New research builds on the pioneering use of machine learning algorithms with brain imaging technology to "mind read." For the first time, thoughts containing several concepts can be decoded.
Carnegie Mellon University scientists can now use brain activation patterns to identify complex thoughts, such as, "The witness shouted during the trial."
This latest research, led by CMU's Marcel Just, builds on the pioneering use of machine learning algorithms with brain imaging technology to "mind read." The findings indicate that the mind's building blocks for constructing complex thoughts are formed by the brain's various sub-systems and are not word-based. Published in Human Brain Mapping and funded by the Intelligence Advanced Research Projects Activity (IARPA), this study offers new evidence that the neural dimensions of concept representation are universal across people and languages.
"One of the big advances of the human brain was the ability to combine individual concepts into complex thoughts, to think not just of 'bananas,' but 'I like to eat bananas in evening with my friends,'" said Just, a Professor of Psychology in the Dietrich College of Humanities and Social Sciences. "We have finally developed a way to see thoughts of that complexity in the fMRI signal. The discovery of this correspondence between thoughts and brain activation patterns tells us what the thoughts are built of."
Previous work by Just and his team showed that thoughts of familiar objects, like bananas or hammers, evoke activation patterns that involve the neural systems we use to deal with those objects. For example, how you interact with a banana involves how you hold it, how you bite it and what it looks like.
The new study demonstrates that the brain's coding of 240 complex events, sentences like the shouting during the trial scenario uses an alphabet of 42 meaning components, or neurally plausible semantic features – consisting of features like person, setting, size, social interaction and physical action. Each type of information is processed in a different brain system, which is how the brain also processes the information for objects. By measuring the activation in each brain system, the program can tell what types of thoughts are being contemplated.
For seven adult participants, the researchers used a computational model to assess how the brain activation patterns for 239 sentences corresponded to the neurally plausible semantic features that characterised each sentence. The program was then able to decode the features of the 240th left-out sentence. They went through leaving out each of the 240 sentences in turn, in what is called cross-validation.
The model was able to predict the features of the left-out sentence, with 87% accuracy, despite never being exposed to its activation before. It was also able to work in the other direction, to predict the activation pattern of a previously unseen sentence, knowing only its semantic features.
"Our method overcomes the unfortunate property of fMRI to smear together the signals emanating from brain events that occur close together in time, like the reading of two successive words in a sentence," Just said. "This advance makes it possible for the first time to decode thoughts containing several concepts. That's what most human thoughts are composed of."
He added, "A next step might be to decode the general type of topic a person is thinking about, such as geology or skateboarding. We are on the way to making a map of all the types of knowledge in the brain." CMU's Jing Wang and Vladimir L. Cherkassky also participated in the study.
Discovering how the brain decodes complex thoughts is one of the many brain research breakthroughs to happen at Carnegie Mellon. CMU has created some of the first cognitive tutors, helped to develop the Jeopardy-winning Watson, founded a groundbreaking doctoral program in neural computation, and is the birthplace of artificial intelligence and cognitive psychology. Building on its strengths in biology, computer science, psychology, statistics and engineering, CMU launched BrainHub, an initiative that focuses on how the structure and activity of the brain give rise to complex behaviours.
In a study involving simulated out-of-hospital cardiac arrests, drones carrying an automated external defibrillator arrived in less time than emergency medical services.
Drones carrying an automated external defibrillator could dramatically improve the response time for heart emergencies – potentially saving many thousands of lives each year – according to a study published by the Journal of the American Medical Association (JAMA).
Out-of-hospital cardiac arrest (OHCA) in the United States has a low survival rate (less than 10%), with reducing time to defibrillation as the most important factor for increasing survival. Drones can be activated by a dispatcher and sent to an address provided by a 911 caller and may carry an automated external defibrillator (AED) to the location so that a bystander can use it. Whether drones could actually reduce response times in a real-life situation is unknown. Researchers from the Karolinska Institutet in Stockholm, Sweden, compared the time to delivery of an AED using fully autonomous drones for simulated OHCAs vs emergency medical services (EMS).
A drone was developed and certified by the Swedish Transportation Agency and equipped with an AED weighing 771 grams (1.7 lbs), then placed at a fire station in a municipality north of Stockholm. The drone was equipped with a global positioning system (GPS) and high-definition camera and integrated with an autopilot software system. It was dispatched to locations where cardiac arrests within a 10 km (6.2 mile) radius of the fire station had previously occurred.
A total of 18 remotely operated flights were performed with a median flight distance of about two miles. The median time from call to dispatch of the EMS was 3:00 minutes, while the median time from dispatch to drone launch was three seconds. The median time from dispatch to arrival of the drone was 5:21 minutes vs 22:00 minutes for EMS. The drone arrived more quickly than EMS in all cases with a median reduction in response time of 16:39 minutes.
"Saving 16 minutes is likely to be clinically important," the authors write. "Nonetheless, further test flights, technological development, and evaluation of integration with dispatch centers and aviation administrators are needed. The outcomes of OHCA using the drone-delivered AED by bystanders vs resuscitation by EMS should be studied."
Researchers from the Netherlands and Germany have identified seven risk genes for insomnia.
An international team of researchers has found, for the first time, seven risk genes for insomnia. This discovery is an important step forward in understanding the biological mechanisms of sleep. In addition, it proves that insomnia is not, as is often claimed, a purely psychological condition.
Insomnia is among the most common health complaints – affecting between 10% and 30% of adults worldwide at any given point in time and up to half in a given year. Even after treatment, poor sleep can remain a persistent vulnerability for many people. Professor Van Someren, a sleep specialist from the Vrije Universiteit Amsterdam (VU), believes his team's findings could lead to an understanding of insomnia at the level of communication within and between neurons, providing new ways of treating the condition. He also hopes this breakthrough will improve the recognition of insomnia.
