From the horse's mouth, we're hearing some unfortunate news: Google has taken to its Spanish support pages to announce that the Samsung Galaxy Nexus is not on the list of devices to receive Android 4.4 KitKat. This seems a bit odd, given the new update's focus on "the next billion" and offering solid performance to other budget devices, but at the moment things aren't looking up for owners of the phone -- or any older Nexus devices, for that matter. We've reached out to Google for clarification on this and will update you if and when we hear back.
He's had his fair share of drama dealing with the custody battle of his little girl, and now it appears Pauly D's baby mama Amanda Markert is finally reaching out to him.
On Wednesday (October 30), Amanda took to her Twitter account to tweet the "Jersey Store" star about their daughter Amabella.
"This is getting out of hand, you've had my number since day 1. Come bond with her any day, any time you and your family want," Miss Markert shared.
This online offering surfaced a week after meeting with lawyers to discuss a custody agreement between the DJ and his former fling.
During a recent interview, the 33-year-old revealed his nerves and excitement about becoming a dad, touching on his relationship with Amanda. "It's for the baby, and it could be best to have the original mother, and I'm obviously the father, so I want to take care of the baby."
He continued, "I want to give the baby the best life she ever had, and when I see the pictures.. she's the first girl to ever steal my heart. She's adorable, I love her and I cannot wait."
Also discussing the situation between he and Amanda, Pauly states that they are in "a custody battle, so I want to see the baby as much as I can, so I don't know how that works my first time, but I want my baby, so we'll see what happens. It's in the lawyers' hands now."
In regards to Miss Markert's intentions, the reality star admits that he believes 100 percent that she's only out for her 15 minutes of fame.
In this 2012 image provided by the Department of Veterinary Medicine, University of Bari, a dog, bottom right, watches a video of the silhouette of another dog wagging its tail to its left. At top right is an inset image of the dog's heart rate while the dog was watching the video. A few years ago, researchers discovered a subtle difference in how dogs wag their tails. When a dog sees something positive, such as its owner, it tends to wags its tail more to its right. The wagging tends to go left when it sees something negative, like an unfamiliar dominant dog. In the Thursday, Oct. 31, 2013 issue of the journal Current Biology, the same Italian researchers report that other dogs pick up on that difference, and it’s reflected in their behavior and even their heart rates. (AP Photo/Department of Veterinary Medicine, University of Bari)
In this 2012 image provided by the Department of Veterinary Medicine, University of Bari, a dog, bottom right, watches a video of the silhouette of another dog wagging its tail to its left. At top right is an inset image of the dog's heart rate while the dog was watching the video. A few years ago, researchers discovered a subtle difference in how dogs wag their tails. When a dog sees something positive, such as its owner, it tends to wags its tail more to its right. The wagging tends to go left when it sees something negative, like an unfamiliar dominant dog. In the Thursday, Oct. 31, 2013 issue of the journal Current Biology, the same Italian researchers report that other dogs pick up on that difference, and it’s reflected in their behavior and even their heart rates. (AP Photo/Department of Veterinary Medicine, University of Bari)
NEW YORK (AP) — The way Fido wags his tail might reveal more about him than you know. Just ask another dog.
A few years ago, researchers discovered a subtle difference in how dogs wag their tails. When a dog sees something positive, such as its owner, it tends to wags its tail more to its right. The wagging tends to go left when it sees something negative, like an unfamiliar dominant dog.
Now, the same Italian researchers report that other dogs pick up on that difference, and it's reflected in their behavior and even their heart rates. Experts say the tail-wagging difference appears to be one way that dogs gauge how other dogs will respond to them.
"It's just fascinating that dogs pick up on it," said Evan MacLean, co-director of Duke University's Canine Cognition Center. For humans, he said, "it's a difficult thing to see."
MacLean was not involved with the study, reported Thursday in the journal Current Biology.
Giorgio Vallortigara of the University of Trento in Italy, an author of the study, said Fido is not deliberately sending a message. Instead, the tail-wagging behavior stems from how different emotional cues activate different parts of the brain, he said in an email.
For the experiment, Vallortigara and co-authors used videos of a dog or its silhouette, wagging its tail mostly to one side or the other, or not wagging at all. They showed the videos to 43 dogs, including such breeds as Rottweilers, beagles, boxers, border collies and German shepherds as well as mongrels.
When the dog in the video wagged mostly to its left, the sign of a negative response, observer dogs tended to have faster heartbeats than when it wagged the other way or not at all. Their behavior also indicated a higher degree of stress.
Alexandra Horowitz, who studies mental abilities of dogs at Barnard College in New York, said that the wagging difference is probably not a primary signal between Fido and Rover in daily life, but it may play a minor role.
___
Online:
Current Biology: http://www.cell.com/current-biology
___
Malcolm Ritter can be followed at http://www.twitter.com/malcolmritter
NEW YORK (AP) — A federal appeals court on Thursday blocked a judge's ruling that found the New York Police Department's stop-and-frisk policy was discriminatory and took the unusual step of removing her from the case, saying interviews she gave during the trial called her impartiality into question.
The 2nd U.S. Circuit Court of Appeals in Manhattan said the rulings by U.S. District Judge Shira A. Scheindlin will be stayed pending the outcome of an appeal by the city.
The judge ruled in August the city violated the Constitution in how it carried out its program of stopping and questioning people. The city appealed her findings and her remedial orders, including a decision to assign a monitor to help the police department change its policy and the training program associated with it.
During arguments, lawyers in the case said the police department hasn't had to do anything except meet with a monitor since the judge's decision. But the city said police officers are afraid to stop and frisk people now and the number of stop-and-frisks has dropped dramatically.
The three-judge appeals panel, which heard arguments on the requested stay on Tuesday, noted that the case might be affected in a major way by next week's mayoral election.
Democratic candidate Bill de Blasio, who's leading in polls, has sharply criticized and promised to reform the NYPD's stop-and-frisk technique, saying it unfairly targets minorities. He said he was "extremely disappointed" in Thursday's decision.
