Meaning of Brain Scans For ‘Pain’ Called Into Question University College London

The study, published in JAMA Neurology and funded by the Medical Research Council and European Commission, was designed to test the ‘pain matrix’. This is a pattern of brain activity that has been so consistently observed in almost every neuroimaging study of pain in humans that it is often considered a marker for pain. The association is so pervasive that the ‘pain matrix’ has been used in research to suggest that social rejection or mental effort can cause ‘pain’.

To test whether this pattern actually represents the sense of pain, researchers used functional magnetic resonance imaging (fMRI) to measure brain activity in two rare individuals born without the ability to feel pain and four age-matched healthy volunteers. They were exposed to painful ‘pinprick’ stimuli while their brain activity was measured.

The people with no sense of pain showed the same pattern of brain activity as the healthy volunteers, casting doubt on the theory that this pattern represents pain.

“Our results suggest that these patterns are not in fact ‘pain responses’ but responses to attention-grabbing sensory stimuli regardless of whether a person feels pain,” explains lead author Dr Tim Salomons (University of Reading). “By testing people with no sense of pain, we can categorically rule out that these are pain-specific responses. These people still retain all other senses including non-painful touch, so the brain activity that has been dubbed the ‘pain matrix’ is likely to represent these senses rather than actual pain.”

The findings highlight the need to be cautious when interpreting observed associations between brain activity and human experiences.

“Every science student knows that correlation does not imply causation, and we should not forget this when interpreting brain scans,” says senior author Professor John Wood (UCL Medicine). “Although correlations between pain and brain activity have repeatedly been made, a causal relationship between neuronal activity and pain sensation has yet to be established. 

Just like a sense of beauty or happiness, the precise location of pain sensation in the brain remains elusive for now. It would be therefore misguided to use brain scans to inform diagnosis or drug discovery relating to pain management. In order to understand how our brains give rise to the sense of pain, human brain imaging will need to be supplemented by research in animals where individual cells can be modified and measured.”

Scientists The Oxford University Create First Light Activated Synthetic Tissues

Scientists at the University of Oxford have created synthetic tissues that possess functional properties controlled by light – including the ability to ‘switch on’ the expression of individual genes.

Made up of hundreds of interacting water droplets, these light-activated synthetic tissues could be developed into a platform to study how cells interact, for drug delivery, or even to control living tissues.

The work has demonstrated that it is possible to create synthetic tissues that comprise patterned networks of interconnected compartments, each with a minimal cellular functionality that can be externally controlled by light.

The research is published in the journal Science Advances.

Professor Hagan Bayley of the Department of Chemistry at the University of Oxford, senior author of the study, said: ‘A key objective of bottom-up synthetic biology has been to build synthetic cells capable of performing simple functions. Previous research has concentrated on individual compartments, whereas we have been exploring the next level of organization in synthetic biology: the formation of tissue-like materials.’

Previous work carried out by Professor Bayley’s group has seen the development of a 3D printer that creates soft structures made of hundreds of salt-containing picoliter droplets connected through lipid membranes. These structures can be given functions unattainable with individual droplets, such as the ability to fold into new shapes. However, once built, these tissue-like materials cannot be readily altered.

First author Dr Michael Booth, Junior Research Fellow at Merton College, University of Oxford, and a member of the Bayley group, said: ‘We have endowed these droplets with a minimal cellular functionality: the ability to express proteins from synthetic DNA genes. Furthermore, a tightly regulated light-activated DNA has been created, so protein is only formed upon illumination of the “synthetic cells”.

‘Having induced the expression of transmembrane protein pores in selected cells by directed irradiation, we demonstrate fast directional electrical communication through the 3D printed material under stringent light-activated control. The conductive pathway formed in the 3D-printed tissue is a functional mimic of communication in the nervous system. These synthetic tissues may be developed into a biomaterial that could help repair the nervous system.’

Fourth Annual UMassGives Campaign Collects Record Donations

The University of Massachusetts Amherst’s fourth annual UMassGives campaign, a 36-hour online fundraiser for the campus, has raised a record $162,182 from 2,138 donors. 

The campaign kicked off at noon on April 27 during the university’s annual Founders Day celebration and ran through midnight April 28.

In support of the campaign, the UMass Amherst Foundation Board donated $10,000 in matching funds, and an alumnus matched the first $1,000 in donations for Commonwealth Honors College.

The foundation board also contributed $2,000 bonuses for each group that had the largest number of donors during five challenge hours. The winners were: the Student Alumni Association, the College of Engineering, University Without Walls, the College of Information and Computer Sciences and Friends of Music.

Gifts were made to 115 different designations, with the largest numbers going to Isenberg School of Management, the College of Engineering, the Alumni Association, University Without Walls, and the College of Information and Computer Sciences.

The largest single gift was $5,000; the average, $75.86. Donors hailed from eight countries and 40 states, with the majority of gifts from individuals from Amherst, Northampton, Belchertown, Boston and South Hadley.

