News 19 aug 2009
Listening to rocks helps
researchers better understand earthquakes
When Apollo punished King Midas by giving him donkey ears, only the king and his barber
knew. Unable to keep a secret, the barber dug a hole, whispered into it, "King Midas
has donkey ears," and filled the hole. But plants sprouted from the hole, and with
each passing breeze, shared the king's secret. Earth, as it turns out, has other secrets
to divulge. From the pounding of the surf and the rumbling of thunder, to the gentle
rustling of leaves, Earth is not a quiet planet. The key is knowing how to listen to the
ever-present ambient noise. University of Illinois seismologist Xiaodong Song and graduate
student Zhen J. Xu have become good listeners, especially to the sounds beneath our feet.
Using a technique called "ambient noise correlation," Xu and Song have observed
significant changes in the behavior of parts of Earth's crust that were disturbed by three
major earthquakes. "The observations are important for understanding the aftermath of
a major earthquake at depth," Song said, "and for understanding how the rock
recovers from it and begins again to accumulate stress and strain for future
earthquakes." The pair report their findings in a paper accepted for publication in
the Proceedings of the National Academy of Sciences, and posted on the journal's Web site.
Researchers have used ambient noise to image Earth's interior and to monitor changes in
seismic velocity near active volcanoes.
New DNA Test Uses Nanotechnology to
Find Early Signs of Cancer
Using tiny crystals called quantum dots, Johns Hopkins researchers have developed a highly
sensitive test to look for DNA attachments that often are early warning signs of cancer.
This test, which detects both the presence and the quantity of certain DNA changes, could
alert people who are at risk of developing the disease and could tell doctors how well a
particular cancer treatment is working.The new test was reported in a paper called
“MS-qFRET: a quantum dot-based method for analysis of DNA methylation,”
published in the August issue of the journal Genome Research. The work also was presented
at a conference of the American Association of Cancer Research. “If it leads to early
detection of cancer, this test could have huge clinical implications,” said Jeff
Tza-Huei Wang, an associate professor of mechanical engineering whose lab team played a
leading role in developing the technique. “Doctors usually have the greatest success
in fighting cancer if they can treat it in its early stage.”
Developmental language disorders at
preschool age - no proof of benefit from screening
Language is a central element of social life. It is not only a prerequisite for personal
relationships, but also for employment prospects. If a child's language development is
impaired, this can have far-reaching negative consequences. Thus, it would be beneficial
if those children who would benefit from targeted help could be identified at a very early
stage. However, the Institute for Quality and Efficiency in Health Care (IQWiG) could not
find any proof of benefit from language screening before their 6th birthday for children
with a specific developmental disorder of speech and language. At present, there is a lack
of screening studies and also of reliable diagnostic instruments. This is the conclusion
in the final report, which IQWiG published on 17 August 2009.
Study supports DNA repair-blocker
research in cancer therapy
Scientists at Dana-Farber Cancer Institute have uncovered the mechanism behind a promising
new approach to cancer treatment: damaging cancer cells' DNA with potent drugs while
simultaneously preventing the cells from repairing themselves. The findings being reported
in the Aug. 14 issue of Molecular Cell help explain the promising results being seen in
clinical trials of compounds that force cancer cells with genetic damage to self-destruct
instead of "resting" while their DNA undergoes repairs. "What we have shown
suggests that you can use these drugs to sensitize cancer cells to DNA-damaging
chemotherapy," said Geoffrey Shapiro, MD, PhD, senior author of the report.
