Contents:
New Method to Prevent Heart Attacks

New Method to Prevent Heart
Attacks
Wednesday, March 17, 2010
Cardiovascular disease is by
far the absolute most common national disease in Sweden and a little more than
26,000 people are treated every year at hospitals due to acute cardiac
infarction, according to the Heart and Lung Foundation. KTH researcher Matilda
Larsson at the School of technology and health at KTH has recently defended her
thesis and her research aims at developing methods which can as early as
possible assess the risk of cardiovascular disease.
The earlier the risk of cardiovascular disease
can be identified, the easier it will be to avoid acute cardiac infarction which
will save lives. But even if research and health care has been improved
considerably over the past few years, cardiovascular disease even in the future
will be one of the most common reasons for sickness and mortality in Sweden.
That is why Matilda Larsson's research is, to say the least, of vital
importance.
"One of the problems that we face today is
that the methods used for risk assessment are new, and they need to be
fine-tuned. The people that use the technology that is available must have
considerable experience in being able to interpret the data they receive," says
Matilda Larsson.
To rectify this problem, Matilda Larsson has
developed the existing ultrasound technology so that the information is more
easily accessible.
"By visualising the data, the doctor will find
it easier to interpret the results," says Matilda Larsson.
The usual method is that the doctor measures
the heart's blood flow and how the cardiac valves operate. With the Speckle
tracking method, Matilda Larsson and her colleagues study how the ultrasound
image's greyscale pattern changes, and she can also measure the movement
patterns and deformation of the heart and the vascular tissue.
"The long-term objective is to have access to
a sensitive method which can predict myocardial infarction at an early stage,"
says Matilda Larsson.
Her thesis is called "Quantification and visualisation
of cardiovascular function using ultrasound" and she has applied for a patent
for a method used within this area.
Matilda Larsson originally comes from
Ostervala between Gavle and Uppsala, but she will not be returning there for
quite some time.
"Now I will continue as a post doctoral
student at the university in Leuven, Belgium, where I conducted some of my
thesis work. We will study movements and deformation of the carotis," says
Matilda.
Image
Caption: Matilda Larsson, in the background you can see her research in the form
of a state of the heart diagram. This method provides a picture as to how the
heart works during an entire cardiac cycle.
Image Credit:
KTH Royal Institute of Technology
Source:
KTH
Permalink: http://www.sflorg.com/comm_center/unv_medical/p1012_244.html
Time Stamp:
3/17/2010 at 3:12:23 PM UTC
Fruit flies and test tubes open new window on Alzheimer's disease

Fruit flies and test tubes open new
window on Alzheimer's disease
Tuesday, March 16, 2010
A team of scientists from Cambridge
and Sweden have discovered a molecule that can prevent a toxic protein involved
Alzheimer's disease from building up in the brain. They found that in test tube
studies the molecule not only prevents the protein from forming clumps but can
also reverse this process. Then, using fruit flies with Alzheimer's disease,
they showed that the same molecule effectively "cures" the insects of the
disease.
Alzheimer's disease is the most common
neurodegenerative disorder and is linked to the misfolding and aggregation of a
small protein known as the amyloid β (Aβ) peptide. Previous studies in animal
models have shown that aggregation of Aβ damages neurones (brain cells) causing
memory impairment and cognitive deficits similar to those seen in patients with
Alzheimer's disease. The mechanisms underlying this damage are, however, still
not understood.
The new molecule - designed by scientists in
Sweden - is a small protein known as an Affibody (an engineered binding
protein). In this new study, researchers at the University of Cambridge and the
Swedish University of Agricultural Sciences found that in test-tube experiments
this protein binds to the Aβ peptide, preventing it from forming clumps and
breaking up any clumps already present.
In a second experiment, they studied the
effect of this Affibody in a Drosophila (fruit fly) model of Alzheimer's disease
previously developed at Cambridge.
Working with fruit flies that develop the fly
equivalent of Alzheimer's because they have been genetically engineered to
produce the Aβ protein, they crossed these flies with a second line of flies
genetically engineered to produce the Affibody.
