The Florida Restaurant Franchise Group is a commercial real estate development and holding company that specializes in restaurant operations and retail property development. The company currently owns and or is developing multiple franchise restaurant units for VooDoo BBQ & Grill and Twin Peaks Restaurants. The Principles have more than 30 years of experience in restaurant operations and real estate development and are also licensed attorneys and experienced real estate developers.

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Jafrejo Holdings to Bring Twin Peaks Restaurant to South Florida