Experiments on mice have shown that variants in a gene called ankyrin-B, carried by millions of Americans, could cause cells to store fat, potentially leading to obesity.
Fat cells with ankyrin B-GLUT4 complexes (red isosurface dots) decorating the plasma membrane. Isosurface of lipid droplets and nuclei in gold and in blue, respectively. Credit: Damaris Lorenzo
Obesity is often attributed to a simple equation: people are eating too much and exercising too little. But evidence is growing that at least some of the weight gain that plagues modern humans is predetermined. A new study by researchers from North Carolina suggests that variants in a gene called ankyrin-B – carried by millions of Americans – may cause people to put on pounds through no fault of their own.
The study, conducted on mice, shows that the gene variation causes fat cells to suck up glucose faster than normal – more than doubling their size. When a high-fat diet or aging metabolism is added to the equation, obesity becomes all but inevitable.
"We call it fault-free obesity," said Vann Bennett, PhD, Professor of Biochemistry at Duke University School of Medicine. "We believe this gene might have helped our ancestors store energy in times of famine. In current times, where food is plentiful, ankyrin-B variants could be fuelling the obesity epidemic."
Bennett discovered the protein ankyrin-B over 30 years ago. It is present in every bodily tissue and acts like an "anchor" by tethering important proteins to the inside of the cell's membrane. Bennett and other researchers have linked defects in ankyrin-B to a number of human diseases – including aging, autism, diabetes, irregular heartbeat and muscular dystrophy.
Several years ago, Jane Healey, an MD/PhD student working in the Bennett laboratory, noticed that mice with cardiac arrhythmia caused by mutations in ankyrin-B were fatter than their wildtype litter mates. To figure out why, she created mouse models with common human variants of the gene. It was found that these mice quickly grew fat, locking away most of their calories in fat tissue, rather than sending them to other tissues to burn as energy. These findings were published in 2015 in the Journal of Clinical Investigation.
The experimental mouse on the right lacks a gene for ankyrin-B, causing his fat cells to absorb twice as much glucose and making him fatter than his normal companion at left.
Credit: UNC Nutrition and Obesity Research Center
"The problem is, we still didn't know how this gene worked," said Damaris Lorenzo, PhD, a postdoctoral fellow in the laboratory at the time. "There is this common belief in the field that much of obesity can be traced back to appetite – and the appetite control centres that reside in the brain. But what if it isn't all in our head?"
To study that question, Lorenzo had her research group completely knock out the ankyrin-B gene in the fat tissue of mice. They repeated many of the same experiments that were conducted in the previous mouse models, which carried mutant versions of ankyrin-B. Just as before, the knock-out mice gained weight and their energy-storing white fat cells doubled in size – despite eating and exercising the same as normal mice. What's more, the weight gain increased as the mice aged or were fed a high-fat diet.
"We quickly learned that the increased accumulation of lipids in fat cells 'spilled over' to the liver and muscles," Lorenzo said. "The abnormal accumulation of fat in these tissues led to inflammation and disruption of response to insulin, a hallmark of type II diabetes. A similar cascade of events is what often takes place in humans, and that is why obesity can be so detrimental to our health," Lorenzo said.
After conducting a number of biochemistry experiments, Lorenzo showed that eliminating or mutating ankyrin-B changed the dynamics of Glut4, the protein that allows glucose to enter fat cells. As a result, the floodgates were opened, allowing glucose to flow into the cells more quickly than normal.
Lorenzo wondered if the same mechanism held true for other known human mutations of ankyrin-B. Variants in ankyrin-B are carried by 1.3% of Caucasians and 8.4% of African Americans, accounting for millions of people in the U.S. alone. Lorenzo cultured fat cells carrying these variants and found that they too sucked up glucose at a higher rate. The disease seems to originate in fat tissue, though it likely has effects elsewhere in the body.
"We found that mice can become obese without eating more, and that there is an underlying cellular mechanism to explain that weight gain," Bennett said. "This gene could enable us to identify at-risk individuals who should watch what kind of calories they eat and exercise more in order to keep their body weight under control."
But first, Bennett says their findings in the laboratory must be confirmed in the general population. To do so, the researchers will need to identify individuals with ankyrin-B variants, and then assess family histories, height and weight, and characteristic physiological traits as well as glucose metabolism, to determine the impact of these variants on human health. The team's latest study appears in the journal Proceedings of the National Academy of Sciences.
The FDA has approved "Abilify MyCite" – the first drug in the U.S. with a digital ingestion tracking system. This can record when the medication was taken, via a sensor embedded in the pill.
Credit: Proteus Digital Health
The U.S. Food and Drug Administration (FDA) has this week approved the first drug in the U.S. with a digital ingestion tracking system. Abilify MyCite features an ingestible sensor embedded in the pill that records when medication is taken. The product is approved for the treatment of schizophrenia, acute treatment of manic and mixed episodes associated with bipolar I disorder and for use as an add-on treatment for depression in adults.
