Research Focus 2006:
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The Southwest Association for
Education in Biomedical Research members and other
researchers are continually furthering research. This section
will be to highlight ongoing research. |
Antihistamines Attack Asthma
Recent research with mice has
shown a link between airway infections and allergies such as asthma.
Both are associated with inflammation caused by the release of
histamines. Histamine is produced by so-called mast cells in the upper
airways in response to infection. The researchers tested whether
inflammation of the airways is caused by the release of histamine by
exposing normal mice to a common respiratory infection. A second group
of mice that had been genetically modified to produce no mast cells were
also exposed to infection. The scientists reasoned that the normal mice
would develop pneumonia but that the GM mice would not, because the
absence of mast cells would prevent inflammation. In reality, the GM
mice also showed signs of inflammation and developed pneumonia. The
scientists realized that a different set of cells (neutrophils) located
in the lung also produced histamine and caused inflammation.
Administering antihistamines to the GM mice reduced both the level of
inflammation and the severity of pneumonia. The study shows how
important histamines are in airway infections and associated diseases.
Those with airway infections and allergies, including asthma, might
respond well to antihistamine treatment.- Journal of Experimental
Medicine, DOI: 10.1084/jem.20061232, 11 December 2006
Fatty Acids Fight Infection
How immune cells 'decide' to
become active or inactive may be used to fight cancerous tumors,
autoimmune diseases, and organ transplant rejection. T-cells are part of
the immune system that recognize invaders in the body, such as viruses,
bacteria, tumor cells, or allergens. Normally, T-cells are activated by
a complex series of signals that end with the destruction of the foreign
substance. However, sometimes T-cells are inactivated, so that immune
cells dont attack themselves and other normal body cells and proteins.
Using genetically modified mice, researchers found that small fatty
acids called diacylglycerols (DAGs) are critical for T-cell activation.
When DAGs are chemically modified by enzymes T-cells become 'tolerant'
or inactive. But without the enzymes, the T-cells of the mice were
hyperreactive to foreign antigens (this can cause dangerous
inflammation), and were not 'tolerant' to the mice's cells. The
mechanism of activation/ inactivation could have therapeutic benefits.
If the hyperreactive state could be controlled, some T cells might be
able to eliminate tumors; and promoting the 'tolerant' state could
benefit those with autoimmune disease, or help prevent rejection of
transplants.- Nature Immunology DOI: 10.1038/ni1400, November 2006
Metabolic Treatment for
Epilepsy?
A new way of suppressing
epileptic seizures in rats using glycolysis inhibitors may lead to
needed new epilepsy treatments. Epilepsy affects 1% of people worldwide
but available drugs fail to control seizures in about one-third of
patients. Patients with temporal lobe epilepsy (a common form of
drug-resistant epilepsy) may have severe seizures, which are sometimes
improved by a diet that completely avoids all carbohydrates. This diet
inhibits glycolysis, the process by which carbohydrates are broken down.
Using this human-based knowledge, the scientists treated epileptic rats
with an inhibitor of glycolysis and saw a dramatic reduction in the
number and severity of seizures in the animals. The researchers suspect
that one of the glycolysis end products might increase nerve cell
excitability; inhibiting glycolysis would therefore reduce nerve cell
excitability and the likelihood of seizures. They found that one product
of glycolysis, NADH, increases the expression of certain
pro-excitability genes in nerve cells and inhibiting glycolysis reduced
the expression of these genes. - Nature Neuroscience DOI:
10.1038/nn1791, November 2006
Tumor Gene Has Autism Risk
A gene, MET, known for
its role in secondary cancers, seems to double a person's risk for
autism, according to a new study in mice. MET is expressed in the
brain during fetal development and may have a role in learning and
memory. It is also involved with immune function and gut repair; all of
this is consistent with medical complications in some children with
autism. When the mice had a particular MET gene variant, they
developed social anxiety and seizures, features commonly associated with
autism. These findings seem to apply to autism in people as the
researchers found that this variant was strongly linked with autism
the risk of autism doubled in individuals with two copies. This is not
the first gene linked to autism, but genetic studies have been hard to
replicate. This study represents the largest number of patients tested
(743 families were involved) and could prove the strongest genetic link
to date. Families with more than one child with autism showed the
strongest allelic association. This gene variant seems to confer a
susceptibility to autism it is not the sole determining factor. -
Proceedings of the National Academy of Sciences, early edition DOI:
10.1073/pnas.0605296103, 19 October 2006
Fixing Broken Hearts
Mammalian cardiomyocytes (heart
muscle cells) have limited ability to multiply, and cannot repair the
heart when it is damaged by a heart attack. The resulting scarring of
the connective tissue can impair the heart's ability to pump blood or
cause dangerous fluctuations in the normal heartbeat. Researchers found
that they could trigger re-growth in the damaged areas of the rats'
hearts by injecting two proteins naturally produced by the body. One
promotes the formation of new blood vessels (angiogenesis), and the
other promotes cell division. After MI induction in young rats, they
were given a four-week course of the two proteins. This treatment
resulted in reduced scarring and wall thinning, with noticeably improved
cardiac function. In contrast, the protein that promotes cell division,
given alone, did not rescue heart function even though there was
increased production of heart muscle cells. The two proteins may form
the basis of a new treatment to help humans hearts heal after a heart
attack. - Proceedings of the National Academy of Sciences DOI:
10.1073/pnas.0607382103, 17 October 2006
Grapes for the Sick
Scientists have found that a
chemical in grape juice can block colorectal tumor growth in mice.
Rroanthocyanidins, found in grape seed extract (GSE), are a class of
antioxidant flavonoids that remove harmful free oxygen radicals from
cells and are known to have anti-cancer effects in other types of tumor.
Human colorectal tumors were grafted into nude mice (these have a
deficient immune system, so do not reject grafts), and the mice were fed
GSE five days per week, for 8 weeks. The GSE not only inhibited tumor
growth without any toxicity, but the tumors shrank to almost half their
size. The study also established the molecular mechanism of cancer
growth inhibition by GSE. In tumor cells, the availability of a critical
protein called Cip1/p21 is enhanced by the GSE. This successfully
arrests the cell cycle and usually leads the cancer cell to
self-destruction. Further work is needed to determine the optimum dose
and investigate any potential side-effects. - Clinical Cancer Research,
15 October 2006
Prozac Builds Bones?
People on antidepressants might
have something to feel good about stronger bones. New research shows
that newer types of antidepressants called SSRIs build bone density in
mice. But SSRIs can interfere with the cellular machinery that helps
build and break down bone, although the net effect on overall bone
density has remained unclear. To gauge the impact of SSRIs on the bone,
researchers injected adult mice daily for 6 weeks with the SSRI
fluoxetine at doses approximating what people would take. Then they
measured the density of the femur and a spinal bone. Treated mice had
about 60% more spongy bone, the part most affected by bone loss, than
control animals. However, fluoxetine-treated mice were not protected
against bone loss after removal of their ovaries, suggesting that its
effect requires the presence of oestrogen. Experts hope further studies
will reveal the genetic underpinnings of the drug's influence, and lead
to better treatment plans. - Journal of Cellular Biochemistry, Early
View DOI: 10.1002/jcb.21131, 13 October 2006
Cancer Cell
Executioner
A drug, PAC-1, which exploits
cells' own suicide mechanism, has specifically targeted both lung and
kidney human cancer cells in mice without harming healthy tissue. The
researchers hope that the drug may offer tailored treatments for cancer
patients. PAC-1 converts a dormant protein called procaspase-3 into its
active form, an 'executioner' protein called caspase-3, which is the
final and decisive step in the signaling pathway by which abnormal cells
self-destruct. The treatment works because procaspase-3 is often more
abundant in cancer cells than in healthy cells. In tissue from 23 colon
cancer patients the scientists found that, on average, levels of
procaspase-3 are eightfold higher than in healthy cells sometimes as
much as 20-fold higher. The researchers gave the drug to mice with human
lung and kidney cancers, which contain about five times more
procaspase-3 than healthy cells. After two months of treatment, the
tumors were greatly reduced, whilst the mice that did not receive the
drug had excessive tumor spread. The treatment worked when the drug was
given orally, suggesting it could work as a pill and so be easy to
administer. Another major benefit is that patients can be screened
before treatment to check if they are eligible; if they have a big
disparity in procaspase-3 levels between cancerous and healthy tissue,
PAC-1 could be effective at quite low doses without harming healthy
tissue. - Nature Chemical Biology DOI: 10.1038/nchembio814, 1 October
2006
Monkey See, Monkey Sort
Using rhesus monkeys,
researchers have identified brain cells that seem to be involved in
categorization, the process by which the brain assigns meaning to
sensory stimuli. Through experience, we learn to group stimuli into
categories, such as 'chair', 'table' and 'vehicle', which are critical
for rapidly and appropriately selecting behavioral responses. Much is
known about the neural representation of simple visual stimulus features
(for example, orientation, direction and color), but relatively little
is known about the brain's 'sorting' process of categorization. The
scientists trained the monkeys to divide dots moving on a screen into
two categories, depending on their direction of movement. They were then
retrained to group the same stimuli into two new categories. Neuronal
activity was monitored in two interconnected brain regions known to be
involved in processing visual motion; the lateral intraparietal (LIP)
and middle temporal (MT) areas. The researchers found the activity of
neurons in the LIP known to be involved in visuo-spatial attention,
motor planning, and decision-making determined directions of motion
according to category membership. When the monkeys were retrained, the
activity of neurons in the LIP changed to reflect the new rule. However,
neurons in the MT area were strongly direction selective but carried
little, if any, category information. This discovery suggests neurons in
the LIP play an important part in the process of transforming visual
information into representative forms that allow us to attach abstract
meaning to stimuli. - Nature DOI: 10.1038/nature05078, 7 September 2006
IL-27 Holds Back Immune
System
A cytokine messenger protein
called interleukin-27 (IL-27) inhibits the immune system cells
responsible for chronic inflammatory diseases where the immune system
becomes over stimulated and attacks healthy tissue such as
encephalitis, arthritis, Crohns disease, lupus and even sepsis. To
understand the role of IL-27 in chronic inflammation the scientists
studied mice with the IL-27 receptor knocked out. When infected with the
parasite Toxoplasma gondii the mice developed severe brain inflammation
that was caused by helper T cells, a type of white blood cell that
activates and directs portions of the immune system. Without the ability
of IL-27 to help regulate the immune system, the helper T cell response
to the brain infection went out of control. There are many
immune-mediated diseases with many different causes, but the cell type
that IL-27 inhibits is a major part of the pathway of cellular signals
that lead to inflammation. This means IL-27 may be a useful target for
treating a number of autoimmune diseases: restoring or augmenting the
abilities of IL-27 may be enough to help keep the overactive immune
system under control and halt inflammation. - Nature Immunology DOI:
10.1038/ni1376, September 2006
Too Much of a Good Thing
A study in mice has shown for
the first time that getting rid of 'poisonous' RNA in muscle cells can
reverse myotonic muscular dystrophy (MMD), the most common type of
muscular dystrophy in adults. MMD occurs when there is a fault in the
gene DMPK, and can cause a slow, progressive wasting of the
muscles, irregular heartbeat, cataracts and insulin resistance. The
researchers engineered a new type of mouse model where (normal) DMPK
could be 'switched on' by adding doxycycline, an antibiotic, to the
mice's drinking water. When DMPK was over-expressed, the high
levels of RNA were toxic: the mice developed the hallmarks of type 1 MMD
within a few weeks, including an inability to relax muscles and heart
rhythm abnormalities. When doxycycline was stopped, mice stopped
producing excess RNA and returned to normal except in cases when the
heart had been severely damaged. The cellular mechanism of how muscular
dystrophy develops is still unknown, but the prevailing theory is that
the RNA remains in the nucleus rather than moving out of it, and
proteins get stuck to the RNA and so are prevented from doing their job.
