Influenza infection can enhance the ability of the bacterium Streptococcus pneumoniae to cause ear and throat infections, according to new research

 In the study, the investigators infected mice with either influenza alone, pneumococci alone, or both at once, and then monitored the populations of bacteria and virus over time. They also monitored the mice for development of middle ear infection.

Influenza infection enhanced the bacterium’s ability to colonize the nasopharynx, and to infect the normally sterile middle ear.

 “We learned that once influenza virus is introduced, all of the “rules” regarding phase variants are out the window,” says corresponding author W. Edward Swords of Wake Forest University, Winston-Salem, NC. Phase variation refers to the fact that the colonizing bacteria have transparent cell surfaces, while those that spread within the host have opaque surfaces.

 “However, in the presence of influenza, opaque variants can readily colonize the nasopharynx, and transparent variants can persist in the ear,” says Swords. “This indicates that the host environs are more permissive for infection by the entire bacterial population.”

 Furthermore, recent research had shown that influenza interferes with innate immunity in a way that enables pneumococci to flourish. In this research, Swords shows that that interference manifests as increased inflammatory responses at the mucosal surface in the influenza-infected mice, such as within the middle ear, and in the nasopharynx.

“As with most pneumococcal infections, it should be appreciated that localized nonlethal infections are much more common than the rapidly lethal presentations,” says Swords. “For example, influenza is a contributing factor in otitis media (middle ear infections) in children.”

 “If we can understand why and how viral infection causes bacteria to colonize privileged sites like the middle ear, we will better know what aspects of disease to focus on with preventive or therapeutic treatments,” says Swords. American Society for Microbiology

An Ottawa-led team of researchers describe the role of a specific gene, called Snf2h, in the development of the cerebellum. Snf2h is required for the proper development of a healthy cerebellum, a master control centre in the brain for balance, fine motor control and complex physical movements.

Athletes and artists perform their extraordinary feats relying on the cerebellum. As well, the cerebellum is critical for the everyday tasks and activities that we perform, such as walking, eating and driving a car. By removing Snf2h, researchers found that the cerebellum was smaller than normal, and balance and refined movements were compromised.

Led by Dr. David Picketts, a senior scientist at the Ottawa Hospital Research Institute and professor in the Faculty of Medicine at the University of Ottawa, the team describes the Snf2h gene, which is found in our brain’s neural stem cells and functions as a master regulator. When they removed this gene early on in a mouse’s development, its cerebellum only grew to one-third the normal size. It also had difficulty walking, balancing and coordinating its movements, something called cerebellar ataxia that is a component of many neurodegenerative diseases.

‘As these cerebellar stem cells divide, on their journey toward becoming specialized neurons, this master gene is responsible for deciding which genes are turned on and which genes are packed tightly away,’ said Dr. Picketts. ‘Without Snf2h there to keep things organized, genes that should be packed away are left turned on, while other genes are not properly activated. This disorganization within the cell’s nucleus results in a neuron that doesn’t perform very well—like a car running on five cylinders instead of six.’

The cerebellum contains roughly half the neurons found in the brain. It also develops in response to external stimuli. So, as we practice tasks, certain genes or groups of genes are turned on and off, which strengthens these circuits and helps to stabilize or perfect the task being undertaken. The researchers found that the Snf2h gene orchestrates this complex and ongoing process. These master genes, which adapt to external cues to adjust the genes they turn on and off, are known as epigenetic regulators.

‘These epigenetic regulators are known to affect memory, behaviour and learning,’ said Dr. Picketts. ‘Without Snf2h, not enough cerebellar neurons are produced, and the ones that are produced do not respond and adapt as well to external signals. They also show a progressively disorganized gene expression profile that results in cerebellar ataxia and the premature death of the animal.’

There are no studies showing a direct link between Snf2h mutations and diseases with cerebellar ataxia, but Dr. Picketts added that it ‘is certainly possible and an interesting avenue to explore.’

In 2012, Developmental Cell published a paper by Dr. Picketts’ team showing that mice lacking the sister gene Snf2l were completely normal, but had larger brains, more cells in all areas of the brain and more actively dividing brain stem cells. The balance between Snf2l and Snf2h gene activity is necessary for controlling brain size and for establishing the proper gene expression profiles that underlie the function of neurons in different regions, including the cerebellum. Ottawa Hospital Research Institute

A study by researchers at IRB Barcelona explains the basis for the classification of colon tumours in good or bad prognosis by analysing the tissue surrounding the tumour cells.

The scientists are currently developing a test that enables the identification of patients at risk of relapse after surgical removal of the tumour by measuring 4-6 genes expressed by the tumour microenvironment.

