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

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

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

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 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

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

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-generating stem cells in their testes. If the same is true in men, testes could be used as a source of stem cells for regenerative treatments for humans. The cells can be taken directly from the testes and grown to provide new stem cells, avoiding the need for cloning or destroying embryos. The researchers created a genetically modified breed of mice, in which the sperm-producing stem cells were labeled with a fluorescent marker, to identify the stem cells in their testes. The team then injected these cells into young mouse embryos and implanted these embryos into female mice. 90% of the embryos developed normally. It is unclear whether the cells have this capacity under natural conditions inside the testes, but the techniques used could be used to produce similar results in men using stem cells taken from their testicles. - Nature (advanced online publication) DOI: 10.1038/nature04697, 24 March 2006

New 'Double-whammy' Technique for Tumors

Cancer biologists have used a combination of two existing treatments to create a new experimental technique for improved cancer treatment in mice. The combination of a cancer-killing virus and a tumor-targeting immune cell kills tumors. The scientists identified a type of immune cell called cytokine-induced killer (CIK) cells that target particular molecules on the surface of tumor cells. They inserted the smallpox virus into CIK cells and then injected into mice with cancer.  Between four and seventy-two hours later the vaccine bursts out of the immune cells and destroys cancer cells. This is enough time for the CIK cells to locate tumors and bury deep inside them, to prevent the vaccine cells from infecting or damaging surrounding healthy cells. Two days after injection the CIK cells had targeted the tumors and the vaccine was replicating deep inside the tumors. CIK cells were not detectable in other parts of the body. All eight treated mice completely recovered from their tumors. The study is small but this is the first time researchers have succeeded with this treatment in a clinically relevant setting. - Science DOI: 10.1126/science.1121411, 24 March 2006

Stop Immune System to Save Pancreas

Three independent groups of scientists have reversed diabetes in mice by stopping the immune system before it is able to destroy all the insulin-producing cells in the pancreas. Overstimulating the immune system prevents it from attacking the pancreas and destroying the cells needed to produce insulin. There is a window of time, after the onset of diabetes but before all the cells are destroyed, when the mouse pancreas can be rescued. This new technique shows that it may be possible to make new insulin-producing cells without the need for a pancreatic cell transplant. Each group treated a group of mice with Freund's adjuvant, a mixture of oil, water and parts of dead bacteria. This overstimulates the immune system cells that are attacking the pancreas and causes white blood cells to self-destruct. This stops the immune system from attacking the pancreas. New cells are able to grow and the damaged pancreas is able to heal itself. The researchers hope that the procedure will eventually eliminate the need for pancreatic cell transplants that currently require long-term regimens of immune suppressant drugs. - Science DOI: 10.1126/science.1123500, 24 March 2006

Secrets of 'Cellular Jekyll and Hyde' Revealed

Research in mice and rats shows that immune cells called microglia, which turn on the body and attack the cells that normally protect the nerves, can also have positive effects on the nervous system. Healthy microglia can be damaged by a protein called interferon gamma (IFN-gamma). IFN-gamma is produced by the body's T-cells and stimulates microglia to produce a protein called tumor necrosis factor alpha (TNF-alpha). TNF-alpha strips nerve cells of myelin, their protective covering, leading to muscle spasms and memory difficulties. The researchers looked at the response of microglia to various levels of IFN-gamma, and a related protein called interleukin-4 (IL-4). When IFN-gamma levels are low, microglia protect neurons from damage, but high levels of IFN-gamma stimulate microglia to damage myelin. IL-4 overcomes the malicious effects of IFN-gamma and TNF-alpha and switches the microglia from damaging to protective. Under these conditions, microglia encourage the cells that make myelin to repair damaged neurons. The results are encouraging and offer new directions for the treatment of multiple sclerosis. - Journal of Clinical Investigation (published online) DOI: 10.1172/JCI26836, 23 March 2006

