In a genome-wide association (GWA) study, researchers from Boston University Schools of Medicine (BUSM) and Public Health (BUSPH) have identified several genes which influence degeneration of the hippocampus, the part of the brain most associated with Alzheimer disease (AD). The study, which currently appears online as a Rapid Communication in the Annals of Neurology, demonstrates the efficacy of endophenotypes for broadening the understanding of the genetic basis of and pathways leading to AD.
AD is a progressive neurodegenerative disorder for which there are no prevention methods. Available drugs only marginally affect disease severity and progression, making AD effectively untreatable.
GWA studies using very large samples have increased the number of robust associations to 10 genes, including APOE. However, these genes account for no more than 35 percent of the inherited risk of AD and most of the genetic underpinning of the disorder remains unexplained. According to the researchers, magnetic resonance imaging (MRI) of the brain provides in vivo quantitative measures of neurodegenerative and cerebrovascular brain injury that may represent AD-related changes long before clinical symptoms appear. These measures are more powerful than comparisons of individuals with AD with cognitively healthy persons because they avoid misclassification of normal persons who will develop disease in the future.
BUSM researchers conducted a two-stage GWA study for quantitative measures of hippocampal volume (HV), total cerebral volume (TCV) and white matter hyperintensities (WMH). Brain MRI measures of HV, TCV and WMH were obtained from 981 Caucasian and 419 African-American AD cases and their cognitively normal siblings in the MIRAGE (Multi Institutional Research in Alzheimer's Genetic Epidemiology) Study. In addition, similar MRI measures were obtained from 168 AD cases, 336 individuals with mild cognitive impairment and 188 controls (all Caucasian) in the AD Neuroimaging Initiative (ADNI) Study. The MIRAGE Caucasian families and ADNI subjects were included in the first stage and the MIRAGE African American families were added in stage two. Results from the two Caucasians data sets were combined by meta-analysis.
In stage two, one genetic marker (i.e. single nucleotide polymorphism or SNP) from each of the gene regions that were most significantly associated with AD in the Caucasian data sets was evaluated in the African-American data set.
Novel genome-wide significant associations were observed for HV with SNPs in the APOE, F5/SELP, LHFP, and GCFC2 gene regions. All of these associations were supported by evidence in each data set.
"Our two-stage GWAS identified highly significant associations between a measure of degeneration in the brain region most strongly correlated with AD and several genes in both Caucasian and African American samples containing AD, cognitively impaired and cognitively healthy subjects. One of these associations was with the ?4 variant of APOE which is the most well-established genetic risk factor for AD.
Other associations were demonstrated with markers in F5/SELP, LHFP, and GCFC2, genes not previously implicated in this disease" explained senior author Lindsay Farrer, PhD, chief of biomedical genetics at BUSM. He also noted, "previous studies showed that blood level of P-selectin (the protein encoded by SELP) has been correlated with rate of cognitive decline in AD patients."
Farrer believes it is very likely that the number and specificity of these associations will increase in future studies using larger samples and focused on additional precise structural and functional MRI measures. "These findings will inform experiments designed to increase our understanding of disease-causing mechanism and may lead to new therapeutics targets," added Farrer.
###
Boston University Medical Center: http://www.bmc.org
Thanks to Boston University Medical Center for this article.
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In the fourth quarter of 2011, eBay Marketplaces reported 100 million active users worldwide. According to eBay on its marketplace a woman?s dress sells every 8 seconds and someone buys a cell phone every 5 seconds. ?
EBay is still a very popular buying and selling platform and used by many different types of sellers ? SOHO ecommerce owners, part-time eBay enthusiasts and large businesses. Different sellers need different eBay tools.? While eBay offers its own listing tools, you may find ? like many other people do ? that eBay?s tools don?t provide the listing features you need; for example, listing your inventory across multiple auctions sites in addition to your own Web store.
Many of the inventory management and multiple-channel selling tools for eBay sellers we list below offer a free trial, so you can try different eBay tools to see which ones best suit your business needs before you make a cash investment.
Even if you sell on eBay and make a profit, many sellers prefer to manage their own off-eBay Web store and list the same products on other sites such as Amazon or eBay alternative sites.? The problem is that manually tracking sales across multiple channels and removing products from one online listing when it sells elsewhere is not a good business strategy.
Inventory management and multi-channel ecommerce software can help you to create your own online store if you don?t have one and synchronize your inventory and stock levels across all the places you do business. Here are 13 options to help you better manage a multiple channel selling strategy for eBay.
1.? AuctionBlox eMarketConnect provides access to eBay and Amazon.com from your existing online store. By connecting your store with eBay, AuctionBlox allows you to list your products on eBay and to process checkout in your own store. CRE Loaded, oscommerce, Zen Cart and Magento art software is supported. ?AuctionBlox Storefront pricing starts at $99/month.
2.? AuctionSound is eBay auction-management software that helps sellers manage eBay consignment and online inventory. AuctionSound provides image hosting, eBay templates and consignor-management and reporting tools. Pricing starts at a $24.99/month; free 30-day trial.
3. BigCommerce lets you create your own Web shop, plus you can sell on Facebook and eBay.? Extra features include multi-channel retailing, mobile commerce, SEO, and easy upselling. Pricing starts at a $24.95/month.
4.? ChannelMAX is an inventory-management service that lets you create a Web store plus list your inventory to multiple online marketplaces including eBay, Overstock and uBid. You can schedule listings, create listing templates and more.? Pricing starts at $24.99/month.
5.? DesignCart is an online, hosted shopping cart designed for a small to mid-size business that wants to sell products on the Web. It works on any hosting platform and is eBay compatible. DesignCart provides capability to list and complete payment for your eBay auctions. Winning bidders will be presented with an add-button via email, and upon successful payment, the cart will update the eBay auction status automatically. Pricing starts at $18/month; free 14-day trial.
6.? Infopia offers SaaS (Software as a Service) ecommerce solutions including a Marketplaces product to build a multi-channel business by optimizing product sales across your own website and online marketplaces like eBay and Amazon. Sellers can manage all online inventory, marketplace listings, and orders from one place.? Contact Infopia for pricing details.
7.? Kosmos CentraleBay ecommerce integration software lets you upload items from your online store to your eBay account, and download orders from eBay to your ecommerce website ? integrating all purchases into one system to keep your eBay and online storefronts in sync. You?ll find pricing for different Kosmos services on its website.
8.? Mercantec E-Commerce Express offers an entry-level storefront and cart service so you can sell in a number of places including your own site and eBay. You can use E-Commerce Express for auction (and other types of online checkouts including eBay fixed price listings. Mercantec lets you create an Instant Storefront or generate Snippets that are embedded into existing content. E-Commerce Express is a free service.
9.? ProStores offers sellers a complete ecommerce platform, including Web store, shopping cart, built-in templates and more. EBay sellers can sync eBay and ProStores inventory and also list on eBay from the ProStores interface. Pricing starts at $20.95/month in addition to per transaction fees; free 30-day trial.
10.? Solid Commerce is a multi-channel ecommerce platform that allows you to sell and list items across a number of sites including eBay and Amazon. Inventory management features lets you synchronize your inventory stock levels in real-time across your various sale channels and manage your business from a central interface.? Pricing is based on monthly sales revenue.
