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Adobe Carousel hits the App Store

Adobe has released their photo management and editing app Adobe Carousel, today. With Adobe Carousel, you can keep an updated photo library on your iPhone, iPad, and Mac. It even comes with some basic editing tools to help improve the look of your images. One of the...

Source: http://feedproxy.google.com/~r/TheIphoneBlog/~3/Zqs_ky1-OKk/

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China considers new law better defining terrorism (AP)

BEIJING ? China said Tuesday that it is considering new legislation to better define terrorism and allow for the public listing of terrorist groups, in an effort to strengthen prosecution against domestic threats and bolster Beijing's role in international cooperation.

A proposal before the national legislature would provide more specific legal definitions for terrorists and terrorist acts based on Chinese and international precedents, making it easier to bring terrorism charges, the official Xinhua News Agency said.

The proposal targets those using violence, sabotage or threats in hopes of intimidating or coercing governments or international organizations. Incitement, funding or providing other support would also be considered terrorism.

Terrorist groups would be publicly named and the legislation would strengthen existing rules on seizing their domestic assets.

"Current legislation lacks specific regulations defining terrorism, terrorist organizations and individual terrorists, affecting the fight against terrorism, control over terrorist assets and international anti-terrorism cooperation," Xinhua said, quoting deputy Public Security Minister Yang Huanning.

China says it faces an organized terrorist threat from radical Muslim groups in the northwestern region of Xinjiang, although critics say Chinese economic policies and strict rules over cultural and religious expression are creating anger and resentment among the region's traditional Turkic Uighur (WEE'-gur) ethnic group.

China has been accused of exploiting terrorism fears to justify crackdowns on legitimate dissent, and the U.S. has refused demands to hand over Uighurs captured in Afghanistan and Pakistan and held at Guantanamo Bay. While Beijing has at times accused Tibetan activists of plotting terrorism, opposition to Chinese rule in the Himalayan region has been mainly peaceful.

The proposed legislation is on track to eventually become a new anti-terrorism law, said Li Wei, a counterterrorism expert at the China Institute of Contemporary International Relations, a think tank affiliated with the government's main intelligence agency, the Ministry of State Security.

That would for the first time provide a comprehensive mechanism for specifically prosecuting terrorism, including defining such crimes and clarifying the roles of anti-terrorism bodies, as well as laying out procedures for seizing terrorist funds, Li said.

"How often it is used depends on how often such acts occur, but China will now have a law which deals specifically with terrorist crimes," he said.

Foreign Ministry spokeswoman Jiang Yu said that the ministry was following the drafting of the new law and that China was drawing from the experiences of other countries in dealing with terrorism.

"China will continue to deepen cooperation with regional countries and international organizations to step up contacts and coordination," Jiang said at a daily news briefing.

Most of the government's terrorist accusations focus on groups in Xinjiang, which has been on edge since nearly 200 people were killed in fighting between Uighurs and Han Chinese in 2009 in Urumqi, the regional capital. China accused overseas Uighur activists of orchestrating the violence, but provided no direct evidence.

Violence this year flared anew July 18, when a group of Uighurs stormed a police station in Hotan and took hostages, killing four. Then, on July 30 and 31, Uighurs in Kashgar hijacked a truck, set a restaurant on fire and stabbed people in the street.

Authorities said that 14 of the attackers were shot by police in Hotan, and that five assailants were killed in the violence in Kashgar.

China again blamed overseas activists for what it described as organized terrorist attacks, specifically Pakistan-based militants affiliated with al-Qaida. One group, the Turkistan Islamic Party, claimed one of the attackers in Hotan had previously visited one of its training camps.

___

Associated Press writer Gillian Wong contributed to this report.

Source: http://us.rd.yahoo.com/dailynews/rss/terrorism/*http%3A//news.yahoo.com/s/ap/20111025/ap_on_re_as/as_china_terrorism

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Last Nuclear ?Monster Weapon? Gets Dismantled [War]

In the 1960s, the skies above the United States were patrolled by agents of the apocalypse. Air Force B-52 Stratofortresses circled the North American continent, 24 hours a day, cradling two megabombs in their bellies. More »


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Tax haven crackdown yields 14 billion euros: OECD (Reuters)

PARIS (Reuters) ? An international drive against offshore tax havens has reaped nearly 14 billion euros from would-be tax evaders, the Organization for Economic Cooperation and Development (OECD) said on Tuesday.

