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Apr. 29, 2013 ? University of North Carolina researchers have discovered that disrupting a gene that acts as a regulatory switch to turn on other genes can keep blood vessels from forming and developing properly.
Further study of this gene -- a "transcription factor" called CASZ1 -- may uncover a regulatory network that influences the development of cardiovascular disease. A number of other studies have already shown a genetic link between mutations in CASZ1 and hypertension.
The UNC research, which was carried out in a frog model as well as human cells, will be published April 29, 2013, in the journal Developmental Cell.
"There has been a lot of interest in studying the vasculature because of its role in a wide range of disease states, as well as human development. But there are very few transcription factors that are known to affect the vasculature. To find a new one is quite unique, and then to be able to link it up to a known network of vascular development is surprising and encouraging," said senior study author Frank Conlon, PhD, an associate professor of genetics in the UNC School of Medicine.
During vascular development, specialized cells coalesce into three-dimensional "cords" that then hollow out to provide a path for transporting blood throughout the body. This process involves the complex coordination of molecular entities like growth factors and signaling molecules, defects that have been associated with human illnesses such as cancer, stroke, and atherosclerosis.
Conlon has long been interested in understanding how these various molecular players come together in the cardiovascular system. In 2008, his laboratory showed that a gene called CASZ1 is involved in the development of heart muscle. In this study, he and his colleagues decided to look for its role in the development of blood vessels.
Marta S. Charpentier and Kathleen S. Christine, lead authors of the study and graduate students in Conlon's laboratory, removed CASZ1 from frog embryos and looked to see how its absence affected the development of the vasculature. Without CASZ1, the frogs failed to form branched and functional blood vessels. When they removed the CASZ1 gene from cultured human cells, Charpentier and Christine saw similar defects: the cells did not sprout or branch correctly due to their inability to maintain proper adhesions with the surrounding extracellular matrix.
"If you take out CASZ1, these cultured human cells try to migrate by sending out these filopodia or little feet, but what happens is it is like someone nails down the back end of those growing vessels. They try to move and keep getting thinner and thinner, and like an elastic band it gets to be too much and just snaps back. It appears to cause an adhesion defect that makes the cells too sticky to form normal vessels," said Conlon.
CASZ1 is a transcription factor, a master switch that controls when and where other genes are expressed. Therefore, Charpentier and Christine did a series of experiments to explore CASZ1's influence on a known vascular network, involving other genes called Egfl7 and RhoA. When Charpentier and Christine added the Egfl7 gene to her CASZ1-depleted cells, the defect in blood vessel formation went away, suggesting that the two genes are connected. They then showed that CASZ1 directly acts on the Egfl7 gene, and that this activity in turn activates the RhoA gene, which is known to be required for cellular behaviors associated with adhesion and migration.
Transcription factors themselves are so essential that they are generally considered to be "undruggable," but the researchers say that further studies into how specific transcription factors work and the targets they control could eventually lead to new drug candidates.
"Egfl7 is a therapeutic target of interest, because companies such as Genentech are already working on it for cancer therapy," said Charpentier. "Figuring out how it is regulated is important not just for understanding the biology of it, but also for discovering targets that could trigger the development of innovative therapeutic strategies for cardiovascular disease."
The research was a collaboration between the Conlon, Taylor, and Bautch labs at the McAllister Heart Institute at UNC and was funded by the National Institutes of Health and the American Heart Association. Study co-authors from UNC were Nirav M. Amin, PhD; Kerry M. Dorr; Erich J. Kushner, PhD; Victoria L. Bautch, PhD; and Joan M. Taylor, PhD.
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The above story is reprinted from materials provided by University of North Carolina School of Medicine, via Newswise.
Note: Materials may be edited for content and length. For further information, please contact the source cited above.
Journal Reference:
Marta?S. Charpentier, Kathleen?S. Christine, Nirav?M. Amin, Kerry?M. Dorr, Erich?J. Kushner, Victoria?L. Bautch, Joan?M. Taylor, Frank?L. Conlon. CASZ1 Promotes Vascular Assembly and Morphogenesis through the Direct Regulation of an EGFL7/RhoA-Mediated Pathway. Developmental Cell, 2013; 25 (2): 132 DOI: 10.1016/j.devcel.2013.03.003
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.