11.? Techwave Free Shopping Cartsoftware provides everything you need to build, update and maintain an online store. Techwave is fully integrated with Microsoft CRM, Sugar CRM for organized business and sharing procedure, and also offers an EBay Integration Module for Techwave Ecommerce that will fully integrate your ecommerce website with an eBay store.? Contact Techwave for pricing details.
12.? T-HUB for QuickBooks is an order-management solution designed to integrate your ecommerce stores with QuickBooks and Shipping services (UPS/FedEx/USPS).? T-HUB works with several leading ecommerce platforms and shopping carts such as Amazon, eBay, Yahoo stores, Magento, Volusion, GoDaddy, X-Cart, BigCommerce, AmeriCommerce, osCommerce, AspDotNetStorefront and others. Pricing starts at $550 for standard software purchase, with Pro and Advanced versions available.
13.? Vendio eBay Listing Software is part of the Vendio Platform and is an eBay listing tool that you can use to create and manage your online auction pages. It?s a multi-channel solution that can manage sales across eBay, Amazon, a Vendio Store and more.? Pricing for Vendio Marketplace starts at $19.95/month (a basic plan is free).
If you?re not ready to list across multiple selling channels, and you?re happy to stick with just eBay right now, the following eBay auction-management tools will help you create eBay auction pages, manage images and give you options for professional eBay templates to make your pages more appealing to potential buyers.
14.? AuctionSplash is a desktop tool that gives eBay sellers access to listing templates, picture hosting (up to eight photos) and scheduling. It works with eBay U.S., eBay UK, eBay CA, eBay AU and others. The service offers a no-hassle single page listing screen.? AuctionSplash is free to use.
15.? Auctiva auction management provides eBay sellers with a number of tools including professional eBay templates, marketing tools, image hosting, listing software, and inventory management.? The unlimited plan is $9.99/month; a free basic plan for image hosting is available.
16.? Blackthorne Basic is a software application that lets you create professional listings in bulk, track the status of sales, and manage buyer communication and feedback. And it integrates in your eBay selling manager. Pricing starts at $9.99/month; free 30-day trial.
17.? Blackthorne Pro includes all the features of Blackthorne Basic, plus additional options for inventory management, reporting, multiple user profiles, and is available in a desktop version. Pricing is $24.99/month; free 30-day trial.
18.? eBay Selling Manager is free for all eBay sellers and can be accessed from within your ?My eBay? tab. The tool is designed to help medium-volume sellers manage their eBay listings. Features include the option to track active listings, generate bulk feedback, and print invoices and labels in bulk.? The eBay Selling Manager is free via an eBay account.
19.? eBay Turbo Lister is a free tool that lets sellers list multiple items and upload in bulk to eBay. Turbo Lister offers bulk editing capability, search tools, and a toolbar for better control of your listings. The eBay Turbo Lister is free via an eBay account.
20.? EZLister.Net is a Web-based auction business management solution. Sellers can use EZLister.Net to automate routine tasks associated with listing and managing eBay auctions and item listings. Pricing is based on a per-listing fee, and it starts at $56 for 250 listings.
21.? Supreme Auction is an eBay Compatible application that lets you create multiple listings and submit them to eBay. The application offers free template designs, widgets, images and more. With this tool you can list on eBay U.S., eBay UK, eBay Germany. Supreme Auction is free, and there are optional paid upgrades available.? A basic version with all features is free, and sellers can upgrade to a paid Premium account.
EcommerceGuide.com wants to know: What is your favorite eBay selling tool? Tell us about it in the comments section below.
From beginner guides to expert tips, our selection of eBay and Web shop articles can help you to better manage your ecommerce business.
Based in Nova Scotia, Canada, Vangie Beal has spent the last decade contributing featured articles and reviews to more than 20 technology-focused publications, including Webopedia and Ecommerce-Guide. You can tweet with her online @AuroraGG.
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In June, 2012, Smith was accused of driving under the influence and of spitting blood on law enforcement officers in Volusia County, Fla.
Raymond Carl Knudson
Raymond Carl Knudson pleaded guilty June 25 to sticking up a Bank of America branch in April, a crime he confessed within minutes of committing.
Kola J. McGrath
Kola J. McGrath was arrested for sneaking into her boyfriend's apartment complex by hiding in a small pink suitcase in Portland, Ore. The police searched the apartment of Curtis T. Lowe after being informed that a man had kidnapped a woman, put her in a suitcase, and taken her into the building. They found McGrath hiding in a closet.
Houaka Yang
Houaka Yang, 20, of Wisconsin, accidentally videotaped his confession and identified himself on tape with a camcorder he stole. Once the video camera was recovered, the victim uploaded <a href="http://www.youtube.com/watch?feature=player_embedded&v=wmY_gFcBsvw" target="_hplink">Yang's clip to YouTube.</a>
Pocahontas
Luerissie Ashley Ross -- who is also a stripper called Pocahontas -- was arrested in February after she allegedly lured a man to his death and shot another in two robberies in Houston. <a href="http://www.huffingtonpost.com/2012/05/15/stripper-pocahontas-shootings-luerissie-ross_n_1517518.html?ref=crime" target="_hplink">Read more.</a>
Clyde Hobbs
Clyde Hobbs was arrested in May, 2012 for allegedly calling 911 at least 17 times -- to talk dirty to operators. He'd been arrested several times in the past for the same crime. When cops arrived to collar him, Hobbs asked, "Are you here to arrest me again?" <a href="http://www.huffingtonpost.com/2012/05/09/clyde-hobbs-called-911-to-talk-sex_n_1502536.html?1336569858" target="_hplink">Read more.</a>
Patricia Krentcil
Patricia Krentcil was charged with child endangerment for allegedly allowing her 5-year-old to use a tanning booth, but the New Jersey mom says the child got a sunburn from playing outside.
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Eugene Carl Kotelman
Largo (Fla.) Police pulled over Kotelman allegedly for speeding and driving drunk on May 3. Cops checked the trunk and say they found a small monkey tucked inside.
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Aaron Latham
Latham, 22, allegedly got naked, stole a man's truck and then ran it into the front of a home at 50 mph.
<a href="http://www.huffingtonpost.com/2012/04/30/aaron-latham-nude-man-steals-truck-crashes-through-house-delaware_n_1464836.html" target="_hplink">Read more.</a>
Joseph Hannah
Sheriff's deputies in Albuquerque, N.M. arrested Joseph Hannah for allegedly posing as a police officer. He's accused of pointing a gun at a group of teenage boys and allegedly urinating on a hat belonging to one of them. Two women told police that he pulled them over and flirted with them in separate incidents.
<a href="http://www.huffingtonpost.com/2012/04/26/joseph-hannah-impersonated-cop-urinated-hat_n_1455881.html" target="_hplink">Read more.</a>
Michael Baker
Michael Baker was arrested after posting a Facebook photo of himself stealing gas from a police car in Jenkins, Ky.
<a href="http://www.huffingtonpost.com/2012/04/19/michael-baker-stole-gas-cop-car-facebook-photo-kentucky_n_1437057.html" target="_hplink">Read more.</a>
Ronaldo Silva
Ronaldo Silva allegedly broke out of a Brazilian prison by dressing in drag in April, 2012. He was caught less than an hour by a cop who noticed that he walked funny in heels.
<a href="http://www.huffingtonpost.com/2012/04/17/prison-escape-in-drag_n_1431558.html" target="_hplink">Read more.</a>
Ray Woods
Ray Woods allegedly tied 89 bags of heroin and cocaine to his penis. When cops found him out, he reportedly urinated all over himself.