Horses, Mice and Bird Flu

Scientists have used antibodies produced in horses to treat bird flu in mice. The technique could, in theory, be used to produce antibodies against a pandemic strain of the bird flu virus H5N1. The scientists injected horses with a chicken vaccine against H5N1, to make them produce antibodies against the virus. They then collected the horses' blood, separated out the antibodies and treated them so that they were less likely to cause an allergic reaction when injected into another animal.  The researchers gave mice a dose of the H5N1 virus and then injected them with the horse-derived antibodies 24 hours later. All the mice survived the normally lethal bird flu infection. The results provide the evidence needed to proceed to future monkey or human trials of horse-derived antibodies to treat bird flu. - Respiratory Research DOI: 10.1186/1465-9921-7-43, 23 March 2006

Scientists Discover Long-forgotten Memory Gene

Scientists have located one of the genes behind long-term memory and the possible genetic causes of long-term memory loss. The researchers genetically engineered mice to remove both copies of the clb-b gene, and then compared how well the genetically engineered mice performed in memory tasks compared to normal mice. Both groups of mice were tested to see if they could remember the location of a hidden platform in a water maze. The normal mice had no long-term memory of performing the task, but the experimental mice without the clb-b gene were able to remember the task six weeks later. The results are of particular interest to Alzheimer's researchers as they provide an important opportunity to trace the mechanisms behind long-term memory loss. - Proceedings of the National Academy of Science (early edition) DOI: 10.1073/pnas.0601043103, 20 March 2006

Mouse Cancer Vaccine

Scientists have identified a molecule that could be used to vaccinate against growing tumors. The outcome of their research in mice points towards new methods of treating metastases – the spread of cancer to other parts of the body and the most common cause of death from cancer.  The researchers investigated the function of a type of immune cell called cytotoxic T-lymphocytes (CTLs) that recognizes other cells that have defects similar to those in growing tumors. These defects allow the cell to avoid the immune system response that CTLs normally produce. The researchers identified a short peptide molecule that CTLs recognize which they used to vaccinate and protect against the spread of tumors from different tissues in mice. - Nature Medicine (advanced online publication) DOI: 10.1038/nm1381, 19 March 2006

New Hepatitis C Strain Infects Animals

Developing a treatment for Hepatitis C (HCV) has been hindered by the difficulty in isolating the live virus from infected patients and growing it in the laboratory. Now scientists have shown that a strain of HCV they created and grew in the lab is also infectious in mice and chimpanzees. The researchers used a strain of HCV they grew in the lab called HCVcc. Chimpanzees and mice carrying grafted pieces of human liver were infected with HCVcc, and in both cases the infection lasted as long as 15 weeks. The infected mice were able to pass the infection onto other mice. Samples from both animals were able to be extracted and grown in the laboratory and were more infectious than the original HCVcc. The ability to study a genetically engineered virus in the test tube and in living animals allows scientists to study the HCV life cycle, and will help them develop an effective treatment for the liver disease. - Proceedings of the National Academy of Sciences DOI: 10.1073/pnas.0511218103, 7 March 2006

Medical researchers have used a combination of different techniques to treat Duchenne muscular dystrophy (DMD) in mice. DMD is a muscle disease caused by mutations in the gene for dystrophin, a skeletal muscle protein. Mutations in the dystrophin gene cannot normally be treated by replacing the mutated gene with a normal one. To get gene therapy to work, scientists injected mice with a virus which contained a short strand of antisense RNA. The strand is complementary to the genetic material produced by the dystrophin gene, and so binds to it and partially corrects the defect of the mutated dystrophin gene. Once injected into the mice the genetic material was taken up and produced in all parts of the body, including the heart and the diaphragm; the organs most seriously affected in humans with DMD. Although the dystrophin protein produced is shorter than normal, it functions enough to improve muscle performance and running endurance. This technique could provide a basis for the use of gene therapy in the treatment of Duchenne muscular dystrophy in humans. - Proceeding of the National Academy of Science, Early Edition DOI: 10.1073.pnas.0508917103, 24 February 2006

Sex Gene Linked to Parkinson's in Men

Scientists have discovered that a sex gene also has a role in the development of Parkinson's disease. A new study in rats shows that the Sry gene, which is responsible for determining the sex of male embryos, is also produced in the same regions of the brain that are affected by Parkinson's. The research could explain why men are up to one and a half times more likely to develop Parkinson's than women. The team found that Sry is expressed in the nerve cells of a particular region of the brain in adult male rats associated with motor control, the substantia nigra. Lower levels of the SRY protein also lowers the level of an enzyme called tyrosine hydroxylase, which is involved in the production of dopamine. The level of the enzyme was unaffected in female rats. This may explain why men are more likely to suffer from Parkinson's disease: lowered dopamine levels cause the gradual loss of motor control that is characteristic of the illness in humans. - Current Biology, 21 February 2006

