INDIANAPOLIS ? Playing football as a youngster, Luke Joeckel was an offensive lineman trapped in a quarterback?s body. He was perhaps the only football player ever who liked throwing blocks more than passes.
In high school, Joeckel?s body began to fill out, allowing him to play the position he truly wanted.
?I love offensive line,? Joeckel, the Texas A&M offensive tackle, said Thursday at the NFL scouting combine. ?Growing up, I thought I was too athletic for the position. I was a quarterback in junior high.
?I ended up on the offensive line just because I was the biggest guy on the team. Offensive line is what I was born to play. I love the position and the physical aspect of it. You finish every single play with a one-on-one block. There aren?t many positions on the field like that.?
Joeckel at Texas A&M played tackle well enough that he?s considered the best available at his position in this year?s NFL Draft. He?s also one of the top players at any position and could be of interest to the Chiefs with the top pick in the draft.
Their left tackle, Branden Albert, is a potential free agent. Chiefs coach Andy Reid was non-committal about their interest in re-signing Albert.
If Albert signs with another team and the Chiefs don?t replace him in free agency, Joeckel could easily wind up as the number one pick in the draft and play in Kansas City.
?It?s crazy to think about,? Joeckel said. ?Starting football in the second grade, you really don?t think about that stuff.
?It would be a cool place to go. I?ve been to Kansas City once before and I loved the barbecue.?
Reid said his homework on Joeckel had only begun.
?I?d heard he was a good football player,? Reid said. ?I put on the film and he was a good football player.?
Joeckel?s twin brother Matt is a backup quarterback at Texas A&M. Matt Joeckel will be a junior next season. The two are in the same year in school but Matt Joeckel redshirted as a freshman and Luke declared for the draft after his junior season.
For awhile, they were dueling quarterbacks. Then Luke started his growth spurt, leaving his brother and the quarterback position behind.
?I grew up probably fighting multiple times a day with my twin brother,? Luke said. ?When we were little, we were closer in size, only about five or 10 pounds apart. Now, we?re about 70 or 80 pounds, so he doesn?t mess with me much anymore.?
Luke blocked for Matt in high school in Arlington, Texas. Luke recalled a play in which he knocked down the player he was blocking, but sent him flying into Matt, resulting in a sack.
?I got up and instead of him yelling at me, I was yelling at him,? Joeckel said. ?He didn?t chew me out for giving up a sack. I chewed him out once for me giving up a sack.?
That?s the type of player the Chiefs would be getting if they drafted Joeckel. He blocked as a sophomore at Texas A&M for Ryan Tannehill, who was drafted in the first round last year by Miami.
Last season his quarterback was Johnny Manziel, the Heisman Trophy winner. Joeckel said he believed he improved while blocking for Manziel, whose scrambling style allowed him to extend many passing plays.
?Definitely it made me better,? Joeckel said. ?You see how he extends plays and you?ve got to learn quickly how to hold your block longer. That definitely made me a better pass blocker. It made me more conditioned, which I think is huge.?
Another of the draft?s top tackles is Eric Fisher of Central Michigan. He impressed scouts with a strong showing at last month?s Senior Bowl, where he got a chance to play against top competition.
?My goal here is to prove to everybody that I am the number one tackle in the nation,? Fisher said.
Like Joeckel, he is a late bloomer. Fisher weighed only about 235 pounds coming out of high school, so the bigger colleges weren?t interested.
?The only Big Ten schools I talked to were Michigan State and Purdue and neither of them really wanted anything to do with me,? he said. ?It doesn?t matter where you start. It?s where you end up. That?s a big thing I take to heart.
?I think I have a lot of room to improve. I definitely don?t think I?ve played my best football. I still have a lot to grow into my body. Physically, I feel a lot better because I came in and put on over 70 pounds (since going to college). It took a while into develop into that. But I?m finally starting to feel good and getting used to a solid 300, 310 pounds.?
Reid, a former offensive-line coach, said he wasn?t adverse to playing a rookie at left tackle if that?s what it came to for the Chiefs.
?I?m going to play the best players,? Reid said. ?If that?s who it is, I would tell you yes. I?ve got to go through and evaluate those guys and see if any of them are worthy of that spot.
?Can you do that? Yeah, you can do that. You see it throughout the league. Guys do it.?
Cal and Arizona State enter the field while SEC teams show they have work to do
Selection Sunday is less than a month away, and the picture for who?s in and who?s out of the NCAA Tournament is becoming more clear.
In general, most of the 68 spots are fairly certain. Of the 32 conferences, we?ve tabbed 20 as being one-bid leagues, determined solely by conference tournaments. On the other end of the spectrum, at least 30 teams are safely in the field barring a total collapse between now and March 17.
That leaves the bubble, where every win and loss is magnified and every result from November and December takes on a renewed significance.
Here?s our look at the NCAA Tournament field for 2013. This is not intended to be a prediction, per se, but a snapshot at how the field may look right now.
We looked at RPI, strength of schedule, good wins and bad losses in our projections. You will also see references to Ken Pomeroy?s rankings. The selection committee is not instructed to use the rankings during the selection process, but we include them as an added resource.
NCAA TOURNAMENT BRACKET PROJECTIONS: FEB. 21
TOP FOUR SEEDS Indiana Miami Duke Michigan State
ACC (5) In: Duke, Miami, North Carolina, NC State, Virginia Worth a mention: Florida State, Maryland Bubble notes: Virginia entered the field last week and remains in despite road losses to North Carolina and Miami. The Cavs missed a golden chance to all but clinch a bid with the 54-50 road loss to the Hurricanes on Tuesday. Maryland moved one step forward with a win over Duke on Saturday and then one step back by losing to Boston College on Tuesday. The regular season finale between the Terps and Cavs in Charlottesville may be a key game for both. Other than a season sweep of Maryland, Florida State is running low on quality ACC wins.
Related: This week's college basketball power rankings
Atlantic 10 (5) In: Butler, La Salle, Saint Louis, Temple, VCU Worth a mention: Charlotte, UMass, Xavier Bubble notes: VCU has a good resume numbers-wise, but the Rams missed an opportunity to solidify their profile by losing to Saint Louis on Tuesday. Their best win remains Memphis in the Battle 4 Atlantis. Temple put itself into a precarious position by losing to Duquesne, which is ranked outside the top 200 in the RPI. Three wins over the Syracuse and Saint Louis, plus wins over bubble teams Charlotte, Villanova and UMass could work in the Owls? favor. Charlotte is hovering just inside the top 50 in the RPI with its worst loss coming to George Washington on the road. The 49ers two standout wins, however. (La Salle, at Butler). UMass lost on the road to St. Bonaventure on Wednesday, making the Minutemen an at-large longshot.