SUMMERVILLE, S.C. ? South Carolina?s First Congressional District is known for the churning Port of Charleston, growing suburbs to the north, and stately homes with wrap-around porches from Beaufort to Mount Pleasant. The white, well-heeled voters who dominate the district favored Republican presidential nominee Mitt Romney by 18 percentage points.
RELATED: Stephen Colbert's Sister Is Polling Pretty Well Against Mark Sanford
This coastal strip is also home to a more blue-collar, solidly Democratic population; about one out of five of the district?s residents are African-American. Their turnout in the May 7 special congressional election is key to an upset by the Democratic nominee, Elizabeth Colbert Busch.
RELATED: Mark Sanford Is One Step Closer to Redemption
Inside her campaign office here, having come straight from church in their Sunday best, Dot Brown and Ethel Campbell are planning an afternoon of phone banking and door knocking. Local television stations aren?t carrying the only debate pitting Colbert Busch against Sanford on Monday night.
RELATED: Who Is Stephen Colbert's Sister? (Aside from Being Stephen Colbert's Sister)
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?Most people we come across tend not to understand the importance of a special election, so you have got to get out and let them know,? said Brown, 67 years old, dressed in a marigold suit and bright pink scarf.
RELATED: The Appalachian Trail Ad Democrats Were Waiting to Air
Campbell, 62, who immediately kicked off her pumps once she sat down, said she tries to explain to voters that electing another Democrat to Congress will help President Obama. ?I say, ?You had his back in 2012. Do you have his back in 2013?? "
RELATED: Mark Sanford's Bare-All Apology Tour Isn't Working
But Colbert Busch has flaunted her independence from a president unpopular in most of the district, assailing his budget plan for raising taxes, not cutting enough spending and meddling with Social Security. ?Not only does President Obama?s plan fail to put our finances back in order, it would cut benefits for our seniors, which is wrong,? she said in a statement. Colbert Busch also declined to say whether she would have supported Obama's economic stimulus plan in his first term.? ?She?s trying to be all things to all people,?? said Sanford spokesman Joel Sawyer.
Interviews with black voters on Sunday found few knew much about the businesswoman and political novice -- beyond the fact that she?s the sister of comedian Stephen Colbert. ?If they vote, disgust with her Republican opponent, former Gov. Mark Sanford, is more likely to be the driving force. The governor left office in 2011, over a year?after admitting he disappeared from public view for several days to visit his girlfriend in Argentina.
?We don?t need people like him who set a bad example,? said 78-year-old Virginia Rosemond, her wide-brimmed, red hat shielding her from a drizzly rain as left the Baum Temple AME Zion Church. Will she vote for Colbert Busch? ??If I get a ride,? she responded.
Fellow churchgoer Charles Logan, 67, said he ?might? vote for Colbert Busch. ??I?m not messing with him,? he said of Sanford. ?He left his wife. He left his office. What makes you think he won?t go to Washington and do the same thing??
Colbert Busch?s campaign did not respond to e-mails and phone calls about its outreach to African-American voters. Appealing to moderate Republicans and independents is also crucial to her success, so there is a political risk in appearing eager to court black Democrats. When she campaigned at historically black Burke High School in Charleston last week, the event was billed as a rally for women voters.
But the campaign?s radio ad linking Sanford to allegations of voter suppression makes her intentions clear. With Isaac Hayes? soundtrack from the 1971 movie about a black private detective as backdrop, the ad assails a new South Carolina law that requires voters to show photo identification.? A federal court blocked the law from going into effect until after the 2012 election. ?Somebody doesn?t want African Americans to vote, and it doesn?t take Shaft to figure out who,? a narrator says in the radio spot. ?Tuesday May 7th is your chance to show them they can?t get away with it.?
The spot doesn?t mention that the ID law was signed after Sanford left office by Gov. Nikki Haley. A spokesman for the Sanford campaign, Joel Sawyer, released a written statement when the ad first aired earlier this month that called it a ?negative radio ad with some very unfortunate overtones.?
Jaime Harrison, vice chairman of the South Carolina Democratic Party, defended the spot.