The appeals court said the judge needed to be removed because she ran afoul of the code of conduct for U.S. judges in part by compromising the necessity for a judge to avoid the appearance of partiality. It noted she had given a series of media interviews and public statements responding to criticism of the court. In a footnote, it cited interviews with the New York Law Journal, The Associated Press and The New Yorker magazine.
The judge said Thursday that quotes from her written opinions gave the appearance she had commented on the case in interviews. But she said a careful reading of each interview will reveal no such comments were made.
The 2nd Circuit said cases challenging stop-and-frisk policies will be assigned to a different judge chosen randomly. It said the new presiding judge shall stay all proceedings pending further rulings by it.
After a 10-week civil trial that ended in the spring, Scheindlin ruled that police officers violated the civil rights of tens of thousands of people by wrongly targeting black and Hispanic men with the stop-and-frisk program. She appointed an outside monitor to oversee major changes, including reforms in policies, training and supervision, and she ordered a pilot program to test body-worn cameras.
The Center for Constitutional Rights, which represented plaintiffs in the case, said it was dismayed that the appeals court delayed "the long-overdue process to remedy the NYPD's unconstitutional stop-and-frisk practices" and was shocked that it "cast aspersions" on the judge's professional conduct and reassigned the case.
The city said it was pleased with the federal appeals court ruling. City lawyer Michael Cardozo said it allows for a fresh and independent look at the issue.
Stop-and-frisk, which has been criticized by civil rights advocates, has been around for decades, but recorded stops increased dramatically under Mayor Michael Bloomberg's administration to an all-time high in 2011 of 684,330, mostly of black and Hispanic men. A lawsuit was filed in 2004 by four men, all minorities, and became a class action case.
About 5 million stops have been made in New York in the past decade, with frisks occurring about half the time. To make a stop, police must have reasonable suspicion that a crime is about to occur or has occurred, a standard lower than the probable cause needed to justify an arrest. Only about 10 percent of the stops result in arrests or summonses, and weapons are found about 2 percent of the time.
Supporters of changes to the NYPD's stop-and-frisk program say the changes will end unfair practices, will mold a more trusted police force and can affect how other police departments use the policy. Opponents say the changes will lower police morale but not crime.
The judge noted she wasn't putting an end to the stop-and-frisk practice, which is constitutional, but was reforming the way the NYPD implemented its stops.
FILE - In this Oct. 3, 2011 file photo, Dr. Conrad Murray listens to testimony seated near his attorney Nareg Gourjian, right, during Murray's trial in the death of pop star Michael Jackson, in Los Angeles. Murray, who was convicted in Jackson's death is suing the state of Texas for stripping his right to practice medicine, and his attorney said Thursday, Oct. 31, 2013, that the cardiologist has former patients eager for him to work again.(AP Photo/Mario Anzuoni, Pool, File)
AUSTIN, Texas (AP) — The Texas doctor convicted in the death of pop superstar Michael Jackson is suing the state for stripping his right to practice medicine, and his attorney said Thursday that the cardiologist has former patients eager for him to work again.
Conrad Murray, who was released from a California jail this week after serving less than two years for involuntary manslaughter in Jackson's death, accuses the Texas Medical Board of prematurely revoking his license. Murray claims in his lawsuit filed in Austin that his 2011 conviction isn't final in California until his appeals are exhausted.
Murray states in an affidavit that he is more than $400,000 in debt and can't afford to pay court costs.
"Anybody who wants to work in this country ought to be able to have the right to do so. Dr. Murray is like everyone else, in that he needs to be able to do his line of work," said Charles Peckham, Murray's attorney.
Texas Medical Board spokesman Jarrett Schneider said the agency cannot comment on pending litigation.
Murray was convicted of causing Jackson's death in June 2009 by providing him with the powerful anesthetic propofol as a sleep aid. Jackson was in the midst of preparations for a series of comeback concerts and Murray was serving as his physician.
Murray filed the lawsuit Friday, three days before he was freed after serving half of a maximum four-year sentence.
Murray previously maintained clinics in Houston and Las Vegas. His medical license is currently suspended in California.
In court papers filed in Texas, Murray expresses concern that the revocation of his Texas license could give California reason to take the same action.
"The Texas Medical Board, in taking my license puts me in imminent harm of irreparable injury," Murray said in court papers.
Brian Panish, an attorney for the Jackson family, has said Murray should not have "a chance to hurt anyone else" by practicing medicine.
___
Follow Paul J. Weber on Twitter: www.twitter.com/pauljweber
NEW YORK (AP) — Picking the guy who will play Rocky Balboa onstage was no easy task. Just ask Sylvester Stallone, who helped cast Broadway veteran Andy Karl.
"Having gone through literally hundreds, maybe thousands, of prospects, Andy was one of our first choices and he just had it," Stallone said last month during a sit-down with the actor who will be playing his most famous character.
"He has what it takes — there's no arrogance, there's a natural humility about him, and that's what is important," Stallone said.
"No matter how threatening he may look, you're going to like him, it just comes through. And that's not so easy to find. Tough guys are a dime a dozen; a sensitive tough guy, pretty rare."
The musical "Rocky" will open on Broadway at the Winter Garden Theatre in March 2014. Based on the Oscar-winning 1976 film by Stallone, the musical features a score by "Ragtime" veterans Stephen Flaherty and Lynn Ahrens, and a story by Thomas Meehan, who wrote "The Producers" and "Hairspray."
Karl's Broadway credits include "The Mystery of Edwin Drood," ''Jersey Boys," ''9 to 5," ''Legally Blonde," ''The Wedding Singer" and "Saturday Night Fever." Margo Seibert, making her Broadway debut, will star as Adrian, Balboa's love interest.
The musical stays close to the film, which charted the rise and romance of amateur boxer and debt collector Rocky Balboa, who gets his shot against undefeated heavyweight champion Apollo Creed.
The film made famous the image of Balboa running up the steps of the Philadelphia Museum of Art and the quote "Yo, Adrian!" The trumpet-laden funky theme "Gonna Fly Now" and the anthem "Eye of the Tiger" will be in the Broadway version.