"Compared to the severity, prevalence and risks of insomnia, only few studies targeted its causes," he says. "Insomnia is all too often dismissed as being 'all in your head'. Our research brings a new perspective: insomnia is also in the genes."
From a sample of 113,000 individuals, the researchers found seven genes for insomnia. These play a role in the regulation of transcription, the process where DNA is read in order to make an RNA copy of it, and exocytosis, the release of molecules by cells in order to communicate with their environment. One of the identified genes, MEIS1, has previously been related to two other sleep disorders: Periodic Limb Movements of Sleep (PLMS) and Restless Legs Syndrome (RLS). By collaborating with Konrad Oexle and colleagues from the Institute of Neurogenomics in Munich, Germany, they concluded that variants in the gene seem to contribute to all three disorders. Strikingly, PLMS and RLS are characterised by restless movement and sensation, respectively, whereas insomnia is characterised mainly by a restless stream of consciousness.
The researchers also found a strong genetic overlap with other traits – such as anxiety disorders, depression, neuroticism, and low subjective wellbeing: "This is an interesting finding, because these characteristics tend to go hand in hand with insomnia. We now know that this is partly due to the shared genetic basis," says neuroscientist Anke Hammerschlag (VU), PhD student and first author of the study.
The team also studied whether the same genetic variants were important for men and women. "Part of the genetic variants turned out to be different," says Professor Danielle Posthuma, a statistical geneticist at VU Amsterdam. "This suggests that, for some part, different biological mechanisms may lead to insomnia in men and women. We also found a difference between men and women in terms of prevalence: in the sample we studied, including mainly people older than 50, 33% of the women reported to suffer from insomnia. For men, this was 24%."
Human blood stem cells have been grown in the laboratory for the first time by researchers at Boston Children's Hospital.
Researchers at Boston Children's Hospital have, for the first time, generated blood-forming stem cells in the lab using pluripotent stem cells, which can make virtually every cell type in the body. The advance, published in the journal Nature, opens new avenues for research into the root causes of blood diseases and to creating immune-matched blood cells for treatment purposes, derived from patients' own cells.
"We're tantalisingly close to generating bona fide human blood stem cells in a dish," says senior investigator George Daley, PhD, who heads a research lab in Boston Children's Hospital's Stem Cell Program and is dean of Harvard Medical School. "This work is the culmination of over 20 years of striving."
"This is a very big deal," said Carolina Guibentif at the University of Cambridge, who was not involved in the research. "If you can develop [these cells] in the lab in a safe way and in high enough numbers, you wouldn't be dependent on donors."
Although the cells made from the pluripotent stem cells are a mix of true blood stem cells and other cells known as blood progenitor cells, they proved capable of generating multiple types of human blood cells when put into mice.
"This step opens up an opportunity to take cells from patients with genetic blood disorders, use gene editing to correct their genetic defect and make functional blood cells," comments Ryohichi (Rio) Sugimura, PhD, the paper's first author. "This also gives us the potential to have a limitless supply of blood stem cells and blood by taking cells from universal donors. This could potentially augment the blood supply for patients who need transfusions."
Since human embryonic stem (ES) cells were first isolated in 1998, scientists have been trying, with little success, to use them to make blood-forming stem cells. During 2007, three groups (including the Daley lab) generated the first induced pluripotent stem (iPS) cells from human skin cells through genetic reprogramming. iPS cells were later used to generate multiple human cell types, such as neurons and heart cells – yet blood-forming stem cells remained elusive.
Sugimura, Daley and colleagues combined two previous approaches. First, they exposed human pluripotent stem cells (both ES and iPS cells) to chemical signals that direct stem cells to differentiate into specialised cells and tissues during normal embryonic development. This generated hemogenic endothelium, an early embryonic tissue that eventually gives rise to blood stem cells, although the transition to blood stem cells had never been achieved in a dish.
In the second step, the team added genetic regulatory factors (called transcription factors) to push the hemogenic endothelium toward a blood-forming state. Starting with 26 transcription factors identified as likely candidates, they eventually came down to just five (RUNX1, ERG, LCOR, HOXA5 and HOXA9) that were both necessary and sufficient for creating blood stem cells. They delivered the factors into the cells with a lentivirus, as used in some forms of gene therapy.
Finally, they transplanted the genetically engineered hemogenic endothelial cells into mice. Weeks later, a small number of the animals carried multiple types of human blood cells in their bone marrow and blood circulation. These included red blood cell precursors, myeloid cells (precursors of monocytes, macrophages, neutrophils, platelets and other cells), and T and B lymphocytes. Some mice were able to mount a human immune response after vaccination.
ES cells and iPS cells were similarly good at creating blood stem and progenitor cells when the technique was applied. But the researchers are most interested in iPS cells, which offer the added ability to derive cells directly from patients and model disease.
"We're now able to model human blood function in so-called 'humanised mice,'" says Daley. "This is a major step forward for our ability to investigate genetic blood disease."
One challenge in making bona-fide human blood stem cells is that no one's been able to fully characterise them: "It's proved challenging to 'see' these cells," says Sugimura. "You can roughly characterise blood stem cells based on surface markers, but even with this, it may not be a true blood stem cell. And once it starts to differentiate and make blood cells, you can't go back and study it – it's already gone. A better characterisation of human blood stem cells and a better understanding of how they develop would give us clues to making bona-fide human blood stem cells."
The first synthetic retina using soft biological tissues has been created by a student at the University of Oxford.