?Voter ID has been a very hot button issue in the African-American community,? said Harrison, who if elected chairman next month would be the first black to lead the party in South Carolina. ?Many folks who grew up in the civil rights movement have called it modern-day Jim Crow. The ad will help to pique the awareness of African-Americans in that district.?
Sanford is not opposed to the law, Sawyer said, but he did not recall the ex-governor ever speaking publicly about it. Sawyer also noted that Sanford appointed a record number of African-Americans to his Cabinet and joined the state Supreme Court?s chief justice in 2006 in calling for more diverse appointments to the bench. In 2003, Sanford offered an official apology for the ?Orangeburg Massacre,? the 1968 shootings by South Carolina highway patrol officers that killed three black students ?protesting a segregated bowling alley.
The uncertainty of black turnout in the May 7 special election comes on the heels of an Associated Press analysis that found blacks voted at a higher rate than other minority groups in 2012 and largely surpassed white turnout for the first time. If black turnout had matched 2004, Romney would have won in 2012.
In one of Colbert Busch?s only campaign events aimed at African-Americans, she spoke at a black history celebration in February at Summerville High school. ?I give her credit for that,? said Ava Graham, a 44-year-old child care worker whose daughter sang with her church choir at the event. Colbert Bush spoke about the impact of Martin Luther King and Robert F. Kennedy on her life. ?I hope the black community comes out,? Graham said, ?because the Republicans want this seat and are going to do what they have to do.??
Many employees receive their pay on a weekly or biweekly schedule, Hamm writes. Meanwhile, most bills come on a monthly basis, some even less frequently. There are some tips for reconciling the two.
By Trent Hamm,?Guest blogger / April 28, 2013
Some workers struggle to create a monthly budget when they are paid on a weekly or bi-weekly basis.
Ann Hermes/Staff
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Every so often, I?ll get a question like this one, from Gina:
Skip to next paragraph Trent Hamm
The Simple Dollar is a blog for those of us who need both cents and sense: people fighting debt and bad spending habits while building a financially secure future and still affording a latte or two. Our busy lives are crazy enough without having to compare five hundred mutual funds ? we just want simple ways to manage our finances and save a little money.
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I am a federal employee and I get my paycheck every two weeks but all of my bills are monthly. What?s an easy budgeting system?
This is a pretty consistent problem, actually.?Many?employees receive their pay on a weekly or biweekly schedule. Meanwhile,?most?bills come on a monthly basis, some even less frequently.
How do you easily reconcile the two and take on a budgeting plan?
This is a problem I had to deal with in the past. Prior to 2008, I was employed in a situation that paid me every two weeks. It was a bit of a struggle to find a good balance between the paycheck and the monthly bills. My wife was also on a biweekly system, but her paydays were on different days than mine.?
Rear seat design -- a priority for children's safety in carsPublic release date: 29-Apr-2013 [ | E-mail | Share ]
Contact: Dana Mortensen mortensen@email.chop.edu 267-426-6092 Children's Hospital of Philadelphia
New report recommends technology, policy changes to better protect older children and adolescents in crashes
2013 A research report released today from The Children's Hospital of Philadelphia (CHOP) provides specific recommendations for optimizing the rear seat of passenger vehicles to better protect its most common occupants children and adolescents. By bringing technologies already protecting front seat passengers to the rear seat and modifying the geometry of the rear seat to better fit this age group, the US could achieve important reductions in serious injury and death. Motor vehicle crashes remain the leading cause of death for children older than 4 years and resulted in 952 fatalities in 2010 for children age 15 and younger.
"Our review of the current science and data regarding rear seat occupant safety found clear evidence that use of a child restraint system (CRS) is protective for younger children. However, older children who have outgrown child safety seats and booster seats are at greater risk of injury," says Kristy Arbogast, PhD, lead author of the report and director of engineering at the Center for Injury Research and Prevention at CHOP. "Many technologies that protect front seat passengers, such as load limiters and pretensioners, are not commonly found in the rear seat even though sled tests and computer modeling suggest that these seat belt features have the potential to reduce the risk of serious head and chest injury for rear seated occupants."
In addition to front seat restraints, CHOP researchers suggest that cues can be taken from booster seat design to determine how to keep kids who have outgrown boosters properly positioned in vehicle seat belts so the restraint can perform properly. They propose that adjustments to the geometry of the rear seat including shorter seat cushions, lower seat belt anchorages and contoured seats could increase comfort, keep the shoulder belt in position and, in side impact crashes, reduce lateral movement.
