How the brain biases beliefs: Proposed neural circuit may underlie motivation to cling to desirable notions about the future

People’s motivation to cling to desirable notions about future outlooks results from interactions between prefrontal cortex regions, according to a human neuroimaging study published in JNeurosci.

Bojana Kuzmanovic and colleagues uncovered circuits in the brain that support belief updating by asking participants to estimate their own and a peer’s likelihood of experiencing an adverse life event, such as receiving a cancer diagnosis, and then presenting them with the actual federal statistics. Participants then reevaluated their personal risk in light of this new information.

The researchers found that the difference between the two estimates was greater when participants initially overestimated their risk of the adverse event, demonstrating the well-known optimism bias. An analysis of brain activity and the underlying circuitry revealed that this phenomenon depends on the influence of the brain’s valuation system on reasoning processes.

The proposed circuit involves the dorsolateral, ventromedial, and dorsomedial prefrontal cortex, which together bias integration of new information to support a preferred conclusion.

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Discovery presents treatment hope for Alzheimer’s and other neurodegenerative diseases

There is new hope for the treatment of Alzheimer’s and other neurological diseases following a ground-breaking discovery made by an Australian-Chinese research collaboration.

Researchers from the University of South Australia and the Third Military Medical University in China have discovered a signal pathway within cells, and also invented a potential drug that could stop degeneration and actually improve learning and memory in affected patients.

UniSA’s Professor Xin-Fu Zhou and colleagues have been investigating tauopathies — which refers to a class of diseases caused by misfolding of the tau protein inside nerve cells that results in cell damage and eventually cell death.

These diseases include Alzheimer’s, Parkinson’s and Motor Neuron Disease, all of which presently have no cure.

Specifically, the team has looked into frontotemporal lobe degeneration (FTLD), a term representing a group of clinical syndromes related to cognitive impairment, behavioural abnormalities and speech disorders.

Professor Zhou says that previously it was unknown how the gene mutation was responsible for causing cell death or damage — referred to generally as neurodegeneration, and dementia in patients with FTLD and other motor neuron diseases. “Right now there is no treatment available at all,” Prof Zhou says. “We have been investigating how these tauopathies (diseases) have some common pathology, including a particular tau protein that plays a critical role in nerve cell function.”

Tau protein is a protein that stabilises microtubules and it is specifically abundant in neurons of the nervous system, but not in elsewhere.

“Our research found that in both the animal model and human brains, the signal of neurotrophins and receptors is abnormal in brains with FTLD,” Prof Zhou says.

“We discovered an increase in the neurotrophin signalling pathway that is related to life and death of nerve cells, known as proNGF/p75, and then found blocking its functions was shown to reduce cell damage.

“Thus, in this paper we not only discovered a signaling pathway but also invented a potential drug for treatment of such diseases.”

Given this strong evidence now available, the next stage is a clinical trial and South Australian biotech company Tiantai Medical Technology Pty Ltd has recently acquired a licence to further develop and commercialise this medical technology.

Professor Zhou says this industry involvement means there is an opportunity to translate the discovery into a treatment of Alzheimer’s disease and other tauopathies.

The paper published in Molecular Psychiatry is a collaborative work between two laboratories led by Professor Xin-Fu Zhou, University of South Australia and Professor Yanjiang Wang, the Third Military Medical University.

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Brain iron levels may predict multiple sclerosis disabilities

A new, highly accurate MRI technique can monitor iron levels in the brains of multiple sclerosis (MS) patients and help identify those at a higher risk for developing physical disability, according to a study published in the journal Radiology.

MS is a disease that attacks three critical components of the central nervous system: the neurons (nerve fibers), myelin (the protective sheath around the neurons), and the cells that produce myelin. Common symptoms of MS include weakness, spasticity and pain. The disease can progress in many patients, leaving them severely disabled. Brain atrophy is the current gold standard for predicting cognitive and physical decline in MS, but it has limitations, said study lead author Robert Zivadinov, M.D., Ph.D., professor of neurology at the Jacobs School of Medicine and Biomedical Sciences at the University at Buffalo (UB) in Buffalo, N.Y. He is director of the Buffalo Neuroimaging Analysis Center in the Jacobs School and the Center for Biomedical Imaging at UB’s Clinical and Translational Science Institute.

“Brain atrophy takes a long time to see,” he said. “We need an earlier measure of who will develop MS-related disability.”