Enzyme Frees Bacteria from DNA Nets

Researchers have found that Streptococcus A bacteria use an enzyme to escape the body's immune system. This new research in mice could lead to new treatments for the bacterial infections the bacteria cause. The 'Strep A' bacteria are responsible for some skin and throat infections, toxic shock syndrome and the 'flesh-eating' disease (necrotizing fasciitis). Scientists examined the interaction of Strep bacteria with neutrophils, specialized white blood cells that release 'nets' composed of DNA and toxic compounds to trap and kill invading bacteria. The team removed the gene for an enzyme that normally allows Strep A bacteria to break down the DNA in the neutrophil nets. Mice injected with this strain of the bacteria did not develop a Strep A infection. Non-infectious bacteria into which the gene had been inserted were able to break down DNA, escape killing by neutrophils, and produce a skin ulcer in the mice. Mice infected with Strep A and then injected with a chemical that blocks the action of the DNA-degrading enzyme had lower bacterial counts and less tissue damage than mice given a placebo. The findings could lead to novel treatments for Strep-related diseases that inhibit the Strep DNA-degrading enzyme instead of killing the bacteria with standard antibiotics. - Current Biology, 21 February 2006

Brain Communicates via 'Addiction Molecule'

A protein in the brain that is essential for wakefulness and appetite also has a central role in the development of addiction. Research in rats shows how the protein orexin A works at the molecular level, and may provide a new target for potential drugs to treat addiction. Orexin A is involved in the communication between the nerve cells in the brain that release dopamine, a chemical central to learning and memory. This communication also plays a key role in the symptoms of drug abuse; the experience of a high and drug cravings. Orexin A interacts with NMDA-receptors: proteins that detect the presence of dopamine at the connections between nerve cells in the brain. This interaction enhances the ability of the receptors to promote the release of dopamine. This in turn promotes the communication between nerve cells in the brain that leads to addiction. The scientists injected the rats with a molecule that blocks the action of orexin A. This weakened the critical communication between nerve cells in the brain, and prevented cravings in rats treated with cocaine. These promising results point to a novel target for new medicines to treat drug addiction and prevent relapse. - Neuron, 16 February 2006

Botox Targets Tumors

A study in mice indicates that the cosmetic treatment Botox may have a new use increasing the efficacy of chemotherapy and radiation treatments in cancer therapy. MRI scans showed stunted tumor growth after Botulinum neurotoxin type A injections into two types of mouse tumors. The researchers found that the Botox injections caused the tumors’ blood vessels to open by temporarily paralyzing the vessels' muscular contractions – allowing for more effective destruction of previously resistant cancer cells. The study is the first to test the idea of using Botox against cancer and marks a relatively new area of cancer research, which focuses on briefly opening blood vessels that feed tumor cells for better delivery of therapeutic agents. Until recently, much cancer research has focused on the opposite: reduction of blood vessel growth, which starves tumor cells of nutrients and oxygen (hypoxia). Unfortunately, hypoxic tumors are more resistant to radiation and chemotherapy, requiring increasing doses. The temporary opening of the blood vessels allows the tumor to reoxygenate, restoring susceptibility to radiation and chemotherapy. The levels of Botox used in the mice are comparable with those already used in cosmetic treatments, indicating that toxicity is unlikely to be a problem. - Clinical Cancer Research, 15 February 2006

New Movements in Ataxia Treatment

Scientists have used mice to understand the causes of ataxia, an inherited disorder that causes poor balance, loss of posture and difficulty completing rapid coordinated movements. This new information could lead to improved treatments of the disease. Episodic ataxia type-2 results from gene mutations that affect calcium channels, which are involved in releasing neurotransmitters in the brain and regulating excitability in neurons. The researchers investigated the causes of this type of ataxia by studying specialized cells in the brain's cerebellum called Purkinje cells, which are rich in calcium channels and help to coordinate movement. By studying mice with impaired calcium channels in their Purkinje cells, the researchers found the Purkinje cells could not interpret nerve signals or direct muscle movements. This led to a loss of muscle control in the mice. The researchers were able to reverse this effect with a drug called EBIO, which improved the muscle control of the ataxic mice. The scientists are hopeful that their findings will lead to drugs that will improve the lives of people with this ataxia. - Nature Neuroscience, online DOI: 10.1038/nn1648
12 February 2006