The system works by sending a message from the pill's sensor to a wearable patch. The patch transmits the information to a mobile application so that patients can track the ingestion of medication on their smartphone. The patch also records activity levels, sleeping patterns, steps taken, activity and heart rate. Patients can permit their doctor and up to four other people including family members to access the data through a web-based portal.
The sensor itself is made of silicon, copper and magnesium. It produces an electrical signal that is activated upon contact with stomach acid; the sensor then passes through the body naturally.
"Being able to track ingestion of medications prescribed for mental illness may be useful for some patients," said Mitchell Mathis, M.D., a director at the FDA's Center for Drug Evaluation and Research. "The FDA supports the development and use of new technology in prescription drugs and is committed to working with companies to understand how technology might benefit patients and prescribers."
Credit: Proteus Digital Health
Abilify MyCite was developed in a joint collaboration between Japanese pharmaceutical company Otsuka (which makes the oral aripiprazole tablets) and California-based Proteus (which created the sensor). The pill could help to reduce the problem of non-adherence to prescriptions, which is estimated to cost $100bn in the U.S. each year. It will be particularly useful for elderly people with failing memories to ensure they are taking their drugs properly.
"The approval of Abilify MyCite – the first digital medicine system – means that for the first time in my years of experience as a psychiatrist, there is an innovative way to provide individuals with serious mental illness, and selected members of their families and care teams, with information on objective medication taking patterns to help inform the patient's illness management and personalised treatment plan. This allows the opportunity for an open dialogue with the patient," said John Kane, MD, Vice President for Behavioural Health Services at Northwell Health, New York. "Until now, pharmacologic therapy for serious mental illness has been missing a systematic approach to objectively track and signal that a patient has taken their drug."
"The time is right for the category of Digital Medicines to be available to patients with serious mental illness," said Andrew Thompson, CEO of Proteus. "Consumers already manage important tasks like banking, shopping, and communicating with friends and family by using their smartphones, as they go about their daily lives. With this FDA approval, we can help enable individuals with serious mental illness to engage with their care team about their treatment plan in a new way."
Proteus raised around $400 million from investors to bring its sensor to commercial use. Otsuka has not yet revealed a price for Abilify MyCite, which will be rolled out during 2018, initially to a limited number of health plans. This approval is likely to result in many more "digital pills" for other conditions besides mental health. The FDA is planning to hire more staff with a "deep understanding" of software development in relation to medical devices and engage with entrepreneurs on new guidelines.
Researchers from the University of Aberdeen report that a single dose of the drug Trodusquemine can "melt away" fat inside mouse arteries.
A drug being trialled for treating breast cancer and diabetes has been shown to 'melt away' the fat inside arteries that can cause heart attacks and strokes. Researchers from the University of Aberdeen, using pre-clinical mouse models, showed that just a single dose of the drug (Trodusquemine) completely reversed the effects of a disease that causes a host of heart problems.
Atherosclerosis is the build-up of fatty material inside the arteries. Over time, this fatty material can grow bigger until your arteries become so narrow that not enough blood can pass through. Atherosclerosis is the most common condition that causes heart attacks and strokes.
In pre-clinical tests, mice with set-in atherosclerosis – mimicking what happens in humans – had less fatty plaques in their arteries whether they had regular doses over time or just a single dose of Trodusquemine.
The drug works by stopping an enzyme called PTP1B, which is normally increased in people with obesity or diabetes and conditions involving prolonged inflammation such as sepsis, inflamed diabetic foot ulcers and allergic lung inflammation. The researchers found that it also stimulated the action of another protein (AMPK), which effectively mimics exercise and reduces chronic inflammation. It has already been shown to be effective with diabetes and breast cancer patients, but this is the first time the drug has been shown to have benefits for long-term cardiovascular disease.
Professor Mirela Delibegovic and Dr Dawn Thompson from the University of Aberdeen's Institute of Medical Sciences who led the study said: "All humans have some level of atherosclerosis. As you age, you start to develop these fatty streaks inside your arteries. It is a big problem for people who are overweight or have underlying cardiovascular conditions."
"Trodusquemine has already been trialled for treatment of diabetes and breast cancer, but this is the first time it has been used in models of atherosclerosis. These have only been tested at pre-clinical level, in mice, so far – but the results were quite impressive and showed that just a single dose of this drug seemed to completely reverse the effects of atherosclerosis. The next step is to test the ability of this drug to improve outcomes in human patients with developed atherosclerosis and cardiovascular disease."