Related: Key games with postseason implications to watch this week
Big 12 (5) In: Iowa State, Kansas, Kansas State, Oklahoma, Oklahoma State Worth a mention: Baylor Bubble notes: In a game between bubble teams Wednesday, Iowa State defeated Baylor 87-82 for a regular season sweep. If Baylor is left out of the field, it will be due to the Bears' poor performance against the Tournament-bound teams in the Big 12: Baylor's only win over the "in" group was over Oklahoma State at home in January.
Related: Ben McLemore, Marcus Smart or Anthony Bennett: Who is the best freshman?
Big East (8) In: Cincinnati, Georgetown, Louisville, Marquette, Notre Dame, Pittsburgh, Syracuse, Villanova Worth a mention: St. John?s Bubble notes: By defeating RPI No. 32 Connecticut on the road on Saturday, Villanova moves back into the field. The win gave the Wildcats their first top-100 road win, joining a resume that already includes victories over Louisville and Syracuse. ?Nova has a bad loss to No. 254 Columbia, but that is the Wildcats? only loss to a team outside of the top 100. St. John?s is fading with three losses in its last five games, albeit all three on the road against Tournament-bound teams (Georgetown, Syracuse and Louisville). Remaining games against Pittsburgh, Notre Dame (on the road) and Marquette may be must-win situations.
Big Ten (7) In: Illinois, Indiana, Michigan, Michigan State, Minnesota, Ohio State, Wisconsin Worth a mention: Iowa Bubble notes: After enduring a 2-7 start to Big Ten play, Illinois looked like it would work its way onto the bubble despite a stellar non-conference performance. Since the lackluster conference start, Illinois has gone on a four-game win streak, defeating Indiana and Minnesota two weeks ago and then 20-point routs of Purdue and Northwestern. Iowa?s case to join the field is getting stronger with Sunday?s 72-51 win over Minnesota, its third RPI top-50 win of the season, all of which at home. The Hawkeyes are being dragged down by a weak non-conference schedule.
Related: Key stats from Feb. 11-17
Conference USA (1) In: Memphis Worth a mention: Southern Miss Bubble notes:Southern Miss has only two top-100 wins (Denver and UTEP), leaving Conference USA as a possible one-bid league if Memphis wins the tournament. The Tigers? at-large credentials aren?t great, either, with a win at Southern Miss being Memphis? signature achievement this season. Missouri Valley (2) In: Creighton, Wichita State Worth a mention: Indiana State, Northern Iowa Bubble notes: The at-large profiles coming out of the Missouri Valley will give the selection committee much to ponder. Wichita State recovered from a three-game losing streak to win four of a row, including Tuesday?s win over NCAA hopeful Indiana State (RPI No. 64) on the road. Creighton ended its own three-game losing streak Saturday with a come-from-behind win at Evansville before dispatching Southern Illinois on Tuesday. A BracketBuster game at Saint Mary?s on Saturday could help both teams? at-large credentials. Indiana State had been flirting with a spot in the Tournament, but the Sycamores? three-game losing streak will be tough to overcome. Indiana State lost to RPI No. 226 Missouri State on Feb. 12 and No. 177 Bradley on Saturday. Mountain West (5) In: Boise State, Colorado State, New Mexico, San Diego State, UNLV Worth a mention: Air Force Bubble notes: A win over Air Force on Wednesday night combined with a loss by Ole Miss helped Boise State return to the field. The Broncos have top two top-50 wins at Creighton (RPI No. 47) and UNLV (No. 17), which is better than most teams on the bubble. The Broncos have lost their last five MWC road games for a 5-6 mark in the league, but they have a chance to end that streak with a trip to RPI No. 146 Fresno State. Home dates with Colorado State and San Diego State could help the Broncos clinch an at-large bid.
Pac-12 (6) In: Arizona State, Arizona, Cal, Colorado, Oregon, UCLA Worth a mention:Stanford Bubble notes: Colorado split with the Arizona schools last week, which turns out to be good for both the Buffaloes and Arizona State. In the last two weeks, Colorado has a win at RPI No. 38 Oregon for a crucial road victory, and a win at home over No. 11 Arizona. Cal entered the field this week after stringing together back-to-back wins over Arizona on the road and RPI No. 41 UCLA at home. With three top-50 wins and no losses to teams outside the top 100, Cal should feel pretty good. The Sun Devils also entered our field this week with a season sweep of Colorado, defeating the No. 23 Buffaloes in Boulder on Saturday. With losses to Stanford and Utah in the last three games (plus a home loss to DePaul in December), Arizona State doesn?t have much wiggle room. The Sun Devils? RPI is dangerously low at 67. Stanford entered last week on the bubble and lost at home to UCLA and USC, giving the Cardinal a season sweep to the Trojans, who are ranked 97th.
SEC (2) In: Florida, Missouri Worth a mention: Alabama, Arkansas, Kentucky Bubble notes: With five losses in the last seven games, Ole Miss may have played itself out of a bid. The Rebels endured their worst loss of the season with a 63-62 defeat to South Carolina on Wednesday. Unfortunately for Kentucky, the selection committee will take injuries into account, and a 30-point loss to Tennessee without Nerlens Noel won?t help the Wildcats? case. Alabama is in the same spot it was in two seasons ago with a great SEC record but a bubble resume thanks to losses to Dayton, Tulane, Mercer and Auburn. Arkansas should be mentioned for its wins over Florida and Missouri in recent weeks, but the Razorbacks still have a low RPI (74) and a dismal road record (1-6).
West Coast (2) In: Gonzaga, Saint Mary's Worth a mention: BYU Bubble notes: Saint Mary?s could have eased its fears of making the Tournament by defeating Gonzaga, but the Gaels lost 77-60. A BracketBuster game against Creighton on Saturday can?t be understated. Other than a possible rematch with Gonzaga in the WCC tournament, this game will be Saint Mary?s last chance for a top-50 win.
Approximately 150 federal and state law enforcement agents launched a massive raid on one of the biggest?perpetrators?of government fraud in America: The Scooter Store. Yes, that's right. The nation's largest provider of single-person electric vehicles and power chairs is the target of a federal investigation, probably because many of the people who ride around their "personal mobility?devices" don't actually need them.
RELATED: Huge Round of Arrests for $450 Million in Medicare Fraud
In January, CBS This Morning ran a cutting expos? on the company,?detailing how it "railroads" doctors into prescribing the chair for their patients, most of whom are on Medicare or Medicaid. That way they can bill the?government?for their highly dubious medical device, while the patient gets a cool new scooter without paying for it, and The Scooter Store makes a nice profit. Doctors and former employees told CBS that the company would harass physicians with non-stop phone calls and offices drop-ins in order to wear them down. The company even has a special department devoted to getting chairs for patients who had already been ruled ineligible by Medicare. No doubt the pressure comes because their ads guarantee that the chair will be free if they can't get you qualified.?
