MOSCOW (AP) ? Russian police and security agents detained 140 people at a mosque in Moscow on Friday on suspicion of involvement with Islamic extremism.
A statement from the Federal Security Agency reported by Russian news agencies said among those detained were 30 citizens of unspecified foreign countries.
The detentions come a week after the two suspects in the fatal Boston Marathon bombings were identified as Russian-born ethnic Chechens who sympathized with Islamic extremists.
There were no immediate reports of charges being filed. The security agency referred The Associated Press to a district office, where the telephone was not answered.
The reports cited the agency as saying the mosque previously has been visited by people who had been involved in preparing or carrying out terrorist attacks.
A Chechen separatist insurgency that began in the 1990s increasingly took on a fundamentalist Muslim character and spread to neighboring Russian Caucasus regions, including Dagestan, where Boston bombing suspects Tamerlan and Dzhokhar Tsarnaev and their family lived for a period before emigrating to the United States in 2002 or 2003.
The Tsarnaevs' parents later returned to Dagestan, and Tamerlan, who was killed in a shootout with police last week, made a long visit in 2012. Investigators are trying to find out details of what he did on the six-month sojourn, especially whether he met with any extremists.
Caucasus extremists have carried out gruesome attacks on civilians in Russia, including the 2004 seizure of a school in the town of Beslan that ended in the deaths of 330 people, about half of them children. They also claimed responsibility for the 2011 bombing of Russia's busiest airport, killing 36 people.
In 2011, U.S. authorities questioned Tamerlan Tsarnaev at Russia's request, but found nothing that sparked their interest and stopped watching him.
On Friday, officials briefed on the investigation told the AP that U.S. intelligence agencies had added the mother of the suspects, Zubeidat, to a government terrorism database 18 months before the bombings. The officials spoke to the AP on condition of anonymity because they were not allowed to speak publicly about the ongoing case.
The mother called the information "lies and hypocrisy" and said she has never been linked to crimes or terrorism.
Throughout the past week, we?ve focused on many of the individual details in the Schumer/Rubio bill.? However, it?s important to step back and look at the bill in totality.? Between all of the amnesties, guest worker programs, and massive expansions in legal immigration, this bill will set off a seismic chain migration.? The effects on the welfare system and our ability to absorb so many immigrants will be felt within 5-10 years.? Yesterday, Senator Sessions broke down the comprehensive effects of the bill on chain migration as follows:
Those who qualify for the broad DREAM fast-track amnesty under S. 744?estimated by the Center for Immigration Studies? Steve Camarota to be between two and three million people?are able to become citizens after being in registered provisional immigrant (RPI) status (the general amnesty) for five years. Those five years are deemed as having been spent in legal permanent resident status (under current law LPRs must wait five years before becoming citizens).
There is NO AGE CAP on eligibility
The Secretary of Homeland Security can allow a deported DREAM beneficiary who is outside the U.S. or who has re-entered the U.S. illegally after the December 31, 2011 cut-off date to apply for this status.
Illegal agriculture workers will also be placed on an expedited path: green cards in five years and citizenship in 10. This could apply to almost a million people or more.
DREAM beneficiaries will also be able to get green cards for their parents, spouses, and children five years from enactment. Those family members will then be eligible for citizenship five years after that. Therefore, the DREAM provision of the bill alone could be responsible for potentially as many as 10 million new citizens over an approximate 10-plus year time frame.
S. 744 would allow unlimited visas for the spouses and children of all green card holders?both those currently illegal and new legal immigrants, leading to exponential chain migration.
In addition, under S. 744, any LPR can petition for visas for adult unmarried sons and daughters (but they must wait for a visa to become available). A citizen also will be able to petition for their married sons and daughters under the age of 31 if visas are available under the family-based visa cap.
S. 744 appears to allow those who have been granted status under President Obama?s Deferred Action for Childhood Arrivals policy (DACA) to immediately adjust to LPR status under a ?streamlined procedure? determined by the Secretary and consistent with the DACA requirements. These individuals may petition for visas for family members in the same manner as the LPRs described above. According to USCIS statistics, 472,004 DACA applications were accepted for review between August 2012 and March 2013; 268,361 were approved, 16,778 were deemed incomplete and required resubmission, and only 1,377 were denied.
As with all illegal immigrants under S.744, eligibility is extended to those with two misdemeanor criminal convictions, those who have overstayed their visas, forged documents, absconded from removal proceedings, had felony arrests, etc.
Taking into account the expedited legalization of illegal immigrants, the expansion of low-skill legal immigration, and the new avenues for chain migration, the bill would exponentially increase the number of people granted legal status.
Also, remember that the minute any of them have a baby, that kid is an American citizen, making the family eligible immediately for welfare.? This is something that is lost on those who say they have to wait 5-10 years to collect benefits.? Just yesterday, the Washington Examiner reported that the USDA is advertising in foreign consulates that you need not be a legal resident to collect food stamps:
The USDA said the program is designed to help American children. ?[The USDA Food and Nutrition Service] understands that mixed status households may be particularly vulnerable,? FNS? Yibo Wood wrote to Mexican embassy officials in a January 2012 email. ? ?Many of these households contain a non-citizen parent and a citizen child.?
Therein lies the big lie about the welfare issue.? You simply cannot have open borders, chain migration, unqualified birthright citizenship, and a welfare state at the same time.? In the context of the time we live in, we need to have a targeted immigration process that identifies those who will benefit the country at large (not a few special interests), and make it easier and cheaper for them to go through the process.? Random chain migration will spell the end of the Republic.
Apr. 26, 2013 ? Drive technology has an electric future -- of this Fraunhofer research scientists are in no doubt. At the Sensor + Test measurement fair in Nuremberg from May 14 -16, they will use an electric racing car to present novel solutions for battery management and electronic sensor systems together with an industry partner. The scientists are following a new trend, as even FIA, the governing body for world motor sport, federation of the world's leading motoring organizations and organizer of Formula 1, is planning a racing series for electric vehicles.
From 0 to 100 in 3.6 seconds -- we're not talking about the rapid acceleration of a Porsche Carrera or Ferrari Scaglietti, but of EVE, a racing car with a very quiet engine. EVE is powered by two electric motors, one for each rear wheel. With a maximum output of 60 kilowatts, they get the e-racer going at 4500 rotations per minute. The sprinter can reach a top speed of 140 km/h, and has a range of 22 km thanks to two lithium polymer batteries, with a combined capacity of 8 kWh. Electrical engineering students from the e-racing team at the Hochschule Esslingen University of Applied Sciences designed the 300 kg car as a voluntary project alongside their studies, and they have already competed in it at the international Formula Student Electric (FSE) race in Italy. From May 14-16, the racing car will be on show at the Sensor + Test measurement fair in Nuremberg at the joint Fraunhofer trade show booth (Hall 12, Booth 537). Scientists from the Fraunhofer Institute for Integrated Circuits IIS in Erlangen developed the entire electronic sensor system in close collaboration with Seuffer GmbH & Co.KG, an industry partner with whom the institute has been working for over 11 years. Seuffer GmbH & Co.KG is based in Calw in Baden-W?rttemberg, southern Germany, and sponsors the students of the E.Stall racing team.
