UT Southwestern reports promising new approach to drug-resistant infections

Public release date: 15-Oct-2013
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Contact: Debbie Bolles
debbie.bolles@utsouthwestern.edu
214-648-3404
UT Southwestern Medical Center

DALLAS Oct. 15, 2013 A new type of antibiotic called a PPMO, which works by blocking genes essential for bacterial reproduction, successfully killed a multidrug-resistant germ common to health care settings, UT Southwestern Medical Center researchers report.

The technology and new approach offer potential promise against the growing problem of antibiotic resistance, the researchers said.

The pathogen (germ) called Acinetobacter can cause infections from pneumonia to serious blood or wound infections, posing greater risk to people with weakened immune systems, chronic lung disease, or diabetes, according to the Centers for Disease Control and Prevention (CDC). Acinetobacter infection mainly affects hospitalized patients or those in long-term care facilities, such as those on ventilators or with urinary catheters or patients treated for open wounds. The CDC considers Acinetobacter, which is resistant to many antibiotics, one of the top bacterial infection threats in the U.S.

In the study in todays Journal of Infectious Diseases, PPMOs designed to combat two strains of Acinetobacter reduced the number of infectious bacteria in mice by more than 90 percent. Survival of infected mice also improved with the treatment. One of the targeted strains was A. baumannii, a dangerous type that accounts for about 80 percent of reported Acinetobacter infections, according to the CDC.

We set out to target specific genes in Acinetobacter in an effort to inhibit the bacteriums growth, said Dr. David Greenberg, assistant professor of internal medicine and microbiology and senior author of the study. With infections from drug-resistant pathogens rising rapidly, there is an urgent need to come up with new approaches such as the use of PPMOs to spur antibiotic development.

The technology that created the synthetic PPMO could be used to develop similar antibiotics targeting other bacteria and viruses, he added.

We believe there is a lot of promise in developing new antibiotics that target specific pathogens as opposed to so-called broad-spectrum antibiotics that target whole classes of bacteria, said Dr. Greenberg.

Whereas broad-spectrum antibiotics can kill off multiple pathogens, PPMOs are pathogen-specific and work by silencing essential genes that help that particular strain of bacteria or virus grow. A PPMO, or peptide-conjugated phosphorodiamidate morpholino oligomer, mimics the structure of a nucleic acid and binds to mRNA, preventing the formation of proteins. PPMOs have not been tested in humans, although a compound of similar chemical structure is being tested as a therapy in Duchenne muscular dystrophy patients.

More research is needed before the PPMOs are ready for human testing, said Dr. Greenberg, who was assisted in the study by Kimberly Marshall-Batty, a senior research associate in internal medicine.

Future studies will involve development and testing of PPMOs targeting other specific bacteria and virus types. Researchers also may try to create a PPMO that silences genes involved in antibiotic resistance.

###

The study involved researchers from UT Southwestern, Oregon State University, and Sarepta Inc., a Massachusetts-based pharmaceutical company that supplied the PPMOs for testing. Support for the study was provided by the National Institutes of Health. Prior to this study, Dr. Greenberg had served as a consultant to Sarepta. The studys lead author at Oregon State formerly worked at AVI BioPharma, now called Sarepta, and holds several PPMO patents. Neither holds any equity interest or options in Sarepta.

About UT Southwestern Medical Center

UT Southwestern, one of the premier academic medical centers in the nation, integrates pioneering biomedical research with exceptional clinical care and education. The institutions faculty includes many distinguished members, including five who have been awarded Nobel Prizes since 1985. Numbering more than 2,700, the faculty is responsible for groundbreaking medical advances and is committed to translating science-driven research quickly to new clinical treatments. UT Southwestern physicians provide medical care in 40 specialties to nearly 90,000 hospitalized patients and oversee more than 1.9 million outpatient visits a year.

This news release is available on our home page at utsouthwestern.edu/home/news/index.html

To automatically receive news releases from UT Southwestern via email, subscribe at utsouthwestern.edu/receivenews

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Public release date: 15-Oct-2013
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Contact: Debbie Bolles
debbie.bolles@utsouthwestern.edu
214-648-3404
UT Southwestern Medical Center

DALLAS Oct. 15, 2013 A new type of antibiotic called a PPMO, which works by blocking genes essential for bacterial reproduction, successfully killed a multidrug-resistant germ common to health care settings, UT Southwestern Medical Center researchers report.