"This is a mechanism by which these inhibitory drugs may be synergistic with
DNA-damaging agents." Interestingly, Shapiro said, when the same repair-blocking
drugs were administered to normal, non-cancerous cells, the cells became less sensitive to
DNA damage from a chemotherapy drug. This is an encouraging indication that
repair-blocking drugs may selectively make cancer cells vulnerable to chemotherapy while
protecting normal cells from DNA damage, the scientists said. Cells' native capacity for
fixing DNA damage is normally beneficial, but it can be problematic for cancer therapy as
it enables tumor cells to become resistant to a number of standard drug agents. All cells
progress through a series of phases -- called the cell cycle -- including quiescence, or
resting, growth, and cell division. The transition from one phase to the next is regulated
by "checkpoint" proteins that, among other things, are designed to prevent
damaged, potentially dangerous cells from reproducing. The body deals with DNA-damaged
cells in two ways. It can order them to self-destruct through "programmed cell
death," also known as apoptosis. Or, it can issue signals from the checkpoint
proteins to put the cells into "cell cycle arrest," causing them to remain
quiescent while the broken DNA is fixed before they resume normal activity.
Children with headache
Family quarrels and a lack of free time can promote headaches in children. This is what
Jennifer Gassmann and her coauthors concluded in their study on risk factors, which
appears in the current issue of the Deutsches Ärzteblatt International (Dtsch Arztebl Int
2009; 106[31-32]: 509-16). This investigation was a component of a large-scale study
entitled "Children, Adolescents, and Headache" (Kinder, Jugendliche und
Kopfschmerz—KiJuKo), in which data were collected in four annual "waves"
from 2003 to 2006. Out of a multitude of variables tested in the larger study, the authors
chose to look at the ones that concerned the children's family and leisure time. Up to 30%
of all children around the world complain of headache symptoms arising at least once per
week. Boys who experienced more than one family quarrel per week had a 1.8 times higher
risk of developing headaches. The amount of free time available to them seemed to be even
more important: boys who only sometimes had time to themselves had a 2.1 times higher risk
of developing headaches. Parents' behavior when their child complains of headache also
seemed to play a major role. Either positive or negative reinforcement from the parents
teaches the child that he or she can gain certain advantages from headache symptoms. The
parents' responses had a particularly strong effect on the frequency of symptoms in girls:
reinforcing parental responses raised their risk of recurrent headaches by 25%. The sexes
also differed with respect to the frequency of headache. Twice as many girls as boys had
their symptoms at least once a week. The children's age, however, seemed to have no more
than a minor effect on headache manifestations.
Mother's immune system may block
fetal treatments for blood diseases
Pediatric researchers have resolved an apparent contradiction in the field of prenatal
cell transplantation— a medical approach that holds future promise in correcting
sickle cell disease and other serious congenital blood disorders. In a new study in
animals, the researchers showed that the mother's immune response interferes with the
offspring's earlier ability to tolerate transplanted donor cells. The study team concludes
that focusing on transplant techniques that avoid the maternal immune response may allow
scientists to take advantage of fetal tolerance to achieve a long-sought goal of treating
blood diseases prenatally. While cautioning that much work must be done to understand how
these animal findings apply to humans, the current findings are "surprising but
reassuring," said study leader Alan W. Flake, M.D., of the Children's Center for
Clinical Research at The Children's Hospital of Philadelphia. The study appeared online
August 3 in the Journal of Clinical Investigation. For over 50 years, explained Flake, it
has been a fundamental precept of immunology that a fetus tolerates foreign antigens in a
window-of-opportunity period before its immune system fully develops the capacity to mount
an immune response. Scientists assumed that by carefully introducing donor cells and
stimulating a fetus to develop tolerance to those cells, one could set the stage for a
later organ or cellular transplant that would not be rejected by a more mature immune
system. As prenatal diagnosis has continued to become available for a greater number of
congenital diseases, scientists have considered the possibility of correcting blood
disorders such as sickle cell disease or thalassemia. After first transplanting a small
number of healthy cells in an early-stage fetus to establish tolerance, a second dose of
transplanted cells later in gestation would proliferate, and treat the blood disorder
before birth. Researchers use hematopoietic cells—stem cells that that develop into
blood cells—in this technique, in utero hematopoietic cell transplantation (IUHCT).
