News 20 juli 2009
Stress and Depression Worsen
Childhood Asthma, UB Researchers Show
Young people with asthma have nearly twice the incidence of depression compared to their
peers without asthma, and studies have shown that depression is associated with increased
asthma symptoms and, in some cases, death. How stress and depression play upon one another
to worsen asthma is a lingering question. A new study by researchers at the University at
Buffalo has shown that depressed children with asthma exhibit a dysregulation of the
autonomic nervous system along with increased airway compromise.
Estrogen can reduce stroke damage
by inactivating protein
Estrogen can halt stroke damage by inactivating a tumor-suppressing protein known to
prevent many cancers, Medical College of Georgia researchers say. "Our research
suggests that estrogen suppresses p53 after stroke, which stops the damage," says
Limor Raz, a fourth-year Ph.D. student in the MCG School of Graduate Studies. P53, the
protein in the mitochondria, or powerhouse, of the cell, is known as "the guardian of
the genome" because it regulates the cell cycle and prevents genome mutation. It also
can prevent cancer by suppressing tumor growth. It is known that stressful conditions such
as a stroke activate p53, triggering unfavorable changes in the cell. One change is the
activation of another protein called PUMA, which signals a cascading effect that destroys
the mitochondria and causes cell death, or apoptosis.
Researchers investigate high-risk
populations for bladder-cancer screenings
A new study by UT Southwestern Medical Center researchers sheds light on the challenges
involved in identifying which high-risk population would benefit most from bladder-cancer
screening. Large-scale screening of people at high risk for developing invasive bladder
cancer could result in earlier diagnosis and improved survival rates. Bladder cancer is
the fourth most common cancer in men and the fifth most common cancer overall. In the
early stages of the disease, it’s common to have no signs or symptoms. Smoking has
been proven to increase the risk of the disease. “At this time bladder cancer
screening is not the standard of care,” said Dr. Yair Lotan, associate professor of
urology and senior author of the study appearing online and in a future edition of The
Journal of Urology. “Although progress has been made in diagnosis, those efforts have
translated into minimal survival benefit. In order to get the most benefit from the added
cost of screening, we need to identify the appropriate population to screen.” In the
study researchers used a point-of-care urine-based test called NMP22 BladderChek to screen
1,502 subjects without symptoms who are at high risk for bladder cancer based on age,
smoking history and occupational exposure.
USC study finds links between
obesity and adolescents' social networks
Study finds overweight youth are twice as likely to have overweight friends. Researchers
from the Institute of Prevention Research at the Keck School of Medicine of the University
of Southern California (USC) found in a recent study that overweight youth were twice as
likely to have overweight friends. "Although this link between obesity and social
networks was expected, it was surprising how strong the peer effect is and how early in
life it starts," says lead author Thomas Valente, Ph.D., professor of preventive
medicine at the Keck School of Medicine. Previous data had shown a connection between
overweight adults and their social peers. However, the USC study used more advanced
statistical modeling techniques than previous research and the association remained
strong, Valente says. "The findings certainly raise health concerns because when kids
start associating only with others who have a similar weight status it can reinforce the
negative behaviors that cause obesity," he says. In-school surveys were conducted
among 617 students ages 11-13 from the greater Los Angeles area. In addition to finding
that overweight adolescents were more likely to have overweight friends than their
normal-weight peers, the researchers also found that overweight girls were more likely to
name more friends, but less likely to be named as a friend than normal-weight girls.
DNA Repair Is a Quirky Process
The “sloppier copier” discovered by USC biologists is also the best sixth man in
the DNA repair game, an article in the journal Nature shows. The enzyme known as DNA
polymerase V (pol V) comes off the bench when a cell’s DNA is reeling from radiation
damage or other serious blows. Pol V copies the damaged DNA as best it can - saving the
life of the bacterial cell at the cost of adding hundreds of random mutations.The July 16
Nature study reveals pol V’s key attributes: economy of motion and quickness to
engage. The study also solves two stubborn mysteries about the mechanics of DNA repair:
the exact composition of the active form of pol V and the crucial role of a protein
filament, known as RecA*, that is always present around DNA repair sites, but was never
shown to be directly involved.The three findings together describe an exquisitely
efficient process.