"Electromobility as a topic is becoming ever more important. The racing car serves as a showcase for us to demonstrate novel sensor solutions as well as battery and energy management concepts," says Klaus-Dieter Taschka, an engineer at Fraunhofer IIS. Besides wheels, brakes, damper unit, batteries and electric motors, EVE is equipped with numerous sensors. These include braking pressure, crash, temperature and acce- leration sensors as well as sensors that monitor the accelerator and brake pedals, speed, steering angle, wheel speed and power. These last six functions could all be performed by HallinOne? sensors developed by Fraunhofer IIS, 3D magnetic-field sensors that are already a standard feature in washing machines, where they are used to determine the position and orientation of the drum.
Electronic sensors determine charge state of the battery
The two electronic sensors attached at the sides of the batteries use 3D magnetic-field sensor technology developed by Fraunhofer IIS to measure the magnetic field generated by the flow of electrical current and thus to determine the battery's level of charge. What's special about this is that the contactless sensors measure both the current that flows from the battery to the engine and the current that flows back again when the vehicle brakes. The integrated sensor system is able to eliminate disturbances and foreign magnetic fields, thus guaranteeing very precise measurements. A further advantage is that the system is also able to measure other aspects of the battery such as its voltage and temperature. The data is collected and sent to the power control unit (PCU) and the battery management system (BMS), which controls the charging and discharging processes.
Intelligent battery management system extends battery life
Battery running times and battery life are limiting factors for all electric vehicles. The BMS developed by Fraunhofer IIS in Nuremberg tackles this problem by determining the impedance spectrum of all battery cells and constantly testing whether the cells are functioning properly. This allows cells' condition, current capacity and potential service life to be ascertained and running times to be predicted more accurately.
As individual battery cells age, they are able to store less and less energy. The challenge lies in optimizing cell utilization. "Until now, a battery system was able to provide only as much energy as was available in its weakest cell. The energy stored in other cells remained unused. Our BMS has an active cell balancing system that moves energy between stronger and weaker cells. This means that all cells share the load equally, allowing the maximum capacity of the battery as a whole to be utilized," explains Dr.-Ing. Peter Spies, group manager at Fraunhofer IIS in Nuremberg. Actively balancing out the cells during the charging and discharging process extends the battery's service life and range. "EVE's current BMS is a system developed in house by E.Stall, but our solution could take its place," says Spies.
Polarization camera detects cracks in bodywork
EVE's compact design is built on a tubular steel space frame housed within a carbon fiber body. Racing around the track puts a great deal of stress on the plastic fibers, and this can lead to tiny cracks developing in the material. Fraunhofer IIS in Erlangen has developed POLKA, a polarization camera that can detect such damage at an early stage by measuring stresses within unpainted surfaces of the carbon structure. This compact camera makes any scratches visible by registering properties of light that are imperceptible to the human eye: polarization. Material stresses in the plastic cause changes in polarization. POLKA is able to collect all the polarization information for each pixel in a single shot at speeds of up to 250 frames per second. Using real-time color coding, the dedicated software translates the information collected about the intensity, angle and degree of polarization into a visual display that is accessible to the human eye. The system will also be presented at the joint Fraunhofer booth.
"We are convinced that EVE's innovative technology will allow the vehicle to perform very well while demonstrating excellent environmental awareness," says Rolf Kleiner, group manager of the battery technology department at Seuffer. And the students of team E.Stall will soon have a chance to prove it: This year EVE will be in the lineup for the Formula Student race in Italy, Spain and Czechia.
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ALBANY, N.Y. (AP) ? Three scientists at universities in Pennsylvania, Illinois and Oregon whose research has helped transform cancer treatment will share one of the richest prizes in medicine and biomedical research.
Dr. Peter Nowell of the University of Pennsylvania, Dr. Janet Rowley of the University of Chicago and Dr. Brian Druker of Oregon Health and Science University will receive the $500,000 annual Albany Medical Center Prize in Medicine and Biomedical Research next month, the medical center announced Tuesday. The prize, one of the largest in medicine and science in the United States, is awarded to those who have changed the course of medical research.
Medical center officials called the trio "visionary scientists" whose work has given hope to cancer patients around the world. The researchers will officially receive the award May 17 at a ceremony at the medical center.
"These individuals exemplify the extraordinary impact that painstaking research can have on the lives of countless individuals," said James J. Barba, president and chief executive officer of Albany Medical Center.
Nowell's research at Penn in Philadelphia was the first to show that a genetic defect could be responsible for cancer, His work has led to numerous discoveries into the growth of cells related to cancers and other disorders.
Rowley's discoveries of chromosome abnormalities in leukemia secured a common agreement among scientists, physicians and the general public that cancer is, in fact, a genetic disease.
Druker, an oncologist in Portland, Ore., used earlier work by Nowell and Rowley to develop a lifesaving treatment for chronic myeloid leukemia that specifically targets the leukemia cells without harming healthy cells.
The Albany Medical Center Prize was established in 2000 by the late Morris "Marty" Silverman, a New York City businessman who wanted to encourage health and biomedical research.
With the decreasing popularity of coal and increasing volatility of petroleum prices, natural gas is emerging as a major energy resource in the the United States. And while we have plenty of reserves, an estimated 318 Trillion cubic feet (Tcf), it's still a non-renewable resource that must be used sparingly whenever possible—like this new natural gas power plant prototype from the Department of Energy. It produces just as much electricity with 20 percent less gas every time the sun shines. More »
FILE - In this April 10, 2013 file photo, Sen. Joe Manchin, D-W.Va., right, accompanied by Sen. Patrick Toomey, R-Pa., announce that they have reached a bipartisan deal on expanding background checks to more gun buyers,, on Capitol Hill in Washington. The number of Republican senators who might back expanded background checks is now dwindling, threatening a bipartisan effort to subject more gun buyers to the checks. A vote on the compromise, the heart of Congress' gun control effort, is expected this week. (AP Photo/J. Scott Applewhite, File)
FILE - In this April 10, 2013 file photo, Sen. Joe Manchin, D-W.Va., right, accompanied by Sen. Patrick Toomey, R-Pa., announce that they have reached a bipartisan deal on expanding background checks to more gun buyers,, on Capitol Hill in Washington. The number of Republican senators who might back expanded background checks is now dwindling, threatening a bipartisan effort to subject more gun buyers to the checks. A vote on the compromise, the heart of Congress' gun control effort, is expected this week. (AP Photo/J. Scott Applewhite, File)
WASHINGTON (AP) ? Republican opposition is growing to a bipartisan Senate plan for expanding background checks for firearms buyers, enough to put the proposal's fate in jeopardy. But the measure may change as both sides compete for support in one of the pivotal fights in the battle over curbing guns.
The Senate was continuing debate Tuesday on a wide-ranging gun control bill, with the focus on a background check compromise struck last week between Sens. Patrick Toomey, R-Pa., and Joe Manchin, D-W.Va. Manchin said the vote on that amendment was likely to be delayed from midweek to late in the week, a move that would give both sides more time to win over supporters.
Underscoring the bargaining under way, the two sponsors seemed willing to consider a change to their deal that would exempt gun buyers from background checks if they live hundreds of miles from licensed firearms dealers, one Senate aide said.
The change might help win support from senators from Alaska and perhaps North Dakota, said the aide, who spoke on condition of anonymity because the discussions were private.
