New info in the fight against flu:

The changing form of influenza virus, a challenge

Influenza virus can rapidly evolve from one form to another, complicating the effectiveness of vaccines and anti-viral drugs used to treat it. By first understanding the complex host cell pathways that the flu uses for replication, researchers are finding new strategies for therapies and vaccines, according to a study. The researchers studied RNA interference to determine the host genes influenza uses for virus replication.

All viruses act as parasites by latching onto healthy cells and hijacking the cells' components, essentially turning the cell into a factory that produces copies of the virus. This process begins when influenza binds to sugars found on the surface of host cells in the lung and respiratory tract.

Nucleus

Once attached, the virus downloads its genetic information into the nucleus of the cell, and virus replication begins. "Viruses contain very minimal genetic information and have evolved to parasitise host cell machinery to package and replicate virus cells. Because virus replication is dependent on host cell components, determining the genes needed for this process allows for the development of novel disease intervention strategies that include anti-virals and vaccines," said study co-author Ralph Tripp, a Georgia Research Alliance Eminent Scholar.

"We have the technology today that allows us to target specific genes in human cells and silence those genes to inhibit the production of virus in the cells," he said.

Pathways

RNA interference, which was first discovered as the mechanism that effects colour change in petunia breeding, is now being applied to medical advancements. Using RNAi silencing technologies, Tripp's lab was able to identify key host cell pathways needed by influenza virus for replication. "We have a very limited toolbox for treating influenza," Tripp said. "There are two medications currently used to treat flu infections, but virus resistance has developed to these drugs.

Our studies have identified several novel host genes and associated cell pathways that can be targeted with existing drugs to silence virus replication." Understanding which genes can be silenced to inhibit growth of viruses opens the medicine cabinet for the repurposing of existing drugs.

Existing anti-viral drugs slow influenza virus replication by preventing the virus from releasing itself from its host cell. These treatments target the virus, which is able to rapidly mutate to avoid drug sensitivity.

In contrast, drugs that target host genes work more effectively because host genes rarely change or mutate. "If we target a host gene, the virus can't adapt," Tripp said.

The influenza virus "may look for other host genes in the same pathway to use, which may be many, but we have identified the majority of preferred genes and can target these genes for silencing."

The influenza A virus has eight single RNA strands that code for 11 proteins. Recent studies suggest it may need several dozen host genes to reproduce.

Turning off the apex, or signalling, gene can cause the reproduction sequence to stall.

"Through this research we can repurpose previously approved drugs and apply those to influenza treatments, drastically reducing the time from the laboratory to human medicine," said Victoria Meliopoulos, a UGA graduate student and co-author of the study.

Meliopoulos said these discoveries can be used to create new anti-viral drugs and develop better vaccines that can be used to treat patients with influenza.

Influenza is the world's leading cause of morbidity and mortality; seasonal viruses affect up to 15 percent of the human population and cause severe illness in 5 million people a year, according to the Centers for Disease Control and Prevention.

MNT

Protein plays a key role in storing long-term memories

Memories in our brains are maintained by connections between neurons called "synapses". But how do these synapses stay strong and keep memories alive for decades? Neuroscientists at the Stowers Institute for Medical Research have discovered a major clue from a study in fruit flies: Hardy, self-copying clusters or oligomers of a synapse protein are an essential ingredient for the formation of long-term memory.

Memory

The finding supports a surprising new theory about memory, and may have a profound impact on explaining other oligomer-linked functions and diseases in the brain, including Alzheimer's disease.

"Self-sustaining populations of oligomers at synapses may be the key to the long-term synaptic changes that underlie memory; in fact, our finding hints that oligomers play a wider role in the brain than has been thought," said Kausik Si, an associate investigator at the Stowers Institute, and senior author of the new study.

Si's investigations in this area began nearly a decade ago during his doctoral research in the Columbia University laboratory of Nobel-winning neuroscientist Eric Kandel. He found that in the sea slug Aplysia californica, which has long been favoured by neuroscientists for memory experiments because of its large, easily-studied neurons, a synapse-maintenance protein known as CPEB (Cytoplasmic Polyadenylation Element Binding protein) has an unexpected property.

