May 15, 2013 ? These days, phylogeneticists -- experts who painstakingly map the complex branches of the tree of life -- suffer from an embarrassment of riches. The genomics revolution has given them mountains of DNA data that they can sift through to reconstruct the evolutionary history that connects all living beings. But the unprecedented quantity has also caused a serious problem: The trees produced by a number of well-supported studies have come to contradictory conclusions.
"It has become common for top-notch studies to report genealogies that strongly contradict each other in where certain organisms sprang from, such as the place of sponges on the animal tree or of snails on the tree of mollusks," said Antonis Rokas, Cornelius Vanderbilt Chair in Biological Sciences at Vanderbilt University.
In a study published online May 8 by the journal Nature, Rokas and graduate student Leonidas Salichos analyze the reasons for these differences and propose a suite of novel techniques that can resolve the contradictions and provide greater accuracy in deciphering the deep branches of life's tree.
"The study by Salichos and Rokas comes at a critical time when scientists are grappling with how best to detect the signature of evolutionary history from a deluge of genetic data. These authors provide intriguing insights into our standard analytical toolbox, and suggest it may be time to abandon some of our most trusted tools when it comes to the analysis of big data sets. This significant work will certainly challenge the community of evolutionary biologists to rethink how best to reconstruct phylogeny," said Michael F. Whiting, program director of systematics and biodiversity science at the National Science Foundation, which funded the study.
To gain insight into this paradox, Salichos assembled and analyzed more than 1,000 genes -- approximately 20 percent of the entire yeast genome -- from each of 23 yeast species. He quickly realized that the histories of the 1,000-plus genes were all slightly different from each other as well as different from the genealogy constructed from a simultaneous analysis of all the genes.
"I was quite surprised by this result," Salichos pointed out.
By adapting an algorithm from information theory, the researchers found that they could use these distinct gene genealogies to quantify the conflict and focus on those parts of the tree that are problematic.
In broad terms, Rokas and Salichos found that genetic data is less reliable during periods of rapid radiation, when new species were formed rapidly. A case in point is the Cambrian explosion, the sudden appearance about 540 million years ago of a remarkable diversity of animal species, without apparent predecessors. Before about 580 million years ago, most organisms were very simple, consisting of single cells occasionally organized into colonies.
"A lot of the debate on the differences in the trees has been between studies concerning the 'bushy' branches that took place in these 'radiations'," Rokas said.
The researchers also found that the further back in time they went the less reliable the genetic data becomes. "Radioactive dating methods are only accurate over a certain time span," said Rokas. "We think that the value of DNA data might have a similar limit, posing considerable challenges to existing algorithms to resolve radiations that took place in deep time."
The research was supported by National Science Foundation CAREER award DEB-0844968.
>>>our next guest says mistakes are an essential part of his field. not toure. he is a renowned physicist and says the errors from the most famous scientists from einstein to darwin to kelvin are every bit as important to the world as their successes. according to him, the march toward our understanding of evolution and the earth around us has been filled with false starts and botched theories and we are all better for it. joining us now is mario, the astrophysicist at the
hubble space science institute
and the author of brilliant blunders. let's start there. why blunders? why are they productive? what was the goal of the book?
>>so there were three goals to the book. one is to make us all feel a little bit better. namely that even the biggest geniuses make some serious blunders. second is to correct the misconception that some people think that science marches on a straight line from a to b when in fact it is really a
zig zag
path that encounters many, many blunders. and third to convey this notion that if you want to
think outside the box
, be prepared to meet some blunders along the way.
>>chars darwin didn't know any genetics and we cannot blame him for that because nobody knew genetics at the time. but the theory of genetics with which he was operating was like mixing of paints. you take qualities of the father and the mother and mix them. or you would do gin andtonic. what he didn't realize was that if that was the correct theory,
natural selection
could never have worked. because you know, you think of one
black cat
, 100 white cats. every time they mate, you mix those paints, no way even if black gives some advantage will take over. because you know, it will just get diluted and diluted.
