Protecting genes, one molecule at a time

Public release date: 9-Sep-2012
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Contact: Caroline Clancy
caroline.clancy@bristol.ac.uk
44-011-792-88086
University of Bristol

An international team of scientists have shown at an unprecedented level of detail how cells prioritise the repair of genes containing potentially dangerous damage. The research, published in the journal Nature and involving academics from the University of Bristol, the Institut Jacques-Monod in France and Rockefeller University in the US, studied the action of individual molecules in order to understand how cellular repair pathways are triggered.

The genetic information that forms the "instruction booklet" for cells is encoded in the molecular building blocks of DNA, and can be damaged by mutagens such as ultraviolet light or tobacco smoke, as well as by normal "wear and tear" as the cells age. If left unrepaired, such damage can kill the cells or cause them to change their behaviour and perhaps cause disease.

Cells protect themselves by producing proteins that detect the damaged building blocks, cut them out and replace them with a patch of new DNA. Most cells, including bacteria and humans, contain mechanisms that ensure that the genes that are currently in use are repaired most quickly.

The team, led by Dr Terence Strick of the Institut Jacques Monod, Paris, used single molecules of DNA stretched in a magnetic field to watch individual proteins work on an active, damaged gene. They found that more steps are needed to repair the damage than previously thought, and that the length of time that the proteins reading the gene hesitate when they reach the damage is likely to be critical for a successful handover to the proteins that repair the gene.

Dr Nigel Savery from the University's School of Biochemistry, who led the Bristol-based part of the project, said: "Finding out how different parts of the genome are repaired at different rates is critical to understanding processes as diverse as generation of antibiotic resistance in bacteria and the patterns of mutations that give rise to cancer. Studying these processes at the level of single molecules has allowed us to detect important steps that are hidden when large numbers of molecules are studied together."

###

The work in Bristol was funded by the Biotechnology and Biological Research Council (BBSRC), UK.

Paper

Paper Initiation of transcription-coupled repair characterized at single-molecule resolution" is published online (ahead of print) in the journal Nature on 9 September 2012. doi: 10.1038/nature11430

Kvin Howan1, Abigail J. Smith2, Lars F. Westblade3, Nicolas Joly1, Wilfried Grange1, Sylvain Zorman1, Seth A. Darst3, Nigel J. Savery2 & Terence R. Strick1

1. Institut Jacques Monod, CNRS, UMR 7592, University Paris Diderot, Paris, France.

2. DNA-Protein Interactions Unit, School of Biochemistry, University of Bristol, England

3. The Rockefeller University, 1230 York Avenue, New York, USA

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Public release date: 9-Sep-2012
[ | E-mail | Share ]

Contact: Caroline Clancy
caroline.clancy@bristol.ac.uk
44-011-792-88086
University of Bristol

An international team of scientists have shown at an unprecedented level of detail how cells prioritise the repair of genes containing potentially dangerous damage. The research, published in the journal Nature and involving academics from the University of Bristol, the Institut Jacques-Monod in France and Rockefeller University in the US, studied the action of individual molecules in order to understand how cellular repair pathways are triggered.

The genetic information that forms the "instruction booklet" for cells is encoded in the molecular building blocks of DNA, and can be damaged by mutagens such as ultraviolet light or tobacco smoke, as well as by normal "wear and tear" as the cells age. If left unrepaired, such damage can kill the cells or cause them to change their behaviour and perhaps cause disease.

Cells protect themselves by producing proteins that detect the damaged building blocks, cut them out and replace them with a patch of new DNA. Most cells, including bacteria and humans, contain mechanisms that ensure that the genes that are currently in use are repaired most quickly.

The team, led by Dr Terence Strick of the Institut Jacques Monod, Paris, used single molecules of DNA stretched in a magnetic field to watch individual proteins work on an active, damaged gene. They found that more steps are needed to repair the damage than previously thought, and that the length of time that the proteins reading the gene hesitate when they reach the damage is likely to be critical for a successful handover to the proteins that repair the gene.

Dr Nigel Savery from the University's School of Biochemistry, who led the Bristol-based part of the project, said: "Finding out how different parts of the genome are repaired at different rates is critical to understanding processes as diverse as generation of antibiotic resistance in bacteria and the patterns of mutations that give rise to cancer. Studying these processes at the level of single molecules has allowed us to detect important steps that are hidden when large numbers of molecules are studied together."

###

The work in Bristol was funded by the Biotechnology and Biological Research Council (BBSRC), UK.

