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Research Focus 2006:

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 don’t 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 didn’t 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 brain’s 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 body’s 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 monkey’s 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 body’s 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