>>i want to talk about the
big bang
for a hot second. you look at the review of when we had the
big bang
on one side and the
steady state theory
on the other. you tell the story of
fred hoyle
. a big believer in the
steady state theory
. that the universe doesn't change
over time
. it basically has no beginning or end. kind of a cool concept. that ultimately the
big bang
won out. that's the idea that the universe began as hot dense matter and then it expanded and cooled
over time
. you explain that fred basically knew a lot of stuff and better, but he couldn't get away from the study staeady
state theory
. you wrote being wrong in a major enterprise constitutes a trauma. why was hoyle traumatized by the fact the
steady state theory
was failing?
>>you know,
fred hoyle
had this idea of a
steady state
, that the universe isn't changing. this was a very elegant idea, and he got, you know, in some way
fell in love
with that idea. and so that every time, you know, people said no, actually it started with a
big bang
and so on, you know, he's -- what's amazing is that he coined the term "
big bang
." you know, he said it all started in one
big bang
, and this is the term we use ever since. but he never believed in that. and the main blunder really, in his case, is that just stubbornly refusing to accept even as evidence was mounting that the
big bang
was the correct theory.
>>are you saying that he used the term "big boang" dericively?
>>this was in a radio address. he wanted to create a mental picture for his listeners. basically he said on one hand we have this theory, and on the other, there are those who say it all started in one
big bang
.
>>mario, you'll be happy to know in all of my science classes i almost always made blunders and that's why i'm here today and not in a lab somewhere. but, you know, legend has it that
thomas edison
famously said, no, no, no, i didn't fail a thousand times to make a
light bulb
work, i came up with a thousand ways how not to make a
light bulb
. but are there any
happy accidents
that come out of these blunders where maybe you don't stumble through science to get to the point you were hoping, but you do sort of go off route and find something else? some other wonderful discovery?
>>well, yes. there are a number of such examples and
discovery of penicillin
is one such example. but, in fact, you will notice that i called the book "brilliant blunders" because of the reason that, in fact, all of the blunders i describe here eventually actually led to breakthroughs. i mean, the idea is that to make a really big discovery, you need to
think outside the box
. and to
think outside the box
really means that sometimes you're going to make blunders.
>>right.
>>and this is the way science really progresses.
>>all right.
mario livio
, interesting things and certainly makes us all who have made a blue blunders feel better that geniuses have also made blunders. so thank you so much for the book and for joining us.
>>thank you for having me.
>>>all right. up next, s.e.'s take on the
real life
episode of "scandal" unfolding in washington right now. we had
Contact: Karen Mallet km463@georgetown.edu Georgetown University Medical Center
WASHINGTON Continuous infusion of a novel agent not only halted the progression of Ewing sarcoma in rats, while some tumors also regressed to the point that cancer cells could not be detected microscopically, say researchers at Georgetown Lombardi Comprehensive Cancer Center. Their study, which will be presented at the 2013 annual meeting of the American Society of Clinical Oncology, provides pre-clinical evidence necessary to initiate a clinical trial.
"This agent has the potential to be more effective, and considerably less toxic, than the current drugs now used to treat this rare cancer," says the study's lead investigator, Jeffrey Toretsky, MD, a pediatric oncologist and researcher at Georgetown Lombardi, part of Georgetown University Medical Center.
The agent, (S)-YK-4-279, was developed by Toretsky and his colleagues, including scientists in GUMC's Center for Drug Discovery. Based on early promising studies of the compound, Toretsky established TDP Biotherapeutics, Inc. to manufacture the agent. Toretsky says TDP Biotherapeutics, Inc. is preparing a U.S. Food and Drug Administration (FDA) investigational new drug (IND) application for (S)-YK-4-279 so that a clinical trial can be initiated.
