Scientists have finally identified a direct role for the missing protein that leaves cystic fibrosis patients open to attack from lung-damaging bacteria, the main reason most of them die before their 35th birthday, scientists heard at the Society for General Microbiology's Autumn meeting being held this week at Trinity College, Dublin.

"Chronic lung infections are by far and away the biggest problem with the genetic disease cystic fibrosis, affecting almost 90% of patients. The majority of these bad infections are caused by one particular type of bacteria called Pseudomonas aeruginosa," said Professor Gerald Pier from Harvard Medical School in Boston, USA. "Once a chronic infection starts in a cystic fibrosis patient it is almost never cleared and will go on getting worse and causing lung damage over many years before killing the patient by the age of 35 years."

The US scientists trying to work out why cystic fibrosis patients get this infection have discovered that the protein called CFTR that is either missing or not working properly in their lungs is needed by our bodies to recognise when Pseudomonas aeruginosa bacteria are inhaled. People whose CFTR protein is working correctly can rapidly clear the infectious bacteria out of their lungs.

"In cystic fibrosis patients the recognition system is deficient or absent, and the patient does not rapidly expel the bacteria, allowing the microbes to settle into the lungs and cause a chronic infection," said Professor Pier.

By understanding how our lung cells use CFTR to recognize and properly respond to Pseudomonas aeruginosa infections the Harvard team hopes that they will be able to identify points of intervention that could be activated in cystic fibrosis lungs to increase their resistance to infection.

"At the moment our research is more geared to identifying the molecules that lung cells use to resist infection, although our longer term goal is to find ways to restore the resistance of the lung to infection," said Professor Pier. "Our major path right now is to further understand the general process of resistance to infection, using cystic fibrosis as a model as well as a real disease. But the next step will be to try some drug interventions to improve the resistance of cystic fibrosis patients to infection which will undoubtedly prolong their lives and enhance the quality of their life as well".

Professor Tsuyoshi Miyakawa of Fujita Health University, National Institute for Physiological Sciences (NIPS), and Kyoto University led a research team in Japan, with support from the CREST program of Japan Science and Technology Agency (JST).

First, the team investigated behaviors by conducting a systematic and well-defined behavioral test battery with alpha-CaMKII mutant mice, an animal model of schizophrenia. These mice showed abnormal behaviors similar to those of schizophrenic patients.

Next, the team found the dentate gyrus neurons in hippocampus of the brain of these mice were not matured morphologically and physiologically. By a gene expression analysis, changes of gene expression related to the maturation of dentate gyrus neurons were also found in the brains of schizophrenic patients.

Taken together, the immaturity of the dentate gyrus may be an underlying cause for schizophrenia.

Among their findings, mice heterozygous for a null mutation of the alpha-isoform of calcium/calmodulin-dependent protein kinase II show profoundly dysregulated behaviors, including a severe working memory deficit and an exaggerated infradian rhythm (cycle of increases and decreases in locomotor activity in their home cage; 2-3 weeks/cycle), which are comparable to the symptoms observed in patients with schizophrenia, bipolar disorder and other psychiatric disorders.

Despite extensive research, the brain mechanisms of schizophrenia remain largely unknown. According to Professor Miyakawa, one reason for this is that clinical diagnosis in the area of psychiatry is based solely on subjective observations and not on biologically or objectively solid criteria, "As a result of this limitation, most of the psychiatric disorders currently diagnosed as a single disorder are likely to comprise several biologically distinct heterogeneous populations. Therefore, the identification and investigation of more reliable biomarkers that characterize a single subpopulation of a specific psychiatric disorder are essential for increasing the understanding of the pathogenesis/pathophysiology of such disorders."

Vitamin B12, a nutrient found in meat, fish and milk, may protect against brain volume loss in older people, according to a study published in the September 9, 2008, issue of Neurology.

For the study, 107 people between the ages of 61 and 87 underwent brain scans, memory testing and physical exams. Researchers also collected blood samples to check vitamin B12 levels. Brain scans and memory tests were also performed again five years later.

The study found that people who had higher vitamin B12 levels were six times less likely to experience brain shrinkage compared with those who had lower levels of the vitamin in their blood. None of the people in the study had vitamin B12 deficiency.

"Many factors that affect brain health are thought to be out of our control, but this study suggests that simply adjusting our diets to consume more vitamin B12 through eating meat, fish, fortified cereals or milk may be something we can easily adjust to prevent brain shrinkage and so perhaps save our memory," said study author Anna Vogiatzoglou, MSc, with the University of Oxford in the United Kingdom. "Research shows that vitamin B12 deficiency is a public health problem, especially among the elderly, so more vitamin B12 intake could help reverse this problem. Without carrying out a clinical trial, we acknowledge that it is still not known whether B12 supplementation would actually make a difference in elderly persons at risk for brain shrinkage."

"Previous research on the vitamin has had mixed results and few studies have been done specifically with brain scans in elderly populations. We tested for vitamin B12 levels in a unique, more accurate way by looking at two certain markers for it in the blood," said Vogiatzoglou.

