Molecular biology mystery unravelled

The nature of the machinery responsible for the entry of proteins into cell membranes has been unravelled by scientists, who hope the breakthrough could ultimately be exploited for the design of new anti-bacterial drugs.

Groups of researchers from the University of Bristol and the European Molecular Biology Laboratory (EMBL) used new genetic engineering technologies to reconstruct and isolate the cell’s protein trafficking machinery. Its analysis has shed new light on a process which had previously been a mystery for molecular biologists.

The findings, published this week in the Proceedings of the National Academy of Sciences (PNAS), could also have applications for synthetic biology - an emerging field of science and technology, for the development of novel membrane proteins with useful activities.

Proteins are the building blocks of all life and are essential for the growth of cells and tissue repair. The proteins in the membrane typically help the cell interact with its environment and conserve energy. 

Researchers were able to identify the ‘holo-translocon’ as the machinery which inserts proteins into the membrane. It is a large membrane protein complex and is uniquely capable of both protein-secretion and membrane-insertion.

Professor Ian Collinson, from the School of Biochemistry at Bristol University, said: “These findings are important as they address outstanding questions in one of the central pillars of biology, a process essential in every cell in every organism. Having unravelled how this vital holo-translocon works, we’re now in a position to look at its components to see if they can help in the design or screening for new anti-bacterial drugs.”

Why does the brain remember dreams?

Some people recall a dream every morning, whereas others rarely recall one. A team led by Perrine Ruby, an Inserm Research Fellow at the Lyon Neuroscience Research Center (Inserm/CNRS/Université Claude Bernard Lyon 1), has studied the brain activity of these two types of dreamers in order to understand the differences between them. In a study published in the journal Neuropsychopharmacology, the researchers show that the temporo-parietal junction, an information-processing hub in the brain, is more active in high dream recallers. Increased activity in this brain region might facilitate attention orienting toward external stimuli and promote intrasleep wakefulness, thereby facilitating the encoding of dreams in memory.

The reason for dreaming is still a mystery for the researchers who study the difference between “high dream recallers,” who recall dreams regularly, and “low dream recallers,” who recall dreams rarely. In January 2013 (work published in the journal Cerebral Cortex), the team led by Perrine Ruby, Inserm researcher at the Lyon Neuroscience Research Center, made the following two observations: “high dream recallers” have twice as many time of wakefulness during sleep as “low dream recallers” and their brains are more reactive to auditory stimuli during sleep and wakefulness. This increased brain reactivity may promote awakenings during the night, and may thus facilitate memorisation of dreams during brief periods of wakefulness.

In this new study, the research team sought to identify which areas of the brain differentiate high and low dream recallers. They used Positron Emission Tomography (PET) to measure the spontaneous brain activity of 41 volunteers during wakefulness and sleep. The volunteers were classified into 2 groups: 21 “high dream recallers” who recalled dreams 5.2 mornings  per week in average, and 20 “low dream recallers,” who reported 2 dreams per month in average. High dream recallers, both while awake and while asleep, showed stronger spontaneous brain activity in the medial prefrontal cortex (mPFC) and in the temporo-parietal junction (TPJ), an area of the brain involved in attention orienting toward external stimuli.

Scientists discover hormone released after exercise can ‘predict’ biological age

Scientists from Aston University have discovered a potential molecular link between Irisin, a recently identified hormone released from muscle after bouts of exercise, and the ageing process.

Irisin, which is naturally present in humans, is capable of reprograming the body’s fat cells to burn energy instead of storing it. This increases the metabolic rate and is thought to have potential anti-obesity effects which in turn could help with conditions such as type-2 diabetes.

The research team led by Dr James Brown have proven a significant link exists between Irisin levels in the blood and a biological marker of ageing called telomere length. Telomeres are small regions found at the end of chromosomes that shorten as cells within the body replicate. Short telomere length has been linked to many age-related diseases including cancer, heart disease and Alzheimer’s disease.

Using a population of healthy, non-obese individuals, the team has shown those individuals who had higher levels of Irisin were found to have longer telomeres. The finding provides a potential molecular link between keeping active and healthy ageing with those having higher Irisin levels more ‘biological young’ than those with lower levels of the hormone.

Dr James Brown from Aston’s Research Centre for Healthy Ageing, said; “Exercise is known to have wide ranging benefits, from cardiovascular protection to weight loss. Recent research has suggested that exercise can protect people from both physical and mental decline with ageing. Our latest findings now provide a potential molecular link between keeping active and a healthy ageing process.”

The Aston Research Centre for Healthy Ageing takes a multidisciplinary approach to successful ageing by asking how technological, therapeutic and psychosocial strategies can be employed to understand and arrest age-related decline and degeneration.

How Well Do Football Helmets Protect Players from Concussions?

A new study finds that football helmets currently used on the field may do little to protect against hits to the side of the head, or rotational force, an often dangerous source of brain injury and encephalopathy. The study released today will be presented at the American Academy of Neurology’s 66th Annual Meeting in Philadelphia, April 26 to May 3, 2014.