As lobbying escalated, wounded former Rep. Gabrielle Giffords, D-Ariz., and husband Mark Kelly, a retired astronaut, were planning a news conference Tuesday with Manchin and Toomey, said a Senate aide speaking on condition of anonymity to describe an event not publicly announced.
Many consider the Manchin-Toomey compromise the best hope for winning Senate approval to widen the background check system, designed to screen out the severely mentally ill, criminals and others from getting firearms. Background checks are widely considered the heart of the gun control drive.
Background checks are required only for sales handled by licensed gun dealers. The Manchin-Toomey measure would extend that to sales at advertised venues like gun shows and online, while exempting other transactions like those between relatives and friends.
The two senators' deal doesn't go as far as President Barack Obama wanted in response to the slayings of 26 schoolchildren and aides at Sandy Hook Elementary School in Newtown, Conn. But he has said it would represent progress.
From a group of 16 GOP senators gun control advocates have considered possible allies, at least nine have now said they oppose the background check compromise and one said he is leaning against it.
Combined with the 31 senators who voted against debating the overall gun bill last week, that could bring potential opponents of expanding background checks to 41 ? just enough votes to block the Senate from considering the compromise. But in the heated political climate and heavy lobbying certain in the run-up to the vote, minds on both sides could change.
One of those expressing opposition was Sen. Jeff Flake, R-Ariz., who said Monday the measure would cover too many gun transactions.
"It would likely even extend to message boards, like the one in an office kitchen. This simply goes too far," he posted on his Facebook page.
Flake has been a primary target of pressure from gun control groups. He comes from the same state Giffords represented until she was severely wounded in a 2011 mass shooting in Tucson. In addition, Flake's senior colleague, Sen. John McCain, R-Ariz., said he is leaning strongly toward supporting the background check plan.
Opponents say expanded checks would violate the Constitution's right to bear arms and would be ignored by criminals. They are forcing supporters of the background check plan to win 60 of the Senate's 100 votes, a high hurdle.
Fifty Democrats and two Democratic-leaning senators voted last week to begin debate. If all of them support the Manchin-Toomey plan ? which is not guaranteed ? they would still need eight additional votes.
So far, three Republicans who backed beginning debate have said they will vote for the Manchin-Toomey plan: Toomey himself and Sens. Mark Kirk of Illinois and Susan Collins of Maine.
Sen. Frank Lautenberg, D-N.J., missed last week's vote after saying he was suffering from muscle weakness, but spokesman Caley Gray said he hopes to be in the Senate for votes this week.
Two Democrats, both facing re-election next year in GOP-leaning states, voted against beginning the gun control debate last week. Sens. Mark Begich of Alaska and Mark Pryor of Arkansas both said they are still deciding on the Manchin-Toomey plan.
___
Associated Press writer Nedra Pickler contributed to this report.
HOT SPRINGS, Ark. (AP) ? Mike Repole wasn't sure what to make of a disappointing start of the year for his standout 3-year-old, Overanalyze, after a fifth-place finish at the Gotham Stakes last month.
The owner decided to give the colt a six-week break afterward, a move that paid off in convincing fashion Saturday.
Ridden by Rafael Bejarano for the first time, Overanalyze stormed down the home stretch to pull away and win the $1 million Arkansas Derby ? making a three-time winner out of trainer Todd Pletcher.
The colt, who struggled so mightily in his only other start of the year, once again found the form that made him a winner in three of five races last year as a 2-year-old. He won by 4? lengths and earned Pletcher his first win in the 1 1/8-mile Kentucky Derby prep since winning back-to-back Arkansas derbies in 2000 and 2001.
He also more than made up for his difficult first start of the year, a race in which he was favored and among the leaders on the final turn before fading.
"I think he more than redeemed himself," Repole said. "... I was waiting for the move, and the move came. It just came six weeks later in the Arkansas Derby."
Repole was counting on Overanalyze to be a Kentucky Derby contender this year, particularly after the colt earned more than $350,000 last year, and he wasn't sure what to make of the colt's first start in three months on March 2 at the Gotham.
"He kind of sat down," jockey John Velazquez told Repole. "It just looked like he needed a race."
Overanalyze made a prophet on Saturday out of Velazquez, who ceded his position on the colt to Bejarano due to injury. The colt also confirmed for Repole that is was indeed the right decision to rest him for six weeks after the Gotham.
"He really took a lot of steps forward since the Gotham race," Repole said. "I'm not really surprised that he won. I think I'm really shocked how easy he won and by how much he won."
Trained by Pletcher, Overanalyze started in the No. 9 gate in the 10-horse race and trailed with a second group for much of the race. He charged ahead after the final turn, however and easily pulled away from runner-up Frac Daddy and third-place finisher Carve.
Overanalyze paid $9.40, $5.60 and $4.60. Frac Daddy returned $16.80 and $11, and Carve paid $8.60 to show. Overanalyze earned 100 points in the race for a spot in the Kentucky Derby, while Frac Daddy earned 40 and Carve 20.
Bejarano, who won the 2009 Arkansas Derby on Papa Clem, said he even pulled up on the final 1/16th of the race in order to save stamina for Overanalyze.
"I'm sure he's going to be ready for the Kentucky Derby," Bejarano said.
Overanalyze had run only once previously this year after his stellar 2-year-old campaign, his fifth-place finish at the Gotham.
The Repole Stable-owned 3-year-old had no such problems on Saturday in front of 66,158 in attendance at Oaklawn ? running in 1:51.94 and holding off a field that included two Bob Baffert-trained horses.
Baffert's pre-race favorite, War Academy, pulled up on the back stretch before walking off the Oaklawn Park track under his own power. The colt garnered much of the pre-race focus after two wins in three races before backing out of the gate before the race and breaking stride on the back stretch.
"He was just very uncertain over the surface and I tried to get him to settle," jockey Mike Smith said. "He was OK on the first turn, but then he took four or five really awkward steps.
"I didn't see anything major causing it, but I just felt really awkward on him and figured better safe than sorry so I pulled him up. I didn't want to take any chances."
The Hall of Fame trainer's other horse, Den's Legacy, also generated plenty of attention as Baffert attempted to win his second straight Arkansas Derby after Bodemesiter's win a year ago.
It was Pletcher, however, who stole the show with Overanalyze. The former assistant to trainer D. Wayne Lukas, and 2010 Kentucky Derby winner with Super Saver, won his first Arkansas Derby since Graeme Hall in 2000 and Balto Star in 2001.
Overanalyze earned $600,000 with the win, while Frac Daddy ? at 24-1 ? won $200,000 and Carve $100,000.
The race's other favorite, Oxbow, never threatened. The Lukas-trained colt, second in the Rebel Stakes, finished a disappointing fifth.
There was no such disappointment for Overanalyze, who made a three-time winner out of Pletcher in the Arkansas Derby and a first-time winner out of Repole in his first race at Oaklawn.
All backers still on-track to receive their unit by May 25, one quarter of which will come before the end of April
Ouya founder and CEO Julie Uhrman has sent out a message to the Kickstarter backers of the Ouya console that gives a peek at their projected shipping schedule. We see a sharp uptick today, and another near the end of the month when "larger-scale" weekly shipments are expected.
She also mentions that they have made a tweaks to the process that could shave days off the shipping time. We imagine building, sorting, and shipping out consoles to all the backers is not an easy job. Things can (and often do) go wrong, throwing off projections. Here's hoping everything goes smoothly and backers have their unit in hand soon.