Paper

Paper Initiation of transcription-coupled repair characterized at single-molecule resolution" is published online (ahead of print) in the journal Nature on 9 September 2012. doi: 10.1038/nature11430

Kvin Howan1, Abigail J. Smith2, Lars F. Westblade3, Nicolas Joly1, Wilfried Grange1, Sylvain Zorman1, Seth A. Darst3, Nigel J. Savery2 & Terence R. Strick1

1. Institut Jacques Monod, CNRS, UMR 7592, University Paris Diderot, Paris, France.

2. DNA-Protein Interactions Unit, School of Biochemistry, University of Bristol, England

3. The Rockefeller University, 1230 York Avenue, New York, USA

---

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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/2012-09/uob-pgo090712.php

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Obama, Democrats to make their case as convention opens

CHARLOTTE, North Carolina (Reuters) - Democrats launch their case for Barack Obama's re-election at their party convention on Tuesday, looking to draw a sharp contrast with Republican Mitt Romney and convince voters that the U.S. president deserves four more years to fix the economy.

A speech by first lady Michelle Obama caps the opening night of the three-day gathering in Charlotte, North Carolina, which concludes with Obama's acceptance of the nomination in an address on Thursday in a 74,000-seat downtown football stadium.

The convention gives Obama a chance to recapture the political spotlight from Romney and Republicans, who used their gathering last week to repeatedly attack Obama's economic leadership.

The task for Obama and his allies will be to persuade voters disappointed by his first White House term that things will be better the second time around, while portraying the budget-slashing economic remedies offered by Romney and his running mate, congressman Paul Ryan, as unacceptable alternatives.

"The real issue now in the election is: who's got the best plan going forward?" Democratic Senate candidate Elizabeth Warren of Massachusetts, who speaks to the convention on Wednesday, said on ABC's "Good Morning America" program.

"Mitt Romney has made clear what his plan is: cut taxes for the richest Americans and the biggest corporations, increase taxes on the middle class and don't make any investments in the future. Barack Obama says that's not the right way to do it," she said.

Ryan and Republicans kept the pressure on Democrats with a question they highlighted after their convention last week: Are voters better off after nearly four years of Obama?

"We're not better off than we were four years ago. Look at all the statistics," Ryan said on "Good Morning America," citing the slow economic recovery and 8.3 percent unemployment rate.

Republicans also criticized Obama for telling a Colorado television reporter on Monday night that he would give himself a grade of "incomplete" for his first term.

'A PASSING GRADE?'

"If President Obama can't even give himself a passing grade, why would the American people give him another four years?" Romney campaign spokeswoman Amanda Henneberg said.

Romney and Obama are running close in opinion polls ahead of the November 6 election, but Obama hopes to get more of a convention "bounce" in polls than Romney, who gained a few percentage points at most from the Tampa, Florida, event.

A Gallup poll on Monday showed Romney's speech last week got the worst scores of any convention acceptance address going back to 1996, when it began measuring them. Thirty-eight percent rated the speech as excellent or good; the previous worst had been Republican John McCain's in 2008, at 47 percent.

Democrats plan to use their convention to highlight the party's diversity, featuring a lineup of black, Hispanic and young speakers to appeal to the voting blocs that helped propel Obama to a comfortable victory in 2008.

The keynote speaker on Tuesday will be San Antonio Mayor Julian Castro, a Hispanic rising star in the party.

Michelle Obama's speech will counter a successful Republican convention appearance last week by Romney's wife, Ann, who helped present a softer and more personal side of Romney to voters, who polls show have had a hard time warming up to the sometimes stiff former Massachusetts governor.

"I think the first lady plays a special role because she will have personal perspective on the president's leadership - his grit and determination during a challenging time for our nation," Obama campaign spokesman Ben LaBolt said.

"She is a character witness for the president and someone who can address how he has made decisions as the nation has confronted these challenges," he said.

While Republicans focused at their convention on attacking Obama and helping voters get to know Romney, Democrats have in some ways a more difficult task of keeping up voter enthusiasm for an incumbent in tough economic times.

They will spell out Obama's successes during his first term - from ordering the mission that killed al Qaeda leader Osama bin Laden to the bailout of the auto industry.

The opening session will convene at 5 p.m. EDT, and Democrats will approve their non-binding party platform, which includes calls for higher taxes on the wealthiest Americans and support for same-sex marriage and a woman's right to abortion.

