New stroke gene discovery could lead to tailored treatments

A study led by King’s College London has identified a new genetic variant associated with stroke. By exploring the genetic variants linked with blood clotting – a process that can lead to a stroke – scientists have discovered a gene which is associated with large vessel and cardioembolic stroke but has no connection to small vessel stroke.

Published in the journal Annals of Neurology, the study provides a potential new target for treatment and highlights genetic differences between different types of stroke, demonstrating the need for tailored treatments.

Approximately 152,000 people in Britain have a stroke each year, costing the UK over £8.2 billion. While there are thought to be 1.2 million stroke survivors in the UK, more than half have been left with disabilities that affect their daily lives.

A stroke occurs when the blood supply to the brain is cut off, often due to a blood clot blocking an artery that carries blood to the brain, which then leads to brain cell damage. Coagulation (blood clotting) abnormalities, particularly easy clotting of the blood, are therefore common contributing factors in the development of stroke.

Dr Frances Williams, Senior Lecturer from the Department of Twin Research and Genetic Epidemiology at King’s and lead author of the paper, said: ‘Previous studies have demonstrated the influence of genetic factors on the components of coagulation. The goal of this study was to extend these observations to determine if they were further associated with different types of stroke.’

The research was carried out in three stages. The first consisted of a genome-wide association study (GWAS) in 2100 healthy volunteers which identified 23 independent genetic variants that were involved in coagulation. The second stage examined the 23 variants in 4200 stroke and non-stroke cases from centres across Europe (Wellcome Trust Case Control Consortium 2 and MORGAM collections) and found that a particular mutation on the ABO gene was significantly associated with stroke.

Stage three of the study used the MetaStroke cohort, a project of the International Stroke Genetics Consortium which comprises 8900 stroke cases recruited from centres in the Europe, USA and Australia, whose DNA has been collected and undergone GWA scan. It was confirmed that a variant in the ABO blood type gene was associated with stroke, a finding specific to large vessel and cardioembolic stroke.

Dr Williams said: ‘The discovery of the association between this genetic variant and stroke identifies a new target for potential treatments, which could help to reduce the risk of stroke in the future. It is also significant that no association was found with small vessel disease, as this suggests that stroke subtypes involve different genetic mechanisms which emphasises the need for individualised treatment.’

With Evolved Brains, Robots Creep Closer To Animal-Like Learning

The most nightmare-inducing characteristic of Big Dog, DARPA’s robotic military mule, might be the way it moves so stiffly, yet unrelentingly, over treacherous battleground. Turns out the repetitive mechanical gait that calls to mind some coming robopocalypse is also a huge headache for Big Dog’s makers—and lots of the big thinkers behind walking bots envisioned for everyday domestic use.

Units like Big Dog move so awkwardly because of their rudimentary brains, which require pre-programming for every little action. A four-legged walking bot could jump smoothly over rocks or weave through trees with the fluid grace and reflexes of a cheetah—if it only had a better brain. One that was more animal-like. Thanks to breakthroughs in understanding how biological brains evolve, a team of robotic researchers say they’re close.

“We are working on evolving brains that can be downloaded onto a robot, wake up, and begin exploring their environment to figure out how to accomplish the high-level objectives we give them (e.g. avoid getting damaged, find recharging stations, locate survivors, pick up trash, etc.),” says Jeffrey Clune, Assistant Professor of Computer Science at the University of Wyoming, who is part of the robotics team.

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City Life Changes How Our Brains Deal With Distractions

City life requires a lot of attention. Navigating a busy sidewalk while processing loud storefronts and avoiding rogue pigeons may feel like second-nature at times, but it’s actually quite a bit of work for the human brain. Psychologists do know that quick walks through the park can restore our focus, but they’re still getting a handle on just what urbanization means for human cognition.

A new series of behavioral studies offers some of the richest evidence to date on the mental exhaustion of urban living. In an upcoming issue of the Journal of Experimental Psychology: Human Perception and Performance, a group of British psychologists reports that people who live in cities show diminished powers of general attention compared to people from remote areas. With so much going on around them, urbanites don’t pay much attention to surroundings unless they’re highly engaging.

Mapping the living cell

To get a clear picture of what’s happening inside a cell, scientists need to know the locations of thousands of proteins and other molecules. MIT chemists have now developed a technique that can tag all of the proteins in a particular region of a cell, allowing them to more accurately map those proteins.