The technology and new approach offer potential promise against the growing problem of antibiotic resistance, the researchers said.

The pathogen (germ) called Acinetobacter can cause infections from pneumonia to serious blood or wound infections, posing greater risk to people with weakened immune systems, chronic lung disease, or diabetes, according to the Centers for Disease Control and Prevention (CDC). Acinetobacter infection mainly affects hospitalized patients or those in long-term care facilities, such as those on ventilators or with urinary catheters or patients treated for open wounds. The CDC considers Acinetobacter, which is resistant to many antibiotics, one of the top bacterial infection threats in the U.S.

In the study in todays Journal of Infectious Diseases, PPMOs designed to combat two strains of Acinetobacter reduced the number of infectious bacteria in mice by more than 90 percent. Survival of infected mice also improved with the treatment. One of the targeted strains was A. baumannii, a dangerous type that accounts for about 80 percent of reported Acinetobacter infections, according to the CDC.

We set out to target specific genes in Acinetobacter in an effort to inhibit the bacteriums growth, said Dr. David Greenberg, assistant professor of internal medicine and microbiology and senior author of the study. With infections from drug-resistant pathogens rising rapidly, there is an urgent need to come up with new approaches such as the use of PPMOs to spur antibiotic development.

The technology that created the synthetic PPMO could be used to develop similar antibiotics targeting other bacteria and viruses, he added.

We believe there is a lot of promise in developing new antibiotics that target specific pathogens as opposed to so-called broad-spectrum antibiotics that target whole classes of bacteria, said Dr. Greenberg.

Whereas broad-spectrum antibiotics can kill off multiple pathogens, PPMOs are pathogen-specific and work by silencing essential genes that help that particular strain of bacteria or virus grow. A PPMO, or peptide-conjugated phosphorodiamidate morpholino oligomer, mimics the structure of a nucleic acid and binds to mRNA, preventing the formation of proteins. PPMOs have not been tested in humans, although a compound of similar chemical structure is being tested as a therapy in Duchenne muscular dystrophy patients.

More research is needed before the PPMOs are ready for human testing, said Dr. Greenberg, who was assisted in the study by Kimberly Marshall-Batty, a senior research associate in internal medicine.

Future studies will involve development and testing of PPMOs targeting other specific bacteria and virus types. Researchers also may try to create a PPMO that silences genes involved in antibiotic resistance.

###

The study involved researchers from UT Southwestern, Oregon State University, and Sarepta Inc., a Massachusetts-based pharmaceutical company that supplied the PPMOs for testing. Support for the study was provided by the National Institutes of Health. Prior to this study, Dr. Greenberg had served as a consultant to Sarepta. The studys lead author at Oregon State formerly worked at AVI BioPharma, now called Sarepta, and holds several PPMO patents. Neither holds any equity interest or options in Sarepta.

About UT Southwestern Medical Center

UT Southwestern, one of the premier academic medical centers in the nation, integrates pioneering biomedical research with exceptional clinical care and education. The institutions faculty includes many distinguished members, including five who have been awarded Nobel Prizes since 1985. Numbering more than 2,700, the faculty is responsible for groundbreaking medical advances and is committed to translating science-driven research quickly to new clinical treatments. UT Southwestern physicians provide medical care in 40 specialties to nearly 90,000 hospitalized patients and oversee more than 1.9 million outpatient visits a year.

This news release is available on our home page at utsouthwestern.edu/home/news/index.html

To automatically receive news releases from UT Southwestern via email, subscribe at utsouthwestern.edu/receivenews

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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/2013-10/usmc-usr101513.php
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Title beckons as Vettel denies Grosjean and Webber for fourth Suzuka win | 2013 Japanese Grand Prix review

Sebastian Vettel^[1] scored his fourth victory at Suzuka in five years to move within touching distance of the world championship.