Of the total, 1,001 gifts came from people who listed their university affiliation as alumni; 367 selected faculty/staff; 310 student; 286 parent, and 278 friend. (Some donors were recorded in more than one category.

Gifts made during UMassGives are counted toward the UMass Rising Campaign, which surpassed its $300 million goal last spring and to date has raised $350 million. The campaign, publicly launched in April 2013 during the university’s sesquicentennial year, concludes June 30.

In 2015, UMassGives raised more than $100,000 from nearly1,700 donors.

Maiden Voyage of Stanford's University Humanoid Robotic Diver Recovers

Oussama Khatib held his breath as he swam through the wreck of La Lune, 100 meters below the Mediterranean. The flagship of King Louis XIV sank here in 1664, 20 miles off the southern coast of France, and no human had touched the ruins – or the countless treasures and artifacts the ship once carried – in the centuries since.

OceanOne, a humanoid robotic diver from Stanford, allows new underwater exploration capabilities.

With guidance from a team of skilled deep-sea archaeologists who had studied the site, Khatib, a professor of computer science at Stanford, spotted a grapefruit-size vase. He hovered precisely over the vase, reached out, felt its contours and weight, and stuck a finger inside to get a good grip. He swam over to a recovery basket, gently laid down the vase and shut the lid. Then he stood up and high-fived the dozen archaeologists and engineers who had been crowded around him.

This entire time Khatib had been sitting comfortably in a boat, using a set of joysticks to control OceanOne, a humanoid diving robot outfitted with human vision, haptic force feedback and an artificial brain – in essence, a virtual diver.

When the vase returned to the boat, Khatib was the first person to touch it in hundreds of years. It was in remarkably good condition, though it showed every day of its time underwater: The surface was covered in ocean detritus, and it smelled like raw oysters. The team members were overjoyed, and when they popped bottles of champagne, they made sure to give their heroic robot a celebratory bath.

The expedition to La Lune was OceanOne’s maiden voyage. Based on its astonishing success, Khatib hopes that the robot will one day take on highly skilled underwater tasks too dangerous for human divers, as well as open up a whole new realm of ocean exploration.

“OceanOne will be your avatar,” Khatib said. “The intent here is to have a human diving virtually, to put the human out of harm’s way. Having a machine that has human characteristics that can project the human diver’s embodiment at depth is going to be amazing.”

Anatomy of a robo-mermaid

The concept for OceanOne was born from the need to study coral reefs deep in the Red Sea, far below the comfortable range of human divers. No existing robotic submarine can dive with the skill and care of a human diver, so OceanOne was conceived and built from the ground up, a successful marriage of robotics, artificial intelligence and haptic feedback systems.

OceanOne looks something like a robo-mermaid. Roughly five feet long from end to end, its torso features a head with stereoscopic vision that shows the pilot exactly what the robot sees, and two fully articulated arms. The “tail” section houses batteries, computers and eight multi-directional thrusters.

The body looks far unlike conventional boxy robotic submersibles, but it’s the hands that really set OceanOne apart. Each fully articulated wrist is fitted with force sensors that relay haptic feedback to the pilot’s controls, so the human can feel whether the robot is grasping something firm and heavy, or light and delicate. (Eventually, each finger will be covered with tactile sensors.) The ‘bot’s brain also reads the data and makes sure that its hands keep a firm grip on objects, but that they don’t damage things by squeezing too tightly. In addition to exploring shipwrecks, this makes it adept at manipulating delicate coral reef research and precisely placing underwater sensors.

“You can feel exactly what the robot is doing,” Khatib said. 

“It’s almost like you are there; with the sense of touch you create a new dimension of perception.”

The pilot can take control at any moment, but most frequently won’t need to lift a finger. Sensors 

throughout the robot gauge current and turbulence, automatically activating the thrusters to keep the robot in place. And even as the body moves, quick-firing motors adjust the arms to keep its hands steady as it works. Navigation relies on perception of the environment, from both sensors and cameras, and these data run through smart algorithms that help OceanOne avoid collisions. If it senses that its thrusters won’t slow it down quickly enough, it can quickly brace for impact with its arms, an advantage of a humanoid body build.

A human touch

The humanoid form also means that when OceanOne dives alongside actual humans, its pilot can communicate through hand gestures during complex tasks or scientific experiments. Ultimately, though, Khatib designed OceanOne with an eye toward getting human divers out of harm’s way. Every aspect of the robot’s design is meant to allow it to take on tasks that are either dangerous – deep-water mining, oil-rig maintenance or underwater disaster situations like the Fukushima Daiichi power plant – or simply beyond the physical limits of human divers.

“We connect the human to the robot in very intuitive and meaningful way. The human can provide intuition and expertise and cognitive abilities to the robot,” Khatib said. “The two bring together an amazing synergy. The human and robot can do things in areas too dangerous for a human, while the human is still there.”

Khatib was forced to showcase this attribute while recovering the vase. As OceanOne swam through the wreck, it wedged itself between two cannons. Firing the thrusters in reverse wouldn’t extricate it, so Khatib took control of the arms, motioned for the bot to perform a sort of pushup, and OceanOne was free.

