Culture

Thursday, 29 August 2019 - Adults with cerebral palsy are about twice as likely to develop cardiovascular disease and chronic respiratory disease compared to adults without cerebral palsy, according to a new study led by RCSI (Royal College of Surgeons in Ireland) and Brunel University London.

The study compared 1,700 adults with cerebral palsy and 5,000 adults without cerebral palsy to identify how many developed non-infectious diseases, such as asthma or stroke. The research is published in the current edition of Neurology.

Patients with cerebral palsy were overall 75% more likely to have a non-communicable disease. After adjusting for other variables, the study found that adults with cerebral palsy were around twice as likely to develop cardiovascular disease and chronic respiratory disease, such as asthma, but not more likely to develop diabetes or cancer.

Adults with cerebral palsy were specifically 2.6 times more likely to develop heart failure, 5.5 times more likely to have a stroke, 2.2 times more likely to develop asthma, 1.6 times more likely to develop hypertension and 2.3 times more likely to develop ischaemic heart disease.

Globally, approximately 17 million people have cerebral palsy. Although cerebral palsy was historically considered a paediatric condition, the majority of children with cerebral palsy now survive into adulthood and many adults with cerebral palsy have a near normal life expectancy.

Cerebral palsy is not a progressive condition. However, at least a quarter of young adults report that their ability to walk gets worse, which may contribute to the development of chronic health conditions.

"Until recently, we did not know much about the consequences of ageing with cerebral palsy. Our findings highlight the need for further research into the management of non-communicable diseases in this population," said Jennifer Ryan, the study's lead author and StAR Research Lecturer at RCSI and Senior Lecturer at Brunel University London.

"Recent clinical guidelines for adults with cerebral palsy in the UK recommended that pathways need to be developed that allow adults with cerebral palsy access to a multidisciplinary team. However, adults with cerebral palsy in Ireland lack access to co-ordinated multidisciplinary support."

Being able to access health professionals, such as physiotherapists, orthopaedic surgeons and neurologists with knowledge of cerebral palsy early, may slow deterioration in the patient's function and prevent development of secondary conditions with age.

Dr Neil O'Connell, co-author, physiotherapist and senior lecturer at Brunel University London said:

"Our results clearly emphasise the importance of reframing how cerebral palsy is traditionally viewed; to recognise that it is not simply a condition of childhood. Health services should be designed and delivered with the aim of supporting people with cerebral palsy to be healthy and active throughout their lives."

The study was funded by the Brunel University London Research Catalyst Fund, and it involved collaborators from Brunel University London, University of Michigan-Medicine, London School of Hygiene and Tropical Medicine, Aberdeen Royal Infirmary, Hospital Clinico San Carlos, University of Surrey and Queen Mary University London.

Clues from Canadian rocks formed billions of year ago reveal a previously unknown loss of life even greater than that of the mass extinction of the dinosaurs 65 million years ago, when Earth lost nearly three-quarters of its plant and animal species.

Rather than prowling animals, this die-off involved miniscule microorganisms that shaped the Earth's atmosphere and ultimately paved the way for those larger animals to thrive.

"This shows that even when biology on Earth is comprised entirely of microbes, you can still have what could be considered an enormous die-off event that otherwise is not recorded in the fossil record," said Malcolm Hodgskiss, co-lead author of a new study published in Proceedings of the National Academy of Sciences.

Invisible clues

Because this time period preceded complex life, researchers cannot simply dig up fossils to learn what was living 2 billion years ago. Even clues left behind in mud and rocks can be difficult to uncover and analyze.

Instead, the group turned to barite, a mineral collected from the Belcher Islands in Hudson Bay, Canada, that encapsulates a record of oxygen in the atmosphere. Those samples revealed that Earth experienced huge changes to its biosphere - the part of the planet occupied by living organisms - ending with an enormous drop in life approximately 2.05 billion years ago that may also be linked to declining oxygen levels.

"The fact that this geochemical signature was preserved was very surprising," Hodgskiss said. "What was especially unusual about these barites is that they clearly had a complex history."

Looking at the Earth's productivity through ancient history provides a glimpse into how life is likely to behave over its entire existence - in addition to informing observations of atmospheres on planets outside our solar system.

"The size of the biosphere through geologic time has always been one of our biggest questions in studying the history of the Earth," said Erik Sperling, an assistant professor of geological sciences at Stanford who was not involved with the study. "This new proxy demonstrates how interlinked the biosphere and levels of oxygen and carbon dioxide in the atmosphere are."

Biological angle

This relationship between the proliferation of life and atmospheric oxygen has given researchers new evidence of the hypothesized "oxygen overshoot." According to this theory, photosynthesis from ancient microorganisms and the weathering of rocks created a huge amount of oxygen in the atmosphere that later waned as oxygen-emitting organisms exhausted their nutrient supply in the ocean and became less abundant. This situation is in contrast to the stable atmosphere we know on Earth today, where the oxygen created and consumed balances out. The researchers' measurements of oxygen, sulfur and barium isotopes in barite support this oxygen overshoot hypothesis.

The research helps scientists hone their estimates of the size of the oxygen overshoot by revealing the significant biological consequences of oxygen levels above or below the capacity of the planet.

"Some of these oxygen estimates likely require too many microorganisms living in the ocean in Earth's past," said co-lead author Peter Crockford, a postdoctoral researcher at the Weizmann Institute of Science and Princeton University. "So we can now start to narrow in on what the composition of the atmosphere could have been through this biological angle."

Drugs that help prevent the formation of unwanted or harmful proteins are currently being developed to treat a number of diseases, including cancer. The drugs are based on small interfering RNA, or siRNA, which are pieces of nucleic acids that work by interfering with the production of proteins. But getting these drugs to the right target, such as to a tumor, remains challenging because siRNAs can degrade rapidly in the body -- making systemic delivery inefficient. They also can have some difficulty entering cells where they do their work.