The director is Alex Timbers, who directed Broadway's "The Pee-wee Herman Show" and directed and wrote the book for "Bloody Bloody Andrew Jackson." The boxing choreography is being done by Steven Hoggett, who choreographed "American Idiot," ''Peter and the Starcatcher" and "Once."
TUESDAY, APRIL 20, 2010, AT 6:19 PM Tornado Kills at Least Five in Oklahoma
FRIDAY, APRIL 29, 2011, AT 3:07 PM Obama Gets Firsthand Look at a Tornado Damage
TUESDAY, APRIL 20, 2010, AT 6:19 PM Tornado Kills at Least Five in Oklahoma. Very long title. Long long long. Tornado Kills at Least Five in Oklahoma. Very long title. Long long long.
TUESDAY, APRIL 20, 2010, AT 6:19 PM Tornado Kills at Least Five in Oklahoma. Very long title. Long long long. Tornado Kills at Least Five in Oklahoma. Very long title. Long long long.
She’s been working hard on her next directorial project “Unbroken,” and Angelina Jolie just released new photos from the set via Entertainment Weekly.
The “Changeling” chick has been filming in Moreton Bay with stars Garett Hedlund, Finn Wittrock, Jai Courtney, CJ Valleroy, Domhnall Gleeson, and Jack O’Connell, and from the look of the pictures things are getting pretty intense.
Based on the New York Times bestselling book “Unbroken: A World War II Story of Survival, Resilience, and Redemption,” “Unbroken” is slated to hit theaters on December 25th, 2014.
Per the synopsis, “The story follows the incredible life story of Olympian and war hero Louis Zamperini who, along with two other crewmen, survived in a raft for 47 days after a near-fatal plane crash in WWII—only to be caught by the Japanese Navy and sent to a prisoner-of-war camp.”
October 31, 2013 It's Halloween! Watch a live Tiny Desk Concert featuring Neko Case and Kelly Hogan, as well as Eric Bachmann of Crooked Fingers and Archers of Loaf. Case is keeping her outfit under wraps for now, but promises a reveal worthy of the occasion. Come back to this page at 2 p.m. ET to watch.
If you've been having trouble upgrading from Windows 8 to Windows 8.1, and are encountering Blue Screens marked 0xc1900101 - 0x40017 or 0xC1900101-0x20017, 0xC1900101-0x40019 or 0xc1900101 - 0x30018, there may be a fix for your problems. But if none of the remedies offered here get you upgraded, please head to the Microsoft Answers forum and post details about your configuration. Because after two weeks of trying, Microsoft still hasn't figured out what's causing the problem, and your input may help.
On Oct. 18 I wrote about the show-stopper bug for many people upgrading from Windows 8 to Windows 8.1. Martin Dixon posted the original description on the Microsoft Answers forum, shortly after the Windows 8.1 upgrade rolled out:
I have downloaded the Windows 8.1 update from the store but cannot get it to install. Each time I try, I get to the point where it is "getting my devices ready", then the PC restarts to a blue screen with error message. It then tries to recover the installation, fails, then restores Windows 8. When the system boots up after this, I get a message saying:
"Couldn't update to Windows 8.1
Sorry, we couldn't complete the update to Windows 8.1. We've restored your previous version of Windows to this PC.
0xC1900101 - 0x40017"
There is no explanation as to why the update couldn't be completed. Any ideas how to resolve this?
To date, almost 400 posts on that thread -- plus hundreds more on severaladditional, similarthreads -- have led to a small handful of customer-discovered solutions, but no definitive workaround that everyone can apply.
Here are the approaches that seem to work for some people:
If you have SteelSeries peripherals, running the SteelSeries Engine driver, uninstall it before re-trying the upgrade.
If you have an Asus N53 dual-band PCI-e wireless adapter, pull it. If necessary, find another way to download the upgrade.
Maintenance work on Outlook.com's calendar application is now in its second week, and the lengthy, ongoing tune-up could be causing problems for users.
The maintenance began on Oct. 23, according to a note posted on Microsoft's Live Status dashboard, where people can check on the status of the company's consumer online services.
"You might see error messages when creating/editing birthdays. The checkbox to get notifications in the Options page may also be disabled during this time," the announcement says.
Asked for an update, a Microsoft spokesman confirmed on Wednesday that the work hasn't been finished. "We apologize for any inconvenience and expect the updates to be completed soon," he wrote via email.
It's not clear in what ways Outlook.com's calendar is being improved.
Outlook.com is Microsoft's new Webmail service. It made its debut in mid-2012 and has since replaced Hotmail.
Microsoft describes Outlook.com as a total reinvention of webmail, from the user interface to the back-end platform. It's supposed to give Microsoft a stronger competitor to Google's Gmail and Yahoo Mail.
It malfunctioned in August in various ways for several days and experienced a prolonged outage in March.
Juan Carlos Perez covers enterprise communication/collaboration suites, operating systems, browsers and general technology breaking news for The IDG News Service. Follow Juan on Twitter at @JuanCPerezIDG.
Legendary rock musician Lou Reeddied at the age of 71 on Sunday, Oct. 27. According to Rolling Stone, the cause of death is still unknown. Reed is best known for his work with The Velvet Underground and his solo career that spanned over several decades. The Brooklyn native is survived by his wife Laurie Anderson.
Immediately following the news, messages started to pour in on Twitter. Among those who expressed grief over Reed's death were Judd Apatow, Darren Criss and Olivia Wilde. Read on for their reactions, and others:
Dave Navarro: F-ck! One of my all time heroes and friends has passed. RIP Lou!
Judd Apatow: I met Lou Reed and told him he gave me tinnitus at a concert in 1989 that never went away and it was worth it. Dirty Blvd. Love to Lou.
Miguel: wow, just getting to my phone... RIP Lou Reed
Jaime King: We will miss you Lou Reed. Rest is peace.
Miles Teller: RIP Lou Reed
Soleil Moon Frye: I always believed that I have something important to say and I said it. - Lou Reed
Darren Criss: Very sad to hear the news of Lou Reed's passing. Another rocknroll legend has left us mere mortals behind. Thanks for the inspiration, Lou.
