News 17 aug 2009
New Strategy for Inhibiting Virus
Replication
Cellular protein as a new target for treatment of chronic hepatitis C / Virologists from
Heidelberg publish in PLoS Pathogens. Viruses need living cells for replication and
production of virus progeny. Thus far, antiviral therapy primarily targets viral factors
but often induces therapy resistance. New improved therapies attempt to targets cellular
factors that are essential for viral replication.The team led by Professor Dr. Ralf
Bartenschlager, Director of the Department of Molecular Virology at the Hygiene Institute
of Heidelberg University Hospital, has identified a protein in infected liver cells that
is essential for hepatitis C virus replication. Inhibiting this protein is highly
efficient in blocking virus replication. The study is to be published in the prestigious
journal Public Library of Science Pathogens.
Doing what the brain does - how
computers learn to listen
We see, hear and feel, and make sense of countless diverse, quickly changing stimuli in
our environment seemingly without effort. However, doing what our brains do with ease is
often an impossible task for computers. Researchers at the Leipzig Max Planck Institute
for Human Cognitive and Brain Sciences and the Wellcome Trust Centre for Neuroimaging in
London have now developed a mathematical model which could significantly improve the
automatic recognition and processing of spoken language. In the future, this kind of
algorithms which imitate brain mechanisms could help machines to perceive the world around
them. (PLoS Computational Biology, August 12th, 2009) Many people will have personal
experience of how difficult it is for computers to deal with spoken language. For example,
people who 'communicate' with automated telephone systems now commonly used by many
organisations need a great deal of patience. If you speak just a little too quickly or
slowly, if your pronunciation isn’t clear, or if there is background noise, the
system often fails to work properly. The reason for this is that until now the computer
programs that have been used rely on processes that are particularly sensitive to
perturbations. When computers process language, they primarily attempt to recognise
characteristic features in the frequencies of the voice in order to recognise words. 'It
is likely that the brain uses a different process', says Stefan Kiebel from the Leipzig
Max Planck Institute for Human Cognitive and Brain Sciences. The researcher presumes that
the analysis of temporal sequences plays an important role in this. 'Many perceptual
stimuli in our environment could be described as temporal sequences.' Music and spoken
language, for example, are comprised of sequences of different length which are
hierarchically ordered. According to the scientist’s hypothesis, the brain classifies
the various signals from the smallest, fast-changing components (e.g., single sound units
like 'e' or 'u') up to big, slow-changing elements (e.g., the topic). The significance of
the information at various temporal levels is probably much greater than previously
thought for the processing of perceptual stimuli. 'The brain permanently searches for
temporal structure in the environment in order to deduce what will happen next', the
scientist explains. In this way, the brain can, for example, often predict the next sound
units based on the slow-changing information. Thus, if the topic of conversation is the
hot summer, 'su…' will more likely be the beginning of the word 'sun' than the word
'supper'.
Proteins as resistance fighters
Friction limits the speed and efficiency of macroscopic engines. Is this also true for
nanomachines? A Dresden research team used laser tweezers to measure the friction between
a single motor protein molecule and its track. The team found that also within our cells,
motors work against the resistance of friction and are restrained in its
operation—usually by far not as much though as their macroscopic counterparts. These
first experimental measurements of protein friction could help researchers to better
understand key cellular processes such as cell division which is driven by such molecular
machines.
Raising the alarm when DNA goes bad
Our genome is constantly under attack from things like UV light and toxins, which can
damage or even break DNA strands and ultimately lead to cancer and other diseases.
Scientists have known for a long time that when DNA is damaged, a key enzyme sets off a
cellular ‘alarm bell’ to alert the cell to start the repair process, but until
recently little was known about how the cell detects and responds to this alarm. In a
study published today in Nature Structural and Molecular Biology, researchers at the
European Molecular Biology Laboratory (EMBL) in Heidelberg, Germany, have identified a
whole family of proteins capable of a direct response to the alarm signal. Our genome is a
huge repository of information guiding the construction and function of all the cells in
our bodies. Cells sustain many hits to their DNA every day, which can lead tomutations, so
they maintain a fleet of DNA repair machinery that can be rapidly mobilised and sent to
damaged sites in an emergency.
Energy efficient sewage plants
High-rate digestion with microfiltration is state-of-the-art in large sewage plants. It
effectively removes accumulated sludge and produces biogas to generate energy. A study now
reveals that even small plants can benefit from this process. Sewage plants remove organic
matter from wastewater. If the accumulating sludge decays, biogas is generated as a
by-product. However, only 1156 of the 10,200 sewage plants in Germany have a digestion
tank. Smaller operations, especially, baulk at the costs of a new digestion tank. Instead,
they enrich the sludge with oxygen in the existing activation basin, and stabilize it.
“Activation basins require a lot of electricity. At the same time, enormous energy
potential is lost, since no biogas is produced,” says Dr. Brigitte Kempter-Regel of
the Fraunhofer Institute for Interfacial Engineering and Biotechnology IGB in Stuttgart.
“A sewage plant eats up more electricity in the municipalities than their hospitals
do”.
Cancer Mortality Rates Experience
Steady Decline
The number of cancer deaths has declined steadily in the last three decades. Although
younger people have experienced the steepest declines, all age groups have shown some
improvement, according to a recent report in Cancer Research, a journal of the American
Association for Cancer Research. “Our efforts against cancer, including prevention,
early detection and better treatment, have resulted in profound gains, but these gains are
often unappreciated by the public due to the way the data are usually reported,” said
Eric Kort, M.D., who completed the study while employed as a research scientist at Van
Andel Research Institute (VARI) in Grand Rapids, Mich. Cancer mortality rates are usually
reported as composite age-adjusted rates. These rates have been declining modestly since
the 1990's. However, these statistics heavily emphasize the experience of the oldest
Americans for whom mortality rates are the highest. As a result, trends emerging in
younger Americans can be concealed.