Eben Alsberg, the Richard and Loan Hill Professor of Bioengineering and Orthopaedics at the University of Illinois at Chicago, and colleagues report on a hydrogel-based carrier that can deliver siRNAs directly to where they are needed. They report their findings in Science Advances.

Other researchers have had some success in linking the siRNA molecules with other materials to form nanoparticles that help to prevent siRNA degradation and help the drugs enter cells. But systemically delivered nanoparticle-incorporated drugs tend to have low rates of reaching targeted cells, necessitating multiple doses to have the desired effect, which increases the risk of negative side effects.

Biologically compatible hydrogels have been used to deliver biologics or drugs directly to specific areas in the body. A drug-infused hydrogel plug or sheet can be placed directly where the drug is needed -- say in a joint or at a break in bone, or even injected.

But one problem has been that drugs loaded into hydrogels often diffuse out rapidly to surrounding cells and tissues, providing an initial burst of drug and not much more. The release can be delayed by changing the porosity of the hydrogel, its degradation rate and by tinkering with the affinity of the drug for the hydrogel.

Alsberg together with Matthew Levy, associate professor of biochemistry at Albert Einstein College of Medicine, and their colleagues developed a unique hydrogel strategy that allows for more control over the release of siRNAs over time. By chemically coupling the siRNA to the hydrogel via a linker that can degrade in the body, they can control the release of the drug. When the hydrogel is placed in a water-based environment, such as a biological organism, water breaks the linker between the siRNA and the hydrogel, releasing the drug. In this kind of system, release of the drug is prolonged compared with when the siRNA is only physically trapped within the hydrogel.

"We may be able to use this technology in the future to, for example, prevent the production of certain proteins that are known to promote certain diseases, or to help transform stem cells into cells needed to repair damaged tissue such as bone or cartilage," Alsberg said.

Temperate grasslands are the most endangered but least protected ecosystems on Earth. Grassland restorations are crucial for recovering this important but highly degraded ecosystem. Restored grasslands, however, tend to be more species poor and lose diversity through time as compared to remnant, or never-been plowed, grasslands. A new study from the University of Missouri found that milkweeds and other plants that have seeds carried by the wind are an important source for enriching the diversity of plants in these valuable ecosystems.

"There are many benefits for why we should care about grasslands. They provide food for livestock, habitat for wildlife, prevent soil erosion, support pollinators, and capture a lot of the world's carbon. These benefits derive primarily from the diverse grasses and flowering plants that comprise grassland communities. When we lose that diversity, we risk losing those benefits," said Lauren Sullivan, a grassland ecologist with the Division of Biological Sciences. "We found that spillover, especially of wind-dispersed plant species, is an important means for promoting biodiversity in restored grasslands."

Ecologists describe spillover as the natural movement of species from one habitat to another. The concept is commonly associated with marine habitats, where fish spillover from protected areas can be used to improve adjacent fisheries. Unlike fish, plants rely on external forces, like wind and animals, to move their seeds. Where seeds land also can determine whether they will grow.

"Because plant dispersal and establishment depend not only on who's producing seed but also where the seed is landing, we wanted to know whether and under what conditions spillover could be used to increase biodiversity in grassland systems," said Sullivan.

To do this, Sullivan and her colleagues studied restored prairies that are adjacent to remnant prairies in northwest Minnesota. They included restored prairies with varying levels of diversity. To measure spillover, they cataloged every plant species across the entirety of the remnant site and then in the adjacent restored prairie up to 400 feet from the boundary between the prairies. Plant species included in the original seed mix for the restored prairie were removed from the list, leaving only species that could have arrived by spillover. They examined whether the species richness of the restored prairies and individual plant dispersal traits affected the spillover they observed.

The researchers found evidence of spillover in restorations seeded with a low diversity of species. They also found more spillover of wind-dispersed species than those dispersed by animals or passive mechanisms. They concluded that spillover from remnant prairies is an important factor increasing biodiversity in restored grasslands, but that context matters.

"In the case of grassland ecosystems, we found spillover depends on who you are and where you land. If you have movement mechanisms that allow you to travel further, like wind, you are more likely to spillover and if you are landing in a low diversity environment you are more likely to establish," said Katie P. Sperry, who led the project and is first and corresponding author of the new study. "Importantly, spillover represents a source of species not typically included in seed mixes, such as several members of the daisy and milkweed families."

The research and its findings are highlighted in an Applied Ecologists Blog authored by Lars Brudvig with Michigan State University. According to Brudvig, strategically installing restorations adjacent to remnant grasslands and prioritizing plant species that do not arrive by spillover in seed mixes are two practical applications of the research. "The findings [also] illustrate the broad importance of landscape considerations during restoration and illustrate that connectivity-driven spillover effects may explain some of the variation we observe among restoration efforts." Brudvig was not affiliated with the study.

A team of paleontologists from the Borissiak Paleontological Institute of Russian Academy of Sciences (Moscow) discovered four new species of extinct insects with sucking mouthparts in mid-Cretaceous Burmese amber. Researchers believe that they visited first angiosperm flowers, but eventually went extinct due to the inefficient design of the proboscis. According to the research, Paradoxosisyrinae, the group to which these creatures belong, is a kind of «Nature's failed experiment». The results of the study are published in the Cretaceous Research journal.

In recent years, Burmese amber makes headlines as a source of dinosaur remains, toothed birds and other incredible vertebrate findings. However, insects found there are often no less bizarre. This is especially true for Paradoxosisyrinae, a subfamily of Sisyridae, or spongeflies, which was described from Burmese amber based on a single specimen in 2016. Neither living spongeflies nor any of their extant relatives from insect order Neuroptera, such as green lacewings and ant lions, have sucking mouthparts. In contrast, members of Paradoxosisyrinae were equipped with a well-developed proboscis -- which is a paradox indeed, as their name suggests.