<a href="http://www.huffingtonpost.com/2012/04/12/89-bags-of-heroin-tied-to-penis_n_1420733.html" target="_hplink">Read more.</a>
Keith Fehr
Keith Fehr is accused of wearing a black dress and exposed himself to children at a park in Illinois.
<a href="http://www.huffingtonpost.com/2012/04/05/keith-fehr-little-black-dress-indecent-exposure_n_1406703.html" target="_hplink">Read more. </a>
Raymond Foley
Raymond Foley, an IT guy at an insurance company in West Des Moines, allegedly peed on four female co-workers' chairs over the course of five months. The company installed surveillance cameras in April, 2012 when the women complained, and reportedly caught Foley yellow handed.
<a href="http://www.huffingtonpost.com/2012/04/03/it-guy-peed-on-chairs_n_1399398.html" target="_hplink">Read more.</a>
Jesse James Thomas
Jesse James Thomas, arrested March 28 for public drunkenness, Thomas was wearing a sombrero when he jumped on an
officer's parked patrol car screaming his name, according to an account in the <em>Sacramento Bee</em>.
<a href="http://www.huffingtonpost.com/2012/03/30/jesse-james-thomas-sombrero-jumps-on-cop-car_n_1392754.html" target="_hplink">Read more. </a>
William Bliss
William Bliss was arrested in March, 2012 after claiming four men made him carry a nuclear bomb -- while he was naked and drunk in the middle of an Iowa City street.
<a href="http://www.huffingtonpost.com/2012/03/20/forced-to-handle-nuclear-weapon_n_1366879.html" target="_hplink">Read more.</a>
Christina Lopez
Salem police say surveillance video shows Christina Lopez watched her 17-year-old daughter dance at Presley's Playhouse Cabaret, a strip club in Oregon.
<a href="http://www.huffingtonpost.com/2012/03/18/christina-lopez-watched-daughter-strip_n_1356975.html" target="_hplink">Read more. </a>
Briana Rios
Accused teenage Bookie Briana Rios of Florida is accused of taking bets on NBA and NFL games.
<a href="http://www.huffingtonpost.com/2012/03/17/briana-rios-fla-teenager-bookie_n_1355315.html" target="_hplink">Read more. </a>
Matthew Ibarria
Matthew Ibarria, a fugitive from Florida wanted for allegedly attacking a relative, was arrested after jumping naked from a car in Georgia. This dashboard video from a Kingsland Police Department vehicle allegedly shows him running away.
<a href="http://www.huffingtonpost.com/2012/03/09/naked-man-matthew-ibarria-police-chase_n_1334638.html" target="_hplink">Read more.</a>
Jacob Lee Bovia
Jacob Lee Bovia is facing real indecent exposure charges for exposing his fake genitalia to a group of women on Maryland's Anne Arundel Community College campus.
<a href="http://www.huffingtonpost.com/2012/03/07/jacob-lee-bovia-arrested-exposing-fake-penis-maryland_n_1326558.html" target="_hplink">Read more. </a>
John Jardini
John Jardini, 26, of Pittsburgh allegedly robbed a woman for $60 -- and then asked her out on a date by cell phone. The "love" story gets worse. Read more <a href="http://www.huffingtonpost.com/2012/03/06/robber-called-victim-for-date_n_1324449.html?ref=weird-news&ir=Weird News" target="_hplink">here.</a>
Jason Engel
Jason Engel, 21, of Pittsburgh, was arrested after he skipped a court hearing on charges that he stole $400 from a 2-year-old's piggy bank. Read more <a href="http://www.huffingtonpost.com/2012/03/01/jason-engel-steals-from-piggy-bank_n_1313144.html?ref=crime&ir=Crime" target="_hplink">here.</a>
Michael Conley
Former Elvis impersonator Michael Conley blamed his diabetes for starting a standoff with Florida police, in which he threatened to use a weapon of mass destruction against them. He allegedly held up a vial of what he called Ricin -- a highly potent toxin -- as he barricaded himself in a motel in February, 2012. He was arrested about four hours later. Read more <a href="http://www.huffingtonpost.com/2012/02/29/wmd-suspect-diabetes_n_1310202.html" target="_hplink">here.</a>
Michael Barker
Barker called 911 repeatedly in Hudson, Fla. asking them to fetch him a taxi and saying that he lost his football. Cops arrested him for allegedly misusing the emergency system on Feb. 20, 2012. Read more <a href="http://www.huffingtonpost.com/2012/02/23/911-caller-wants-taxi-michael-barker-florida_n_1296979.html" target="_hplink">here.</a>
Mark Loescher
Those who attempt to arrest Mark Loescher have their work cut out for them. When he was arrested for assault, he not only told officers that he was Elvis Presley's brother, a friend of President Bush, and director of the CIA, but he was also half-orangutan. Read more <a href="http://www.huffingtonpost.com/2012/02/21/mark-loescher-says-hes-half-orangutan_n_1290576.html" target="_hplink">here.</a>
Ramon Blair
A Martin County sheriff's deputy in Florida arrested Ramon Blair, 28, based on tips from informants that Blair would have hundreds of dollars of crack cocaine "on his person." An initial search turned no results, but a more thorough search while in custody revealed that Blair had hidden the crack in, well, his crack. Blair was told to undress, squat, and cough -- and police found what appeared to be a white piece of paper in his buttocks, which contained crack cocaine. Read more <a href="http://www.huffingtonpost.com/2012/02/17/police-find-crack-in-butt_n_1285604.html" target="_hplink">here.</a>
Verdon Taylor
Clothes be darned: Verdon Taylor was arrested in February, 2012 for allegedly stripping naked in the parking lot of a Walmart, walking inside and putting on socks, then shopping. Almost needless to say, he was eventually Tased. Read more <a href="http://www.huffingtonpost.com/2012/02/17/naked-man-steals-socks_n_1284139.html" target="_hplink">here.</a>
Nikolas Harbar and Stephanie Pelzner
Portland, Ore. couple Nikolas Harbar and Stephanie Pelzner were arrested on Valentine's Day, 2012 after Harbar allegedly bound his naked girlfriend and threw her in the back of a car -- in the pursuit of a sexy role-play romp. Cops, after a long search, found that Pelzner wasn't a kidnapping victim, but that both were disorderly conduct suspects. Read more <a href="http://www.huffingtonpost.com/2012/02/15/bound-naked-role-play_n_1278598.html" target="_hplink">here.</a>
Misty Lawson
Misty Lawson, 30, a self-described "professional baby maker" on her Facebook page, allegedly punched her son in the face and body several times during an in-home, state-mandated anger management course. Read more <a href="http://www.huffingtonpost.com/2012/02/13/punch-during-anger-management-misty-lawson_n_1272915.html" target="_hplink">here.</a>
Harold Wayne Hadley, Jr.