"For children under age 13, the rear seat is still the safer seating position as compared to the front seat of passenger vehicles," says Dr. Arbogast. "But we can do a better job at protecting children who have outgrown add-on restraints."
The report authors recommend the development of regulatory procedures or vehicle performance assessment programs for consumers that evaluate protection of rear seat occupants. Common vehicle rating systems do not evaluate the safety of rear seat occupants in frontal crashes. In addition to engineering solutions, the report also recommends policies and programs to increase rear seat restraint use, which remains lower than front seat restraint use and is a key risk factor for dying in a crash. Additional research is needed to further inform these priorities.
###
To download the full report, made possible with support from Global Automakers, and additional materials including a one-page overview of CIRP's recommendations and an infographic, visit http://injury.research.chop.edu.
About The Center for Injury Research and Prevention at The Children's Hospital of Philadelphia
The Center for Injury Research and Prevention at The Children's Hospital of Philadelphia was established in 1998 to advance the safety and health of children, adolescents, and young adults through comprehensive research that encompasses before-the-injury prevention to after-the-injury healing. The Center's multidisciplinary research team, with expertise in Behavioral Sciences; Medicine; Engineering, Epidemiology and Biostatistics; Human Factors; Public Health; and Communication, translates rigorous scientific research into practical tools and guidelines for families, professionals, and policymakers to ensure research results extend to the real world. For more information on the Center and its research initiatives, visit injury.research.chop.edu.
About Global Automakers
The Association of Global Automakers represents international motor vehicle manufacturers, original equipment suppliers, and other automotive-related trade associations. We work with industry leaders, legislators, and regulators to create the kind of public policy that improves vehicle safety, encourages technological innovation, and protects our planet. Our goal is to foster a competitive environment in which more vehicles are designed and built to enhance Americans' quality of life. For more information, visit http://www.globalautomakers.org.
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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.
Rear seat design -- a priority for children's safety in carsPublic release date: 29-Apr-2013 [ | E-mail | Share ]
Contact: Dana Mortensen mortensen@email.chop.edu 267-426-6092 Children's Hospital of Philadelphia
New report recommends technology, policy changes to better protect older children and adolescents in crashes
2013 A research report released today from The Children's Hospital of Philadelphia (CHOP) provides specific recommendations for optimizing the rear seat of passenger vehicles to better protect its most common occupants children and adolescents. By bringing technologies already protecting front seat passengers to the rear seat and modifying the geometry of the rear seat to better fit this age group, the US could achieve important reductions in serious injury and death. Motor vehicle crashes remain the leading cause of death for children older than 4 years and resulted in 952 fatalities in 2010 for children age 15 and younger.
"Our review of the current science and data regarding rear seat occupant safety found clear evidence that use of a child restraint system (CRS) is protective for younger children. However, older children who have outgrown child safety seats and booster seats are at greater risk of injury," says Kristy Arbogast, PhD, lead author of the report and director of engineering at the Center for Injury Research and Prevention at CHOP. "Many technologies that protect front seat passengers, such as load limiters and pretensioners, are not commonly found in the rear seat even though sled tests and computer modeling suggest that these seat belt features have the potential to reduce the risk of serious head and chest injury for rear seated occupants."
In addition to front seat restraints, CHOP researchers suggest that cues can be taken from booster seat design to determine how to keep kids who have outgrown boosters properly positioned in vehicle seat belts so the restraint can perform properly. They propose that adjustments to the geometry of the rear seat including shorter seat cushions, lower seat belt anchorages and contoured seats could increase comfort, keep the shoulder belt in position and, in side impact crashes, reduce lateral movement.
"For children under age 13, the rear seat is still the safer seating position as compared to the front seat of passenger vehicles," says Dr. Arbogast. "But we can do a better job at protecting children who have outgrown add-on restraints."
The report authors recommend the development of regulatory procedures or vehicle performance assessment programs for consumers that evaluate protection of rear seat occupants. Common vehicle rating systems do not evaluate the safety of rear seat occupants in frontal crashes. In addition to engineering solutions, the report also recommends policies and programs to increase rear seat restraint use, which remains lower than front seat restraint use and is a key risk factor for dying in a crash. Additional research is needed to further inform these priorities.