Susan Sarandon: NY lost one of its originals with Lou Reed's passing. So sad. RIP.
Juliette Lewis: Me too #LouReed RT “@studiodog: Feeling John Lennon sad right now”
Andy Cohen: Jackie is just speeding away Thought she was James Dean for a day Then I guess she had to crash Valium would have helped that bash #LouReed
Carson Daly: RIP Lou Reed. The Velvet Underground broke all the rules and made music and art become one in NYC during a special era- best to his family
Piper Perabo: Heaven just got cooler, thank you for all you have given us Lou Reed
Samuel L. Jackson: R.I.P. Lou Reed. Just met at the GQ Awards. The music of my generation. Still Relevant!
Rainn Wilson: Lou Reed was carried away on a Satellite of Love to the Dirty Little Boulevard in the sky. (Sorry, couldn't resist) He's in the pantheo ..
Chris Daughtry: Sad to hear of the tragic loss in rock n roll today. #RIPLouReed
Whoopi Goldberg: The great & amazing Lou Reed has died my condolences 2 his wife Laurie Anderson.Lou was1of a kind & this colored girl still says dededede...
David Boreanaz: R.I.P. Lou Reed. Your voice and music will forever be in my soul and heart.
DENVER (AP) — Colorado Avalanche goalie Semyon Varlamov surrendered to Denver police on an arrest warrant on charges of kidnapping and third-degree assault in what authorities are calling a domestic violence incident.
Police released few details about the case Wednesday night during a brief news conference and declined to elaborate, other than to say it involved someone who Varlamov was in an intimate relationship with.
Sgt. Steve Warneke said the 25-year-old Russian goalie went to police Wednesday at about 6 p.m. Warneke didn't know if Varlamov had an attorney.
An email was left by The Associated Press with Varlamov's agent.
The Avalanche said in a statement they were aware of the allegations but wouldn't comment further until the conclusion of the investigation. Varlamov practiced with the team earlier in the day.
Varlamov was still in custody Wednesday night, and was due in court for his first court appearance at 10 a.m. Thursday, according to the Denver County sheriff's website.
Asked if Varlamov will be treated any differently in custody because of his celebrity status, Warneke said: "I don't know what happens once they get to Denver Sheriff's, if they do any particulars for high profile, in regards to keeping them safe.
"I do know we consider every criminal prosecution equally important," Warneke said. "We're concerned about the rights of the victim, the rights of everybody involved. Our goal every time is to provide everybody with a fair and balanced opportunity to go through the judicial system without corrupting that through releasing things that could jeopardize any sort of criminal case."
Acquired from Washington in a 2011 trade, Varlamov is 7-1 this season with a 1.76 goals-against average. On Sunday night, he made 24 saves in a 3-2 home victory over Winnipeg.
The Avalanche play at Dallas on Friday night and Varlamov was scheduled to start. His backup, Jean-Sebastien Giguere, has been just as good in net, recording two shutouts.
Varlamov is in the midst of a resurgent season under new coach Patrick Roy and a staff that includes goalie guru Francois Allaire, who once mentored Roy and Giguere.
Between Roy and Allaire, they've restored Varlamov's confidence a year after he allowed three goals a game. Varlamov said he credits his improvement to Allaire altering his form in goal. Just minor tweaks, he said, but wouldn't elaborate on the specifics of what they were.
Whatever was changed, it has been paying off as he's among the NHL leaders in goals-against, wins and save percentage (.945).
After practice Wednesday, Avalanche defenseman Erik Johhson said it was "pretty cool to see Varly transition into an elite NHL goalie."
___
Associated Press Writer Ivan Moreno contributed to this report.
Here’s the ObamaCare rollout in two sentences: Millions of Americans are losing their health insurance policies because of the law. And many of the soon to be uninsured can’t sign up for the new federal benefits because the Obama administration screwed up its Web site.
COLLEGE STATION Meclizine, an over-the-counter drug used for decades to treat nausea and motion sickness, has the potential for new uses to treat certain infectious diseases and some forms of cancer, according to Dr. Vishal M. Gohil, Texas A&M AgriLife Research biochemist.
"Clearly this drug has many potential new applications," Gohil said. "And now that we know its new target within the cell, we can start to explore ways of using it to treat other diseases. We can 'repurpose' this drug."
The research on meclizine appears in the current online version of the Journal of Biological Chemistry.
"We found a particular enzyme which is inhibited by meclizine has been proposed (in other research) to be a drug target for the treatment of many diseases, including infectious diseases like malaria and African sleeping sickness," Gohil said. "And this pathway has also been proposed to be a critical pathway for the proliferation of cancer cells."
Gohil said his research, which included collaboration with scientists at Harvard Medical School and Massachusetts General Hospital, the University of Rochester and the University of Guelph, had already shown that the drug also works in the treatment of heart attack and stroke.
Meclizine is an antihistamine, synthesized in the 1950s and later found to be useful for treating nausea, motion sickness and vertigo.
Gohil, who also is an assistant professor of biochemistry and biophysics at Texas A&M University, said he started working on the compound when he identified it in a drug-screening experiment aimed at discovering compounds or drugs that inhibit mitochondrial respiration, a process that provides energy to cells.
Mitochondria are structures found in the cells of all eukaryotes, organisms with one or more cells containing a nuclei and organelles that perform specific tasks. Enclosed in membrane, mitochondria are responsible for supplying the cell with energy and are connected to a cell's life and death.
"When that drug screen identified meclizine, it was a bit of a surprise for us, because this compound had been in the market for several years and had never been linked to mitochondrial respiration," Gohil said. "It's a known drug, and was known to target a few of the molecules within the cell."
But unlike other classes of antihistamine, he noted, meclizine has a unique property which allows it to be used for the treatment of nausea and motion sickness, while most other antihistamines cannot.
"So there was this unique thing about this particular antihistamine," Gohil noted. "And it is well-tolerated so the toxicological profile is very acceptable, so it doesn't have to be sold under strict regulations."