The expedition to La Lune was made possible in large part thanks to the efforts of Michel L’Hour, the director of underwater archaeology research in France’s Ministry of Culture. Previous remote studies of the shipwreck conducted by L’Hour’s team made it possible for OceanOne to navigate the site. 

Vincent Creuze of the Universite de Montpellier in France commanded the support underwater vehicle that provided third-person visuals of OceanOne and held its support tether at a safe distance.

Several students played key roles in OceanOne’s success, including graduate students Gerald Brantner, Xiyang Yeh, Boyeon Kim, Brian Soe and Hannah Stuart, who joined Khatib in France for the expedition, as well as Shameek Ganguly, Mikael Jorda, Shiquan Wang and a number of undergraduate and graduate students. Khatib also drew on the expertise of Mark Cutkosky, a professor of mechanical engineering, and his students for designing and building the robotic hands.

Next month, OceanOne will return to the Stanford campus, where Khatib and his students will continue iterating on the platform. The prototype robot is a fleet of one, but Khatib hopes to build more units, which would work in concert during a dive.

In addition to Stanford, the development of the robot was supported by Meka Robotics and the King Abdullah University of Science and Technology (KAUST) in Saudi Arabia.

Stanford University Researchers Improve Understanding of Protein that Could Improve Bioengineered Tissues

 

Collagen is an essential protein for living tissue. It forms the stiff scaffolding that provides structure and stability for tissues and the cells within them. It is also nature’s packaging material, imbued with qualities that allow it to support and cushion cells, miraculously alternating between states of moderate elasticity and quasi-fluidity, depending on the physical forces acting upon it.

Stanford researchers are studying the way collagen moves between stiff and elastic states in the human body. (Image credit: Sebastian Kaulitzki.

These seemingly contradictory characteristics stiff or semi-fluid as circumstances demand  make collagen viscoelastic, similar to Silly Putty.

Now, a group of Stanford researchers have learned how the protein transitions between these properties. Writing in the Proceedings of the National Academy of Sciences, the researchers report that the stiffer collagen networks become in response to a deformation, the more quickly they relax viscously.

The researchers think that this insight could lead to new techniques for bioengineering tissue for regenerative medicine. By targeting mechanical forces acting upon cells, scientists might be able to encourage them to grow in particular ways to, for instance, heal wounds or replace tissues carved away during surgery.

“People tend to think that cells only respond to chemical cues,” said Ovijit Chaudhuri, an assistant professor of mechanical engineering at Stanford. “But they are also exquisitely sensitive to mechanical cues, to the relative stiffness of the collagen networks that surround many cells, for example.”

Chaudhuri applies this physical-force perspective to a truly interdisciplinary effort – investigating how the mechanics of the tissue affect breast cancer progression and how the mechanical properties of biomaterials can be engineered to promote tissue regeneration by cells.

“It has been found that enhanced tissue stiffness promotes breast cancer progression and that altered stiffness can even cue stem cells to differentiate in certain ways,” Chaudhuri said. “We’re learning that the mechanics of the microenvironment, mediated through the physical forces cells exert on the microenvironment, play major roles in cell function.”

The researchers investigated the mechanics of collagen networks through traditional mechanical testing, computational modeling, and using atomic force microscopy to apply force at the molecular scale.

Their key finding is that the degree of deformation exerted on collagen is directly related to the subsequent viscoelastic response: More deformation on the collagen – technically, more strain-stiffening – results in accelerated viscoelasticity as the collagen reverts to a relaxed state.

Collagen biopolymers are “cross-linked,” meaning they are connected like the strands of a fishing net, said co-author Sungmin Nam, a mechanical engineering graduate student.

“These cross-links, however, are not always particularly strong, and can be quite weak,” Nam said. “Our work suggests that these weak cross-links exhibit force-dependent unbinding. In other words, the greater the force on the cross-links, the quicker they unbind. So the more force on the collagen in general, the quicker you’ll see a subsequent relaxation.”

Cell behaviors are deeply influenced by mechanical properties, so the research implicates that the distinctive mechanics of collagen could play a major role in regulating cell behaviors. Nam said this improved understanding of collagen’s varying elastic and viscoelastic qualities have significant implications for regenerative medical research.

“We know that cells interact strongly with their microenvironments, and that (collagen) polymers affect these microenvironments through strain-stiffening and viscoelasticity,” Nam said. “As we gain insights into cell-collagen interactions, it could help us develop new techniques for 3D cell culture and tissue regeneration.”

Chaudhuri is an associate member of the Stanford Cancer Institute and a member of Bio-X, ChEM-H, and the Stanford Biophysics Program. His coauthors on the study include Manish J. Butte, an assistant professor of pediatrics at the Stanford School of Medicine, and Kenneth H. Hu, a Stanford graduate student in biophysics.

Research was supported by the Jeongsong Cultural Foundation and Samsung Scholarship for S.N., the NIH/NIGMS, and grants from the Stanford Child Health Research Institute and DARPA.