In the United States, about 500 children and young adults are diagnosed with the cancer annually, and they are treated with a combination of five different chemotherapy drugs. Between 60 to 70 percent of patients survive more than five years, but with many late effects from therapy. Few treatments lead to a cure for patients whose cancer progresses, Toretsky says.
Ewing sarcoma is caused by the exchange of DNA between two chromosomes. The resulting EWSR1-FLI1 gene produces a fusion protein, EWS-FLI1, responsible for development of the cancer. In 2006, Toretsky and his team discovered that the fusion protein binds to another protein, RNA helicase A (RHA), which is important for cancer progression.
The (S)-YK-4-279 agent they developed is considered unique because it stops the two proteins EWS-FLI1 and RHA from interacting. "Scientists have long thought it impossible to block protein-protein interaction because the surface of these proteins are too slippery and flexible for a drug to bind to," Toretsky says. "Our agent challenges that conventional thinking."
To test the agent, the researchers developed a rat model of Ewing sarcoma and figured out how to deliver a continuous drip of the drug to the animals. "We found that cancer cells need a continuous exposure at low concentrations for the drug to be of maximum effectiveness," Toretsky says. "And this strategy works extremely well in these animal models. The drug appears to be very successful."
Toretsky is an inventor on a patent application that has been filed by Georgetown University related to the technology described. He has an ownership interest in TDP Biotherapeutics, to which the technology has been licensed for research and development.
###
The FDA has granted the TDP Biotherapeutics company orphan drug status (Orphan Drug Act), which qualifies the sponsor of a product to receive tax credit and marketing incentives. The study was funded by a grant from the National Cancer Institute (RC4 CA156509) issued under the American Recovery and Reinvestment Act (R01CA138212).
About Georgetown Lombardi Comprehensive Cancer Center
Georgetown Lombardi Comprehensive Cancer Center, part of Georgetown University Medical Center and MedStar Georgetown University Hospital, seeks to improve the diagnosis, treatment, and prevention of cancer through innovative basic and clinical research, patient care, community education and outreach, and the training of cancer specialists of the future. Georgetown Lombardi is one of only 41 comprehensive cancer centers in the nation, as designated by the National Cancer Institute (grant #P30 CA051008), and the only one in the Washington, DC area. For more information, go to http://lombardi.georgetown.edu.
About Georgetown University Medical Center
Georgetown University Medical Center is an internationally recognized academic medical center with a three-part mission of research, teaching and patient care (through MedStar Health). GUMC's mission is carried out with a strong emphasis on public service and a dedication to the Catholic, Jesuit principle of cura personalis -- or "care of the whole person." The Medical Center includes the School of Medicine and the School of Nursing & Health Studies, both nationally ranked; Georgetown Lombardi Comprehensive Cancer Center, designated as a comprehensive cancer center by the National Cancer Institute; and the Biomedical Graduate Research Organization (BGRO), which accounts for the majority of externally funded research at GUMC including a Clinical Translation and Science Award from the National Institutes of Health.
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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.
Contact: Karen Mallet km463@georgetown.edu Georgetown University Medical Center
WASHINGTON Continuous infusion of a novel agent not only halted the progression of Ewing sarcoma in rats, while some tumors also regressed to the point that cancer cells could not be detected microscopically, say researchers at Georgetown Lombardi Comprehensive Cancer Center. Their study, which will be presented at the 2013 annual meeting of the American Society of Clinical Oncology, provides pre-clinical evidence necessary to initiate a clinical trial.
"This agent has the potential to be more effective, and considerably less toxic, than the current drugs now used to treat this rare cancer," says the study's lead investigator, Jeffrey Toretsky, MD, a pediatric oncologist and researcher at Georgetown Lombardi, part of Georgetown University Medical Center.
The agent, (S)-YK-4-279, was developed by Toretsky and his colleagues, including scientists in GUMC's Center for Drug Discovery. Based on early promising studies of the compound, Toretsky established TDP Biotherapeutics, Inc. to manufacture the agent. Toretsky says TDP Biotherapeutics, Inc. is preparing a U.S. Food and Drug Administration (FDA) investigational new drug (IND) application for (S)-YK-4-279 so that a clinical trial can be initiated.