"With that kind of profile, when we saw it in our drug screen we got excited about it because we could see that it decreases cellular oxygen consumption or respiration," he said. "We started trying to figure out the mechanism and to see if it could have any clinical benefit and application."
Gohil said for certain diseases like stroke, heart attack and some neurological diseases, previous medical research has shown that if mitochondrial respiration can be turned down, it could be beneficial for treatment.
"The way many of the cells die during the heart attack or stroke is connected to mitochondrial respiration, so the idea was that if you can turn down the respiration, then it will prevent death," he said. "This is exactly what we found when used meclizine in models of heart attack, stroke and even Huntington disease. We have a drug with a known clinical use and have identified a new biochemical target within the cells, so that opens up new applications."
He said when he and colleagues started studying the mechanism of this drug in terms of how it is inhibiting mitochondrial respiration, they made a couple of fundamental observations. "First, when we add this drug to the whole cells, we see reduced respiration, not rapidly but slowly," he said.
The researchers then added the drug to isolated mitochondria, which is the main site of respiration within the cells.
"But we did not see an effect, so that gave us the idea that this drug may not be directly targeting one of the enzymes of mitochondria which are required for or participates in consuming oxygen," Gohil said. "We used that clue to figure out how non-mitochondrial pathways could be targeted by this drug."
He used an unbiased metabolic profiling approach, a new technology that gives a snapshot of metabolite levels before and after the treatment of a drug so researchers can get an idea of how this drug is perturbing these metabolites.
"Through metabolic profiling, we found one particular metabolite - phosphoethanolamine - was in fact 'going through the roof' within a few hours of the treatment," Gohil said. "We got excited about that."
He explained that phosphoethanolamine is an intermediate in a biosynthetic pathway of a common phospholipid that forms the membrane around the cells. It is present in all living matter from the lower organisms such as bacteria all the way to humans. Thus, finding that the metabolite that was elevated when cells were treated with meclizine indicated a link between this pathway, or metabolite, and respiration.
"Our research showed that if we just take this metabolite and directly add it to mitochondria, it actually inhibits the respiration," Gohil said. "The reason we could use the drug for infectious disease or cancer is not because it inhibits respiration but because it inhibits a phospholipid biosynthetic enzyme that is required to form the building blocks of membranes."
###
[
| E-mail
Share
]
AAAS and EurekAlert! are not responsible for the accuracy of news releases posted to EurekAlert! by contributing institutions or for the use of any information through the EurekAlert! system.
Old drug may teach new tricks in treating infectious diseases, cancer
COLLEGE STATION Meclizine, an over-the-counter drug used for decades to treat nausea and motion sickness, has the potential for new uses to treat certain infectious diseases and some forms of cancer, according to Dr. Vishal M. Gohil, Texas A&M AgriLife Research biochemist.
"Clearly this drug has many potential new applications," Gohil said. "And now that we know its new target within the cell, we can start to explore ways of using it to treat other diseases. We can 'repurpose' this drug."
The research on meclizine appears in the current online version of the Journal of Biological Chemistry.
"We found a particular enzyme which is inhibited by meclizine has been proposed (in other research) to be a drug target for the treatment of many diseases, including infectious diseases like malaria and African sleeping sickness," Gohil said. "And this pathway has also been proposed to be a critical pathway for the proliferation of cancer cells."
Gohil said his research, which included collaboration with scientists at Harvard Medical School and Massachusetts General Hospital, the University of Rochester and the University of Guelph, had already shown that the drug also works in the treatment of heart attack and stroke.
Meclizine is an antihistamine, synthesized in the 1950s and later found to be useful for treating nausea, motion sickness and vertigo.
Gohil, who also is an assistant professor of biochemistry and biophysics at Texas A&M University, said he started working on the compound when he identified it in a drug-screening experiment aimed at discovering compounds or drugs that inhibit mitochondrial respiration, a process that provides energy to cells.
Mitochondria are structures found in the cells of all eukaryotes, organisms with one or more cells containing a nuclei and organelles that perform specific tasks. Enclosed in membrane, mitochondria are responsible for supplying the cell with energy and are connected to a cell's life and death.
"When that drug screen identified meclizine, it was a bit of a surprise for us, because this compound had been in the market for several years and had never been linked to mitochondrial respiration," Gohil said. "It's a known drug, and was known to target a few of the molecules within the cell."
But unlike other classes of antihistamine, he noted, meclizine has a unique property which allows it to be used for the treatment of nausea and motion sickness, while most other antihistamines cannot.
"So there was this unique thing about this particular antihistamine," Gohil noted. "And it is well-tolerated so the toxicological profile is very acceptable, so it doesn't have to be sold under strict regulations."
"With that kind of profile, when we saw it in our drug screen we got excited about it because we could see that it decreases cellular oxygen consumption or respiration," he said. "We started trying to figure out the mechanism and to see if it could have any clinical benefit and application."
Gohil said for certain diseases like stroke, heart attack and some neurological diseases, previous medical research has shown that if mitochondrial respiration can be turned down, it could be beneficial for treatment.
"The way many of the cells die during the heart attack or stroke is connected to mitochondrial respiration, so the idea was that if you can turn down the respiration, then it will prevent death," he said. "This is exactly what we found when used meclizine in models of heart attack, stroke and even Huntington disease. We have a drug with a known clinical use and have identified a new biochemical target within the cells, so that opens up new applications."
He said when he and colleagues started studying the mechanism of this drug in terms of how it is inhibiting mitochondrial respiration, they made a couple of fundamental observations. "First, when we add this drug to the whole cells, we see reduced respiration, not rapidly but slowly," he said.
The researchers then added the drug to isolated mitochondria, which is the main site of respiration within the cells.
"But we did not see an effect, so that gave us the idea that this drug may not be directly targeting one of the enzymes of mitochondria which are required for or participates in consuming oxygen," Gohil said. "We used that clue to figure out how non-mitochondrial pathways could be targeted by this drug."