Sleep patterns in children and
teenagers could indicate risk for depression, researcher finds
Sleep patterns can help predict which adolescents might be at greatest risk for developing
depression, a researcher at UT Southwestern Medical Center has found in a five-year study.
Sleep is a biological factor known to be associated with adult depression. Depressed
adults experience rapid-eye-movement (REM) sleep earlier in the sleep cycle than people
who are not depressed. Until this study, available online and in the July edition of
Neuropsychopharmacology, it had been unclear whether this relationship held true in
adolescents. Dr. Uma Rao, professor of psychiatry at UT Southwestern and lead author of
the study, found that adolescents with a familial risk for depression but without a
depression diagnosis experienced shorter REM latency, meaning they reached the REM stage
more quickly. Those adolescents were more likely to develop depression by the end of the
five-year study period than those who reached REM sleep later in the cycle.“Sleep is
probably more helpful in determining who is at risk for developing depression than in
being a diagnostic marker for depression since REM latency of those adolescents was
shorter before they even developed the illness,” Dr. Rao said. Adolescent depression
is complex to prevent and to treat in part because baseline levels of sleep and other
factors used to diagnosis depression are not clearly defined. For example, in clinical
studies, adolescents without manifestation of mental illness can be labeled erroneously as
control group members because they haven’t yet reached the highest -risk period for
developing depression – mid- to late-adolescence and early adulthood.
Changes in net flow of ocean heat
correlate with past climate anomalies
Physicists at the University of Rochester have combed through data from satellites and
ocean buoys and found evidence that in the last 50 years, the net flow of heat into and
out of the oceans has changed direction three times. These shifts in the balance of heat
absorbed from the sun and radiated from the oceans correlate well with past anomalies that
have been associated with abrupt shifts in the earth's climate, say the researchers. These
anomalies include changes in normal storm intensities, unusual land temperatures, and a
large drop in salmon populations along the western United States. The physicists also say
these changes in ocean heat-flow direction should be taken into account when predicting
global climate because the oceans represent 90 percent of the total heat in the earth's
climate system. The study, which will appear in an upcoming issue of Physics Letters A,
differs from most previous studies in two ways, the researchers say. First, the physicists
look at the overall heat content of the Earth's climate system, measuring the net balance
of radiation from both the sun and Earth. And second, it analyzes more completely the data
sets the researchers believe are of the highest quality, and not those that are less
robust. "These shifts happened relatively abruptly," says David Douglass,
professor of physics at the University of Rochester, and co-author of the paper.
"One, for example, happened between 1976 and 1977, right when a number of other
climate-related phenomenona were happening, such as significant changes in U. S.
precipitation." Douglass says the last oceanic shift occurred about 10 years ago, and
that the oceans are currently emitting slightly more radiation than they are receiving.
Early fire use ignites discussion
about the evolution of human brainpower
New evidence that early modern humans used fire in southern Africa in a controlled way to
increase the quality and efficiency of stone tools is changing how researchers understand
the evolution of human behavior, and in particular, the evolution of human brain power.
Curtis Marean, a paleoanthropologist with the Institute of Human Origins at Arizona State
University, and an international team of researchers with members from South Africa,
England, Australia and France found 72,000-year-old, silcrete rocks that had been fired
and flaked to make stone tools in a cave along the coast of the southern tip of Africa in
Mossel Bay. The finding indicates that humans' ability to solve complex problems may have
occurred at the same time their modern genetic lineage appeared, rather than developing
later as has been widely speculated.
Active ingredients in marijuana
found to spread and prolong pain
Imagine that you're working on your back porch, hammering in a nail. Suddenly you slip and
hit your thumb instead — hard. The pain is incredibly intense, but it only lasts a
moment. After a few seconds (and a few unprintable words) you're ready to start hammering
again. How can such severe pain vanish so quickly? And why is it that other kinds of
equally terrible pain refuse to go away, and instead torment their victims for years?
University of Texas Medical Branch at Galveston researchers think they've found at least
part of the answer—and believe it or not, it's in a group of compounds that includes
the active ingredients in marijuana, the cannabinoids. Interestingly enough, given recent
interest in the medical use of marijuana for pain relief, experiments with rodents and
humans described in a paper published in the current issue of Science suggest these
"endocannabinoids," which are made within the human body, can actually amplify
and prolong pain rather than damping it down. "In the spinal cord there's a balance
of systems that control what information, including information about pain, is transmitted
to the brain," said UTMB professor Volker Neugebauer, one of the authors of the
Science article, along with UTMB senior research scientist Guangchen Ji and collaborators
from Switzerland, Hungary, Japan, Germany, France and Venezuela. "Excitatory systems
act like a car's accelerator, and inhibitory ones act like the brakes. What we found is
that in the spinal cord endocannabinoids can disable the brakes." To get to this
conclusion, the researchers began by studying what happened when they applied a
biochemical mimic of an endocannabinoid to inhibitory neurons (the brakes, in Neugebauer's
analogy) on slices of mouse spinal cord. Electrical signals that would ordinarily have
elicited an inhibitory response were ignored. They then repeated the procedure using
slices of spinal cord from mice genetically engineered to lack receptors where the
endocannabinoid molecules could dock, and found that in that case, the "brakes"
worked. Finally, using electron microscopy, they confirmed that the receptors were in fact
on inhibitory, not excitatory neurons. Endocannabinoids docking with them would suppress
the inhibitor neurons, and leave pain signals with a straight shot to the brain.