Harold Wayne Hadley, Jr. was arrested in February 2012 for allegedly threatening to blow up his Mississippi school -- but he maintains it was a fart joke. He allegedly wrote, on a piece of toilet paper, that he "passed a bomb in the library." He was held on $20,000 bail. Read more <a href="http://www.huffingtonpost.com/2012/02/10/fart-joke-leads-to-bomb-scare_n_1268713.html" target="_hplink">here.</a>
Andrew Toothman
He had a real sweet tooth. Cops say they found 22-year-old Andrew Toothman lying down inside Kentucky Food World IGA market on Feb. 2, completely covered in chocolate and peanut butter. He'd also allegedly written "Sorry" in NyQuil on the floor. Read more <a href="http://www.huffingtonpost.com/2012/02/09/naked-chocolate-peanut-butter_n_1265639.html" target="_hplink">here.</a>
Agustin Sanchez
Rogue cuddler Agustin Sanchez allegedly snuck into his ex-girlfriend's home and crawled into bed with her for a snuggle. The spooning attempt was thwarted, however, when the woman notified police. Read more <a href="http://www.huffingtonpost.com/2012/01/10/cuddle-break-in-augustin-sanchez_n_1196323.html" target="_hplink">here.</a>
Timothy Randall Clark
Timothy Clark probably didn't think his plan through when he allegedly shoplifted from a Wal-Mart at the same time that police were holding their "Shop With A Cop" charity event.
<a href="http://www.huffingtonpost.com/2011/12/07/timothy-clark-shop-with-cop-arrest_n_1134064.html" target="_hplink">Read more.</a>
Oneal Morris
Oneal Morris is accused of posing as a doctor and filling a women's buttocks with cement, mineral oil and flat-tire sealant.
The woman wanted to work at a nightclub and searched for someone who could perform plastic surgery at a cheap price to give her a curvier body.
Police say Oneal was was born a man but identifies as a woman.
<a href="http://www.huffingtonpost.com/2011/11/20/butt-implants-fake-doc_n_1103933.html" target="_hplink">Read more.</a>
Olivia Ornelas
Police in Illinois say that Olivia Ornelas blamed her DUI and crashed vehicle on her boyfriend's failure to take her, as he promised, to the new "Twilight" movie.
<a href="http://www.huffingtonpost.com/2011/11/21/illinois-twilight-fan-arrested_n_1105740.html" target="_hplink">Read more.</a>
Ranaldo Jack
Authorities in Georgia found Ranaldo Jack stuck in a woman's chimney. He was charged in connection with an attempted burglary.
<a href="http://www.huffingtonpost.com/2011/11/17/man-stuck-in-chimney-arrested_n_1099252.html" target="_hplink">Read more.</a>
Marsia Emanuel
Marsia Emanuel allegedly flagged a school bus in Winter Haven, Fla., boarded and beat the bus driver in front of her daughter, a student riding it already. Cops found Emanuel later at home where she dropped her underpants in front of them, they said. It's unclear what was her motive.
<a href="http://www.huffingtonpost.com/2011/11/11/marsia-emanuel-allegedly-_n_1088096.html" target="_hplink">Read more.</a>
Bug Spray Bandit
Investigators in California are trying to track down a man who robbed a bank armed with pesticide. The suspect appeared to be carrying a black semi-automatic handgun and a plastic container of pesticide when he held up the Pacific Western Bank in Rancho Santa Fe on Nov. 4, 2011.
<a href="http://www.huffingtonpost.com/2011/11/08/bank-robbery-pesticide_n_1082447.html" target="_hplink">Read more.</a>
Karen Henry
Police in Florida arrested Karen Henry, 45, after she allegedly threatened her 80-year-old father with a knife for not sharing his potato salad.
<a href="http://www.huffingtonpost.com/2011/10/31/karen-henry-arrested-potato-salad_n_1067172.html" target="_hplink">Read more.</a>
Gregory Liascos
This camouflage might work well in nature, but it really stands out in the police station. Oregon investigators believe Gregory Liascos, 36, was wearing this "ghillie" camouflage when he attempted to break into the Rice Northwest Museum of Rocks and Minerals last week. After setting off alarms, the suspect allegedly fled into a wooded area nearby. Officers only found Liascos when a police dog bit what appeared to be a patch of grass -- which yelped in pain. On Oct. 12, 2011, authorities said Liascos failed to show up for his trial. A warrant has been issued for his arrest.
Albert Tejeda
Sheriff's deputies in Pinal County, Ariz., say Albert Tejeda's unique tattoos -- and his lengthy rap sheet -- leave him with a face they'll never forget. After Tejeda allegedly fled during a traffic stop, deputies claim they knew exactly who they were looking for and later found the 31-year-old walking around Casa Grande with a samurai sword.
Juan Aguirre
Even if Juan Aguirre got away, he would have ended up empty handed. Police said the 21-year-old Kansan stole six empty DVD boxes from a local adult entertainment shop.
'Vampire' Josephine Smith
Josephine Smith is seen in this booking photo from the Pinellas County Jail. Smith was arrested after allegedly attacking and biting a piece of skin off a homeless man in St. Petersburg after proclaiming "I am a vampire, I am going to eat you".
Edwin Tobergta
Edwin Tobergta, 32, is seen in this booking photo from the Butler County Sheriff's Office. Tobergta was arrested after allegedly having sex with an inflatable pool raft.
Joshua Greene
It's not easy to be the most most memorable visitor when thousands of NASCAR fans come to town, but West Virginia's Joshua Greene made a pretty good run for that honor when police caught the streaking 27-year-old with a raccoon in his car.
Ismael Ambrosio
We're not saying there's guilt written all over his face, but Ismael Ambrosio is seen in this Aug. 9 booking photo from the Pinellas County (Fla.) Jail with a facial tattoo that could not have pleased police officers.
Dumb Crime: Masterminds Need Not Apply
The hand of justice makes an appearance in this mug shot. Nichlous Peternik -- and the arm of a law enforcement official in Redding, Calif. -- are featured prominently in this memorable booking photo taken after Peternik was arrested on suspicion of burglary. Officials say they were forced to reach into the frame when Peternik refused to pull his hair back from over his face.
Man Charged with DWI for Driving Motorized Cooler
An Australian man caught driving a motorized cooler box through a beachside resort town appeared in court charged with drunk driving, The Courier Mail reported Monday. Christopher Ian Petrie, 23, faces charges of driving under the influence and driving without a license after police caught him on the makeshift vehicle, which was powered by a 50cc engine.
Lorena Tavera
Former Miss El Paso USA Lorena Tavera was arrested for allegedly shoplifting a $69 shirt in El Paso.
Cory Smits
Cory Smits, 29, is seen in this booking photo from the Manitowoc County Sheriff's Department. Smits was found guilty July 7 on his fifth offense of operating a vehicle while intoxicated.
Patrick Francis Brooks
This booking photo from the Shasta County Sheriff's Office in California shows Patrick Francis Brooks and his obscene tattoo after his July 11 arrest on charges of burglary, receiving stolen property, forgery and violating the terms of his parole for a previous conviction.
Mark Anthony Richardson Jr.
Mark Anthony Richardson Jr. wore diapers and faked being autistic to get women to babysit him. He was sentenced to three years in prison in July 2011 for groping an 18-year-old daughter of one of the conned nannies.
Mug Shot:
Levon T. Sarkisyan, allegedly broke into a Connecticut home and smashed statues and furniture, because he claimed God told him to do it, according to police.
Dumb Crime: Masterminds Need Not Apply
Police in Phoenix, Ariz., have accused Randon Reid of the crime of flight -- and a crime against flight. Investigators say the 26-year-old suspect opened fire on an airplane parked at Deer Valley Airport, then fled from authorities who tried to pull him over. He has reportedly been charged with felony flight and driving under the influence.
