News 27 feb 2009
Expression of the Multiple
Sclerosis-Associated MHC Class II Allele HLA-DRB1*1501 Is Regulated by Vitamin D
Multiple Sclerosis (MS) is a complex
neurological disease with a strong genetic component. The Major Histocompatibility Complex
(MHC) on chromosome 6 exerts the strongest genetic effect on disease risk. A region at or
near the HLA-DRB1 locus in the MHC influences the risk of MS. HLA-DRB1 has over 400
different alleles. The dominant haplotype of Northern Europe, marked by the presence of
DRB1*1501, increases risk of MS by 3-fold. The environment also plays a key role in MS.
The most striking illustration of this is the geographical distribution of the disease in
populations matched for ethnicity. This has led to the proposal that sunshine, and in
particular, vitamin D, is an environmental factor influencing the risk of MS.
Circumstantial evidence supporting this comes from studies showing the involvement of
vitamin D in immune and nervous system function. The current investigation sought to
uncover any relationship between vitamin D and HLA-DRB1. It was found that vitamin D
specifically interacts with HLA-DRB1*1501 to influence its expression. This study
therefore provides more direct support for the already strong epidemiological evidence
implicating sunlight and vitamin D in the determination of MS risk, and implies that
vitamin D supplementation at critical time periods may be key to disease prevention.
Compounds Protect Against Cerebral
Palsy
The new compounds Silverman and his team
developed inhibit an enzyme found in brain cells that produces nitric oxide, thus lowering
nitric oxide levels. At normal levels, nitric oxide acts as a neurotransmitter and is
important to neuronal functioning, but at high levels it has been shown to damage brain
tissue. An overabundance of nitric oxide is believed to play a role in cerebral palsy.
Scientists unlock the secrets of C. difficile's protective shell, paving the way for new
superbug drugs and vaccines.
Newly discovered gene plays vital
role in cancer
Gene p53 protects against cancer and is
usually described as the most important gene in cancer research. However, scientists at
Karolinska Institutet have now shown that a previously unknown gene, Wrap53, controls the
activity of p53. As the regulation mechanism is relatively unexplored, the study opens up
new routes to solving the mystery of cancer.The p53 gene makes sure that cells with
damaged DNA either repair themselves or commit suicide. If p53 itself is damaged, which is
the case in roughly half of all cancer tumours, cells that are on their way to becoming
cancerous are allowed to survive. Much cancer research revolves around the cell processes
that p53 induces. A group of researchers at Karolinska Institutet have now identified a
new gene, called Wrap53, that regulates the activity of p53. The study, which is published
in the journal Molecular Cell, demonstrates that Wrap53 gives rise to a molecule, called
antisense RNA, the presence of which is necessary for the production of sufficient
quantities of p53 protein in the event of DNA damage. According to Marianne Farnebo, one
of the scientists involved in the study, the results indicate that damage to Wrap53 can
indirectly cause cancer. Wrap53 is therefore a new potential target for future cancer
therapies.
Prehistoric global cooling caused
by CO2, research finds
Ice in Antarctica suddenly appeared —
in geologic terms — about 35 million years ago. For the previous 100 million years
the continent had been essentially ice-free. The question for science has been, why? What
triggered glaciers to form at the South Pole? Matthew Huber, assistant professor of earth
and atmospheric sciences at Purdue University, says no evidence of global cooling during
the period had been found.
"Previous evidence points paradoxically to a stable climate at the same time this
event, one of the biggest climate events in Earth's history, was happening," Huber
says. However, in a paper published this week in the journal Science, a team of
researchers found evidence of widespread cooling. Additional computer modeling of the
cooling suggests that the cooling was caused by a reduction of greenhouse gases in the
atmosphere.
Researchers identify ALS gene
mutation
Research that has discovered a new gene
whose mutations cause 5 percent of inherited cases of ALS (amyotrophic lateral sclerosis)
is part of a national study led by the Northwestern University Feinberg School of
Medicine. The study reported in Science today (Feb. 27) points to a common cellular
deficiency in the fatal neurological disorder, said Teepu Siddique, M.D., Les Turner ALS
Foundation/Herbert C. Wenske Foundation Professor in the Davee Department of Neurology and
Clinical Neurosciences and Department of Cell and Molecular Biology and Director of the
Division of Neuromuscular Medicine at the Feinberg School.
The new research is part of a national collaboration directed by Siddique, the principal
investigator for the "Genetics of ALS" project funded at Feinberg by the
National Institutes of Health. Earlier research by Siddique and colleagues extended the
genetic knowledge of familial (inherited) ALS by identifying the first and second ALS
genes (the SOD1 gene in 1993 and the ALSIN gene in 2001), in addition to identifying loci
on chromosomes 9, 15, 16, and X. The study published today discovered aFUS/TLS gene
mutations in ALS families collected through efforts of the NIH-funded multi-center project
and included among others a large Italian family previously studied by Siddique and
Cortelli.