MMD is the first example of a disease caused by 'toxic' RNA. Silencing
the expression of the gene giving rise to the toxic RNA molecule could
be a viable approach for treating people with MMD. - Nature Genetics DOI:
10.1038/ng1857, September 2006
Enzyme Restores Memory in
Alzheimer Mice
Giving mice with Alzheimer's
disease (AD) the enzyme ubiquitin C-terminal hydrolase L1 (Uch-L1) seems
to restore their ability to form new memories. The researchers fused
Uch-L1 with the transduction domain of another protein, the HIV-transactivator
protein. When given to the AD mice, enzymatic activity and synaptic
function were restored. Uch-L1 is required for normal synaptic and
cognitive function as it is a component of the neuronal ubiquitin/
proteasomal pathway. This pathway, which has been implicated in the
pathogenesis of AD, regulates the CREB molecule necessary for normal
memory in mice. CREB is inhibited by the amyloid beta proteins that are
produced in the brains of mice and humans with Alzheimer's disease and
cause the memory impairment and brain damage typical of the disorder.
What makes this newly discovered enzyme exciting as a potentially
effective therapy is that it restores memory without destroying amyloid
beta proteins. Amyloid beta proteins play important roles in the rest of
the body in both mice and humans so it is not possible to eliminate them
to slow AD. The researchers also found that the Uch-L1 fusion protein
improved the retention of contextual learning over time in the AD mice.
- Cell, 25 August 2006
Established Drugs May Also
Treat Diabetes
Drugs for liver disease and a
rare blood disorder may help treat the most common form of diabetes
(type 2 diabetes) in overweight people. The medicines, ursodiol, for the
liver and gallbladder, and Buphenyl, which fights a sometimes-fatal
genetic disorder, lowered blood sugar to normal levels in the cells of
severely obese and insulin-resistant mice. Endoplasmic reticulum stress
is a key link between obesity, insulin resistance, and type 2 diabetes
where the body does not produce enough insulin. The stress of obesity on
liver and fat cells can disrupt the glucose-lowering actions of insulin,
and lead to diabetes. A gene called JNK interferes with insulin
sensitivity. This study showed that ursodiol and Buphenyl reduced
endoplasmic reticulum stress, prevented JNK activation in the mice and
restored insulin sensitivity. These compounds fixed the problem at the
core of the disease, rather than the symptoms of the disease. If these
results are replicated in humans it provides fertile ground for thinking
about new treatments for type 2 diabetes. - Science DOI:
10.1126/science.1128294, 25 August 2006
Bad Taste in Your Mouth?
Mammals taste many compounds
yet use a sensory palette consisting of only five basic taste
modalities: sweet, bitter, sour, salty and umami (the taste of
monosodium glutamate). Although this repertoire may seem modest, it
provides animals with critical information about the nature and quality
of food. The ability to detect 'sourness' could be important as a
warning to mammals against eating acidic food that might be spoiled or
unripe. A subset of taste receptor cells on the tongue detect sourness
(other subsets are responsible for sweet, bitter and umami tastes); this
subset expresses the protein PKD2L1. Mice genetically engineered to lack
this subset cannot respond to acidic, sour-tasting stimuli, showing that
PDK2L1 is essential for detecting 'sourness'. Responses to other tastes
were unaffected. PDK2L1 is also active in certain neurons in the spinal
cord and so may be involved in detecting the acidity of cerebrospinal
fluid. This suggests a common chemosensory mechanism for detection of
acidity and monitoring the 'quality' of critical body fluids: for
example, the body controls respiration in part by monitoring the acidity
of the blood, as an increase in carbon dioxide dissolved in the blood
increases acidity. Defects in these blood, spinal or brain fluid-sensing
systems might underlie a wide range of disorders. - Nature DOI:
10.1038/nature05084, 24 August 2006
Genetic Origin of
Cardiomyopathy Identified
A study in transgenic mice
identifies conclusively for the first time genetic origins of
cardiomyopathy, one of the leading causes of sudden cardiac death in
young adults. Arrhythmogenic Right Ventricular Cardiomyopathy (ARVC) is
a rare, progressive condition that causes diseased heart muscle and
impairs cardiac function. In many cases, ARVC leads to fatigue,
irregular heartbeat (arrhythmia), and, potentially, heart failure and
sudden cardiac death. The researchers implanted a mutant version of the
human gene Desmoplakin, which encodes a protein in the
connecting junction between heart cells, into the mice. This resulted in
dilation of the right ventricle, scar and fatty build-up, and
arrhythmia. They hope the ability to diagnose based on a blood test of
the gene will lead to new targeted therapies. - Circulation Research,
online DOI: 10.1161/01.RES.0000241482.19382.c6, 17 August 2006
First Mouse Model for CLL
A study by cancer researchers
reveals that a new strain of transgenic mice, called TCL-1, offers the
first real animal model for an incurable form of leukemia, chronic
lymphocytic leukemia (CLL). This should greatly aid the development of
new drugs for CLL, which causes the proliferation of white blood cells
(lymphocytes). Other symptoms include severe anaemia and a high risk of
viral, bacterial and fungal infections. Average survival after diagnosis
is eight to 12 years. The standard treatment for CLL is the drug
fludarabine, but patients often become resistant to the drug. The TCL-1
mice develop a malignancy that closely mimics CLL: they share many of
the molecular and genetic features of human CLL; respond to drugs
typically used to treat the disease; and develop drug resistance that
renders treatment ineffective, as often happens in CLL patients. The
lack of an animal model has greatly hampered the development of new
treatments for CLL as well as research into its causes and the changes
that drive drug resistance. The researchers will use the TCL-1 mice to
screen new drugs for development; and to study the molecular changes
that lead to fludarabine resistance and perhaps learn how to circumvent
it. - Blood DOI: 10.1182/blood-2005-12-011213, 15 August 2006
Old Eyes, New Tricks
Although the nervous system
generally degenerates with age, nerve cells in the retinas of elderly
mice show an unexpected and purposeful burst of growth late in life. The
neural cells in the retina cover another layer containing the
light-sensitive cells. The retinal neurons collect signals from the
light-sensitive (photoreceptor) layer and relay them back to the brain.
The researchers noticed that in mice more than a year old middle-aged
in human terms the retinal neurons sprouted tendrils into the
photoreceptor layer. The older the mice, the more growth that took
place. At the same time, the photoreceptor cells are shrinking and
pulling back so the neurons appear to be following them, perhaps
compensating for those effects. Similar sprouting occurs in damaged or
detached retinas but this is the first time such an effect has been seen
in the normal, aging eye. The scientists have preliminary evidence that
the same process takes place in the eyes of elderly humans. The nerves
of the eye are really a part of the brain so this discovery means that
it might be possible to encourage other parts of the aging brain to grow
back. - Proceedings of the National Academy of Sciences DOI:
10.1073/pnas.0605211103, 8 August 2006
Minty Pain Relief
A study on rats suggests that
cooling sensations can relieve chronic pain. Scientists investigated the
analgesic qualities of a chemical called icilin, related to menthol. The
researchers looked at rats with chronic pain in one of their feet. When
the rats were given icilin, either injected or rubbed onto the painful
area, they were able to withstand pressure to their paw indicating the
compound had had a painkilling effect, even at minute quantities. They
discovered that the chemical was activating a protein called TRPM8,
which is expressed in the nerve cells in the skin and mediates the
sensation of coolness. Selectively activating the TRPM8 receptor may
suppress other sensory inputs into the nervous system that carry pain
information, giving pain relief. This is a specific mechanism which
means that this careful chemical-induced cooling can give relief to
people with chronic pain it does not affect acute pain. Chronic pain
is continuous, long-term pain, caused by diseases like arthritis or by
nerve damage. It affects millions of people worldwide and can be
difficult to treat because medication is needed over long periods and
may have side-effects. - Current Biology, 22 August 2006
Mending Broken Hearts
Researchers have successfully
used gene therapy to restore normal heart rhythms in pigs with
electronic pacemakers, reducing dependence on the implanted devices.
This work suggests that scientists are one step closer to making
bioengineering a reality for treatment of the millions affected by
irregular heartbeats. Radiofrequency ablation, a minimally invasive
technique regularly used in human treatment, was used to destroy the
sinoatrial (SA) nodes in pigs' hearts. This is the spot in the heart
that regulates heart beats. The team then implanted electronic cardiac
pacemakers like those used in humans, and injected an adenovirus
carrying a gene encoding for an engineered HCN protein into the heart
muscle. Expression of this gene converted the normal muscle cells of the
heart into pacemaker cells. Although heart cells do not normally
regenerate, within days of the gene transfer, the pigs' hearts had
generated bioartificial nodes at the injection sites; two weeks later
the new nodes were able to take over pacemaking function from the
electronic devices. Large animals such as pigs realistically mimic heart
conditions because their anatomy, physiology and heart rate are similar
to humans. - Circulation, published online before print DOI:
10.1161/CIRCULATIONAHA.106.615385,m 21 August 2006
Rare Heart Disease Gene
Discovered
A genetic discovery in mice has
shed new light on the cause of a rare heart disease that is one of
leading causes of sudden death in young adults. Arrhythmogenic right
ventricular cardiomyopathy (ARVC) is a rare, progressive condition that
damages heart muscle and impairs heart function. In many cases, ARVC
leads to fatigue, irregular heartbeat, and potentially, heart failure
and death. The authors implanted a mutant human gene for
desmoplakin, a protein that connects different heart cells to each
other, into mice. This affected how well the mice's hearts were able to
work, leading to dilation of the right ventricle, the build-up of scar
and fatty tissue, and irregular heartbeat. The new findings will help
pediatric and adult cardiology experts better understand the root cause
of ARVC and advance the care of patients with this specific abnormality.