Dumb Crime: Masterminds Need Not Apply
Holy handcuffs! Police in a smog-clotted town in northwest Michigan are touting the arrest of Batman. The legendary caped crusader was reportedly nabbed while dangling from a 30-foot-high building. The unmasked superhero wannabe is actually a local resident named Mark Wayne Williams.
Dumb Crime: Masterminds Need Not Apply
Some people have guilt written all over their faces, and others, like assault suspect Robert Norton Kennedy, have apologies tattooed across their foreheads. A booking photo released by the authorities in Horry County, S.C., appears to show the 51-year-old sporting a facial tattoo that reads: "Please forgive me if I say or do anything stupid. Thank You!" <a href="http://weirdnews.aol.com/2011/05/10/robert-norton-forehead-tattoo_n_859931.html#s276809&title=Dumb_Crime_Masterminds" target="_blank"><b>(Read More)</a></b>
Dumb Crime: Masterminds Need Not Apply
A South Carolina man who twice pleaded guilty to having sex with a horse has been released from prison and put on probation, under the condition that he keep his distance from the horse. Rodell Vereen, pictured in this file photo, was released from prison after serving 16 months.
Dumb Crime: Masterminds Need Not Apply
It was almost a kiss of death. Deputies in Florida say 92-year-old Helen Staudinger opened fire on her neighbor's house after the much younger resident refused to give her a kiss. Investigators at the Marion County Sheriff's Office claim Staudinger refused to leave 53-year-old Dwight Bettner unless her neighbor gave her a kiss. She allegedly returned with a gun.
Dumb Crime: Masterminds Need Not Apply
It's always best to practice what you preach. Police in Florida say they arrested the former president of a local chapter of Mother's Against Drunk Driving for driving under the influence. Debra Oberlin has been charged with drunk driving for the Feb. 18 incident.
Dumb Crime: Masterminds Need Not Apply
Police in Michigan say a man claimed he was royalty before trying to steal a pack of Marlboros from a 7-Eleven. Joseph Lawrence Borowiak is charged with strong-arm robbery and resisting arrest after allegedly wrestling a store clerk over a pack of cigarettes. Borowiak reportedly stated, "The king doesn't pay for cigarettes."
Dumb Crime: Masterminds Need Not Apply
Jerome Smith's forehead says he's a "Genius," but police say he wasn't being smart when he allegedly struck a pregnant woman with a handgun. The Cincinnati, Ohio, resident is accused of repeatedly pistol-whipping a woman who was eight months pregnant in late January.
Leo Earl Sharp
When police caught 87-year-old Leo Earl Sharp allegedly transporting 228 pounds of cocaine, the suspect told them that he was forced "at gunpoint" to transport the drugs.
Andrei Bibbs, 54, of the 3000 block of Coopers Grove Court, was arrested Jan. 7 Illinois State Police and charged with driving while under the influence of alcohol. He <a href="http://www.huffingtonpost.com/2012/01/12/andrei-bibbs-blue-island-_n_1201547.html" target="_hplink">was clearly shocked by the change. </a>
Michael Belton
Belton lost his wig, sunglasses and $115,000 worth of casino chips when security wrestled him to the floor during a botched weekend heist, according to authorities.
Dumb Crime: Masterminds Need Not Apply
Tiffany Pocock, 27, of Bellevue, Ohio, spat blood on the cops who were arresting her in late May 2012. After being detained for driving a vehicle while impaired, Pocock also began banging her head repeatedly against the door of the police vehicle, sustaining personal injuries that resulted in her hospitalization.
<a href="http://www.huffingtonpost.com/2012/05/21/woman-spits-bood-on-cop-ohio_n_1534392.html?ref=crime" target="_hplink">Read more.</a>
Dylan DiFalco told a Sheriff's deputy he had to urinate and, when the cop told him he'd have to wait, he peed in the cop car, according to an arrest report. "I told you I had to go you stupid cop," Difalco said, according to the report.
Milton Hodges
Hodges, 20, of Florida, allegedly fled to a nudist colony and threatened residents there after committing an armed robbery at a nearby Lowe's. The fully-clothed Hodges was reported to have been easily identified by his pursuers in the naked environment.
Timothy Paul Shelby
Shelby, 53, was arrested in South Florida on June 1, 2012 for driving without a license -- immediately after leaving a courthouse after he appeared for the same offense.
Nicole Okrzesik
Okrzesik is accused of helping to kill 19-year-old Juliana Mensch in March. She allegedly sent incriminating text messages and conducted fishy <a href="http://blogs.browardpalmbeach.com/pulp/2012/05/nicole_okrzesik_mensch_ayers_google-search.php" target="_hplink">Google searches</a> implicating herself in the crime.
Nikoleta Karoly
Karoly is accused of choking her boyfriend because he refused to marry her so she could get a new Visa.
Bradley Pope
Pope was arrested for DUI. He allegedly told police that he was a "covert agent" and that he had drank 100 beers.
Tracy Mabb
Mabb is accused of exposing herself at an intersection in Pompano Beach, Fla. She allegedly told police she didn't "give a f--k" about her actions, according to a police report.
Everett Lages
Lages was arrested when he allegedly called 911 after he was not allowed to bring his kitten inside a strip club.
Is Survivor about to get its first player who has his own bobblehead doll? According to the site Survivor Fever, Jeff Kent will be among the contestants when the venerable game show kicks off its 25th season (over 12 years) in September. Also on board, according to Survivior Fever, will be Miss Teen USA 2010 Angelia Layton and (the big news) Lisa Welchel ? better known as Blair from The Facts of Life. The gang will be in the Caramoan Islands, the Philippines, this time.
Kent, 44, was the National League MVP in 2000 and played in the 2002 World Series for the Giants. But more importantly he was a contestant on Superstars in 2009, so there?s the athletic game show background. He also came out against gay marriage in the Prop. 8 debate in 2008, which also must have been very attractive to the Survivor producers. They love stirring the pot by cramming the island with a bunch of divergent viewpoints.
As for me, my unblemished record of never seeing an entire episode of Survivor is expected to continue. The only way to break it is if they had both Kent and Barry Bonds on the same season.
New Report Spices Market (2011-2016) by MarketsandMarkets Albany Times Union Among spices, the chief spices which are largely demanded are black pepper, cardamom, chilies, ginger, turmeric, coriander, cumin, celery, fennel, fenugreek, ...
Over the past several decades, U.S. industries have injected more than 30 trillion gallons of toxic liquid deep into the earth, using broad expanses of the nation's geology as an invisible dumping ground.
No company would be allowed to pour such dangerous chemicals into the rivers or onto the soil. But until recently, scientists and environmental officials have assumed that deep layers of rock beneath the earth would safely entomb the waste for millennia.
There are growing signs they were mistaken.
Records from disparate corners of the United States show that wells drilled to bury this waste deep beneath the ground have repeatedly leaked, sending dangerous chemicals and waste gurgling to the surface or, on occasion, seeping into shallow aquifers that store a significant portion of the nation's drinking water.
In 2010, contaminants from such a well bubbled up in a west Los Angeles dog park. Within the past three years, similar fountains of oil and gas drilling waste have appeared in Oklahoma and Louisiana. In South Florida, 20 of the nation's most stringently regulated disposal wells failed in the early 1990s, releasing partly treated sewage into aquifers that may one day be needed to supply Miami's drinking water.