Ancient Fish DNA Treats Hemophilia

Scientists have treated hemophilia in mice using an ancient 'parasitic' form of DNA found in fish that inserts itself into the genome. The discovery may lead to a safe way to stimulate the production of a missing protein in patients with the most common form of the hereditary bleeding disorder, which causes excessive blood loss. The most common form of hemophilia, hemophilia A, is caused when people do not produce enough of a protein called Factor VIII. The less Factor VIII a person produces, the more severe the hemophilia is. The researchers used the ancient fish DNA to transport a functional copy of Factor VIII into the mouse genome, replacing the faulty gene. Higher levels of Factor VIII were detected in the bloodstream, and the mice no longer showed the symptoms of hemophilia A. This study shows that it may be feasible to transfer genes into humans as a treatment for hemophilia. Currently the only safe treatment for hemophilia is Factor VIII injections, which are expensive and have only short-term effects. - Molecular Therapy, online DOI: 10.1016/j.ymthe.2005.11.021, 7 February 2006

Loneliness Bothers Females Less than Males

Female rats cope with stress and social isolation better than males. New research into the physical ways that female rats cope with stress and loneliness may also shed light on why women also seem to be better at handling loneliness than men. Using 120 rats, researchers studied the long-term effects that isolation from other rats and physical stress would have on their immune system. The rats were isolated for three months and then injected with seaweed. The rats that had been neglected and prevented from interacting with other rats showed a delayed immune response. The difference between male and female rats was seen when the isolation was followed by a 30-minute period of acute physical stress. Several weeks after the isolation and stress, male rats still showed a slower inflammatory response than female rats when injected with seaweed. This study may shed light on why socially isolated men are more vulnerable to disease and death than isolated women. - American Journal of Physiology – Regulatory, Integrative and Comparative Physiology DOI: 10.1152/ajpregu.00368.20050363-6119, February 2006

As in man, policing is essential for achieving social stability in primates. Research on a captive group of pigtailed macaques shows that 'conflict management' has a positive effect on social networks. The researchers studied the effect on social networks – grooming, play, contact-sitting and proximity – within a group when individuals who were key 'policing figures' were removed. They found that individuals have significantly more play and grooming partners in the presence of policing and are more willing to mix with others. In the absence of policing, individuals are more likely to form cliques and tend to sit in areas away from others, in order to avoid conflict. It seems that policing gives rise to larger, more structured social networks by encouraging large groups of individuals to groom and play together, and reducing disruption that can lead to group fragmentation. The social networks are important behavioral assets as they increase infant survival and encourage cooperative behavior, social learning and cultural traditions. The study has implications for how animal social organizations are built. - Nature, 26 January 2006

New Tumor Suppressor Gene

Using mice, researchers have identified a new tumor suppressor gene, TCF21. This gene is not inactivated by a genetic mutation but by a chemical process called DNA methylation, which can be reversed to restore gene activity. Silencing TCF21 can alter normal epithelial cells, causing them to change to a more primitive state that is capable of migrating to other tissues which could aid the metastasis of tumors. Epithelial cells form the skin and line the body's passageways and hollow organs; they are the source of the most common forms of cancer. The researchers showed that TCF21 can be silenced by DNA methylation, and that drugs to reverse methylation can reactive it. Mice injected with lung-tumor cells that had an active TCF21 gene developed tumors that were two to three times smaller than tumors that developed from cancer cells with a silent TCF21 gene. TCF21 is often silenced or lost in a variety of human cancers, including breast and ovarian cancer, melanoma and lymphoma. The findings might therefore lead to new strategies for the treatment and early detection of cancers, and to a better understanding of the molecular changes that occur in tumor cells during cancer progression. - Proceedings of the National Academy of Sciences, 24 January 2006

Leptin an Antidepressant?