New findings show increased ocean
acidification in Alaska waters
The same things that make Alaska's marine waters among the most productive in the world
may also make them the most vulnerable to ocean acidification. According to new findings
by a University of Alaska Fairbanks scientist, Alaska's oceans are becoming increasingly
acidic, which could damage Alaska's king crab and salmon fisheries. This spring, chemical
oceanographer Jeremy Mathis returned from a cruise armed with seawater samples collected
from the depths of the Gulf of Alaska. When he tested the samples' acidity in his lab, the
results were higher than expected. They show that ocean acidification is likely more
severe and is happening more rapidly in Alaska than in tropical waters. The results also
matched his recent findings in the Chukchi and Bering Seas. "It seems like everywhere
we look in Alaska's coastal oceans, we see signs of increased ocean acidification,"
said Mathis. Often referred to as the "sister problem to climate change," ocean
acidification is a term to describe increasing acidity in the world's oceans. The ocean
absorbs carbon dioxide from the air. As the ocean absorbs more carbon dioxide, seawater
becomes more acidic. Scientists estimate that the ocean is 25 percent more acidic today
than it was 300 years ago. "The increasing acidification of Alaska waters could have
a destructive effect on all of our commercial fisheries. This is a problem that we have to
think about in terms of the next decade instead of the next century," said Mathis.
Study finds higher pathogen loads
in collapsed honeybee colonies
Honeybees in colonies affected by colony collapse disorder (CCD) have higher levels of
pathogens and are co-infected with a greater number of pathogens than their non-CCD
counterparts, but no individual pathogen can be singled out as the cause of CCD, according
to a study by an international team of researchers. The researchers, who represented Penn
State's College of Agricultural Sciences, University of Liege, Gembloux Agricultural
University, North Carolina State University and the U.S. Department of Agriculture's
Agricultural Research Service (ARS), collected samples of adult bees, wax comb, pollen and
brood – developing larvae – from 91 colonies in 13 apiaries in Florida and
California and quantified more than 200 variables, including the presence of parasites
such as varroa and tracheal mites; infection by bacteria, viruses and fungi; pesticide
levels; nutritional factors; and bee physiology. No single factor was found consistently
only in those colonies suffering from CCD. The study's findings, which were published in
the online journal PLoS ONE, illustrate the complexity of solving the CCD problem,
according to lead author and Penn State entomologist Dennis vanEngelsdorp. "Our
results suggest that this condition may be contagious or the result of exposure to a
common risk factor that impairs the bees' immune systems, making them more susceptible to
pathogens," said vanEngelsdorp, who also is acting state apiarist for the
Pennsylvania Department of Agriculture. VanEngelsdorp noted that higher pathogen loads are
likely to have caused CCD symptoms, but what causes the bees to become infected with so
many pathogens is still not known. "Although pathogens seem likely to play a critical
role in CCD, that role may be secondary, much like AIDS patients die from secondary
diseases," he added. No one of the screened pathogens had a higher prevalence in
colonies that had CCD. There also was no significant difference in the prevalence nor in
the total load of varroa or tracheal mites and Nosema, a protozoan that causes disease in
bees. But overall, CCD colonies were co-infected with a greater number of pathogens --
viruses, bacteria and microparasites such as Nosema. For instance, 55 percent of CCD
colonies were infected with three or more viruses compared to 28 percent of non-CCD
colonies. The researchers also found detectable levels of residues from 50 different
pesticides in all of the sampled colonies, but there was no association between increased
pesticide levels and CCD.
Mango seeds may protect against
deadly food bacteria
Life in the fruit bowl is no longer the pits, thanks to a University of Alberta
researcher. Christina Engels has found a way to turn the throwaway kernels in mangos into
a natural food preservative that could help prevent Listeriosis outbreaks like the one
that killed 21 Canadians last year. The findings can also apply to other fruit seeds like
grapes, said Engels, who conducted the research to earn her master's degree from the
Department of Agricultural, Food and Nutritional Science at the U of A. The research is
published in the latest Journal of Agricultural and Food Chemistry:
http://pubs.acs.org/doi/pdf/10.1021/jf901621m Pure tannins, a plant component extracted
from otherwise useless mango kernels by Engels, have proven inhibitory effects against
various strains of bacteria including Listeria, a potentially deadly pathogen that
infected some packaged meats and caused an outbreak of disease in Canada in 2008. Engels'
research focuses on a way to recycle wood-like mango kernels, which are usually thrown
away or burned. "By processing the kernels for their tannins, businesses have a way
to completely utilize all fruit parts and therefore increase their profit," she said.
Currently, mangos are one of the main fruits marketed globally, ranked fifth in world
production among the major fruit crops.