Hey everybody! Happy Friday! I bet you can't wait to get that weekend started. Too bad these last few hours of work are crawling by, right? Well here's an idea to help your afternoon fly by ? join the Gizmodo staff on this thread, and for the next hour, we'll talk about anything you want. C'mon, I dare you. More »
Sophie Coldwell's parents blame no one for her death and hope what happened to her can help save other lives
Sent home from NHS walk-in centre but died in hospital 10 days later
Boyfriend's tribute to 'amazing' girl: 'My world, my rock, my shoulder'
By Hugo Gye
PUBLISHED: 05:14 EST, 11 April 2013 | UPDATED: 06:22 EST, 12 April 2013
A teenage girl died from a rare form of leukaemia just 10 days after doctors told her she was only suffering from tonsillitis and fatigue.
Sophie Coldwell, 17, had been feeling tired for some time, but her parents attributed it to the increased burden of schoolwork.
In fact, she was suffering from a cancer so aggressive that a hospital consultant said he had never seen anything like it - and now her family hopes to save others by raising awareness of the devastating condition.
Tragic: Sophie Coldwell, 17, died after falling victim to a rare and aggressive form of leukaemia last month
Sophie visited an NHS walk-in centre on March 7, but was sent home after being diagnosed with chronic fatigue, tonsillitis and inflamed gums.
But her condition failed to improve in the following days, and on March 16 her parents called an ambulance to their home in Yardley, Birmingham when her breathing became shallow and raspy.
She lost consciousness on the way to Solihull Hospital and although she was later transferred to Heartlands Hospital she never recovered, dying in the early hours of March 17 from suspected acute monoblastic myeloid leukaemia.
Helpless: Doctors sent her home 10 days earlier, and her parents thought she was just tired from working harder at school
Sophie's father Andy, 46, a manager at Jaguar Land Rover, said today that he hoped the news of her sudden death could save lives in the future.
'Sophie wasn't feeling that well,' he said. 'She couldn't eat because her mouth was that sore. She had a tough 10 days, really.
'She felt tired. At the time, we put that down to it being her first year in college, it was longer hours - it didn't really raise any concerns at the time.
'As a father, I question everything I did and whether any more could have been done. The fact it took everybody by surprise doesn't mean you still don't do that as parents.
'The consultant said teams would learn from this because of how aggressive and quickly it happened.'
Her mother Sherry, 46, a receptionist at a doctor's surgery, added: 'The consultant said he had never seen anything so aggressive. How quickly it happened was just something he had not seen before.'
Sophie was a student at Solihull Sixth Form College, and had been going out with her boyfriend Matt Robinson since November last year.
The 18-year-old knew his girlfriend was unwell, but had no idea how serious her condition would turn out to be.
In a moving last text he wrote to Sophie, he said: 'You've gone from a girl I added on Facebook to being my life, my heart, my soul, my world, my rock, my shoulder, my everything.
'You're just amazing. Everything about you is stunning, from your smile to your eyes, from your hair to your half-painted nails, from your freckles on top of your shoulders to the freckles on your forehead my perfection.'
Death: Sophie lost consciousness on the way to Heartlands Hospital, pictured, and never recovered
Her sister Katie, 14, wrote a poignant letter to Sophie which was printed in the order of service at her funeral.
SYMPTOMS OF LEUKAEMIA
The five most common signs of cancer in young people aged 13 to 24 are persistent and unexplained pain, extreme tiredness, weight loss, an unexplained lump, bump or swelling or changes in a mole.
Other symptoms of acute myeloid leukaemia include: pale skin, breathlessness, having repeated infections over a short space of time, unusual and frequent bleeding (such as bleeding gums or nose bleeds).
Easily bruised skin, excessive sweating and bone and joint pain are others.
She wrote: 'Your life was only just beginning, there is so much that you're going to miss out on, but I know that you will be watching over me and making sure that I make the right decisions, which is all I can ask from you.
'I hope that you are okay up there and I bet you're still saying "Get out of my room". One day, we will be together again. I just wish that I was there to say goodbye.'
Mr Coldwell said: 'Every day is a struggle, and that's really down to how quickly it happened. It's taken a while for us to get our heads around.
'We have had really fantastic support from family, friends and Sophie's friends, who are taking Katie out and promise to look after her.
'She met Matt in November. I'm a typical father but Matt, right from the start, hit it off with Sophie and with us. From a dad point of view, he ticked all the boxes straight away. You could almost see the connection they had.'
For more information: http://www.nhs.uk/Conditions/Leukaemia-acute/Pages/Symptoms.aspx http://www.teenagecancertrust.org/
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Big cats use their paws, tongues and noises to create artworkPaintings can sell for up to ?130Profits are pumped back into the Big Cat Rescue Sanctuary in TampaMaking art keeps the animals mentally stimulated By Janine Yaqoob PUBLISHED: 06:22 EST, 12 April 2013 | UPDATED: 06:23 EST, 12 April 2013 Meet the paw-casso painters creating artworks worth up to ?130 at a Florida zoo -...
Photo Credit Comstock/Comstock/Getty Images Branch-chain amino acid powders are a common supplement choice for exercisers and sports enthusiasts. Unlike protein powder, branch-chain amino acids supplements claim to improve athletic performance by boosting the effects of the individual amino acids in your body. However, creatine protein powders have been a long-time staple among bodybuilders and athletes, and have been studied more extensively. For best results, compare the different benefits of either mixture to help you choose the supplement that best meets your nutrition and exercise needs.
Branch-chain amino acid supplements are formed by combining different essential amino acids, such as isoleucine, leucine and valine. According to a report published in a 2005 issue of the ?Journal of the International Society of Sports Nutrition,? amino acid supplements are theorized to enhance athletic performance by increasing the secretion of anabolic hormones and modifying the use of fuel during exercise. Branch-chain amino acids are also purported to prevent some adverse effects of overtraining, while preventing mental fatigue. This happens as a result of the relationship between branch-chain amino acids and serotonin levels in the brain, which may delay central nervous system fatigue. Because of these purported benefits, some exercisers prefer to take amino acid supplements in place of standard creatine protein powders. Creatine is one of the most common chemicals used in the creation of protein powders and exercise shakes. Like all types of animal protein, creatine also contains certain types of amino acids. What makes branch-chain amino supplements so distinctive is the individual combinations of different amino acids that they combine in specific doses. However, according to a study published in a 2008 issue of the ?Journal of Sports Medicine and Physical Fitness,? branch-chain amino acid supplements are more effective at boosting muscle recovery and immune regulation than muscle building. Comparatively, creatine protein powders have been linked to increased muscle mass in athletes and older adults, according to MedlinePlus. Based on the available information, creatine protein powders are likely to be more beneficial in building muscle, while branch-chain amino acids are more effective for muscle recovery and injury prevention. If you are currently focusing on building muscle mass through weight lifting, creatine protein powders are more likely to provide the best results for your exercise goals. However, endurance and aerobic athletes may prefer the delayed fatigue and accelerated recovery perks of branch-chain amino acid supplements. If possible, try out one or the other for three months at a time, to see which type of supplementation provides the best results for your activity.Talk to your doctor before taking any type of protein or amino acid supplement if you are currently taking prescription or over-the-counter medications, dietary supplements or herbal remedies. While no specific interactions have been recorded for amino acid-based nutritional supplementation, Drugs.com lists 37 different brand name and generic drugs that interact with creatine, including: Xanax, fish oil, DHEA, Crestor, L-arginine, gingko biloba, Lyrica, Singulair, valerian root, coenzyme Q10 and Viagra.