Barrow researchers identify new
brain receptor, possible target for Alzheimer's treatment
Barrow Neurological Institute researchers have identified a novel receptor in the brain
that is extremely sensitive to beta-amyloid peptide (AB) and may play a key role in early
stages of Alzheimer's disease. Published in the Journal of Neuroscience, the research lead
by Jie Wu, MD, PhD, has identified a new candidate for therapeutic intervention in
Alzheimer's. The novel receptor was found in the basal forebrain, an area of the brain
that plays a critical role in memory and learning and is one of the first areas of the
brain to degenerate with Alzheimer's. That degeneration is associated with losses of the
chemical messenger, acetylcholine, and some of the molecules that translate
acetylcholine's messages, called nicotinic receptors. The forming of large aggregates or
plaques of AB also is a hallmark of Alzheimer's disease. While these two features have
been under examination in Alzheimer's research, it is not clear how they interrelate. At
Barrow, Dr. Wu and his colleagues made the unexpected finding during a study examining
effects of AB on basal forebrain nicotinic receptors. They first found that acetylcholine
signaling at those receptors was highly sensitive to blockage even by low levels of AB.
They also found that AB as small aggregates -- and not large plaques of AB -- had this
same blocking effect. They next found that the type of nicotinic receptors showing this
high sensitivity to AB has a different composition than other nicotinic receptor types
previously identified and shown to be less sensitive to AB. "We now believe that most
of the nicotinic receptors in the basal forebrain have this unique composition and high
sensitivity to AB," says Dr. Wu. "Our hypothesis is that as AB begins to
increase, it first blocks acetylcholine signaling at these receptors, perhaps triggering
events that eventually lead to neurodegeneration."
Solar cycle linked to global
climate
Establishing a key link between the solar cycle and global climate, research led by
scientists at the National Science Foundation (NSF)-funded National Center for Atmospheric
Research (NCAR) in Boulder, Colo., shows that maximum solar activity and its aftermath
have impacts on Earth that resemble La Niña and El Niño events in the tropical Pacific
Ocean. The research may pave the way toward predictions of temperature and precipitation
patterns at certain times during the approximately 11-year solar cycle. "These
results are striking in that they point to a scientifically feasible series of events that
link the 11-year solar cycle with ENSO, the tropical Pacific phenomenon that so strongly
influences climate variability around the world," says Jay Fein, program director in
NSF's Division of Atmospheric Sciences. "The next step is to confirm or dispute these
intriguing model results with observational data analyses and targeted new
observations." The total energy reaching Earth from the sun varies by only 0.1
percent across the solar cycle. Scientists have sought for decades to link these ups and
downs to natural weather and climate variations and distinguish their subtle effects from
the larger pattern of human-caused global warming. Building on previous work, the NCAR
researchers used computer models of global climate and more than a century of ocean
temperature to answer longstanding questions about the connection between solar activity
and global climate. The research, published this month in a paper in the Journal of
Climate, was funded by NSF, NCAR's sponsor, and by the U.S. Department of Energy. "We
have fleshed out the effects of a new mechanism to understand what happens in the tropical
Pacific when there is a maximum of solar activity," says NCAR scientist Gerald Meehl,
the paper's lead author. "When the sun's output peaks, it has far-ranging and often
subtle impacts on tropical precipitation and on weather systems around much of the
world." The new paper, along with an earlier one by Meehl and colleagues, shows that
as the Sun reaches maximum activity, it heats cloud-free parts of the Pacific Ocean enough
to increase evaporation, intensify tropical rainfall and the trade winds, and cool the
eastern tropical Pacific. The result of this chain of events is similar to a La Niña
event, although the cooling of about 1-2 degrees Fahrenheit is focused further east and is
only about half as strong as for a typical La Niña.