MRI studies of iron concentration have emerged recently as a promising measure of changes in the brain associated with MS progression. Iron is vital for various cellular functions in the brain, including myelination of neurons, and both iron overload and iron deficiencies can be harmful.

“It is known that there is more iron in the deep gray matter structures in MS patients, but also we’ve seen in recent literature that there are regions where we find less iron in the brains of these patients,” Dr. Zivadinov said.

Dr. Zivadinov and colleagues recently compared brain iron levels in people with MS to those of a healthy control group using an advanced MRI technique called quantitative susceptibility mapping. A brain region with more iron would have higher magnetic susceptibility, and one with less iron would have lower susceptibility.

The researchers performed the mapping technique on 600 MS patients, including 452 with early-stage disease and 148 whose disease had progressed.

Compared to 250 healthy control participants, MS patients had higher levels of iron in the basal ganglia, a group of structures deep in the brain that are central to movement. However, the MS patients had lower levels of iron in their thalamus, an important brain region that helps process sensory input by acting as a relay between certain brain structures and the spinal cord. The lower iron content in the thalamus and higher iron content in other deep gray matter structures of people with MS were associated with longer disease duration, higher disability degree and disease progression.

This association with clinical disability persisted even after adjusting for changes in the brain volumes of each individual structure.

“In this large cohort of MS patients and healthy controls, we have reported, for the first time, iron increasing in the basal ganglia but decreasing in thalamic structures,” Dr. Zivadinov said. “Iron depletion or increase in several structures of the brain is an independent predictor of disability related to MS.”

The results point to a potential role for quantitative susceptibility mapping in clinical trials of promising new drugs, Dr. Zivadinov said. Current treatments involving anti-inflammatory drugs do not prevent MS patients from developing disability.

“Susceptibility is an interesting imaging marker of disease severity that can predict which patients are at severe risk of progressing,” Dr. Zivadinov said. “To be able to act against changes in susceptibility would be extremely beneficial.”

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How does Parkinson’s disease develop? Study raises doubts on theory of Parkinson’s disease

Parkinson’s disease was first described by a British doctor more than 200 years’ ago. The exact causes of this neurodegenerative disease are still unknown. In a study recently published in eLife, a team of researchers led by Prof. Henning Stahlberg from the Biozentrum of the University of Basel has now questioned the previous understanding of this disease.

The arms and legs tremble incessantly, the muscles become weaker and the movements slower ? these are typical symptoms that many Parkinson’s patients suffer from. More than six million people are affected worldwide. In these patients, the dopamine-producing nerve cells in the brain slowly die off. The resulting lack of this neurotransmitter impairs motor function and often also affects the cognitive abilities.

Questionable: protein fibrils cause Parkinson’s disease

So far, it was assumed that the protein alpha-synuclein is one of the trigger factors. This protein can clump together and form small needles, so-called fibrils, which accumulate and deposit as Lewy bodies in the nerve cells. These toxic fibrils damage the affected brain cells. A team of scientists led by Prof. Henning Stahlberg from the Biozentrum of the University of Basel, in collaboration with researchers from Hoffmann-La Roche Ltd. and the ETH Zurich, have now artificially generated an alpha-synuclein fibril in the test tube. They have been able to visualize for the first time its three-dimensional structure with atomic resolution. “Contrary to our expectations, the results seem to raise more questions than they can hope to answer,” says Stahlberg.

It is important to know that in some congenital forms of Parkinson’s disease, affected persons carry genetic defects in the alpha-synuclein gene. These mutations, it is suspected, eventually cause the protein to fold incorrectly, thus forming dangerous fibrils. “However, our 3D structure reveals that a mutated alpha-synuclein protein should not be able to form these type of fibrils,” says Stahlberg. “Because of their location, most of these mutations would rather hinder the formation of the fibril structure that we have found.” In brief, if the fibril structure causes Parkinson’s disease, the genetic defect would have to protect against the disease. But this is not the case. So, it could be possible that a different type of fibril or another form of the protein triggers the disease in these patients.

Study poses new questions

More investigations are now needed to understand this fibril structure. What are the effects of the alpha-synuclein mutations? Do they lead to distinct forms of protein aggregates? What is the role of the fibrils for the nerve cells, and why do these cells die? To date, the exact physiological function of alpha-synuclein is still not known. Since only the symptoms of this neurodegenerative disease can be alleviated with the current medications, new concepts are urgently needed.

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New method discovered to view proteins inside human cells: Scientists develop tagging device using Ferritin

Scientists at the University of Warwick have created a new way to view proteins that are inside human cells.