- Circulation Research (OnLine First) DOI:
10.1161/01.RES.0000241482.19382.c6, 17 August 2006
Making a Hunger Map
Scientists have been able to
map the activity of large bundles of nerve cells in the brains of rats,
to help them study which areas of the brain control the motivation and
desire to eat when we are hungry. The researchers implanted electrodes
in areas of rats' brain known to be involved in feeding, motivation, and
behavior. They then recorded nerve cell activity in those regions
throughout a feeding cycle, in which the rats became hungry, fed on
sugar water to satisfy that hunger, and then grew hungry again. By
isolating and comparing signals from particular neurons in the various
regions at various times in the cycle, the researchers gained insight
into the roles played by different parts of the brain in feeding
motivation and satisfaction. The researchers found that they could
distinguish nerve cells that were sensitive to changes in satiety states
as the animals satisfied their hunger. They could also measure how
populations of nerve cells changed their activity over the different
phases of a feeding cycle, reflecting the physiological state of the
animals. The results show that while single nerve cells preferentially
respond to variations in metabolism, nerve cell bundles can also work
together to integrate several different signals. - Neuron, 17 August
2006
siRNAs Target Ovarian Tumors
A molecular 'off' switch
packaged in a tiny sphere called a liposome can penetrate deeply into
ovarian cancer tumor cells in mice, stifling a protein that helps
ovarian cancer cells survive and spread, and reducing the size of
tumors. Researchers used short protein sequences called
short-interfering RNAs (siRNAs) and rolled them into a liposome. They
injected the liposomes into mice that had been infected with human
ovarian cancer cells. The liposomes contained: siRNA targeted to stifle
the cancer-causing protein; or a control siRNA; or the chemotherapy
docetaxel; or were empty. After 3-5 weeks of treatment, the tumors in
the mice that received the protein-silencing liposome shrunk in weight,
in some cases by almost three quarters. Combining the protein-silencing
liposome with chemotherapy reduced the weight of the tumors by nearly
100%. In addition to its anti-tumor effect, the researchers found that
the therapeutic liposome attacked the tumor's blood supply, especially
when combined with chemotherapy. - Clinical Cancer Research, 15 August
2006
Everlasting Happiness
The TREK-1 protein is a channel
that allows potassium in and out of brain cells. It is regulated by
various neurotransmitters (chemical messengers) including serotonin.
Serotonin plays an important role in mood, sleep and sexuality, but the
molecular mechanism is poorly understood. Mice with the TREK-1 gene
knocked-out have more efficient serotonin neurotransmission, and have a
reduced physiological response to stress. The mice are permanently
'cheerful' and depression-resistant. The mice were tested using separate
behavioral, electrophysiological and biochemical measures known to gauge
'depression' in animals. The results were surprising; the mice acted as
if they had been treated with antidepressants for at least three weeks.
This research is the first time depression has been eliminated through
genetic alteration of an animal. The discovery of a link between TREK-1
and depression could ultimately lead to the development of a new
generation of antidepressant drugs that target this potassium channel.
Depression affects around 10% of people at some point in their life but
current medications for clinical depression are ineffective for a third
of patients, which is why the development of alternative treatments is
so important. - Nature Neuroscience, published online DOI:
10.1038/nn1749, 6 August 2006
Premature Babies at Risk
from Artificial Lights
Constant exposure to artificial
hospital lighting may damage the development of premature babies'
biological clocks. Baby mice exposed to constant light did not develop
the master biological clock in their brains properly. Researchers say
this could contribute to an increased risk of mood disorders, such as
depression. In all mammals the master biological clock is located in an
area of the brain called the suprachiasmatic nuclei (SCN). It influences
the activity of many organs, including the brain, heart, liver and lungs
and regulates the daily activity cycles known as circadian rhythms. The
SCN is filled with special 'clock cells' whose activity is synchronized
to follow the 24-hour day/night cycle. The nerve cells in mice exposed
to constant light were unable to maintain coherent rhythms. However,
when these animals were then exposed to a normal cycle of light their
nerve cells quickly readjusted. Some mice were then exposed to constant
light for a much longer period - and two-thirds were unable to establish
a regular pattern of activity on an exercise wheel. The researchers say
their findings suggest special care baby units should try to minimize a
baby's exposure to artificial hospital lighting. - Pediatric Research
(published online before print) DOI: 10.1203/01.pdr.0000233114.18403.66,
20 July 2006
Immune System 'Thermostat'
New research by scientists
working with mice has revealed that the immune system controls its own
'thermostat' and balances the different proteins in the immune system to
control the body's response to infection. When pathogens infect the
body, the cells of the immune system release protein compounds that kill
invaders but also trigger inflammation that, if unchecked, can destroy
tissue, and potentially kill the host. So immune system cells let loose
another protein compound to 'cool down' the immune response. Precisely
how this immune system 'thermostat' operates was unclear. But new
research shows that proteins called cytokines operate in harmony and are
controlled by the same master cell. Researchers infected mutant mice
with the parasite Toxoplasma gondii. They found that the 'coolant'
protein Interleukin 10 is switched on by another protein,
Interferon-gamma, which is made by white blood cells known as T helper 1
cells. Indirectly, Interferon-gamma is made by another protein called
tyrosine kinase 2, which controls 'hot' inflammatory cytokines. This new
knowledge will be important to drug companies developing new drugs for
arthritis and autoimmune diseases, in which the immune system thermostat
is often compromised. - Journal of Immunology, June 2006
Protein Boost Prevents
Seizures
A naturally occurring protein
in our brains could be the basis for a more promising epilepsy treatment
without the nasty side effects caused by many of the current
medications. A study in rats shows that the drug valproic acid (VPA)
boosts the amount of the protein neuropeptide Y, an anti-epileptic
compound in the brain that helps transmit signals between the nerves
cells that generate and transmit thoughts in the brain. VPA has long
been a mainstay in treating epilepsy, although how it suppressed
seizures was a mystery. This latest discovery suggests that it does this
by increasing the amount of neuropeptideY. After giving rats doses of
VPA in concentrations known to be large enough to suppress seizures,
levels of neuropeptide Y were higher in certain parts of the brain the
thalamus and hippocampus, areas associated respectively with petit mal
and temporal lobe epileptic seizures. Also, after treatment with VPA,
both the duration of the seizures and the extent to which they spread
from their site of origin were reduced. This finding emphasizes that our
brains have the inherent capacity to stop seizures; although there may
be more than one mechanism by which our brains do this, an increase in
neuropeptide Y is clearly one of them. - Journal of Neuroscience DOI:
10.1523/JNEUROSCI.5320-05.2006, June 2006
Cigarettes Reduce the Effects
of Alcohol
New research helps to explain
why people are more likely to smoke when they drink, and drink when they
smoke. Work in rats shows that nicotine can halve the amount of alcohol
in the blood. If cigarettes are proved to have the same effect on how
intoxicated people become when they drink, it could mean that smokers
need to drink more than non-smokers to get the same buzz. Researchers
studied the effects of binge drinking in rats. They injected the rats'
stomachs with double the American legal blood alcohol level. They also
gave the rats a range of light, moderate and heavy doses of nicotine.
After an hour, the nicotine cut the blood alcohol levels of the
'heavy-smoking rats by half. The blood alcohol level of moderate smoking
rats was reduced by more than a quarter. The blood alcohol level of
light smoking rats was unaffected. A lower blood-alcohol level means
that the nicotine-dosed rats were less drunk than their non-smoking
friends. But smoking does not ameliorate the other effects of alcohol or
prevent a hangover, because the toxic by-products of alcohol breakdown
still remain in the body. - Alcoholism: Clinical Experimental Research
DOI: 10.1111/j.1530-0277.2006.00168.x, August 2006
Muscular Dystrophy Reversal
Clue
Scientists have found a way to
reverse the most common form of muscular dystrophy in mice, offering
hope to patients with the muscle-wasting disease. The experimental
therapy targets a particular type of toxic molecule to 'silence' its
presence in the diseased muscle. The treatment meant that heart and
other muscles worked again. Myotonic dystrophy occurs because a section
of DNA code is duplicated many times. The result is a build-up of
faulty, toxic messenger RNA molecules in cells. These abnormalities lead
to progressive muscle weakness and wasting and heart problems. The
researchers wanted to get rid of the messenger RNA molecules, to see if
this would reverse the disease. They created mice with faulty DNA that
could be turned on and off by adding or removing an antibiotic to their
drinking water. When the DNA was switched on the mice showed all the
symptoms of myotonic dystrophy. But when the DNA was turned off most,
but not all, of the mice had normally functioning muscles. Although the
treatment was not 100% effective, the researchers believe their results
provide the proof needed to demonstrate that it might be possible to
reverse muscular dystrophy. - Nature Genetics (advanced online
publication) DOI: 10.1038/ng1857, 30 July 2006
A Nose for What Makes
Animals Attractive
Scientists have proven that
love may indeed be in the air. Results from a mouse study provide
evidence for human pheromones, and suggests that people might be able to
smell the chemical signals of sexual attraction given off by others. The
team of researchers discovered a new class of receptors used by mice to
detect pheromones, the sex hormones released by a potential mate. The
gene for the receptors is also found in humans, suggesting that they too
may be influenced by chemicals used in the dating game. Like other
mammals, mice can detect pheromones using odor receptors attached to
special cells in the nose. The newly-found class of receptors, known as
trace amine-associated receptors (TAAR), detects several chemical
'mating signals' present in the urine of mice. The gene that codes for
the receptor is found not only in mice but also in fish and humans,
suggesting that the behavior of a diverse group of animals is influenced
by pheromones. - Nature advanced online publication DOI:
10.1038/nature05066, 30 July 2006
Gene Therapy for the Heart
A new way of delivering the
genes that correct hereditary heart diseases into the veins of mice
holds promise for human diseases. Researchers have used a single
injection to reverse the symptoms in mice with a form of muscular
dystrophy that affects the heart. The technique has also been used
successfully in monkeys. The researchers compared three different
viruses as ways of inserting genes into the muscles of newborn and adult
mice: viruses called AAV-1, AAV-8 and AAV-9. Of the three, AAV-9 had a
strong affinity for heart muscle cells and was absorbed the most 200
times more that AAV-1. Because AAV-9 was so readily taken up by cells, a
lower dose could be used to achieve a therapeutic effect. It also has a
unique outer shell that helps it break through blood vessel walls so it
can be readily taken up by cells requiring repair. Tests in monkeys
showed that AAV-9 easily passes into the heart muscle in primates after
a single intravenous injection, and the effects were long lasting. -
Circulation Research (published online before print) DOI:
10.1161/01.RES.0000237661.18885.f6, 27 July 2006
Gene Therapy Reverses
Disabling Muscle Contractions
Scientists have used gene
therapy to prevent the disabling muscle contractions that occur in mice
with the equivalent of adult-onset, or myotonic, dystrophy. Myotonic
dystrophy is found in one in every 8,000 people and is caused by
malfunctioning genes that block the action of key proteins in cells,
including one called the muscleblind protein. Researchers used mice that
had certain mutated genes, including muscleblind, and so developed
typical myotonic dystrophy muscle problems. They inserted the
functioning gene for muscleblind into a virus called the adeno-associated
virus (AAV). The virus then copied the gene, producing many copies of
the muscleblind protein, and the researchers then injected the virus
into a muscle in the shins of the mutant mice. Four weeks after
the injection, the symptoms of the condition had improved and after 23
weeks they were completely eliminated. Six control mice that were
injected with a fluorescent protein did not show any signs of
improvement. Scientists eventually hope to find out whether correcting
myotonic dystrophy early by replacing defective muscleblind protein
might prevent at least some of the muscle loss associated with the
disease. - Proceedings of the National Academy of Sciences (early
edition) DOI: 10.1073/pnas.0604970103, 24 July 2006
Stress Makes Ovarian Cancer
Worse
When mice with ovarian cancer
are stressed, their tumors grow and spread more quickly. The results
provide the first measurable link between psychological stress and the
biological processes that make ovarian tumors grow and spread.