Gliomas exploit immune cells of the
brain for rapid expansion
Gliomas are among the most common and most malignant brain tumors. These tumors infiltrate
normal brain tissue and grow very rapidly. As a result, surgery can never completely
remove the tumor. Now, the neurosurgeons Dr. Darko S. Markovic (Helios Klinikum
Berlin-Buch) and Dr. Michael Synowitz (Charité) as well as Dr. Rainer Glass and Professor
Helmut Kettenmann (both Max Delbrück Center for Molecular Medicine, MDC, Berlin-Buch),
have been able to show that glioma cells exploit microglia, the immune cells of the brain,
for their expansion (PNAS Early Edition)*. Microglial cells are the immune cells of the
brain/central nervous system. They constantly screen the brain environment. On their
surface they use sensors to detect changes in their environment due to brain damage or
infections. An important family of these sensors are Toll-like receptors (TLR). However,
microglia do not attack glioma cells. On the contrary: they support the growth of the
tumor and, thus, make the disease worse. Together with researchers in Warsaw, Poland,
Amsterdam, The Netherlands, and Bethesda, USA, the researchers in Berlin have been able to
show how the immune cells promote the tumor growth. Microglial cells are attracted toward
the glioma cells and gather in and around the tumor in large numbers. Interestingly,
gliomas consist of up to 30 per cent of microglia, especially at the tumor edge. Gliomas
release certain enzymes, metalloproteases, which digest the extracellular matrix, and also
dissolve the ties between cells. However, the metalloproteases are produced and released
as inactive precursor protein which need to be cleaved to be activated. This cleavage is
accomplished by another enzyme, which is produced by the microglial cells. This enzyme is
anchored in the membrane and was therefore named membrane type 1 metalloprotease
(MT1-MMP). MT1-MMP activates the metalloproteases which clear the way for the glioma cells
and allows them to infiltrate normal brain tissue and expand very rapidly.
Researchers find that eating high
levels of fructose impairs memory in rats
Researchers at Georgia State University have found that diets high in fructose — a
type of sugar found in most processed foods and beverages — impaired the spatial
memory of adult rats. Amy Ross, a graduate student in the lab of Marise Parent, associate
professor at Georgia State's Neuroscience Institute and Department of Psychology, fed a
group of Sprague-Dawley rats a diet where fructose represented 60 percent of calories
ingested during the day. She placed the rats in a pool of water to test their ability to
learn to find a submerged platform, which allowed them to get out of the water. She then
returned them to the pool two days later with no platform present to see if the rats could
remember to swim to the platform's location. "What we discovered is that the fructose
diet doesn't affect their ability to learn," Parent said. "But they can't seem
to remember as well where the platform was when you take it away. They swam more randomly
than rats fed a control diet." Fructose, unlike another sugar, glucose, is processed
almost solely by the liver, and produces an excessive amount of triglycerides — fat
which get into the bloodstream. Triglycerides can interfere with insulin signaling in the
brain, which plays a major role in brain cell survival and plasticity, or the ability for
the brain to change based on new experiences. Results were similar in adolescent rats, but
it is unclear whether the effects of high fructose consumption are permanent, she said.
Obesity raises risk of
complications in pregnancy, study shows
Expectant mothers who are obese are much more likely to suffer from minor complications
such as heart burn and chest infections during pregnancy, a study suggests Expectant
mothers who are obese are much more likely to suffer from minor complications such as
heart burn and chest infections during pregnancy, a study suggests. Research by the
University of Edinburgh found that obese mothers-to-be were nearly 10 times more likely to
suffer from chest infections, and more than twice as likely to suffer from headaches and
heartburn, compared with pregnant women of a healthy weight. Researchers studied the
records of more than 650 pregnant women, of whom nearly half were overweight or obese at
the beginning of their pregnancy. The study took into account factors such as age and
smoking. Obese pregnant women were three times more likely to have carpal tunnel syndrome,
which occurs when an increase in fluid causes swelling in the wrist. The condition can
lead to tingling, pain, numbness and lack of coordination in the hands. The study,
published in the British Journal of Obstetrics and Gynaecology, also found that obese
women had a more than three-fold increased risk of suffering from a condition known as
symphysis-pubis dysfunction, which affects the pelvic joints and may cause walking
difficulties if severe. The costs of treating minor complications in obese women were
estimated to be more than three times that of treating women of a healthy body weight.