Former President Jimmy Carter will be featured in a video on Tuesday. Former President Bill Clinton will highlight Wednesday's slate of speakers in an address that could remind voters of his Democratic-led economic growth in the 1990s while appealing to the white working-class Democrats that Obama has had difficulty winning over.

The Obama campaign also plans to use the convention and Obama's speech on Thursday as an organizing tool to help them in North Carolina, a battleground state that Obama won in 2008 but polls show is too close to call this time around.

Organizers were nervously watching the weather as scattered thunderstorms were predicted for Thursday night when Obama was due to give his speech in an open-air stadium.

(Additional reporting by Eric Johnson and Susan Heavey; Editing by Alistair Bell and Eric Beech)

Source: http://news.yahoo.com/obama-democrats-case-convention-opens-050224895.html

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Iran could strike US bases if Israel attacks: Hezbollah

BEIRUT (Reuters) - Iran could hit U.S. bases in the Middle East in response to any Israeli strike on its nuclear facilities even if American forces played no role in the attack, the leader of Lebanon's Iranian-backed militant group Hezbollah said on Monday.

"A decision has been taken to respond and the response will be very great," Hezbollah Secretary-General Sayyed Hassan Nasrallah said in an interview with the Beirut-based Al Mayadeen television.

"The response will not be just inside the Israeli entity - American bases in the whole region could be Iranian targets," he said, citing information he said was from Iranian officials. "If Israel targets Iran, America bears responsibility."

Heightened Israeli rhetoric about Tehran's nuclear facilities, which the West says could be part of a weapons program, has stoked speculation that it may attack Iran before U.S. elections in November.

Prime Minister Benjamin Netanyahu urged world powers on Sunday to set a "clear red line" to convince Iran they would prevent it from obtaining nuclear arms.

Israel, thought to be the Middle East's only nuclear-armed power, views Iran's nuclear program as a threat to its regional dominance and to its very existence. Tehran says the atomic work is for peaceful purposes only.

But Netanyahu's cabinet is divided over the wisdom of attacking Iran, and Israeli officials have dropped heavy hints of a climbdown strategy, under which Netanyahu would shelve threats of an attack now in return for a stronger public pledge from President Barack Obama on conditions that would provoke U.S. action in future.

Nasrallah said there were divisions in Israel over attacking Iran. "Personally I do not expect the Israeli enemy - at least in the coming months or foreseeable future - (to wage) an attack on the Islamic Republic of Iran," he said.

Nasrallah pointed to the fragile global economy, which would be weakened further by any sharp rise in crude oil prices stemming from conflict in the Gulf, and to likely Israeli casualties in any war with Iran.

"Netanyahu and (Defence Minister Ehud) Barak inflate the benefit and play down the cost," he said, referring to Barak's estimates that Israel could suffer up to 500 fatalities in any conflict aimed at wiping out Iran's nuclear facilities.

Hezbollah guerrillas fought a 34-day war with Israel six years ago in which 1,200 people in Lebanon, mostly civilians, and 160 people in Israel, mostly soldiers, were killed.

War with Iran would be more deadly, Nasrallah said. "We don't know what will happen in the region."

NO CHEMICAL WEAPONS

He repeated a warning he made last month that Hezbollah could cause widespread destruction if it came into conflict with Israel again, but denied that the Shi'ite Islamist guerrilla and political movement would ever use chemical weapons.

"We do not have chemical weapons and we will not use chemical weapons," Nasrallah said. "The use of chemical weapons is forbidden - for us that is absolute.

Unrest in neighboring Syria, which acknowledged for the first time in July that it possessed chemical or biological weapons, has led to Western fears that those weapons might fall into the hands of Islamist groups including Hezbollah.

"I do not need chemical weapons - regardless of the religious or practical position," Nasrallah said, addressing Israel. "You have factories, and you have bases, and compounds, and I have rockets."

Israel had several "weak points" which could be targeted, including "economic, industrial, electrical, chemical and nuclear" sites, the Hezbollah leader said.

Even if Israel launched a first strike attack on Lebanon, destroying a large part of Hezbollah's missile arsenal, the militant group would retain the capacity to hit back with deadly force, he added.

Two weeks ago Nasrallah said Hezbollah could kill tens of thousands of Israelis by hitting targets with what he described as precision-guided missiles.

"Hitting these targets with a small number of rockets will turn ... the lives of hundreds of thousands of Zionists to real hell," he said at the time.