Until now, functions of Paradoxosisyrinae's proboscis have remained unclear. It was hypothesized that Paradoxosisyrinae used their elongated mouthparts for piercing insect cuticle or frog skin. Contrary to this, the new research based on newly available specimens shows that in all probability these insects were not predators or bloodsuckers -- instead, they were harmless nectar feeders. Scientists said that Paradoxosisyrinae simply could not pierce any dense substrates because of loosely coupled arrangement of the mouthparts, devoid of a supportive sheath, and the presence of long hairs at the mouthpart tips.

With the help of microscope examination and virtual 3D-models scientists came to a conclusion that proboscis of Paradoxosisyrinae, rather than having a common food canal, consists of two independent straws or tubes, each one formed by two halves loosely joined together without any special devices suitable to lock them tightly. Since Paradoxosisyrinae could not seal their proboscis to produce a pressure gradient, as modern flies and moths do, they had to rely exclusively on capillary forces for nectar uptake, while other nectar feeders use also the muscular sucking pump. All this means that the proboscis of Paradoxosisyrinae, less than 1 mm in length, destined to be short forever, which undercut their ability to draw nectar from flowers with deep corolla tubes.

«These insects were a nature"s unsuccessful attempt to make nectar feeding insects in response to the rise of the flowering plants in the Early Cretaceous period. Soon they were outcompeted by bees, flies and other nectar feeders with more cleverly designed mouthparts», said Alexander Khramov, study"s leading author and a senior researcher at the Borissiak Paleontological Institute.

Discovery of four new species of Paradoxosisyrinae, in addition to the only previously known member of this subfamily, dramatically expands our knowledge about diversity of these extinct nectar feeders. One of the new species was named Buratina truncata after the long-nosed fiction character Buratino, the Russian analogue of Pinocchio. Body of Buratina truncata as well as of other newly described species was covered with dense hairs, the condition seen in modern pollinators, which allows them to carry pollen grains between plants. The researchers say that Paradoxosisyrinae could feed on small shallow flowers like Tropidogyne which are commonly occur in Burmese amber.

Elaborate burial sites can provide insight to the development of socio-political hierarchies in early human communities, according to a study released August 28, 2019 in the open-access journal PLOS ONE by an international team of archaeologists, anthropologists and neuroscientists of the Ba'ja Neolithic Project hosted at the Free University of Berlin in cooperation with the Department of Antiquities of Jordan. The interdisciplinary investigations on the 9000-year-old extraordinary grave studied here gives new evidence on emerging leadership in the first farming villages of the Near East.

As early farming communities gave rise to larger, more complex sedentary societies, new social hierarchies arose, presenting opportunities for individual people to achieve positions of importance. The authors cite two archetypal "pathways to power" such individuals might follow: one self-aggrandizing and often autocratic, and the other more group-oriented and egalitarian. But how these "pathways" were expressed in early cultures remains unclear.

This study focused on a single burial in the Ba'ja settlement of southern Jordan, dating between 7,500-6,900 BC, during the Late Pre-Pottery B Period. The elaborate construction of this grave and sophistication of associated symbolic objects suggest the deceased was a person of importance in the ancient society. The authors suggest that the presence of exotic items in the grave indicate a person who achieved individual prestige by access to trade networks, while the proximity of the grave to other less elaborate graves indicates that they were nonetheless considered close in status to the broader community, not neatly fitting either archetype of a powerful individual.

The authors propose that this sort of data can provide insights into cultural views toward leadership and social hierarchy in early cultures. They also suggest that further investigations of this body and others in Ba'ja, including ancient DNA analysis to illuminate familial relationships, may combine with grave information to create a more refined picture of early community social structures.

The authors add: "We suggest that leadership can be understood only by studying the social contexts and the pathways to power (not only the burials of extraordinary individuals). In fact, studying rich tombs to interpret social structures has been done before, but our new approach emphasizes the social environments of leadership. The key study of the elaborate burial of the late PPNB site of Ba'ja lets us surmise that access to leadership was possible through corporate leadership-type of primus inter pares than by autocratic coercive power."

A study of 31 recreational weightlifters suggests that a real-time, music-based feedback system helps improve deadlift technique. Valerio Lorenzoni of Ghent University, Belgium, and colleagues present these findings in the open-access journal PLOS ONE on August 28, 2019.

Sensors placed on the body can provide real-time measurements that help an individual monitor their own athletic performance or progress during rehabilitation. Known as biofeedback, this approach may be especially useful when access to a trainer or therapist is unfeasible, such as during in-home workouts.

For the new study, Lorenzoni and colleagues designed a music-based biofeedback system for helping weightlifters improve their technique while performing a weightlifting exercise known as the deadlift. A person using the system dons 22 body sensors that monitor deadlift technique. Then, they perform deadlifts while listening to music composed by the researchers. Bad technique lowers the sound quality of the music, while improved technique restores it.

To test this system, the scientists recruited 31 recreational weightlifters and divided them into two groups. One group performed deadlifts while receiving the music-based feedback, while the other group received feedback directly from instructors. For simplicity, feedback was provided for only two deadlift technique parameters.

The researchers found that both feedback types resulted in improved deadlift technique among the participants. Both resulted in similar levels of improvement, and participants reported similar levels of clarity and enjoyment for both. These findings suggest that music-based biofeedback could be a useful tool for weight training.

The authors note that future research could explore the long-term effectiveness of their new feedback system. They also suggest that the system could be improved by increasing its portability, and it could be applied to additional parameters of weight training technique.