First human gene implicated in
regulating length of human sleep
Scientists have discovered the first gene involved in regulating the optimal length of
human sleep, offering a window into a key aspect of slumber, an enigmatic phenomenon that
is critical to human physical and mental health. The team, reporting in the Aug. 14, 2009
issue of Science, identified a mutated gene that allows two members of an extended family
to thrive on six hours of sleep a day rather than the eight to eight-and-a-half hours that
studies have shown humans need over time to maintain optimal health. Working from this
discovery, the scientists genetically engineered mice and fruit flies to express the
mutated gene and study its impact. While most Americans obtain less than eight hours of
sleep a night (the average on non-work days is 7.4 hours), and some may feel they succeed
with less when engaged in exhilarating work, domestic life or recreation, scientific
evidence indicates that, over time, the body suffers from this regimen, the researchers
say. "Short term and chronic disruptions in the length of optimal sleep can have
serious consequences on cognition, mood and physical health, including cancer and
endocrine function," says the senior author of the study, Ying-Hui Fu, PhD, UCSF
professor of neurology. However, teasing out this impact can be challenging, she says,
given access to such stimuli as coffee and chocolate. The finding, she says, offers an
opportunity to unravel the regulatory mechanism of sleep. While the mutation may be rare,
it could offer a probe more generally into the regulatory mechanisms of sleep quality and
quantity. Understanding these mechanisms could lead to interventions to alleviate
pathologies associated with sleep disturbance. Sleep remains a relatively inscrutable
biological phenomenon. Scientists know that it is regulated in large part by two
processes: 1) circadian rhythms -- genetic, biochemical and physiological mechanisms that
wax and wane during a 24 hour period to regulate the timing of sleep, 2) and homeostasis
– unknown mechanisms that ensure that the body acquires over time the necessary
amount of sleep, nudging it toward sleep when it has been deprived, prompting it out of
sleep when it has received enough. This regulation of sleep intensity is measured in non
rapid eye movement sleep and REM sleep. Interactions between the circadian rhythms and
homeostatic mechanisms influence the timing, duration and quality of sleep and
wakefulness. But "the details in the process are really completely unknown,"
says Fu.
Protein plays unexpected role
protecting chromosome tips
A protein specialist that opens the genomic door for DNA repair and gene expression also
turns out to be a multi-tasking workhorse that protects the tips of chromosomes and
dabbles in a protein-destruction complex, a team lead by researchers at The University of
Texas M. D. Anderson Cancer Center reports in the Aug. 13 edition of Molecular Cell.
"Instead of being a really important tool dedicated just to regulation of gene
transcription, Gcn5 is more like a Swiss Army knife that performs different functions
depending on what needs to be done in the cell," said senior author Sharon Dent,
Ph.D., professor in M. D. Anderson's Department of Biochemistry and Molecular Biology. The
researchers document a chain of events that starts with depletion of Gcn5, which leads to
decreased activity by another protein that protects yet a third protein from destruction.
That last protein, TRF1, protects telomeres, dense structures at the end of chromosomes
which, like the compressed plastic tips on the ends of a shoelace, keep the chromosome
ends intact. Variation in the gene that expresses the middle protein in this model,
ubiquitin specific protease 22 (USP22), is part of an 11-gene signature associated with
highly metastatic cancers and poor prognosis, the authors note. "Our results indicate
that the Gcn5 complex regulates not just gene transcription but also protein
stability," Dent said. "They also suggest that the role of USP22 in highly
aggressive cancers might be due to these new functions."
Brain innately separates living and
non-living objects for processing
For unknown reasons, the human brain distinctly separates the handling of images of living
things from images of non-living things, processing each image type in a different area of
the brain. For years, many scientists have assumed the brain segregated visual information
in this manner to optimize processing the images themselves, but new research shows that
even in people who have been blind since birth the brain still separates the concepts of
living and non-living objects. The research, published in today's issue of Neuron, implies
that the brain categorizes objects based on the different types of subsequent
consideration they demand—such as whether an object is edible, or is a landmark on
the way home, or is a predator to run from. They are not categorized entirely by their
appearance. "If both sighted people and people with blindness process the same ideas
in the same parts of the brain, then it follows that visual experience is not necessary in
order for those aspects of brain organization to develop," says Bradford Mahon,
postdoctoral fellow in the Department of Brain and Cognitive Sciences at the University of
Rochester, and lead author of the study. "We think this means significant parts of
the brain are innately structured around a few domains of knowledge that were critical in
humans' evolutionary history." Previous studies have shown that the sight of certain
objects, such as a table or mountain, activate regions of the brain other than does the
sight of living objects, such as an animal or face—but why the brain would choose to
process these two categories differently has remained a mystery, says Mahon. Since the
regions were known to activate when the objects were seen, scientists wondered if
something about the visual appearance of the objects determined how the brain would
process them. For instance, says Mahon, most living things have curved forms, and so many
scientists thought the brain prefers to processes images of living things in an area that
is optimized for curved forms. To see if the appearance of objects is indeed key to how
the brain conducts its processing, Mahon and his team, led by Alfonso Caramazza, director
of the Cognitive Neuropsychology Laboratory at Harvard University, asked people who have
been blind since birth to think about certain living and non-living objects. These people
had no visual experience at all, so their brains necessarily determined where to do the
processing using some criteria other than an object's appearance.
Obesity increases risk of prostate
cancer recurrence for both blacks and whites
A new look at a large database of prostate cancer patients shows that obesity plays no
favorites when it comes to increasing the risk of recurrence after surgery: Being way
overweight is equally bad for blacks and whites, say researchers at Duke University
Medical Center. Studies have shown that obesity is linked to generally worse outcomes in
many cancers, including prostate cancer. Because blacks are more likely than whites to
develop and die from prostate cancer – and because there is a higher prevalence of
obesity among black men with prostate cancer, compared to whites – some studies have
suggested that obesity might be a more ominous risk factor for blacks than whites.