The researchers also propose to test in patients a particular drug that blocks the metastatic capacity of colorectal cancers in mice.

This drug has been tested using novel technology that allows the growth of mini colon cancers, also known as organoids, derived from patient samples.
About 40–50% of all colorectal patients relapse in the form of metastasis. In the last three years, several molecular classifications have been proposed to identify colorectal cancer patients at risk of relapse. Scientists headed by ICREA researcher Eduard Batlle at the Institute for Research in Biomedicine (IRB Barcelona) explain why these classifications work and reveal, in fact, that they can be simplified and improved by looking exclusively at the genes that are expressed in the tissue around the tumour, known as the stroma or tumour microenvironment.

“We have re-evaluated the classifications under our perspective and confirmed that colon cancer relapse occurs in patients in which tumour cells have the capacity to disrupt the tissue surrounding the tumour,” explains Eduard Batlle, head of the Colorectal Cancer Laboratory at IRB Barcelona. The team of scientists have examined the genetic profile of around 1,000 tumours from patients all over the world. “The conclusion is indisputable. The key to the classifications lies in whether the stroma of the tumour is altered or not and it is this property that confers malignancy to colon tumours. Patients with unaltered stroma are essentially cured after surgery.”

This new approach to addressing different types of colon tumour will soon have a practical application for doctors. On one hand, the scientists demonstrate that tumour cells communicate with the stroma through the hormone TGF-beta and that metastasis could be prevented in these patients by interfering with this communication. “We propose exploring the possibility of using TGF-beta inhibitors to treat colon cancer”. Several TGF-beta inhibitors are being tested for other kinds of tumours. “The data are impressive. It would be most pertinent for oncologists and pharmaceutical companies to come to an agreement in order to start clinical assays in patients with poor prognosis colon cancer” says Alexandre Calon, postdoctoral researcher and first author of the article. To test the use of these inhibitors, the scientists at IRB Barcelona have developed technology that allows them to grow mini colon tumours in vitro, also known as organoids, from samples taken from patients. “These organoids reproduce the behaviour of the original tumour and are therefore a powerful tool for personalised cancer treatment,” explains Batlle. 

Furthermore, the IRB Barcelona researchers are very close to achieving a diagnostic test named Colostage to identify those patients at the greatest risk of a relapse in the form of metastasis. “By focusing on the genetic programme of the tissue surrounding the tumour we can identify the vast majority of patients that will experience relapse. This would allow better discrimination of which patients to treat and follow up, as the use of radiotherapy or chemotherapy would benefit only this group” ensures the researcher. In addition, this test will help identify those patients more likely to benefit from the use of TGF-beta inhibitors in clinical trials. IRB Barcelona

A new study led by researchers at King’s College London in collaboration with the University of Manchester and the University of Dundee has found a strong link between exposure to peanut protein in household dust during infancy and the development of peanut allergy in children genetically predisposed to a skin barrier defect.

Around 2% of school children in the UK and the US are allergic to peanuts. Severe eczema in early infancy has been linked to food allergies, particularly peanut allergy. A major break-through in the understanding of eczema developed with the discovery of the FLG gene which codes for the skin barrier protein filaggrin. Mutations in the FLG gene result in an impaired skin barrier which is thought to allow allergens to penetrate the skin and predispose the body towards an allergic response.

Immunology, looked at the amount of peanut protein children were exposed to in household dust in their first year of life by vacuuming dust from the living room sofa and measuring peanut in the dust. A group of 577 children were assessed at 8 and 11 years of age for peanut allergy and their DNA was checked for FLG mutations. The study was conducted in children recruited to the Manchester Asthma and Allergy Study.

A strong link was found between early-life exposure to peanut protein in household dust and peanut allergy in children with FLG mutations. A three-fold increase in house dust peanut exposure during infancy was associated with a three-fold increase in risk of school-age peanut allergy. One in five children with peanut allergy had an FLG mutation. There was no significant effect of environmental peanut exposure in children without FLG mutations.

Dr Helen A Brough, first author from the Department of Paediatric Allergy, Division of Asthma, Allergy & Lung Biology, King’s College London, said: “Our findings provide evidence that peanut allergy may develop via the skin in children with mutations in the gene that codes for filaggrin which damage the function of this important skin protein. These findings are also an example of how an individual’s response to their environment can be modified by their genes. Our study raises the possibility of being able to identify a group of children with FLG mutations through genetic testing in the future, and altering their environmental exposure to peanut early in life to reduce the risk of developing peanut allergy.” King’s College London