But this was no straightforward lights-to-flag win. As well as the anticipated threat from pole sitting team mate Mark Webber^[2] he also had to repeal an unexpected attack from another rival.

Grosjean gets a flier

With two Red Bulls occupying the front row of the grid and Webber ahead for the first time this year, pre-race speculation centred on how Red Bull would manage the inevitable fight for victory between two mutually hostile drivers.

As Romain Grosjean^[3] headed to the grid he was preoccupied by thoughts of his collision with Webber at the start of the same race last year. Thoughts of taking on the Red Bulls were far from his mind.

“We never thought we would be able to challenge the Red Bulls,” he said after the chequered flag had fallen. That had all changed within seconds of the red lights going out.

“When I dropped the clutch I said ‘woah, woah, that’s a good one, come on, come on go for it!’” was how Grosjean described his rocket ship getaway from the second row of the grid. While the Red Bulls dawdled the black-and-gold E21 dodged past them on the right and shot into an unlikely lead.

Lewis Hamilton^[4] had also got away better than the Red Bulls from third place, but in trying to squeeze between them had made slight contact with Vettel’s front wing. That punctured his tyre, causing damage to the rear of the car which later proved terminal.

There were anxious faces on the Red Bull pit wall as they scrutinised images of Vettel’s wing and data from the car. Back in Milton Keynes Adrian Newey pored over the same material. The team gave the thumbs-up.

Massa rebels

The marshals quickly recovered the wrecks of Jules Bianchi^[5] and Giedo van der Garde’s cars following their first-lap tangle without the need for the Safety Car. Webber gave Grosjean a few laps of attention with his DRS before dropping out of range on lap six.

Vettel didn’t even bother pressing the cars ahead at this point, allowing the usual two-second gap to open up quickly: “We took into account that we lap a second a lap slower for two or three laps compared to them in order to get the range in the next stint and then tried to extend that to really put them under pressure towards the end.”

He wasn’t under threat from Nico Rosberg^[6] behind. Next were the two Ferraris, Felipe Massa leading Fernando Alonso.

This was very much against the expressed wishes of the team who wanted Massa to pull over^[7] as he had done three races ago at Monza. But that was before his contract with the team was terminated, and Massa was now making good on his promise to put his interests before his team mate’s.

“Multi function strategy A now please” urged race engineer Rob Smedley, the last two words a dead giveaway that Massa was not complying. Sauber took advantage of the situation, bringing Nico Hulkenberg^[8] in early enough to claim an advantage over both Ferraris.

Hulkenberg said it was a “brilliant call by the team to pit early [and], undercut the Ferraris”.

“And then we found ourselves again in front of them they’d be really upset and angry about that because again I think they lost a lot of time behind us because really they were quicker than us.”

Strategy switch at Red Bull

Webber was the first of the lead trio to pit on lap 11. Tellingly, he hadn’t closed up to Grosjean in the preceding laps: this was a stop out of necessity, not an attempt to leapfrog the Lotus.

“Mark was going through the tyre quicker than Sebastian,” confirmed Christian Horner after the race. “We had to pit because effectively he’d run out of tyres on that stint which then puts the next two stints under pressure.”

Grosjean covered off Webber on the next lap. He switched to the hard tyres which Lotus had struggled with during practice after missing some running on Friday when Kimi Raikkonen^[9] had spun. “The pace dropped a little bit,” said Grosjean.

Vettel locked up as he reached the pit lane speed limit lane when he made his first pit stop on lap 14. Like Grosjean, this was to be his first of two pit stops.

Just 11 laps later, Webber was back in for the second time as the team opted to switch him to a three-stop strategy. “I was a little bit surprised,” he said.

“I asked was it the right thing to do because I felt we could get to the lap we were looking to get to.” It dropped him immediately into clear air as problems for cars behind gave Red Bull the chance to put their cars on differing strategies and maximise the pressure they were applying to Grosjean^[10].

Alonso makes gains

A gap had opened up behind them as Massa and Rosberg had been taken out of the equation with drive-through penalties for pit lane infractions.