Researchers kept mice in a small space for either two, four or six hours
a day. The confinement meant that the mice produced more of a stress
hormone that humans produce when they are under stress. Cancer cells
make proteins that can recognizes these hormones and set in motion a
chain of events that grows new blood vessels, which allow tumors to grow
and spread more rapidly. After three weeks, the researchers measured the
number and size of tumors in the mice. The number of tumors was two and
a half times greater in the mice that had been in the 2-hour stress
group and four times greater in the 6-hour stress group compared to the
mice with no stress. In addition, the tumors in the no-stress mice did
not spread, but did spread to the liver or spleen in half of the
stressed mice. - Nature Medicine DOI: 10.1038/nm1447, 23 July 2006
Chemo Drug Toxic to Heart
A drug used to treat a type of
leukemia can be dangerous for the heart. Research in mice showed that
imatinib, which is prescribed for chronic myeloid leukemia (CML) under
the name Glivec, could lead to heart problems and heart failure in CML
patients. Researchers began investigating the drug's side-effects after
10 patients, who had no previous history of heart disease, developed
severe heart failure after taking imatinib. The drug's target, the ABL
protein, helps keep heart muscle cells healthy. While the cancer is
treated effectively, there may be a small percentage of patients who
could experience heart problems. Mice treated with imatinib developed
problems in the left ventricles of their hearts the same heart
condition seen in the 10 imatinib-treated patients who developed heart
failure. The same effect was seen in human heart cells exposed to
imatinib in a Petri dish. People with CML have too much of an enzyme
called ABL, which causes them to produce too many white blood cells,
resulting in leukemia. Imatinib works by blocking the harmful action of
ABL, amongst other targets. But ABL is also needed to keep heart muscle
cells healthy. So blocking the action of ABL may also cause damage to
the heart. - Nature Medicine DOI: 10.1038/nm1446, 23 July 2006
Tipping the Scales in Favor
of Weight-loss Drugs
Most major weight-loss drugs
work by increasing the effect of a brain chemical called serotonin. By
working with mice, researchers have pinpointed precisely how serotonin
suppresses the appetite and reduces the urge to eat. Researchers tested
whether serotonin works on a nervous circuit in a part of the brain
called the hypothalamus that controls the body's energy balance. Their
experiments showed that receptors for serotonin are expressed on
particular nerve cells in the hypothalamus that monitor food intake and
body weight. The researchers found that both serotonin and drugs that
affect serotonin's action acted on these nerve cells to reduce the
release of a protein called AgRP that stimulates appetite and aids
release of other proteins that curb the appetite. The researchers also
tested the effects of drugs that either enhance or interfere with eating
habits in mice. The drugs disrupted the function of compounds that react
with a protein called melanocortin, a critical target of the serotonin
pathway, which appears to be central to appetite regulation. - Neuron,
20 July 2006
Antioxidants Slow Rate of
Vision Loss
Scientists have prevented
blindness in mice with a form of human disease by treating them with
antioxidants. If supported by evidence from future experiments, this may
provide scientists with a way to maintain the vision of people with
inherited blinding diseases. In patients with retinitis pigmentosa (RP),
a mutation causes the light-detecting cells called rods in the eye to
die. When the rods die the oxygen levels in the retina go up, and this
increase in oxygen also kills other light-detecting cells, called cones.
The oxygen damage can be reduced by compounds called antioxidants. In
mice with damaged retinas all the rods are destroyed 18 days after
birth, and all the cones 35 days after birth. The researchers injected
such mice with with vitamin E, vitamin C, and two other antioxidant
chemicals. Twice as many mice treated with antioxidants survived than
untreated mice. Antioxidants naturally occur in some fruits and
vegetables, and are available as supplements, but it remains unclear
whether antioxidants consumed in foods provide any benefit to people
with these types of vision impairments. - Proceedings of the National
Academy of Sciences (early edition) DOI: 10.1073/pnas.0604056103, 18
July 2006
Veggie-rich Diet May Protect
from Asthma
A compound found in herbs,
fruits and vegetables suppresses the levels of an antibody in the immune
system that is linked with asthma and other allergic reaction when fed
to mice. The results suggest that a diet rich in the compounds, called
flavonoids, could protect and/or reduce asthma and other allergies
caused by the antibody, called IgE. Researchers added a flavonoid
compound called apigenin to the food given to mice, and measured the
levels of certain antibodies in the immune system including IgE. After
two weeks the level of IgE was half that in a control group of mice that
were not given apigenin in their diet. Apigenin is found in a variety of
foods as well as plant-based drinks like tea and wine. However, the
researchers stressed that the results from this study need further
thorough investigation. - Journal of Agricultural and Food Chemistry DOI:
10.1021/jf0607361, 13 July 2006
Enzyme Makes Mice Leaner,
Not Meaner
Mice bred without an enzyme
called MKP-1 do not gain weight even if they are fed a diet of large
amounts of high-fat foods. This study gives new molecular clues into how
weight gain is controlled, and the possibility of new therapies to
combat obesity. Researchers bred mice without MKP-1, one of a group of
enzymes that switches on the function of other proteins is cells, to try
to work out what the enzyme does. Initially, the mice lacking the enzyme
were a normal size and weight. Then the researchers noticed that the
enzyme-less mice gained weight much more slowly than normal mice when
they were fed both a regular diet and a high-fat diet. The mice lacking
MKP-1 also burned calories at a significantly higher rate than the
control mice, and they had no trouble controlling their blood sugar
levels. Further research will try to understand how MKP-1 is involved in
controlling the expression of genes that regulate body weight. - Cell
Metabolism, July 2006
Mergla Protein Can Prevent
Muscle Wastage
Scientists have found a
chemical 'switch' in the body that they can use to stop the damage to
muscles caused by ageing, lack of use and some cancers. They now know
that a protein called mergla, which is found in skeletal muscles, is
directly linked to muscle wastage. The findings may one day help those
who are bedridden and, as a result, lose muscle mass or limb function.
Muscle wastage in mice can be treated by gene therapy and by drug
treatment, but the drug used in laboratory experiments is not suitable
for use in humans as it causes potential heart problems. But researchers
have now found the protein that is capable of sensing that muscles are
not being used this protein would be a target for new drugs. The team
used drugs which are designed to manipulate this target protein, and the
drug prevented muscle wastage: the muscles of mice treated with these
drugs were almost normal size. Testing and approval for a drug that can
prevent muscle wastage without affecting the heart will be a long
process but such a drug would improve the quality of life for ageing
people, improve rehabilitation of people who are bedridden and possibly
prolong the life of cancer patients. - Federation of American Societies
for Experimental Biology (FASEB) Journal DOI: 10.1096/fj.05-5350fje,
July 2006
Radiation Vaccines More
Effective in Mice
Vaccines made with bacteria
that are killed using gamma radiation, rather than standard methods of
killing bacteria like heat or chemical inactivation, are more effective
at protecting mice from infections. Gamma-radiated vaccines are also
storable at room temperatures, and so offer an advantage in areas where
refrigeration is impractical. In experiments with mice a vaccine made
from irradiated Listeria monocytogenes bacteria, unlike a vaccine made
from heat-killed bacteria, provides protection against Listeria
infection. The irradiated bacteria also caused the production of immune
system cells called T cells. Previously, it was thought that only
vaccines made from live, weakened Listeria bacteria were capable of
making the body produce an immune response. This advance is potentially
important in meeting the challenge of creating vaccines that are safe,
effective and simple to manufacture and transport. - Immunity, July 2006
Ibuprofen Worsens Brain
Performance
The long-term use of ibuprofen
after brain injury can worsen cognitive abilities. The preliminary
results from experiments in rats have important implications for people
who have had traumatic brain injuries, who are often prescribed
painkillers like ibuprofen to help them manage their pain. Researchers
divided rats that had sustained brain injuries into two groups. They
gave one group scaled-down doses of ibuprofen equivalent to those taken
by humans in their food. The other group did not receive any ibuprofen.
Over four months, both groups got worse at performing tasks such as
finding an underwater platform in a maze. Although most untreated
injured animals could find the platform, they were much slower to learn
its location than non-injured animals. In contrast, almost none of the
treated, injured animals could find the platform at all. The effects of
long-term treatment with NSAIDS like ibuprofen after a head injury are
poorly understood, and further research is needed. - FedLaw Experimental
Neurology DOI: FedLaw 10.1016/j.expneurol.2006.04.008, 9 June 2006
Out with the Old H5n1
Vaccine, in with the New
Scientists have announced that
a vaccine they developed a few years ago against one form of the bird
flu virus H5N1 could protect humans against future variants of the
virus. The vaccine, which was tested on ferrets, could be suitable for
stockpiling for use during a pandemic until a new vaccine could be
developed specifically against the variant causing the outbreak. The
vaccine completely protected ferrets from a lethal dose of the original
virus the vaccine was made to thwart, and the newer variant that has
already proved fatal to humans. The infections also failed to spread
from the site of infection in the upper respiratory tract to the lungs
or brain. This "cross-protection" would allow the use of a stockpiled
vaccine until a vaccine against the specific variant causing the
outbreak is developed. The best strategy for vaccinating humans would be
to use two doses: in the ferrets this triggered more immune protection
than a single dose. These findings are promising because ferrets are
known to be excellent models of influenza infection and immune response
in humans. - Journal of Infectious Diseases, 15 July 2006
Allergy Drug Could Be
Malaria Cure
A drug used to treat allergies
could be a potential cure for malaria. When tested in mice the drug,
called astemizole, killed the parasite which infects the blood and
causes the disease. The drug is already licensed for use in humans and
is no longer under patent, and so if the tests were successfully
repeated in humans it could be widely and cheaply available in as little
as a year. Time and cost are major roadblocks to the development of new
anti-malarial drugs. Most of the money goes on the final stages of
development and testing in humans. Using medicines that have already
been passed as safe in humans would reduce these costs. Moderate doses
of the drug reduced the parasite in the animals' bloodstream by
four-fifths, and nearly half of the parasites had become resistant to
standard anti-malarial drugs. Higher doses of the drug killed off the
parasites completely. The next step will be to study how to make the
drug work best in people, and figure out the optimum dose. - Nature
Chemical Biology (advanced online publication) DOI: 10.1038/nchembio806,
2 July 2006
Exploring Tropical Disease
Mice lacking a gene crucial for
the correct functioning of the immune system do not become ill when they
are exposed to a parasite that causes leishmaniasis, an infection of the
liver and the spleen. If left untreated leishmaniasis is almost always
fatal. The disease, which is transmitted through the bite of a sand fly,
is common in tropical and subtropical countries. The researchers
infected groups of mice with the parasite that causes leishmaniasis.