There are more than 680,000 underground waste and injection wells nationwide, more than 150,000 of which shoot industrial fluids thousands of feet below the surface. Scientists and federal regulators acknowledge they do not know how many of the sites are leaking.
Federal officials and many geologists insist that the risks posed by all this dumping are minimal. Accidents are uncommon, they say, and groundwater reserves ? from which most Americans get their drinking water ? remain safe and far exceed any plausible threat posed by injecting toxic chemicals into the ground.
But in interviews, several key experts acknowledged that the idea that injection is safe rests on science that has not kept pace with reality, and on oversight that doesn't always work.
"In 10 to 100 years we are going to find out that most of our groundwater is polluted," said Mario Salazar, an engineer who worked for 25 years as a technical expert with the EPA's underground injection program in Washington. "A lot of people are going to get sick, and a lot of people may die."
The boom in oil and natural gas drilling is deepening the uncertainties, geologists acknowledge. Drilling produces copious amounts of waste, burdening regulators and demanding hundreds of additional disposal wells. Those wells ? more holes punched in the ground ? are changing the earth's geology, adding man-made fractures that allow water and waste to flow more freely.
"There is no certainty at all in any of this, and whoever tells you the opposite is not telling you the truth,' said Stefan Finsterle, a leading hydrogeologist at Lawrence Berkeley National Laboratory who specializes in understanding the properties of rock layers and modeling how fluid flows through them. "You have changed the system with pressure and temperature and fracturing, so you don't know how it will behave."
A ProPublica review of well records, case histories and government summaries of more than 220,000 well inspections found that structural failures inside injection wells are routine. From late 2007 to late 2010, one well integrity violation was issued for every six deep injection wells examined ? more than 17,000 violations nationally. More than 7,000 wells showed signs that their walls were leaking. Records also show wells are frequently operated in violation of safety regulations and under conditions that greatly increase the risk of fluid leakage and the threat of water contamination.
Mother Monster takes to Twitter to let her dad know she is doing fine after a concert head injury. By Jocelyn Vena
<P>A little more than a week after <a href="http://www.mtv.com/music/artist/lady_gaga/artist.jhtml">Lady Gaga</a> suffered a <a href="/news/articles/1687007/lady-gaga-concussion-concert-madonna.jhtml">concussion</a> and some <a href="/news/articles/1687141/lady-gaga-on-stage-concussion-photo.jhtml">bruises</a> from an onstage collision with a metal set piece on her <i>Born This Way</i> Ball, the singer got some good news: She's doing just fine.</P><P>"Went for an MRI," she <a href="https://twitter.com/ladygaga/status/215379987283443712" target="_blank">tweeted</a> on Wednesday (June 20). "No harm from the concussion but it appears my brain is just water and a large floating jellyfish." She then shared just <i>who</i> she got the check-up for, adding a little note to her dad. "@germanottajoe i had them check my noodle," she wrote. "that was your father's day present Il mio babbo!! I thought they were taking me to the zoo. TRICKS."</P><P></p><div class="player-placeholder right" title="Lady Gaga Will Bring a 'Personal' Touch To 'Born This Way' Tour" id="vid:717952" width="415" height="255"></div><p></P><P>The injury took place on June 10 while the Mother Monster was in New Zealand when a dancer accidentally hit her with a set piece mid-song. She walked off during "Judas" only to return to the stage after a short break to perform 16 more songs. "I want to apologize," she later told the crowd. "I did hit my head and I think I may have a concussion. But don't you worry, I will finish this show."</P><P>Gaga will play several shows in Sydney, including a gig on Wednesday night. She'll play Australia through the remainder of this month before hitting up Europe in July. She has dates slated right through December abroad. She has yet to announce North American dates for her elaborate <i>Born This Way</i> Ball, with a gothic castle serving as the tour's main visual.</P><P>In addition to touring through the rest of 2012, Gaga will also release <a href="/news/articles/1687383/lady-gaga-fame-perfume.jhtml">her first fragrance, Fame</a>, in September, which also happens to be the month she will announce the title of her next album, the <a href="/news/articles/1686922/lady-gaga-new-album-title.jhtml">follow-up to 2011's <i>Born This Way</i></a>.</P><P><a href="http://www.mtv.com/photos/?fid=1617615"><img src="http://www.mtv.com/news/photos/s/spotted/banner/spotted.jpg"></a></p>
Clutching a bright pink notebook, Katie Holmes was spotted stepping out of her apartment in New York City, New York earlier this morning (June 19).
The "Dawson's Creek" cutie gave the cameras a slight smile as she made her way out onto the Big Apple streets wearing skinny jeans and a loose blue blouse with bright blue flats.
Katie donned a similar loose fitting shirt while stepping out yesterday (June 18) to grab cupcakes with her daughter, Suri Cruise.
If you haven't already, be sure to check out the pictures of the 33-year-old actress leaving her Manhattan apartment on Monday.
Enjoy the photos of Katie Holmes leaving her apartment in New York City, New York (June 19).
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Governments of the world: arm all nuclear launch codes, disband your legislatures, and send your drones to the sky: Taco Bell is preparing not one but two new flavors of its diabolical Doritos Locos Tacos. This time, prepare. More »
The eighth annual Major League Baseball? ?Major League BaseballLatest from The Business JournalsCountdown: Multi-sport towns comparable to ColumbusWest Coast Novelty heads to SouthavenMathews leverages unique business model for legal field Follow this company All-Star Red Carpet Show in Kansas City will offer baseball fans an up-close look at members of the 2012 All-Star teams.
The event is at 1 p.m. on July 10. George Brett, MLB All-Star Ambassador and 13-time MLB All-Star, will serve as grand marshal, leading the parade through the streets. Then Ron Washington and Tony La Russa ? the American League and National League All-Star team managers, respectively ? will lead their teams down the carpet in Chevrolet Camaro Convertibles.
Players, riding in 2012 Chevrolet Silverado pickups, will wind half a mile through the Country Club Plaza? ?Country Club PlazaLatest from The Business JournalsBlanc Burgers + Bottles will bottle its ketchup for retail saleSaint Luke?s Hospital hires COOLockton?s Plaza lease extension gets Kansas City aid after all Follow this company . The parade starts at the corner of Ward Parkway and Wornall Road, and it ends at Nichols Road and Central Street.
The event ?is a unique and unforgettable way for baseball fans in Kansas City to take part in All-Star Week,? Tim Brosnan, executive vice president of business for Major League Baseball, said in a release.
The Red Carpet show will be broadcast nationally on the MLB Network.
The All-Star game will be played later that evening. The game determines which league has home field advantage in the World Series.
James reports about banking, financial services, manufacturing and sports business.
ATHENS (Reuters) - Greece's conservative leader began talks to form a government on Monday after winning an election that sets him the task of imposing punishing austerity measures in a near-bankrupt economy while containing rising social tensions.
New Democracy conservative leader Antonis Samaras was due to meet Evangelos Venizelos, the head of the Socialist PASOK party, at 11:00 a.m. EDT after he received a mandate to form a government from the president.
The once-mighty PASOK, now reduced to third place after the dramatic rise of the radical leftist anti-bailout party SYRIZA, said it would support Samaras but had not yet decided whether to join the government or just offer parliamentary backing.
Samaras's narrow defeat of SYRIZA caused relief across the euro zone, where countries had said Greece's future in the single currency depended on its meeting conditions attached to a bailout, which SYRIZA had vowed to tear up.