Credit: Oxford University
A synthetic, soft tissue retina developed by an Oxford University student could offer fresh hope to visually impaired people. Until now, all artificial retinal research has used only rigid, hard materials. However, new research by Vanessa Restrepo-Schild, a 24-year-old Dphil student and researcher at Oxford University's Department of Chemistry, is the first to successfully use biological, synthetic tissues, developed in a laboratory. The study could revolutionise the bionic implant industry and the development of new, less invasive technologies that more closely resemble human body tissues, helping to treat degenerative eye conditions.
Just as photography depends on camera pixels reacting to light, our vision relies on the retina performing the same function. The retina sits at the back of the human eye, and contains protein cells that convert light into electrical signals that travel through the nervous system, triggering a response from the brain, ultimately building a picture of the scene being viewed.
Restrepo-Schild led the team in developing a new synthetic, double layered retina that closely mimics the natural human retinal process. The retina replica consists of soft water droplets (hydrogels) and biological cell membrane proteins. Designed like a camera, the cells act as pixels, detecting and reacting to light to create a greyscale image. Restrepo-Schild explains: "The synthetic material can generate electrical signals, which stimulate the neurons at the back of our eye – just like the original retina."
The study, published in Scientific Reports, shows that unlike existing artificial retinal implants, the cell cultures are created from natural, biodegradable materials and do not contain foreign bodies or living entities. In this way, the implant is less invasive than a mechanical device, and is less likely to have an adverse reaction on the body. Miss Restrepo-Schild adds: "The human eye is incredibly sensitive, which is why foreign bodies like metal retinal implants can be so damaging – leading to inflammation and/or scarring. But a biological synthetic implant is soft and water based, so much more friendly to the eye environment."
Of the motivation behind her ground-breaking study, Miss Restrepo-Schild says: "I have always been fascinated by the human body, and want to prove that current technology could be used to replicate the function of human tissues, without having to actually use living cells.
"I have taken the principals behind vital bodily functions, e.g. our sense of hearing, touch and the ability to detect light, and replicated them in a laboratory environment with natural, synthetic components. I hope my research is the first step in a journey towards building technology that is soft and biodegradable instead of hard and wasteful."
Although at present the synthetic retina has only been tested in laboratory conditions, Miss Restrepo-Schild is keen to build on her initial work and explore potential uses with living tissues. This next step is vital in demonstrating how the material performs as a bionic implant.
Restrepo-Schild has filed a patent for the technology and the next phase of work will expand the replica's function to include recognising colours and potentially even shapes and symbols. Looking further ahead, the team will begin to include animal testing and then a series of clinical trials in humans.
The University of Utah has revealed a new robotic drill system for greatly speeding up surgical procedures. One type of complex cranial surgery could be done in a fiftieth of the normal time, decreasing from two hours to just two and a half minutes.
A computer-driven automated drill, similar to those used to machine auto parts, could play a pivotal role in future surgical procedures. The new machine can make one type of complex cranial surgery 50 times faster than standard procedures, decreasing from two hours to two and a half minutes. Researchers at the University of Utah developed a drill that produces fast, clean and safe cuts – reducing the time the wound is open and the patient is anesthetised, thereby decreasing the incidence of infection, human error, and surgical cost. The findings are reported in Neurosurgical Focus.
To perform complex surgeries – especially cranial surgeries – surgeons typically use hand drills to make intricate openings, adding hours to a procedure: "It was like doing archaeology," said William Couldwell, study author and neurosurgeon at the University of Utah Health. "We had to slowly take away the bone to avoid sensitive structures."
Couldwell saw a need for a device that could alleviate this burden and make the process more efficient: "We knew the technology was already available in the machine world, but no one ever applied it to medical applications."
"My expertise is dealing with the removal of metal quickly, so a neurosurgical drill was a new concept for me," explained A. K. Balaji, associate professor in mechanical engineering. "I was interested in developing a low-cost drill that could do a lot of the grunt work to reduce surgeon fatigue."
Credit: University of Utah
The team developed the drill from scratch, as well as new software to calculate the safest cutting path. First, the patient is imaged using CT scans to gather bone data and identify the exact location of sensitive structures, such as nerves, veins and arteries that must be avoided. Surgeons then use this information to program a cutting path for the drill: "The software lets the surgeon choose the optimum path from point A to point B, like Google Maps," says Balaji. In addition, the surgeon can program safety barriers along the cutting path within 1 mm of sensitive structures. "Think of the barriers like a construction zone," says Balaji. "You slow down to navigate it safety."
The translabyrinthine surgery is performed thousands of times a year to expose slow-growing, benign tumours that can form at auditory nerves. This cut must avoid several sensitive features, including facial nerves and the venous sinus, a large vein that drains blood from the brain. Risks of this surgery include loss of facial movement. The system developed at Utah has an automatic emergency shut-off switch. During surgery, facial nerves are monitored for any signs of irritation: "If the drill gets too close to the facial nerve and irritation is monitored, the drill automatically turns off," says Couldwell.
The new drill could reduce the duration of this complex procedure from two hours for hand-drilling by an experienced surgeon to two and a half minutes. The shorter surgery is expected to lower the chance of infection and improve post-operative recovery. It also has potential to substantially reduce the cost of surgery, because it shaves hours from operating room time.
The team has now demonstrated the safety and speed of the drill by performing this complex cut – but Couldwell stresses that it can be applied to many other procedures: "This drill can be used for a variety of surgeries, like machining the perfect receptacle opening in the bone for a hip implant," he said.
The varied application of the drill highlights another factor that drew Balaji to the project: "I was motivated by the fact that this technology could democratise health care by levelling the playing field so more people can receive quality care," he said. The team is now examining opportunities to commercialise the drill to ensure that it is more widely available for other surgical procedures.