A study has shown that the appetite-control hormone leptin staves off symptoms of stress in rats, and might lead to new ways to fight human depression. Researchers stressed rats, for example by separating them from other animals. The rats' leptin levels plunged at the same time that they showed behavioral changes such as losing interest in a sugary drink; the kind of apathy that is often associated with human depression. The forced swim test is widely used to screen for new antidepressants, as depressed and apathetic rats 'give up' much sooner than happy ones. Injections of leptin into stressed, but otherwise healthy, animals produced results at least as good as one proven depression treatment. This could lead to new therapies for depression; important as many patients do not respond to existing treatments. However, much more work is needed because the hormone also exerts effects on appetite, reproduction and the immune system – scientists would probably need to find molecules that can specifically mimic leptin's anti-depressant effects on the brain without causing unwanted side effects. - Proceedings of the National Academy of Sciences, Early Edition DOI: 10.1073/pnas.0508901103 19 January 2006

Lethargy Is Fat Burning

Constant darkness throws a molecular switch in mammals that shifts the body's fuel consumption from glucose to fat, and induces a state of torpor in mice. A series of darkness experiments pinpointed a messenger hormone called 5'-AMP as the key mediator of the constant darkness effect, switching mice from a glucose-burning, fat-storing state to a fat-burning, glucose-conserving lethargy. Mice injected with the hormone were found to have a lower body temperature, a sign of torpor, and core body temperature measurements confirmed their lethargic state. Mice kept in constant dark also ate less, lost weight, and showed evidence of increased fat consumption, all hallmarks of hibernation in larger mammals. The hormone has previously been shown to regulate enzymes controlling glucose usage and production. The brain requires glucose to function. By switching the primary source of energy in other organs from glucose to fat, 5'-AMP saves glucose for brain function. As well as providing insight into mammalian hibernation, the researchers note that the hormone may also provide new directions in obesity and type 2 diabetes research. - Nature, 19 January 2006

Another Use for 'Junk'

DNA A study in rats has found a new mechanism for regulating brain function. The researchers have discovered a microRNA from non-coding regions of the genome (often called 'junk' DNA) affects the development of synapses in the brain. MicroRNAs regulate gene activity by suppressing gene expression. Experiments in rats showed that a microRNA called miR-134 regulates the size of a nerve's 'dendritic spines' (part of the synapse, these protrusions receive signals from other nerves). When exposed to miR-134, spines shrank which weakened the synapse. When miR-134 was blocked, spines grew which strengthened the synapse. miR-134 works by blocking a gene called Limk1, which causes dendritic spines to grow. The researchers believe that miR-134 – and other microRNAs – may play a role in fine-tuning cognitive function by selectively controlling synapse development in response to environmental stimuli. They also speculate that miR-134 may be relevant to mental retardation and autism: loss of Limk1 due to a chromosomal deletion is associated with Williams syndrome, and the pathway that activates Limk1 includes proteins that are disabled in tuberous sclerosis and Fragile X syndrome. All three genetic disorders can cause cognitive impairment and autistic-like behaviors. - Nature, 19 January 2006

Sight and Sound

Scientists report a link between sight and sound in the barn owl's brain, a phenomenon previously reported only in primates. The experiment demonstrated a fundamental principle of how the brain pays attention and concluded that the circuits in the brain that process sounds are strongly influenced by the circuits that control where the animal is looking – the direction of gaze. The ability to hear and the direction of gaze aren't necessarily linked as sounds originating from any direction don't usually need to be seen to be heard. In primates, the circuits in the brain that control gaze direction affect how the brain processes auditory information; the finding that this occurs in owls as well means there are many more opportunities for research in different kinds of animals to study how the brain is able to sort out incoming sensory information. The fundamental mechanisms are likely to be the same in all vertebrates, as even frogs and fish have gaze control.  Learning more about brain mechanisms that control attention may help improve understanding of human attention and learning disorders, as well as schizophrenia. - Nature, 19 January 2006