If SYRIZA had won - and claimed the 50 extra seats in parliament for the party that placed first - it would have been impossible to form a government supporting the bailout.
European leaders viewed Samaras's victory as an aversion of catastrophe. But any relief in financial markets vanished within hours as a rally on Monday quickly reversed.
Samaras still wants a better deal from Europe. He said Greece would meet its bailout commitments, but added: "We will simultaneously have to make some necessary amendments to the bailout agreement, in order to relieve the people of crippling unemployment and huge hardships."
The small Democratic Left party indicated it would be ready to support Samaras if the bailout deal could be softened.
SYRIZA leader Alexis Tsipras again ruled out joining a pro-bailout coalition government.
Germany, the euro zone's paymaster, gave little sign it was willing accept more than minor changes to the timing of some targets in the 130 billion euro ($164 billion) rescue agreed with the European Union and International Monetary Fund.
In deep recession, crushed under its huge public debt and forced to slash public spending and hike taxes repeatedly, Greece is struggling to restore its near-bankrupt economy. A new government could face protests soon after taking office.
"The crisis has been postponed, not necessarily averted," said Theodore Couloumbis, political analyst and vice-president of Athens-based think-tank ELIAMEP.
"For this government to last it has to show results. You can't continue with 50 percent youth unemployment and a fifth straight year of recession," he said.
SYRIZA scored strongly in the election, particularly among young voters, and party leader Tsipras, 37, promised to continue opposition to painful austerity measures.
"I don't think anything good will come out of these elections," said Dinos Arabatzis, a 56 year-old taxi driver who voted for New Democracy. "Whoever is in power now will get burned. Samaras will get burned, and Tsipras will come out much stronger if we go to elections again - that's what worries me."
The election was a rerun of a poll on May 6, which Samaras had forced by withdrawing support from a previous government, but which had left him with too few seats to form a cabinet and Greece in a state of political disarray. Sunday's victory appears to justify his gamble, at least for now.
With nearly 100 percent of ballots counted, New Democracy won 29.7 percent of the vote, ahead of SYRIZA on 27 percent and PASOK on 12.3 percent.
With New Democracy's 50-seat bonus for placing first, a theoretical New Democracy-PASOK alliance would have 162 seats in the 300-seat parliament. Adding the Democratic Left would give it an even more comfortable 179 seat majority.
"The result showed people want the euro, but society remains divided. SYRIZA will be a militant opposition, possibly complicating the new government's efforts," a senior New Democracy official said on condition of anonymity.
"The new government must deliver a positive development soon - an easing of the bailout terms or a positive sign in the economy - or people will lose trust in a week."
MARKET RELIEF EVAPORATES
In the markets, trust had an even shorter shelf life. Though the FTSEurofirst 300 index rose 1.1 percent at the open, the index had shed all those gains before two hours were up, as the underlying problems in the euro zone brought investors back to earth. The euro's rise also evaporated.
More worryingly, Italian and Spanish borrowing costs rose strongly with yields on Spain's 10-year bonds at dangerously high levels of over 7 percent and equivalent Italian debt over 6 percent, showing that the euro zone crisis was intensifying.
The new government may get some help from peers in the 17-member euro zone, relieved Greece is not on course for a euro exit with incalculable consequences for the rest of the bloc.
However, European leaders have offered no prospect of any major overhaul of the bailout agreement, which requires Greece to find 11.7 billion euros in spending cuts in June to qualify for the next loan installment. Greece has enough funds to last only for a few weeks without more aid.
German Foreign Minister Guido Westerwelle said the substance of the bailout agreement was "not negotiable", but he said creditors might be willing to offer some flexibility on timing for some of the targets, given the time lost in campaigning.
"We're ready to talk about the time frame as we can't ignore the lost weeks, and we don't want people to suffer because of that," he told German radio on Monday.
However, even if Athens were granted some leeway, a coalition that won only 40 percent of the vote would struggle to push through reforms in the face of deep public resentment of repeated rounds of tax hikes and pay and pension cuts.
Despite his loss Tsipras appeared buoyed by the election, declaring that it had shown Greeks rejected austerity and had given his party a strong mandate for opposition.
"We should not let that go to waste," he said on Monday.
His attitude has raised fears of a return to the anti-austerity protests that have seen buildings torched, marble paving stones smashed up and much of Athens plastered with graffiti and patrolled by squads of police in riot gear.
"Obviously I voted for SYRIZA so it could win, but the left is becoming stronger by the day and I'm happy about that," said Panagiotis Panagiotou, 55, a butcher in central Athens whose business has been hit by the crisis.
"SYRIZA will be a very powerful opposition party and when we have elections again - which we will - it will be even stronger, if not first."
Underlining the potential instability, the ultra-nationalist Golden Dawn party took 18 seats, repeating its success of May 6 and confirming its status as a force in Greek politics, carried by an angry mood of public protest.
(Additional reporting by Dina Kyriakidou and Karolina Tagaris, Writing by James Mackenzie; Editing by Peter Graff)
Antitoxin strategy may help target other pathogens Public release date: 18-Jun-2012 [ | E-mail | Share ]
Contact: Thomas Keppeler tom.keppeler@tufts.edu 508-839-7910 Tufts University, Health Sciences Campus
'Beads on a string' approach may reduce cost and development time for agents that neutralize and clear pathogenic molecules
North Grafton, MA, June 14, 2012 -- Researchers have unveiled a novel strategy for neutralizing unwanted molecules and clearing them from the body.
The strategy employs chains of binding agents, like "beads on a string", which target two sites on one or more pathogenic molecules to neutralize their activity and promote their clearance by the body's immune system. The low-cost, easy-to-replicate tool has demonstrated applications against several different toxins, from those found in contaminated food to those used in bioterrorism, and may also prove effective in targeting other types of pathogens.
The research team, based at Tufts University's Cummings School of Veterinary Medicine, demonstrated the method's efficacy in preventing the symptoms of botulism, a rare but deadly disease caused by Clostridium botulinum neurotoxin (BoNT), considered one of the most dangerous bioterror threat agents. The findings were presented earlier this year in PLoS ONE.
"Currently, antitoxins are difficult to produce and have a short shelf life, making them very expensive. This new approach provides a low-cost way to develop highly effective antitoxins," said senior author Charles B. Shoemaker, PhD, professor of biomedical sciences at Tufts University's Cummings School of Veterinary Medicine.
"This method has the potential to target a number of pathogens not only toxins such as BoNT, but viruses or inflammatory cytokines. It is an important platform through which to address other significant diseases," says co-author Saul Tzipori, BVSc., DSc, PhD, professor of biomedical sciences and director of the Division of Infectious Diseases at the Cummings School.
Shoemaker and team had earlier found that pools of small 'tagged' binding agents were highly effective in targeting toxins, neutralizing their function, and flagging them for removal via the body's immune system in the presence of an anti-tag monoclonal antibody.
In the newly published in vivo study, the researchers have advanced this approach by linking two BoNT-binding agents together and including two copies of the tag. The binding agents are small, stable proteins derived genetically from unusual antibodies produced by toxin-immune alpacas. The resulting molecule, called a 'double-tagged heterodimer,' binds to two separate sites on the toxin. Binding of this single heterodimeric agent much more effectively neutralizes the toxin than the unlinked monomer binding agents used in the prior research. In addition, attaching two tags to each of the two linked agents leads to toxin decoration by up to four anti-tag monoclonal antibodies, which promotes rapid toxin clearance from the blood, the researchers found (see figure).