He used an unbiased metabolic profiling approach, a new technology that gives a snapshot of metabolite levels before and after the treatment of a drug so researchers can get an idea of how this drug is perturbing these metabolites.
"Through metabolic profiling, we found one particular metabolite - phosphoethanolamine - was in fact 'going through the roof' within a few hours of the treatment," Gohil said. "We got excited about that."
He explained that phosphoethanolamine is an intermediate in a biosynthetic pathway of a common phospholipid that forms the membrane around the cells. It is present in all living matter from the lower organisms such as bacteria all the way to humans. Thus, finding that the metabolite that was elevated when cells were treated with meclizine indicated a link between this pathway, or metabolite, and respiration.
"Our research showed that if we just take this metabolite and directly add it to mitochondria, it actually inhibits the respiration," Gohil said. "The reason we could use the drug for infectious disease or cancer is not because it inhibits respiration but because it inhibits a phospholipid biosynthetic enzyme that is required to form the building blocks of membranes."
###
[
| E-mail
Share
]
AAAS and EurekAlert! are not responsible for the accuracy of news releases posted to EurekAlert! by contributing institutions or for the use of any information through the EurekAlert! system.
Health and Human Services Secretary Kathleen Sebelius testifies on Capitol Hill in Washington, Wednesday, Oct. 30, 2013, before the House Energy and Commerce Committee hearing on the difficulties plaguing the implementation of the Affordable Care Act. Partisan sparks were flying in Congress on Tuesday as Sebelius, President Barack Obama's top health official apologized for wasting consumers' time as they tried to use the crippled website that allows them to buy government mandated health insurance under the overhaul known as Obamacare. (AP Photo/J. Scott Applewhite)
Health and Human Services Secretary Kathleen Sebelius testifies on Capitol Hill in Washington, Wednesday, Oct. 30, 2013, before the House Energy and Commerce Committee hearing on the difficulties plaguing the implementation of the Affordable Care Act. Partisan sparks were flying in Congress on Tuesday as Sebelius, President Barack Obama's top health official apologized for wasting consumers' time as they tried to use the crippled website that allows them to buy government mandated health insurance under the overhaul known as Obamacare. (AP Photo/J. Scott Applewhite)
Rep. Cory Gardner, R-Colo., holds up a letter he wrote to Health and Human Services Secretary Kathleen Sebelius asking that she consider waiving "Obamacare" for the 4th Congressional District of Colorado, as she testified before the House Energy and Commerce Committee about the difficulties plaguing the debut of the healthcare program, on Capitol Hill in Washington, Wednesday, Oct. 30, 2013. (AP Photo/J. Scott Applewhite)
Health and Human Services Secretary Kathleen Sebelius testifies on Capitol Hill in Washington, Wednesday, Oct. 30, 2013, before the House Energy and Commerce Committee hearing on the difficulties plaguing the implementation of the Affordable Care Act. Partisan sparks were flying in Congress on Tuesday as Sebelius, President Barack Obama's top health official apologized for wasting consumers' time as they tried to use the crippled website that allows them to buy government mandated health insurance under the overhaul known as Obamacare. (AP Photo/ Evan Vucci)
WASHINGTON (AP) — Here's what some Republicans want to know: If Health and Human Services Secretary Kathleen Sebelius thinks the new health insurance marketplace is going to be so great, why doesn't she get her own coverage from it?
As a Medicare beneficiary, she can't.
But her response to Republicans who pressed her Wednesday to sign up under a health insurance exchange was problematic. She said that because she's part of the federal employee health plan, she's not eligible to switch to the exchanges.
In fact, Americans who have workplace health insurance, as most with coverage do, can drop it in favor of individual policies offered by the exchanges. But doing so would not make financial sense for most.
A look at the back and forth at a House hearing, with underlying facts:
REP. CORY GARDNER, R-Colo.: "You're in charge of this law, correct? Why aren't you in the exchange?"
SEBELIUS: "Because I'm part of the federal employee health benefit plan. ... I'm not eligible for the exchange."
GARDNER: "You can decide to drop your coverage of your employer. You have the choice to decide not to choose ..."
SEBELIUS: "Not true, sir."
GARDNER: "I would encourage you to be just like the American people and enter the exchange and agree to find a way ..."
SEBELIUS: "It's illegal."
GOP Rep. Billy Long of Missouri also tried.
LONG: "You're architect of the whole program and you won't go into it with the rest of the American public."
SEBELIUS: "I did not say that, sir. I think it's illegal for me to."
LONG: "If you can, will you?"
SEBELIUS: "I will take a look at it."
___
THE FACTS:
It would be financially nonsensical for most with federal employee health insurance to step away from it in favor of an individual policy in the exchange. Doing so would mean losing the employer contribution to the health plan. It's also unlikely they would qualify for subsidized coverage available to many who seek insurance in the exchanges because they don't have access to workplace coverage.
But Sebelius' point that she can't do it because her federal employee insurance disqualifies her doesn't hold up.
What does block her from enrolling in an exchange is her status as a Medicare beneficiary, which she did not mention at the hearing. Plans offered by the exchanges cannot be sold to people on Medicare, and her department said in a statement that "the secretary is a Medicare enrollee."
Gardner told the hearing his family chose to have a private policy in Colorado "so we could be in the same boat as every one of my constituents."
But individual private policies are not the norm. Employer-based group coverage is. In that sense, Sebelius is already "just like the American people," as Gardner implored her to become.
It's no secret that Facebook likes its targeted advertising. However, that affinity may soon blossom into a full-fledged love affair. The social network's Ken Rudin tells the Wall Street Journal that his company is testing a system which targets ads based on where users' mouse cursors hover; it can also tell whether or not mobile users see their news feeds. Neither tracking technology is new, but the scale of behavioral data collection would be unprecedented when Facebook has almost 1.2 billion users. Don't be too quick to close your account in protest, though. Rudin notes that there won't be a decision on the technology for another "couple of months," and it may never see the light of day. If you don't like the idea of Facebook monitoring your on-screen habits, we'd suggest making yourself heard.