The authors summarize: "The sonic-instructor is a music-based biofeedback system able to help people improve weightlifting technique for performance improvement and injury prevention."

VANCOUVER, British Columbia -- Humans and machines worked together to help train an artificial intelligence -- AI -- model that outperformed other clickbait detectors, according to researchers at Penn State and Arizona State University. In addition, the new AI-based solution was also able to tell the difference between clickbait headlines that were generated by machines -- or bots -- and ones written by people, they said.

In a study, the researchers asked people to write their own clickbait -- an interesting, but misleading, news headline designed to attract readers to click on links to other online stories. The researchers also programmed machines to generate artificial clickbaits. Then, the headlines made by both people and machines were used as data to train a clickbait-detection algorithm.

The resulting algorithm's ability to predict clickbait headlines was about 14.5 percent better than other systems, according to the researchers, who released their findings today (Aug. 28) at the 2019 IEEE/ACM International Conference on Advances in Social Networks Analysis (ASONAM) at Vancouver, Canada.

Beyond its use in clickbait detection, the team's approach may help improve machine learning performance in general, said Dongwon Lee, the principal investigator of the project and an associate professor in the College of Information Sciences and Technology. Lee is also an affiliate of Penn State's Institute for CyberScience (ICS), which provides Penn State researchers access to supercomputing resources.

"This result is quite interesting as we successfully demonstrated that machine-generated clickbait training data can be fed back into the training pipeline to train a wide variety of machine learning models to have improved performance," said Lee. "This is the step toward addressing the fundamental bottleneck of supervised machine learning that requires a large amount of high-quality training data."

According to Thai Le, a doctoral student in the College of Information Sciences and Technology, Penn State, one of the challenges confronting the development of clickbait detection is the lack of labeled data. Just like people need teachers and study guides to help them learn, AI models need data that is labeled to help them learn to make the correct connections and associations.

"One of the things we realized when we started this project is that we don't have many positive data points," said Le. "In order to identify clickbait, we need to have humans label that training data. There is a need to increase the amount of positive data points so that, later on, we can train better models."

While finding clickbait on the internet can be easy, the many variations of clickbait add another layer of difficulty, according to S. Shyam Sundar, James P. Jimirro Professor of Media Effects and co-director of the Media Effects Research Laboratory in the Donald P. Bellisario College of Communications, and an ICS affiliate.

"There are clickbaits that are lists, or listicles; there are clickbaits that are phrased as questions; there are ones that start with who-what-where-when; and all kinds of other variations of clickbait that we have identified in our research over the years," said Sundar. "So, finding sufficient samples of all these types of clickbait is a challenge. Even though we all moan about the number of clickbaits around, when you get around to obtaining them and labeling them, there aren't many of those datasets."

According to the researchers, the study revealed differences in how people and machines approached the creation of headlines. Compared to the machine-generated clickbait, headlines generated by people tended to have more determiners -- words such as "which" and "that" -- in their headlines.

Training also seemed to prompt differences in clickbait creation. For example, trained writers, such as journalists, tended to use longer words and more pronouns than other participants. Journalists also were likely to use numbers to start their headlines.

The researchers plan to use these findings to guide their investigations into a more robust fake-news detection system, among other applications, according to Sundar.

"For us, clickbait is just one of many elements that make up fake news, but this research is a useful preparatory step to make sure we have a good clickbait detection system set up," said Sundar.

To find human clickbait writers for the study, the researchers recruited journalism students and workers from Amazon Turk, an online crowdsource site. They recruited 125 students and 85 workers from the site. The participants first read a definition of clickbait and then were asked to read a short -- about 500 words -- article. The participants were then asked to write a clickbait headline for each article.

The machine-generated clickbait headlines were developed by using a machine learning model called a Variational Autoencoders -- or VAE -- generative model, which relies on probabilities to find patterns in data.

The researchers tested their algorithm against top-performing systems from Clickbait Challenge 2017, an online clickbait detection competition.

MIT engineers have developed a magnetically steerable, thread-like robot that can actively glide through narrow, winding pathways, such as the labrynthine vasculature of the brain.

In the future, this robotic thread may be paired with existing endovascular technologies, enabling doctors to remotely guide the robot through a patient's brain vessels to quickly treat blockages and lesions, such as those that occur in aneurysms and stroke.

"Stroke is the number five cause of death and a leading cause of disability in the United States. If acute stroke can be treated within the first 90 minutes or so, patients' survival rates could increase significantly," says Xuanhe Zhao, associate professor of mechanical engineering and of civil and environmental engineering at MIT. "If we could design a device to reverse blood vessel blockage within this 'golden hour,' we could potentially avoid permanent brain damage. That's our hope."

Zhao and his team, including lead author Yoonho Kim, a graduate student in MIT's Department of Mechanical Engineering, describe their soft robotic design in the journal Science Robotics. The paper's other co-authors are MIT graduate student German Alberto Parada and visiting student Shengduo Liu.

In a tight spot

To clear blood clots in the brain, doctors often perform an endovascular procedure, a minimally invasive surgery in which a surgeon inserts a thin wire through a patient's main artery, usually in the leg or groin. Guided by a fluoroscope that simultaneously images the blood vessels using X-rays, the surgeon then manually rotates the wire up into the damaged brain vessel. A catheter can then be threaded up along the wire to deliver drugs or clot-retrieval devices to the affected region.

Kim says the procedure can be physically taxing, requiring surgeons, who must be specifically trained in the task, to endure repeated radiation exposure from fluoroscopy.

"It's a demanding skill, and there are simply not enough surgeons for the patients, especially in suburban or rural areas," Kim says.

The medical guidewires used in such procedures are passive, meaning they must be manipulated manually, and are typically made from a core of metallic alloys, coated in polymer, a material that Kim says could potentially generate friction and damage vessel linings if the wire were to get temporarily stuck in a particularly tight space.