U of I study shows benefits of
hormone found in fat tissue
It's called the obesity paradox. Although
obese people are more apt to suffer from inflammatory diseases, such as diabetes, heart
disease, and stroke, they are also more likely to survive a major attack caused by one of
those conditions. University of Illinois scientists Gregory Freund and Christina Sherry
shed light on the reasons for this phenomenon in a study in this month's issue of
Endocrinology. "Fat is a very complex and active tissue—it has important
functions beyond providing energy and insulating us from the cold," said Freund, a
professor in the U of I College of Medicine's Department of Pathology and a faculty member
in the U of I Division of Nutritional Sciences. "We now know that leptin, a hormone
secreted by fat tissue, plays a key role in regulating the immune system. When we exposed
mice to hypoxia (simulating an event, such as a heart attack, in which a part of the body
is deprived of oxygen), leptin triggered the immune system to increase production of an
anti-inflammatory molecule, interleukin-1 receptor antagonist (IL-1RA)," he said.
"And, when we gave non-obese mice leptin injections, they recovered three times
faster. Leptin did not hasten recovery though in IL-1RA knockout mice," Sherry said.
That earlier work was published in a recent issue of Brain, Behavior, and Immunity.
Daytime sleepiness provides red
flag for cardiovascular disease
Clinicians should be alert to patients
reporting "excessive" day time sleepiness (EDS), says the European Society of
Cardiology, after a French study found healthy elderly people who regularly report feeling
sleepy during the day have a significantly higher risk of dying from cardiovascular
disease. The Three City study, published in Stroke, by the American Heart Association
(Thursday, February 26), found that elderly people who reported excessive day time
sleepiness have a 49 % relative risk increase of cardiovascular death (from
cerebrovascular disease, myocardial infarction and heart failure) , compared to those who
do not report sleepiness."Based on this study asking patients the simple question of
whether they feel sleepy during the day, is a useful way of identifying a subgroup of
elderly patients at higher risk of cardiovascular disease who require a more thorough
follow up," said Professor Guy DeBacker, from the Division of Cardiology at the
University of Gent, Belgium, and former chair of the European Society of Cardiology Joint
Prevention Committee.Professor Torben Jorgensen, from the Research Centre for Prevention
and Health, Glostrup, Denmark, commented: "The study offers the opportunity to
practice prevention by investigating the underlying causes of patient's sleep problems,
and then introducing lifestyle changes with the intention of preventing later
cardiovascular complications." The Three City study represents the largest yet
investigation exploring the prospective association between EDS and mortality in the
community dwelling elderly, and the only study yet to have been conducted in Europe –
all the other studies were undertaken in North America. Criticisms of the study include a
low responder rate (37%) that could introduce an element of bias, and the fact that it
lacked objective measures of day time sleepiness (such as polysomnography readings),
instead using self reported patient responses.
Muscular dystrophy mystery solved;
Mizzou scientist moves closer to MD solution
Muscular dystrophy, which affects
approximately 250,000 people in the United States, occurs when damaged muscle tissue is
replaced with fibrous, bony or fatty tissue and loses function. While scientists have
identified one protein, dystrophin, as an important piece to curing the disease, another
part of the mystery has eluded scientists for the past 14 years. Now, one University of
Missouri scientist and his team have identified the location of the genetic material
responsible for a molecular compound that is vital to curing the disease. Duchenne
muscular dystrophy (DMD), predominantly affecting males, is the most common type of
muscular dystrophy. Patients with Duchenne muscular dystrophy have a gene mutation that
disrupts the production of dystrophin. Absence of dystrophin starts a chain reaction that
eventually leads to muscle cell degeneration and death. A previous study by Dongsheng
Duan, associate professor of molecular microbiology and immunology, discovered a potential
delivery method to replace the mutated genes with healthy genes. Following the replacement
of these genes, Duan observed that dystrophin production was restarted in animals with
muscular dystrophy. However, while dystrophin is vital for muscle development, the protein
also needs several "helpers" to maintain the muscle tissue. One of these
"helper" molecular compounds is nNOS, which produces nitric oxide. This is
important for muscles that are in use during high intensity movements, such as exercise.
"When you exercise, not only does the muscle contract, but the blood vessels are
constricted," Duan said. "nNOS is important because it produces nitric oxide
that relaxes the blood vessels, helping to maintain the muscle with a healthy blood
supply. If no blood reaches the muscle cells, they will eventually die. In DMD patients,
this means the disease will progress as the muscle cells are replaced by the fibrous, bony
or fatty tissue."
How yeast is helping us to
understand Parkinson's Disease
Teams of scientists from Australia and the
United States have used yeast and mammalian cells to discover a connection between genetic
and environmental causes of Parkinson's disease. Yeasts are single cell organisms, used
widely in biological research because their structure resembles that of cells found in
animals and humans. Yeasts share many genes, or their functional equivalents, with humans
and offer the ability to screen or test thousands of genes and analysing their effects.