A South Korean military vehicle passes by gates leading to the North Korean city of Kaesong at the customs, immigration and quarantine office near the border village of Panmunjom, which has separated the two Koreas since the Korean War, in Paju, north of Seoul, South Korea, Monday, April 8, 2013. A top South Korean national security official said Sunday that North Korea may be setting the stage for a missile test or another provocative act with its warning that it soon will be unable to guarantee diplomats' safety in Pyongyang. But he added that the North's clearest objective is to extract concessions from Washington and Seoul. (AP Photo/Lee Jin-man)
A South Korean military vehicle passes by gates leading to the North Korean city of Kaesong at the customs, immigration and quarantine office near the border village of Panmunjom, which has separated the two Koreas since the Korean War, in Paju, north of Seoul, South Korea, Monday, April 8, 2013. A top South Korean national security official said Sunday that North Korea may be setting the stage for a missile test or another provocative act with its warning that it soon will be unable to guarantee diplomats' safety in Pyongyang. But he added that the North's clearest objective is to extract concessions from Washington and Seoul. (AP Photo/Lee Jin-man)
A South Korean worker, left, who arrives with electronic products from North Korea's Kaesong is helped by a South Korean woman who greeted him at the customs, immigration and quarantine office near the border village of Panmunjom, that has separated the two Koreas since the Korean War, in Paju, north of Seoul, South Korea, Monday, April 8, 2013. A top South Korean national security official said Sunday that North Korea may be setting the stage for a missile test or another provocative act with its warning that it soon will be unable to guarantee diplomats' safety in Pyongyang. But he added that the North's clearest objective is to extract concessions from Washington and Seoul. (AP Photo/Lee Jin-man)
FILE - In this Sept. 21, 2012 file photo, 2012, two North Korean men working for ShinWon, a South Korean clothing maker, prepare garments for production at a factory in Kaesong, North Korea. North Korea says it will recall 51,000 North Korean workers and suspend operations at a factory complex that is the last major symbol of co-operation with its southern rival. Pyongyang's statement Monday, April 8, 2013, comes amid weeks of war threats and other efforts to punish South Korea and the U.S. for ongoing joint military drills. (AP Photo/Jean H. Lee, File)
A South Korean worker, left, who arrives with electronic products from North Korea's Kaesong, is helped by a South Korean woman who greeted him, after returning from the North at the customs, immigration and quarantine office near the border village of Panmunjom, that has separated the two Koreas since the Korean War, in Paju, north of Seoul, South Korea, Monday, April 8, 2013. A top South Korean national security official said Sunday that North Korea may be setting the stage for a missile test or another provocative act with its warning that it soon will be unable to guarantee diplomats' safety in Pyongyang. But he added that the North's clearest objective is to extract concessions from Washington and Seoul. (AP Photo/Lee Jin-man)
A South Korean soldier salutes a military vehicle as it leads South Korean vehicles from the North Korean city of Kaesong at the customs, immigration and quarantine office near the border village of Panmunjom, which has separated the two Koreas since the Korean War, in Paju, north of Seoul, South Korea, Monday, April 8, 2013. A top South Korean national security official said Sunday that North Korea may be setting the stage for a missile test or another provocative act with its warning that it soon will be unable to guarantee diplomats' safety in Pyongyang. But he added that the North's clearest objective is to extract concessions from Washington and Seoul. (AP Photo/Lee Jin-man)
SEOUL, South Korea (AP) ? North Korea said Monday it will suspend operations at a factory complex it has jointly run with South Korea, pulling out more than 53,000 North Korean workers and moving closer to severing its last economic link with its rival as tensions escalate.
The Kaesong industrial complex just north of the Demilitarized Zone is the biggest employer in North Korea's third-largest city. Shutting it down, even temporarily, would show that the destitute country is willing to hurt its own economy to display its anger with South Korea and the United States.
Pyongyang's move follows weeks of threatening rhetoric and provocations aimed at Seoul and its U.S. ally following U.N. sanctions punishing the North for its third nuclear test, on Feb. 12. In recent days there have also been worries in Seoul of an even larger provocation from Pyongyang, including another possible nuclear test or rocket launch.
The point of the threats and possible future provocations, analysts say, isn't a full-scale war, which North Korea would certainly lose. It's seen instead as an effort to force new, Pyongyang-friendly policies in South Korea and Washington and to boost domestic loyalty for Kim Jong Un, the country's young, still relatively untested new leader.
The statement about Kaesong came from Kim Yang Gon, secretary of the Central Committee of the Workers' Party of Korea. It did not say what would happen to the 475 South Korean managers still at the Kaesong industrial complex. The statement also did not say whether the North Korean workers would be recalled immediately, and a South Korean manager at Kaesong said he had heard nothing from the North Korean government.
"North Korean workers left work at 6 o'clock today as they usually do. We'll know tomorrow whether they will come to work," said the manager, who declined to be identified because he was not authorized to speak to the media. North Korea had asked South Korean managers to say when they intended to leave by Wednesday; the manager said he did not know whether he and his South Korean colleagues now will be forced to leave.
Kim's statement said North Korea will now consider whether to close the complex permanently. "How the situation will develop in the days ahead will entirely depend on the attitude" of South Korean authorities, it said.
Yoo Ho-yeol, a North Korea expert at Korea University in South Korea, said the North probably will close the park. "North Korea will wait to see what kind of message we will send ... but there is no message that we can send to North Korea," he said.
Yoo said he expects the South Korean managers will be deported, Pyongyang will convert the park for military use, and the fates of the North Korean workers and their families will not be considered. "It's a wrong decision but they won't change it because it's not their top priority," he said.
Another analyst, however, believes North Korea will reopen the complex after South Korea-U.S. drills end in late April. Cheong Seong-chang at the private Sejong Institute in South Korea said the complex depends on raw materials and even electricity from South Korea. He also noted that workers at the complex are paid in U.S. dollars that North Korea would have a hard time replacing because of international sanctions.
Cheong also thinks that although North Korea would put recalled workers on other projects, it would "face a burden that it has to provide the similar quality of livelihood to them. ... There would be voices calling for the normalization of the Kaesong complex."
South Korea's Unification Ministry, which is responsible for relations with the North, issued a statement saying South Korea will act "calmly and firmly" and will make its best efforts to secure the safety of South Koreans at Kaesong.
The Kaesong complex is the last remaining symbol of inter-Korean rapprochement projects from previous eras of cooperation. Other projects such as reunions of families separated by war and tours to a scenic North Korean mountain became stalled amid confrontation between the rival Koreas in recent years.
Last month, North Korea cut the communications with South Korea that had helped regulate border crossings at Kaesong, and last week it barred South Korean workers and cargo from entering North Korea. Operations continued and South Koreans already at Kaesong were allowed to stay, but dwindling personnel and supplies had forced about a dozen of the more than 120 companies operating at Kaesong to close by Sunday.
Kim, the party secretary, visited the complex Monday. He said in remarks carried by the Korean Central News Agency that Kaesong "has been reduced to a theater of confrontation."