Researchers at Sahlgrenska Academy – part of the University of Gothenburg, Sweden – have generated cartilage tissue by printing stem cells using a 3D-bioprinter.
The fact that the stem cells survived being printed in this manner is a success in itself. In addition, the research team was able to influence the cells to multiply and differentiate to form chondrocytes (cartilage cells) in the printed structure. The findings are published in Scientific Reports.
This research project was a collaboration with scientists at Chalmers University of Technology who are experts in the 3D printing of biological materials, as well as orthopaedic researchers from Kungsbacka.
The team used cartilage cells from patients who had recently undergone knee surgery. These cells were then manipulated in a laboratory, causing them to rejuvenate and revert into "pluripotent" stem cells, i.e. stem cells that have the potential to develop into many different types of cells. The stem cells were then expanded and encapsulated in a composition of nanofibrillated cellulose and printed into a structure using a 3D bioprinter. Following printing, the stem cells were treated with growth factors that caused them to differentiate correctly, so that they formed cartilage tissue.
Credit: Elin Lindström Claessen
"In nature, the differentiation of stem cells into cartilage is a simple process, but it's much more complicated to accomplish in a test tube. We're the first to succeed with it, and we did so without any animal testing whatsoever," says Stina Simonsson, Associate Professor of Cell Biology, who led the research team's three-year effort.
Most of their work involved developing a procedure whereby the cells could survive printing, multiply and then differentiate to form cartilage. One of the key insights gained from their study was that it is necessary to use large amounts of live stem cells to form tissue in this manner.
"We investigated various methods and combined different growth factors," Simonsson explains. "Each individual stem cell is encased in nanocellulose, allowing it to survive the process of being printed into a 3D structure. We also harvested mediums from other cells, which contain the signals that stem cells use to communicate with each other. In layman's terms, our theory is that we managed to trick the cells into thinking that they weren't alone. Therefore the cells multiplied before we differentiated them."
The cartilage formed by stem cells in the 3D bioprinted structure was extremely similar to normal human cartilage. Experienced surgeons who examined the artificial bioprinted tissue saw no difference when they compared it to the real thing, and have stated that the material has properties similar to their patients' natural cartilage. Just like normal cartilage, the lab-grown material contains Type II collagen – and under the microscope, the cells appear to be perfectly formed, with structures similar to those observed in samples of human-harvested cartilage.
This study represents a giant step forward in the ability to generate new, endogenous cartilage tissue. In the not-too-distant future, it should be possible to use 3D bioprinting to generate cartilage based on a patient's own, "backed-up" stem cells. This artificial tissue could then be used to repair cartilage damage, or to treat osteoarthritis, in which joint cartilage degenerates and breaks down. The condition is very common – one in four Swedes over the age of 45 suffer from some degree of osteoarthritis.
In theory, this research has created the opportunity to generate large amounts of cartilage, but one major issue must be resolved before the findings can be used in practice to benefit patients.
"The structure of the cellulose we used might not be optimal for use in the human body," adds Simonsson. "Before we begin to explore the possibility of incorporating the use of 3D bioprinted cartilage into the surgical treatment of patients, we need to find another material that can be broken down and absorbed by the body, so that only the endogenous cartilage remains. The most important thing for use in a clinical setting is safety."
A new drug, evolocumab, is shown to reduce bad cholesterol by 59%.
Coronary heart disease is the single biggest killer worldwide – causing over 7 million deaths each year – and "bad" LDL-cholesterol is a major cause. Statins can reduce the risk of heart disease, but they are not tolerated by everyone and only reduce cholesterol by a certain amount.
This month, the results of a major clinical trial have shown that a new cholesterol-lowering drug could further reduce the risk of heart attack or stroke for those already taking statins. The study of evolocumab (trade name Repatha) is published in the New England Journal of Medicine. This looked at over 27,500 patients in 49 countries living with heart disease and taking statins. The drug was found to lower cholesterol by an average of 59% and reduced the risk of a heart attack by 27% and stroke by 21% in the two years of follow-up.
Repatha is a human monoclonal antibody that inhibits PCSK9, an enzyme encoded by the PCSK9 gene. Repatha binds to PCSK9 and prevents it from binding to the Low-Density Lipoprotein Receptor (LDL-R), increasing the number of LDL-Rs available to clear bad cholesterol from the blood.
"It is much more effective than statins," said Prof. Peter Sever, from Imperial College London, a member of the study's executive committee. "It is probably the most important trial result of a cholesterol-lowering drug in over 20 years."
"This trial is a significant advance," said Prof. Sir Nilesh Samani, Medical Director at the British Heart Foundation. "Giving patients evolocumab, a PCSK9 inhibitor, on top of statins, not only helped to further reduce LDL-cholesterol, but also reduced the risk of cardiovascular events in people already affected by heart disease, without causing major side effects."
"We now have definitive data that by adding evolocumab to a background of statin therapy, we can significantly improve cardiovascular outcomes and do so safely," said Dr Marc Sabatine, of Harvard Medical School in Boston. "We need to treat LDL cholesterol more aggressively, and now we have a new validated means to do so."
A new study on mice has found a possible treatment for DNA damage from aging and radiation. This finding could be especially helpful for astronauts in space, who are at greater risk of DNA damage from cosmic radiation.
Credit: David Sinclair, Harvard Medical School
An international team – including researchers from Harvard and the University of New South Wales (UNSW) – has made a discovery that could lead to a revolutionary drug for reversing aspects of the aging process, improving DNA repair and ensuring the long-term survival of colonists on Mars.