However, over the years, Flake's team and other research groups found that IUHCT studies
in animal models yielded inconsistent results, ranging from no tolerance to transplants to
full tolerance and every degree of tolerance in between. Contrary to the concept of fetal
tolerance, an immune barrier seemed to be acting against transplanted cells.
Agricultural methods of early
civilizations may have altered global climate, study suggests
Massive burning of forests for agriculture thousands of years ago may have increased
atmospheric carbon dioxide enough to alter global climate and usher in a warming trend
that continues today, according to a new study that appears online Aug. 17 in the journal
Quaternary Science Reviews. Researchers at the University of Virginia and the University
of Maryland-Baltimore County say that today's 6 billion people use about 90 percent less
land per person for growing food than was used by far smaller populations early in the
development of civilization. Those early societies likely relied on slash-and-burn
techniques to clear large tracts of land for relatively small levels of food production.
"They used more land for farming because they had little incentive to maximize yield
from less land, and because there was plenty of forest to burn," said William
Ruddiman, the lead author and a professor emeritus of environmental sciences at the
University of Virginia. "They may have inadvertently altered the climate."
Ruddiman is a climate scientist who specializes in investigating ocean-sediment and
ice-core records. In recent years he has searched across scientific disciplines –
anthropology, archaeology, population dynamics, climatology – to gain insight into
how humans may have affected climate over the millennia. He said that early populations
likely used a land-clearing method that involved burning forests, then planting crop seed
among the dead stumps in the enriched soil. They would use a large plot until the yield
began to decline, and then would burn off another area of forest for planting. They would
continue this form of rotation farming, ever expanding the cleared areas as their
populations grew. They possibly cleared five or more times more land than they actually
farmed at any given time. It was only as populations grew much larger, and less land was
available for farming or for laying fallow, that societies adopted more intensive farming
techniques and slowly gained more food yield from less land.
Cancer's break-in tools possibly
identified at Duke
A single cell in a 1-millimeter nematode worm is providing valuable new clues into
cancer's deadliest behavior -- its ability to put down roots in new tissues after
spreading throughout the body. Duke University biologist David Sherwood has spent the last
several years studying the mechanics of a single cell in the developing body of a worm
called Caenorhabditis elegans. It's called the anchor cell and one of its jobs is to
connect the developing animal's uterus with its vulva, a crucial step in ensuring the
worm's fertility. To establish this slender connection, the anchor cell must work its way
through two layers of basement membrane, a dense, sheet-like barrier structure lining most
tissues, including the epithelial cells in humans that are the hosts of many cancers. In a
paper appearing online Aug. 17 in the journal Developmental Cell, Sherwood and colleagues
describe how the nematode's anchor cell uses a series of molecular signals to create a
stretched opening in the membrane. They believe the process is essentially the same as the
one cancer cells use to invade new tissues. Together, these molecules, called integrin and
netrin, may be a valuable new target in the efforts to halt cancer's spread via
metastasis.
Gene vital to brain's stem cells
implicated in deadly brain cancer
Researchers from Columbia University Medical Center's Herbert Irving Comprehensive Cancer
Center have identified a protein that activates brain stem cells to make new neurons
– but that may be hijacked later in life to cause brain cancer in humans. The protein
called Huwe1 normally functions to eliminate other unnecessary proteins and was found to
act as a tumor suppressor in brain cancer. These findings, published in the August 18
issue of Developmental Cell, were co-led by Antonio Iavarone, M.D., associate professor of
neurology and pathology & cell biology and Anna Lasorella, M.D., assistant professor
of pediatrics and pathology & cell biology, both of Columbia's Institute for Cancer
Genetics at the Herbert Irving Comprehensive Cancer Center. "By identifying the
normal function of Huwe1, we were able to learn that deregulation of Huwe1 function is
involved in tumor development," say Dr. Iavarone. "This demonstrates that a
gene's basic function must be understood before we can learn how it also plays a role in
the development of cancer," says Dr. Lasorella. During normal brain development,
neural stem cells grow and divide rapidly before developing into neurons. To successfully
change into neurons, they must remove all proteins that keep the cells in an immature,
stem cell state. To understand how brain tumors develop, Drs. Iavarone's and Lasorella's
teams decided that they needed to understand the development of normal neural stem cells.