"Not so," says Stephen Freedland, M.D., an associate professor of urology and
pathology in the Duke Prostate Center and the senior author of the study appearing in the
journal Cancer. "Obesity leads to worse cancer in both groups." Freedland and
Jayakrishnan Jayachandran, M.D. a urologic oncology fellow at Duke and the lead author of
the paper, examined the records of 1,415 men enrolled in the Shared Equal Access Regional
Cancer Hospital (SEARCH) database who had undergone a radical prostatectomy. Black men
comprised almost half (47 percent) of the sample. After adjusting for various preoperative
characteristics, researchers analyzed the relationship between body mass index (BMI) and
the aggressiveness of the cancer, as measured by the risk of recurrence. In contrast to
other studies, investigators found no association between race and obesity. Almost a third
of the men were obese, regardless of race. "We found that higher BMI was associated
with significantly increased risk of cancer recurrence for both blacks and whites,"
said Jayachandran. "Though prior SEARCH-based studies from our group found that
obesity was associated with a higher risk of disease progression as measured by a rising
PSA after surgery, it now appears that being obese just means a poorer prognosis, period,
regardless of race." As for why that might be, Jayachandran says he's not sure, but
he says it may have something to do with altered hormone levels.
Scarring key to link between
obesity and diabetes
The team, in collaboration with University Hospital Aintree, the University of Warwick and
researchers in Sweden, found that people classified as obese and those with pre-diabetes
have raised levels of a protein called SPARC, that can cause tissue scarring. The research
revealed that an increase in insulin, a hormone that controls blood sugar levels, and
leptin, a hormone that regulates appetite, can trigger an increase in SPARC, which can
prevent the proper storage of fat in fat tissue cells. It is thought that leptin, in an
attempt to balance energy levels in the body, could trigger SPARC to limit the storage of
fat. SPARC can do this by increasing the formation of scars in fat tissue, which can
prevent fat being stored safely in the body. Researchers found that this process could
predispose obese patients to type 2 diabetes. Professor John Wilding, from the
University's School of Clinical Science, explains: "We tested fat tissue of patients
at University Hospital Aintree and found that an increase in leptin also increases SPARC
levels, which reduces the safe storage of fat through the development of abnormal tissue
scarring. Scarring of fat tissue is known to increase as we gain weight and we found that
this is exacerbated by leptin, as well as an increase in insulin, produced by the
pancreas." Dr Katarina Kos, lead author of the research, added: "Leptin is
produced in fat cells to regulate appetite, but the body becomes resistant to the effects
of appetite reduction in obese patients. Leptin continues to increase in response to
overall fat mass and promotes scarring through increased SPARC levels. Once scarring
occurs, the excess nutritional energy from fat cannot be taken up by fat cells and so
remains in the blood and begins to gather around organs. As a result, fat cells of people
classified as obese, may not fulfil their natural purpose to store fat." Diabetes is
caused by the cells' inability to respond to insulin, which would normally enable uptake
of sugar from the blood. To compensate, the pancreas creates more insulin to clear blood
sugar from the circulation. The pancreas becomes exhausted and is unable to produce
sufficient insulin to keep up with the demands of the body. This results in the
development of type 2 diabetes, which can cause problems such as lack of energy to the
cells and, over time, damage to the eyes, kidneys and heart. The research team, working
with the Swedish fast food study group at Linkoping University, also found that weight
gain, induced by more than doubling calorie intake through eating 'junk food', causes
SPARC levels to increase by 33%. In a further study with the University of Gothenburg,
scientists found that a reduced calorie diet can decrease SPARC levels and the stimulus
for tissue scarring. Researchers are now investigating why some people are more prone to
fat tissue scarring than others and how further understanding of SPARC could contribute to
future treatments for diabetes.
MRC scientists advance
understanding of cell death
Medical Research Council (MRC) scientists have made an important advance in understanding
the biological processes involved when cells are prompted to die. The work may help
scientists to eventually develop new treatments for the many common diseases and
conditions which occur when cell death goes wrong. The research, published in leading
journal Molecular Cell [1] today (Friday 14 August 2009) was carried out by a team of
scientists, at the MRC Toxicology Unit at the University of Leicester and a subsequent
patent application has been filed by MRC Technology, the commercial arm of the MRC. cells
in the human body are continually dying and most of these cells kill themselves by a form
of cell death, commonly referred to as apoptosis. In a healthy body, the number of cells
stays constant. Millions of new cells are produced every second, and millions of others
are lost or kill themselves. Failure of the normal apoptosis process plays a role in
different diseases including cancer, certain neurodegenerative disorders such as
Parkinson's and immune diseases, such as autoimmune lymphoproliferative syndrome (ALPS).
One of the study's authors, Dr Marion MacFarlane, MRC Toxicology Unit, explained:
"This new research takes us a step closer to understanding how the DISC triggers
cells to die. The challenge now is to try and use this fundamental knowledge to help work
towards finding better treatments for conditions which occur when DISC-mediated cell death
goes wrong." Previous research has shown that a complex called the 'DISC', which is
made up of different proteins and is formed following activation of molecules called
'Death Receptors', can trigger apoptosis by 'switching on' key players in the cell death
process. However, previous research has found that the DISC can also activate cell
survival, thus raising the question as to how paradoxically the 'DISC' can trigger these
opposing cellular outcomes? Now, scientists at the MRC Toxicology Unit have found that the
DISC can trigger cell death or cell survival by switching the activity of key
death-promoting molecules. Stopping the 'DISC' from functioning properly prevents the cell
death programme from being carried out efficiently and instead results in cell survival.