In a paper published by the journal Science, they describe a critical step in the molecular process that allows cells to repair damaged DNA. Their tests on mice suggest a treatment is possible for humans exposed to radiation. It is so promising that it has attracted the attention of NASA, which believes the treatment can help its Mars mission during the 2030s.
While our cells have an innate capability to repair DNA damage − which happens every time we go out into the Sun, for example – their ability to do this declines as we age. The scientists identified that the metabolite NAD+, which is naturally present in every cell of our body, has a key role as a regulator in protein-to-protein interactions that control DNA repair. Treating mice with a NAD+ precursor, or "booster," called NMN improved their cells' ability to repair DNA damage caused by radiation exposure or old age.
"The cells of the old mice were indistinguishable from the young mice, after just one week of treatment," said the lead author, Professor David Sinclair of UNSW School of Medical Sciences and Harvard Medical School. Human trials of NMN therapy will begin within six months. "This is the closest we are to a safe and effective anti-aging drug that's perhaps only three to five years away from being on the market if the trials go well," says Sinclair.
The work has excited NASA, which faces the challenge of keeping its astronauts healthy during a four-year mission to Mars. Even on short missions, humans can experience accelerated aging from cosmic radiation, and suffer muscle weakness, memory loss and other symptoms when they return. On a trip to Mars the situation would be far worse: five per cent of the astronauts' cells would die and their chances of cancer would approach 100 per cent.
Cosmic radiation is not only an issue for astronauts. We're all exposed to it aboard aircraft, with a London-Singapore-Melbourne flight roughly equivalent in radiation to a chest x-ray. In theory, the same treatment could mitigate any effects of DNA damage for frequent flyers.
The other group that could benefit from this work is survivors of childhood cancers. 96 per cent of childhood cancer survivors suffer a chronic illness by age 45, including cardiovascular disease, Type 2 diabetes, Alzheimer's disease, and cancers unrelated to the original cancer.
"All of this adds up to the fact they have accelerated ageing, which is devastating," explains Sinclair's colleague, Dr Lindsay Wu. "It would be great to do something about that, and we believe we can with this molecule."
Dutch scientists have announced a new drug treatment able to reverse aspects of aging in old mice – restoring their stamina, coat of fur and even some organ function – by flushing out "senescent" cells in the body that have stopped dividing. Human trials are now planned.
Researchers at the Erasmus University Medical Centre in Rotterdam, Netherlands, have found a way to turn back aging. By giving old mice a peptide that disrupts the binding between two proteins, the mice became fitter and more alert, their coat of fur became fuller again, and organ functions improved. This discovery was published yesterday in the leading scientific journal Cell.
Key player in the study is proxofim, a substance developed by the researchers themselves. It disrupts the binding between the proteins FOXO4 and p53. In contrast to existing substances used by researcher to intervene with aging, proxofim was found to have no adverse effects on the health of the mice. "The platelet count and the liver function, for example, remained normal," said Peter de Keizer, a researcher in Erasmus MC's department of Molecular Genetics and a lead author in this study.
Proxofim can deal with so-called "senescent" cells that play a significant role in aging. These are cells that have ceased to divide, but are not really dead: "In fact, their metabolism does continue, which means they continue to secrete all kinds of proteins, including inflammatory cytokines," says De Keizer. "These in turn cause more rapid aging of tissues and poorer organ function. They also play a role in cancer. The senescent cells make cancer less sensitive to chemotherapy and can accelerate the growth of tumours. In other words, we actually want to get rid of these cells."
Proxofim kills these senescent cells "and it stimulates the surrounding stem cells to create new tissue. It is a peptide, a small protein that can easily penetrate into cells."
When applied to mice, this had a major effect. After just three weeks, their running wheel activity nearly tripled, their organ function improved and after ten days their coat of fur became fuller again. The researchers would now like to start clinical trials on humans: "We first want to investigate the safety and efficacy further. We then hope to expand the study to patients with aggressive forms of cancer within one to two years, and then eventually to study geriatric ailments. We do not seek eternal life, but a longer life without ailments and in excellent health would be great."
Since the early 1970s, scientists have been developing brain-machine interfaces; the main application being the use of neural prosthesis in paralysed patients or amputees. A prosthetic limb directly controlled by brain activity can partially recover the lost motor function. This is achieved by decoding neuronal activity recorded with electrodes and translating it into robotic movements. However, such systems have limited precision, due to the absence of sensory feedback from the artificial limb.
Neuroscientists at the University of Geneva (UNIGE), Switzerland, looked at whether it was possible to transmit this missing sensation back to the brain by stimulating neural activity in the cortex. They discovered that not only was it possible to create an artificial sensation of neuroprosthetic movements, but that the underlying learning process occurs very rapidly. These findings, published in the scientific journal Neuron, were obtained by using modern imaging and optical stimulation tools, an alternative to the classical electrode approach.
Motor function is at the heart of all behaviour and allows us to interact with the world. Therefore, replacing a lost limb with a robotic prosthesis is the subject of much research, yet successful outcomes are rare. Why is that? Until now, brain-machine interfaces have been operated by relying largely on visual perception: the robotic arm is controlled by looking at it. The direct flow of information between the brain and machine thus remains unidirectional. However, movement perception is not only based on vision, but mostly on proprioception – the sensation of where the limb is located in space.
“We have therefore asked whether it was possible to establish a bidirectional communication in a brain-machine interface: to simultaneously read out neural activity, translate it into prosthetic movement and reinject sensory feedback of this movement back in the brain,” explains Daniel Huber, professor in the Department of Basic Neurosciences at UNIGE.