Some 100,000 taxpayers in 20 major economies surveyed by the OECD have revealed previously undetected offshore assets in the last two years, allowing tax authorities to collect the equivalent of nearly $19 billion.

"As cash-strapped governments look to pay down their deficits, this will make a substantial contribution to fiscal consolidation," OECD Secretary General Angel Gurria said at the opening of a two-day meeting on tax transparency.

"Just as important -- most of the additional revenues has been secured from citizens trying to evade taxes," he added. "At a time when many governments are forced to ask their citizens to accept higher taxes and reduced public services, everyone must pay their fair share."

Italy has so far been the biggest beneficiary of the crackdown. An scheme there to promote voluntary disclosure of offshore assets had helped bring in additional tax revenues of 5.6 billion euros, the OECD said.

A similar scheme in the United States helped recover 2.7 billion dollars from more than 30,000 taxpayers. Germany had raised additional tax revenues of 1.8 billion euros from as many as 30,000 taxpayers.

Berlin is expected to net billions more from a recent deal to formalize the taxation of money stashed by German citizens in secret Swiss accounts.

Switzerland reached a similar agreement with Britain earlier this month is inching toward a settling a dispute with the United States over Swiss banks helping wealthy Americans to dodge taxes.

The Group of 20 countries agreed at a summit in London in 2009 to step up efforts to clamp down on offshore tax havens. The OECD has since led efforts to force such jurisdictions to sign international standards on data disclosure, and publishes lists exposing those countries that refuse to comply.

The OECD said the number of requests for tax information from jurisdictions previously considered to be tax havens had surged from nearly zero into the thousands, with Switzerland alone getting hundreds of requests since 2009.

($1 = 0.720 Euros)

(Reporting by Leigh Thomas; Editing by John Stonestreet)

Source: http://us.rd.yahoo.com/dailynews/rss/economy/*http%3A//news.yahoo.com/s/nm/20111025/bs_nm/us_oecd_tax

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'Occupy' camps provide food, shelter for homeless (AP)

PORTLAND, Ore. ? When Occupy Wall Street protesters took over two parks in Portland's soggy downtown, they pitched 300 tents and offered free food, medical care and shelter to anyone. They weren't just building, like so many of their brethren across the nation, a community to protest what they see as corporate greed.

They also created an ideal place for the homeless. Some were already living in the parks, while others were drawn from elsewhere to the encampment's open doors.

Now, protesters from Portland to Los Angeles to Atlanta are trying to distinguish between homeless people who are joining their movement and those who are there for the amenities. When night falls in Portland, for instance, protesters have been dealing with fights, drunken arguments and the display of the occasional knife.

However, many homeless say the protests have helped them speak out against the economic troubles that sent them to the streets in the first place.

"The city wasn't giving us what we needed," said Joseph Gordon, 31, who trekked his way from Cincinnati two months ago and noted that there is nearly always enough food but never enough shelter. "You can't feed your problem away. It took this camp to show people how it really is."

As protesters across the country try to coalescence around an agenda in the coming weeks and months, they are trying to make life work in camps that have become small-scale replicas of the cities in which they were erected. And just like those cities, they are dealing with many of the same problems the local governments have struggled for decades to solve.

Some organizers see the protest and the inclusion of the homeless as an opportunity to demonstrate their political ideals. They see the possibility to show that the homeless are not hopeless and that they, too, can become a functional part of society.

In Portland, the protest has swallowed up two square blocks. There are shaggy haired college kids, do-gooder hippies, and couples with their young children. They came by the dozen, in cars and vans, on bikes and on foot and in rides hitched on the highway. Rain falls daily and dry socks are at a premium.

At the center of the camp are the medical, information, library and wellness tents. Along one side are families, who established a play area for children. On the opposite side is the "A-Camp" ? for anarchist. It's where the city's anarchist faction and long-term homeless sleep.

"We're here to spoil each other," said Kat Enyeart, a 25-year-old medic who says she spends half her time tending to the homeless, some of whom are physically and mentally ill. "It's a big, messy, beautiful thing."