Before Massa served his penalty Alonso had forcibly taken his position, capitalising on a momentary hold-up as they passed Daniel Ricciardo^[11], who ran a long first stint on hard tyres.

Raikkonen also took the opportunity to demote Esteban Gutierrez who had shot forward from 14th on the grid to run in the points places.

It took until lap 46 for Alonso to find a way past the increasingly tyre-troubled Hulkenberg. “It was a bit of a deja vu from Korea,” said the Sauber driver. “I could see Alonso fighting and biting into his steering wheel and trying everything.” He eventually got a run in the DRS zone and reclaimed the place.

Vettel attacks

Having cosseted his tyres for 37 laps Vettel cashed in his chips with 16 laps to go, pitting for an unused set of hard tyres that would see him through till the end of the race. His tyres were eight laps younger than Grosjean’s and he immediately went on maximum attack, hounding the Lotus into the chicane.

Accelerating towards the start line Vettel had the DRS advantage and Grosjean couldn’t move across quickly enough to stop the Red Bull drawing alongside and past. But that only put Vettel into second place. His team mate was up ahead, until two laps later he pitted for the last time and came out four seconds behind Grosjean.

“I knew that in the last stint, once we got past Romain, I knew that Mark was the biggest threat from behind,” said Vettel. “He was on fresher tyres and pretty quick.”

While he tried to leave something in his tyres to fight with if he needed it, Vettel fumed at the lapped traffic, most of all Perez who he urged race director Charlie Whiting to show blue flags to. “Charlie get him out the way that is not fair,” pleaded Vettel.

Despite the advantage of softer tyres than Grosjean, and ones that were most likely several laps newer, Webber spent half-a-dozen laps staring at the Lotus’s rear wing. “At the end of the race, the DRS is not as effective because you’re on the [rev] limiter,” he explained.

But while Perez had vexed Vettel, he inadvertently helped out Webber. Grosjean went deep at the hairpin as he caught the McLaren on lap 50. They passed the silver car in the right-hander approaching Spoon and Webber drew alongside Grosjean, forcing him off-line. The Red Bull tracked the Lotus down the hill and through the chicane, and finally Webber was close enough and quick enough to take the DRS advantage and complete the pass.

Webber was generous in his assessment of a rival who he’d labelled a “first-lap nutcase” after being taken out by him on the first lap 12 months ago. “The backmarkers didn’t work out for Romain, it’s a bit of a nightmare when you catch so many guys,” he said. “They all want the DRS, they all want to fight and in the end, it was beneficial for me to pounce when Romain got not the best run with the backmarkers, which was no fault of his own.”

Despite having finally passed Grosjean, Webber’s hopes of catching Vettel were over. The other RB9 was nine seconds up the road and the race was almost over.

Last-lap scraps

Also on the list of drivers Perez had irritated was Rosberg. The Mercedes driver took exception to his defending at the chicane which resulted in contact between the two.

Rosberg had little sympathy for the consequences that had for Perez’s race: “It was very good that he punctured his tyre and I had nothing,” he said. “It worked out perfectly, it got him out of the way.”

But perhaps the hardest racing was going on between two team mates. Pastor Maldonado^[12] lunged down the inside of Valtteri Bottas on the final lap, barging the other Williams aside to claim an inconsequential 16th place.

Bottas made his displeasure clear afterwards but given the miserable year the team has endured deputy team principal Claire Williams has far bigger things to worry about. “We allow our drivers to race and that’s what they were doing on that last lap,” she stated afterwards.

The chicane was the place to watch in the closing laps as Raikkonen executed a superb move on the outside of Hulkenberg for fifth place. Hulkenberg having fallen to sixth, Gutierrez joined him in the points for the first time this year.

Rosberg had to settle for eighth ahead of Jenson Button^[13], who persevered in a duel with Massa.

Vettel set to clinch title

In the second half of 2013 Vettel has turned a successful season into crushing, 2011-style dominance. Suzuka was his fifth win in a row – a standard achieved only by an elite few drivers the sport’s 64-year history.

An even greater feat – a fourth consecutive world championship – now beckons. It will take a surprise result in India to delay it any further.