(Writing by Dominic Evans; Editing by Alison Williams)

Source: http://news.yahoo.com/iran-could-strike-u-bases-israel-attacks-hezbollah-193805679.html

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15 police injured in N. Ireland sectarian riots

Fifteen Northern Irish police officers were injured during a second consecutive night of sectarian rioting in north Belfast, police said Tuesday.

Officers fired six baton rounds and used water cannons during the unrest, which first erupted on Sunday when loyalists from the Protestant community attempted to disrupt a march by Catholic republicans.

It bought the total number of police injured over both nights to 62 after 47 officers were hurt in Sunday night's disorder, including four officers who received hospital treatment before being released.

Three of the officers injured on Monday were also hospitalised but later released, the Police Service of Northern Ireland said.

On both nights, loyalists and republicans gathered in the Carlisle Circus area in the north of the city and pelted police with petrol bombs, bricks, stones and fireworks as they tried to keep the two groups apart.

A van was also hijacked on Monday and pushed into police lines prompting police to deploy four water cannons.

The chairman of the Northern Ireland Police Federation, Terry Spence, praised the "bravery and courage" of the frontline officers, saying it was "in stark contrast to that of the cowardly thugs responsible for trying to murder them".

Northern Irish assistant chief constable Will Kerr said: "I am very proud of how my colleagues stood in the face of danger, working to bring this situation under control.

"But I am saddened and angry that again we find ourselves subject to serious violence from the communities we serve.

"Let me be clear, we have made seven arrests already and with a robust criminal justice strategy in place, there will be more."

Around 3,500 people died in the three decades of sectarian violence between Northern Ireland's Catholics and Protestants that largely ended with a 1998 peace agreement, though sporadic unrest and bomb threats continue.

Source: http://news.yahoo.com/47-police-injured-n-ireland-sectarian-rioting-082641421.html

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San Diego Commercial Plumbing Contractors - IdeaMarketers.com

by artmark12 Mark
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Request Reprint | Print | About Author | Report Problem | Tweet This Despite the fact that you are constructing a flat or a hotel or any other new building for commercial purposes, the end product is going to be good if and only if you hire the best contractors. For plumbing services in San Diego, you should insist on getting San Diego Commercial Plumbing Contractors who experienced & are on familiar terms with the best plumbing systems based on your needs. When getting into a contract with San Diego Commercial Plumbing Contractors, you must make sure that your San Diego Commercial Plumbing Contractors include the following mandatory plumbing services in the contract:

* Your San Diego Commercial Plumbing Contractors must make use of water source heat pumps as these pumps make use of heat exchangers so as to transmit heat from water into the building. So San Diego Commercial Plumbing Contractors must provide these as they seem to be the best Real Energy Savers for any commercial place.

* Your San Diego Commercial Plumbing Contractors must also provide climate control systems namely four pipe chilled & hot water systems as they are very important for making the working environment a healthy & comfortable as these systems keep the humidity & temperature levels at a constant level so that the paint finishes, art work & other decorations will last long for a life time.

* Your San Diego Commercial Plumbing Contractors must also provide quality underground piping as a part of the contract. They should ensure that it is dope properly avoiding regular cost for repairs.

* Your San Diego Commercial Plumbing Contractors must as well do proper septic & sewage piping. As it is a known fact that having a toilet back up is a major problem in the house itself so now one think of how huge the problem can turn out to be at commercial places like large hotels where there is no proper septic & sewage piping. Your San Diego Commercial Plumbing Contractors must make use of the latest technologies and quality materials for constructing the septic and sewage systems which require minimal maintenance & are problem free.

These are just a few mandatory plumbing services your San Diego Commercial Plumbing Contractors must provide as a part of the commercial plumbing contracts.

If you are an online enthusiast, who is looking for information on Sandiegocommercialplumbing, the reviews and articles provided by the author could be the best option. You will find all the necessary information and details on San Diego Commercial Plumbing Contractors.

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Attend the 23rd Annual Colorado Brewers' Festival ... - Scott K. James

Nothing indicates a greater love for beer than a willingness to risk the need to visit a porta-potty on a 100-degree day. NoCo?must be rife with beer lovers because that fear did not keep folks away from the twenty-third annual Colorado Brewers? Festival at Civic Center Park in Old Town Fort Collins last weekend.

Over forty Colorado breweries and dozens of food and merchandise vendors braved the heat at this year?s festival to serve the thirsty thousands who attended. Sure the thermometer pushed triple digits, but it only seemed appropriate as we set out to complete NoCo50 Challenge No. 24: Attend the Colorado Brewers? Festival.

