New synthetic molecules treat autoimmune disease in mice

Tuesday, December 27, 2011

A team of Weizmann Institute scientists has turned the tables on an autoimmune disease. In such diseases, including Crohn's and rheumatoid arthritis, the immune system mistakenly attacks the body's tissues. But the scientists managed to trick the immune systems of mice into targeting one of the body's players in autoimmune processes, an enzyme known as MMP9. The results of their research appear today in Nature Medicine.

Prof. Irit Sagi of the Biological Regulation Department and her research group have spent years looking for ways to home in on and block members of the matrix metalloproteinase (MMP) enzyme family. These proteins cut through such support materials in our bodies as collagen, which makes them crucial for cellular mobilization, proliferation and wound healing, among other things. But when some members of the family, especially MMP9, get out of control, they can aid and abet autoimmune disease and cancer metastasis. Blocking these proteins might lead to effective treatments for a number of diseases.

Originally, Sagi and others had designed synthetic drug molecules to directly target MMPs. But these drugs proved to be fairly crude tools that had extremely severe side effects. The body normally produces its own MMP inhibitors, known as TIMPs, as part of the tight regulation program that keeps these enzymes in line. As opposed to the synthetic drugs, these work in a highly selective manner. An arm on each TIMP is precisely constructed to reach into a cleft in the enzyme that shelters the active bit ? a metal zinc ion surrounded by three histidine peptides ? closing it off like a snug cork. 'Unfortunately,' says Sagi, 'it is quite difficult to reproduce this precision synthetically.'

Dr. Netta Sela-Passwell began working on an alternative approach as an M.Sc. student in Sagi's lab, and continued on through her Ph.D. research. She and Sagi decided that, rather than attempting to design a synthetic molecule to directly attack MMPs, they would try trick the immune system to create natural antibodies that target MMP-9 through immunization. Just as immunization with a killed virus induces the immune system to create antibodies that then attack live viruses, an MMP immunization would trick the body into creating antibodies that block the enzyme at its active site.

Together with Prof. Abraham Shanzer of the Organic Chemistry Department, they created an artificial version of the metal zinc-histidine complex at the heart of the MMP9 active site. They then injected these small, synthetic molecules into mice and afterward checked the mice's blood for signs of immune activity against the MMPs. The antibodies they found, which they dubbed 'metallobodies,' were similar but not identical to TIMPS, and a detailed analysis of their atomic structure suggested they work in a similar way ? reaching into the enzyme's cleft and blocking the active site. The metallobodies were selective for just two members of the MMP family ? MMP2 and 9 ? and they bound tightly to both the mouse versions of these enzymes and the human ones.

As they hoped, when they had induced an inflammatory condition that mimics Crohn's disease in mice, the symptoms were prevented when mice were treated with metallobodies. 'We are excited not only by the potential of this method to treat Crohn's,' says Sagi, but by the potential of using this approach to explore novel treatments for many other diseases.' Yeda, the technology transfer arm of the Weizmann Institute has applied for a patent for the synthetic immunization molecules as well as the generated metallobodies.

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Weizmann Institute of Science: http://www.weizmann.ac.il

Thanks to Weizmann Institute of Science for this article.

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Source: http://www.labspaces.net/116320/New_synthetic_molecules_treat_autoimmune_disease_in_mice

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Chiquita Oil Sands Boycott Sparks Outcry in Canada

A U.S. banana company's boycott of oil from Canada's tar sands provoked an outcry and a counter boycott of Chiquita bananas on Tuesday. Ethicaloil.org launched an online and radio campaign calling on Canadians to stop buying bananas until Chiquita Brands International reverses its ban on using oil from the Alberta oil sands to truck its products to market. Chiquita made its announcement last week that it would direct trucking companies it uses to try to avoid using fuel refined from the oil sands. Immigration Minister Jason Kenney said on Twitter: "I gather that Chiquita Bananas has no problem with Iranian oil, but is boycotting Canadian oil. No more Chiquita bananas for me." He was echoed by MP Scott Armstrong who said, "Stand up for Canada boycott Chiquita products!" And Alberta politician Danielle Smith who is planning to challenge for the leadership of the province in the next election issued a statement calling Chiquita's actions "disappointing." "Alberta's oil sands are the most safe, secure and reliable source of energy in the world, and tremendous progress has been made in reducing emissions and environmental impacts," she said. "Personally, I will boycott Chiquita products until they reverse their ill-informed decision to avoid fuel from Alberta's oilsands. I am proud of Alberta's record of responsible resource development."

Source: http://www.industryweek.com/ReadArticle.aspx?ArticleID=26231

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Man in Santa suit killed 6 relatives: Texas police

DANNY ROBBINS Associated Press

GRAPEVINE, TEXAS ? Police in a quiet Fort Worth suburb worked Monday to piece together a family history after a man dressed in a Santa Claus suit apparently shot six relatives and himself on Christmas.