Professor Jeremy Pearson, Associate Medical Director at the British Heart Foundation, said: "Trodusquemine is in early clinical trials for the treatment of diabetes. This study shows it can also limit the build-up of fatty atherosclerotic plaques in mice. If we see the same effect in patients, the drug may prove even more useful than currently hoped for."
Atherosclerosis generally starts when a person is young and worsens with age. Almost all people are affected to some degree by the age of 65. It is the number one cause of death and disability in the developed world. If successfully trialled in humans, this new drug, alongside other treatments, may help in reducing deaths from cardiovascular disease to negligible levels by the 2040s, as predicted on our timeline.
In yet another breakthrough for aging research, a new way to rejuvenate old cells in the laboratory has been discovered, making them not only look younger, but start to behave more like young cells.
Researchers at the University of Exeter have found a new way to rejuvenate inactive senescent cells. Within hours of treatment, the older cells started to divide and had longer telomeres – the "caps" on the ends of chromosomes that shorten as we age. This discovery builds on earlier findings from the Exeter group that showed how a class of genes called "splicing factors" are progressively switched off as we age. The Exeter team, working with Professor Richard Faragher and Dr Elizabeth Ostler from the University of Brighton, found that splicing factors can be switched back on with chemicals, making senescent cells not only look physically younger, but start to actually behave more like young cells and start dividing.
The researchers applied compounds called resveratrol analogues – chemicals based on a substance naturally found in red wine, dark chocolate, red grapes and blueberries – to cells in culture. These chemicals caused splicing factors to be switched back on. Within hours, the cells looked younger and started to rejuvenate, behaving like young cells and dividing.
The researchers say their discovery could lead to therapies for helping people age better, without experiencing some of the degenerative effects of getting old. Most people by the age of 85 have experienced some kind of chronic illness, and as people get older they are more prone to stroke, heart disease and cancer.
“This is a first step in trying to make people live normal lifespans, but with health for their entire life,” said Lorna Harries, Professor of Molecular Genetics at the University of Exeter. “Our data suggests that using chemicals to switch back on the major class of genes that are switched off as we age might provide a means to restore function to old cells.”
Chemicals used in the study – resveratrol analogues. Credit: Eva Latorre et al.
Dr Eva Latorre, Research Associate at the University of Exeter, was surprised by the extent and rapidity of the changes in the cells: “When I saw some of the cells in the culture dish rejuvenating, I couldn’t believe it. These old cells were looking like young cells. It was like magic. I repeated the experiments several times and in each case, the cells rejuvenated. I am very excited by the implications and potential for this research.”
As we age, our tissues accumulate senescent cells. These are alive, but do not grow or function as they should. These old "zombie cells" lose the ability to correctly regulate the output of their genes. This is one reason why tissues and organs become susceptible to disease as we age. When activated, genes make a message giving instructions for the cell to behave in a certain way. Most genes can make more than one message, which determines how the cell acts.
Splicing factors are crucial in ensuring that genes perform their full range of functions. One gene can send out several messages to the body – such as the decision whether or not to grow new blood vessels – and splicing factors decide which message to send. As people age, the splicing factors tend to work less efficiently or not at all, restricting the ability of cells to respond to challenges in their environment. Senescent cells, which can be found in most organs from older people, also have fewer splicing factors.
Professor Harries added: “This demonstrates that when you treat old cells with molecules that restore the levels of the splicing factors, the cells regain some features of youth. They are able to grow, and their telomeres – caps on the ends of the chromosomes that shorten as we age – are now longer, as they are in young cells. Far more research is needed now to establish the true potential for these sort of approaches to address the degenerative effects of aging.”
“At a time when our capacity to translate new knowledge about the mechanisms of aging into medicines and lifestyle advice is limited only by a chronic shortage of funds, older people are ill-served by self-indulgent science fiction,” said Professor Richard Faragher of the University of Brighton. “They need practical action to restore their health and they need it yesterday. Our discovery of cell rejuvenation using these simple compounds shows the enormous potential of aging research to improve the lives of older people.”
Scientists funded by DARPA have developed a non-invasive cap that stimulates parts of the brain via electrical currents and is shown to improve the learning abilities of macaques. In the not-too-distant future, this technology could be used by humans.
Researchers from HRL Laboratories (California), McGill University (Montreal, Canada), and Soterix Medical (New York) have collaborated on a study of transcranial direct current stimulation (tDCS) in monkeys. Funded by the Defense Advanced Research Projects Agency (DARPA), their work is published in the peer-reviewed journal Cell.
tDCS is a form of neurostimulation that uses constant, low direct currents delivered via electrodes on the head. When these electrodes are placed in the region of interest, the current induces intracerebral current flow. This can increase or decrease neuronal excitability in the specific area being stimulated, based on which type of stimulation is used. The change of neuronal excitability alters brain function, which can be used in therapies as well as to provide more information about the functioning of the human brain. In recent years, it has been used by neuroscientists to link specific brain regions to specific cognitive tasks or psychological phenomena. As of 2017, it has not yet been approved for medical use by the US FDA. It is, however, approved in Europe for treatment of major depressive disorder. The number of studies involving tDCS is growing exponentially.