Mice in one group lacked the gene that makes a protein called STAT1,
which activates other key immune substances, including another protein
called T-bet. Mice in another group lacked the gene that makes T-bet. A
group of mice with both STAT1 and T-bet genes intact
served as a control. Two weeks after they were infected the mice without
STAT1 had 25 times fewer parasites in their liver than the normal mice,
and about 100 times fewer parasites than the mice without T-bet.
Leishmaniasis did not develop in the mice without STAT1, and the same
was seen two months after infection. The finding may lend insight into
creating new drugs to treat different diseases that affect the liver. -
Journal of Immunology, July 2006
Rats Reduce Asthma Risk
Laboratory workers who
frequently handle rats have fewer allergic reactions to them than people
who have had no exposure. This research supports the 'hygiene
hypothesis', in which exposure to naturally occurring infections and
microbes helps protect against the development of asthma and allergies.
Researchers studied blood samples taken from 689 lab workers, including
scientists, animal technicians and cage cleaners, who had been exposed
to lab rats. They tested the lab worker's blood samples for antibodies;
proteins that had been made in the blood in response to exposure to the
rats. They found the most antibodies in those lab workers who had
handled the greatest number of rodents. Lab workers who had
rat-stimulated-antibodies in their blood were half as likely to develop
work-related chest symptoms as those who had other antibodies in their
blood. This research helps us understand the risks people may face when
working with animals, but there is still have much to learn about
allergen exposure and the risk of developing asthma. - American Journal
of Respiratory and Critical Care Medicine DOI:
10.1164/rccm.200506-964OC, 1 July 2006
Same Genes in Mice and Human
Liver Cancer
Scientists have identified two
genes that cause mice to develop liver cancer; the same two genes also
trigger the growth of tumors in human livers. The researchers delivered
stem cells destined to become liver cells into the spleens of mice. The
cells grew abnormally to form liver cancer. The researchers then used
special gene technology to identify which genes were working overtime,
or not enough. The scientists discovered that liver tumors grow when
either of two genes called cIAP1 and YAP are not
working correctly. The tumors grow even faster when both genes are
abnormally activated. The first gene, cIAP1, stops cells from
dying. The YAP gene controls other genes. When the scientists
interfered with the function of these other genes, they slowed the
growth of the liver cancer. The researchers have identified the same two
genes in human liver cancers, and think they can use the same techniques
to find other cancer-causing genes. - Cell, 30 June 2006
Mice Are Nice about Each
Other's Pain
A new study provides evidence
that mice might experience empathy, which scientists previously thought
was only felt in humans and higher primates. Mice that are familiar with
each other and were able to see others that their cagemates were in pain
were more sensitive to pain than those that were either tested alone or
those that saw mice they were not familiar with in pain. The results
suggest that some aspects of mice behavior may be influenced by the
"emotions" of others, and shed light on how known social factors play a
role in pain management. The findings are not only unprecedented in what
they tell us about animals, but may ultimately be relevant to
understanding pain in humans. - Science DOI: 10.1126/science.1128322, 30
June 2006
Stem Cells Prevent Stroke
Paralysis
Scientists have used stem cells
to reverse the damage done to brain cells of rats that had suffered
strokes. This work may lead to the development of treatments that will
encourage the body to heal itself. In humans, strokes damage and kill
brain cells, which often results in paralysis. The scientists tested
rats whose brains had been denied oxygen, to simulate the effects of a
stroke. They stimulated a protein called Notch on the surface of stem
cells in the rats' brains. Notch caused reactions that produced new
brain cells. Fewer of the rodents that were given the stem cell therapy
after a stroke were left paralysed, compared with untreated rats. The
technique has wide implications for stem cell research. The findings
might lead to strategies that can activate cells to be able to repair
different cells and organs. - Nature (online advanced publication) DOI:
10.1038/nature04940, 25 June 2006
Rats Help Solve the Ritalin
Riddle
Research in rats has shed new
light on precisely how Ritalin, the drug prescribed for Attention
Deficit Hyperactivity Disorder (ADHD) affects the part of the brain
called the prefrontal cortex (PFC). The PFC is associated with
attention, decision-making, and personality. The finding could prove
invaluable in the search for new ADHD treatments. Researchers used a
type of brain probe known as microdialysis to measure the amounts of
chemicals called dopamine and norepinephrine in three different areas of
the brain in the presence and absence of low doses of drugs that
stimulate ADHD. Under the influence of ADHD drugs, dopamine and
norepinephrine levels increased in the rats' PFC. This work provides
important information on the importance of the PFC in treating ADHD. -
Biological Psychiatry (article in press) DOI:
10.1016/j.biopsych.2006.04.022, 23 June 2006
Learning How Mice Learn
Nerve cells in the brains of
mice grow new connections when the animal has to learn new things or
adjust to new experiences. The new connections alter the communication
between nerve cells, like humans learning skills such as riding a
bicycle or typing on a computer. Researchers genetically altered mice to
produce a green fluorescent protein in specific nerve cells in the
neocortex, a region of the brain that is known to adapt to new
experiences. The researchers followed the growth of the cells in the
region of the neocortex that processes information from the animals'
whiskers. The scientists used a microscope aimed through a small glass
window in the animals' skulls to see the changes in the nerve cells. The
researchers then trimmed the animals' whiskers, selectively cutting some
but leaving neighboring whiskers, in a chessboard pattern. Over time,
this selective grooming caused the animals' nerve cells to rewire
themselves to adapt to loss of the whiskers. This reduces dependence on
lost whiskers and enhances input from intact whiskers. The discovery
suggests new ideas for future studies aimed at understanding the nerve
cell wiring process in greater detail. - Nature DOI:
10.1038/nature04783, 22 June 2006
T-cells Linked with Stomach
Cancer
Scientists have found a link
between a particular type of gastrointestinal cancer and the functioning
of T-cells in the immune system. Children with the syndrome familial
juvenile polyposis, or FJP, develop gastrointestinal polyps that can
sometimes become cancerous. Around half of all patients carry an
inherited mutation in one copy of a gene called SMAD4, and
doctors think that gastrointestinal cancer develops if the remaining
copy becomes damaged in the cells that line the stomach and
gastrointestinal tract, called epithelial cells. The researchers deleted
the Smad4 gene from mice epithelial cells. These mice did not
develop cancer. But when the gene was deleted in T cells, which play a
role in the immune system, mice developed cancers throughout their
gastrointestinal tract. Although the role of T cells in FJP has yet to
be determined, the scientists say the findings show a genetic alteration
in one cell type can induce cancer in a different cell type. - Nature
DOI: 10.1038/nature04846, 22 June 2006
RNA Interferes with Female
Mouse's Brain
Scientists have used a genetic
technique called RNA interference (RNAi) to stop the effect of oestrogen
on the brain, whilst not affecting the rest of the body. The changes led
to striking changes in the behavior of female mice, and the results will
help scientists to map the human brain's circuitry. The researchers
injected a piece of genetic information called RNA into a part of the
brain of female mice that is responsible for female sexual behavior. The
RNA attaches to a gene for a protein called oestrogen receptor alpha,
preventing the protein from being made. In normal mice this protein
allows oestrogen to function properly. The mice that received the RNAi
treatment were more likely to aggressively reject the sexual advances of
males, and kick males who attempted to mount them. This suggests that
the effects of oestrogen on sexual behavior occur during adult life, and
not during development. - Proceedings of the National Academy of
Sciences (early edition) DOI: 10.1073/pnas.0603045103, 22 June 2006
'Herbal' Drug Blocks Lung
Cancer in Mice
Scientists have shown that
silibinin, a drug derived from milk thistle, destroys lung cancer in
mice. Herbal extract of milk thistle is commonly available in health
shops, and often taken as an alternative treatment for liver diseases
such as cirrhosis, jaundice, hepatitis, and also gallbladder disease.
Mice with lung cancer were given diets containing different amounts of
silibinin. Mice fed silibinin had fewer and smaller lung tumors than
untreated mice. Further analysis showed that silibinin seemed to reduce
the number of blood vessels that provide nutrients to the tumors,
allowing them to grow. Further laboratory studies of silibinin for lung
cancer are now being done and clinical trials of silibinin in lung
cancer patients are expected. - Journal of the National Cancer Institute
DOI: 10.1093/jnci/djj231, 22 June 2006
Successful Pig to Mouse
Transplant
Scientists have transplanted
cells from the pancreas of pig embryos into mice. This success supports
the notion that embryonic pig pancreas cells could be a source of tissue
for transplantation into human patients with diabetes. The researchers
transplanted cells from pig embryos of different ages into mice that
lacked working immune systems. Cells that were taken from embryos
between 42 and 56 days old grew better than tissue taken earlier or
later, made more pig insulin and were better at keeping the amount of
sugar in the blood at a normal level. The researchers then tested if the
transplanted cells triggered an immune reaction by seeing how well they
survived when human immune system cells were also transplanted into the
mice. Tissue from 42-day-old embryos came out best in this test too,
suggesting that transplanted cells did not cause a direct immune
reaction. Next, the team tried the experiment on mice with fully
functioning immune systems, after destroying the insulin-producing cells
in their pancreases. By giving these mice drugs to suppress their immune
systems, the implanted cells worked correctly, producing insulin and
maintaining the mice's blood sugar at normal levels. - Public Library of
Science Medicine DOI: 10.1371/journal.pmed.0030215, 20 June 2006
Avoiding Carbs May Avoid
Alzheimer's A low-calorie,
low-carbohydrates diet may reduce or even reverse the symptoms of
Alzheimer's disease, a new study in mice suggests. Restricting
carbohydrates may help prevent Alzheimer's by boosting brain activity.
Alzheimer's disease is caused by increased amounts of proteins in the
brain called beta-amyloid peptides. These peptides stimulate a protein,
called SIRT1, which affects ageing. Researchers fed mice a low-calorie,
low-carbohydrate diet to see how it affected the presence of beta-amyloid
peptides in the brain. The restricted diet reduced the amount of
peptides in the brain, while a diet high in saturated fat appeared to
cause higher concentrations of peptides. These preliminary findings
further unlock the mystery of Alzheimer's and the scientists hope to
apply them to ongoing research to help the millions of people suffering
from this disease. - Journal of Biological Chemistry DOI:
10.1074/jbc.M602909200, 2 June 2006
You Dirty Rat!