RELATED: F.B.I. Asks for Help with a Murder Case Code
The Scooter Store is so good at getting the chairs that a government audit found that they had overbilled Medicare by over $100 million between 2009-2012.?It's no wonder their ads brag that?"No other company will work harder to make you mobile."
RELATED: How the FBI Vetted Steve Jobs
RELATED: Meet the Shirtless FBI Agent from the Petraeus Love Pentagon
FBI agents would not provide details on any crimes or possible charges behind the search warrant, but 1,200 employees of the company were escorted from the headquarters in?New Braunfels,?Texas, on Wednesday, and were not allowed back into today, as investigators continue to dig for clues. Police also searched a related management company that The Scooter Store's sales records.
RELATED: Apparently Tweeting Explicit Photos Is the Only Way to Get Attention
Unfortunately, the FBI won't be going after the handful of customers who know they don't need a scooter or wheelchair, but still want the government to buy them one. Sort of like the people at airports who experience "wheelchair miracles" leaping up and running to their gate after an airport employee has helpfully pushed them most of the way. Officials at Los Angeles International Airport?estimate?that 15 percent of the people who request wheelchair?assistance?are faking it, because they want to skip lines and get on board their flights faster.?We're sure most Scooter Store customers are unhealthy people, innocently going along with the company's promises of getting out of the house more, but the disability fakers are the real criminals if you ask us.
Many jobseekers report never hearing back after applying for a job.
By Allison Linn, TODAY
Maybe you weren?t expecting to?land the job. But if you?ve been applying for jobs recently, chances are you hoped to?hear something back.
And chances are, you?ve been disappointed at least once.
A new survey finds that 75 percent of employed people who applied for a job in the past year never heard from at least one potential employer.
The results were part of a broad survey of more than 3,900 workers conducted last November by Harris Interactive for jobs website CareerBuilder. Of the 1,083 workers who said they had applied for a job in the past year, more than 800 reported never hearing a peep at least once.
Miss Manners might not approve, but experts say it?s not unusual these days for jobseekers to find their job applications ignored. Blame a combination of the still-tough job market, which can mean that hundreds or thousands of people are applying for the same positions, and technology that makes it all too easy for people to apply for dozens if not hundreds of jobs.
?It is pretty common, unfortunately,? said Lynn Taylor, a workplace expert and author of ?Tame Your Terrible Office Tyrant,? who was not involved in the CareerBuilder survey.
The CareerBuilder survey found that overall, about one fourth of the full pool of 3,900 workers had had a bad experience as a job applicant. Those experiences included never hearing the decision after a job interview, finding out the actual job didn?t match the original description and having a job application ignored, according to?CareerBuilder.
Not surprisingly, more than 4 in 10 workers said that if they were treated badly they wouldn?t seek employment with that company again.
Taylor, the workplace expert, said ignoring resumes or not following up after an interview could harm a company?s reputation. But in the current job market, with unemployment still hovering around 8 percent, she said most employers probably figure they can get away with it because so many people are desperate for work.
Related: Are you a struggling single parent? We want to hear from you.
With hiring so tight, she noted, companies also may not have the manpower to follow up with each applicant.
?Yes, it?s the right thing to, but .. the reality is that it?s not going to happen as much as it used to,? she said. ?That?s the harsh reality of today.?
Instead of sulking about not hearing back, Taylor said that jobseekers who really want the job need to be proactive about following up with the hiring manager themselves.
That can be true later in the hiring process as well, she said.
If you make it to the interview stage, Taylor recommends asking during the interview what the time frame is for filling the position and what the next steps are. You could even consider asking how you stack up against other applicants, she said.
After sending your thank-you note, she said it?s also appropriate to follow-up again in a week or so, to check on where things stand and perhaps to offer another tidbit of information about yourself.
Still, she noted that it?s a fine line between following up and harassing. If you check in three times and never hear back, it?s probably best to stop pestering them ? and wonder if you really want to work for a company like that in the first place.
Do you think employers should follow up with every person who applies for a job?
In a surprising move, President Obama proposed during the State of the Union address to increasing the federal minimum wage to $9 an hour. A perpetually controversial issue, the minimum wage remains a flashpoint between progressives and conservatives, with proponents saying it keeps full-time workers out of poverty and opponents arguing it increases unemployment.
As the map above shows, only a handful of countries lack minimum wage laws. Most countries have a minimum-wage law or agreement. In many cases, those laws guarantee a minimum wage only to workers in certain industries or locations. And many countries with minimum-wage laws struggle to enforce them.
Correction, Feb. 21, 2013:?Due to an editing error, this article originally stated that Congo, Kenya, and Pakistan do not have minimum wage laws. They have partial minimum wage laws.
El presidente reelecto de Ecuador, Rafael Correa, afirm? que su Alianza Pa?s logr? m?s de dos tercios de las bancas de la Asamblea Nacional (parlamento unicameral), que se renov? totalmente en las elecciones generales del domingo pasado pero sobre la cual no se conoc?an hasta esta tarde datos oficiales del escrutinio. ?Hemos obtenido, gracias a Dios y al favor del pueblo ecuatoriano, la victoria en una sola vuelta (en los comicios presidenciales) y m?s de dos tercios de la Asamblea Nacional?, se?al? Correa al inaugurar el nuevo aeropuerto de Quito. Correa obtuvo el domingo su reelecci?n con casi 57% de los votos v?lidos, seg?n datos oficiales del Consejo Nacional Electoral (CNE), e iniciar? en mayo un nuevo mandato de cuatro a?os. (Fuente: Agencias)
Feb. 19, 2013 ? Understanding how and why diversification occurs is important for understanding why there are so many species on Earth. In a new study published on 19 February in the open access journal PLOS Biology, researchers show that similar -- or even identical -- mutations can occur during diversification in completely separate populations of E. coli evolving in different environments over more than 1000 generations. Evolution, therefore, can be surprisingly predictable.
The experiment, conducted by Matthew Herron, research assistant professor at the University of Montana, and Professor Michael Doebeli of the University of British Columbia, involved 3 different populations of bacteria. At the start of the experiment, each population consisted of generalists competing for two different sources of dietary carbon (glucose and acetate), but after 1200 generations they had evolved into two coexisting types each with a specialized physiology adapted to one of the carbon sources. Herron and Doebeli were able to sequence the genomes of populations of bacteria frozen at 16 different points during their evolution, and discovered a surprising amount of similarity in their evolution.
"In all three populations it seems to be more or less the same core set of genes that are causing the two phenotypes that we see," Herron said. "In a few cases, it's even the exact same genetic change."
Recent advances in sequencing technology allowed Herron and Doebeli to sequence large numbers of whole bacterial genomes and provide evidence that there is predictability in evolutionary diversity. Any evolutionary process is some combination of predictable and unpredictable processes with random mutations, but seeing the same genetic changes in different populations showed that selection can be deterministic.
"There are about 4.5 million nucleotides in the E. coli genome," he said. "Finding in four cases that the exact same change had happened independently in different populations was intriguing."