In their experiments, the DARPA-funded team used tDCS on a group of macaques. They stimulated the prefrontal cortex at the front of the brain, an area known to be involved in complex processes like reason, logic, problem solving, planning and memory. The animals were made to perform a task based on associative learning. To obtain a reward, they had to learn associations between a visual cue and a location. The macaques would hunt for each reward after getting the visual cue.
The initial foraging trials took around 15 seconds, and once the animal learned the location of the reward, it took approximately two seconds to recall and find the target. Subjects in a control group (i.e. without neurostimulation) needed an average of 22 trials to learn to obtain the reward immediately. With tDCS, however, they required an average of just 12 trials.
The results of these trials showed that overall, learning was accelerated by 40% when 2 milliamps (mA) were sent noninvasively to the prefrontal cortex without increased neuronal firing. The study showed it was modulated connectivity between brain areas – not the neuron firing rates – that accounted for the increased learning speed.
“In this experiment, we targeted the prefrontal cortex with individualised non-invasive stimulation montages,” said Dr. Praveen Pilly, HRL's principal investigator on the study. “That is the region that controls many executive functions including decision-making, cognitive control, and contextual memory retrieval. It is connected to almost all the other cortical areas of the brain, and stimulating it has widespread effects. It is also the target of choice in most published behavioural enhancement studies and case studies with transcranial stimulation. We placed the tDCS electrodes on the scalp in both our control and stimulation conditions. The behavioural effect was revealed when they learned to find the reward faster.”
“The improved long-range connectivity between brain areas in the high frequency bands and reduced connectivity in the low frequency bands were the determining factors in our study that could explain the learning improvements with tDCS of the prefrontal cortex,” Pilly said. “Just because neurons can be more brisk in their firing may not lead to changes in performance. Boosting memory function likely requires better coordination of task-relevant information across the cortex.”
The team concludes: “These results are consistent with the idea that tDCS leads to widespread changes in brain activity and suggest that it may be a valuable method for cheaply and non-invasively altering functional connectivity in humans.”
Researchers have identified four genes responsible for how long patients survive with pancreatic cancer.
Alterations in four main genes are responsible for how long patients survive with pancreatic cancer, according to a new study in JAMA Oncology.
Until now, the presence and patterns between the genes and disease progression was not clearly established. One key difference in this study is the relatively large size: it involved 356 patients, all with pancreatic adenocarcinoma (by far the most common type of pancreas tumour) that could be surgically removed. Ninety of the patients were treated at the University of Rochester Medical Center's Wilmot Cancer Institute; the others at Dana Farber/Brigham and Women's Cancer Center in Boston and Stanford Cancer Institute.
In all cases after the tumours were removed, scientists extracted DNA from the cancerous tissue and nearby normal tissue, and conducted next-generation DNA sequencing on the specimens.
The analysis centred on the activity of the KRAS, CDKN2A, SMAD4, and TP53 genes. Results showed that patients who had three or four of the altered genes had worse disease-free survival (time between surgery and when the cancer returns), and overall survival (from surgery to death), compared to patients with a single or two altered genes.
"This research helps us to understand how the molecular features of pancreatic cancer impact prognosis on an individual level and gives us more facts to guide patients, and importantly, to design future research studies," said study co-author Aram Hezel, M.D., a gastrointestinal cancer expert.
Pancreatic cancer is aggressive and generally has poor survival odds. Patients who can undergo surgery as part of treatment often survive longer and some patients fare best when they can receive chemotherapy prior to surgery. But having customised, molecular information will provide an even greater understanding of how the disease is likely to progress in each patient.
An improved version of the genetic engineering technique known as CRISPR has been published in the journals Science and Nature.
Two separate studies have demonstrated a powerful new method of genetic engineering, which could be used to improve the research and treatment of diseases in the future.
In the first study, scientists directly and permanently changed single base pairs of DNA from A*T to G*C. This could one day enable precise DNA surgery to correct mutations. In the second, RNA was edited rather than DNA, which has potential to treat diseases without permanently affecting the genome.
The Howard Hughes Medical Institute, which led the first study, created a new enzyme known as a "base editor". This allows researchers to edit the individual base pairs of DNA that form the instructions of life. By altering the molecular structure of one base – adenine (A), cytosine (C), guanine (G) or thymine (T) – and converting it to another, genetic faults that cause diseases could be fixed with high levels of precision. Researchers can now manipulate all four bases. Howard Hughes scientists took cells from patients and used base editing to correct hemochromatosis, an inherited condition that leads to dangerously high levels of iron in the blood.