In the United States, about 500 children and young adults are diagnosed with the cancer annually, and they are treated with a combination of five different chemotherapy drugs. Between 60 to 70 percent of patients survive more than five years, but with many late effects from therapy. Few treatments lead to a cure for patients whose cancer progresses, Toretsky says.
Ewing sarcoma is caused by the exchange of DNA between two chromosomes. The resulting EWSR1-FLI1 gene produces a fusion protein, EWS-FLI1, responsible for development of the cancer. In 2006, Toretsky and his team discovered that the fusion protein binds to another protein, RNA helicase A (RHA), which is important for cancer progression.
The (S)-YK-4-279 agent they developed is considered unique because it stops the two proteins EWS-FLI1 and RHA from interacting. "Scientists have long thought it impossible to block protein-protein interaction because the surface of these proteins are too slippery and flexible for a drug to bind to," Toretsky says. "Our agent challenges that conventional thinking."
To test the agent, the researchers developed a rat model of Ewing sarcoma and figured out how to deliver a continuous drip of the drug to the animals. "We found that cancer cells need a continuous exposure at low concentrations for the drug to be of maximum effectiveness," Toretsky says. "And this strategy works extremely well in these animal models. The drug appears to be very successful."
Toretsky is an inventor on a patent application that has been filed by Georgetown University related to the technology described. He has an ownership interest in TDP Biotherapeutics, to which the technology has been licensed for research and development.
###
The FDA has granted the TDP Biotherapeutics company orphan drug status (Orphan Drug Act), which qualifies the sponsor of a product to receive tax credit and marketing incentives. The study was funded by a grant from the National Cancer Institute (RC4 CA156509) issued under the American Recovery and Reinvestment Act (R01CA138212).
About Georgetown Lombardi Comprehensive Cancer Center
Georgetown Lombardi Comprehensive Cancer Center, part of Georgetown University Medical Center and MedStar Georgetown University Hospital, seeks to improve the diagnosis, treatment, and prevention of cancer through innovative basic and clinical research, patient care, community education and outreach, and the training of cancer specialists of the future. Georgetown Lombardi is one of only 41 comprehensive cancer centers in the nation, as designated by the National Cancer Institute (grant #P30 CA051008), and the only one in the Washington, DC area. For more information, go to http://lombardi.georgetown.edu.
About Georgetown University Medical Center
Georgetown University Medical Center is an internationally recognized academic medical center with a three-part mission of research, teaching and patient care (through MedStar Health). GUMC's mission is carried out with a strong emphasis on public service and a dedication to the Catholic, Jesuit principle of cura personalis -- or "care of the whole person." The Medical Center includes the School of Medicine and the School of Nursing & Health Studies, both nationally ranked; Georgetown Lombardi Comprehensive Cancer Center, designated as a comprehensive cancer center by the National Cancer Institute; and the Biomedical Graduate Research Organization (BGRO), which accounts for the majority of externally funded research at GUMC including a Clinical Translation and Science Award from the National Institutes of Health.
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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.
Summer approacheth, and with summer comes festivals?all sorts of festivals! Whether you're a music buff, renaissance enthusiast, or food and wine connoisseur there's a festival out there somewhere waiting for you. Now an actual Swiss Army knife is handy to have, but probably won't do you too much good at any of the above. A festival-specific Swiss Army app though? Just what ye olde doctor ordered.
What does it do?
Helps you take care of every problem you might come across at any sort of festival the summer season can throw at you. For friends prone to wandering, the app will help you track down lost friends, assuming they've left a pin for you to find. Or if you just so happen to be that friend, it'll also help you find your way back to a previously marked campsite. Group messaging, "sound flare" (for those times when you need an adult), up to the minute weather info, and packing checklists make sure that whatever the potential problem, you've already got a solution at hand.