As the occupation enters its fourth week, divisions have begun to emerge. Without the ability to enforce laws and with little capacity to deal with disruptive or even violent people, the camp is holding together as it struggles to maintain a sense of order and purpose.

One man recently created a stir when he registered with police as a sex offender living in the park. A man with mental health problems threatened to spread AIDS via a syringe. At night, the park echoes with screaming matches and scuffles over space, blankets, tents or nothing at all.

Last week, a homeless man menaced a crowd of spectators with a pair of scissors. Micaiah Dutt, a four-tour veteran of the Iraq War, and two other former soldiers had no problem tackling and subduing the man. Other members of the protest's volunteer security detail have been punched and threatened with knives.

Dutt said he felt helpless at times and noted that the man he helped subdue could, in theory, press assault charges against him.

"I served four tours in Iraq, and I felt more safe there at times than here," he told a gathering of protest organizers under a drizzly evening sky. "There, I had a weapon and knew the people around me were with me. Here, I don't know."

Dutt said the protests are not just about the radicals and the politicians. "It's about our community taking care of itself because the city, county and federal governments have neglected this population," he said.

In Los Angeles, protesters are dealing with similar issues: Homeless transplants from the city's Skid Row have set up their tents within the larger tent city. No violence has been reported, but protest organizers are attempting to discourage people who are only at the encampment for the amenities.

Some, like Steven Pierieto, said they've fallen on difficult times but are at the protest because they support the movement. They scorn those who come for the sandwiches but never lift a protest sign. Life in camp, Pierieto said, is far better than life on Skid Row.

"I'm very comfortable right here," Pierieto said. "I don't have to smell urine. I don't have to see people smoking crack. I have porta-potties right here. It's peaceful."

In Oakland, Calif., where the camp on the City Hall lawn has become a tourist attraction, organizer Susanne Sarley said getting along for a common cause will be an ongoing challenge. "This is the homeless people's turf," Sarley said. "This area we're occupying is their home. We can't move them. We have to cooperate and respect the community that we're in."

The friction between the homeless and the protesters has not been the case in other cities. In Atlanta, for instance, it has been a benefit. The homeless have helped newbie protesters learn how to put up tents that can withstand wind gusts, maintain peace in close quarters and survive the outdoors.

Billy Jones, 28, provides security at the protests. Jones said he's not just looking for free food.

"Don't have the misconception that most homeless people are always out for a meal," Jones said. "I'm here because there are things I can lend that are helpful to the movement. I can get food anywhere. I don't have to be at Occupy Atlanta to get food."

In Salt Lake City, protesters see working with the homeless as an opportunity to demonstrate their political views. "We can help people get out of homelessness," said organizer Jesse Fruhwirth, 30. "We have already surpassed any effort the state or city has ever made to create a sober, happy space for the homeless."

Brent Jackson, 46, is one of the homeless who has been recruited as a volunteer and is an active member of a planning group. He said the protest's message rings especially true with homeless people. "The homeless are the bottom of the 99 percent," Jackson said, referring to the percent of Americans the protest says it represents.

"We have a lot of disillusioned Americans, but they don't think what happened to us can happen to them," he said. "Except it can."

___

Cristian Salazar in New York, Christina Hoag in Los Angeles, Harry R. Weber in Atlanta, Josh Loftin in Salt Lake City and Terry Collins in Oakland. Calif. contributed to this report.

Source: http://us.rd.yahoo.com/dailynews/rss/us/*http%3A//news.yahoo.com/s/ap/20111022/ap_on_re_us/us_occupy_wall_street_homeless

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Sildenafil may benefit children with PAH

[ Back to EurekAlert! ] Public release date: 24-Oct-2011
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Contact: Sue Roberts
sroberts@chestnet.org
847-498-8334
American College of Chest Physicians

(HONOLULU, HAWAII, OCTOBER 24, 2011) Sildenafil is currently approved for adult pulmonary arterial hypertension (PAH); however, new research presented at CHEST 2011, the 77th annual meeting of the American College of Chest Physicians (ACCP), shows the drug may also provide significant benefits for children with PAH, helping to improve both oxygen delivery and exercise capacity.