A portion of the structure is self-complementary and - much like empty egg cartons - can easily stack up with other copies of itself. CPEB thus exists in neurons partly in the form of oligomers, which increase in number when neuronal synapses strengthen.

Resistance

These oligomers have a hardy resistance to ordinary solvents, and within neurons may be much more stable than single-copy "monomers" of CPEB. They also seem to actively sustain their population by serving as templates for the formation of new oligomers from free monomers in the vicinity.

In the new study, Si and his colleagues examined a Drosophila fruit fly CPEB protein known as Orb2. Like its counterpart in Aplysia, it forms oligomers within neurons.

Oligomers

"We found that these Orb2 oligomers become more numerous in neurons whose synapses are stimulated, and that this increase in oligomers happens near synapses," said lead author Amitabha Majumdar, a post doctoral researcher in Si's lab.

The key was to show that the disruption of Orb2 oligomerisation on its own impairs Orb2's function in stabilising memory. Majumdar was able to do this by generating an Orb2 mutant that lacks the normal ability to oligomerise yet maintains a near-normal concentration in neurons.

Fruit flies carrying this mutant form of Orb2 lost their ability to form long-term memories.

"For the first 24 hours after a memory-forming stimulus, the memory was there, but by 48 hours it was gone, whereas in flies with normal Orb2 the memory persisted," Majumdar said.

Si and his team are now following up with experiments to determine for how long Orb2 oligomers are needed to keep a memory alive.

Neuroscience

"We suspect that they need to be continuously present, because they are self-sustaining in a way that Orb2 monomers are not," says Si.

The team's research also suggests some intriguing possibilities for other areas of neuroscience.

This study revealed that Orb2 proteins in the Drosophila nervous system come in a rare, highly oligomerisation-prone form (Orb2A) and a much more common, much less oligomerisation-prone form (Orb2B).

"The rare form seems to be the one that is regulated, and it seems to act like a seed for the initial oligomerisation, which pulls in copies of the more abundant form," Si said.

"This may turn out to be a basic pattern for functional oligomers."

The findings may help scientists understand disease-causing oligomers too.

Alzheimer's, Parkinson's and Huntington's disease, all involve the spread in the brain of apparently toxic oligomers of various proteins.

One such protein, strongly implicated in Alzheimer's disease, is amyloid beta; like Orb2 it comes in two forms, the highly oligomerizing amyloid-beta-42 and the relatively inert amyloid-beta-40.

- sciencedaily.com

All itches are not equal

New research from a world-renowned itch expert Gil Yosipovitch, shows that how good scratching an itch feels is related to the itch's location.

While previous studies by Yosipovitch have shown the pleasurability of itching, analysis of itch relief at different body sites and related pleasurability had not been performed until now.

"The goal of this study was to examine the role of the pleasurability of scratching in providing relief for itch," Yosipovitch said.

"We first evaluated whether itch intensity was perceived differently at three body sites, and then we investigated the potential correlation between the pleasurability and the itch relief induced by scratching."

Legume

Yosipovitch and colleagues induced itch on the ankles, forearms and backs of 18 study participants with cowhage spicules, which come from a type of legume found in tropical areas that are known to cause intense itching.

The spicules were rubbed gently in a circular motion for 45 seconds within a small area of the skin and removed with adhesive tape once itch was induced. Itch intensity and scratching pleasurability were assessed every 30 seconds for a duration of five minutes using a Visual Analog Scale (VAS) to rate intensity - 0 for no itch, up to 10 for maximum unbearable itch. Their results show that itch was perceived most intensely at the ankle and back, while the perception of itch and scratching relief were less pronounced on the forearm.

Another major finding of the paper, as Yosipovitch explains, is that "the pleasurability of scratching the ankle appears to be longer lived compared to the other two sites."

Disease

Yosipovitch said this research helps lead to a better understanding of itch and how to relieve it for people who have skin disease.

"We see commonly involved areas such as the ankle and back in itchy patients with skin disorders caused by eczema or psoriasis," he said.

"We never understood why those areas were more affected, and now we better understand that itch in these areas is more intense and pleasurable to scratch."