Why do we like it?
Most festivals these days will often come with their own "helpful" festival guide in the form of an app, but these are usually overrun with annoying ads, glitchy, and often not much more than extra exposure for whatever your festival of choice might be hocking. The folks behind the Swiss Army Knife, though, obviously have a knack for design, and they've made this app with you in mind?not the entertainment. It's a far more pleasant experience, making sure your fun-having goes as seamlessly as possible.
Festival Ready, Download this app for: iOS and Android, Free
The Best: Beautiful navigation feature
The Worst: Your friends can only be found if they so choose
GOMA, Congo (AP) ? In a story May 11 about the arrival of Tanzanian troops in eastern Congo, The Associated Press erroneously cited United Nations mission spokesman Col. Felix Basse. The information should have been attributed to Alexandre Essome, press information officer for the U.N. peacekeeping mission in the eastern province of North Kivu.
A corrected version of the story is below:
A contingent of about 100 Tanzanian troops arrived in eastern Congo Saturday, a first step in assembling the new United Nations intervention brigade, said a UN spokesman.
The troops arrived on Friday and Saturday, and the rest of the brigade will arrive in successive waves, said Alexandre Essome, press information officer for the U.N. peacekeeping mission in the eastern province of North Kivu.
The Tanzanian troops are the first batch to arrive in eastern Congo to start forming the U.N. intervention brigade to be deployed in eastern Congo following a Security Council resolution in March.
On March 28th, the U.N. Security Council voted a resolution that renewed the mandate of the U.N. peacekeeping mission in Congo for one year, and created a special intervention brigade that has an aggressive mandate that allows it to fight armed groups, rather than merely defend civilians.
The intervention brigade commander arrived in Goma on the 23rd April, but troops meant to arrive by the end of April have only just started arriving in eastern Congo. The rest of the troops will arrive in stages, but no clear deadline has been given so far.
Malawi and South Africa have pledged to contribute troops to the U.N. force.
The need for an intervention force became clear in November, when the U.N. peacekeepers merely stood by as Congo's M23 rebels took the provincial capital of Goma. The rebels eventually withdrew from the city two weeks later, but the fall of Goma convinced the international community to create a brigade with a more assertive mandate to try to put an end to the turmoil in which has plagued eastern Congo for years.
But with just over 3,000 special troops to battle more than 25 armed groups in the Kivu region alone, the new U.N. brigade risks being spread too thin, say military experts. Already eastern Congo's M23 rebels are training fighters in guerrilla tactics to fight the U.N. troops.
The Congolese army, with poor discipline and lacking resources, has been unable to contain the rebels maintain order in the east. Congo's authorities have put a lot of hope that the new U.N. brigade will help solve the security crisis in the east.
"With the first Tanzanian troops landing, a new dynamic will emerge in the east. Security problems cannot be solved in one day," said Congo's prime minister, Augustin Matata Ponyo, to the Associated Press from his office in Kinshasa, Congo's capital. "The most important thing is that the government is aware of this problem and is working to solve it."
___
Associated Press writer Saleh Mwanamilongo contributed to this report from Kinshasa, Congo.
May 13, 2013 ? Human intelligence cannot be explained by the size of the brain's frontal lobes, say researchers.
Research into the comparative size of the frontal lobes in humans and other species has determined that they are not -- as previously thought -- disproportionately enlarged relative to other areas of the brain, according to the most accurate and conclusive study of this area of the brain.
It concludes that the size of our frontal lobes cannot solely account for humans' superior cognitive abilities.
The study by Durham and Reading universities suggests that supposedly more 'primitive' areas, such as the cerebellum, were equally important in the expansion of the human brain. These areas may therefore play unexpectedly important roles in human cognition and its disorders, such as autism and dyslexia, say the researchers.
The study is published in the Proceedings of the National Academy of Sciences (PNAS) today.