PAH is a rare disease, and it is even more rare in children. But the disease is horrific, with the average lifespan less than one year in children if untreated; however, with appropriate treatment, 5year survival should be over 80 percent, said study author Robyn Barst, MD, FCCP, Columbia University, New York, NY. This is a landmark study the first, and to date, the only study that has adequately evaluated a drug for the treatment of PAH in children. PAH, characterized by narrowing of the small arteries that carry blood from the heart to the lungs, leads to shortness of breath, chest pain, swelling in the lower body, fatigue, and heart failure.

Not only is PAH rare in children, it is also difficult to diagnose and treat. Diagnosis from onset of symptoms is often 2 years or more because patients often have nondescript symptoms such as breathlessness with exercise and fatigue, said Dr. Barst. If PAH is not suspected, the appropriate tests will not be performed until the disease has progressed, often to the point the patient has fainting episodes or heart failure. Once PAH is diagnosed, managing the condition in children brings new challenges. Although the disease is similar in children and adults, optimal treatment is not necessarily the same.

Children are not just small adults. Before prescribing drugs for children, we need to know if the drug works, what dose should we use, is the drug well tolerated, what side effects the drug has, and is it safe in the short term and long term said Dr. Barst. In addition, adequate clinical studies are needed to provide evidence-based treatment guidelines for children with PAH.

To address this issue, Dr. Barst and colleagues conducted a randomized, double-blind study involving 32 medical centers in 16 countries, to assess the outcomes of sildenafil therapy in 234 children (aged 1-17 years) with PAH, as they received low, medium, or high-dose sildenafil, or placebo for 16 weeks. Cardiopulmonary exercise testing, peak oxygen consumption (pVO2), and minute ventilation to carbon dioxide output (VE/VCO2) levels were determined at baseline and at week 16 in all children who could reliably exercise on a bicycle (n=106). Although the primary endpoint of % change in pVO2 did not meet predefined criteria (p = 0.056), children receiving sildenafil therapy at medium and high dose had greater improvements in pVO2 and VE/VCO2 slope (ie, the relationship between the two variables) vs placebo, signifying an improvement in both oxygen delivery and blood flow through the lungs. Sildenafil also increased the amount of exercise the children could perform and made it easier for them to exercise. In addition, sildenafil improved the gas exchange efficiency of the lungs during exercise. Outcomes appeared better for patients with idiopathic/heritable PAH vs congenital heart defect-associated PAH. Long-term follow-up of these patients three years after the initial trial revealed a concern for increased mortality in the high dose group, suggesting that the medium dose may have the best risk-benefit ratio.

Although sildenafil is not yet approved for use in pediatric patients with PAH, this study is the first step to evaluate the safety and effectiveness of treatments for children. The goal in treating the children is to improve their overall quality of life, in addition to hopefully improving their survival, said Dr. Barst. We want to make the children feel better and not just live longer. Thus, a thorough evaluation is difficult, but it is critically important.

Historically, PAH has been difficult to manage; however, treatments have been advancing rapidly, said David Gutterman, MD, FCCP, President of the American College of Chest Physicians. Continued research and well-controlled clinical trials should lead to further improvements in the treatment of this very challenging disease.

###

CHEST 2011 is the 77th annual meeting of the American College of Chest Physicians, held October 22 -26 in Honolulu, Hawaii. The ACCP represents 18,300 members who provide patient care in the areas of pulmonary, critical care, and sleep medicine in the United States and throughout the world. The mission of the ACCP is to promote the prevention, diagnosis, and treatment of chest diseases through education, communication, and research. For more information about the ACCP, please visit the ACCP Web site at www.chestnet.org.


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[ Back to EurekAlert! ] Public release date: 24-Oct-2011
[ | E-mail | Share Share ]

Contact: Sue Roberts
sroberts@chestnet.org
847-498-8334
American College of Chest Physicians

(HONOLULU, HAWAII, OCTOBER 24, 2011) Sildenafil is currently approved for adult pulmonary arterial hypertension (PAH); however, new research presented at CHEST 2011, the 77th annual meeting of the American College of Chest Physicians (ACCP), shows the drug may also provide significant benefits for children with PAH, helping to improve both oxygen delivery and exercise capacity.