###
To download the full report, made possible with support from Global Automakers, and additional materials including a one-page overview of CIRP's recommendations and an infographic, visit http://injury.research.chop.edu.
About The Center for Injury Research and Prevention at The Children's Hospital of Philadelphia
The Center for Injury Research and Prevention at The Children's Hospital of Philadelphia was established in 1998 to advance the safety and health of children, adolescents, and young adults through comprehensive research that encompasses before-the-injury prevention to after-the-injury healing. The Center's multidisciplinary research team, with expertise in Behavioral Sciences; Medicine; Engineering, Epidemiology and Biostatistics; Human Factors; Public Health; and Communication, translates rigorous scientific research into practical tools and guidelines for families, professionals, and policymakers to ensure research results extend to the real world. For more information on the Center and its research initiatives, visit injury.research.chop.edu.
About Global Automakers
The Association of Global Automakers represents international motor vehicle manufacturers, original equipment suppliers, and other automotive-related trade associations. We work with industry leaders, legislators, and regulators to create the kind of public policy that improves vehicle safety, encourages technological innovation, and protects our planet. Our goal is to foster a competitive environment in which more vehicles are designed and built to enhance Americans' quality of life. For more information, visit http://www.globalautomakers.org.
[ | E-mail | Share ]
?
AAAS and EurekAlert! are not responsible for the accuracy of news releases posted to EurekAlert! by contributing institutions or for the use of any information through the EurekAlert! system.
Apr. 29, 2013 ? Having to explain how a political policy works leads people to express less extreme attitudes toward the policy, according to new research published in Psychological Science, a journal of the Association for Psychological Science.
The research suggests that people may hold extreme policy positions because they are under an illusion of understanding -- attempting to explain the nuts and bolts of how a policy works forces them to acknowledge that they don't know as much about the policy as they initially thought.
Psychological scientist Philip Fernbach of the Leeds School of Business at the University of Colorado, Boulder and his co-authors were interested in exploring some of the factors that could contribute to what they see as increasing political polarization in the United States.
"We wanted to know how it's possible that people can maintain such strong positions on issues that are so complex -- such as macroeconomics, health care, foreign relations -- and yet seem to be so ill-informed about those issues," says Fernbach.
Drawing on previous research on the illusion of understanding, Fernbach and colleagues speculated that one reason for the apparent paradox may be that voters think they understand how policies work better than they actually do.
In their first study, the researchers asked participants taking an online survey to rate how well they understood six political policies, including raising the retirement age for Social Security, instituting a national flat tax, and implementing merit-based pay for teachers. The participants were randomly assigned to explain two of the policies and then asked to re-rate how well they understood the policies.
As the researchers predicted, people reported lower understanding of all six policies after they had to explain them, and their positions on the policies were less extreme. In fact, the data showed that the more people's understanding decreased, the more uncertain they were about the position, and the less extreme their position was in the end.
The act of explaining also affected participants' behavior. People who initially held a strong position softened their position after having to explain it, making them less likely to donate bonus money to a related organization when they were given the opportunity to do so.
Importantly, the results affected people along the whole political spectrum, from self-identified Democrats to Republicans to Independents.
According to the researchers, these findings shed light on a psychological process that may help people to open the lines of communication in the context of a heated debate or negotiation.
"This research is important because political polarization is hard to combat," says Fernbach. "There are many psychological processes that act to create greater extremism and polarization, but this is a rare case where asking people to attempt to explain makes them back off their extreme positions."
In addition to Fernbach, co-authors include Todd Rogers of the Harvard Kennedy School; Craig R. Fox of the University of California, Los Angeles; and Steven A. Sloman of Brown University.
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The above story is reprinted from materials provided by Association for Psychological Science.
Note: Materials may be edited for content and length. For further information, please contact the source cited above.
Journal Reference:
P. M. Fernbach, T. Rogers, C. R. Fox, S. A. Sloman. Political Extremism Is Supported by an Illusion of Understanding. Psychological Science, 2013; DOI: 10.1177/0956797612464058
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.
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Public release date: 29-Apr-2013
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