But Vettel’s affection for Suzuka runs deep and in the immediate aftermath of it was this he wanted to savour – even more so than the prospect of another title.

“I’ve won now four times here in Suzuka, which is incredible,” he said. “I’m really looking forward to next year, to be honest.”

“I think we’ve proven in the last couple of years that we never give up. I think we’ve won one or two championships because of that. Obviously this year it looks very good at this stage – but it’s not over before it’s over.”

2013 Japanese Grand Prix

Browse all 2013 Japanese Grand Prix articles^[14]

Images © Red Bull/Getty, Ferrari/Ercole Colombo, Lotus/LAT, Sauber

Share this with your friends:

References

1. ^{^} Sebastian Vettel (www.f1fanatic.co.uk)
2. ^{^} Mark Webber (www.f1fanatic.co.uk)
3. ^{^} Romain Grosjean (www.f1fanatic.co.uk)
4. ^{^} Lewis Hamilton (www.f1fanatic.co.uk)
5. ^{^} Jules Bianchi (www.f1fanatic.co.uk)
6. ^{^} Nico Rosberg (www.f1fanatic.co.uk)
7. ^{^} 2013 Japanese Grand Prix lap times and fastest laps (www.f1fanatic.co.uk)
8. ^{^} Nico Hulkenberg (www.f1fanatic.co.uk)
9. ^{^} Kimi Raikkonen (www.f1fanatic.co.uk)
10. ^{^} 2013 Japanese GP tyre strategies and pit stops (www.f1fanatic.co.uk)
11. ^{^} Daniel Ricciardo (www.f1fanatic.co.uk)
12. ^{^} Pastor Maldonado (www.f1fanatic.co.uk)
13. ^{^} Jenson Button (www.f1fanatic.co.uk)
14. ^{^} Browse all 2013 Japanese Grand Prix articles (www.f1fanatic.co.uk)

Source: http://feedproxy.google.com/~r/f1fanatic/~3/JcbkV519Kx4/
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Colts lead Chargers 3-0 on Vinatieri's field goal

SAN DIEGO (AP) — Adam Vinatieri kicked a 30-yard field goal on the game's first possession, and the Indianapolis Colts led the San Diego Chargers 3-0 after one quarter Monday night.

The Colts opened the game with a flea-flicker, with Trent Richardson taking the handoff and tossing the ball back to Andrew Luck, who completed a 35-yard pass to Reggie Wayne. The drive bogged down at the Chargers 11, leading to Vinatieri's field goal.

Philip Rivers' first four passes for San Diego were incomplete. Then he connected with rookie Keenan Allen on a 13-yarder on third-and-15 from the Chargers 33.

The Colts were trying to take a two-game lead in the AFC South.

Colts coach Chuck Pagano is the older brother of Chargers defensive coordinator John Pagano.

The Chargers were without three starters: linebackers Jarret Johnson and Donald Butler, and left guard Chad Rinehart. The Colts were without safety LaRon Landry.

___

AP NFL website: www.pro32.ap.org

Source: http://news.yahoo.com/colts-lead-chargers-3-0-vinatieris-field-goal-012533305--spt.html
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Five Essential Tools for the Left-Handed Chef

With only about one in 11 people actually being left-handed, it's no wonder why the world is built for righties. Still, this design discrepancy can make mundane household tasks far more dismemberful than need be. Here are five kitchen tools every southpaw should own.

Read more...

Source: http://gizmodo.com/five-essential-tools-for-the-left-handed-chef-1443996982
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Petting May Be Stressful for Some Cats

If your cats resist cuddling, it may be for good reason. New research suggests petting might stress out some felines.

What's more, cats living a multi-cat home may be better equipped to deal with the strains of domestic life than their solitary peers, the study researchers found.

A group of researchers aimed to find out whether there is any truth to the assumption that cats kept as single pets are more likely to have a better life than cats that share their home with other felines. [Here, Kitty, Kitty: 10 Facts for Cat Lovers]

"Many people keep groups of cats in their home and although they might seem happy together, some people have argued that because this is an unnatural setup, it is not good for their welfare," Daniel Mills, professor of veterinary behavioral medicine at England's University of Lincoln, said in a statement. "Our research shows this is not necessarily the case."