PAH is a rare disease, and it is even more rare in children. But the disease is horrific, with the average lifespan less than one year in children if untreated; however, with appropriate treatment, 5year survival should be over 80 percent, said study author Robyn Barst, MD, FCCP, Columbia University, New York, NY. This is a landmark study the first, and to date, the only study that has adequately evaluated a drug for the treatment of PAH in children. PAH, characterized by narrowing of the small arteries that carry blood from the heart to the lungs, leads to shortness of breath, chest pain, swelling in the lower body, fatigue, and heart failure.

Not only is PAH rare in children, it is also difficult to diagnose and treat. Diagnosis from onset of symptoms is often 2 years or more because patients often have nondescript symptoms such as breathlessness with exercise and fatigue, said Dr. Barst. If PAH is not suspected, the appropriate tests will not be performed until the disease has progressed, often to the point the patient has fainting episodes or heart failure. Once PAH is diagnosed, managing the condition in children brings new challenges. Although the disease is similar in children and adults, optimal treatment is not necessarily the same.

Children are not just small adults. Before prescribing drugs for children, we need to know if the drug works, what dose should we use, is the drug well tolerated, what side effects the drug has, and is it safe in the short term and long term said Dr. Barst. In addition, adequate clinical studies are needed to provide evidence-based treatment guidelines for children with PAH.

To address this issue, Dr. Barst and colleagues conducted a randomized, double-blind study involving 32 medical centers in 16 countries, to assess the outcomes of sildenafil therapy in 234 children (aged 1-17 years) with PAH, as they received low, medium, or high-dose sildenafil, or placebo for 16 weeks. Cardiopulmonary exercise testing, peak oxygen consumption (pVO2), and minute ventilation to carbon dioxide output (VE/VCO2) levels were determined at baseline and at week 16 in all children who could reliably exercise on a bicycle (n=106). Although the primary endpoint of % change in pVO2 did not meet predefined criteria (p = 0.056), children receiving sildenafil therapy at medium and high dose had greater improvements in pVO2 and VE/VCO2 slope (ie, the relationship between the two variables) vs placebo, signifying an improvement in both oxygen delivery and blood flow through the lungs. Sildenafil also increased the amount of exercise the children could perform and made it easier for them to exercise. In addition, sildenafil improved the gas exchange efficiency of the lungs during exercise. Outcomes appeared better for patients with idiopathic/heritable PAH vs congenital heart defect-associated PAH. Long-term follow-up of these patients three years after the initial trial revealed a concern for increased mortality in the high dose group, suggesting that the medium dose may have the best risk-benefit ratio.

Although sildenafil is not yet approved for use in pediatric patients with PAH, this study is the first step to evaluate the safety and effectiveness of treatments for children. The goal in treating the children is to improve their overall quality of life, in addition to hopefully improving their survival, said Dr. Barst. We want to make the children feel better and not just live longer. Thus, a thorough evaluation is difficult, but it is critically important.

Historically, PAH has been difficult to manage; however, treatments have been advancing rapidly, said David Gutterman, MD, FCCP, President of the American College of Chest Physicians. Continued research and well-controlled clinical trials should lead to further improvements in the treatment of this very challenging disease.

###

CHEST 2011 is the 77th annual meeting of the American College of Chest Physicians, held October 22 -26 in Honolulu, Hawaii. The ACCP represents 18,300 members who provide patient care in the areas of pulmonary, critical care, and sleep medicine in the United States and throughout the world. The mission of the ACCP is to promote the prevention, diagnosis, and treatment of chest diseases through education, communication, and research. For more information about the ACCP, please visit the ACCP Web site at www.chestnet.org.


[ Back to EurekAlert! ] [ | E-mail | Share 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.


Source: http://www.eurekalert.org/pub_releases/2011-10/acoc-smb101011.php

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Researchers generate first complete 3-D structures of bacterial chromosome

[ Back to EurekAlert! ] Public release date: 21-Oct-2011
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Contact: Jim Fessenden
james.fessenden@umassmed.edu
508-856-2000
University of Massachusetts Medical School

3-D models yield new insights into role of parS sites in bacterial cells

WORCESTER, Mass. A team of researchers at the University of Massachusetts Medical School, Harvard Medical School, Stanford University and the Prince Felipe Research Centre in Spain have deciphered the complete three-dimensional structure of the bacterium Caulobacter crescentus's chromosome. Analysis of the resulting structure published this week in Molecular Cell has revealed new insights into the function of genetic sequences responsible for the shape and structure of this genome.