The double-tagged heterodimer antitoxin agent strategy was shown to be efficacious against two types of BoNT in the PLoS ONE report. The antitoxin agents were administered at the time of exposure, or shortly after. Treated mice did not show any symptoms of botulism including the lethal paralysis which characterizes the disease, even when exposed to high toxin doses. Thus, the benefits of complex antitoxins were equaled or bettered by administration of two easy-to-produce agents; a heterodimer binding agent and an anti-tag monoclonal antibody.
According to Shoemaker, a major advantage of this approach is that, unlike treatments that only neutralize toxins, this treatment both neutralizes toxins and ensures their rapid clearance from the body. "Agents that only neutralize their pathogenic target will eventually dissociate which will allow the pathogen to continue doing damage if it is not eliminated," he said.
The group has now successfully taken the research further by building longer strings of binding agents that target multiple toxins with a single moleculefor example, the two types of Shiga toxins that are produced by some E. coli found in contaminated foods or the two toxins produced by hospital-acquired C. difficile infections.
###
The work was funded in part by the National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), the Department of Health and Human Services, and the Intramural Research Program of the NIAID.
Additional authors on the paper are co-first authors Jean Mukherjee and Jacqueline M. Tremblay; and Kwasi Ofori, Karen Baldwin, Xiochuan Feng, all in the Department of Biomedical Sciences, and Daniela Bedenice of the Department of Clinical Sciences at the Cummings School. Clinton E. Leysath, of the NIAID, and Robert P. Webb, Patrick M. Wright, and Leonard A. Smith, all of the United States Army Medical Research Institute for Infectious Diseases, also contributed.
Mukherjee J, Tremblay JM, Leysath CE, Ofori K, Baldwin K, et al. "A Novel Strategy for Development of Recombinant Antitoxin Therapeutics Tested in a Mouse Botulism Model." PLoS ONE 7(1): e29941. Published online January 6, 2012, doi: 10.1371/journal.pone.0029941
About the Cummings School of Veterinary Medicine at Tufts University
Founded in 1978 in North Grafton, Mass., Cummings School of Veterinary Medicine at Tufts University is internationally esteemed for academic programs that impact society and the practice of veterinary medicine; three hospitals and two clinics that combined log more than 80,000 animal cases each year; and groundbreaking research that benefits animal, public, and environmental health.
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Antitoxin strategy may help target other pathogens Public release date: 18-Jun-2012 [ | E-mail | Share ]
Contact: Thomas Keppeler tom.keppeler@tufts.edu 508-839-7910 Tufts University, Health Sciences Campus
'Beads on a string' approach may reduce cost and development time for agents that neutralize and clear pathogenic molecules
North Grafton, MA, June 14, 2012 -- Researchers have unveiled a novel strategy for neutralizing unwanted molecules and clearing them from the body.
The strategy employs chains of binding agents, like "beads on a string", which target two sites on one or more pathogenic molecules to neutralize their activity and promote their clearance by the body's immune system. The low-cost, easy-to-replicate tool has demonstrated applications against several different toxins, from those found in contaminated food to those used in bioterrorism, and may also prove effective in targeting other types of pathogens.
The research team, based at Tufts University's Cummings School of Veterinary Medicine, demonstrated the method's efficacy in preventing the symptoms of botulism, a rare but deadly disease caused by Clostridium botulinum neurotoxin (BoNT), considered one of the most dangerous bioterror threat agents. The findings were presented earlier this year in PLoS ONE.
"Currently, antitoxins are difficult to produce and have a short shelf life, making them very expensive. This new approach provides a low-cost way to develop highly effective antitoxins," said senior author Charles B. Shoemaker, PhD, professor of biomedical sciences at Tufts University's Cummings School of Veterinary Medicine.
"This method has the potential to target a number of pathogens not only toxins such as BoNT, but viruses or inflammatory cytokines. It is an important platform through which to address other significant diseases," says co-author Saul Tzipori, BVSc., DSc, PhD, professor of biomedical sciences and director of the Division of Infectious Diseases at the Cummings School.
Shoemaker and team had earlier found that pools of small 'tagged' binding agents were highly effective in targeting toxins, neutralizing their function, and flagging them for removal via the body's immune system in the presence of an anti-tag monoclonal antibody.
In the newly published in vivo study, the researchers have advanced this approach by linking two BoNT-binding agents together and including two copies of the tag. The binding agents are small, stable proteins derived genetically from unusual antibodies produced by toxin-immune alpacas. The resulting molecule, called a 'double-tagged heterodimer,' binds to two separate sites on the toxin. Binding of this single heterodimeric agent much more effectively neutralizes the toxin than the unlinked monomer binding agents used in the prior research. In addition, attaching two tags to each of the two linked agents leads to toxin decoration by up to four anti-tag monoclonal antibodies, which promotes rapid toxin clearance from the blood, the researchers found (see figure).
The double-tagged heterodimer antitoxin agent strategy was shown to be efficacious against two types of BoNT in the PLoS ONE report. The antitoxin agents were administered at the time of exposure, or shortly after. Treated mice did not show any symptoms of botulism including the lethal paralysis which characterizes the disease, even when exposed to high toxin doses. Thus, the benefits of complex antitoxins were equaled or bettered by administration of two easy-to-produce agents; a heterodimer binding agent and an anti-tag monoclonal antibody.
According to Shoemaker, a major advantage of this approach is that, unlike treatments that only neutralize toxins, this treatment both neutralizes toxins and ensures their rapid clearance from the body. "Agents that only neutralize their pathogenic target will eventually dissociate which will allow the pathogen to continue doing damage if it is not eliminated," he said.
The group has now successfully taken the research further by building longer strings of binding agents that target multiple toxins with a single moleculefor example, the two types of Shiga toxins that are produced by some E. coli found in contaminated foods or the two toxins produced by hospital-acquired C. difficile infections.
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The work was funded in part by the National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), the Department of Health and Human Services, and the Intramural Research Program of the NIAID.
Additional authors on the paper are co-first authors Jean Mukherjee and Jacqueline M. Tremblay; and Kwasi Ofori, Karen Baldwin, Xiochuan Feng, all in the Department of Biomedical Sciences, and Daniela Bedenice of the Department of Clinical Sciences at the Cummings School. Clinton E. Leysath, of the NIAID, and Robert P. Webb, Patrick M. Wright, and Leonard A. Smith, all of the United States Army Medical Research Institute for Infectious Diseases, also contributed.
Mukherjee J, Tremblay JM, Leysath CE, Ofori K, Baldwin K, et al. "A Novel Strategy for Development of Recombinant Antitoxin Therapeutics Tested in a Mouse Botulism Model." PLoS ONE 7(1): e29941. Published online January 6, 2012, doi: 10.1371/journal.pone.0029941
About the Cummings School of Veterinary Medicine at Tufts University
Founded in 1978 in North Grafton, Mass., Cummings School of Veterinary Medicine at Tufts University is internationally esteemed for academic programs that impact society and the practice of veterinary medicine; three hospitals and two clinics that combined log more than 80,000 animal cases each year; and groundbreaking research that benefits animal, public, and environmental health.
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Public release date: 18-Jun-2012
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