Two new studies indicate that
the rats and mice living in filthy conditions in drains and sewers
around the country have healthier immune systems than those that have
only ever lived in clean laboratories. These results lend weight to the
'hygiene hypothesis' that clean living may make us sick and is
increasing the rate of allergies, asthma and autoimmune diseases.
Researchers compared the activity of immune cells called IgE and IgG
cells in laboratory rodents to those of wild rats captured in cities and
on farms, and found significant differences between the two. When the
researchers stimulated the immune cells in wild rats the cells did not
produce an immune response. The same treatment caused the immune cells
in laboratory rats to over-react to stimulation. The wild mice and rats
had as much as four times higher levels of immune cells, but didnt
become sick, showing an immune system tuned to fight crucial germs, not
minor irritants. The researchers say what happens in rats is likely to
occur in humans. Immune systems are not challenged regularly overreact
to the smallest of problems. Challenged immune develop fewer allergies.
- Scandinavian Journal of Immunology DOI:
10.1111/j.1365-3083.2006.01785.x, June 2006
Septum Sets the Tempo of
Brain's Electrical Activity
The brain's septum a thin
structure separating two fluid-filled pockets in the brain helps
prevents epileptic seizures in rats by orchestrating brain impulses as
they pass from one part of the brain to another. By controlling the
nerve cells in the septum, researchers prevented up to 9 in 10 epileptic
seizures. Nerve cells in the brain are constantly chatting with each
other through electrical impulses. When the chatter is not kept in check
it can escalate, causing an epileptic seizure. The researchers injected
rats with a drug that excites the brain's nerve cells to produce chronic
epileptic seizures. The researchers then used electrodes to study
individual nerve cells within the rats' septum. The epileptic rats
suffered significantly more epileptic episodes when the brain did not
have the proper rhythm of electrical activity, called the "theta
rhythm". The researchers also found that when the theta rhythm was
induced in the rats, nearly nine out of 10 epileptic seizures were
avoided. The research may ultimately result in new treatments dedicated
to protecting the brains normal electric rhythm. - Journal of
Neurophysiology DOI: 10.1152/jn.00040.2006, June 2006
Citrus
Juice Sees off Osteoporosis
Drinking citrus fruit juice
drinks every day may help prevent fractures caused by osteoporosis, a
crippling bone-thinning disease. Regular doses of grapefruit and orange
juice helped prevent osteoporosis and strengthened the bones of male
rats with low levels of the hormone testosterone in their blood.
Scientists divided the rats into three groups: those with no change in
diet; those who received orange juice; and those who received grapefruit
juice. The rodents were fed fresh juice supplemented with sodium
bicarbonate, to reduce acidity, every morning. The rats given daily
drinks of citrus juice had denser bones that were less prone to breaks
and fractures. The next step for the researchers is to study the
cellular makeup of the rats' bones to determine how the juice actually
improved bone strength. The researchers hope that if they can maintain
the strength of bones they can prevent osteoporosis. - Nutrition DOI:
10.1016/j.nut.2005.12.002, May 2006
Dolphins Give Themselves
Names
Dolphins are known for their intelligence and
highly developed social order. Dolphins can also communicate with each
other on an individual level, by using unique whistles to identify
themselves and others. This means that apart from humans, dolphins are
the only mammals able to communicate information about their identity.
Scientists captured wild dolphins in nets and recorded their whistles
before synthesizing and coding them using a computer. They then played
the whistles back to other dolphins, which recognized the whistles and
responded. Despite being able to hear for distances of up 15 miles
dolphins have to filter out background noises. The individual whistles
help dolphins to tell their friends and family where food and predators
are. The individual whistles develop in the first few months of life,
similar to babies who begin to recognize their own name at a similar
age. - Proceedings of the National Academy of Sciences (early edition)
DOI: 10.1073/pnas.0509918103, 12 May 2006
Strain of 'Cancer-resistant' Mice
A strain of laboratory mice appears to be
resistant to injections of cancer cells that kills ordinary mice. The
immune system cells from these mice, when injected into normal mice,
cure them of cancer. This discovery could be applied to human patients.
The scientists bred the mice from a strain that is commonly used in
research laboratories around the world. The first mice were injected
with a normally lethal strain of mouse cancer cells in 1999. Of the
original batch that received the first injection only one mouse
survived. After the same mouse survived repeated injections, the
scientists began bred a strain from it that had 'cancer resistance'. The
scientists took a sample of white blood cells from resistant mice and
injected them into normal, non-resistant mice that had already been
infected with cancer. The injection caused the tumors in the
non-resistant mice to disappear. As yet, the gene or genes responsible
for cancer resistance in these mice have not been identified because it
appears to move from one chromosome to another. - Proceedings of the
National Academy of Sciences (early edition) DOI:
10.1073/pnas.0602382103, 8 May 2006
Obesity Gene Increases Diabetes
Through experiments in obese mice scientists
have found that a gene called Sorcs1 plays an important role in
the development of type 2 diabetes. Obese individuals often have type 2
diabetes, which is caused when the pancreas cannot produce enough
insulin or when the body's response to insulin is reduced. Researchers
used genetic tests to compare two strains of obese mice to identify
which genes were responsible for which physical characteristics, like
susceptibility to insulin. The Sorcs1 gene is needed for the
pancreas to attract a type of cell essential for building the walls of
blood vessels. If there are changes in this gene the blood vessels in
the pancreas may not form properly. This may have several effects. It
may mean that not all cells in the pancreas receive enough blood to
survive; that they may not receive the proper signals to secrete
insulin; or that the blood vessels cannot receive all the insulin the
cells produce. Genetic factors could account for roughly half the causes
of type 2 diabetes. Knowing which genes are involved can help
researchers identify those at the greatest risk. - Nature Genetics
(advanced online publication) DOI: 10.1038/ng1796, 7 May 2006
Happy Solution for Hay Fever
Scientists are moving closer to providing long
term relief for sufferers of hay fever and other allergies. They have
found a gene in mice prevents T cells immune cells that are released
in response to an allergic reaction from traveling to the lungs and
causing an allergic reaction. When we are exposed to things we are
allergic to like pollen, house dust and animal fur, this stimulates the
release of a chemical called histamine. Histamine causes the common
symptoms of allergies: itchy eyes and nose, sneezing and swelling of the
airways. Scientists bred mice without a properly functioning protein
called the histamine 1 receptor (H1R). These mice produce T cells after
being exposed to an allergen, but the T cells are not able to travel to
the site of allergen exposure the lungs. Normally, histamine attracts
T cells to the lung, but in mice without H1R T cells do not travel to
the lungs and so do not create the typical allergic reaction. This new
information indicates that blocking H1R with currently available drugs
might have potential benefits in the treatment of allergic diseases. -
Journal of Clinical Investigation (published online) DOI:
10.1172/JCI26150, 4 May 2006
Vision Affects Genes
What we see can turn up the expression of some
genes and turn down the expression of other genes. New research in rats
shows that during different stages of life, different genes become
active in response to visual cues. These results may have implications
for how some eye diseases are treated. Scientists studied rats during a
critical stage of their development when visual inputs can determine the
nerve connections formed in the brain. This occurs shortly after rats
first open their eyes and begin to see. The team impaired the rats'
vision in several ways, including removing one eye and leaving the other
intact. They compared which genes were expressed in the cortex region of
the brains in rats with impaired vision to rats with normal vision. The
changes in the visual inputs changed the level of expression of 11
genes. This suggests that visual experience influences different genes
in the brain depending on age and past experience. These discoveries may
lead to new ways of thinking about genetic therapies to correct early
vision disorders. - Nature Neuroscience DOI: 10.1038/nn1674, May 2006
STD Vaccine Shows Promising Results
A vaccine against chancroid, a sexually
transmitted disease, could reduce the transmission of HIV/AIDS by up to
ten times. Chancroid is a sexually transmitted disease that causes
genital ulcers. It is rare in Western Europe but is dangerous in African
communities that have little or no access to healthcare. Recent studies
showed that genital ulcer diseases such as chancroid can enhance HIV
transmission three- to 10-fold. Chancroid is caused by bacteria called
Hemophilus ducreyi. These bacteria are unable to manufacture a protein
called haem, the iron-containing part of hemoglobin, which is needed to
transport oxygen around the body. Instead, the bacterium uses the hem of
the person it infects. Vaccinating pigs with a protein that attaches
itself to hemoglobin protected the animals from infection. This study
suggests that developing a chancroid vaccine would be a relatively
simple task, with potential benefits for the stopping the spread of
HIV/AIDS. - Infection and Immunity DOI: 10.1128/IAI.74.4.2224-2232.2006,
May 2006
Hormone Affects How Brain Listens
In many animal species including humans,
reproductive hormones influence how animals respond to courting signals.
New research shows that hormones may affect how birds listen to
courtship songs during the mating season. Scientists treated female
white-throated sparrows with the sex hormone estrogen, and compared them
to untreated females. The birds listened to recordings of either the
seductive male song or artificial beeps that had the same frequency as
the male song. Both groups of female birds responded as expected.
The estrogen treated group performed mating rituals and the untreated
group did not return courtship displays. The main difference between the
two groups was not that estrogen increased the response to song but that
it decreased the response to the beeps. This decrease could help the
birds to 'tune out' irrelevant sounds and focus on the signals important
for breeding. The results indicate how hormones affect sensory
processing in general, and fit with studies showing that women's
preferences for masculine faces, voices and body odors change over the
menstrual cycle, as hormones are changing. - European Journal of
Neuroscience DOI: 10.1111/j.1460-9568.2006.04673.x, May 2006
Stressed Hamsters Eat More
Scientists are using hamsters to study human
obesity. When hamsters, which are normally solitary, are placed in a
group-living situation, they gain weight in a similar response to
non-traumatic stress commonly seen in humans. They study will help
researchers to understand the complex factors that lead people to eat
when under stress. The scientists placed 11-week old hamsters in a cage
with an older, more dominant and aggressive hamster for seven minutes at
a time over a period of 33 days. As a result of the stress of being
placed in the home cage of a larger resident, intruder hamsters ate
significantly more, gained more weight and had a larger proportion of
body fat. The weight gain in the 'submissive' hamsters was seen when the
hamsters were placed in the cage as few as four times. The scientists
hope that the information can eventually be used to block appetites when
stress leads to over-eating. - American Journal of Physiology
Regulatory, Integrative and Comparative Physiology DOI:
10.1152/ajpregu.00437.2005, May 2006
Can New Neurons Learn New Tricks?