Scientists know that the three-dimensional shape of a cell's chromosome plays a role in how genetic sequences and genes are regulated. However, technical challenges have limited genome-wide analysis of a chromosome's architecture that would allow for simultaneous identification of the elements involved in shaping it and analysis of specific features of the structure. In this study, researchers used high-throughput chromatin interaction detection; next-generation DNA sequencing; computational modeling; and fluorescent microscopy to build the first 3D model of the architecture of the bacteria's chromosome and analyze the resulting structures. This new experimental approach revealed novel characteristics of a specific genetic sequence called the parS site, which helps to define the chromosome's shape.

"What we've shown is that it's possible to combine molecular biology with 3D modeling technology to perform studies that tell us novel things about how genomes fold and identify the genetic sequences that are responsible." said Job Dekker, PhD, a pioneer in chromosome interaction detection technologies, professor of biochemistry & molecular pharmacology at the University of Massachusetts Medical School, and one of the authors on the study.

Dekker and colleagues used "5C" technology to map more than 28,700 contact points in the Caulobacter crescentus's genome and used these contacts to approximate spatial distance in the folded chromosome. Plugged into a computational model, these contact points yielded a structural model of the bacterial chromosome which was strikingly beautiful: ellipsoidal in shape with arms helically arranged on either side.

Marc A. Marti-Renom, PhD, a computational biologist who leads the Structural Genomics Laboratory at the Prince Felipe Research Center in Spain, and study author said "This work demonstrates that hybrid methods combining 5C maps with the Integrative Modeling Platform can produce genome-wide 3D models of unprecedented resolution, which for the first time allows for spatially pinpointing regulatory elements responsible of organizing the structure of a genome."

The resulting 3D models of the Caulobacter crescentus genome, in conjunction with fluorescent microscopy, illustrate that the parS sequence, located in the pole of one arm of the chromosome, potentially served as an anchor for the genome and were instrumental in defining its overall structure.

To unravel the role the parS site plays in the 3D organization of the chromosomal structure, Dekker and colleagues constructed mutant bacteria in which the parS site had been moved away from its normal position. Building 3D models of the shape of the mutated bacteria, they observed a change in the chromosome's structure; the entire genome had rotated clockwise.

Changing the position of the parS site had resulted in a large-scale reorganization of the chromosome's shape that repositioned these sites at the cell's poles. Mark Umbarger, a post doctoral fellow at Harvard Medical School and study author notes, "Strikingly, we found that moving sequence elements which are no larger than 500 base pairs, led to a change in the conformation of all of the 4 million base-pairs of the chromosome!"

"Our study is the first to test the effect of altering chromosome architecture. We were able to show that a very simple system, with a single anchor, can orient the whole chromosome inside of the cell." said Esteban Toro, PhD, one of the study authors and now a post doctoral fellow at the University of Pennsylvania. "These results suggest that the parS site in Caulobacter crescentus determines the orientation and global structure of the entire chromosome and are the only sequence elements that stably anchor the chromosome to the cell."

The ability for scientists to perform structure function studies on chromosomes has the potential to yield powerful new insights into the biology of genomes. "When we began this project, most scientists were assessing the positions of a handful of genomic loci and attempting to derive general conclusions about genome structure. We were unhappy with this approach and sought to develop an integrated experimental approach to generate higher-resolution, and genome-wide insights," Umbarger said.

"This isn't something we could have predicted from just looking at the DNA sequence," said Dekker. "This study illustrates how an investigation of 3D genomic structure can provide insights into how the complex relationships between genome sequence and structure can impact function. By studying genomic architecture we can potentially identify new classes of genomic sequences that are important in chromosome function and structure that we otherwise couldn't."