This artist's rendering provided by the Harvard-Smithsonian Center for Astrophysics on Wednesday, Oct. 30, 2013 shows the planet Kepler-78b, foreground, orbiting less than one million miles from its sun. Astrophysicists reported Wednesday in the journal Nature that the exoplanet appears to be made of rock and iron just like Earth. (AP Photo/Harvard-Smithsonian Center for Astrophysics, David A. Aguilar)
This artist's rendering provided by the Harvard-Smithsonian Center for Astrophysics on Wednesday, Oct. 30, 2013 shows the planet Kepler-78b, foreground, orbiting less than one million miles from its sun. Astrophysicists reported Wednesday in the journal Nature that the exoplanet appears to be made of rock and iron just like Earth. (AP Photo/Harvard-Smithsonian Center for Astrophysics, David A. Aguilar)
This artist's rendering provided by the Harvard-Smithsonian Center for Astrophysics on Wednesday, Oct. 30, 2013 shows a comparison between the Earth and planet Kepler 78b which is located in the Cygnus constellation hundreds of light-years away. Astrophysicists reported Wednesday in the journal Nature that the exoplanet appears to be made of rock and iron just like Earth. Kepler-78b is about 20 percent larger, with a diameter of 9,200 miles, and weighs roughly 1.8 times as much as Earth. (AP Photo/Harvard-Smithsonian Center for Astrophysics, David A. Aguilar)
CAPE CANAVERAL, Fla. (AP) — Scientists have found a planet way out in the cosmos that's close in size and content to Earth — an astronomical first.
But hold off on the travel plans. This rocky world is so close to its sun that it's at least 2,000 degrees hotter than here, almost certainly too hot for life.
Astrophysicists reported Wednesday in the journal Nature that the exoplanet Kepler-78b appears to be made of rock and iron just like Earth. They measured the planet's mass to determine its density and content. It's actually a little bigger than Earth and nearly double its mass, or weight.
Kepler-78b is located in the Cygnus constellation hundreds of light-years away. Incredibly, it orbits its sun every 8½ hours, a mystery to astronomers who doubt it could have formed or moved that close to a star. They agree the planet will be sucked up by the sun in a few billion years, so its time remaining, astronomically speaking, is short.
More than 1,000 exoplanets — worlds outside our solar system — have been confirmed so far.
NASA's Kepler Space Telescope, used to discover Kepler-78b, has identified 3,500 more potential candidates. The telescope lost its precise pointing ability earlier this year, and NASA has given up trying to fix it.
Scientific teams in the United States and Switzerland used ground observatories to measure Kepler-78b.
FILe - This Sept. 22, 2013 file photo shows actress Claire Danes at the 65th Primetime Emmy Awards at Nokia Theatre in Los Angeles. Danes has been tapped to host the 20th anniversary Nobel Peace Prize concert in December. The Emmy-winning “Homeland” actress will host the Dec. 11 event in Oslo, Norway. (Photo by Dan Steinberg/Invision/AP, File)
NEW YORK (AP) — Claire Danes has been tapped to host the 20th anniversary Nobel Peace Prize concert in December.
The Emmy-winning "Homeland" actress will host the Dec. 11 event in Oslo, Norway.
The concert will celebrate the Organization for the Prohibition of Chemical Weapons, which was awarded the prestigious honor earlier this month.
The watchdog agency works to eliminate the world's chemical weapons and received the prize days after OPCW inspectors started arriving in war-torn Syria to oversee the dismantling of President Bashar Assad's chemical arsenal.
The Nobel Peace Prize concert typically attracts top celebrities. Past luminaries have included Paul McCartney, Rihanna, and Tony Bennett. The lineup for this year's concert has yet to be announced.
BOSTON (AP) — A look at Game 6 of the World Series at Fenway Park on Wednesday night as the St. Louis Cardinals take on the Boston Red Sox:
___
THREE OUTS AWAY: Brandon Workman pitches a perfect eighth inning to protect a 6-1 lead for the Red Sox.
Singing, chanting crowd can hardly wait.
___
JOB WELL DONE: John Lackey exits with the bases loaded and two outs in the seventh inning, tips his cap to the cheering crowd at Fenway.
Cardinals had cut it to 6-1 on Carlos Beltran's run-scoring single, but Junichi Tazawa keeps it right there by retiring Allen Craig on a grounder.
___
RUNNING OUT OF TIME: Matt Holliday flies out with runners at the corners to end the fifth, and the Cardinals are 0 for 7 with runners in scoring position tonight. That makes them 6 for 40 (.150) in the Series. They've stranded six overall tonight.
St. Louis caught a break in the fourth when Gold Glove second baseman Dustin Pedroia botched a grounder that should have been an inning-ending double play. John Lackey, however, pitched out of trouble again by retiring Matt Adams on a liner to left and throwing a called third strike past David Freese.
___
OPENING UP: Even slumping Stephen Drew gets in on the act with a home run on the first pitch of the fourth. Red Sox lead 4-0 against Michael Wacha.
Jacoby Ellsbury also tees off for a rocket that hits the low wall in right-field near the 380-foot sign. It's a double, and Wacha gets pulled after an intentional walk to Big Papi that puts runners at the corners with two outs.
It's the third walk for Ortiz tonight — two intentional. Cardinals have obviously seen enough of him in this Series.
Ellsbury scores on Mike Napoli's single off Lance Lynn, and a walk to Jonny Gomes brings up Shane Victorino with the bases loaded again. Just an RBI single this time to make it 6-0.
___
BOBBY V: Wonder what Bobby Valentine is thinking tonight. Bet he's watching, maybe at his restaurant in Connecticut?
___
BAGS FULL: Shane Victorino does it again with the bases loaded.
His three-run double high off the Green Monster gives Boston a 3-0 lead in the third inning. It was Victorino's first hit since that go-ahead grand slam in the ALCS clincher against Detroit.
Victorino was 0 for 10 in the Series before connecting. He sat out the previous two games with a stiff back, but returned for this one and was dropped from his regular No. 2 spot to sixth in the lineup.
Jonny Gomes was hit by a pitch to load the bases — the first batter rookie Michael Wacha had ever hit in his career.