Thus, in diseases such as ALPS, where a crucial death-promoting protein is often not
active the DISC fails to function properly.
New study suggests possible genetic
links between environmental toxins and multiple myeloma
The International Myeloma Foundation (IMF)—supporting research and providing
education, advocacy and support for myeloma patients, families, researchers and
physicians—today said newly published data may provide a possible genetic link
between environmental toxins and bone disease in multiple myeloma. Myeloma, also called
multiple myeloma, is a cancer of cells in the bone marrow that affect production of blood
cells and can damage bone. Once considered a "rare disease of the elderly," it
is increasingly being diagnosed in patients under 45 years old, including some of the
early responders to the 9/11 World Trade Center site. Now a study published this week may
help explain why. The study from researchers with the IMF gene bank, Bank on a Cure®,
identified several changes in DNA sequences called SNPs (single nucleotide polymorphisms)
that are associated with a risk of bone disease in myeloma. Further analyses showed that
many of these DNA changes may be involved with the way the human body responds to certain
environmental toxins, providing a possible link between myeloma and the environment. The
findings were published in the latest issue of the journal Leukemia*. Brian G.M. Durie,
M.D., lead author of the study and Chairman of the IMF said: "This is a
hypothesis-generating study. While the functional role of many SNPs is still uncertain,
this study is supportive of the notion that genetic factors affecting toxin breakdown may
be related to the development of myeloma. This gives us an important starting point for
further studies." The findings may help explain a widely reported study this week in
the Journal of Occupational and Environmental Medicine, that found more cases of myeloma
among younger responders to the 9/11 World Trade Center site than would normally be
expected. The findings are also supportive of a study published earlier this year that
suggests a link between certain pesticide exposures in agricultural workers and a
precursor to multiple myeloma. Previous studies have also shown an increased risk for
myeloma among firefighters, and the IMF has issued guidelines for firefighters for the
prevention and treatment of this disease. "Multiple myeloma is not a familiar cancer
to patients or even to many doctors, but taken together, these studies say it should not
be overlooked," said Susie Novis, President and Co-founder of the IMF. "While
multiple myeloma cannot be cured, it can be treated with new, targeted therapies including
REVLIMID®, VELCADE® and THALOMID®. These studies tell us it is critically important for
medical practitioners to know the possible risk factors for myeloma along with the early
warning signs so they will be alerted to test for it." Myeloma affects an estimated
750,000 people worldwide, and in industrialized countries it is being diagnosed in growing
numbers and in increasingly younger people.
First compound that specifically
kills cancer stem cells found
The cancer stem cells that drive tumor growth and resist chemotherapies and radiation
treatments that kill other cancer cells aren't invincible after all. Researchers reporting
online on August 13th in the journal Cell, a Cell Press publication, have discovered the
first compound that targets those cancer stem cells directly. "It wasn't clear it
would be possible to find compounds that selectively kill cancer stem cells," said
Piyush Gupta of the Massachusetts Institute of Technology (MIT) and the Broad Institute.
"We've shown it can be done." The team including MIT's Robert Weinberg and the
Broad Institute's Eric Lander developed a new high-throughput screening method that makes
it possible for the first time to systematically look for agents that kill cancer stem
cells. That ability had previously eluded researchers due to the rarity of those cells
within tumor cell populations and their relative instability in laboratory culture. In the
new study, the researchers manipulated cultured breast cancer cells to greatly enrich for
those with the stem-like properties, including increased resistance to standard cancer
drugs. They then screened a library of 16,000 natural and commercial chemical compounds
for their ability to kill those stem-like cells and not other cancer cells. That screen
turned up 32 contenders. The researchers narrowed that list down to a handful of chemicals
that they could readily get in sufficient quantities for further testing on normal cancer
stem cells. Of those, one called salinomycin was the clear winner. Salinomycin reduced the
proportion of breast cancer stem cells by more than 100-fold compared to a commonly used
chemotherapeutic drug for breast cancer called paclitaxel (aka Taxol™).
Salinomycin-treated cells were less able than paclitaxel-treated ones to seed tumors when
injected into mice, they report. Salinomycin treatment also slowed the growth of the
animals' tumors.
New method takes aim at aggressive
cancer cells
A multi-institutional team of Boston-area researchers has discovered a chemical that works
in mice to kill the rare but aggressive cells within breast cancers that have the ability
to seed new tumors. These cells, known as cancer stem cells, are thought to enable cancers
to spread — and to reemerge after seemingly successful treatment. Although further
work is needed to determine whether this specific chemical holds therapeutic promise for
humans, the study shows that it is possible to find chemicals that selectively kill cancer
stem cells. The scientists' findings appear in the August 13 advance online issue of Cell.
"Evidence is accumulating rapidly that cancer stem cells are responsible for the
aggressive powers of many tumors," says Robert Weinberg, a Member of Whitehead
Institute for Biomedical Research and one of the authors of the study. "The ability
to generate such cells in the laboratory, together with the powerful techniques available
at the Broad Institute, made it possible to identify this chemical. There surely will be
dozens of others with similar properties found over the next several
years.""Many therapies kill the bulk of a tumor only to see it regrow,"
says Eric Lander, Director of the Broad Institute of MIT and Harvard, and an author of the
Cell paper. "This raises the prospect of new kinds of anti-cancer therapies." An
emerging idea in cancer biology is that tumors (breast, prostate, colon, lung, etc.)
harbor a group of cells with the unique ability to regenerate cancers. In addition to
promoting tumor growth, these so-called cancer stem cells are largely resistant to current
cancer therapies. If it were possible to identify chemicals that selectively kill cancer
stem cells, such chemicals might become critical candidates for future drug development.