The team realized that developments in their lab could help improve such endovascular procedures, both in the design of the guidewire and in reducing doctors' exposure to any associated radiation.

Threading a needle

Over the past few years, the team has built up expertise in both hydrogels -- biocompatible materials made mostly of water -- and 3-D-printed magnetically-actuated materials that can be designed to crawl, jump, and even catch a ball, simply by following the direction of a magnet.

In this new paper, the researchers combined their work in hydrogels and in magnetic actuation, to produce a magnetically steerable, hydrogel-coated robotic thread, or guidewire, which they were able to make thin enough to magnetically guide through a life-size silicone replica of the brain's blood vessels.

The core of the robotic thread is made from nickel-titanium alloy, or "nitinol," a material that is both bendy and springy. Unlike a clothes hanger, which would retain its shape when bent, a nitinol wire would return to its original shape, giving it more flexibility in winding through tight, tortuous vessels. The team coated the wire's core in a rubbery paste, or ink, which they embedded throughout with magnetic particles.

Finally, they used a chemical process they developed previously, to coat and bond the magnetic covering with hydrogel -- a material that does not affect the responsiveness of the underlying magnetic particles and yet provides the wire with a smooth, friction-free, biocompatible surface.

They demonstrated the robotic thread's precision and activation by using a large magnet, much like the strings of a marionette, to steer the thread through an obstacle course of small rings, reminiscent of a thread working its way through the eye of a needle.

The researchers also tested the thread in a life-size silicone replica of the brain's major blood vessels, including clots and aneurysms, modeled after the CT scans of an actual patient's brain. The team filled the silicone vessels with a liquid simulating the viscosity of blood, then manually manipulated a large magnet around the model to steer the robot through the vessels' winding, narrow paths.

Kim says the robotic thread can be functionalized, meaning that features can be added -- for example, to deliver clot-reducing drugs or break up blockages with laser light. To demonstrate the latter, the team replaced the thread's nitinol core with an optical fiber and found that they could magnetically steer the robot and activate the laser once the robot reached a target region.

When the researchers ran comparisons between the robotic thread coated versus uncoated with hydrogel, they found that the hydrogel gave the thread a much-needed, slippery advantage, allowing it to glide through tighter spaces without getting stuck. In an endovascular surgery, this property would be key to preventing friction and injury to vessel linings as the thread works its way through.

And just how can this new robotic thread keep surgeons radiation-free? Kim says that a magnetically steerable guidewire does away with the necessity for surgeons to physically push a wire through a patient's blood vessels. This means that doctors also wouldn't have to be in close proximity to a patient, and more importantly, the radiation-generating fluoroscope.

In the near future, he envisions endovascular surgeries that incorporate existing magnetic technologies, such as pairs of large magnets, the directions of which doctors can manipulate from just outside the operating room, away from the fluoroscope imaging the patient's brain, or even in an entirely different location.

"Existing platforms could apply magnetic field and do the fluoroscopy procedure at the same time to the patient, and the doctor could be in the other room, or even in a different city, controlling the magnetic field with a joystick," Kim says. "Our hope is to leverage existing technologies to test our robotic thread in vivo in the next step."

The 3.8 million-year-old fossil cranium represents a time interval between 4.1 and 3.6 million years ago, when A. anamensis gave rise to A. afarensis. Researchers used morphological features of the cranium to identify which species the fossil represents. "Features of the upper jaw and canine tooth were fundamental in determining that MRD was attributable to A. anamensis", said Melillo. "It is good to finally be able to put a face to the name." The MRD cranium, together with other fossils previously known from the Afar, show that A. anamensis and A. afarensis co-existed for approximately 100,000 years. This temporal overlap challenges the widely-accepted idea of a linear transition between these two early human ancestors. Haile-Selassie said: "This is a game changer in our understanding of human evolution during the Pliocene."

Working for the past 15 years at the site, the team discovered the cranium (MRD-VP-1/1, here referred to as "MRD") in February 2016. In the years following their discovery, paleoanthropologists of the project conducted extensive analyses of MRD, while project geologists worked on determining the age and context of the specimen. The results of the team's findings are published online in two papers in the international scientific journal Nature.

Discovery of the cranium

The Woranso-Mille project has been conducting field research in the central Afar region of Ethiopia since 2004. The project has collected more than 12,600 fossil specimens representing about 85 mammalian species. The fossil collection includes about 230 fossil hominin specimens dating to between more than 3.8 and about 3.0 million years ago. The first piece of MRD, the upper jaw, was found by Ali Bereino (a local Afar worker) on February 10, 2016 at a locality known as Miro Dora, Mille district of the Afar Regional State. The specimen was exposed on the surface and further investigation of the area resulted in the recovery of the rest of the cranium. "I couldn't believe my eyes when I spotted the rest of the cranium. It was a eureka moment and a dream come true", said Haile-Selassie.

Geology and age determination

In a companion paper published in the same issue of Nature, Beverly Saylor of Case Western Reserve University and her colleagues determined the age of the fossil as 3.8 million years by dating minerals in layers of volcanic rocks nearby. They mapped the dated levels to the fossil site using field observations and the chemistry and magnetic properties of rock layers. Saylor and her colleagues combined the field observations with analysis of microscopic biological remains to reconstruct the landscape, vegetation and hydrology where MRD died.

MRD was found in the sandy deposits of a delta where a river entered a lake. The river likely originated in the highlands of the Ethiopian plateau while the lake developed at lower elevations where rift activity caused the Earth surface to stretch and thin, creating the lowlands of the Afar region. Fossil pollen grains and chemical remains of fossil plant and algae that are preserved in the lake and delta sediments provide clues about the ancient environmental conditions. Specifically they indicate that the watershed of the lake was mostly dry but that there were also forested areas on the shores of the delta or along the side the river that fed the delta and lake system. "MRD lived near a large lake in a region that was dry. We're eager to conduct more work in these deposits to understand the environment of the MRD specimen, the relationship to climate change and how it affected human evolution, if at all", said Naomi Levin, a co-author on the study from University of Michigan.