Grapevine police spokesman Sgt. Robert Eberling said the shooter showed up in the Santa outfit shortly before gunfire erupted and that the family appeared to have been opening Christmas presents. Police responding to a 911 call found four women and three men dead, along with two handguns.

?We think he was just inside there celebrating Christmas with the rest of them and decided for whatever reason that?s how he?s going to end things,? Eberling told The Associated Press.

Investigators worked through Sunday night and into Monday morning, meticulously searching the apartment where the bodies were found, along with vehicles parked outside. Police said they believe the victims were related, though some were visiting and didn?t live in the apartment.

Eberling said investigators are piecing together a ?family history,? but he declined to get into specifics. Autopsies of the shooter and the victims were being done Monday by the Tarrant County medical examiner, but it would probably be Tuesday before their identities were released, he said.

?We?re getting a clearer picture, but we?re not ready to go on the record with anything until we find out from the medical examiner absolute confirmation of identities and the manner of death,? Eberling said.

Roger Metcalf, a spokesman for the medical examiner?s office, said the victims have been tentatively identified, but the office couldn?t confirm the names because the state driver?s license fingerprint database wasn?t available on the holiday.

?In addition, we need to locate next of kin before information can be released, and our investigators are working on that as well,? Metcalf wrote in an email to the AP.

Late Sunday evening, police intently searched a sport utility vehicle parked outside the apartment. The vehicle is registered to a man who listed his residence as a home two miles away in the neighbouring suburb of Colleyville.

Thomas Ehrlich, who lives near the home in Colleyville, told the AP he heard from neighbours that police went to the house Sunday. He said it was his understanding that the man and women who once lived there were estranged.

Records show the couple had financial problems and that their home, most recently valued on the county tax rolls at $336,200, had been sold in 2010 at a foreclosure auction.

Police and firefighters rushed to the Lincoln Vineyards complex about 11:30 a.m. Sunday after receiving a 911 call in which no one was on the other end of the line. Because no one responded on the phone, police went into the apartment, located at the back of the complex.

They found the seven, aged 18 to 60, dead.

Many of the nearby apartments are vacant, and police said no neighbours reported hearing anything on a quiet Christmas morning when many people were not around.

The apparent murder-suicide involved the first homicides in Grapevine in more than a year and a half.

Source: http://www.thestar.com/news/world/article/1106995--man-in-santa-suit-killed-6-relatives-texas-police

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Rare white Christmas graces Texas panhandle (Reuters)

AUSTIN, Texas (Reuters) ? A light dusting of snow in north Texas delivered a rare white Christmas to this drought-stricken state, but the majority of the nation was seeing mild weather on Sunday.

Snow showers glazed parts of the Northeast as well, with snowy road conditions cited as a factor in a two-vehicle traffic collision that left four men dead in the town of Palermo, Maine, on Sunday.

But weather forecasters said 99 percent of Americans would see more green and brown for their Yuletide celebrations -- along with plenty of rain, according to Accuweather.com.

Other fair-weather exceptions included freeze warnings posted in the farm-rich Central Valley of California, gale warnings near the Great Lakes, and high winds that left thousands of homes without power in and around Seattle.

The wet Christmas in the Texas panhandle and Permian Basin brought some cheer for drought-weary Texans, who were seeing snow in Lubbock and Amarillo on Christmas morning and rain in the eastern part of the state.

The worst drought on record in Texas this year stoked devastating wildfires, killed as many as half a billion trees, and prompted the most serious urban water-use restrictions ever in the state.

By mid-afternoon on Sunday, at least 4 inches of snow had fallen in Amarillo, making it the second snowiest Christmas in that city's history, National Weather Service forecaster Stephen Bilodeau said.

And with winter weather advisories in effect until 6 a.m. on Monday, there was a chance that Amarillo's record for snow accumulation might be broken before midnight.

Bilodeau said he would have preferred that the snow quit early and left the afternoon safer for Christmas Day travel.

"It's a little bit too much," he said. "The white Christmas through the beginning of the day was good, but now these poor people are getting out into this stuff. There have been a few accidents, and it's ruining a few people's day today."

Not so for native Texan and conservationist Don Alexander, 55, who was spending the holiday with his wife's family in Midland, and enjoying his very first white Christmas.

"The snow is a nifty bonus," Alexander said, as his college-aged daughter posted snow pictures on her Facebook page. "The snow will certainly make this particular Christmas memorable. Winter isn't very scenic in West Texas, so the layer of snow is a nice effect. The bad part is having to wipe down the dog's paws every time he goes outside and then back in."

Far to the north, public safety officials in Maine said four men were killed in a head-on crash between an SUV and another vehicle on a road made slippery by light snowfall in Palermo, about 60 miles northeast of Portland. Police said the collision ranks as Maine's deadliest traffic wreck this year.

In the Midwest, a lack of snow was especially welcome news in Minneapolis, where a pre-Christmas storm last year dumped 17 inches of snow, causing the roof of the Metrodome, the Minnesota Viking's football stadium, to collapse.