Vogiatzoglou says the study did not look at whether taking vitamin B12 supplements would have the same effect on memory.

Researchers in Switzerland and Australia are reporting identification of proteins in human breast-milk — not present in cow's milk — that may fight disease by helping remove bacteria, viruses and other dangerous pathogen's from an infant's gastrointestinal tract.

Niclas Karlsson and colleagues point out that researchers have known for years that breast milk appears to provide a variety of health benefits, including lower rates of diarrhea, rashes, allergies, and other medical problems in comparison to babies fed with cow's milk. However, the biological reasons behind this association remain unclear.

To find out, the scientists collected human and cow's milk samples and analyzed their content of milk fat. They found that fat particles in human milk are coated with particular variants of two sugar-based proteins, called MUC-1 and MUC-4.

Previous studies by others have shown that these proteins can block certain receptors in the GI tract that are the main attachment sites for E. coli, Helicobacter pylori and other disease-causing microbes, thereby preventing infection. By contrast, since cow's milk lacks these protein variants, it may not offer the same disease protection, the researchers say.

Milk may help prevent potentially dangerous bacteria like Staphylococcus from being killed by antibiotics used to treat animals, scientists heard September 8, 2008 at the Society for General Microbiology's Autumn meeting being held at Trinity College, Dublin.

Bacteria sometimes form structures called biofilms that protect them against antibiotics and the body's natural defences. Now scientists have discovered that one of the most important micro-organisms that causes mastitis in cows and sheep, called Staphylococcus, can evade the animal's defences and veterinary medicines by forming these protective biofilms. Mastitis is an infection of the udder in cattle and sheep. It is often a painful condition for the cows and can even cause death.

"Mastitis is a difficult disease to control. It causes risks for public health if people drink infected milk and is expensive for farmers as it usually causes severe milk production losses, increased treatment costs and means the animals may have to be culled," said Dr Manuela Oliveira from the Faculty of Veterinary Medicine at the Technical University of Lisbon, Portugal. "When the staphylococci produce a biofilm, the structure protects them against host defences and antibiotic treatment, allowing the bacteria to persist in the udder."

In the past, scientists studying mastitis have conducted most of their experiments under laboratory conditions rather than mimicking the conditions found in living animals. This may mean that they have missed important contributory factors. However, Dr Oliveira and her colleagues have used realistic conditions to overcome this problem.

"We have discovered that milk may also protect bacteria against low concentrations of antibiotics – in the presence of milk, three of the five antibiotics tested, penicillin, gentamicin and sulphamethoxazole combined with trimethoprim, were less effective against Staphylococcus when compared with the same experiment performed in the absence of milk," said Dr Oliveira.

The Lisbon team is currently trying to identify the correct antibiotic concentrations needed to stop biofilms forming in the first place and also the concentrations needed to destroy a biofilm that has already formed. The scientists are also looking at the influence of the forces acting inside an udder during milking to see whether these help or hinder the bacteria in producing biofilms.

"This will allow for a better control of staphylococcal mastitis, cut disease costs and give an important improvement in the protection of consumers' health," said Dr Manuela Oliveira. "If we can get the doses right, and the animals are cured quicker, we will have less antibiotic residue in the environment and the risk of bacteria such as Staphylococcus aureus developing and spreading antibiotic resistance is lower."

Researchers have discovered two new genes that increase the risk of developing inflammatory bowel disease (IBD) in childhood.

While further study is needed to identify the specific disease-causing mutations in these new genes, the researchers say the genes are particularly strong candidates to be added to the list of genes already known to affect IBD. "As we continue to find genes that interact with each other and with environmental influences in this complex, chronic disease, we are building the foundation for personalized treatments tailored to a patient's genetic profile," said co-first author Robert N. Baldassano, M.D., director of the Center for Pediatric Inflammatory Bowel Disease at The Children's Hospital of Philadelphia.

"We will resequence the gene regions we have identified to pinpoint the causative mutations in these genes," added study leader Hakon Hakonarson, M.D., Ph.D., director of the Center for Applied Genomics at Children's Hospital. "We strongly suspect one gene will provide a compelling target for drug development, given what's known about its biology."

Both authors direct research programs at Children's Hospital and are also faculty members of the University Of Pennsylvania School Of Medicine. Their study, performed in collaboration with researchers from the Medical College of Wisconsin, The University of Utah, Cincinnati Children's Hospital and two research hospitals in Italy, appears in advance online publication Aug. 31 in Nature Genetics.

IBD is a painful, chronic inflammation of the gastrointestinal tract, affecting about two million children and adults in the United States. Of that number, about half suffer from Crohn's disease, which can affect any part of the gastrointestinal tract, and half have ulcerative colitis, which is limited to the large intestine.

IBD that begins in childhood tends to be more severe than adult-onset disease, and is more likely to affect the colon than other areas of the GI tract. Those age-related differences in IBD spurred the current research team to do their gene hunting in childhood-onset disease. "Although the gene variants we found may have a stronger signal in pediatric IBD than in adult-onset IBD, we do not believe them to be limited to varieties of the disease that begin in childhood," said Baldassano.