"Protection against concussion and complications of brain injury is especially important for young players, including elementary and middle school, high school and college athletes, whose still-developing brains are more susceptible to the lasting effects of trauma," said study co- author Frank Conidi, MD, DO, MS, director of the Florida Center for Headache and Sports Neurology and Assistant Clinical Professor of Neurology at Florida State University College of Medicine in Port Saint Lucie, Fla. Conidi is also the vice chair of the American Academy of Neurology’s Sports Neurology Section.                                        

For the study, researchers modified the standard drop test system, approved by the National Operating Committee on Standards for Athletic Equipment, that tests impacts and helmet safety. The researchers used a crash test dummy head and neck to simulate impact. Sensors were also placed in the dummy’s head to measure linear and rotational responses to repeated 12 mile-per-hour impacts. The scientists conducted 330 tests to measure how well 10 popular football helmet designs protected against traumatic brain injury, including: Adams a2000, Rawlings Quantum, Riddell 360, Riddell Revolution, Riddell Revolution Speed, Riddell VSR4, Schutt Air Advantage, Schutt DNA Pro+, Xenith X1 and Xenith X2.

The study found that football helmets on average reduced the risk of traumatic brain injury by only 20 percent compared to not wearing a helmet. Of the 10 helmet brands tested, the Adams a2000 provided the best protection against concussion and the Schutt Air Advantage the worst. Overall, the Riddell 360 provided the most protection against closed head injury and the Adams a2000 the least, despite rating the best against concussion.

"Alarmingly, those that offered the least protection are among the most popular on the field," said Conidi. "Biomechanics researchers have long understood that rotational forces, not linear forces, are responsible for serious brain damage including concussion, brain injury complications and brain bleeds. Yet generations of football and other sports participants have been under the assumption that their brains are protected by their investment in headwear protection."

The study found that football helmets provided protection from linear impacts, or those leading to bruising and skull fracture. Compared to tests using dummies with no helmets, leading football helmets reduced the risk of skull fracture by 60 to 70 percent and reduced the risk of focal brain tissue bruising by 70 to 80 percent.

The study was supported by BRAINS, Inc., a research and development company based in San Antonio, Fla., focused on biomechanics of traumatic brain injury.

Learning to see better in life and baseball

With a little practice on a computer or iPad—25 minutes a day, 4 days a week, for 2 months—our brains can learn to see better, according to a study of University of California, Riverside baseball players reported in the Cell Press journal Current Biology on February 17. The new evidence also shows that a visual training program can sometimes make the difference between winning and losing.

The study is the first, as far as the researchers know, to show that perceptual learning can produce improvements in vision in normally seeing individuals.

"The demonstration that seven players reached 20/7.5 acuity—the ability to read text at three times the distance of a normal observer—is dramatic and required players to stand forty feet back from the eye chart in order to get a measurement of their vision," says Aaron Seitz of the University of California, Riverside. For reference, 20/20 is considered normal visual acuity.

In the training game, the players’ task was to find and select visual patterns modeled after stimuli to which neurons in the early visual cortex of the brain respond best, Seitz explains. As game play commenced, those patterns were made dimmer and dimmer, exercising the players’ vision as they searched.

"The goal of the program is to train the brain to better respond to the inputs that it gets from the eye," Seitz says. "As with most other aspects of our function, our potential is greater than our normative level of performance. When we go to the gym and exercise, we are able to increase our physical fitness; it’s the same thing with the brain. By exercising our mental processes we can promote our mental fitness."

After the 2 month training period, players reported “seeing the ball much better,” “greater peripheral vision,” “easy to see further,” “able to distinguish lower-contrasting things,” “eyes feel stronger, they don’t get tired as much,” and so on.

The players also showed greater-than-expected improvements in their game. They were less likely to strike out and got more runs. The researchers estimate that those gains in batting statistics may have given the team an additional four or five wins in the 2013 season.

The researchers are now extending their work to include different groups, including members of the Los Angeles and Riverside Police Departments and people with low vision due to cataracts, macular degeneration, or amblyopia. They will also apply the same principles to other aspects of cognition, including memory and attention.

It all comes down to one thing: “Understanding the rules of brain plasticity unlocks great potential for improvement of health and wellbeing,” Seitz says.

Thinking it through: Scientists seek to unlock mysteries of the brain

Understanding the human brain is one of the greatest challenges facing 21st century science. If we can rise to this challenge, we will gain profound insights into what makes us human, develop new treatments for brain diseases, and build revolutionary new computing technologies that will have far reaching effects, not only in neuroscience.

Scientists at the European Human Brain Project—set to announce more than a dozen new research partnerships worth Eur 8.3 million in funding later this month—the Allen Institute for Brain Science, and the US BRAIN Initiative are developing new paradigms for understanding how the human brain works in health and disease. Today, their international and collaborative projects are defined, explored, and compared during “Inventing New Ways to Understand the Human Brain,” at the 2014 AAAS Annual Meeting in Chicago.

Brain Simulation, Big Data, and a New Computing Paradigm

Henry Markram from the Ecole Polytechnique Fédérale de Lausanne (EPFL), in Switzerland, where the Human Brain Project is based, describes how the project will leverage available experimental data and basic principles of brain organization to reconstruct the detailed structure of the brain in computer models. The models will allow the HBP to run super-computer based simulations of the inner working of the brain.