They found that offspring - despite producing
the Aβ protein - did not develop the symptoms of Alzheimer's disease.
According to lead author Dr Leila Luheshi of
the Department of Genetics at University of Cambridge: "When we examined these
flies we found that the Affibody not only prevented and reversed the formation
of Aβ clumps, it also promoted clearance of the toxic Aβ clumps from the flies'
brains."
"Finding a way of preventing these clumps from
forming in the brain, and being able to get rid of them, is a promising strategy
for preventing Alzheimer's disease. Affibody proteins give us a window into the
Alzheimer's brain: by helping us understand how these clumps damage brain cells,
they should help us unravel the Alzheimer's disease process."
According to Professor Torleif Hard of the
Swedish University of Agricultural Sciences and one of the senior authors of the
study: "Our work shows that protein engineering could open up new possibilities
in Alzheimer's therapy development."
Source: University of Cambridge
Permalink: http://www.sflorg.com/comm_center/unv_science/p1011_260.html
Time Stamp: 3/16/2010 at 4:45:31 PM
UTC
Researchers Identify Gene that May Play Role in Atherosclerosis

Researchers Identify Gene that May Play
Role in Atherosclerosis
Monday, March 15, 2010
To understand the role
of inflammation in cardiovascular and other diseases, it is essential to
identify and characterize genes that induce an inflammatory response in the body
-- and the genes that regulate them.
A study published online this week in the
journal Proceedings of the National Academy of Sciences suggests that a
gene called Hu antigen R (HuR) plays a critical role in inducing and mediating
an inflammatory response in cells experiencing mechanical and chemical stresses.
The study was supported by the National Institutes of Health.
The findings may open up new possibilities for
developing treatments of metabolic diseases associated with inflammation, such
as atherosclerosis. Atherosclerosis typically occurs in branched or curved
regions of arteries where plaques form because of cholesterol build-up.
Inflammation can alter the structure of plaques so that they become more likely
to rupture, causing a blood vessel blockage and leading to heart attack or
stroke.
"This is the first systematic study showing
that HuR not only responds to external stimuli as a stress-sensitive gene, but
it also regulates other stress-sensitive genes," said senior author Gang Bao,
the Robert A. Milton Chair in Biomedical Engineering in the Wallace H. Coulter
Department of Biomedical Engineering at Georgia Tech and Emory
University.
The study results show that HuR promotes the expression of
genes that support atherosclerosis and inhibits the expression of genes that
combat atherosclerosis.
"We found that suppressing expression of HuR
inhibited the inflammatory response of cells, which shows that designing drugs
that block HuR function may reduce the risk of plaques rupturing," explained
Bao.
Bao guided Won Jong Rhee, a former
postdoctoral fellow in his laboratory, to conduct a series of experiments
investigating the biology, behavior and pathways of HuR.
The researchers first studied how the HuR gene
responds to different flow environments and chemical treatments. They exposed
human umbilical vein endothelial cells to disturbed flow -- which occurs in
artery regions where plaques form -- and found that the cells expressed higher
levels of HuR than when they experienced a static or laminar flow environment.
This finding was validated in tissue experiments with results showing increased
amounts of HuR in regions of a mouse aorta that were exposed to disturbed
flow.
Then the researchers treated endothelial cells
with statins, medications used to treat atherosclerosis by reducing the number
of cholesterol-containing low-density lipoprotein (LDL) molecules in the blood
and inhibiting inflammation. The results indicated a decreased level of HuR with
statin treatment.
After establishing HuR as a stress-sensitive
gene regulated by external stimuli, including flow and statin treatment, the
researchers conducted experiments to determine whether HuR regulates the
expression of other stress-sensitive genes. They found that reducing the level
of HuR in cells increased the levels of two genes that combat atherosclerosis --
Kruppel-like factor 2 (Klf2) and endothelial nitric oxide synthase (eNOS). The
reduction in HuR also decreased the expression of bone morphogenic protein-4
(BMP-4), a gene that supports atherosclerosis.