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[ Back to EurekAlert! ] Public release date: 21-Oct-2011
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Contact: Jim Fessenden
james.fessenden@umassmed.edu
508-856-2000
University of Massachusetts Medical School

3-D models yield new insights into role of parS sites in bacterial cells

WORCESTER, Mass. A team of researchers at the University of Massachusetts Medical School, Harvard Medical School, Stanford University and the Prince Felipe Research Centre in Spain have deciphered the complete three-dimensional structure of the bacterium Caulobacter crescentus's chromosome. Analysis of the resulting structure published this week in Molecular Cell has revealed new insights into the function of genetic sequences responsible for the shape and structure of this genome.

Scientists know that the three-dimensional shape of a cell's chromosome plays a role in how genetic sequences and genes are regulated. However, technical challenges have limited genome-wide analysis of a chromosome's architecture that would allow for simultaneous identification of the elements involved in shaping it and analysis of specific features of the structure. In this study, researchers used high-throughput chromatin interaction detection; next-generation DNA sequencing; computational modeling; and fluorescent microscopy to build the first 3D model of the architecture of the bacteria's chromosome and analyze the resulting structures. This new experimental approach revealed novel characteristics of a specific genetic sequence called the parS site, which helps to define the chromosome's shape.

"What we've shown is that it's possible to combine molecular biology with 3D modeling technology to perform studies that tell us novel things about how genomes fold and identify the genetic sequences that are responsible." said Job Dekker, PhD, a pioneer in chromosome interaction detection technologies, professor of biochemistry & molecular pharmacology at the University of Massachusetts Medical School, and one of the authors on the study.

Dekker and colleagues used "5C" technology to map more than 28,700 contact points in the Caulobacter crescentus's genome and used these contacts to approximate spatial distance in the folded chromosome. Plugged into a computational model, these contact points yielded a structural model of the bacterial chromosome which was strikingly beautiful: ellipsoidal in shape with arms helically arranged on either side.

Marc A. Marti-Renom, PhD, a computational biologist who leads the Structural Genomics Laboratory at the Prince Felipe Research Center in Spain, and study author said "This work demonstrates that hybrid methods combining 5C maps with the Integrative Modeling Platform can produce genome-wide 3D models of unprecedented resolution, which for the first time allows for spatially pinpointing regulatory elements responsible of organizing the structure of a genome."

The resulting 3D models of the Caulobacter crescentus genome, in conjunction with fluorescent microscopy, illustrate that the parS sequence, located in the pole of one arm of the chromosome, potentially served as an anchor for the genome and were instrumental in defining its overall structure.

To unravel the role the parS site plays in the 3D organization of the chromosomal structure, Dekker and colleagues constructed mutant bacteria in which the parS site had been moved away from its normal position. Building 3D models of the shape of the mutated bacteria, they observed a change in the chromosome's structure; the entire genome had rotated clockwise.

Changing the position of the parS site had resulted in a large-scale reorganization of the chromosome's shape that repositioned these sites at the cell's poles. Mark Umbarger, a post doctoral fellow at Harvard Medical School and study author notes, "Strikingly, we found that moving sequence elements which are no larger than 500 base pairs, led to a change in the conformation of all of the 4 million base-pairs of the chromosome!"

"Our study is the first to test the effect of altering chromosome architecture. We were able to show that a very simple system, with a single anchor, can orient the whole chromosome inside of the cell." said Esteban Toro, PhD, one of the study authors and now a post doctoral fellow at the University of Pennsylvania. "These results suggest that the parS site in Caulobacter crescentus determines the orientation and global structure of the entire chromosome and are the only sequence elements that stably anchor the chromosome to the cell."

The ability for scientists to perform structure function studies on chromosomes has the potential to yield powerful new insights into the biology of genomes. "When we began this project, most scientists were assessing the positions of a handful of genomic loci and attempting to derive general conclusions about genome structure. We were unhappy with this approach and sought to develop an integrated experimental approach to generate higher-resolution, and genome-wide insights," Umbarger said.

"This isn't something we could have predicted from just looking at the DNA sequence," said Dekker. "This study illustrates how an investigation of 3D genomic structure can provide insights into how the complex relationships between genome sequence and structure can impact function. By studying genomic architecture we can potentially identify new classes of genomic sequences that are important in chromosome function and structure that we otherwise couldn't."

###


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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.


Source: http://www.eurekalert.org/pub_releases/2011-10/uomm-rgf102111.php

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