Mice given space and stimulation grow new nerve
cells in a part of their brain called the hippocampus. At the same time,
their spatial awareness increases and they become less anxious about the
surroundings. But the growth of new nerve cells and the changes in mouse
behavior are not linked. This new research contradicts the popular
assumption among scientists that new nerves in the hippocampus
contribute to the intellectual boost that comes with a more stimulating
environment. Scientists treated mice with a dose of radiation to stop
new nerve cells from growing in the hippocampus. They then divided the
mice into two groups and placed one group in normal cages and the other
in bigger cages with toys to stimulate the mice to use their brains
more. Six weeks later the animals in more comfortable cages had improved
spatial memory skills and were less anxious than mice in smaller cages,
despite not having any new neurons in their hippocampuses. This result
highlights that new nerve growth is not the most important factor in
changes how the brain functions in response to changes in environment. -
Nature Neuroscience (advanced online publication) DOI: 10.1038/nn1696,
30 April 2006
Mice on Sushi Diet
Good news for sushi lovers: scientists have
found that large amounts of taurine, a chemical found in sushi and
seafood, prevents mice on a high fat diet from gaining weight. A common
belief is that cuisines containing large amounts of fish and seafood
help to promote a healthy heart and reduce obesity. Scientists fed mice
either a high-carbohydrate or high-fat diet. The mice fed a high-fat
diet had less taurine in their blood, and lower amounts of the proteins
needed to make taurine than those given a high-carbohydrate diet. The
decrease in the production of taurine occurred 14 days or more after the
high-fat diet was started. The scientists think that the decrease in
taurine is caused by diet-induced changes in the cells that produce the
chemical. The team also gave the mice a daily injection of taurine. In
mice fed a high-fat diet this prevented them from becoming obese. The
researchers also measured how much energy the mice burned off: a
high-fat diet plus taurine burned the fat faster because these mice used
more energy whilst at rest. - Endocrinology (online) DOI:
10.1210/en.2005-1007, 20 April 2006
Self-defeating Gene Linked to
Lethal Infections
One fifth of people of African
descent have the gene for caspase-12, a protein which shuts down the
bodys immune system, leaving it prone to potentially lethal infections.
Scientists have now uncovered how caspase-12 sabotages the immune
system, which will allow them to develop methods to counter its damaging
effects. Scientists do not know why only African populations retained
this enzyme when other ethnic groups lost it around 60,000 years ago.
It's possible that in Africa the protein could once have had a
protective function fighting autoimmune diseases or perhaps parasites,
like malaria. Today caspase-12 provides no benefit to those who carry
it, and often leaves the body more vulnerable to serious infections.
Scientists conducted laboratory experiments using mice deficient in the
caspase-12 gene and discovered that the protein blocks the body's
inflammatory response to infection by stopping the activity of an enzyme
called caspase-1. The discovery will allow researchers to develop
treatments that may help strengthen the immune system of those people
unfortunate enough to have the caspase-12 gene. - Nature DOI:
10.1038/nature04656, 8 May 2006
'Autistic Mice' Provide
Insight into Disorder
Scientists have altered the
genes of mice to give them the same traits seen in humans with autism.
Deleting a gene from certain parts of their brains makes mice highly
sensitive with poor social interaction skills similar to symptoms seen
in autistic people. This may lead to a better understanding of what
causes autism and autism spectrum disorders. An autistic spectrum
disorder is a developmental disability that affects the way a person
communicates and interacts with those around them. It affects more than
half a million people in the UK. The scientists deleted the Pten
gene from the parts of the mouse brain called the cerebral cortex and
the hippocampus, regions associated with learning and memory. The
genetically altered mice were less socially skilled, interacted poorly
with others, were less nurturing of their young and highly sensitive to
stressful stimuli. Their brains were also bigger, mirroring the increase
in brain size and enlarged heads sometimes seen in people with autistic
spectrum disorders. This new study adds to the understanding of how
genes expressed in the brain may have specific functions relating to
behavior and autistic spectrum disorders. - Neuron. 8 May 2006
Nanotechnology Brightens
Ultrasound
The emerging field of
nanotechnology may one day help scientists to detect diseases like
cancer in their early stages, by improving the quality of ultrasound
images. The ultrasound scans of mice injected with nano-sized particles
produced clearer images, which would make tumors easier to diagnose. The
researchers injected a solution of nanoparticles into the tail vein of
each mouse. They then gave the mice an anaesthetic and took ultrasound
images of their livers every five minutes for 90 minutes after the
injection. The nanoparticles accumulated in the livers. The ultrasound
images grew brighter over the 90-minute period. The ultrasound image
from scans of control mice stayed the same. This study is one of the
first reports showing that ultrasound can detect these tiny particles
when they are inside the body. Nanoparticles may make it possible for
doctors to screen for tumors very quickly, and lessen the need for a
biopsy in some cases. - Physics in Medicine and Biology DOI:
10.1088/0031-9155/51/9/004, 7 May 2006
Brain Cells Choose Carefully
Many people find making
important decisions difficult, and scientists have shown that
indecisiveness may not be an exclusively human trait. Research in
monkeys shows that certain brain cells assign value to different items,
and this helps us to select between different items or goods. The
scientists found these cells in an area of the brain known as the
orbitofrontal cortex (OFC) while studying macaque monkeys which had to
choose between different flavors and quantities of juices. The
researchers correlated the animals' choices with the activity of neurons
in the OFC. Some brain cells would be highly active when the monkeys
selected three drops of grape juice, for example, or 10 drops of apple
juice. Other brain cells encoded the value of only the orange juice or
grape juice. The new findings show an association between the activity
of the cells in the OFC and the processes underlying choice how we make
our choices. - Nature (advance online publication) DOI:
10.1038/nature04676, 3 May 2006
Vaccine plus Antibiotic
Equals Anthrax Protection
Combining an anthrax vaccine
with a short course of antibiotics may be a more effective and practical
way of treating people who are exposed to the deadly bacteria. Monkeys
vaccinated against anthrax and given antibiotics recovered sooner and
survived for longer than monkeys given either treatment individually.
Inhaled anthrax is dangerous because it can form spores that lodge in
the lungs and can remain there for several weeks. Anthrax is easily
treated with antibiotics but once the symptoms of inhaled anthrax begin
it is almost impossible to treat because the bacteria have already
pumped out lethal amounts of toxin. The researchers exposed two groups
of 10 rhesus macaques each to anthrax spores and gave antibiotics for
two weeks. One group also received three doses of the licensed human
anthrax vaccine. Only four monkeys given antibiotics alone lived,
compared to all 10 who got the vaccine also. These animals were immune
to anthrax up to 11 months later, suggesting a long-term benefit from
the vaccine that may also be true for humans. - Proceedings of the
National Academy of Science (early edition) DOI:
10.1073/pnas.0602748103, 3 May 2006
Virus Makes Tumor Cells
Hungry
Scientists have engineered a
virus that tracks down and infects the most common and dangerous form of
brain tumor, and kills the tumor cells by triggering them to 'eat'
themselves. The virus homes in on brain tumors called gliomas in mice,
and causes the cells to digest themselves in a process called autophagy.
Autophagy is a protective process that cells use to consume part of
themselves when nutrients are scarce or to destroy parts of themselves
in order to recycle their components. The viruses infected the tumor
cells and triggered them to digest themselves by inactivating a process
that normally prevents this from happening. Compared to control mice,
the tumors in mice injected with the virus were five times smaller. The
injected mice also survived for longer and the tumor cells showed the
telltale signs of self-digestion. This study shows that identifying
molecules that control self-digestion in cancer cells is key to
understanding how this process is associated with cell death in human
cancers. - Journal of the National Cancer Institute DOI: 10.1093/jnci/djj161,
3 May 2006
Stem Cell Expansion
Scientists working with monkeys
have developed a way to overcome the difficulties of stem cell
transplantation by growing the stem cells in the laboratory and then
transplanting them into monkeys. Stem cell transplants can replace stem
cells damaged or destroyed by cancer therapy, but it is hard to obtain
sufficient quantities for a successful transplant. Switching on a gene
called HOXB4 instructs certain stem cells, called hematopoietic
stem cells (HSCs) to divide and make more stem cells. The scientists
grew stem cells that produced more of the HOXB4 protein than normal.
They then tested the stem cells by transplanting them into monkeys that
had received a lethal dose of radiation. The stem cells improved the
monkeys immune and blood systems. HOXB4 could eventually be used to
improve stem cells transplants in patients. Public Library of Science
Medicine DOI: 10.1371/journal.pmed.0030173, 2 May 2006
Understanding Skin Diseases
Research in mice shows that the
excessive production of a protein called connexion-26 disrupts the
protective properties of the skin, allowing particles to enter the body
and trigger an inflammation cycle. This in turn triggers psoriasis and
may play a role in similar illnesses like asthma, hay fever and eczema.
Connexion 26 connects individual skin cells into a protective barrier
against allergic particles. Scientists bred a strain of mice that
over-produce connexin 26. The mice develop psoriatic-type skin sores,
just like humans with psoriasis. Overproduction of connexion-26 makes
the skin barrier more porous to inflammatory particles, allowing
particles that trigger an immune response to enter the body and cause an
inflammatory reaction that, in turn, causes skin cells to grow rapidly,
further diminishing the protective function of the skin. This cycle
eventually produces common skin conditions such as psoriasis and eczema.
The discovery improves the understanding of psoriasis and eczema, and
may well contribute to other conditions that arise when allergens
penetrate the tissue barrier in the lungs and nose, such as hay fever
and asthma. - Journal of Clinical Investigation DOI: 10.1172/JCI27186, 1
May 2006
New Vaccine Against Deadly
Virus
For the first time scientists
have used an experimental vaccine against the deadly Marburg virus. The
virus, which is similar to that which causes Ebola fever, causes fever
and severe hemorrhaging and can be fatal within a week of infection.
Monkeys given the vaccine were protected from the virus even if they
were not given the vaccine until after they are infected. There is no
cure and no treatment for Marburg disease, which kills between 80 and
90% of infected patients. Epidemics of the disease have occurred in
Angola, and other African countries. Scientists injected eight monkeys
with an extremely high dose of the virus, and gave the vaccine between
20 and 30 minutes later. The vaccinated animals all survived for at
least 80 days, but the unvaccinated monkeys died within 12 days. The
researchers think that the vaccine would probably still work if given up
to 48 hours after a person was infected. The new finding means that one
day it may be possible to immunize researchers infected in laboratory
accidents, as well as health care workers and family members exposed to
the virus while caring for the sick during outbreaks. - The Lancet DOI:
10.1016/S0140-6736(06)68546-2, 29 April 2006
Gene Therapy Could Be Risky
The gene therapy techniques
used to treat children born without a working immune system could be
riskier than scientists originally thought. The therapy is used to treat
children with X-SCID, a genetic disorder that leaves people with little
or no immunity to infection. New research in mice shows that the
treatment may cause cancer. X-SCID is caused by mutations in the
IL2RG gene, which governs the behavior of a protein involved in the
development of a number of immune system cells. Without the protein, the
cells cannot develop normally, and are unable to protect the body.
Doctors use gene therapy to replace the faulty gene with a working one.