In DNA, each base on one strand is joined with its "partner" base on an opposing strand – so that, for example, adenine pairs with thymine (A*T), while guanine pairs with cytosine (G*C). Some genome editing tools, such as CRISPR/Cas9, cut both strands of DNA and rely on the cell's own molecular machinery to fill in the gap with a desired DNA sequence. Base editors, however, can rewrite the individual chemical units of DNA. Last year, the team at Howard Hughes described a base editor that could change C*G base pairs into T*A. But they didn't have the ability to convert A*T to G*C, until now. Mutations in which a G*C mutates into an A*T account for nearly half of the roughly 32,000 single point mutations associated with human diseases.
"CRISPR is like scissors, and base editors are like pencils," says David Liu, Professor of Chemical Biology. He and his colleagues are now "hard at work trying to translate base editing technology into human therapeutics."
The new system – which relies on the evolution of engineered bacterial colonies to generate the enzyme – is a "really exciting addition to the genome engineering toolbox," explains Feng Zhang, molecular biologist at the Broad Institute of MIT and Harvard, who was not involved in this study, but took part in the second. "It's a great example of how we can harness natural enzymes and processes to accelerate scientific research."
A newly created DNA base editor: atom-rearranging enzyme (red), guide RNA (green) and Cas9 nickase (blue). Credit: Gaudelli et al./ Nature 2017
In the second study, by the Broad Institute of MIT and Harvard, researchers adapted CRISPR to edit single RNA letters in human cells. This new system is called RNA Editing for Programmable A to I Replacement, or "REPAIR". RNA is usually single-stranded, and does not form into a double helix as does DNA. Unlike the permanent changes to the genome required for DNA editing, RNA editing provides a safer and more flexible way to make corrections. It has major potential as a tool for disease research and treatment.
"REPAIR can fix mutations without tampering with the genome – and because RNA naturally degrades, it's a potentially reversible fix," explains co-author David Cox, a graduate student in Feng Zhang's lab.
Like the base editors in the first study, REPAIR has the ability to target individual RNA letters – switching adenosines (A) to inosines (recognised as guanosines (G) by the cell) – without cutting the transcript or relying on the cell's native machinery. These letters are involved in single-base changes, known to regularly cause disease in humans. A mutation from G to A is extremely common; these alterations have been implicated in cases of epilepsy, muscular dystrophy and Parkinson's disease, for example. REPAIR can reverse the impact of any pathogenic G-to-A mutation – regardless of its surrounding letter sequence, with the potential to operate in any cell type. Zhang and his colleagues tested REPAIR on human cells in the laboratory, using this RNA approach to correct an inherited form of anaemia.
"The ability to correct disease-causing mutations is one of the primary goals of genome editing," said Professor Zhang. "So far, we've gotten very good at deactivating genes – but actually recovering lost protein function is much more challenging. This new ability to edit RNA opens up more potential opportunities to recover that function and treat many diseases, in almost any kind of cell."
Zhang, along with the Broad Institute and MIT, plan to share the REPAIR system widely. As with earlier CRISPR tools, they will make this technology freely available for academic research, via the plasmid-sharing website Addgene, through which the Zhang laboratory has already shared reagents over 42,000 times with researchers at 2,200 labs in 61 countries around the world.
Credit: Broad Communications, Susanna M. Hamilton
"This is an exciting week for genetic research," said Dr Helen O'Neill, at University College London. "These papers highlight the fast pace of the field and the continuous improvements being made in genome editing, bringing it closer and closer to the clinic."
"The science is moving fast in the sense it is becoming less risky, more certain, more precise and more effective," said Dr Sarah Chan, a bioethicist at the University of Edinburgh, in a BBC interview. "It is absolutely past time for us to engage more widely with the public on the issue of gene editing."
Scientists at Rutgers University have found an efficient way to enhance the nutritional value of corn, by inserting a bacterial gene from E. coli that stimulates production of a key nutrient called methionine, an amino acid usually found in meat.
A genetic discovery by Rutgers University could benefit millions of people in developing countries, such as in South America and Africa, who depend on corn as a staple. It could also significantly reduce worldwide animal feed costs.
“We improved the nutritional value of corn, the largest commodity crop grown on Earth,” said Thomas Leustek, study co-author and professor in the Department of Plant Biology in the School of Environmental and Biological Sciences. “Most corn is used for animal feed, but it lacks methionine – a key amino acid – and we found an effective way to add it.”
Methionine, found in meat, is one of the nine essential amino acids that humans get from food. It is needed for growth and tissue repair, improves the tone and flexibility of skin and hair, and strengthens nails. The sulphur in methionine protects cells from pollutants, slows cell aging and is essential for absorbing selenium and zinc. Worldwide, several billion dollars of synthetic methionine is added to corn seeds annually, but the process is costly and energy-intensive.