For their study, conducted in São Paulo, Brazil, Mills and colleagues collected data on 23 single-cat households, 20 two-cat households and 17 households with three or four cats. The owners completed surveys about their pets' personalities and behavior, and they also handed over samples of their felines' feces, which contain telltale traces of a stress hormone.

The cats' stress levels didn't seem to vary significantly as a function of their personality type. (The researchers had the owners rate their cats as bossy, timid or easygoing.) But younger cats (those less than 2 years old) living on their own were generally more stressed than younger cats sharing their home, the study found.

The researchers speculate that even if cats living under the same roof don't seem too chummy, they might be able to organize themselves in such a way as to avoid each other, and thus avoid stress.

"Also, and I think very intriguingly, our data suggests that cats who tolerate, rather than enjoy or dislike being petted, seem to be the most stressed," Mills added in a statement. The researchers think this finding suggests the cats that don't like petting can avoid the affectionate hand of their owners if there are other cats in the house that enjoy or tolerate petting.

The researchers warned their results should be treated with caution since there were only four cats in the study that disliked petting, according to their owners, while 13 were put in the "tolerating category" and 85 in the "enjoying" lot.

If anything, the researchers say their results highlight the importance of giving individual pets control over their environment, and cat owners shouldn't impose themselves on their pets.

"If you have several cats you should give them the choice of sharing or having their own special areas to eat, drink and go to the toilet," Mills said.

The results were detailed in the journal Physiology and Behavior.

Follow Megan Gannon on Twitter and Google+. Follow us @livescience, Facebook & Google+. Original article on LiveScience.

Copyright 2013 LiveScience, a TechMediaNetwork company. All rights reserved. This material may not be published, broadcast, rewritten or redistributed.

Source: http://news.yahoo.com/petting-may-stressful-cats-201645626.html
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STOCKS NEWS SINGAPORE-Index little changed, Noble falls

Singapore shares were little changed by midday as weakness

in commodity stocks such as Noble Group was offset by

small gains in market heavyweight Singapore Telecommunications

.

The market lacked inspiration from Wall Street, where the

S&P 500 index eased slightly after an eight-day run of gains.

The Straits Times Index was down 0.11 percent at

3,271.27 points. The MSCI index of Asia-Pacific shares outside

Japan was up 0.7 percent.

Noble fell 2.8 percent to S$1.215, while SingTel gained 0.87

percent to S$3.48. Noble was suspended from Argentina's grains

register for an investigation into unpaid taxes, according to a

media report.

"The fall is a knee-jerk reaction to the suspension but it

is unlikely to be material," said a trader.

"The index seems to be stuck in the range of 3250-3280,"

said OCBC investment analyst Carey Wong, adding that the market

is awaiting results from property firms for direction.

Property firms have been in play recently after the

Singapore government introduced new measures to cool the

residential property market.

The move triggered selling in most property stocks, but the

larger ones such as CapitaLand have rebounded.

Source: http://news.yahoo.com/stocks-news-singapore-index-little-changed-noble-falls-042357448--sector.html

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RIM unveils lower BlackBerry World price tiers, starts with the Euro, British Pound

BlackBerry-toting penny-pinchers have cause to rejoice, as RIM is introducing lower price tiers in BlackBerry World, starting with the British Pound and Euro. New price tags have yet to take hold across the board, but the the UK will see their lowest level fall from £1.00 to £0.75. When it comes to the Euro, prices will vary by country, and we spotted apps as low as €0.75 on Spain's version of the shop. According to RIM, the tweak takes currency exchange rates and VAT requirements into account, and is an effort to gain a competitive edge and catch the eyes of consumers. If you're hankering to save coin in other countries, more currencies are set to follow suit shortly after this round of changes take effect. RIM says the price adjustment is automatic, but developers who yearn to change their asking prices can sort things out at BlackBerry World's vendor portal.

Filed under: Mobile, RIM

Comments

Via: N4BB

Source: BlackBerry Developer Blog

Source: http://www.engadget.com/2013/01/28/rim-lower-pricing-tiers-blackberry-world-apps/

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