However, researchers have struggled to study cancer stem cells directly in the laboratory.
The cells' relative scarcity compared to other tumor cells, combined with a tendency to
lose their stem cell-like properties when grown outside of the body, have severely limited
the amount of material available for analysis.
An apple a day keeps kidney stones
away
Researchers have found another reason to eat well: a healthy diet helps prevent kidney
stones. Loading up on fruits, vegetables, nuts, low-fat dairy products, and whole grains,
while limiting salt, red and processed meats, and sweetened beverages is an effective way
to ward off kidney stones, according to a study appearing in an upcoming issue of the
Journal of the American Society Nephrology (JASN). Because kidney stones are linked to
higher rates of hypertension, diabetes, increased body weight, and other risk factors for
heart disease, the findings have considerable health implications. Eric Taylor, MD (Maine
Medical Center) and his colleagues at Brigham and Women's Hospital conducted a large study
to determine the effects of healthy eating habits on the formation of kidney stones. The
investigators collected information from individuals enrolled in three clinical studies:
the Health Professionals Follow-up Study (45,821 men followed for 18 years), the Nurses'
Health Study I (94,108 older women followed for 18 years), and the Nurses' Health Study II
(101,837 younger women followed for 14 years). Dr. Taylor's team assigned a score to each
participant based on eight components of a DASH (Dietary Approaches to Stop Hypertension)
style diet: high intake of fruits, vegetables, nuts and legumes, low-fat dairy products,
and whole grains and low intake of salt, sweetened beverages, and red and processed meats.
Individuals with higher DASH scores consumed diets that were higher in calcium, potassium,
magnesium, oxalate, and vitamin C and lower in sodium. A total of 5,645 incident kidney
stones developed in the participants in the three studies. In each study, participants
with the highest DASH scores were between 40% and 45% less likely to develop kidney stones
than participants with the lowest DASH scores. The reductions in kidney stone risk were
independent of age, body size, fluid intake, and other factors. Because a DASH-style diet
may affect the development of hypertension, diabetes, and other chronic diseases
associated with kidney stones, the researchers also performed an analysis limited to study
participants without hypertension or diabetes. Even among those individuals the DASH diet
reduced the risk of kidney stones. Many of the medications used to treat kidney stones
have unpleasant side effects. This study indicates that adopting a DASH-style diet may be
an effective alternative.
Carnegie Mellon develops innovative
method to detect genetic causes of complex diseases
Computational biologists at Carnegie Mellon University have developed an analytical
technique to detect the multiple genetic variations that contribute to complex disease
syndromes such as diabetes, asthma and cancer, which are characterized by multiple
clinical and molecular traits. Rather than searching one at a time for genetic alterations
that cause a particular symptom or trait, as in most conventional approaches, the Carnegie
Mellon scientists use a statistical method that enables them to uncover genome variations
underlying an entire regulatory network of genes or traits that are responsible for
complex diseases. Professor Eric P. Xing and postdoctoral scientist Seyoung Kim report
today in the online journal Public Library of Science (PLoS) Genetics that their
graph-guided fused lasso (GFlasso) method showed increased power in detecting gene
variants associated with complex symptoms compared with other methods. In one test,
GFlasso successfully detected a gene variant already implicated in severe asthma and
identified two additional variants that had not previously been associated with the
condition. More study of the two variants will be necessary to confirm the association,
Xing and Kim said. "We know that some of the most common and most serious diseases
that plague humans are caused not by a single genetic mutation, but by a combination of
many genetic and environmental factors," said Xing, an associate professor of machine
learning, language technologies and computer science. "Complicating the situation is
that most complex diseases have a large number of clinical traits such as various
symptoms, body metrics and family history, and that genome-wide gene expression profiling
can identify tens of thousands of molecular traits associated with the disease."
Novel Treatment Reduces Swollen
Livers
A novel treatment strategy for patients with many cysts in their liver led to a surprising
result, reported in the online version of Gastroenterology by researchers from Radboud
University Nijmegen Medical Centre, The Netherlands. A six month treatment with a
synthetic gastrointestinal hormone lanreotide significantly decreased swollen cystic
livers by approximately five percent, compared to a ‘wait and see’ policy. At
least five percent of the population has one or two cysts in the liver. Cysts are
fluid-filled cavities. There are also many patients who have numerous cysts, which then is
termed a polycystic liver. These cysts cause the liver to grow to four to six times its
normal size. Until recently, surgery was the only possible treatment for these patients,
but this approach leads to many complications, and the outcome is not always successful.
Ultimately, these patients need a liver transplantation, but in view of the limited
availability of organs, only few are actually transplanted.
Bad news for coffee drinkers who
get headaches
People who consume high amounts of caffeine each day are more likely to suffer occasional
headaches than those with low caffeine consumption, a team of researchers at the Norwegian
University of Science and Technology (NTNU) reports in a study recently published in the
Journal of Headache Pain. But in findings that had “no obvious reason”, the
researchers, led by Knut Hagen from NTNU’s Faculty of Medicine, also reported that
low caffeine consumption was associated with a greater likelihood of chronic headaches,
defined as headaches for 14 or more days each month. The results are drawn from a large
cross-sectional study of 50,483 people who answered a questionnaire about caffeine
consumption and headache prevalence as a part of the Nord-Trøndelag Health Survey (HUNT
2), a county-wide health survey conducted in 1995-1997 on a wide range of health topics.