Herron and Doebeli argue that a particular form of selection -- negative frequency dependence -- plays an important role in driving diversification. When bacteria are either glucose specialists or acetate specialists, a higher density of one type will mean fewer resources for that type, so bacteria specializing on the alternative resource will be at an advantage.
"We think it's likely that some kind of negative frequency dependence -- some kind of rare type advantage -- is important in many cases of diversification, especially when there's no geographic isolation," Herron said.
As technology advances, Herron believes that similar experiments in larger organisms will soon be possible. Some examples of diversification without geographic isolation are known in plants and animals, but it remains to be seen whether or not the underlying evolutionary processes are similar to those in bacteria.
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The above story is reprinted from materials provided by Public Library of Science.
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Journal Reference:
Herron MD, Doebeli M. Parallel Evolutionary Dynamics of Adaptive Diversification in Escherichia coli. PLOS Biol, 11(2): e1001490 DOI: 10.1371/journal.pbio.1001490
Note: If no author is given, the source is cited instead.
Disclaimer: Views expressed in this article do not necessarily reflect those of ScienceDaily or its staff.
Feb. 20, 2013 ? Fetal alcohol syndrome is the leading preventable cause of developmental disorders in developed countries. And fetal alcohol spectrum disorder (FASD), a range of alcohol-related birth defects that includes fetal alcohol syndrome, is thought to affect as many as 1 in 100 children born in the United States.
Any amount of alcohol consumed by the mother during pregnancy poses a risk of FASD, a condition that can include the distinct pattern of facial features and growth retardation associated with fetal alcohol syndrome as well as intellectual disabilities, speech and language delays, and poor social skills. But drinking can have radically different outcomes for different women and their babies. While twin studies have suggested a genetic component to susceptibility to FASD, researchers have had little success identifying who is at greatest risk or what genes are at play.
Research from Harvard Medical School and Veterans Affairs Boston Healthcare System sheds new light on this question, identifying for the first time a signaling pathway that might determine genetic susceptibility for the development of FASD. The study was published online Feb. 19 in the journal Proceedings of the National Academy of Sciences.
"Our work points to candidate genes for FASD susceptibility and identifies a path for the rational development of drugs that prevent ethanol neurotoxicity," said Michael Charness, chief of staff at VA Boston Healthcare System and HMS professor of neurology. "And importantly, identifying those mothers whose fetuses are most at risk could help providers better target intensive efforts at reducing drinking during pregnancy."
The discovery also solves a riddle that had intrigued Charness and other researchers for nearly two decades. In 1996, Charness and colleagues discovered that alcohol disrupted the work of a human protein critical to fetal neural development -- a major clue to the biological processes of FASD. The protein, L1, projects through the surface of a cell to help it adhere to its neighbors. When Charness and his team introduced the protein to a culture of mouse fibroblasts cells, L1 increased cell adhesion. Tellingly, the effect was erased in the presence of ethanol (beverage alcohol).
Charness and his team went on to develop multiple cell lines from that first culture, and that's where they encountered the riddle: In some of those lines, alcohol disrupted L1's adhesive effect, while in others it did not.
"How could it be possible that a cell that expresses L1 is completely sensitive to alcohol, and others that express it are completely insensitive?" asked Charness, who is also faculty associate dean for veterans hospital programs at HMS and assistant dean at Boston University School of Medicine.
Clearly, something else was affecting the protein's sensitivity to alcohol -- but what? Studies of twins provided one clue: Identical twins are more likely than fraternal twins to have the same diagnosis, positive or negative, for FASD. "That concordance suggests that there are modifying genes, susceptibility genes, that predispose to this condition," Charness said.
In the current study, Charness' team and collaborators at the University of North Carolina School of Medicine in Chapel Hill conducted cell culture experiments to identify specific molecular events that contribute to the alcohol sensitivity of L1 adhesion molecules. They focused on what was happening to the L1 molecule inside a cell that could affect an event outside the cell such as disruption by alcohol.
"We found that phosphorylation events that begin inside the cell can render the external portion of the L1 adhesion molecule more vulnerable to inhibition by alcohol," said Xiaowei Dou, HMS instructor in neurology in the Charness Lab and first author on the new study. "Phosphorylation was controlled by the enzyme ERK2, and occurred at a specific location on the internal portion of the L1molecule."
Phosphorylation plays a significant role in a wide range of cellular processes. By adding a phosphate group to a protein or other molecule, phosphorylation turns many protein enzymes on and off, and thereby alters their function and activity.
The researchers also found that variations in ERK2 activity correlated with differences in L1 sensitivity to alcohol that they observed across cell lines and among different strains of mice. "Dou showed that he could take these cells that had been insensitive to alcohol for 13-14 years, and make them sensitive by ramping up the activity of this kinase" Charness said.
These variations suggest that genes for ERK2 and the signaling molecules that regulate ERK2 activity might influence genetic susceptibility to FASD. Moreover, their identification of a specific locus that regulates the alcohol sensitivity of L1 might facilitate the rational design of drugs that block alcohol neurotoxicity.
"The only thing this modification blocked was alcohol's ability to inhibit L1," Charness said. "If you're looking for a drug, ideally you're looking for it to block the effects of the toxin without interfering with the target molecule of the toxin."
The findings will also help guide an international consortium in its search for genes linked to families with fetal alcohol spectrum disorders.
"Prenatal alcohol exposure is the leading preventable cause of birth defects and developmental disorders in the United States," said Kenneth Warren, acting director of the National Institute on Alcohol Abuse and Alcoholism (NIAAA),which supported the study. "These new findings are yet another important contribution from researchers who have been at the forefront of scientific discovery in FASD."
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The above story is reprinted from materials provided by Harvard Medical School. The original article was written by R. Alan Leo.
Note: Materials may be edited for content and length. For further information, please contact the source cited above.
Journal Reference:
X. Dou, M. F. Wilkemeyer, C. E. Menkari, S. E. Parnell, K. K. Sulik, M. E. Charness. Mitogen-activated protein kinase modulates ethanol inhibition of cell adhesion mediated by the L1 neural cell adhesion molecule. Proceedings of the National Academy of Sciences, 2013; DOI: 10.1073/pnas.1221386110
Note: If no author is given, the source is cited instead.
Disclaimer: This article is not intended to provide medical advice, diagnosis or treatment. Views expressed here do not necessarily reflect those of ScienceDaily or its staff.
A mating pair of strashilids, fossil insects from the Jurassic that resemble modern aquatic flies.
By Stephanie Pappas LiveScience
A group of Jurassic insects thought to have been parasites of feathered dinosaurs were falsely accused, new research finds. Instead, the tiny creatures were aquatic flies, similar to some still living today.
The findings don't change the reality that dinosaurs really did have lice and other parasites, Nanjing Institute of Geology and Paleontology researcher Diying Huang and his colleagues write in the Thursday issue of the journal Nature. Huang and his colleagues had previously discovered dino-fleas 10 times the size of the ones that plague mammals today.