A new face in the crowd

Australopithecus anamensis is the oldest known member of the genus Australopithecus. Due to the cranium's rare near-complete state, the researchers identified never-before-seen facial features in the species. "MRD has a mix of primitive and derived facial and cranial features that I didn't expect to see on a single individual", Haile-Selassie said. Some characteristics were shared with later species, while others had more in common with those of even older and more primitive early human ancestor groups such as Ardipithecus and Sahelanthropus. "Until now, we had a big gap between the earliest-known human ancestors, which are about 6 million years old, and species like 'Lucy', which are two to three million years old. One of the most exciting aspects of this discovery is how it bridges the morphological space between these two groups", said Melillo.

Branching out

Among the most important findings was the team's conclusion that A. anamensis and its descendant species, the well-known A. afarensis, coexisted for a period of at least 100,000 years. This finding contradicts the long-held notion of an anagenetic relationship between these two taxa, instead supporting a branching pattern of evolution. Melillo explains: "We used to think that A. anamensis gradually turned into A. afarensis over time. We still think that these two species had an ancestor-descendent relationship, but this new discovery suggests that the two species were actually living together in the Afar for quite some time. It changes our understanding of the evolutionary process and brings up new questions - were these animals competing for food or space?"

This conclusion is based on the assignment of the 3.8-million-year-old MRD to A. anamensis and the 3.9-million-year-old hominin cranial fragment commonly known as the Belohdelie frontal, to A. afarensis. The Belohdelie frontal was discovered in the Middle Awash of Ethiopia by a team of paleontologists in 1981, but its taxonomic status has been questioned in the intervening years.

The new MRD cranium enabled the researchers to characterize frontal morphology in A. anamensis for the first time and to recognize that these features differed from the morphology common to the Belohdelie frontal and to other cranial specimens already known for Lucy's species. As a result, the new study confirms that the Belohdelie frontal belonged to an individual of Lucy's species. This identification extends the earliest record of A. afarensis back to 3.9 million years ago, while the discovery of MRD nudges the last appearance date of A. anamensis forward to 3.8 million years - indicating the overlap period of at least 100,000 years.

Within each cell, the power houses called mitochondria continuously break down molecules derived from food to generate energy as well as to produce new molecules that serve as building blocks of cells. Balancing these two opposing processes is accomplished by an enzyme called proton-translocating transhydrogenase or NNT (nicotinamide nucleotide transhydrogenase). NNT sits in the mitochondria's membrane and uses the electrochemical proton gradient generated by cellular respiration to provide the mitochondria with just the right amount of the co-enzyme NADPH, a vital metabolic precursor. The proper functioning of NNT is crucial for metabolic regulation in all animals including humans. However, the details of how NNT accomplishes the coordinated transfer of protons across the membrane and synthesis of NADPH have remained obscure due to the lack of knowledge about the enzyme's atomic structure. Domen Kampjut, PhD student at IST Austria, and his supervisor and group leader Professor Leonid Sazanov have now for the first time visualized the molecule of mammalian NNT at a scale that allowed them to identify the structural principles of the enzyme's channel gating--and thus to gain a deeper understanding of its functioning (and malfunctioning).

"Resolution revolution" at IST Austria

The atomic analysis of the enzyme NNT was only possible by taking advantage of state-of-the-art technology developments in cryo-electron microscopy (cryo-EM), the so-called "resolution revolution". Parts of the current study's data were generated using a new cryo-electron microscope installed at IST Austria only in fall 2018 and are the first to be published using one of three new machines, the "300 kV FEI Titan Krios", in Klosterneuburg.

The cryo-EM analysis of NNT--which involved extensive time- and effort-consuming image processing and the support of the experts of the centrally organized and well-established Electron Microscopy Facility at IST Austria--delivered near atomic-resolution images of the molecule's three different domains in various conformational states.

Opening the gate for protons--and new forms of medical treatment

With these images, the structural biologists could show how the domain that binds NADPH can open the proton channel to either side of the mitochondrial membrane. First author Domen Kampjut: "NNT has been studied for a few decades, but classical imaging methods such as X-ray crystallography have failed to give a detailed look into its structure because it is highly dynamic. Furthermore, membrane proteins like NNT are particularly challenging to study as they are fragile and difficult to purify in large amounts needed for crystallography. Thus, only with cryo-EM could we finally see clearly how the proton transfer works--and with this, find a missing piece of the puzzle on the way to understanding what to do if it does not work."

Professor Leonid Sazanov adds: "These structures are particularly exciting because transhydrogenase performs an amazing volte-face by rotating an entire, quite large, NADPH-binding domain 180 degrees 'up' or 'down'. This is, as far as we know, unique among studied enzyme mechanisms. However, such a rotation now makes complete sense in view of our proposed mechanism and it shows how nature can 'creatively' solve challenging tasks."

The results are an important further step towards the development of novel therapies. For instance, the development of currently unavailable NNT inhibitors has great therapeutic potential with regard to metabolic dysfunctions including metabolic syndrome, and some cancers.

The healthy cells immediately surrounding a tumour become more stem cell-like and support cancer growth, reveals a new study published in Nature.

The discovery was made using a new state-of-the-art technique developed by researchers in Ilaria Malanchi's lab at the Crick in order to study the tissue around a tumour - called the tumour microenvironment - known to influence the growth and spread of cancer, as well as treatment response.