New Peptide Vaccines

Mouse studies have given important information about a new type of vaccine being developed. 'Protein-based' or 'peptide' vaccines teach the body how to recognize viruses by exposing the immune system to harmless snippets of viral proteins. This causes the body to produce T cells that remember these proteins in case they are encountered again. A common concern with any type of vaccine, however, is whether it can cause adverse affects if the person has already been exposed to the virus in question. The researchers investigated this by infecting four mice with lymphocytic choriomeningitis virus (LCMV). Eight days later, the team vaccinated these mice either with a fragment of LCMV protein or with saline. The saline-injected mice had a normal T-cell response with no harmful side effects. The peptide-injected mice had a much larger pool of active T cells, but rather than the extra T cells being of benefit, these mice developed hypothermia and other symptoms and died within hours of injection. The reason is that T cells secrete toxic compounds, so too many can harm the host. This study has implications for improving the design of such vaccines for humans: it does not mean that peptide vaccines are not practical, but that the dose must be carefully determined. - Journal of Clinical Investigation, online DOI: 10.1172/JCI25608  19 January 2006

Mice Mimic Alzheimer's Well

A new study indicates that mice, which do not have the extensive nerve death or the severe behavioral symptoms of Alzheimer's, can nevertheless accurately mimic the early cellular processes that lead to the disease. The study suggests that Alzheimer's may be triggered when adult brain cells try to divide. For unknown reasons, neurons affected by Alzheimer's (and other neurodegenerative diseases) often start to divide before they die. The researchers compared the brains of three different mouse models of Alzheimer's with brains from normal mice. They showed that abnormal cell division starts six months before amyloid plaques or other markers of the disease appear. It is therefore unlikely that the plaques themselves trigger the disease process.  The likely cause of Alzheimer's symptoms is tiny clumps made up of several amyloid beta molecules (called micro-molecular aggregates) that form before the plaques: all three mouse models had mutations in the gene that codes for amyloid precursor protein. The similarity between affected brain regions in these mice and in people with Alzheimer's also supports this hypothesis.  If the cell division could be stopped, it might stop neurons from dying prematurely. This could result in a potential new therapy for Alzheimer's and other diseases, including stroke, amyotrophic lateral sclerosis (also known as Lou Gehrig's disease), and HIV dementia. - The Journal of Neuroscience, online DOI: 10.1523/JNEUROSCI.3707-05.2006 18 January 2006

Skin Cancer Signaling

Researchers have identified two key protein degradation signals that directly affect tumor development in mice with a type of human skin cancer, basal cell carcinoma (BBC). These signals mediate the Sonic Hedgehog (Shh) developmental signaling pathway within cells. Abnormal Shh signaling is implicated in about a quarter of human tumors. The signals are two sequences in the Gli1 protein, Dn and Dc, which are recognized by the proteasome (cell proteins that degrade damaged or unwanted proteins) and therefore assist Gli protein destruction. Mutations in these sequences prevent Gli1 breakdown, so Gli1 protein builds up, – leading to increased tumorigenesis. In other words, normal cells have a way of protecting themselves from too much active Gli protein by marking it for destruction, but cancer cells appear to have disarmed that ability. The researchers used transgenic mice with different forms of Gli1 to show the link between Gli1 accumulation and tumor development. Mice with a mutated form of Dn or Dc (some breakdown of Gli1 still occurred) developed tumors sooner than those with normal Dn and Dc sequences. Remarkably, mice with mutated forms of both Dn and Dc, (Gli1 was not degraded at all) die at birth, showing severe skin lesions similar to human BBC tumors. This study could lead to ways to enhance the cell's ability to get rid of Gli and halt cancer development. - Genes and Development, online advance DOI: 10.1101/gad.1380906 18 January 2006

Cloned ES Cells Genetically Normal

Scientists report that stem cells derived from cloned embryos appear genetically identical to those created by fertilization in mice. The study compared five stem cell lines from cloned mouse embryos with another five lines from conventionally fertilized embryos using microarray chips, which enable the expression of thousands of genes to be investigated. Each chip contains probes that match particular gene sequences and fluoresce according to the levels of genetic expression. In total, the group analyzed the activity of about 5,000 different genes in the stem cell lines. They found no significant difference in gene expression. This suggests that there are no genes that are universally activated or disabled in cloned stem cells as compared with their normal stem cell counterparts – i.e. cloned embryos are indistinguishable from naturally fertilized ones. This is reassuring as it addresses the concern that stem cells from cloned embryos might contain unusual genetic features that could make them unsuitable for therapeutic purposes. Proceedings of the National Academy of Sciences, Early Edition DOI: 10.1073/pnas.0510485103 17 January 2006