Obstructive sleep apnea is
prevalent in adults with Down syndrome
A study in the Aug. 15 issue of the Journal of Clinical Sleep Medicine shows that adults
with Down syndrome also frequently suffer from obstructive sleep apnea (OSA). However,
complications of untreated OSA such as cardiovascular disease, daytime sleepiness and
impaired cognitive functioning overlap with the manifestations of Down syndrome;
therefore, OSA may not be detected. Results indicate that 94 percent of subjects with Down
syndrome had OSA; 88 percent had at least moderate OSA with an apnea-hypopnea index (AHI)
of more than 15 breathing pauses per hour of sleep; and 69 percent had severe OSA with an
AHI of more than 30. Twelve of the 16 subjects with Down syndrome were obese, and there
was a significant correlation between body mass index (BMI) and AHI. Total sleep time in
subjects with Down syndrome (307 minutes) was more than an hour less than in controls (380
minutes). Despite the severity of OSA in the study group, medical evaluation had been
sought in only one case. According to senior author Carole Marcus, M.B.B.Ch., professor of
pediatrics at the University of Pennsylvania and director of the Children's Hospital of
Philadelphia Sleep Center, it is well known that children with Down syndrome are at risk
for OSA, with a prevalence of 30 to 55 percent, and adults with Down syndrome have even
more predisposing factors for OSA than children, as they still have the craniofacial
anomalies and are more likely to be obese or hypothyroid. "Patients with Down
syndrome have a great deal of risk factors for OSA (based on their narrow midface, large
tongue, floppy muscle tone, tendency towards being overweight, and thyroid disease),"
said Marcus. "However, the fact that almost all of the subjects studied had OSA was a
much higher prevalence than we expected. It was surprising how severe the illness was, and
how the OSA was unsuspected by their caregivers."
Cognitive Behavioral Therapy for
Insomnia Improves Sleep and Pain in People with Osteoarthritis
A study in the Aug. 15 issue of the Journal of Clinical Sleep Medicine shows that the use
of cognitive behavioral therapy for insomnia (CBT-I) is an effective treatment for older
patients with osteoarthritis and comorbid insomnia.Results show that treatment improved
both immediate and long-term self-reported sleep and pain in older patients with
osteoarthritis and comorbid insomnia without directly addressing pain control.
Participants who received CBT-I reported significantly decreased sleep latency (by an
average of 16.9 minutes initially, and by 11 minutes a year after treatment) and wake
after sleep onset (by an average of 37 minutes initially, and by 19.9 minutes a year after
treatment), significantly reduced pain (by 9.7 points initially, and by 4.7 points a year
after treatment) and increased sleep efficiency (by 13 percent initially, and by 8 percent
a year after treatment). These improvements persisted in CBT-I patients (19 of 23) who
were further assessed for sleep quality and perceived pain at a one-year follow-up visit.
According to lead author Michael V. Vitiello, PhD, professor at the University of
Washington in Seattle, Wash., results indicate that insomnia is not merely a symptom of
osteoarthritis but rather a co-existing illness. Vitiello said improving sleep can result
in an improvement in osteoarthritis, which is particularly important because, at least in
older adults, insomnia rarely exits by itself; rather it typically coexists with other
illnesses, pain conditions and depression. “The particular strength of CBT-I is that
once an individual learns how to improve their sleep, study after study has shown that the
improvement persists for a year or more,” said Vitiello. “What we and others are
showing is that CBT-I can not only improve sleep but that improvement of sleep may lead to
improvement in co-existing medical or psychiatric illnesses, such as osteoarthritis or
depression, and in the case of our study, that these additional benefits can be seen in
the long term.” A total of 23 patients with a mean age of 69 years were randomly
assigned to CBT-I, while 28 patients with a mean age of 66.5 years were assigned to a
stress management and wellness control group. Participants in the control group reported
no significant improvements in any measure.
USC researchers identify
'regulatory' genetic sequences that may predict risk for prostate cancer
Researchers at the Keck School of Medicine of the University of Southern California (USC)
have identified a novel genetic mechanism that may govern an individual's risk of
developing prostate cancer. The findings, published today in the Public Library of Science
(PLoS) Genetics journal, found mechanisms involved in cancer-associated sites in areas
where no genes are present (gene 'deserts') at a chromosomal region called 8q24. The new
findings show that some of these sites have embedded regulatory sequences that act as
enhancers of gene expression, modulated by genetic variation, or single nucleotide
polymorphisms (SNPs). The two-year study, conducted by researchers from USC, Harvard
University and the Weizmann Institute of Tel Aviv, Israel, found novel functions of SNPs
in areas where no genes were present. They found how the SNPs are able to modulate genetic
expression even while they were near no genes. SNPs denote a modest increase in risk for
certain diseases; in this particular chromosomal area, the SNPs appear to be influencing
gene expression for prostate (and other) cancer 'at a genetic distance'. "The real
contribution of this discovery is that we get a feel for a previously unappreciated
mechanism that may be a predisposition to this disease," said Gerhard (Gerry)
Coetzee, Ph.D., professor of urology and preventive medicine at the Keck School of
Medicine and principal investigator on the study. "We have unearthed a new way to
understand the risk for prostate cancer." The study was prompted by discrepancies in
prostate cancer risk among ethnic groups. Currently, risk factors for prostate cancer are
governed by age, and a disproportionate increased risk chiefly among African-American men,
with Caucasian men following and Asian men last. This gene 'desert' featuring versions of
particular SNPs are found more often in African-American men and may explain their
increased risk for the disease.
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