But insects known as the strashilids had been wrongly identified as bloodsuckers, Huang and his colleagues now conclude.
The itsy-bitsy insects, only a few millimeters long, have grasping back legs and what appeared, in fossilized specimens, to be a sucking beak. These remains made scientists think strashilids belonged to an extinct group of dinosaur parasites. But researchers had only discovered a handful of these Jurassic insects.
Now, Huang and his colleagues have examined 13 new specimens of strashilids from 165 million years ago, found in Inner Mongolia. Two of these specimens even preserve males and females having sex. [See Images of the Fossil Flies Having Sex]
The new look at these ancient insects reveals that only male strashilids had grasping back legs, an indication that these limbs were used to hang on to females during sex, not to cling to dinosaur feathers during feeding. What's more, both sexes had vestigial mouthparts, suggesting the short-lived adults didn't feed at all. The insects also had large, membranous wings.
An examination of the insects' genitalia matched them to a modern group of flies, the Nymphomyiidae. These flies have feathery wings and live along rapidly moving streams. Like the Jurassic insects, adults of the present-day flies keep some vestiges of their larval selves. The ancient flies, in particular, often hung on to their abdominal gills, an unusual feature among insects, the researchers report.
Researchers suspect that these flies probably shed their wings toward the end of their lives and returned to the water to mate as their last act. The fossils of flies engaged in the act, which reveal wingless males gripping wingless females, support that theory.
Actual dino-parasites from the Jurassic were larger than strashilids, measuring about 0.7 inches (17 millimeters) in length for species such as Pseudopulex jurassicus and Pseudopulex magnus. In one way, ancient fleas were less scary than modern versions, however ? a 2012 study in the journal Nature found that Jurassic bloodsuckers probably couldn't jump.?
Follow Stephanie Pappas on Twitter @sipappas?or LiveScience @livescience. We're also on Facebook?andGoogle+.
Copyright 2013 LiveScience, a TechMediaNetwork company. All rights reserved. This material may not be published, broadcast, rewritten or redistributed.
Residents gather at the site of a car bomb explosion in Sadr City. (R)
Iraq: Qaeda Claims Responsibility for Wave of Bombings Baghdad, Asharq Al-AwsatThe al-Qaeda-affiliated Islamic State of Iraq has claimed responsibility for a wave of bombings that targeted Shiite areas of Baghdad, killing 28 people yesterday.
The terrorist organization said that it was taking revenge for perceived state repression of Sunni Muslims, in the latest round of violence to hit Iraq...?more
From: Art of the Living Dead by Alex Wild at Compound Eye.
Source: Hashime Murayama (1934)
Like a game of artistic broken telephone Hashime Murayama?s 1934 painting of army ants shows that for scientific illustrators, reference materials matter as much as our observational skill. Inaccurate references lead to illustrations which in turn become new references. In Alex Wild?s post Art of the Living Dead on Compound Eye, Wild shows us the distinct features that change in insects after death, and how a skilled illustrator ended up painting zombie army ants ? enough to give anyone the shivers.
About the Author: Bora Zivkovic is the Blog Editor at Scientific American, chronobiologist, biology teacher, organizer of ScienceOnline conferences and editor of Open Laboratory anthologies of best science writing on the Web. Follow on Twitter @boraz.
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Could an old antidepressant treat sickle cell disease?Public release date: 19-Feb-2013 [ | E-mail | Share ]
Contact: Kara Gavin kegavin@umich.edu 734-764-2220 University of Michigan Health System
Tests in mice & human blood cells look promising
ANN ARBOR, Mich. An antidepressant drug used since the 1960s may also hold promise for treating sickle cell disease, according to a surprising new finding made in mice and human red blood cells by a team from the University of Michigan Medical School.
The discovery that tranylcypromine, or TCP, can essentially reverse the effects of sickle cell disease was made by U-M scientists who have spent more than three decades studying the basic biology of the condition, with funding from the National Institutes of Health.
Their findings, published in Nature Medicine, pave the way for a clinical trial now being planned for adult patients who have the life-threatening condition. The discovery may also lead to other treatments for the disease, which leads misshapen red blood cells to cause vascular damage and premature death.
But the researchers caution it is too soon for the drug to be used in routine treatment of sickle cell anemia, an inherited genetic disease that affects tens of thousands of Americans and millions of others worldwide.
The climax of a decade of discovery
In the new paper, the researchers describe a painstaking effort to test TCP's effect on the body's production of a particular form of hemoglobin the key protein that allows red blood cells to carry oxygen.
The drug acts on a molecule inside red blood cells called LSD1, which is involved in blocking the production of the fetal form of hemoglobin. The U-M team zeroed in on the importance of LSD1 as a drug target after many years of research.
Then, they literally did a Google search to find drugs that act on LSD1. That's how they found TCP, which since 1960 has been used to treat severe depression.
In the new paper, they describe how TCP blocked LSD1 and boosted the production of fetal hemoglobin -- offsetting the devastating impact of the abnormal "adult" form of hemoglobin that sickle cell patients make.
"This is the first time that fetal hemoglobin synthesis was re-activated both in human blood cells and in mice to such a high level using a drug, and it demonstrates that once you understand the basic biological mechanism underlying a disease, you can develop drugs to treat it," says Doug Engel, Ph.D., senior author of the study and chair of U-M's Department of Cell & Developmental Biology. "This grew out of an effort to discover the details of how hemoglobin is made during development, not with an immediate focus on curing sickle cell anemia, but just toward understanding it."
Engel credits the dedication and persistence of his team, including a former research assistant professor, Osamu Tanabe, M.D., Ph.D., now at Japan's Tohoku University, U-M postdoctoral fellow, Lihong Shi, Ph.D., first author of the study, and research instructor Shuaiying Cui, Ph.D..
Together, they have identified LSD1's crucial role, and its epigenetic interaction with two nuclear receptors in the nuclei of red blood cell precursors called TR2 and TR4. Working in tandem, they repress the expression of the gene that makes fetal hemoglobin an effect called gene silencing. So, interfering with this repression allows the fetal hemoglobin subunits to be made.
Treatment with TCP caused fetal hemoglobin to be produced at such high abundance that it made up 30 percent of all hemoglobin in cultured human blood cells a finding Engel called "startling." TCP is FDA-approved, though patients taking it need to follow strict dietary guidelines to avoid drug interactions with certain naturally occurring chemicals in some foods.
Boosting healthy hemoglobin
Sickle cell disease occurs when a person or animal inherits two defective copies of a gene that governs the production of the "adult" form of hemoglobin. James Neel, the first chair of the U-M Department of Human Genetics, co-discovered the genetic basis for the disease in the late 1940s.