"Our new technique allows us to study changes to cells in the tumour microenvironment with unprecedented precision," says Ilaria, who joint-led the project. "This helps us to understand how these changes relate to tumour growth and metastasis, allowing us to develop better strategies to treat the disease.

"We discovered that non-cancerous cells in the tumour microenvironment regress back into a stem-cell like state, and actually support cancer growth. By corrupting its neighbours, cancer transforms its local environment to support its own survival."

This new technique relies on cancer cells engineered to release a cell-penetrating fluorescent protein that gets taken up by its neighbouring cells. These colour-labelled cells can be identified and compared to other (unlabelled) cells that have not come into contact with the tumour. Researchers in Ilaria's lab used this approach in mice to study the cells around breast cancer that had spread to the lungs. Data from Alessandro Ori's lab at the Fritz Lipmann Institute in Germany confirmed that the labelled cells produced different proteins to unlabelled cells.

The researchers found labelled cells from the lung to have stem cell-like features, unlike the lung cells found outside of the tumour microenvironment. The team showed that those cells from the mouse lungs supported tumour growth when mixed with tumour cells in 3D culture in the lab, suggesting that they help the cancer to survive and grow.

In order to further test the potential of the stem-cell like cells in the tumour microenvironment, Ilaria teamed up with Joo-Hyeon Lee at the Wellcome Trust/MRC Stem Cell Institute, who used them to grow lung organoids, or 'mini-lungs'.

The unlabelled healthy lung cells formed mini-lungs, mostly made up of alveolar epithelial cells which line the lung's alveoli - the tiny sacs where gas exchange takes place. By comparison, the labelled cells taken from the tumour microenvironment unexpectedly formed mini-lungs with a wider range of cell types.

"To our amazement, we found that cells receiving proteins from adjacent cancer cells obtained stem-cell-like features", explains Joo-Hyeon Lee, joint senior author of the paper. "They could change their fate to become different cell types. It demonstrates the powerful influence that cancer exerts over its neighbouring cells, making them liable to change easily."

The researchers hope that their approach will be used by other scientists looking to gain a deeper understanding of the local changes triggered by cancer which help it to survive, spread and develop resistance to treatments.

The potential applications are not confined to cancer - a similar approach could enable scientists to study interactions between different cell types in the body.

The cerebral cortex acts as the control centre of our cognitive processes. During embryogenesis, dozens of types of neurons with distinct functions come together to form the circuits that drive our thoughts and actions. These neurons are generated by progenitor cells, which produce them one after the other in a very precise order. While neuroscience textbooks establish the irreversible nature of this specialization process, researchers at the University of Geneva (UNIGE) now provide proof to the contrary. Indeed, when progenitor cells are transplanted into a young mouse embryo, they recover their past skills and rejuvenate. These results are now published in the journal Nature. By revealing an unsuspected progenitor plasticity, they shed new light on how the brain constructs itself. In the long term, they open up new perspectives for the regeneration of damaged cortical circuits.

The circuits of the cerebral cortex underly our ability to understand the world and interact with it. The diversity of cortical neurons and the circuits they compose therefore somehow determine the diversity of our thoughts and of our behaviours. But how are these neurons generated? In mice, on each embryonic day progenitor cells produce a specific type of neurons before moving to another neuron type the next day. Research conducted in the 1990s had shown that this progression was accompanied by a restriction in competence, as if to move on, progenitors have to forget how to produce the previous neuronal type.

The laboratory of Denis Jabaudon, a professor in the Department of Basic Neurosciences at UNIGE Faculty of Medicine, focuses on the development of the cerebral cortex. Last May, his team had already revealed, in the journal Science, the temporal patterns governing the sequential birth of the different types of cortical neurons from progenitors. &laquoThis time, we looked at the potential plasticity of these progenitors. Are the rules of progenitor maturation set in stone? Or can these cells under certain circumstances undergo a temporal rewind and again generate past neuronal types?»

Decoding the plasticity of progenitors

To address these questions, the researchers transplanted progenitors of late mouse embryos into younger ones, as neuroscientists had done in the 1990s, but this time with opposite results: they found that progenitors could rejuvenate in the new environment. &laquoBy using more precise cell isolation techniques, we were able to identify progenitors that act as genuine stem cells. Once in their new environment, they rejuvenate to become essentially identical to non-transplanted progenitors. The environment in which the cell is located therefore acts as a real cure of youth!». In addition, the Geneva neuroscientists identified the molecular mechanism responsible for this cell rejuvenation: the Wnt protein. &laquoWe knew that Wnt signalling was important to keep stem cells in an undifferentiated state, but here it seems able to take a step further by reversing the process of cell maturation,» says Denis Jabaudon.

The researchers then unsuccessfully tried to accelerate the ageing process by transplanting young progenitors into older embryos. &laquoTo our great surprise, our results show the exact contrary of what the scientific community took for granted, namely that rejuvenating progenitors was impossible, but that speeding up their aging was possible. We have managed to temporoally rewind our cells, but not to fast-forward them.»

Thus, the deeply rooted notion that progression in competence implies a restriction in competence does not apply here. Nevertheless, some progenitors appear impervious to this rejuvenation, but why that is remains unknown.

A proof-of-principle for cortical neuroregeneration

As adults have only very few progenitor cells left, how can these discoveries be used for therapeutic purposes? At the end of the differentiation process, progenitors become astrocytes, a cell type that is preserved at all ages of life. Would it be possible, then, to transform astrocytes back into progenitor cells in order to produce a specific type of neurons that would have disappeared following an accident or a disease? &laquoOur work provides a proof-of-principle for cellular malleability,» explains Denis Jabaudon, &laquoIt will be interesting to try and understand whether this phenomenon can be used for regeneration purposes.»