Yosipovitch said that while it is known that small nerve fibres are involved in unpleasant sensations such as itch and pain, he and other researchers now suspect that there are also specific nerve fibres involved in pleasure.

- swellingrelief.com

How cholera bacterium gains a foothold in the gut

A team of biologists at the University of York has made an important advance in our understanding of the way cholera attacks the body.

The discovery could help scientists target treatments for the globally significant intestinal disease which kills more than 100,000 people every year.

The disease is caused by the bacterium Vibrio cholerae, which is able to colonise the intestine usually after consumption of contaminated water or food. Once infection is established, the bacterium secretes a toxin that causes watery diarrhoea and ultimately death if not treated rapidly. Colonisation of the intestine is difficult for incoming bacteria as they have to be highly competitive to gain a foothold among the trillions of other bacteria already in situ. Scientists at York, led by Dr Gavin Thomas have investigated one of the important routes that V. cholera uses to gain this foothold.

To be able to grow in the intestine the bacterium harvests and then eats a sugar, called sialic acid, that is present on the surface of our gut cells.

Collaborators of the York group at the University of Delaware, USA, led by Professor Fidelma Boyd, had shown previously that eating sialic acid was important for the survival of V. cholerae in animal models, but the mechanism by which the bacteria recognise and take up the sialic was unknown.

The York research, funded by the Biotechnology and Biological Sciences Research Council (BBSRC), demonstrates that the pathogen uses a particular kind of transporter called a TRAP transporter to recognise sialic acid and take it up into the cell.

The transporter has particular properties that are suited to scavenging the small amount of available sialic acid.

The research also provided some important basic information about how TRAP transporters work in general.

The leader of the research in York, Dr Gavin Thomas, said: "This work continues our discoveries of how bacteria that grow in our body exploit sialic acid for their survival and help us to take forward our efforts to design chemicals to inhibit these processes in different bacterial pathogens."

- MNT

Psychologists analyse development of prejudices in children

Girls are not as good at playing football as boys, and they do not have a clue about cars. Instead they know better how to dance and do not get into mischief as often as boys. Prejudices like these are cultivated from early childhood by everyone.

"Approximately at the age of three to four years children start to prefer children of the same sex, and later the same ethnic group or nationality," Prof. Dr. Andreas Beelmann of the Friedrich Schiller University Jena (Germany) states. This is part of an entirely normal personality development, the director of the Institute for Psychology explains.

"It only gets problematic when the more positive evaluation of the own social group, which is adopted automatically in the course of identity formation, at some point reverts into bias and discrimination against others," Beelmann continues.

To prevent this, the Jena psychologist and his team have been working on a prevention program for children.

It is designed to reduce prejudice and encourage tolerance for others. But when is the right time to start? Jena psychologists Dr. Tobias Raabe and Prof. Dr. Andreas Beelmann systematically summarise scientific studies on that topic and published the results of their research in the science journal Child Development.

According to this, the development of prejudice increases steadily at pre-school age and reaches its highest level between five and seven years of age. With increasing age this development is reversed and the prejudices decline. "This reflects normal cognitive development of children," Prof. Beelmann explains. "At first they adopt the social categories from their social environment, mainly the parents.

Then they start to build their own social identity according to social groups, before they finally learn to differentiate and individual evaluations of others will prevail over stereotypes." Therefore, the psychologists reckon this age is the ideal time to start well-designed prevention programs against prejudice. "Prevention starting at that age supports the normal course of development," Beelmann says.

As the new study and the experience of the Jena psychologists with their prevention program so far show, the prejudices are strongly diminished at primary school age, when children get in touch with members of so-called social out groups like, for instance children of a different nationality or skin colour. "This also works when they don't even get in touch with real people but learn it instead via books or told stories."

But at the same time the primary school age is a critical time for prejudices to consolidate.

"If there is no or only a few contact to members of social out groups, there is no personal experience to be made and generalising negative evaluations stick longer."

In this, scientists see an explanation for the particularly strong xenophobia in regions with a very low percentage of foreigners or migrants.

- medicalxpress.com