The scientists inserted an E. coli bacterial gene into the corn plant’s genome and grew several generations of corn. The E. coli enzyme – 3′-phosphoadenosine-5′-phosphosulfate reductase (EcPAPR) – spurred methionine production in just the plant’s leaves instead of the entire plant to avoid the accumulation of any toxic by-products. As a result, methionine in corn kernels increased by 57 percent. Tests on chickens at the university showed that the genetically engineered corn was nutritious for them.
In the developed world, including the U.S., meat proteins generally have lots of methionine. But in the developing world, subsistence farmers grow corn for their family’s consumption: “Our study shows that they wouldn’t have to purchase methionine supplements or expensive foods that have higher methionine,” said Leustek.
A 35-year-old man who had been in a vegetative state for 15 years after a car accident is reported to have shown signs of consciousness after neurosurgeons implanted a vagus nerve stimulator into his chest.
A 35-year-old man who had been in a persistent vegetative state (PVS) for 15 years after a car accident has shown signs of consciousness after neurosurgeons implanted a vagus nerve stimulator into his chest. This outcome challenges the general belief that disorders of consciousness persisting longer than 12 months are irreversible, the researchers say.
Their findings, reported this week in Current Biology, show that vagus nerve stimulation (VNS) – a treatment already in use for epilepsy and depression – can help to restore consciousness even after many years in a vegetative state.
By stimulating the vagus nerve, "it is possible to improve a patient's presence in the world," says Prof. Angela Sirigu, at the Institute of Cognitive Science in Lyon, France.
The vagus nerve connects the brain to many other parts of the body. It is the longest nerve of the autonomic nervous system in the human body and is known to be important in waking, alertness, and other essential functions. To test the ability of VNS to restore consciousness, the researchers wanted to select a difficult case, to ensure that any improvements could not be explained by chance. They chose a patient who had been lying in a vegetative state for more than a decade with no sign of improvement.
Credit: Cyberonics, Inc./LivaNova
After one month of vagal nerve stimulation, the man's brain activity significantly improved. Following many years in a vegetative state, he had entered a state of minimal consciousness. The man began responding to simple orders that had been impossible before. For example, he could follow an object with his eyes and turn his head when requested. His mother reported an improved ability to stay awake when listening to his therapist reading a book. The researchers also observed responses to "threat" that had been absent before. For instance, when the examiner's head suddenly approached the patient's face, he reacted with surprise by opening his eyes wide.
Recordings of brain activity also revealed major changes. A theta EEG signal important for distinguishing between a vegetative and minimally conscious state increased significantly in areas of the brain involved in movement, sensation and awareness. VNS also increased the brain's functional connectivity. A PET scan showed increases in metabolic activity in both cortical and subcortical regions of the brain, too.
These findings prove that the right intervention can yield changes in consciousness "even in the most severe clinical cases", the researchers say.
"Brain plasticity and brain repair are still possible even when hope seems to have vanished," Prof. Sirigu says.
The researchers are now planning a large collaborative study to confirm and extend the therapeutic potential of VNS for patients in a vegetative or minimally conscious state. In addition to helping patients, Sirigu says the findings will also advance understanding of "this fascinating capacity of our mind to produce conscious experience."
Molecular researchers from the University of Copenhagen have joined forces with an artificial intelligence company to fight premature aging.
The Centre for Healthy Aging at the University of Copenhagen has announced a research collaboration with a company specialising in artificial intelligence (AI) to develop solutions for preventing early aging. The aim of this partnership is to develop medicines to prevent and cure a broad range of diseases associated with aging.
Alzheimer's, Parkinson's and cardiovascular diseases are strongly associated with aging and share many characteristics on the molecular level. Experts in the genetics of aging at the Department of Cellular and Molecular Medicine partnered with the Baltimore-based company, Insilico Medicine, specializing in AI to find molecules that can be developed into drugs to cure and prevent these diseases. The objective of this collaboration is to increase "health span" for everyone on the planet.
"Many of the diseases of aging are associated with the failure of the DNA repair mechanisms," says assistant professor Morten Scheibye-Knudsen, Centre for Healthy Aging. "The aging processes accelerate as the DNA repair mechanisms lose function. Our collaboration with Insilico Medicine will allow us to find the molecules that repair DNA and prevent accelerated aging."
Insilico Medicine is developing the advanced AI algorithms to study aging processes and discover potential new medical interventions. Many of the molecules being studied could induce the expression of certain genes involved in the endogenous repair processes to slow down and perhaps even reverse age-related diseases. By applying a specific branch of artificial intelligence called Deep Learning (DL) on multi-modal data, the company aims to discover the precise molecules that can stimulate the repair of DNA.