"Brain simulation allows measurements and manipulations impossible in the lab, opening the road to a new kind of in silico experimentation," Markram says.

The data deluge in neuroscience is resulting in a revolutionary amount of brain data with new initiatives planning to acquire even more. But searching, accessing, and analyzing this data remains a key challenge.

Sean Hill, also of EPFL and a speaker at AAAS, leads The Neuroinformatics Platform of the Human Brain Project (HBP). In this scientific panel, he explains how the platform will provide tools to manage, navigate, and annotate spatially referenced brain atlases, which will form the basis for the HBP’s modeling effort—turning Big Data into deep knowledge.

The Neuroinformatics Platform will bring together many different kinds of data. University of Edinburgh’s Seth Grant, a key member of the HBP, describes how he is deriving new methods to decode the molecular principles underlying the brain’s organization, such as how individual proteins assemble into larger complexes. As Grant explains in Chicago, this has important practical applications as many mutations in schizophrenia and autism converge on these so-called supercomplexes in the brain.

As we understand more and more about the way the brain computes we can apply this knowledge to technology. Karlheinz Meier, of Heidelberg University in Germany and a speaker at AAAS, outlines how he is working to create entirely new computing systems as part of the HBP. These Neuromorphic Computing Systems will merge realistic brain models with new hardware for a completely new paradigm of computing—one that more closely resembles how the brain itself processes information.

"The brain has the ability to efficiently perform computations that are impossible even for the most powerful computers while consuming only 30 Watts of power," Meier says.

Brain: Get Ready For Your Close-up

At AAAS, Christof Koch lays out another ambitious, 10-year plan from the Allen Institute for Brain Science: to understand the structure and function of the brain by mapping cell types from mice and humans with computer simulations and figuring out how the cells connect, and how they encode, relay, and process information. The project, Koch says, promises massive, multimodal, and open-access datasets and methodology that will be reproducible and scalable.

At Harvard University, George Church is participating in the Brain Research through Advancing Innovative Neurotechnologies (BRAIN) Initiative, which aims to map every neuron in the brain with rapidly advancing technologies. At AAAS, he describes progress on new tools for measurements of brain cell development, connectivity, and functional state dynamics in rodent and human clinical samples.

What do all of these projects have in common? They seek to help find some of the most elusive answers known to man: what makes us human, how does the brain function, what causes neurological and mental illness, and, most importantly, how can we treat or cure these afflictions?

Promise of a bonus counter-productive in brains with high dopamine levels

Some people perform better and others worse when promised a high bonus. Brain researcher Esther Aarts of the Donders Institute in Nijmegen has demonstrated for the first time that the amount of dopamine in the brain plays a role in this regard. The journal Psychological Science will publish the results on February 13.

It has been known for some time that not everyone performs better after being promised a bonus. Scientists have published contradictory results regarding the cause. The study by Esther Aarts now shows that the differences can be explained by differences in the level of dopamine in the brain. People with a high level of dopamine in a specific brain region – the striatum – perform worse after a being promised a bonus, and people with a low level of dopamine in the same area perform better. Aarts used a PET (Positron Emission Tomography) scanner to examine the amount of dopamine in the brains of subjects. She conducted this research in Berkeley, California (USA), where she worked as a post-doctoral researcher for two years.

Overdose of dopamine
The promise of a bonus provides an additional spurt of the ‘motivation substance’ dopamine in the brain. ‘For people who usually have high levels of dopamine, the promise of a bonus causes a type of dopamine overdose in the striatum’, explains Aarts. ‘Our test subjects were asked to perform a task that required considerable concentration. An overdose of dopamine makes this difficult. People who usually have less dopamine are less likely to have an overdose of dopamine, and they therefore perform better after being promised a bonus.’

Concentration desired
Test subjects performed a computer task that elicited conflicting reactions, therefore requiring considerable concentration: an arrow appears on the screen, pointing either left or right. The word ‘left’ or ‘right’ is written in the middle of the arrow. Subjects were asked to ignore the direction indicated by the arrow and mention only the direction described by the word. For half of the attempts, a bonus of 15 cents was promised for a correct answer. In the other half, the subjects received only 1 cent for each correct answer. People who usually have a high level of dopamine performed better in the low-pay condition than they did in the high-pay condition. The reverse was observed for people with low levels of dopamine: they performed better with high rewards than they did with low rewards.

Flexibility or focus
‘This knowledge could make it possible to apply bonuses more effectively, but it would require observing the standard dopamine levels of people, as well as the nature of the task that they must perform’, reports Aarts. ‘It makes quite a difference whether the task is flexible and creative or whether it requires a great deal of focus. Our research shows how people perform on tasks that require considerable focus’. Given the high cost of PET scans, Aarts is now looking for easier ways of measuring dopamine levels. ‘I hope to be able to relate dopamine levels to scores on questionnaires. In the future, this might eliminate the need for PET scans for determining the quantity of dopamine in the brain’.