The frontal lobes are an area in the brain of mammals located at the front of each cerebral hemisphere, and are thought to be critical for advanced intelligence.
Lead author Professor Robert Barton from the Department of Anthropology at Durham University, said: "Probably the most widespread assumption about how the human brain evolved is that size increase was concentrated in the frontal lobes.
"It has been thought that frontal lobe expansion was particularly crucial to the development of modern human behaviour, thought and language, and that it is our bulging frontal lobes that truly make us human. We show that this is untrue: human frontal lobes are exactly the size expected for a non-human brain scaled up to human size.
"This means that areas traditionally considered to be more primitive were just as important during our evolution. These other areas should now get more attention. In fact there is already some evidence that damage to the cerebellum, for example, is a factor in disorders such as autism and dyslexia."
The scientists argue that many of our high-level abilities are carried out by more extensive brain networks linking many different areas of the brain. They suggest it may be the structure of these extended networks more than the size of any isolated brain region that is critical for cognitive functioning.
Previously, various studies have been conducted to try and establish whether humans' frontal lobes are disproportionately enlarged compared to their size in other primates such as apes and monkeys. They have resulted in a confused picture with use of different methods and measurements leading to inconsistent findings.
May 14, 2013 ? Pregnant mothers' exposure to the flu was associated with a nearly fourfold increased risk that their child would develop bipolar disorder in adulthood, in a study funded by the National Institutes of Health. The findings add to mounting evidence of possible shared underlying causes and illness processes with schizophrenia, which some studies have also linked to prenatal exposure to influenza.
"Prospective mothers should take common sense preventive measures, such as getting flu shots prior to and in the early stages of pregnancy and avoiding contact with people who are symptomatic," said Alan Brown, M.D., M.P.H, of Columbia University and New York State Psychiatric Institute, a grantee of the NIH's National Institute of Mental Health (NIMH). "In spite of public health recommendations, only a relatively small fraction of such women get immunized. The weight of evidence now suggests that benefits of the vaccine likely outweigh any possible risk to the mother or newborn."
Brown and colleagues reported their findings online May 8, 2013 in JAMA Psychiatry.
Although there have been hints of a maternal influenza/bipolar disorder connection, the new study is the first to prospectively follow families in the same HMO, using physician-based diagnoses and structured standardized psychiatric measures. Access to unique Kaiser-Permanente, county and Child Health and Development Study databases made it possible to include more cases with detailed maternal flu exposure information than in previous studies.
Among nearly a third of all children born in a northern California county during 1959-1966, researchers followed, 92 who developed bipolar disorder, comparing rates of maternal flu diagnoses during pregnancy with 722 matched controls.
The nearly fourfold increased risk implicated influenza infection at any time during pregnancy, but there was evidence suggesting slightly higher risk if the flu occurred during the second or third trimesters. Moreover, the researchers linked flu exposure to a nearly sixfold increase in a subtype of bipolar disorder with psychotic features.
A previous study, by Brown and colleagues, in a related northern California sample, found a threefold increased risk for schizophrenia associated with maternal influenza during the first half of pregnancy. Autism has similarly been linked to first trimester maternal viral infections and to possibly related increases in inflammatory molecules.
"Future research might investigate whether this same environmental risk factor might give rise to different disorders, depending on how the timing of the prenatal insult affects the developing fetal brain," suggested Brown.
Bipolar disorder shares with schizophrenia a number of other suspected causes and illness features, the researchers note. For example, both share onset of symptoms in early adulthood, susceptibility genes, run in the same families, affect nearly one percent of the population, show psychotic behaviors and respond to antipsychotic medications.
Increasing evidence of such overlap between traditional diagnostic categories has led to the NIMH Research Domain Criteria (RDoC) project, which is laying the foundation for a new mental disorders classification system based on brain circuits and dimensional mechanisms that cut across traditional diagnostic categories.
The research was also funded by NIH's Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD).
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Public release date: 15-May-2013
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