"Deep learning systems are outperforming human abilities in many tasks including image recognition and autonomous driving," said Alex Zhavoronkov, PhD, founder and CEO of Insilico Medicine, Inc. "But one area, where AI will have the most impact is drug discovery and we are deeply honoured to be able to partner with professor Scheibye-Knudsen's group at the University of Copenhagen, which is one of the most advanced in the world. I hope that together we will be able to find new molecules to extend healthy longevity and make humans more resistant to the various stress factors."
At the advanced laboratories in Copenhagen, the research teams will test the molecules identified using the Deep Learning methods to select the most effective ones for joint development into novel medicines.
"We hope that cooperation can lead to the development of new drugs that can prevent early aging, thus ensuring increased health spans for everyone," says Morten Scheibye-Knudsen. "If we can find molecules that repair our DNA, it is not inconceivable that we can increase the upper limit to how old we may be."
Motorised molecules have been used to drill holes in the membranes of individual cells, and show promise for either bringing therapeutic agents into the cells or directly inducing the cells to die.
Illustration courtesy of the Tour Group
Researchers at Durham (UK), North Carolina State and Rice universities have demonstrated in lab tests how rotors in single-molecule nanomachines can be activated by ultraviolet light to spin at three million rotations per second and pierce membranes in cells. The team developed motors based on the work of Bernard Feringa, who won the Nobel Prize in Chemistry in 2016. The motor itself is a paddle-like chain of atoms that can be prompted to move in a single direction when supplied with energy. Properly mounted as part of the cell-targeting molecule, the motor can be made to spin when activated by a light source.
A team at Rice, led by Professor James Tour, had previously demonstrated molecular motors whose diffusion in a solution was enhanced when activated by ultraviolet light. The rotors needed to spin between 2 and 3 megahertz – 2 to 3 million times per second – to show they could overcome obstacles presented by adjacent molecules and outpace natural Brownian motion (the erratic movement of particles suspended in fluid).
"We thought it might be possible to attach these nanomachines to the cell membrane, and then turn them on to see what happened," said Tour.
The motors, barely a nanometre (nm) in width, can be designed to target a cell's 8-10 nm lipid bilayer membrane, and then either tunnel through to deliver drugs or other payloads, or disrupt it, thereby killing the cell. They can also be functionalised for solubility or fluorescent tracking.
"These nanomachines are so small, we could park 50,000 of them across the diameter of a human hair, yet they have the targeting and actuating components combined in that diminutive package to make molecular machines a reality for treating disease," said Tour.
Tour's laboratory created 10 variants – including motor-bearing molecules in several sizes, and peptide-carrying nanomachines designed to target specific cells for death, as well as control molecules identical to the other nanomachines but without motors. The team found it takes only a minute or so for the motors to tunnel through a membrane. In the future, they hope these nanomachines will help target cancers that resist existing chemotherapy.
"It is highly unlikely that a cell could develop a resistance to molecular mechanical action," Tour said.
The motors were tested on live cells, including human prostate cancer cells. Experiments showed that without an ultraviolet trigger, the motors could locate specific cells of interest, but stayed on the targeted cells' surface and were unable to drill into the cells. When triggered, however, the motors rapidly drilled through the membranes.
"[Our] researchers are already proceeding with experiments in microorganisms and small fish to explore the efficacy in-vivo," Tour said. "The hope is to move this swiftly to rodents, to test the efficacy of nanomachines for a wide range of medicinal therapies."
"Once developed, this approach could provide a potential step change in non-invasive cancer treatment and greatly improve survival rates and patient welfare globally," said Dr Robert Pal from Durham University, who collaborated.
The team's latest study was published yesterday in the journal Nature.
In a potential breakthrough for the treatment of obesity and diabetes, Purdue University scientists have found a way to deliver a drug directly to stored white fat cells to turn them into more easily burned brown fat cells.
Credit: Alexander M. Gokan
White adipose tissue, most associated with obesity, is a type of fat that collects in the body for long-term storage of energy. It's possible humans evolved to store white fat to act as insulation and energy storage. However, as we have become over-fed and less active, we have less need for the energy stored in white fat and it over-accumulates, leading to metabolic diseases such as diabetes and obesity. More than one-third of Americans are obese today, and nearly 10% have diabetes, according to the Centers for Disease Control and Prevention.
Brown fat is more readily burned by the body, dissipating energy into heat. Scientists at Purdue University (Indiana, USA) have been looking for ways to decrease white fat in favour of brown fat, through a signalling pathway that is known to regulate cell differentiation and cell identity.
In so-called Notch signalling, a cell sends a signal to a neighbouring cell to control that neighbour's gene transcription and identity. Disrupting that signal in a progenitor cell destined to become one of the undesirable white fat cells leads to the creation of brown fat.