Researchers looked into the long-term effects of injecting mice with the
same gene given to X-SCID patients. The scientists studied the mice for
an average of 18 months. A third of the animals developed tumors in
their lymph glands. The implications of this research for humans are
complicated as the results are preliminary and the researchers used much
higher doses of the gene than is given to patients. - Nature DOI:
10.1038/4401123a, 27 April 2006
LOX Protein Unlocks Tumor's
Ability to Spread
US scientists have identified a
key molecule that is crucial for the spread of human breast, head and
neck tumors. By blocking the protein the researchers stopped the spread
of tumors in mice, and they hope it may offer a valuable target for
cancer therapies in humans. The researchers first identified the
molecule, called lysyl oxidase (LOX), by growing human breast cancer
cells on an artificial gel to mimic the environment inside the body.
Cancer cells in which the production of LOX was inhibited could not grow
and spread over the gel. The team then created human breast cancer
tumors made of cells that produced less LOX than normal cells, and
injected these into mice. The tumors were not able to spread from their
original site. The same effect was seen when mice with normal tumors
were given an antibody to block the effect of LOX. The results give a
new insight into the mechanisms of invasion and spread of cancer. The
team is now developing human-compatible antibodies to block LOX. -
Nature DOI: 10.1038/nature04695, 27 April 2006
Bacteria Friendly Towards
Gut
Research in rats shows how
probiotic yoghurt drinks may help ease stomach disorders which are
linked to long-term stress, such as Chrohn's disease, irritable bowel
syndrome (IBS) and ulcerative colitis. Rats given drinking water
containing probiotic bacteria showed less stomach damage by harmful
bugs. The researchers stressed rats by putting them through water maze
tests. Psychological stress is known to be a factor in the development
of some stomach diseases. Half the rats were fed drinking water
containing probiotic bacteria for a period of seven days before and
during the stress tests. The stress made the rats' stomachs leakier; and
increased the amount of potentially harmful bacteria sticking the
stomach wall. Harmful bacteria were also found in the lymph nodes,
suggesting that the harmful bacteria had entered the body and activated
the immune system. Probiotic bacteria minimized the changes in the
stomach lining, preventing the harmful bacterial from sticking to it and
moving into the lymph nodes. The researchers believe that probiotics
probably compete for space with harmful bacteria, helping to dampen down
inflammatory responses. - Gut (online first) DOI:
10.1136/gut.2005.080739, 25 April 2006
Which Brain Deposits Affect
Memory?
Mice with the build-up of
proteins in the brain that is usually associated with Alzheimer's
disease still have a normal memory. This suggests a new target for
Alzheimer's drugs and a new way of understanding how the disease damages
the brain. Scientists think that Alzheimer's is caused by a build up of
a toxic protein called amyloid-beta, which is produced when another
protein, amyloid precursor protein (APP), is cut in two. Cutting APP at
another point produces a different protein called C31, which also has
toxic affects on the brain. Scientists used a strain of mice with an
Alzheimer's-like disease, and bred them so that APP couldn't be cut into
C31. The mice still had a build-up of amyloid-beta in the brain, but
their brains were a normal size and contained a higher density of nerve
connections compared with C31-producing mice. The mice also did twice as
well on a standard memory tests. The results question whether APP is the
most damaging protein in Alzheimer's disease. Preventing APP from being
cut into C31 could be an effective strategy in avoiding the memory loss
and brain damage of Alzheimer's. - Proceeding of the National Academy of
Sciences (early edition) DOI: 10.1073/pnas.0509695103, 25 April 2006
Stem Cells Can Regenerate
Damaged Kidneys
Stem cells from bone marrow can
be used to regenerate damaged kidney cells in mice with the equivalent
of Alport syndrome, the second most common genetic cause of kidney
failure in humans. This new knowledge has potential for managing this
inherited kidney disease and offers the first example of how stem cells
may be useful in restoring organ function. In normal kidneys, a protein
called type IV collagen plays a key role in filtering the blood.
However, in patients with Alport syndrome, mutations in three different
genes for type IV collagen cause a breakdown of the kidney's filtration
system. This results in blood and protein leaking into the urine and
eventual kidney failure. The researchers transplanted bone marrow stem
cells into mice genetically altered to mimic Alport syndrome. Within a
period of about four weeks about one tenth of the transplanted stem
cells had been incorporated into the damaged regions of the kidney and
developed into healthy cells. This helped to repair the kidney and
improve its functioning. - Proceedings of the National Academy of
Science (early edition) DOI: 10.1073/pnas.0601436103, 24 April 2006
Cause of Malarial Anemia
Scientists say a protein
produced by the body's immune cells when it is infected by malaria is a
cause of anaemia a severe complication of the disease. Immune cells in
mice produce a protein called MIF, which decreases the production of red
blood cells in the bone marrow. Red blood cells are needed to carry
oxygen around the body. A deficiency in red blood cells leads to anaemia,
which can have serious consequences in patients that are already
infected with malaria. Mice bred without the gene for MIF and infected
with Plasmodium chabaudi, the mouse equivalent of the parasite that
causes the disease in humans, had less severe anaemia and improved
production of red blood cells. More of them survived than normal nice.
The data suggest MIF may influence the immune response to malaria and
the likelihood of complications caused by anaemia. - Journal of
Experimental Medicine DOI: 10.1084/jem.20052398, 24 April 2006
Pituitary Hormone Promotes
Bone Loss
New evidence shows that
estrogen may not be the only hormone that causes the bone disease
osteoporosis. Research in mice shows that high levels of
follicle-stimulating hormone (FSH), a hormone produced in the pituitary
gland, also causes osteoporosis and mice that are resistant to FSH are
also resistant to osteoporosis. Osteoporosis usually affects older
women, whose ovaries no longer produce estrogen. This disrupts the
bodys balance between bone growth and loss, and more bone is lost than
is made. This makes the bones more brittle and prone to breakage.
Mice that either could not produce, or could not detect, FSH became
resistant to bone loss, even when their ovaries stopped producing
estrogen. Mice with normal ovaries and approximately half the normal
concentration of FSH also show an increase in bone mass, due to a
decline in bone loss caused by cells known as osteoclasts, which break
down bone. FSH also causes receptors found on the surface of osteoclasts
leading to form new bone cells. The findings change our perceptions of
how pituitary-derived hormones work, and challenge the long-standing
theory that declining estrogens levels alone lead to osteoporosis after
women go through menopause. - Cell, 21 April 2006
Combination Promises
Diabetes Cure
Scientists have taken a major
step towards a cure for type 1 diabetes. The study combined two
different treatments, which are currently being tested individually in
human clinical trails, in laboratory mice. The scientists found that the
combination treatment reversed type 1 diabetes in the majority of
animals tested. The new approach focuses on teaching the immune system
to tolerate, rather than attack, the cells in the pancreas that produce
insulin. An antibody calms the immune system and lessens the attack on
the pancreas, and an insulin-like protein acts like a vaccine and causes
the release of special regulatory cells that protect the pancreas. The
combination of the two treatments was twice as effective as the
individual treatments have been in humans. The effect of the treatment
lasted longer and had fewer side effects in mice than either therapy has
shown alone in the human studies. The researchers hope to begin testing
the combination therapy in human clinical trials later this year. -
Journal of Clinical Investigation DOI: 10.1172/JCI27191, 20 April 2006
Monkeys Mimic SARS Infection
in Children
Scientists have turned to
monkeys in their bid to investigate the virus that causes SARS, and to
develop vaccines and treatments for us if there is another SARS
outbreak. The scientists infected eight monkeys by injecting the virus
into different parts of the body: four in the lungs, two in the nose and
eye, and two intravenously. All animals were infected by the virus, but
none of the animals developed fever, and only those in the first two
groups had mild-to-moderate symptoms (decreased activity and feeding,
and slightly labored breathing). The animals intravenously infected
animals showed no clinical symptoms. In addition, six animals that were
reinfected with SARS 13 weeks after the first infection were immune to
new infections. In all cases, the infection was less severe in the
monkeys than in humans, and the scientists think the infection is
similar to the milder form of the infection seen in young children. -
Public Library of Science Medicine DOI: 10.1371/journal.pmed.0030149, 18
April 2006
New Nerve Imaging Techniques
Scientists are using innovative
new imaging techniques to study the interactions between muscles and
nerves in living animals. They observed nerve-muscle junction activity
using fluorescently-tagged molecules that bind tightly to acetylcholine.
This naturally-occurring chemical carries messages between muscle-nerve
connections, called synapses. The researchers tagged acetylcholine with
a fluorescent toxin from the green mamba snake, which blocks
acetylcholine activity. They then focused on easily accessed neck
muscles in mice, where there are many synapses that can be studied over
the course of several days. Such insights will help researchers target
treatments more precisely. Understanding the biology of acetylcholine
will help the design of new drugs for curing diseases that damage
nerves. - Journal of Biological Chemistry DOI: 10.1074/jbc.M507502200,
14 April 2006
Depressed Monkey See,
Depressed Monkey Do
Scientists are turning to
monkeys to understand the characteristics of depression. The central
nervous systems of depressed monkeys have the same characteristics as
humans. The finding could lead to new ways to test depression treatments
more effectively. The brain scans of seventeen female monkeys produced
three-dimensional images of 11 parts of the brain. The researchers
injected each monkey with a tracer molecule that binds to serotonin, a
brain chemical that controls mood, to allow them to see in which areas
serotonin binding was lowered. The scans looked at a specific type of
receptor (called the 5-HT1a receptor) that binds to serotonin. Depressed
people have lowered serotonin binding in their brain. The areas of the
monkey's brain that had lower serotonin levels and lowered serotonin
binding are the same regions affected in humans. Monkeys offer a special
opportunity for research because they are among the few animals that
have menstrual cycles and complex cognitive functioning, and so could be
used to test treatments for depression. - Archives of General
Psychiatry, April 2006
Pigs Big on Fatty Acids
Scientists have bred pigs to
produce omega-3 fatty acids. This experimental technique raises the
possibility that omega-3 oils could be gained from a source other than
oily fish. Omega-3 oils are fatty acids found in fish such as salmon,
sardines and tuna. Recent research suggests that omega-3 fatty acids may
lower the risk of heart disease and heart attacks. The researchers
transferred a gene called Fat1, which controls the production of
omega-3 fatty acids from other types of fatty acids, into fetal cells.
They then cloned the fetal cells by transferring the nuclei of the
genetically modified cells into pig egg cells emptied of genetic
material. The eggs were then implanted into a sow, which gave birth to
pigs that produced high levels of omega-3 fatty acids. Studying
pigs provides a model of how increased omega-3 levels in the body help
the heart. There could also be potential benefits if the animals were
put into the food chain, to provide omega-3 fatty acids without relying
solely on diminishing fish supplies or supplements. - Nature
Biotechnology (advanced online publication) DOI: DOI:10.1038/nbt1198, 26
March 2006
Stem Cells Found in Adult
Mouse Testes
Male mice have a constant
supply of sperm-gene |