People with just one copy of the mutated gene normally do not get sick, but if they have a child with another person who carries the same trait, there is a one in four chance the child will develop the disease. An estimated 2.5 million Americans including one in every 12 African Americans and one in every 100 Latinos carry one copy of the mutated globin gene.
In sickle cell disease, the body makes a form of adult hemoglobin that can aggregate to cause red blood cells to become C-shaped or "sickle" shaped, and stiff and sticky. Those cells clog small blood vessels in the limbs and internal organs, causing organ damage, pain, and raising the risk of infection. Life expectancy in these patients is greatly shortened.
In a very small number of sickle cell patients, the 'fetal' form of hemoglobin which is usually only made in the womb and the first couple of months of life keeps being produced throughout life. These patients have symptoms that are either far less severe or nonexistent.
The most common current sickle cell treatment, oral hydroxyurea, aims to boost fetal hemoglobin production. Others, including transfusions and stem cell (bone marrow) transplants from unrelated donors, aim to exchange the source of the overall red blood cell supply.
More study needed
Andrew Campbell, M.D., who directs the Pediatric Comprehensive Sickle Cell program at U-M's C.S. Mott Children's Hospital and has worked with Engel on previous research, finds the new findings are very exciting news for sickle cell patients, since there are not enough treatment options. But, he notes, more clinical research is needed to determine if the findings from mice and cultured human red cell precursors will translate to humans for TCP or even other drugs that inactivate LSD1.
The first such clinical trial is now being planned with the sickle cell team at Wayne State University in Detroit. Further information will be available later this year if it receives approval to go forward. At the same time, U-M is exploring other possible drug candidates targeting the same pathway.
Engel is working with U-M psychiatrist Juan Lopez, M.D., to study the effect of TCP -- and other antidepressants in the class known as monoamine oxidase inhibitors -- on hemoglobin production in adults. The study is still seeking volunteers who are already taking these drugs to treat major depression. To learn more about that study, email gweinber@umich.edu.
###
The study was funded by NIH grants DK086956 and HL24415 and an American Heart Association postdoctoral fellowship, as well as NCI and Medical School support to the Vector, Flow Cytometry, DNA sequencing and Microarray Cores. U-M has filed for a patent on the discovery.
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.
Could an old antidepressant treat sickle cell disease?Public release date: 19-Feb-2013 [ | E-mail | Share ]
Contact: Kara Gavin kegavin@umich.edu 734-764-2220 University of Michigan Health System
Tests in mice & human blood cells look promising
ANN ARBOR, Mich. An antidepressant drug used since the 1960s may also hold promise for treating sickle cell disease, according to a surprising new finding made in mice and human red blood cells by a team from the University of Michigan Medical School.
The discovery that tranylcypromine, or TCP, can essentially reverse the effects of sickle cell disease was made by U-M scientists who have spent more than three decades studying the basic biology of the condition, with funding from the National Institutes of Health.
Their findings, published in Nature Medicine, pave the way for a clinical trial now being planned for adult patients who have the life-threatening condition. The discovery may also lead to other treatments for the disease, which leads misshapen red blood cells to cause vascular damage and premature death.
But the researchers caution it is too soon for the drug to be used in routine treatment of sickle cell anemia, an inherited genetic disease that affects tens of thousands of Americans and millions of others worldwide.
The climax of a decade of discovery
In the new paper, the researchers describe a painstaking effort to test TCP's effect on the body's production of a particular form of hemoglobin the key protein that allows red blood cells to carry oxygen.
The drug acts on a molecule inside red blood cells called LSD1, which is involved in blocking the production of the fetal form of hemoglobin. The U-M team zeroed in on the importance of LSD1 as a drug target after many years of research.
Then, they literally did a Google search to find drugs that act on LSD1. That's how they found TCP, which since 1960 has been used to treat severe depression.
In the new paper, they describe how TCP blocked LSD1 and boosted the production of fetal hemoglobin -- offsetting the devastating impact of the abnormal "adult" form of hemoglobin that sickle cell patients make.
"This is the first time that fetal hemoglobin synthesis was re-activated both in human blood cells and in mice to such a high level using a drug, and it demonstrates that once you understand the basic biological mechanism underlying a disease, you can develop drugs to treat it," says Doug Engel, Ph.D., senior author of the study and chair of U-M's Department of Cell & Developmental Biology. "This grew out of an effort to discover the details of how hemoglobin is made during development, not with an immediate focus on curing sickle cell anemia, but just toward understanding it."
Engel credits the dedication and persistence of his team, including a former research assistant professor, Osamu Tanabe, M.D., Ph.D., now at Japan's Tohoku University, U-M postdoctoral fellow, Lihong Shi, Ph.D., first author of the study, and research instructor Shuaiying Cui, Ph.D..
Together, they have identified LSD1's crucial role, and its epigenetic interaction with two nuclear receptors in the nuclei of red blood cell precursors called TR2 and TR4. Working in tandem, they repress the expression of the gene that makes fetal hemoglobin an effect called gene silencing. So, interfering with this repression allows the fetal hemoglobin subunits to be made.
Treatment with TCP caused fetal hemoglobin to be produced at such high abundance that it made up 30 percent of all hemoglobin in cultured human blood cells a finding Engel called "startling." TCP is FDA-approved, though patients taking it need to follow strict dietary guidelines to avoid drug interactions with certain naturally occurring chemicals in some foods.
Boosting healthy hemoglobin
Sickle cell disease occurs when a person or animal inherits two defective copies of a gene that governs the production of the "adult" form of hemoglobin. James Neel, the first chair of the U-M Department of Human Genetics, co-discovered the genetic basis for the disease in the late 1940s.
People with just one copy of the mutated gene normally do not get sick, but if they have a child with another person who carries the same trait, there is a one in four chance the child will develop the disease. An estimated 2.5 million Americans including one in every 12 African Americans and one in every 100 Latinos carry one copy of the mutated globin gene.
In sickle cell disease, the body makes a form of adult hemoglobin that can aggregate to cause red blood cells to become C-shaped or "sickle" shaped, and stiff and sticky. Those cells clog small blood vessels in the limbs and internal organs, causing organ damage, pain, and raising the risk of infection. Life expectancy in these patients is greatly shortened.
In a very small number of sickle cell patients, the 'fetal' form of hemoglobin which is usually only made in the womb and the first couple of months of life keeps being produced throughout life. These patients have symptoms that are either far less severe or nonexistent.
The most common current sickle cell treatment, oral hydroxyurea, aims to boost fetal hemoglobin production. Others, including transfusions and stem cell (bone marrow) transplants from unrelated donors, aim to exchange the source of the overall red blood cell supply.
More study needed
Andrew Campbell, M.D., who directs the Pediatric Comprehensive Sickle Cell program at U-M's C.S. Mott Children's Hospital and has worked with Engel on previous research, finds the new findings are very exciting news for sickle cell patients, since there are not enough treatment options. But, he notes, more clinical research is needed to determine if the findings from mice and cultured human red cell precursors will translate to humans for TCP or even other drugs that inactivate LSD1.