Researchers have taken a step closer to understanding the basis of a severe epilepsy and mental retardation syndrome by developing a mouse model for a severe brain disorder in newborn children called lissencephaly, or 'smooth brain'. Children with a genetic alteration in a gene called doublecortin suffer from epilepsy and mental retardation due to a defect in how the neuronal stem cells are positioned within the cerebral cortex. Only four, instead of six, layers of cortex are formed, and the cerebral cortex of these patients lacks most or all of the hills and valleys of the normal mammal brain. Scientists removed two genes from the mice; doublecortin and a closely related gene with a similar structure known as doublecortin-like kinase. The mice showed features similar to those expected in human lissencephaly; neuronal stem cells failed to send progeny cells to the correct position within the brain. As a result, the cerebral cortex did not show the normal six-layered structure characteristic of the mammalian brain. This study will allow us to begin to better understand what goes wrong in lissencephaly, and to use these mice to figure out why children with this disease develop seizures and mental retardation. - Neuron, January 2006

Metastasis Suppression

Researchers have shown that a gene, caspase 8, commonly lost during neuroblastoma tumor formation (one of the most aggressive cancers in babies and children) is in fact a 'metastasis suppressor' gene. The findings provide important new insights into the biology of metastatic disease – where tumor cells have the ability to travel to other sites within the body – and lay the necessary groundwork for developing targeted therapies designed to halt the spread of neuroblastoma, and possibly other cancers. Caspase 8's normal role is to act as a suicide gene, killing the cell in response to cues from the immune system, or when the cell is in the wrong place. The latter is a mechanism to ensure cells survive only in appropriate tissues, for example, liver cells in liver tissue and skin cells in skin tissue. Some cancer cells have found a way to escape this safeguard the body has developed. These cells may suppress or even delete caspase 8, freeing themselves to become much more aggressive and survive in distant sites in the body. A number of other cancers may use this same mechanism for regulating their metastatic properties, which the researchers are now studying. This work opens up a new way of thinking about cancer therapy: it may be possible to develop drugs targeted at restoring caspase 8, which could stop secondary tumors. - Nature, online DOI: 10.1038/nature04323, 5 January 2006

On/off Gene Therapy System

Using rats, scientists have developed a new method of signaling therapeutic genes to turn 'off' or 'on', which could enable scientists to fine tune genetic- and stem cell-based therapies so that they are safer, more controllable and more effective. The researchers created a genetic switch system that is turned on in the presence of the antibiotic tetracycline. The switch system also produces a protein called silencer, which completely shuts down gene expression in the 'off' state, thereby preventing leakage of the therapeutic gene when it is no longer needed. This novel vector system is much less likely to create an undesirable immune response in the host and would still respond to infection by wild type adenovirus (a non-engineered virus that causes conjunctivitis and upper respiratory tract infections) which is present in a high percentage of patients undergoing clinical trails. This immune response has been a major obstacle in bringing the testing of genetic therapies to humans. The researchers are planning to use this genetic switch to produce compounds that reverse the symptoms of Parkinson's disease patients and rescue damaged neurons. They hope to begin a Phase 1 trial in humans in the near future. - Journal of Virology, online DOI: 10.1128/JVI.80.1.27-37.2006, January 2006

Soy Bad for HCM Hearts

Transgenic male mice carrying the mutation for hypertrophic cardiomyopathy (HCM) were severely affected when they were fed a soy diet, showing enlarged heart muscles and eventual heart failure. When they were switched to a diet of milk protein their condition improved markedly. However, transgenic female mice with the HCM mutation were relatively unaffected by the soy diet. The researchers believe that heart deterioration in male mice was due at least in part to plant-based estrogens in the soy food diet. HCM is the leading cause of death in young athletes and affects about one in 500 people. Soy foods and diet supplements are perceived to be a health benefit to humans: consumers spent an estimated $4.7 billion on them in 2005. The researchers did not think that normal, healthy people should be alarmed by the results of this study, but the medical community is becoming more cautionary about the ingestion of huge quantities of dietary supplements, including soy phytoestrogens. - Journal of Clinical Investigation, online DOI: 10.1172/JCI24676  January 2006