Their research demonstrated that Huwe1 is responsible for "crowd control" for
the mechanism that regulates the stem cell mass in the developing brain – effectively
weeding out unnecessary stem cell-specific proteins – and promoting neurogenesis.
Without Huwe1, Dr. Lasorella discovered that in mice, too few mature neurons form in the
brain, resulting in the brain failing to properly develop. Because the stem cells and
cancer cells share the capacity for rapid proliferation, but cancer cells have lost crowd
control, Dr. Iavarone then looked for signs of Huwe1 alterations in human brain tumors.
Compared to normal brain tissue, he found that Huwe1 activity in tumors was significantly
lower than in normal brain tissue. "The loss of Huwe1 may be an important factor in
the development of brain cancer, suggesting that Huwe1 protein function may be used for
new therapeutic targets to fight deadly brain cancer," says Dr. Lasorella. "Our
next step will be to analyze the structural changes in Huwe1, and research ways to restore
this gene in brain tumor patients," says Dr. Iavarone. "In mice, giving Huwe1
back blocks the ability of normal stem cells to proliferate and develop tumors. We are
hopeful that if we can restore Huwe1 activity in brain tumor cells resulting from Huwe1
deletion, then we can stop the tumor growth."
Researchers develop new,
more-sensitive assay for detecting DNA methylation in colon cancer
A study published in this week's online issue of Nature Biotechnology, demonstrates a
unique and highly sensitive method for detecting methylation-associated cancers. Chemical
modification of DNA via the addition or deletion of methyl groups has been established as
a common biological means of activating or silencing genes. Abnormal levels of DNA
methylation, which effectively disrupt the genes responsible for normal cell cycle
regulation, has been implicated in a number of different cancers, and has led to the
development of novel cancer biomarkers. However, methylation events are rare and difficult
to detect in clinically relevant samples of blood, serum, sputum, urine or feces using
currently available methods of analysis. In a joint effort between Case Western Reserve
University and John's Hopkins University, researchers have developed a highly sensitive
method for detecting methylated DNA. The authors say the new method, known as
Methyl-BEAMing (beads, emulsion, amplification and magnetics) technology, enables absolute
quantification of the number of methylated molecules in a sample, and can detect as few as
one methylated molecule in approximately 5000 unmethylated molecules in DNA from plasma
and fecal samples, an over 60-fold improvement over an alternative commonly used detection
method. The enhanced sensitivity of the test was achieved through the use of PCR
amplification of individual DNA fragments covalently attached to specially coated magnetic
beads. The process of amplification involved suspending the magnetic beads in tiny
water-based nano-compartments immersed in droplets of oil. The beads contained a DNA
sequence specific for exon1 of the vimentin gene – a gene known to be hypermethylated
in colorectal cancer. If the vimentin gene sequence was present in the sample, subsequent
PCR resulted in thousands of copies of the gene attached to each individual magnetic bead.
Following amplification, the DNA-coated beads could be hybridized with fluorescent probes
specific to the state of methylation, sorted and analyzed using flow cytometry. The
researchers say that this method has enabled the accurate detection of a single copy of
methylated vimentin sequence in a mixture and improved the technical sensitivity for
detecting methylated vimentin exon1 by at least 62 –fold relative to standard
methylation-specific PCR. Using this novel method of digitally detecting methylated DNA,
the researchers demonstrated that the test could be used to detect 59 percent of colon
cancers in the blood, a 4-fold improvement over CEA, a serum marker commonly used to
follow colon cancer patients for recurrence of disease. Additionally, the new method could
detect 41 percent of colon cancers in the stool, as well as half of pre-cancerous polyps.