In contrast to traditional invasive approaches using electrodes, Huber’s team specialises in optical techniques for imaging and stimulating brain activity. Using a method called two-photon microscopy, they routinely measure the activity of hundreds of neurons with single cell resolution: “We wanted to test whether mice could learn to control a neural prosthesis by relying uniquely on an artificial sensory feedback signal”, explains Mario Prsa, researcher at UNIGE and the first author of the study. “We imaged neural activity in the motor cortex. When the mouse activated a specific neuron, the one chosen for neuroprosthetic control, we simultaneously applied stimulation proportional to this activity to the sensory cortex using blue light.”
Neurons of the sensory cortex were rendered photosensitive to this light, allowing them to be activated by a series of optical flashes and thus integrate the artificial sensory feedback signal. The mouse was rewarded upon every above-threshold activation, and just 20 minutes later, once the association was learned, the rodent was able to more frequently generate the correct neuronal activity.
This means that the artificial sensation was not only perceived, but that it was successfully integrated as a feedback of the prosthetic movement. So in this manner, the brain-machine interface functions bidirectionally. The Geneva researchers think that the reason why this fabricated sensation is so rapidly assimilated is because it most likely taps into very basic brain functions. Feeling the position of our limbs occurs automatically, without much thought and probably reflects fundamental neural circuit mechanisms. In the future, this type of bidirectional interface could allow more precisely displacing robotic arms, feeling touched objects or perceiving the necessary force to grasp them.
At present, the neuroscientists at UNIGE are examining how to produce a more efficient sensory feedback. They are currently capable of doing it for a single movement – but is it also possible to provide multiple feedback channels in parallel? This research sets the groundwork for developing a new generation of more precise, bidirectional neural prostheses.
Researchers from the University of Texas at Austin have developed ultra-flexible, nanoelectronic thread (NET) brain probes, designed to achieve more reliable long-term neural recording than existing probes and without causing scar formation when implanted.
A rendering of the ultra-flexible probe in neural tissue gives viewers a sense of the device’s tiny size and footprint in the brain. Credit: Science Advances.
A team led by assistant professor Chong Xie and research scientist Lan Luan, from the University of Texas at Austin, have developed new probes that have mechanical compliances approaching that of brain tissue and are over 1,000 times more flexible than current neural probes. This ultra-flexibility leads to an improved ability to reliably record and track the electrical activity of individual neurons for long periods of time. There is a growing interest in developing long-term tracking of individual neurons for neural interface applications – such as high-performance prostheses for amputees, as well as new methods of following the progression of neurodegenerative and neurovascular diseases such as stroke, Parkinson's and Alzheimer's.
One of the problems with conventional probes is their size and mechanical stiffness; their larger dimensions and stiffer structures often cause damage around the tissue they encompass. Additionally, while it is possible for the conventional electrodes to record brain activity for months, they often provide recordings that are unreliable and degrade over time. It is also hard for conventional electrodes to track individual neurons for more than a few days.
In contrast, the UT Austin team's electrodes are flexible enough to comply with micro-scale movements of tissue and still stay in place. The probe's size also drastically reduces tissue displacement, so the brain interface is more stable, and the readings are more reliable for longer periods of time. To the researchers' knowledge, this new probe – which is as small as 10 microns at a thickness below 1 micron, and has a cross-section that is only a fraction of that of a neuron or blood capillary – is the smallest neural probe ever developed.
Following tests on mice, the researchers found that the probe's flexibility and size prevented the agitation of glial cells, which is the normal biological reaction to a foreign body and leads to scarring and neuronal loss.
"The most surprising part of our work is that the living brain tissue – the biological system – really doesn't mind having an artificial device around for months," Luan said.
The researchers also used advanced imaging techniques in collaboration with biomedical engineering professor Andrew Dunn and neuroscientists Raymond Chitwood and Jenni Siegel from the Institute for Neuroscience at UT Austin, to confirm that the neural interface did not degrade in the mouse model for over four months of experiments. The researchers plan to continue testing their probes in animal models and hope to eventually engage in clinical testing. Their latest research is published in the journal Science Advances.
A study published by The Lancet shows that in many countries, average life expectancy will increase significantly by 2030, exceeding 90 for the first time in South Korea. This trend will be slower in the USA, however – due to obesity, homicides and lack of equal access to healthcare.
Life expectancies in developed countries are projected to continue increasing, with women's life expectancy surpassing 90 in South Korea by 2030, according to a study published in The Lancet.
The study predicts life expectancy is likely to be highest in South Korea (90.8), France (88.6) and Japan (88.4) for women, and in South Korea (84.1), Australia (84.0) and Switzerland (84.0) for men.
The researchers emphasise that people living longer will have major implications for health and social services. Countries will need to adapt and have policies to support healthy aging, increase investment in health and social care, and possibly change their retirement ages.
"As recently as the turn of the century, many researchers believed that life expectancy would never surpass 90 years," said Professor Majid Ezzati from Imperial College London, the study's lead author. "Our predictions of increasing lifespans highlight our public health and healthcare successes. However, it is important that policies to support the growing older population are in place. In particular, we will need to both strengthen our health and social care systems and to establish alternative models of care, such as technology-assisted home care."
Although life expectancy is predicted to increase for all 35 countries in the study, the extent of the increase varies from place to place. Comparing 2010 and 2030, female life expectancy will increase most in South Korea, Slovenia and Portugal (6.6, 4.7 and 4.4 years, respectively). For men, life expectancy will increase most in Hungary, South Korea and Slovenia (7.5, 7.0 and 6.4 years).