Reducing the level of HuR in cells also
significantly inhibited many inflammatory responses of the endothelial cells,
including the expression of two potential atherosclerosis drug targets:
inter-cellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion
molecule-1 (VCAM-1).
Though this study showed that HuR plays a
critical role in inducing and mediating an inflammatory response in cells
subjected to a stressful environment, the underlying mechanism for this
regulation is still not known.
"HuR protein often binds to messenger RNAs to
increase their stability and translation, but we found that regulation of other
stress-sensitive genes by HuR was not due to changes in mRNA stability by direct
protein binding," explained Bao.
To uncover the pathways that lead to HuR's
stress sensitivity, the researchers conducted a series of studies to reveal that
HuR functions by adding a phosphate group to the transcriptional factor nuclear
factor kappa B (NFkB) and its inhibitor IkBa. Additional research is underway to
reveal what mRNAs HuR binds to and the mechanisms used to respond to mechanical
and chemical stresses. Identifying the triggers for inflammation and unraveling
the details of inflammatory pathways may eventually furnish new therapeutic
targets.
Hanjoong Jo, the Coulter Department's Ada Lee
and Pete Correll Professor in Biomedical Engineering, Kyunghwa Chang, graduate
student Chih-Wen Ni and research scientist Zhilan Zheng also contributed to this
research.
Image
Caption: Images showing reduced levels of HuR (red) in the thoracic aorta and an
area with greater curvature, compared to a region with less curvature, which is
prone to atherosclerosis because endothelial cells (blue) are exposed to
disturbed flow there.
Image Credit:
Georgia Tech/Gang Bao
Source:
Georgia Institute of Technology
Permalink: http://www.sflorg.com/comm_center/unv_medical/p1010_243.html
Time Stamp:
3/15/2010 at 7:23:49 PM UTC
Scientists Demonstrate Mammalian Regeneration Through a Single Gene Deletion

Under
Embargo Till: 19:00 UTC March 15, 2010
Posted: 19:00 UTC 03/15/2010
Scientists Demonstrate Mammalian
Regeneration Through a Single Gene Deletion
Monday, March 15, 2010
A quest that began over a decade
ago with a chance observation has reached a milestone: the identification of a
gene that may regulate regeneration in mammals. The absence of this single gene,
called p21, confers a healing potential in mice long thought to have been lost
through evolution and reserved for creatures like flatworms, sponges, and some
species of salamander. In a report published today in the Proceedings of the
National Academy of Sciences, researchers from The Wistar Institute
demonstrate that mice that lack the p21 gene gain the ability to regenerate lost
or damaged tissue.
Unlike typical mammals, which heal wounds by
forming a scar, these mice begin by forming a blastema, a structure associated
with rapid cell growth and de-differentiation as seen in amphibians. According
to the Wistar researchers, the loss of p21 causes the cells of these mice to
behave more like embryonic stem cells than adult mammalian cells, and their
findings provide solid evidence to link tissue regeneration to the control of
cell division.
"Much like a newt that has lost a limb, these
mice will replace missing or damaged tissue with healthy tissue that lacks any
sign of scarring," said the project's lead scientist Ellen Heber-Katz, Ph.D., a
professor in Wistar's Molecular and Cellular Oncogenesis program. "While we are
just beginning to understand the repercussions of these findings, perhaps, one
day we'll be able to accelerate healing in humans by temporarily inactivating
the p21 gene."
Heber-Katz and her colleagues used a p21
knockout mouse to help solve a mystery first encountered in 1996 regarding
another mouse strain in her laboratory. MRL mice, which were being tested in an
autoimmunity experiment, had holes pierced in their ears to create a commonly
used life-long identification marker. A few weeks later, investigators
discovered that the earholes had closed without a trace. While the experiment
was ruined, it left the researchers with a new question: Was the MRL mouse a
window into mammalian regeneration?
The discovery set the Heber-Katz laboratory
off on two parallel paths. Working with geneticists Elizabeth Blankenhorn,
Ph.D., at Drexel University, and James Cheverud, Ph.D., at Washington
University, the laboratory focused on mapping the critical genes that turn MRL
mice into healers.