Cystic fibrosis treatments may have
unseen long-term benefits
Cystic fibrosis medicines that help to break down mucus in the lungs may carry an
unexpected long-term benefit, a study suggests. The treatments not only help breathing in
the short term - they may also make lung infections develop to be less harmful in the long
run, research from the University of Edinburgh shows. Scientists studied how bacteria
which infect the lungs of cystic fibrosis patients gather nutrients from their
surroundings. The work builds on the knowledge that most bacteria co-operate to scavenge
what they need from their environment, but some bacteria do not actively hunt, instead
stealing nutrients from neighbouring bacteria. Scientists found that in a viscous
environment, similar to thick mucus, the co-operating type of bacteria is most common.
However, in a more liquid environment - similar to mucus having been broken down by
medicine - the number of thieving bacteria increases, eventually outnumbering the
scavenging type. In this environment, because the thieving bacteria are less adept at
obtaining food, the bacterial growth slows down. The results suggest that liquefying lung
mucus would be expected to limit the impact of infection in cystic fibrosis.
Targeting MMPs to halt advanced
metastatic breast cancer
An upcoming G&D paper reveals how two specific matrix metalloproteinase (MMP) proteins
contribute to bone metastasis in advanced breast cancer – lending important new
insight into the design of clinically useful small molecule inhibitors. The study was led
by Dr. Yibin Kang in Princeton University in close collaboration with Dr. Joan Massagué
at MSKCC and Dr. Michael Reiss at the Cancer Institute of New Jersey. It will be published
online ahead of print at www.genesdev.org/cgi/doi/10.1101/gad.1824809. "More than 70%
of late stage breast cancer patients have skeletal complications," explains Dr. Yibin
Kang. "It is important to uncover molecular mechanism of bone metastasis in order to
come up with better treatments to reduce the pain and suffering from bone
metastasis." MMPs are a large class of related enzymatic proteins that degrade the
extracellular matrix. Normal MMP activity is tightly regulated, and is necessary for a
number of physiological processes, like tissue remodeling, angiogenesis, ovulation and
wound healing. However, MMP dysregulation facilitates tumor metastasis. MMP1 and ADAMTS1
are two different MMP family members that were previously identified in a genomic screen
for breast cancer bone metastasis genes. Dr. Kang and colleagues now show how alterations
in MMP1 and ADAMTS1 expression promote bone metastasis.
Thalidomide does not improve
survival in small cell lung cancer
Treating patients with thalidomide in combination with chemotherapy for small cell lung
cancer (SCLC) did not improve their survival but did increase their risk of blood clots,
according to a new study published online July 16 in the Journal of the National Cancer
Institute. Siow Ming Lee, M.D., of the Department of Oncology, University Hospital in
London, and colleagues randomly assigned 724 SCLC patients to take either a placebo or
thalidomide. Used in treating some other cancers, thalidomide is an anti-angiogenic drug,
i.e., it targets and suppresses the formation of new blood vessels that tumors need to
survive and grow. In this randomized double-blind trial, patients received 100-200
milligrams daily for up to two years. The researchers found no evidence of a survival
difference between the two groups. The median overall survival for patients who received
the placebo was 10.5 months. For patients who took thalidomide capsules, it was 10.1
months. Patients treated with thalidomide, however, had higher risk of thrombotic events.
"Together, these results suggest that targeting anti-angiogenesis in SCLC may not
work as well as in multiple myeloma or colorectal cancer, perhaps because of differences
in the angiogenic pathways involved in SCLC," the authors write.
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