The researchers performed a genome-wide association study, searching for genetic variations in DNA samples from 1,000 patients with childhood-onset IBD, compared to samples from 4,250 healthy subjects. Both patients and controls were of European ancestry.

In addition to finding gene variations previously reported by other groups, the study team identified two novel gene variants, one on chromosome 20 and the other on chromosome 21. They then replicated their findings with studies using additional samples from other sources.

The researchers say that the TNFRSF6B gene on chromosome 20 is a compelling candidate, because it is already known to participate in the biological pathway of a protein called tumor necrosis factor (TNF). TNF is a cytokine, a chemical messenger that plays a key role in the harmful inflammation characteristic of IBD.

Some current treatments for IBD use monoclonal antibodies that selectively bind to a type of TNF involved in the disease (Among those drugs are infliximab, adalimumab and certolizumab). "As we better understand the complex gene interactions in IBD, we may be able to diagnose patients by their genetic profile to predict who will better respond to anti-TNF drugs," said Hakonarson. Anti-TNF medications such as those mentioned above are currently given intravenously or as injections, said Baldassano, who added, "If better knowledge of the disease pathway enables pharmaceutical companies to develop anti-TNF drugs in pill form, the medications will be easier to deliver as well as more customized to each patient."

The study team also found an association between ulcerative colitis and genes on the major histocompatiblity complex (MHC) on chromosome 6. The MHC is a large group of genes with important roles in the immune system, and this finding may help refine diagnostic techniques that would allow physicians to administer more specific therapies to their patients.

"Smoking during pregnancy is a double-edged sword with respect to SIDS," said Shabih Hasan, M.D., a staff neonatologist and professor in the department of pediatrics at the University of Calgary, and the principal investigator of the new study. "Not only does it raise a mother's likelihood of having a preterm baby, who is already among the most vulnerable to SIDS, but it increases the infant's susceptibility to SIDS even further."

Studies have indicated that a combination of hypoxia (low oxygen) and hypercarbia (excess of carbon dioxide) may be acute precursors to SIDS. Infants at the greatest risk for SIDS have been shown to have both attenuated arousal and ventilatory responses to hypoxia and/or hypercarbia.

"Preterm babies are known to have increased breathing difficulties in proportion to their prematurity and cigarette smoke is known to increase apneas in full-term babies," said Dr. Hasan. "But until now, cigarette smoke exposure and preterm birth have not been investigated together with respect to their potential effects on respiratory dysfunction."

To analyze the effects of cigarette smoke exposure on preterm infants' respiratory health and their risk of SIDS, the researchers recruited 22 preterm infants who had been spontaneously born between 28 and 32 weeks with no other complicating respiratory factors. Twelve of the infants had mothers who had smoked five or more cigarettes every day in pregnancy. The mothers of the other ten infants did not smoke during pregnancy.

They obtained baseline readings on the infants' breathing patterns in normal conditions, assessing breathing rate, pauses in breathing, recovery period and heart rate. Saturation of oxygen in their blood was also monitored. After baseline readings were recorded, the infants were challenged with a five-minute period of decreased oxygen delivered through a nasal cannula. During this period they were monitored very closely with infant resuscitation equipment near at hand.

The two groups were remarkably similar in some measures: respiratory rates and number of breathing pauses were similar among both groups of infants.

But there were significant differences between the two groups of preterm babies with respect to heart rate and recovery period. The cigarette-smoke exposed infants showed increased heart rate during the hypoxemic period compared with their baseline values, but there was no difference in heart rates was observed in control infants, indicating that the oxygen depletion put their bodies under more stress than the control groups.

Furthermore, while blood oxygen levels decreased similarly in both groups during the hypoxemic challenge, infants who were exposed to cigarette smoke did not recover as well, as quickly or as often as the infants born to non-smoking mothers.

"Our study shows that preterm infants make incomplete and/or delayed recovery from interruptions in breathing," said Dr. Hasan. "This has clear implications for their risk of SIDS. But there is even still another reason for concern even after the risk of SIDS has passed. Inability or delayed recovery from repeated low oxygen episodes can also be detrimental to brain development. There is increasing evidence that infants exposed to prenatal cigarette smoke are at high risk for developmental and behavioral disorders."

To explain their findings, the researchers point to evidence that suggests that nicotine interacts with highly selective endogenous neuronal nicotinic acetylcholine receptors, which may in turn affect development of areas in the central nervous system essential for respiratory control. Alternatively, alterations in lung development and lung mechanics could contribute to poor gas exchange leading to poorer recovery seen in the group exposed to cigarette smoke.

Regardless of the mechanism, the study has immediate clinical relevance: "Since preterm infants continue to have significant cardiorespiratory events after discharge from the hospital, our study may help identify the infants at risk for attenuated recovery from hypoxemic episodes while at home," said Dr. Hasan. "Furthermore, it might help distinguish the infants, who will arouse in response to hypoxemia. The infants identified to be at risk can subsequently be further investigated and/or monitored at home."

The research will be published in the first issue for September of the American Thoracic Society's American Journal of Respiratory and Critical Care Medicine.