Meanwhile, cellular studies ongoing at Wistar
revealed that MRL cells behaved very differently than cells from "non-healer"
mouse strains in culture. Khamilia Bedebaeva, M.D., Ph.D., having studied
genetic effects following the Chernobyl reactor radiation accident, noticed
immediately that these cells were atypical, showing profound differences in cell
cycle characteristics and DNA damage. This led Andrew Snyder, Ph.D., to explore
the DNA damage pathway and its effects on cell cycle control.
Snyder found that p21, a cell cycle regulator,
was consistently inactive in cells from the MRL mouse ear. P21 expression is
tightly controlled by the tumor suppressor p53, another regulator of cell
division and a known factor in many forms of cancer. The ultimate experiment was
to show that a mouse lacking p21 would demonstrate a regenerative response
similar to that seen in the MRL mouse. And this indeed was the case. As it
turned out, p21 knockout mice had already been created, were readily available,
and widely used in many studies. What had not been noted was that these mice
could heal their ears.
"In normal cells, p21 acts like a brake to
block cell cycle progression in the event of DNA damage, preventing the cells
from dividing and potentially becoming cancerous," Heber-Katz said. "In these
mice without p21, we do see the expected increase in DNA damage, but
surprisingly no increase in cancer has been reported."
In fact, the researchers saw an increase in
apoptosis in MRL mice -- also known as programmed cell death -- the
cell's self-destruct mechanism that is often switched on when DNA has been
damaged. According to Heber-Katz, this is exactly the sort of behavior seen in
naturally regenerative creatures.
"The combined effects of an increase in highly
regenerative cells and apoptosis may allow the cells of these organisms to
divide rapidly without going out of control and becoming cancerous," Heber-Katz
said. "In fact, it is similar to what is seen in mammalian embryos, where p21
also happens to be inactive after DNA damage. The down regulation of p21
promotes the induced pluripotent state in mammalian cells, highlighting a
correlation between stem cells, tissue regeneration, and the cell
cycle."
The study was supported by grants from the
Harold G. and Leila Y. Mathers Foundation, the F.M. Kirby Foundation, the W.W.
Smith Foundation, the National Institute for General Medical Sciences and
National Cancer Institute.
Study investigators also include Wistar
researchers Paul M. Lieberman, Ph.D.; Dmitri Gourevitch M.D.; Lise Clark D.V.M.,
Ph.D.; Xiang-Ming Zhang; and John Leferovich. Snyder, formerly of the Lieberman
laboratory at Wistar, and Bedebaeva are co-first authors on this paper. James
Cheverud of Washington University is also a co-author on this paper.
The Wistar Institute is an international
leader in biomedical research with special expertise in cancer research and
vaccine development. Founded in 1892 as the first independent nonprofit
biomedical research institute in the country, Wistar has long held the
prestigious Cancer Center designation from the National Cancer Institute. The
Institute works actively to ensure that research advances move from the
laboratory to the clinic as quickly as possible.
Source:
Wistar Institute
Permalink: http://www.sflorg.com/comm_center/science/p1009_29.html
Time Stamp: 3/15/2010 at 19:00:00
UTC
Developing Weed Resistance in Corn Hybrids

Developing Weed Resistance in Corn
Hybrids
Monday, March 15, 2010
Millions of people in the savannas
of west and central Africa rely on maize (corn) as a staple crop, and as an
"insurance" food crop at the beginning of the rainy season. A destructive
parasitic weed, Striga hermonthica, poses a threat to this valuable crop.
Almost 64% of cropland in this area of Africa is affected by the parasite, which
causes an average grain yield loss of 68%. Farmers in Striga-infested areas have
not yet adopted Striga-resistant hybrids.
Scientists at the International Institute of
Tropical Agriculture (IITA) in partnership with scientists in the University of
Ibadan in Nigeria and the National Institute of Agricultural Research in Benin
Republic investigated the relationship between the genetic diversity of maize
inbred lines having different levels of resistance to Striga and the performance
of their hybrids under parasite infestation. The results are reported in the
March-April 2010 edition of
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