How Fatty Diets Cause Diabetes

New research using mice explains the mechanism behind the widely recognized link between a high-fat diet and type 2 diabetes, providing an insight into how high-fat diet-induced diabetes may be prevented. The study identifies a molecular link between the consumption of fatty foods and the disruption of insulin production. A single gene encoding an enzyme called GnT-4a is key to enabling the beta cells in the pancreas to sense blood glucose levels and appropriately produce insulin. However, this enzyme is suppressed by a high-fat diet, resulting in pancreatic beta cell failure and eventually leading to type 2 diabetes. Mice lacking the GnT-4a gene had high blood glucose concentrations, the first measure of diabetes. The consequent failure of beta cells to normally secrete insulin resulted in development of the disease. These findings suggest that susceptibility to type 2 diabetes may result from inherited differences in GnT-4a that may ultimately affect its level or activity. Understanding this mechanism could lead to a new approach to the prevention of diabetes resulting from a high-fat diet. - Cell, December 2005

Old Dogs Can Learn New Tricks

Scientists once thought the adult brain was set in its ways. Using mice, they've now discovered that adult neurons have a remarkable ability to grow and change: some neurons can sprout new branches and retract old ones. These findings add to a growing body of evidence that older brains are still agile. The researchers used mice that had a few neurons labeled with fluorescent dye. They shaved off a small piece of a mouse's skull and covered the opening with glass. Using this 'window', they took high resolution pictures of the fluorescent neurons in the living brain. They captured images of the same neurons over several weeks. They found that dendrites (treelike extensions on neurons which receive information from other brain cells) grew, shrank, and changed over time – types of growth typical during development. Throughout life we learn things so synapses must change in some way, but this suggests that some changes may involve wholesale formation of new synapses or loss of old ones. This fluorescent imaging method could be used to assess the best ways for encouraging brain cells to grow, which would help people with spinal cord injury, stroke and other disorders. - PLoS Biology, online DOI: 10.1371/journal.pbio.0040029  27 December 2005

IBS Relief

A new study in mice has found that low concentrations of carbon monoxide – widely known as a toxic air pollutant, although small quantities are naturally produced in our bodies – soothe a common form of inflammatory bowel disease (IBD) called ulcerative colitis by shutting down the chronic inflammation that causes the condition. Low concentrations of carbon monoxide inhibited the mice's production of a protein called interleukin-12 (IL-12), which is normally produced during infection and helps activate immune cells that attack invading pathogens. Excessive production of IL-12 in the gut results in inflammation that causes ulcerative colitis. The researchers discovered that inhibiting production of IL-12 prevents such inflammation. Learning exactly how carbon monoxide inhibits IL-12 could result in a new treatment for IBD sufferers. - Journal of Experimental Medicine, online DOI: 10.1084/jem.20051047, 19 December 2005

A Little Telomerase Isn't Enough

Telomeres are repetitive stretches of DNA that protect chromosomes in much the same way as plastic shoelace tips prevent them from fraying. When a cell divides, its telomeres get a little shorter: eventually the cell can no longer divide because its critical genetic information is exposed. However, in stem cells a protein called telomerase normally maintains the telomeres' length, allowing the cells to divide indefinitely. A new study with mice has shown the critical link between the health of stem cells and the length of the telomeres within them. Mice engineered to have just half the normal amount of telomerase cannot maintain their stem cells' telomeres, proving that a little telomerase isn't enough. The mice’s capacity to renew tissues was reduced with defects in bone marrow, intestines, and testes that resembled those seen in patients with a condition called dyskeratosis congenita . The progressive worsening of disease with decreasing telomere length suggests that short telomeres, not telomerase level, cause stem cell failure. In addition, offspring of such mice bred to have normal levels of telomerase (but short telomeres) also exhibited early loss of stem cells. This phenomenon could complicate the hunt for disease genes. - Cell, December 2005

Lack of Sleep Kills Brain Cells