The first such clinical trial is now being planned with the sickle cell team at Wayne State University in Detroit. Further information will be available later this year if it receives approval to go forward. At the same time, U-M is exploring other possible drug candidates targeting the same pathway.
Engel is working with U-M psychiatrist Juan Lopez, M.D., to study the effect of TCP -- and other antidepressants in the class known as monoamine oxidase inhibitors -- on hemoglobin production in adults. The study is still seeking volunteers who are already taking these drugs to treat major depression. To learn more about that study, email gweinber@umich.edu.
###
The study was funded by NIH grants DK086956 and HL24415 and an American Heart Association postdoctoral fellowship, as well as NCI and Medical School support to the Vector, Flow Cytometry, DNA sequencing and Microarray Cores. U-M has filed for a patent on the discovery.
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.
A judge being interviewed for a Supreme Court job jokes that women might enjoy rape. A local official takes a 17-year-old second wife, then quickly divorces her by text message.
Both cases reflect attitudes toward women's rights and safety that have persisted for years in this Southeast Asian archipelago nation of 240 million people. The difference now: Both officials are at risk of losing their jobs.
Women in this social-media-obsessed country have been rallying, online and on the streets, against sexist comments and attacks on women. The response is seen as a small step for women's rights in Indonesia, where the government is secular and most people practice a moderate form of Islam.
"We are living in a different era now," said Husein Muhammad of the National Commission on Violence Against Women. "... Now we have supporting laws and social media to bring severe consequences and social sanctions."
Still, rights groups say the country remains far behind on many issues involving gender equality and violence. Rape cases often are not properly investigated, and victims are sometimes blamed.
And although it is rare to divorce by text message, as Aceng Fikri did last summer, unregistered polygamous marriages such as his are common.
Fikri, chief of Garut district in West Java province, called it quits four days after marrying his teenage bride in July. He claimed she was not a virgin, which she denied.
A photo of the couple posted on the Internet slowly began to stoke chatter ? and then rage. The outcry spread by local media and on Twitter, blogs, Facebook and popular mobile phone networking groups such as BlackBerry and Yahoo Messenger.
Thousands of people took to the streets in December to protest. Students and women's rights activists in Garut demanded that he resign, trampling and spitting on photos of his face before setting them ablaze outside his council building.
President Susilo Bambang Yudhoyono responded by issuing a rare public condemnation of the 40-year-old official and his illegal marriage. The Supreme Court late last month recommended that the president dismiss Fikri for violating the marriage law, and police are investigating the case because it involves a minor.
Outrage also erupted in social media in January after Judge Muhammad Daming Sunusi told a parliamentary selection panel for Supreme Court positions that it could be a mistake to impose the death penalty for rape because both the attacker and the victim "might have enjoyed" it. The remark reportedly drew laughter from panel members. Sunusi later apologized and said he been joking.
"Enough is enough!" said Muhammad, of the commission on violence against women. "Our officials should no longer mess around and issue ridiculous statements even as a dumb joke."
Not only was Sunusi rejected for a job on the Supreme Court, but the country's Judicial Commission has recommended that he be dismissed from his position on the South Sumatra High Court. But the Supreme Court would have to agree, and it has said such punishment would be too severe because he made the remark in an interview, not during a trial.
Sunusi is hardly the first in Indonesia to be criticized for his comments about rape.
In 2011, after a woman was gang raped on a minibus, then-Jakarta governor Fauzi Bowo drew protests after warning women not to wear miniskirts on public transportation because it could arouse male passengers. Bowo lost his re-election bid last year.
A sex-trafficking case involving a 14-year-old girl prompted Education Minister Mohammad Nuh to say last year that not all girls who report such crimes are victims: "They do it for fun, and then the girl alleges that it's rape," he said. His response to the criticism he received was that it's difficult to prove whether sexual assault allegations are "real rapes."
Growing concern in Indonesia over women's rights reflects that in India, where a brutal and deadly New Delhi gang rape in December has drawn nationwide protests and demands for change. That case also resonated in Indonesia.
"Let's imagine the suffering of women who are treated badly by their husbands and the rape victims. What if it happened to our own families?" said Ellin Rozana, a women's rights activist in Bandung, capital of West Java province. "We need government officials who will be on the front line to protect women, and judges who can see that violence against women is a serious crime."
In the West Java official's case, it was the text-message divorce that prompted outrage more than his unregistered second marriage, though such weddings raise issues about women's rights. They are regularly performed for Indonesians ranging from poor rice farmers to celebrities, politicians and Muslim clerics.
Polygamy remains common in many Muslim countries, based on Islamic teachings that allow men to take up to four wives.
In Indonesia, men are allowed to marry a second wife only after the first gives her blessing. Since most women refuse to agree to share their husbands, unregistered ceremonies, or "nikah siri," are often secretly carried out by an Islamic cleric outside the law.
Some of the marriages are simply a cover for prostitution. A cleric is paid to conduct "contract marriages" as short as one night in some parts of Indonesia, usually for Middle Eastern tourists.
Practices differ slightly elsewhere, with men in places such as Malaysia sometimes marrying outside the country to avoid informing existing spouses and seeking permission from an Islamic court. Ceremonies in Iraq are often held in secret for the same reason. No approval is needed in the Palestinian territories, but contract marriages are banned.
Without a marriage certificate, wives lack legal rights. Children from the marriage are often considered illegitimate and are typically not issued birth certificates, creating a lifetime of obstacles ranging from attending schools to getting a passport.
However, in another sign of Indonesia's changing attitudes, the Supreme Court this month ordered all judges to obey an earlier Constitutional Court ruling granting rights such as inheritance to children born out of wedlock, and to punish fathers who neglect them.
The women's commission on violence is now pushing for a revision of Indonesia's 1974 marriage law to grant more protections to women and children.
"I hope Indonesian women can take a lesson from Fikri's case," said Ninik Rahayu of the commission. "At least it has awakened their awareness to not marry in an illegal way."
____
Associated Press writers Ibrahim Barzak in Gaza City, Gaza Strip, Sameer N. Yacoub in Baghdad, Iraq and Eileen Ng in Kuala Lumpur, Malaysia, also contributed to this story.
? 2013 The Associated Press. All rights reserved. This material may not be published, broadcast, rewritten or redistributed.
ZURICH (Reuters) - Swiss authorities said on Monday they have not yet been asked to help a U.S. investigation into alleged insider trading in call options of H.J. Heinz Co the day before the company announced it would be sold, even though a Zurich account is at the heart of the matter.
U.S. securities regulators filed suit on Friday against as-yet-unidentified traders in Heinz options alleging they traded on inside information before the company made public the deal to be bought for $23 billion by an investor group made up of Warren Buffett's Berkshire Hathaway Inc and Brazil's 3G Capital Partners.