Life expectancy is predicted to increase least in Macedonia, Bulgaria, Japan and the USA (1.4, 1.5, 1.8 and 2.1 years) for women, and in Macedonia, Greece, Sweden and the USA (2.4, 2.7, 3.0 and 3.0 years) for men.
The USA is predicted to see relatively small improvements (from 81.2 in 2010, to 83.3 in 2030 for women; and 76.5 to 79.5 for men). Its life expectancy is already lower than most other high-income nations, and is expected to fall further behind in 2030 – mainly a result of its large inequalities, absence of universal health care and having the highest homicide rate, body mass index (BMI) and death rates for children and mothers of all high-income nations.
Conversely, South Korea's projected gains will be the result of continued improvements in economic status, improved nutrition for children, access to healthcare and medical technology across the whole population. This results in fewer deaths from infections and better prevention and treatment for chronic diseases, in a way that is more equitable than some Western countries.
The research also indicates that the gap in life expectancy between men and women is closing, as Professor Ezzati explains: "Men traditionally had unhealthier lifestyles, and so shorter life expectancies. They smoked and drank more, and had more road traffic accidents and homicides. However as lifestyles become more similar between men and women, so does their longevity."
"We repeatedly hear that improvements in human longevity are about to come to an end," he continues. "Many people used to believe that 90 years is the upper limit for life expectancy – but this research suggests we will break the 90 year barrier. I don't believe we're anywhere near the upper limit of life expectancy, if there even is one."
The researchers explain that the next step of their research will be to extend their model to specific diseases, as well as to all countries to provide more accurate predictions of life expectancy globally. They are careful to note that their study cannot take into account unprecedented events – such as revolutionary advances in medicine, the potentially disastrous effects of climate change, or political upheaval that may affect social and health systems.
A committee from the US National Academy of Sciences (NAS) and National Academy of Medicine (NAM) has given cautious backing to gene editing of human embryos.
Clinical trials for genome editing of the human germline – adding, removing, or replacing DNA base pairs in gametes or early embryos – could be permitted in the future, but only for serious conditions under stringent oversight, says a new report from the National Academy of Sciences and the National Academy of Medicine. The report outlines criteria that should be met before allowing germline editing clinical trials to go forward. Genome editing has already entered clinical trials for non-heritable applications, but should be allowed only for treating or preventing diseases or disabilities at this time, the report says.
Genome editing is not new. But the emergence of powerful, precise and less costly genome editing tools, such as CRISPR/Cas9, have led to an explosion of new research opportunities and potential clinical applications, both heritable and non-heritable, to address a wide range of human health issues. Recognising the promise and the concerns related to this technology, the NAS and NAM appointed a study committee of international experts to examine the scientific, ethical and governance issues surrounding human genome editing.
Human genome editing is already widely used in basic research and is in the early stages of development and trials for clinical applications that involve somatic (non-heritable) cells. These therapies affect only the patient – not any offspring – and should continue for treatment and prevention of disease and disability, using the existing ethical norms and regulatory framework, the committee says.
However, there is significant public concern about the prospect of using these same techniques for so-called “enhancement” of human traits and capacities such as physical strength, or even for uses that are not possible, such as improving intelligence. The report recommends that genome editing for enhancement should not be allowed at this time, and that broad public input and discussion should be solicited before allowing clinical trials for somatic genome editing for any purpose other than treating or preventing disease or disability.
“Human genome editing holds tremendous promise for understanding, treating, or preventing many devastating genetic diseases, and for improving treatment of many other illnesses,” said Alta Charo, committee co-chair and a Professor of Law and Bioethics at the University of Wisconsin-Madison. “However, genome editing to enhance traits or abilities beyond ordinary health raises concerns about whether the benefits can outweigh the risks, and about fairness if available only to some people.”
Germline genome editing, in contrast, is contentious because genetic changes would be inherited by the next generation. Many view germline editing as crossing an “ethically inviolable” line, the report says. Concerns raised include spiritual objections to interfering with human reproduction to speculation about effects on social attitudes toward people with disabilities to possible risks to the health and safety of future children. But germline genome editing could provide some parents who are carriers of genetic diseases with their best or most acceptable option for having genetically related children who are born free of these diseases.
Heritable germline editing is not ready to be tried in humans. Much more research is needed before it could meet the appropriate risk and benefit standards for clinical trials. The technology is advancing very rapidly, though – making heritable genome editing of early embryos, eggs, sperm, or precursor cells in the foreseeable future “a realistic possibility that deserves serious consideration,” the report says. Although heritable germline genome editing trials must be approached with caution, the committee said, caution does not mean prohibition.
At present, heritable germline editing is not permissible in the United States, due to an ongoing prohibition on the U.S. Food and Drug Administration’s ability to use federal funds to review “research in which a human embryo is intentionally created or modified to include a heritable genetic modification.” Various other countries have signed an international convention that prohibits germline modification.
If current restrictions are removed, and for countries where germline editing would already be permitted, the committee recommended stringent criteria that would need to be met before going forward with clinical trials. They include:
(1) absence of reasonable alternatives;
(2) restriction to editing genes that have been convincingly demonstrated to cause or strongly predispose to a serious disease or condition;
(3) credible pre-clinical and/or clinical data on risks and potential health benefits;
(4) ongoing, rigorous oversight during clinical trials;
(5) comprehensive plans for long-term multigenerational follow-up; and
(6) continued reassessment of both health and societal benefits and risks, with wide-ranging, ongoing input from the public.
"Previously, it was easy for people to say, 'This isn't possible, so we don't have to think about it much,'" said MIT researcher Richard Hynes, who helped lead the committee. "Now we can see a path whereby we might be able to do it, so we have to think about how to make sure it's used only for the right things and not for the wrong things."