South Korea's Unification Ministry estimates 53,000 North Korean workers in Kaesong received $80 million in salary in 2012, an average of $127 a month.
The Unification Ministry says Kaesong accounted for nearly all two-way trade between the Koreas. Cross-border trade, including supplies entering Kaesong and finished products coming out, approached $2 billion annually.
North Korea objects to portrayals in the South of the zone being crucial to the impoverished country's finances. Kim said North Korea "gets few economic benefits from the zone while the south side largely benefits from it." North Korea has also expressed outrage over South Korean discussion of military rescue plans in the event Pyongyang held the managers hostage.
South Korea's finance minister, Hyun Oh-seok, said the government is looking at ways to help Kaesong firms. South Korea offers insurance to the companies in the event of a shutdown or war.
Daemyung Blue Jeans Inc., which does business in Kaesong, is trying to get in touch with its managers in Kaesong and hadn't spoken with them since Monday morning, CEO Choi Dongjin said. "We have seven (South Korean) workers in Kaesong. We don't know what to do about them," he said by phone from Seoul.
North Korea has unnerved the international community by orchestrating an escalating campaign of bombast in recent weeks. It has threatened to fire nuclear missiles at the U.S. and claimed it had scrapped the 1953 armistice that ended fighting in the Korean War.
Last week it told foreign diplomats based in Pyongyang that it will not be able to guarantee their safety as of Wednesday. Embassy workers appeared to be staying put as of Monday.
North Korea has found itself increasingly isolated. China, its most important ally, expressed unusual disappointment when Pyongyang announced last week that it was restarting a plutonium reactor to produce more nuclear-bomb fuel.
Russian President Vladimir Putin, during a visit to Germany, praised the U.S. for postponing a missile test in California that had been set for this week, in the name of lowering tensions. Putin said at a news conference that a conflict on the Korean Peninsula would make the nuclear disaster at Chernobyl "look like a children's story."
The North's threats against the United States are widely dismissed as hyperbole. North Korea is believed to have a few relatively crude nuclear weapons, but analysts say they've seen no evidence it can build a warhead small enough to put on a missile that could hit the U.S. mainland. A direct attack on the U.S. or its allies would result in retaliation that would threaten the existence of the ruling Kim family in Pyongyang, but there are fears the North might launch a smaller-scale attack.
Another possibility is a fourth nuclear test, or a missile test.
The South Korean defense minister said Thursday that North Korea had moved a missile with "considerable range" to its east coast, possibly to conduct a test launch.
Pyongyang's warning to diplomats prompted South Korean President Park Geun-hye's national security director to say Sunday that North Korea may be planning a missile launch or another provocation around Wednesday, according to presidential spokeswoman Kim Haing.
The possibility of a fourth North Korean nuclear test has existed for some time. South Korea has long said the North prepared two tunnels for a nuclear test, but used only one Feb. 12.
Unification Minister Ryoo Kihl-jae generated confusion about South Korean intelligence on the issue Monday in a parliamentary session. When a lawmaker asked whether there have been increased personnel and vehicles at the North's nuclear test site, and whether that is an indication of nuclear test preparation, Ryoo said "there is such an indication."
After Ryoo's initial comments, South Korean Defense Ministry spokesman Kim Min-seok said no increase in activity has been detected at the site, though he added that North Korea can conduct a nuclear test anytime if decides to do so.
The comments in a parliamentary session were recorded on video, but Ryoo later told lawmakers he couldn't remember making them and didn't mean to say them. He said he was "startled" by reports carrying his earlier comments.
___
AP Business Writer Youkyung Lee in Seoul and AP researcher Zhao Liang in Beijing contributed to this report.
Final chapter to 60-year-old blood group mysteryPublic release date: 7-Apr-2013 [ | E-mail | Share ]
Contact: Aileen Sheehy press.office@sanger.ac.uk 44-012-234-96928 Wellcome Trust Sanger Institute
Gene underlies Vel blood group and influences red blood cell traits will lead to safer blood transfusion
Researchers have uncovered the gene at the root of a human blood group that has remained a mystery for the past 60 years. They showed that a genetic deletion on this gene is responsible for the lack of this blood group in some people.
With the discovery of the gene behind the Vel blood group, medical scientists can now develop a more reliable DNA test to identify people who lack this group. This will reduce the risk of severe, and sometimes life threatening, destruction of the Vel-positive donor red blood cells in patients with antibodies against Vel.
The genetic basis of nearly all 34 blood group systems has been resolved over the past century, but identification of the underlying gene of the Vel blood group has withstood persistent attempts since it was first identified 60 years ago. It is estimated that one in 5000 people are Vel-negative, and routine blood transfusions for patients with antibodies against Vel can lead to kidney failure and even death.
"This is really exciting as it shows how the power of modern genomics technologies can directly benefit patient care," says Professor Willem Ouwehand , who heads one of the NHS Blood and Transplant research teams at both the University of Cambridge and the Wellcome Trust Sanger Institute. "This is also a milestone in blood group genetics and the end of long and astounding journey of discoveries in blood group genetics which started with Landsteiner from Austria and Fisher, Coombs and Morgan from England."
The discovery by the team would not have been possible without the colleagues from the blood transfusion services of Denmark, England and the Netherlands who undertook the Herculean effort of identifying the 65 individuals that lacked the Vel blood group by testing the red blood cells from nearly 350,000 donors with antibodies against Vel.
They then sequenced the coding fraction of the genomes of five donors who lack the Vel group to identify the underlying gene.
The team showed that the gene SMIM1 malfunctions in Vel-negative people. SMIM1 is found on chromosome 1 and specifies a small protein, five times smaller than the average human protein. This provides a direct explanation why a discovery by other routes has proven so challenging.
"It has been a remarkable feat to go from gene discovery to function in less than two months", continues Professor Ouwehand.
Current testing for Vel-negative people can be inaccurate but identifying this new role for the gene will make it easier to identify people who lack Vel. The Sanquin Blood Supply research laboratories in Amsterdam and the NHS Blood and Transplant Centre in Cambridge are currently working together to develop a new and affordable DNA test to efficiently identify people who lack the Vel group.
"We already knew of 75 genomic regions that are associated with the haemoglobin levels and other red blood cell traits, but we quickly realised that the SMIM1 gene identified in our study is the same as one of these associated regions," said Dr Pim van der Harst from Groningen University in the Netherlands who led the GWAS analysis for red cell traits in nearly 100,000 individuals. "We had already assumed that a gene in this region of chromosome 1 played a role in the life of red blood cells, but we now have conclusive evidence that it is SMIM1
"We have shown that this gene controls a protein in the membrane of red blood cells. Switching off the SMIM1 gene in zebrafish showed a remarkable reduction in the number of red cells formed and caused anaemia in the fish".
The team observed that the common variant identified by the red blood cell study has a strong effect on how well the SMIM1 gene functions. This not only explains why the level of the Vel blood group varies so extensively in the population, but is also makes it extremely plausible that the Smim1 protein influences haemoglobin levels of red blood cells.
A low haemoglobin level confers a risk of anaemia, which is one of the most frequent reasons for an individual to visit their doctor. The team are pursuing further research to deduce how Smim1 protein regulates red blood cell formation.