The study was led by Bert Vogelstein of John's Hopkins University and Sanford Markowitz,
M.D., Ph.D., the Markowitz-Ingalls Professor of Cancer Genetics at the Case Western
Reserve University School of Medicine and an oncologist at the Ireland Cancer Center of
University Hospitals Case Medical Center. Colon cancer is the second leading cause of
cancer death in the United States. This year 150,000 individuals will develop the disease
and 50,000 will die from it. Researchers say that deaths from colon cancer are completely
preventable when the disease is detected in its early stages, before it has spread beyond
the colon – yet many individuals do not get screened by colonoscopy.
Inherited risk factors increase
odds of developing childhood acute lymphoblastic leukemia
Scientists at St. Jude Children's Research Hospital have identified inherited variations
in two genes that account for 37 percent of childhood acute lymphoblastic leukemia (ALL),
including a gene that may help predict drug response. The findings stem from the first
complete search of the human genetic blueprint or genome to look for inherited risk
factors for ALL, the most common childhood cancer. Published in the August 16 advance
online issue of Nature Genetics, the work offers the first proof based on a complete
survey of the human genome that inheritance play a role in childhood ALL.Mary Relling,
Pharm.D., St. Jude Pharmaceutical Sciences chair and the paper's senior author, estimated
that individuals who inherited variations in genes known as ARID5B or IKZF1 are almost
twice as likely to develop ALL as those without the variations. Even then, she said, the
risk remains low. ALL strikes roughly one in every 75,000 Americans. Sixty percent are
children and teenagers. "The genetic variations alone are not enough to cause the
cancer. Like all cancers, pediatric ALL is a multi-factor disease," Relling
explained. "But these findings may give us a handle on the mechanism of the disease
and drug responsiveness to it." Exactly the same genes, ARID5B and IKZF1, were
confirmed to be altered in British children with ALL. That study was published by the
Institute of Cancer Research in Surrey, England, in the same issue of Nature Genetics. In
the St. Jude study, researchers collaborated with colleagues from the Children's Oncology
Group (COG), who provided additional cases for genetic analysis. COG is an international
group of medical institutions that cooperate in research studies and clinical trials of
childhood cancer treatment. Researchers scanned the genomes of 441 children with ALL and a
control group of 17,958 cancer-free individuals for more than 300,000 common genetic
variations known as single nucleotide polymorphisms or SNPs. The search found 18 SNPs that
differed significantly in frequency between individuals with and without ALL. Six of the
18 SNPs were associated with one of the four main subtypes of ALL.
Up to 90 percent of US paper money
contains traces of cocaine
You probably have cocaine in your wallet, purse, or pocket. Sound unlikely or outrageous?
Think again! In what researchers describe as the largest, most comprehensive analysis to
date of cocaine contamination in banknotes, scientists are reporting that cocaine is
present in up to 90 percent of paper money in the United States, particularly in large
cities such as Baltimore, Boston, and Detroit. The scientists found traces of cocaine in
95 percent of the banknotes analyzed from Washington, D.C., alone. Presented here today at
the 238th National Meeting of the American Chemical Society, the new study suggests that
cocaine abuse is still widespread and may be on the rise in some areas. It could help
raise public awareness about cocaine use and lead to greater emphasis on curbing its
abuse, the researchers say. The scientists tested banknotes from more than 30 cities in
five countries, including the U.S., Canada, Brazil, China, and Japan, and found
"alarming" evidence of cocaine use in many areas. The U.S. and Canada had the
highest levels, with an average contamination rate of between 85 and 90 percent, while
China and Japan had the lowest, between 12 and 20 percent contamination. The study is the
first report about cocaine contamination in Chinese and Japanese currencies, they
say."To my surprise, we're finding more and more cocaine in banknotes," said
study leader Yuegang Zuo, Ph.D., of the University of Massachusetts in Dartmouth. Zuo says
that the high percentage of contaminated U.S. currency observed in the current study
represents nearly a 20 percent jump in comparison to a similar study he conducted two
years ago. That earlier study indicated that 67 percent of bills in the U.S. contained
traces of cocaine. "I'm not sure why we've seen this apparent increase, but it could
be related to the economic downturn, with stressed people turning to cocaine," Zuo
says. Such studies are useful, he noted, because the data can help law enforcement
agencies and forensic specialists identify patterns of drug use in a community.