"These kinds of scenarios used to be science fiction; they used to be seen as far-off hypotheticals," said biotechnologist Marcy Darnovsky from the Centre for Genetics and Society. "But actually, right now, I think they're urgent social justice questions ... [W]e're going to be creating a world in which the already privileged and affluent can use these high-tech procedures to make children [with] biological advantages. And the scenario that plays out is not a pretty one."
Researchers have combined genetic engineering, super-resolution microscopy and biocomputation to witness in 3-D the protein machinery inside living cells. Their method unveils key functional features of protein assemblies that are vital for life, and will make it possible to study cellular protein machinery in health and in disease.
Left: in vivo image of nanomachines using current microscopy techniques. Right: the new method allows 3-D observation of nanomachines in vivo and provides a 25-fold improvement in resolution. Credit: O. Gallego, IRB Barcelona
Scientists at the Institute for Research in Biomedicine (IRB Barcelona) have published a study in which they observed protein nanomachines (also called protein complexes) – the structures responsible for performing cell functions – for the first time in living cells and in 3-D. This work was done in collaboration with researchers at the University of Geneva in Switzerland and the Centro Andaluz de Biología del Desarrollo in Seville.
Currently, biologists who study the function of protein nanomachines isolate these complexes in test tubes, divorced from the cell, and then apply in vitro techniques that allow them to observe their structure up to the atomic level. Alternatively, they use techniques that allow the analysis of these complexes within the living cell, but that give little structural information. In this latest study, however, the scientists have managed to directly observe the structure of the protein machinery in living cells while it is executing its function.
"In vitro techniques allow us to make observations at the atomic level, but the information provided is limited," explains Oriol Gallego, IRB Barcelona researcher and study coordinator. "We will not know how an engine works if we disassemble it and only look at the individual parts. We need to see the engine assembled in the car and running. In biology, we still do not have the tools to observe the inner workings of a living cell, but the technique that we have developed is a step in the right direction. We can now see, in 3-D, how the protein complexes carry out their functions."
The new technique combines super-resolution microscopy – a discovery that was recognised with the 2014 Nobel Prize in Chemistry – cell engineering, and computational modelling. This enables the observation of protein complexes with a precision of 5 nanometres (nm), a resolution "four times better than that offered by super-resolution and that allows us to perform cell biology studies that were previously unfeasible," explains Gallego (*a nm is a millionth of a mm. Human hairs have a width of 100,000 nm).
Cells were genetically modified by the researchers to build artificial supports inside, onto which they could anchor protein complexes. The supports were designed in such a way as to allow them to regulate the angle from which the immobilised nanomachinery was viewed. The 3-D structure of protein complexes was then determined by using super-resolution techniques to measure distances between the different components, then integrating them in a process similar to that used by GPS.
Gallego used this method to study exocytosis, a mechanism that the cell uses to communicate with the cell exterior. For instance, neurons communicate with each other by releasing neurotransmitters via exocytosis. Their study allowed the scientists to reveal the entire structure of a key nanomachine in exocytosis that until now was an enigma: "We now know how this machinery, which is formed by eight proteins, works and what each protein is important for," said Gallego. "This knowledge will help us to better understand the involvement of exocytosis in cancer and metastasis – processes in which this nanomachinery is altered."
Researchers in Madrid have demonstrated a prototype 3-D printer that can print fully functional human skin.
Credit: Image courtesy of Universidad Carlos III de Madrid – Oficina de Información Científica
Scientists from the Universidad Carlos III de Madrid (UC3M), Centre for Energy, Environmental and Technological Research (CIEMAT), Hospital General Universitario Gregorio Marañón, in collaboration with BioDan Group, have announced a prototype 3-D bioprinter that creates fully functional human skin. The skin is adequate for transplanting to patients, or for use in research or the testing of cosmetic, chemical, and pharmaceutical products.
This breakthrough is described in the scientific journal Biofabrication. It replicates the natural structure of the skin, with an external layer, the epidermis with its stratum corneum, which acts as protection against the external environment, together with a thicker, deeper layer, the dermis. This last layer consists of fibroblasts that produce collagen, the protein that gives elasticity and mechanical strength to the skin.
Bioinks are key to 3-D bioprinting, according to the experts. When creating skin, instead of cartridges and coloured inks, injectors with biological components are used. In the words of Juan Francisco del Cañizo, of the Hospital General Universitario: “Knowing how to mix the biological components, in what conditions to work with them so that the cells don’t deteriorate, and how to correctly deposit the product is critical to the system.” The act of depositing these bioinks, which are patented by CIEMAT and licensed by the BioDan Group, is controlled by a computer, which deposits them on a print bed in a precise and orderly manner.
The process for making these tissues can be carried out in two ways: to produce allogeneic skin, from a stock of cells, done on a large scale, for industrial processes; and to create autologous skin, which is made case by case from the patient’s own cells, for therapeutic use, such as in the treatment of severe burns.
“We use only human cells and components to produce skin that is bioactive and can generate its own human collagen, thereby avoiding the use of the animal collagen that is found in other methods,” they note.
There are several advantages to this new technology: “This method of bioprinting allows skin to be generated in a standardised, automated way, and the process is less expensive than manual production,” points out Alfredo Brisac, CEO of BioDan Group, the Spanish bioengineering firm specialising in regenerative medicine that is collaborating on this research and commercialising the printer.
Currently, this development is in the phase of being approved by different European regulatory agencies to guarantee that the skin being produced is adequate for use in transplants on burn patients and those with other skin problems. In addition, these tissues can be used to test pharmaceutical products, as well as cosmetics and consumer chemical products where current regulations require testing that does not use animals.