Victorino, the master of getting hit by pitches, standing almost on top of the plate. He gets ahead 2-0 in the count before pouncing on a 2-1 fastball.
Wacha doesn't have it tonight. In truth, his stuff didn't look as sharp in Game 2 at Fenway as it did during the NL playoffs, but he held Boston in check and won 4-2.
___
DIDN'T MISS A BEAT: Is anyone else amazed at how consistently hard Allen Craig has hit the ball in this Series after missing so much time with that sprained foot? DH, pinch-hitting, hasn't mattered. He's been right on Red Sox pitching. Now 2 for 2 in Game 6 and 6 for 14 in the Series.
___
QUICK WORK: John Lackey needs only five pitches to get through the third inning — even though Matt Carpenter singled with one out.
Daniel Descalso looked at three straight strikes to start the inning. After the single by Carpenter, Carlos Beltran grounded into a double play.
___
EARLY ESCAPES: Both starters pitch out of trouble in the second inning.
St. Louis put two on with none out but failed to score. John Lackey threw a two-out wild pitch that pushed the runners to second and third, then struck out Jon Jay.
That left the Cardinals 6 for 36 with runners in scoring position during the Series after setting a franchise record with a .330 mark in those situations during the regular season.
You get the feeling if the Cardinals can break through for one big hit at the right time in this game, the floodgates might open. But without it, they'll go home lamenting their lack of clutch hitting in this Series.
Matt Adams flied out to deep left, but David Freese skied to shallow center on a hittable breaking ball. Tim McCarver on Fox notes Freese, the hometown star for St. Louis in the 2011 Series, has stranded 15 runners this postseason.
Forgive us, but Freese has looked frozen all Series.
Lackey and Boston manager John Farrell all fired up.
Boston put two on to start the bottom of the second and failed to score, too. Chose not to bunt with rookie Xander Bogaerts. Not a surprise — the Red Sox don't like to sacrifice.
Wacha got two foul popups and a strikeout to keep it scoreless.
___
PACKED HOUSE: Man, oh man, are they fired up in Boston.
Red Sox looking to clinch a World Series title on their own field at fabled Fenway Park for the first time in 95 years, a stretch that's lasted from Babe Ruth to Big Papi.
Needless to say, tickets have been going for quite a pretty penny.
To do it, Boston will have to overcome rookie sensation Michael Wacha, who is 4-0 with a 1.00 ERA in four postseason starts. Can the kid do it again — under save-the-season pressure in this electric environment — and force a Game 7?
Red Sox right-hander John Lackey is trying to become the first pitcher to start and win the clinching game of a World Series for two teams. He won Game 7 of the 2002 World Series for the Anaheim Angels as a rookie against San Francisco.
And we're underway in Game 6. Lackey works a 1-2-3 first inning, helped out by a tough play from second baseman Dustin Pedroia in short right field.
___
BALLPARK BUZZ: Fenway Park was jumping early as fans poured into the old yard, hoping for a big night. Program vendors loudly reminded folks to pick up their souvenirs on the way in.
The ballpark organist tried to set a lucky tone, playing "This Magic Moment" and "Daydream Believer" and "I'm Looking Over a Four-Leaf Clover" during batting practice.
Great version of the national anthem by local band The Dropkick Murphys. Felt like last call at a packed Irish pub.
That came right after Red Sox greats Carlton Fisk and Luis Tiant threw out the first balls. Fisk, still a king at Fenway for the home run that won Game 6 of the 1975 World Series, got right in the spirit that has taken over this team — before his toss, he put on a playful beard for the ceremonies.
By now, you know that the National Security Agency tracks the online movements of US citizens with the cooperation of major Internet corporations. But now, the Washington Post reports that according to documents from NSA whistleblower and fugitive Edward Snowden, the organization is also spying on us through Google and Yahoo, without these companies' knowledge.
As with any company or connected home, these two corporations have gateways to the outer, entirely public Internet. The NSA has successfully tapped into these links, providing them with a wealth of information that they did not yet have, including not just the metadata revealed in Snowden's initial disclosures, but actual content, such as text and video.
The amount of information is staggering. A top-secret report from January 2013 states that this project, called MUSCULAR, acquires millions of records daily from Google and Yahoo. In one 30-day period ending in January, the NSA collected over 181 million new records from these secret sources.
This is in addition to PRISM, the previously Snowden-disclosed program that gathered information on US citizens with the cooperation of Google, Yahoo, and other high-profile Internet companies such as Facebook and Microsoft.
Not surprisingly, Google and Yahoo have publically condemned the reports of government hacking. A Google spokesperson told the Washington Post that the company was “troubled by allegations of the government intercepting traffic between our data centers, and we are not aware of this activity." But the spokesperson also admitted that there were reasons to worry. "We have long been concerned about the possibility of this kind of snooping, which is why we continue to extend encryption across more and more Google services and links.”
And Yahoo has stated that “We have strict controls in place to protect the security of our data centers, and we have not given access to our data centers to the NSA or to any other government agency.”
The NSA didn't do this alone. Their British equivalent, the Government Communications Headquarters (GCHQ) was also involved in MUSCULAR. Like the NSA, the GCHQ has had its own spying scandals. Last June, it was discovered that they had tapped fiber optic cables to intercept the electronic communications, and that they collected data from visiting foreign politicians.
The NSA does its MUSCULAR data mining outside of the country--a legal advantage. The organization must follow relatively strict rules about data gathering in the United States. But if data is picked up overseas, the government can assume that at least one of the people involved is a foreigner, and therefore not subject to as much protection.
According to NSA head Keith Alexander, all of this is entirely justifiable. "None of this shows that [the] NSA is doing something illegal, or that it has not been asked to do," he said in an interview immediately after the leaks. "It's legal, it's necessary, and it's authorized in every case."
[ This sponsored article was written by IDG Creative Lab, a partner of PCWorld. ]
![[ Back to EurekAlert! ]](http://www.eurekalert.org/images/back2e.gif){kind=small}
Share
Source: 