The U.S. Securities and Exchange Commission said in a statement on Friday it had obtained "an emergency court order to freeze assets in a Zurich, Switzerland-based trading account that was used to reap more than $1.7 million from trading in advance of yesterday's public announcement about the acquisition of H.J. Heinz Company."
The order from the U.S. District Court for the Southern District of New York freezes the traders' assets and prohibits them from destroying any evidence, the SEC statement said.
SEC spokesman John Nester said on Monday that the assets concerned had been frozen in the United States, not Switzerland, though the "beneficial owners" were those allegedly behind the Swiss account. He did not respond immediately when asked if the U.S. authorities were in contact with their Swiss counterparts.
With the assets frozen, the SEC would have had no immediate need for Swiss assistance in the case, although it eventually may need help to identify the account holders.
Rainer Borer, a spokesman for the Swiss financial markets watchdog known as FINMA, said a U.S. court cannot by itself freeze assets in an account of a bank operating in Switzerland.
"For that, it has to ask for legal or administrative assistance," he told Reuters. "Up to now, FINMA has not received a U.S. request for administrative assistance in the mentioned case of potential insider trading."
Justice ministry spokesman Folco Galli said the ministry had not received an official request for legal assistance either.
"Either a request for administrative or legal assistance would be necessary because a U.S. court cannot enforce a coercive measure in Switzerland," he said.
U.S. bank Goldman Sachs has said it is co-operating with the SEC probe. The SEC suit filed Friday refers to the account in Switzerland as the "GS Account.
Heinz had no comment, Michael Mullen, a company spokesman, said by email. Berkshire Hathaway and 3G Capital likewise declined to comment, said Gemma Hart, a spokeswoman for the investor group.
(Reporting by Silke Koltrowitz; Additional reporting by Martin de Sa'Pinto in Zurich and Jim Wolf in Washington; Editing by Marguerita Choy)
Tonight on the iMore show I'm joined by special guest Arnold Kim of MacRumors to talk Tim Cook at Goldman Sachs, Apple TV rumors, Apple's retail expansion, and iOS 6 bugs.
We go live at 6pm PST, 9pm EST. If you've got any questions or topic requests, leave them in the comments. Then be here!
TOKYO (Reuters) - Philippine and Australian shares scaled new heights on Tuesday but other Asian shares were mixed, with worries about the risk of an inconclusive outcome in Italy's election and about U.S. budget talks limiting the upside after strong rallies in early February.
European markets looked set to inch higher, with financial spreadbetters predicting London's FTSE 100 <.ftse>, Paris's CAC-40 <.fchi> and Frankfurt's DAX <.gdaxi> would open up 0.1 percent. <.l><.eu/>
U.S. stock futures rose 0.1 percent to suggest Wall Street will reopen with a firmer tone after the President's Day holiday on Monday. <.n/>
"Markets have become top-heavy after rallying through early February on signs of economic recovery in the United States and Europe, and investors now await fresh factors to push prices higher from here," said Tomomichi Akuta, senior economist at Mitsubishi UFJ Research and Consulting in Tokyo.
"The broad sentiment is underpinned by a lack of tail risks, but investors are turning to some potentially worrying elements such as Italian elections and U.S. budget talks," he said.
The MSCI's broadest index of Asia-Pacific shares outside Japan <.miapj0000pus> edged up 0.1 percent. Earlier in the day it had touched a 18-1/2-month high. The index has gained 3.5 percent this year.
Shares in the Philippines <.psi>, where a strong economic growth has led to rising interest in the country as an investment destination, hit a record. The Thai index <.seti> was also up 0.3 percent after recent data showed robust fourth-quarter economic numbers.
Australian shares ended 0.4 percent up at a 4-1/2 year high, continuing a recent rally on better-than-expected corporate earnings.
But Hong Kong shares <.hsi> fell 0.2 percent and Shanghai shares <.ssec> shed 1.1 percent, with real estate and financials leading the declines on concerns that rising property prices would lead to fresh restrictions on the sector.
Tokyo's Nikkei stock average <.n225> ended down 0.3 percent, after surging on Monday to approach its highest level since September 2008 of 11,498.42 tapped on February 6. <.t/>
The concerns about Italy's election this weekend and the talks in Washington over a package of budget cuts set to kick in March 1, also helped limit gains in commodities and also weighed on the euro.
The dollar's strength against a basket of currencies <.dxy> capped gains in gold, with the spot price up 0.2 percent at $1,613.01 an ounce.
London copper steadied at $8,122.50 a metric ton as Monday's three-week low drew bargain hunting given prospects for a slowly improving global economic recovery. Unease over China's limp return to the market from a week-long break held back upside momentum, however.
"I think we've already had the nicest rally that we're going to get this year," Singapore-based Credit Suisse analyst Ivan Szpakowski said. "You can still get some more mild upturns, but frankly as you move to the second half of the year industrial metals are going to trend down.
U.S. crude fell 0.5 percent to $95.43 a barrel while Brent steadied around $117.37.
The euro was steady around $1.3348.
YEN JITTERY
Bank of Japan minutes revealed board members had discussed buying longer-dated government debt at their January meeting, sending the yield on five-year Japanese government bonds to record low.
The yen firmed, however, after Finance Minister Taro Aso told reporters Japan has no plans to buy foreign currency bonds as part of monetary easing and as attention remained focused on who will be the next Bank of Japan governor.
The dollar fell 0.3 percent to 93.61 yen, but remained near its highest since May 2010 of 94.465 hit on February 11. The euro eased 0.4 percent to 125.00 yen, below its peak since April 2010 of 127.71 yen touched on February 6
The yen, which has dropped 20 percent against the dollar since mid-November, fell further at the start of the week after financial leaders from the G20 promised not to devalue their currencies to boost exports and avoided singling out Japan for any direct criticism.
The choice of the next BOJ governor and two deputies has drawn attention as a gauge of how strongly Prime Minister Shinzo Abe is committed to reflating the economy. The G20's message was that as long as Japan pursues aggressive monetary easing to achieve that goal, a weaker yen as a result of such domestic monetary policy will be tolerated, analysts say.
"But that means that some other economy's monetary conditions have been tightened," said Barclays Capital in a note.
"Japan hasn't even changed its policy stance thus far, and the effect of expectations of a looser setting have led to limited moves in domestic interest rates, but the sell-off of the JPY has been marked and has clearly caused unease in other economies," the note said.
(Additional reporting by Melanie Burton in Singapore; Editing by Edwina Gibbs)
Selection Sunday is less than a month away, and the picture for who?s in and who?s out of the NCAA Tournament is becoming more clear.
ACC (5)
Atlantic 10 (5)
Big 12 (5)
Big East (8)
Big Ten (7)
Conference USA (1)
Pac-12 (6)
SEC (2)
West Coast (2)
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