“That’s a holy grail for biology — to be able to get spatially and temporally resolved molecular maps of living cells,” says Alice Ting, the Ellen Swallow Richards Associate Professor of Chemistry at MIT. “We’re still really far from that goal, but the overarching motivation is to get closer to that goal.”

Ting’s new method, developed with researchers from the Broad Institute and Harvard Medical School, combines the strengths of two existing techniques — microscopic imaging and mass spectrometry — to tag proteins in a specific cell location and generate a comprehensive list of all the proteins in that area.

In a paper appearing in the Jan. 31 online edition of Science, Ting and colleagues used the new technique to identify nearly 500 proteins located in the mitochondrial matrix — the innermost compartment of the cellular organelle where energy is generated.

Using fluorescence or electron microscopy, scientists can determine protein locations with high resolution, but only a handful of a cell’s approximately 20,000 proteins can be imaged at once. “It’s a bandwidth problem,” Ting says. “You certainly couldn’t image all the proteins in the proteome at once in a single cell, because there’s no way to spectrally separate that many channels of information.”

With mass spectrometry, which uses ionization to detect the mass and chemical structure of a compound, scientists can analyze a cell’s entire complement of proteins in a single experiment. However, the process requires dissolving the cell membrane to release a cell’s contents, which jumbles all of the proteins together. By purifying the mixture and extracting specific organelles, it is then possible to figure out which proteins were in those organelles, but the process is messy and often unreliable.

The new MIT approach tags proteins within living cells before mass spectrometry is done, allowing spatial information to be captured before the cell is broken apart. This information is then reconstructed during analysis by noting which proteins carry the location tag.

Kynurenines in the CNS: recent advances and new questions

Various pathologies of the central nervous system (CNS) are accompanied by alterations in tryptophan metabolism. The main metabolic route of tryptophan degradation is the kynurenine pathway; its metabolites are responsible for a broad spectrum of effects, including the endogenous regulation of neuronal excitability and the initiation of immune tolerance. This Review highlights the involvement of the kynurenine system in the pathology of neurodegenerative disorders, pain syndromes and autoimmune diseases through a detailed discussion of its potential implications in Huntington’s disease, migraine and multiple sclerosis. The most effective preclinical drug candidates are discussed and attention is paid to currently under-investigated roles of the kynurenine pathway in the CNS, where modulation of kynurenine metabolism might be of therapeutic value.

Even the brains of people with anxiety states can get used to fear

Fear is a protective function against possible dangers that is designed to save our lives. Where there are problems with this fear mechanism, its positive effects are cancelled out: patients who have a social phobia become afraid of perfectly normal, everyday social situations because they are worried about behaving inappropriately or being thought of as stupid by other people. Scientists from the Centre for Medical Physics and Biomedical Technology and the University Department of Psychiatry and Psychotherapy at the MedUni Vienna have now discovered that this fear circuit can be deactivated, at least in part.

In a study by Ronald Sladky, led by Christian Windischberger (Centre for Medical Physics and Biomedical Technology), which has recently been published in the magazine PLOS One, functional magnetic resonance tomography was used to measure the changes in the brain activity of socially phobic patients and healthy test subjects while they were looking at faces. This experiment simulates social confrontation with other people without actually placing the individual in an intolerable situation of anxiety.

Permanent confrontation has a diminishing effect on anxiety
“The study demonstrated that people with social phobia initially exhibit greater activity in the amygdala and in the medial, prefrontal cortex of the brain, however after a few faces this activity recedes,” says Sladky. This contradicts the assumption made thus far that the emotional circuit of socially phobic individuals is unable to adapt adequately to this stress-inducing situation.

Permanent confrontation with the test task not only led to a solution to the “problem” being found more quickly among the patients with anxiety, but also to some areas of the brain being bypassed which otherwise were over-stimulated, a characteristic typical of anxiety. Says Sladky: “We therefore concluded that there are functional control strategies even in the emotional circuits of people with social phobia, although the mechanisms take longer to take effect in these individuals. The misregulation of these parts of the brain can therefore be compensated to a degree.”

These findings could, according to Sladky, provide a starting point for the development of personalised training programmes that will help affected individuals to conquer unpleasant situations in their everyday lives more effectively. In Austria, around 200,000 people a year are affected by some form of social phobia. The number of people who suffer this condition without seeking help for it is likely to be very high, since many affected individuals fail to seek assistance or do so only too late as a result of their anxiety.