This year, Minneapolis was without snow and basking in temperatures that climbed into the relatively balmy high-30s over the weekend, according to the National Weather Service.

Very little fresh snow was expected to fall elsewhere throughout the day on Sunday, according to Accuweather.com. But a storm in southern Ontario was forecast to move into Quebec on Sunday night and drop snow near the Great Lakes, with some accumulation expected overnight.

Residents from Watertown, New York, to Bangor, Maine -- many of whom are off work on Monday in observance of the Christmas holiday -- could wake up to an inch of snow on the ground Monday as that storm moves East.

The Weather Service posted a wind advisory for western Washington state on Sunday, warning of gusts reaching 50 miles per hour through mid-afternoon.

Utility companies reported at least 24,000 homes and businesses without electricity in Seattle and the greater Puget Sound region during the day, mostly from tree limbs blown into power lines.

Most of the Pacific Northwest was experiencing mild weather on Christmas Day, while states like Colorado and New Mexico had lingering snow leftover from a pre-Christmas storm.

(Editing by Tim Gaynor and Steve Gorman)

Source: http://us.rd.yahoo.com/dailynews/rss/us/*http%3A//news.yahoo.com/s/nm/20111226/us_nm/us_weather_christmas

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Man Escapes Death As Satellite Fragment Crashes Through His Roof [Wtf]

Andrei Krivorukov got a wonderful Christmas gift: his very own life. He saved it after a titanium ball from a Russian communication satellite crashed right into his house, escaping death by just a few feet. More »

Source: http://feeds.gawker.com/~r/gizmodo/full/~3/T4hQRtO85JE/man-miraculously-saves-his-life-as-satellite-fragment-crashes-into-his-house

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Study: San Francisco Bay oil spill damaged herring

SAN FRANCISCO -- The cargo ship accident that dumped tens of thousands of gallons of thick, tarry ship fuel into San Francisco Bay caused lasting damage to the region's once-plentiful schools of Pacific herring, the bay's only commercially fished species, according to a study released Monday.

Herring embryos collected from shorelines left coated in oil starting about 3 months after the November 2007 Cosco Busan spill suffered from unusually high death rates and a range of ailments and deformities associated with exposure to the chemicals in crude oil, the study found.

"The majority of embryos in samples from oiled sites were dead on examination in the laboratory," wrote the study's authors, who were led by John Incardona, a toxicologist with the fisheries division of the National Oceanic and Atmospheric Administration.

By 2010, death rates had returned to normal, but the embryos continued to show heart defects that are a common symptom in herring of oil exposure.

The bay's Pacific herring are the largest coastal population in the continental U.S. and a key element of the bay's complex food web, according to the study, which was published online by the Proceedings of the National Academy of Sciences.

The spill that resulted from the massive cargo ship striking one of the pillars of the San Francisco-Oakland Bay Bridge in heavy fog killed more than 6,800 birds and closed beaches to swimmers for weeks.

In 2009, California regulators cancelled the bay's herring fishing season, which typically begins in January. The state said the herring populations in the bay had reached an all-time low, with the causes ranging from drought to pollution from the oil spill.

The north-central San Francisco Bay shorelines left coated in oil and littered with sticky tarballs are one of the historic spawning grounds for the bay's herring. Only about half the oil along those shores was recovered, and an unknown amount remained submerged near the water's edge, the study said.

The study's authors knew from herring harmed in Alaska's Exxon Valdez oil spill in 1989 that those same fish in San Francisco Bay would likely be threatened. Unlike the Valdez spill, which sent hundreds of thousands of barrels of crude oil spilling into Prince William Sound, the Cosco Busan leaked bunker fuel, a mix of diesel and fuel oil left over from the crude oil refining process.

Embryos exposed to chemicals in crude oil suffer from a range of maladies, from heart problems and deformities to swelling and cancer. Similar symptoms were seen in embryos collected for the San Francisco Bay study.

The problems did not seem to be caused naturally or by other pollution in the bay, the study's authors wrote. They said the only common feature of three sites where the embryos were collected was that they were exposed to oil.

Jonathan Maul, a toxicologist with The Institute of Environmental and Human Health at Texas Tech University who was not involved in the study, said the researchers faced difficulty in showing that the toxins came from the Cosco Busan's bunker fuel and not other sources in the environment. He said the study should encourage scientists to look further into the toxic effects of oil contamination.

"Overall I believe it is a valuable study and should garner attention toward impacts to early life stages of fisheries," Maul said.

Because the chemical levels found in the embryos didn't seem high enough to cause the high death rate, the study concluded that exposure to sunlight played a part in making the spill more deadly.

"One or more of these unidentified chemicals likely interacted with natural sunlight in the intertidal zone to kill herring embryos," the study said.

Source: http://www.miamiherald.com/2011/12/26/2562222/study-san-francisco-bay-oil-spill.html

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