Two genes (alpha-synuclein and PARK9) had separately been associated with forms of
Parkinson's disease, while manganese poisoning can cause PD-like symptoms in miners and
welders exposed to high manganese levels. Findings connecting alpha-synuclein, PARK9 and
sensitivity to manganese, made possible by yeast research, have been published online in
the February issue of the prestigious international journal, Nature Genetics. "This
is the first time that we've been able to connect three pieces of the Parkinson's disease
jigsaw puzzle and it tells us we're on the right track to understanding what goes wrong in
this disease" said Dr Antony Cooper from Sydney's Garvan Institute of Medical
Research and head of the project group in Australia. Parkinson's disease involves the
degeneration of neurons that produce the neurotransmitter dopamine. Autopsies show an
abundance of the small protein alpha-synuclein in affected regions of the brain, so
scientists have known for some time that over-expression of the protein is toxic. When a
European group discovered PARK9's involvement in an inherited form of Parkinson's disease
they examined some of the surviving neurons from patients who had 'sporadic' Parkinson's,
as opposed to inherited forms of the disease, and found they contained ten times the
levels of PARK9 when compared with similar parts of the brain in patients without the
disease.
"Its possible that the surviving neurons remained functional, unlike the degenerated
neurons surrounding them, because high levels of PARK9 protected them in some way,"
said Cooper. "Little was known of PARK9's function but as yeast contains an
equivalent gene, we were able to analyse its function."
Health campaigns that promote
exercise may cause people to eat more
New research from the University of
Illinois suggests that weight-loss campaigns that promote exercise may actually cause
people to eat more. People who viewed posters suggesting that they "join a gym"
or "take a walk" ate more food after looking at the posters than people who saw
similarly designed posters prompting them to "make friends" or "be in a
group," the researchers found. Subliminal words about being active had a similar
effect on study participants, said psychology professor Dolores Albarracín, who led the
research. "Viewers of the exercise messages ate significantly more (than their peers,
who viewed other types of messages)," she said. "They ate one-third more when
exposed to the exercise ads." Those exposed to subliminal words about activity during
a computer task ate about 20 percent more than those exposed to neutral words, she said.
The study, which appears in the journal Obesity, builds on previous research by
Albarracín that suggests that general messages to be active can prompt people to behave
in a variety of ways, some of which may have negative consequences.
Discovery provides hope for
sufferers of disfiguring bone disease
Researchers at the University of East
Anglia (UEA) have made a major genetic discovery that could lead to the effective
treatment for sufferers of craniosynostosis - a severe childhood bone disease.
Craniosynostosis develops in the womb and affects one in every 2500 live births. Bones in
the skulls and face of sufferers fuse together prematurely causing a range of distressing
developmental problems. Some of the affected children also suffer from defects in the
limbs, brain, kidneys and lungs. Depending on the severity of their disease and its
underlying cause, children suffering with craniosynostosis survive from as little as a few
days to as long as early adulthood.
Cologne Scientists find Relevance
of genetic Elicitor for Obesity
Obesity has become an epidemic in many
parts of the western hemisphere; over 30 % of the population of Germany are overweight.
Scientists from the University of Cologne, in cooperation with scientists from the
University of Düsseldorf, have been able to verify the relevance of a certain gene with
regard to obesity for the first time. The results of this work have been published in the
international journal of science, Nature. In 2006, scientists discovered increased amounts
of variations of the FTO genes were in overweight people. However, the relevance of this
gene and its regular function remained unclear for a long time. The team working for Prof.
Dr. Jens Brüning, coordinator of the Cluster of Excellence "Cellular Stress
Responses in Aging-Associated Diseases", CECAD Cologne, and Prof. Dr. Ulrich Rüther,
University of Düsseldorf, have now been able to show that mice which do not have FTO
gene, do not become overweight and burn more energy. These findings verify the importance
of the FTO gene for the regulation of body weight. The results of this research will
become very important for the development of new ways of treating obesity
Transport Protein for Vitamin B12
has been identified
Professor Dr. Peter Nürnberg of the
Cologne Center for Genomics (CCG) at the University Cologne and a team of international
researchers have been successful in identifying the cause of the rare genetic disease
CblF. The cause of this disease is a vitamin B12 deficiency (cobalamin-deficiency) caused
by a genetic disorder. Vitamin B12 is important for cell division and haematopoiesis as
well as for a functional nervous system. The body is not able to produce this vitamin
itself and therefore takes it from meat and dairy products. What scientist have always
known is that the vitamin is absorbed by small organelles called lysosomes on its way into
the cell where it is then used. However, the manner in which these organelles entered the
cells has now been discovered. Working with Dr. Frank Rutsch from the paediatric clinic of
the University Hospital of Münster, Prof. Dr. Peter Nürnberg established an
international research team comprising paediatricians, geneticists and biologists from
Germany France Canada and Switzerland. These scientists examined 12 patients suffering
from the rare genetic disorder CblF and were able to identify an infinitesimal segment in
the genetic information which was identical in almost all of the patients and which
featured a defect in a certain gene. From this the team concluded that these patients,
although from different countries, were in fact distantly related and shared a common
ancestor going back eight or max. nine generations, who passed down the defective genetic
information to them. People with one defective chromosome are completely healthy: it is
only when two carriers of this defective chromosome have children that the disease occurs
in the children of the carriers.