The genetics of circadian rhythms have been well studied in recent years, but much less is known about other types of genes that play a role in sleep, specifically those that regulate how much sleep our bodies require. Now, by studying a family with several members who require significantly less sleep than average, a team of researchers has identified a new gene that they believe has a direct impact on how much someone sleeps. They report their findings on August 28 in the journal Neuron.

"It's remarkable that we know so little about sleep, given that the average person spends a third of their lives doing it," says Louis Ptáček, a neurologist at the University of California, San Francisco (UCSF), and one of the paper's two senior authors. "This research is an exciting new frontier that allows us to dissect the complexity of circuits in the brain and the different types of neurons that contribute to sleep and wakefulness."

The family whose DNA led to the identification of this gene is one of several that Ptáček and UCSF geneticist Ying-Hui Fu, the paper's other senior author, are studying and includes several members who function normally on only six hours of sleep. The gene, ADRB1, was identified using genetic linkage studies and whole-exome sequencing, which revealed a novel and very rare variant.

The first step in deciphering the role of the gene variant involved studying its protein in the test tube. "We wanted to determine if these mutations caused any functional alterations compared with the wild type," Fu says. "We found that this gene codes for ß1-adrenergic receptor, and that the mutant version of the protein is much less stable, altering the receptor's function. This suggested it was likely to have functional consequences in the brain."

The researchers then conducted a number of experiments in mice carrying a mutated version of the gene. They found that these mice slept on average 55 minutes less than regular mice. (Humans with the gene sleep two hours less than average.) Further analysis showed that the gene was expressed at high levels in the dorsal pons, a part of the brain stem involved in subconscious activities such as respiration and eye movement as well as sleep.

Additionally, they discovered that normal ADRB1 neurons in this region were more active not only during wakefulness, but also during REM (rapid eye movement) sleep. However, they were quiet during non-REM sleep. Furthermore, they found that the mutant neurons were more active than normal neurons, likely contributing to the short sleep behavior.

"Another way we confirmed the role of the protein was using optogenetics," Fu explains. "When we used light to activate the ADRB1 neurons, the mice immediately woke up from sleep."

Ptáček acknowledges some limitations of using mice to study sleep. One of these is that mice exhibit different sleep patterns than humans, including, for example, sleeping in a fragmented pattern, rather than in a single continuous period. "But it's challenging to study sleep in humans, too, because sleep is a behavior as well as a function of biology," he says. "We drink coffee and stay up late and do other things that go against our natural biological tendencies."

The investigators plan to study the function of the ADRB1 protein in other parts of the brain. They also are looking at other families for additional genes that are likely to be important. "Sleep is complicated," Ptáček notes. "We don't think there's one gene or one region of the brain that's telling our bodies to sleep or wake. This is only one of many parts."

Fu adds that the work may eventually have applications for developing new types of drugs to control sleep and wakefulness. "Sleep is one of the most important things we do," she says. "Not getting enough sleep is linked to an increase in the incidence of many conditions, including cancer, autoimmune disorders, cardiovascular disease, and Alzheimer's."

HAMILTON, ON (August 28, 2019) - Individuals with many different psychiatric disorders have a higher tendency to choose smaller, immediate rewards over larger, delayed rewards, a study led by Hamilton researchers has found.

The findings of a meta-analysis by researchers of McMaster University and St. Joseph's Healthcare Hamilton, which combined data from more than 40 studies, was published in JAMA Psychiatry today.

That this type of decision-making tied to impulsivity, called delay discounting, is heightened in those with certain psychiatric disorders compared to others, is expected to have an important impact on future research and treatment across an array of disorders.

"The revelation that delay discounting is one of these 'trans-diagnostic' processes will have a significant effect on the future of psychiatric diagnosis and treatment," said Michael Amlung, lead author of the study. He is an assistant professor of psychiatry and behavioural neurosciences at McMaster University and researcher for the Peter Boris Centre for Addictions Research at St. Joseph's Healthcare Hamilton.

The study analyzed data from studies across eight different psychiatric disorders, including major depressive disorder, bipolar disorder, borderline personality disorder, schizophrenia, eating disorders, and others. The largest delay discounting effects were found to be associated with bipolar disorder, borderline personality disorder, and schizophrenia.

Previous research has linked a greater preference for immediate rewards and impulsivity to negative health outcomes, such as addiction, obesity, and ADHD. This study reinforced that negative association, finding that impulsive preferences are consistently observed across an even broader range of psychiatric disorders.

Interestingly, the study also found the opposite pattern in those with anorexia nervosa. The researchers explained that the greater preference for delayed over immediate rewards seen in people with anorexia is consistent with excessive self-control of their eating habits.

The study authors say this pattern suggests that delay discounting preferences are best thought of as being on a continuum, with some disorders exhibiting excessively impulsive decisions and other disorders exhibiting excessively self-controlled decisions.

"Examining factors that cut across psychiatric disorders, such as delay discounting, helps to illuminate commonalities and distinguishing characteristics amongst disorders that then guide further research on treatment and prevention," said Randi McCabe, co-author of the paper, psychologist-in-chief at St. Joseph's Healthcare Hamilton and professor of psychiatry and behavioural neurosciences at McMaster.

"The more we understand the nature of psychiatric illness, the better we are equipped to provide effective treatment strategies," she said.

The authors say the study findings support the inclusion of delay discounting in the Research Domain Criteria (RDoC) framework proposed by the National Institute of Mental Health, as a potent indicator of psychiatric illness. RDoC is a biologically-valid framework for understanding mental disorders, and includes research approaches in genetics, neuroscience, and behavioural science.

"Our results provide strong evidence for delay discounting as a core behavioural process within the RDoC framework," Amlung said. "On a broader level, this study underscores the need for future research examining common neurobiological and genetic underpinnings of this type of decision making in order to inform evidence-based treatments across psychiatric disorders."