"As the molecular machinery underlying red blood cell formation has been researched for decades in fish, mice and man, our discovery that a gene which was considered hypothetical until recently actually controls a red blood cell membrane protein with an important role in the regulation of haemoglobin levels is astonishing," says Professor Ellen van der Schoot from the Sanquin research laboratories in Amsterdam. "A better understanding of how the SMIM1 gene is regulated is important and this effort will greatly benefit from the Blueprint project which will be releasing its results on the biology of blood cells and their precursors this year."
"We have worked for nearly a decade to identify the donors across England that lack the Vel blood group so that we can provide matched and safe blood to patients with antibodies against Vel" says Mr Malcolm Needs from NHS Blood and Transplant in Tooting, London. "The discovery of the SMIM1 gene was achieved so quickly and it is truly amazing to see how medical genomics is changing the care landscape for NHS patients."
###
Notes to Editors
Publication Details
Ana Cvejic, Lonneke Haer-Wigman, Jonathan C Stephens et al. (2013) 'SMIM1 underlies the Vel blood group and influences red blood cell traits'
Published in Nature Genetics online 07 April 2013. doi:10.1038/ng.2603
Funding
This study was supported by the British Heart Foundation, European Commission, Medical Research Council, National Institute for Health Research, NHS Blood and Transplant and the Wellcome Trust.
Participating centres
Department of Haematology, University of Cambridge, Cambridge, UK.
Department of Experimental Immunohaematology, Sanquin Research, Amsterdam, The Netherlands.
Landsteiner Laboratory, Academic Medical Centre, University of Amsterdam, Amsterdam, The Netherlands.
National Institute for Health Research (NIHR) Cambridge Biomedical Research Centre, Cambridge, UK.
National Health Service (NHS) Blood and Transplant, Cambridge, UK. 7
European Molecular Biology Laboratory (EMBL)European Bioinformatics Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge, UK.
Department of Hematopoiesis, Sanquin Research, Amsterdam, The Netherlands.
Department of Genetics, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
NHS Blood and Transplant, Tooting, London, UK.
Department of Cardiology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
Houghton St, Somerville, Massachusetts, USA.
Department of Molecular Biology, Faculty of Science, Nijmegen Centre for Molecular Life Sciences, Radboud University, Nijmegen, The Netherlands.
International Blood Group Reference Laboratory, NHS Blood and Transplant, North Bristol Park, Northway, Filton, Bristol, UK.
Medical Research Council (MRC) Biostatistics Unit, Institute of Public Health, Cambridge, UK. 16Department of Clinical Immunology, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark. 17
Department of Experimental Hematology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
Department of Stem Cell Biology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
Laboratory of Genetic, Endocrine and Metabolic Diseases, Department of Laboratory Medicine, Radboud University Medical Centre, Nijmegen, The Netherlands.
Department of Human Genetics, Radboud University Medical Centre, Nijmegen, The Netherlands.
Professor van der Schoot is a consultant to the Sanquin Blood Supply Foundation in the Netherlands which ensures the safe and efficient blood and platelet supply for the Dutch Healthcare system. Sanquin also develops and produces pharmaceutical products, conducts high-quality scientific research, and develops and performs a multitude of diagnostic services.
http://www.sanquin.nl
Professor Ouwehand is a consultant Haematologist for NHS Blood and Transplant.
NHS Blood and Transplant (NHSBT) is a joint England and Wales Special Health Authority. Its remit includes the provision of a reliable, efficient supply of blood and associated services to the NHS in England and North Wales. It is also the organ donor organisation for the UK and is responsible for matching and allocating donated organs. Eight research themes make up NHSBT's planned Research & Development Strategy. The main research sites, in collaboration with University partners, are Cambridge, Oxford, London and Bristol, with specialist activity in Birmingham and Liverpool.
NHSBT,
http://www.nhsbt.nhs.uk/
The mission of the University of Cambridge is to contribute to society through the pursuit of education, learning and research at the highest international levels of excellence. It admits the very best and brightest students, regardless of background, and offers one of the UK's most generous bursary schemes. The University of Cambridge's reputation for excellence is known internationally and reflects the scholastic achievements of its academics and students, as well as the world-class original research carried out by its staff. Some of the most significant scientific breakthroughs occurred at the University, including the splitting of the atom, invention of the jet engine and the discoveries of stem cells, plate tectonics, pulsars and the structure of DNA. From Isaac Newton to Stephen Hawking, the University has nurtured some of history's greatest minds and has produced more Nobel Prize winners than any other UK institution with over 80 laureates.
http://www.cam.ac.uk
The Wellcome Trust Sanger Institute, which receives the majority of its funding from the Wellcome Trust, was founded in 1992. The Institute is responsible for the completion of the sequence of approximately one-third of the human genome as well as genomes of model organisms and more than 90 pathogen genomes. In October 2006, new funding was awarded by the Wellcome Trust to exploit the wealth of genome data now available to answer important questions about health and disease.
http://www.sanger.ac.uk
The Wellcome Trust is a global charitable foundation dedicated to achieving extraordinary improvements in human and animal health. We support the brightest minds in biomedical research and the medical humanities. Our breadth of support includes public engagement, education and the application of research to improve health. We are independent of both political and commercial interests.
http://www.wellcome.ac.uk
Contact details
Don Powell Media Manager
Wellcome Trust Sanger Institute
Hinxton, Cambridge, CB10 1SA, UK
Tel +44 (0)1223 496 928
Mobile +44 (0)7753 7753 97
Email press.office@sanger.ac.uk
[ | E-mail | Share ]
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AAAS and EurekAlert! are not responsible for the accuracy of news releases posted to EurekAlert! by contributing institutions or for the use of any information through the EurekAlert! system.
Final chapter to 60-year-old blood group mysteryPublic release date: 7-Apr-2013 [ | E-mail | Share ]
Contact: Aileen Sheehy press.office@sanger.ac.uk 44-012-234-96928 Wellcome Trust Sanger Institute
Gene underlies Vel blood group and influences red blood cell traits will lead to safer blood transfusion
Researchers have uncovered the gene at the root of a human blood group that has remained a mystery for the past 60 years. They showed that a genetic deletion on this gene is responsible for the lack of this blood group in some people.
With the discovery of the gene behind the Vel blood group, medical scientists can now develop a more reliable DNA test to identify people who lack this group. This will reduce the risk of severe, and sometimes life threatening, destruction of the Vel-positive donor red blood cells in patients with antibodies against Vel.
The genetic basis of nearly all 34 blood group systems has been resolved over the past century, but identification of the underlying gene of the Vel blood group has withstood persistent attempts since it was first identified 60 years ago. It is estimated that one in 5000 people are Vel-negative, and routine blood transfusions for patients with antibodies against Vel can lead to kidney failure and even death.
"This is really exciting as it shows how the power of modern genomics technologies can directly benefit patient care," says Professor Willem Ouwehand , who heads one of the NHS Blood and Transplant research teams at both the University of Cambridge and the Wellcome Trust Sanger Institute. "This is also a milestone in blood group genetics and the end of long and astounding journey of discoveries in blood group genetics which started with Landsteiner from Austria and Fisher, Coombs and Morgan from England."
The discovery by the team would not have been possible without the colleagues from the blood transfusion services of Denmark, England and the Netherlands who undertook the Herculean effort of identifying the 65 individuals that lacked the Vel blood group by testing the red blood cells from nearly 350,000 donors with antibodies against Vel.
They then sequenced the coding fraction of the genomes of five donors who lack the Vel group to identify the underlying gene.