While Sadie is not big on the brewed beverage, I consider myself a beer guy. I like the stuff and have a rather adventuresome barley pop palette. So the Colorado Brewers? Festival presented me with the perfect opportunity to sample the products of so many brewers? hard work.

I am thankful to live in an area many describe as the ?Napa Valley for beer.? I understand why wineries flock to the Napa area: it?s the climate conducive to growing grapes. Barley and hops are not as picky and can be?grown in nearly all temperate climates. So why do brewers choose NoCo?for their home? I asked Russell Fruits, one of the Founders of Grimm Brothers Brewhouse in Loveland, to help me solve that riddle.

?Northern Colorado is home to a very educated, very artistic populace that appreciates nicer things,? said Fruits, who will celebrate Grimm Brothers? second anniversary in July. ?Beer is artistically driven. You can make world class beer anywhere. It?s just reliant on the guy who is brewing it having a consumer who appreciates it. That appreciative consumer is easily found in Northern Colorado.?

Steve Jones is the self-described ?beer maker? at Pateros Creek Brewing Company. Steve added availability of natural resources to Fruits? demand-based beer model.

?We really have great water here to brew some fantastic beer,? Jones explained. ?We also have some outstanding older breweries that have helped pave the way for smaller breweries such as myself. Colorado State University is starting to teach classes in the fermentation sciences. There is also a very large home brewing community here.?

If there was a common theme among the brewers, other than the product itself, it was the fact that many were brewing beer in their kitchens and basements just a few short years ago.

?I started brewing in 2004 when my wife bought me a brew kit from the internet. I stared with a couple batches a month.? Jones said. ?I joined a local homebrew club known as The Liquid Poets. I learned a lot from great brewers in the area and built good relationships in the brewing community. Pateros creek has existed for just over a year now.?

Grimm Brothers? Russel Fruits tells a similar tale.

?My two partners and I all started as home brewers,? said Fruits. ?I?m a huge foodie?and I?ve always been in to really good food and really good beer. All three of us ran up a bunch of credit cards, bought some equipment and started brewing beer. We expanded and began bottling in December. We?re undergoing another expansion now and hope to be statewide in August.?

Judging by the lines at the Grimm Brothers? tent and my personal fondness for their brew named ?Fearless Youth,? the high interest plastic gamble should pay off. The professional judges agree. Grimm Brothers? best selling beer, Little Red Cap, recently earned a gold medal in the Alt category at the Great American Beer Festival.

Home brewers are big attendees of the Colorado Brewers? Festival as well. Adorned in chilly?necks to ward off the heat, Mark and Robin Lindeman of Windsor came to the festival Sunday to enjoy a couple of beers and maybe pick up on a tip or trick. I asked Mark, who just cranked out his second batch of beer, what attracted him to home brewing.

?I like to drink beer,? Lindeman said. I sure can ask the probing questions. ?I had a German Alt beer as my first batch and an IPA as my second. They turned out pretty good!? Lindeman?s pick for favorite went to New Belgium?s ?Lips of Faith? beer.

While I did not sample the wares of every brewer, a new favorite emerged from those I did try; Pateros?Creek?s Cache la Porter. I like dark, robust beers. Not as heavy and lacking in the coffee notes present in most porters, this well balanced brew had a hint of chocolate. I asked Steve Jones from where the inspiration for my new frothy friend came.

?Most of my beers are old, home brew?recipes,? Jones said. ?Cache la Porter is a play on the name of the river Cache la Poudre?and was developed originally for a homebrew competition for the porter style. It was popular among friends and colleagues and has become our flagship beer. It represents us in both flavor and name so it fits really well!?

I found it quite yummy. That?s a highly technical, beer taster?s term. I?m no connoisseur. I just know what I like. Looking for a non-bias and more seasoned opinion, I set out to find a connoisseur. I found Joseph and Kimberly Rodriguez of Fort Collins.

?I am a connoisseur,? Joseph said with the resolution of a child professing his good behavior at Christmas. Already known for my probing questions, I asked what makes someone a beer connoisseur.

?A connoisseur is not only someone who loves beer,? Rodriguez explained, ?They reach out for it. They love the ingredients, the taste, and everything that is involved in the process. They have a desire to try every beer they can. They develop a relationship with beer.?

To think I?ve been accused of struggling to develop and maintain relationships. For those who want to develop a relationship with the brewed and bottled adult beverage, the Colorado Brewers? Festival is a lot like speed dating. Now excuse me, my sixty seconds at this table are up.

Source: http://www.scottkjames.com/?p=754

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