Using Ferritin, a large protein shell that our cells use to store iron, the researchers have found a method they have called FerriTag that allows an electron microscope (EM) to view proteins precisely unlike current methods.

The method allowed the scientists to enable the cell to make the tag itself avoiding damage caused by placing it from the outside of the cell. Their paper FerriTag is a new genetically-encoded inducible tag for correlative light-electron microscopy is published in the journal Nature Communications.

The team set out to precisely localise a protein found in clathrin-coated pits. These are 100 nm wide entry points used by viruses to invade cells and infect them. Using FerriTag, the team were able to see where the protein is found in the pit and on the inside face of the cell’s surface.

The team was led by Dr Stephen Royle Associate Professor and Senior Cancer Research UK Fellow at Warwick Medical School. He said: “Proteins do almost all of the jobs in cells that scientists want to study. We can learn a lot about how proteins work by simply watching them down the microscope. But we need to know their precise location.”

Although light microscopy can be used to view proteins move around the resolution is low, so seeing a protein’s precise location is impossible. This can be overcome by using electron microscopy which gives a higher resolution.

To allow proteins to be viewed by both microscopes and correlate them, the research team developed a method of tagging the proteins so that they can be seen by both types of equipment.

Tagging is widely used and several tags are available however they have established drawbacks; some are not precise enough, or they don’t work on single proteins. To overcome this Dr Royle’s lab created a new tag and fused it with a fluorescent protein.

Dr Royle’s team named the new technique FerriTag because it is based on ferritin which can be viewed by an electron microscope because iron scatters electrons.

Dr Royle said his lab had to defeat another obstacle: “When Ferritin is fused to a protein, we end up with a mush. So, we altered Ferritin so that it could be attached to the protein of interest by using a drug.

“This meant that we could put the FerriTag onto the protein we want to image in a few seconds.

“The cool thing about FerriTag is that it is genetically encoded. That means that we get the cell to make the tag itself and we don’t have to put it in from outside which would damage the cell.”

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New nerve gas detector built with Legos and a smartphone

Researchers at The University of Texas at Austin have designed a way to sense dangerous chemicals using, in part, a simple rig consisting of a smartphone and a box made from Lego bricks, which could help first responders and scientists in the field identify deadly and difficult-to-detect nerve agents such as VX and sarin. The new methodology described in a paper published Wednesday in the open-access journal ACS Central Science combines a chemical sensor with photography to detect and identify different nerve agents — odorless, tasteless chemical weapons that can cause severe illness and death, sometimes within minutes.

Eric Anslyn, a chemistry professor at UT Austin, has been studying nerve agents for nearly 20 years, using safe chemical compounds that behave in the same way as nerve agents and can mimic them in testing. He previously developed chemical compounds that neutralize nerve agents and at the same time create a glow bright enough to be seen with the naked eye.

“Chemical weapons are dangerous threats to humanity,” Anslyn said. “Detection and neutralization are key to saving lives.”

The new device uses affordable, accessible materials to make Anslyn’s earlier compound more useful in real-world scenarios. The chemical sensors, developed by Xiaolong Sun in Anslyn’s lab, generate fluorescence, which is key to the analysis. Different colors and brightness can signal to first responders which of several nerve agents are present and how much. Because different categories of nerve agents require different decontamination procedures and different treatments for victims — and because the weapons act swiftly, making time of the essence — these variations are key.

“Unfortunately, it can be difficult to see differences in the level of florescence with the naked eye in the field. And instruments used in the lab to measure florescence are not portable and cost $30,000,” said Sun. “This device essentially takes photographs of the glowing.”

The camera on a smartphone is sensitive enough to detect the differences in color and brightness in the glowing reaction. The team used an iPhone in the lab. Software, developed by graduate student Alexander Boulgakov and available for free on GitHub, analyzes the color and brightness to identify the type and concentration of the nerve agent. The software can be adapted for multiple smartphone systems.

But researchers also needed a light-tight space to get a good reading on the camera. They considered 3D-printing a box, but realized that 3D printers and the materials used in them can be inaccessible, uneven or cost-prohibitive in some parts of the world. That’s when Pedro Metola, a clinical assistant professor at UT, thought of using Legos.

“Legos are the same everywhere you go,” Metola said.

The only other pieces of equipment needed are an ultraviolet light and standard 96-well test plate. The solution is inexpensive, portable and adjustable on the fly.

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