The team showed that the gene SMIM1 malfunctions in Vel-negative people. SMIM1 is found on chromosome 1 and specifies a small protein, five times smaller than the average human protein. This provides a direct explanation why a discovery by other routes has proven so challenging.
"It has been a remarkable feat to go from gene discovery to function in less than two months", continues Professor Ouwehand.
Current testing for Vel-negative people can be inaccurate but identifying this new role for the gene will make it easier to identify people who lack Vel. The Sanquin Blood Supply research laboratories in Amsterdam and the NHS Blood and Transplant Centre in Cambridge are currently working together to develop a new and affordable DNA test to efficiently identify people who lack the Vel group.
"We already knew of 75 genomic regions that are associated with the haemoglobin levels and other red blood cell traits, but we quickly realised that the SMIM1 gene identified in our study is the same as one of these associated regions," said Dr Pim van der Harst from Groningen University in the Netherlands who led the GWAS analysis for red cell traits in nearly 100,000 individuals. "We had already assumed that a gene in this region of chromosome 1 played a role in the life of red blood cells, but we now have conclusive evidence that it is SMIM1
"We have shown that this gene controls a protein in the membrane of red blood cells. Switching off the SMIM1 gene in zebrafish showed a remarkable reduction in the number of red cells formed and caused anaemia in the fish".
The team observed that the common variant identified by the red blood cell study has a strong effect on how well the SMIM1 gene functions. This not only explains why the level of the Vel blood group varies so extensively in the population, but is also makes it extremely plausible that the Smim1 protein influences haemoglobin levels of red blood cells.
A low haemoglobin level confers a risk of anaemia, which is one of the most frequent reasons for an individual to visit their doctor. The team are pursuing further research to deduce how Smim1 protein regulates red blood cell formation.
"As the molecular machinery underlying red blood cell formation has been researched for decades in fish, mice and man, our discovery that a gene which was considered hypothetical until recently actually controls a red blood cell membrane protein with an important role in the regulation of haemoglobin levels is astonishing," says Professor Ellen van der Schoot from the Sanquin research laboratories in Amsterdam. "A better understanding of how the SMIM1 gene is regulated is important and this effort will greatly benefit from the Blueprint project which will be releasing its results on the biology of blood cells and their precursors this year."
"We have worked for nearly a decade to identify the donors across England that lack the Vel blood group so that we can provide matched and safe blood to patients with antibodies against Vel" says Mr Malcolm Needs from NHS Blood and Transplant in Tooting, London. "The discovery of the SMIM1 gene was achieved so quickly and it is truly amazing to see how medical genomics is changing the care landscape for NHS patients."
###
Notes to Editors
Publication Details
Ana Cvejic, Lonneke Haer-Wigman, Jonathan C Stephens et al. (2013) 'SMIM1 underlies the Vel blood group and influences red blood cell traits'
Published in Nature Genetics online 07 April 2013. doi:10.1038/ng.2603
Funding
This study was supported by the British Heart Foundation, European Commission, Medical Research Council, National Institute for Health Research, NHS Blood and Transplant and the Wellcome Trust.
Participating centres
Department of Haematology, University of Cambridge, Cambridge, UK.
Department of Experimental Immunohaematology, Sanquin Research, Amsterdam, The Netherlands.
Landsteiner Laboratory, Academic Medical Centre, University of Amsterdam, Amsterdam, The Netherlands.
National Institute for Health Research (NIHR) Cambridge Biomedical Research Centre, Cambridge, UK.
National Health Service (NHS) Blood and Transplant, Cambridge, UK. 7
European Molecular Biology Laboratory (EMBL)European Bioinformatics Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge, UK.
Department of Hematopoiesis, Sanquin Research, Amsterdam, The Netherlands.
Department of Genetics, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
NHS Blood and Transplant, Tooting, London, UK.
Department of Cardiology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
Houghton St, Somerville, Massachusetts, USA.
Department of Molecular Biology, Faculty of Science, Nijmegen Centre for Molecular Life Sciences, Radboud University, Nijmegen, The Netherlands.
International Blood Group Reference Laboratory, NHS Blood and Transplant, North Bristol Park, Northway, Filton, Bristol, UK.
Medical Research Council (MRC) Biostatistics Unit, Institute of Public Health, Cambridge, UK. 16Department of Clinical Immunology, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark. 17
Department of Experimental Hematology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
Department of Stem Cell Biology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
Laboratory of Genetic, Endocrine and Metabolic Diseases, Department of Laboratory Medicine, Radboud University Medical Centre, Nijmegen, The Netherlands.
Department of Human Genetics, Radboud University Medical Centre, Nijmegen, The Netherlands.
Professor van der Schoot is a consultant to the Sanquin Blood Supply Foundation in the Netherlands which ensures the safe and efficient blood and platelet supply for the Dutch Healthcare system. Sanquin also develops and produces pharmaceutical products, conducts high-quality scientific research, and develops and performs a multitude of diagnostic services.
http://www.sanquin.nl
Professor Ouwehand is a consultant Haematologist for NHS Blood and Transplant.
NHS Blood and Transplant (NHSBT) is a joint England and Wales Special Health Authority. Its remit includes the provision of a reliable, efficient supply of blood and associated services to the NHS in England and North Wales. It is also the organ donor organisation for the UK and is responsible for matching and allocating donated organs. Eight research themes make up NHSBT's planned Research & Development Strategy. The main research sites, in collaboration with University partners, are Cambridge, Oxford, London and Bristol, with specialist activity in Birmingham and Liverpool.
NHSBT,
http://www.nhsbt.nhs.uk/
The mission of the University of Cambridge is to contribute to society through the pursuit of education, learning and research at the highest international levels of excellence. It admits the very best and brightest students, regardless of background, and offers one of the UK's most generous bursary schemes. The University of Cambridge's reputation for excellence is known internationally and reflects the scholastic achievements of its academics and students, as well as the world-class original research carried out by its staff. Some of the most significant scientific breakthroughs occurred at the University, including the splitting of the atom, invention of the jet engine and the discoveries of stem cells, plate tectonics, pulsars and the structure of DNA. From Isaac Newton to Stephen Hawking, the University has nurtured some of history's greatest minds and has produced more Nobel Prize winners than any other UK institution with over 80 laureates.
http://www.cam.ac.uk
The Wellcome Trust Sanger Institute, which receives the majority of its funding from the Wellcome Trust, was founded in 1992. The Institute is responsible for the completion of the sequence of approximately one-third of the human genome as well as genomes of model organisms and more than 90 pathogen genomes. In October 2006, new funding was awarded by the Wellcome Trust to exploit the wealth of genome data now available to answer important questions about health and disease.
http://www.sanger.ac.uk
The Wellcome Trust is a global charitable foundation dedicated to achieving extraordinary improvements in human and animal health. We support the brightest minds in biomedical research and the medical humanities. Our breadth of support includes public engagement, education and the application of research to improve health. We are independent of both political and commercial interests.
http://www.wellcome.ac.uk
Contact details
Don Powell Media Manager
Wellcome Trust Sanger Institute
Hinxton, Cambridge, CB10 1SA, UK
Tel +44 (0)1223 496 928
Mobile +44 (0)7753 7753 97
Email press.office@sanger.ac.uk
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Public release date: 7-Apr-2013
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