New study expands the list of
hazardous chemicals in smokeless tobacco
Attention all smokeless tobacco users! It's time to banish the comforting notion that
snuff and chewing tobacco are safe because they don't burn and produce inhalable smoke
like cigarettes. A study that looked beyond the well-researched tobacco hazards,
nitrosamines and nicotine, has discovered a single pinch –– the amount in a
portion –– of smokeless tobacco exposes the user to the same amount of another
group of dangerous chemicals as the smoke of five cigarettes. The research on polycyclic
aromatic hydrocarbons (PAH) in smokeless tobacco was reported here today at the 238th
National Meeting of the American Chemical Society (ACS). It adds to existing evidence that
smokeless contains two dozen other carcinogens that cause oral and pancreatic cancers, the
scientists say. "This study once again clearly shows us that smokeless tobacco is not
safe," said Irina Stepanov, Ph.D., who led the research team. "Our finding
places snuff on the same list of major sources of exposure to polycyclic aromatic
hydrocarbons as smoking cigarettes." PAHs are widespread environmental contaminants
formed as a result of incomplete burning of wood, coal, fat in meat, and organic matter.
PAHs form, for instance, during the grilling of burgers, steaks and other meat. The
findings come in the midst of a rise in both marketing and consumption of smokeless
tobacco, which many consumers regard as less dangerous than other forms of tobacco.
Estimates suggest that sales of moist snuff in the United States have doubled since the
1980s.
'Killer spices' provide
eco-friendly pesticides for organic fruits and veggies
Mention rosemary, thyme, clove, and mint and most people think of a delicious meal. Think
bigger…acres bigger. These well-known spices are now becoming organic agriculture's
key weapons against insect pests as the industry tries to satisfy demands for fruits and
veggies among the growing portion of consumers who want food produced in more natural
ways. In a study presented here today at the American Chemical Society's 238th National
Meeting, scientists in Canada are reporting exciting new research on these so-called
"essential oil pesticides" or "killer spices." These substances
represent a relatively new class of natural insecticides that show promise as an
environmentally-friendly alternative to conventional pesticides while also posing less
risk to human and animal health, the researcher says. "We are exploring the potential
use of natural pesticides based on plant essential oils — commonly used in foods and
beverages as flavorings," says study presenter Murray Isman, Ph.D., of the University
of British Columbia. These new pesticides are generally a mixture of tiny amounts of two
to four different spices diluted in water. Some kill insects outright, while others repel
them. Over the past decade, Isman and colleagues tested many plant essential oils and
found that they have a broad range of insecticidal activity against agricultural pests.
Some spiced-based commercial products now being used by farmers have already shown success
in protecting organic strawberry, spinach, and tomato crops against destructive aphids and
mites, the researcher says. "These products expand the limited arsenal of organic
growers to combat pests," explains Isman. "They're still only a small piece of
the insecticide market, but they're growing and gaining momentum." The natural
pesticides have several advantages. Unlike conventional pesticides, these "killer
spices" do not require extensive regulatory approval and are readily available. An
additional advantage is that insects are less likely to evolve resistance — the
ability to shrug off once-effective toxins — Isman says. They're also safer for farm
workers, who are at high risk for pesticide exposure, he notes.
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