Meng Deng, an Assistant Professor in Agricultural and Biological Engineering, and colleague Shihuan Kuang, Professor of Animal Sciences, describe their latest research in the journal Molecular Therapy. They have, for the first time, used an engineered polymeric nanoparticle for controlled delivery of a Notch-signalling inhibitor directly to white fat cells. In a mouse model, the nanoparticle – made of an FDA-approved polymer known as PLGA and containing the drug Dibenzazepine – disrupted Notch signalling and led to the creation of brown fat cells.
"We can control the delivery to specific sites in the body, in this case the bad fat or white fat cells," Deng said. "Once those engineered particles are inside the fat cells, they can slowly release the drug in the cells, potentially limiting the off-target interactions in other tissues and reducing the frequency of dosing."
The particles, which are less than 200 nanometres in size, are readily taken up by the fat cells through a process called endocytotic trafficking and subsequently undergo a rapid endo-lysosome escape to the cytosol within the cell membrane.
"The particle was actually picked up by the cell. It's like it's being eaten by the cells," Kuang said. "This limits the particle from going anywhere else."
Since the nanoparticles containing the drug are injected into fat, Deng said it may be possible to develop therapies that target fat loss in specific parts of the human body. In the mouse model, targeting a specific fat depot with weekly injections of nanoparticles is sufficient to bring about systemic improvements in glucose tolerance and insulin sensitivity. Being overweight is also a factor in developing type 2 diabetes. Removing excess fat would likely decrease the odds of developing the disease.
Deng has filed a patent for the process and has created a startup, Adipo Therapeutics LLC, to continue testing and eventually commercialising the technology for use in humans.
Scientists at the University of Utah report that youthful plasticity has been restored to aging mouse brains by manipulating only a single gene.
Like much of the rest of the body, the brain loses flexibility with age, impacting the ability to learn, remember and adapt. Now, scientists at the University of Utah Health report they can rejuvenate the plasticity of the mouse brain – specifically in the visual cortex – increasing its ability to adapt and change in response to new experiences. Furthermore, manipulating only a single gene is enough to trigger this improvement. The research appears this week in Proceedings of the National Academy of Sciences (PNAS).
"It's exciting because it suggests that by just manipulating one gene in adult brains, we can boost brain plasticity," says lead author Jason Shepherd, Ph.D., Assistant Professor of Neurobiology and Anatomy. "This has implications for potentially reducing normal cognitive decline with aging, or boosting recovery from brain injury after stroke or traumatic brain injury," he says. Additional research will need to be done to determine whether plasticity in humans and mice is regulated in the same way.
In a previous study, Shepherd and his colleagues found that during youth, a "critical window" of brain plasticity is never available to mice lacking a gene known as Arc. Temporarily closing a single eye of a normal young mouse deprived the visual cortex of normal input, and the neurons' electrophysiological response to visual experience changed. By contrast, young mice without Arc could not adapt to the new experience in the same way.
"Given our previous studies, we wondered whether Arc is essential for controlling the critical period of plasticity during normal brain development," explains Shepherd.
Overexpressed Arc in the visual cortex. Credit: Elissa Pastuzyn
If there is no visual plasticity without Arc, then perhaps the gene plays a role in keeping the "critical window" open? In support of this idea, the team's latest investigation finds that in the mouse visual cortex, Arc rises and falls in parallel with visual plasticity. The two peak in teen mice, falling sharply by middle age – suggesting they are linked.
The team probed this connection further in two more ways. First, they tested mice with a strong supply of Arc throughout life. At middle age, these mice responded to visual deprivation as robustly as their juvenile counterparts. By prolonging Arc's availability, the window of plasticity was open for longer.
A second set of experiments raised the bar higher. Viruses were used to deliver Arc to middle age mice, after the critical window had shut. Following this intervention, these older mice responded to visual deprivation just as a youngster would. So even though the window had already closed, Arc enabled it to open once again.
"It was incredible to see that in adult mice, who have gone through normal development and aging, simply overexpressing Arc with a virus restored plasticity," says co-first author Kyle Jenks, a graduate student in Shepherd's lab.
Additional research will now be required to understand precisely how manipulating Arc boosts plasticity. Whether Arc is involved in regulating the plasticity of neurological functions mediated by other brain structures – such as learning, memory, or repair – remains to be tested, but will be examined in the future, says Shepherd.
For the first time, scientists have used the CRISPR system in human embryos to delete faulty DNA responsible for a hereditary heart condition.
Credit: Oregon Health and Science University (OHSU)
Scientists have, for the first time, corrected a disease-causing mutation in early stage human embryos with gene editing. The technique, which uses the CRISPR-Cas9 system, corrected the mutation for a heart condition at the earliest stage of embryonic development so that the defect would not be passed on to future generations.
The work, described today in the journal Nature, is a collaboration between the Salk Institute, Oregon Health and Science University (OHSU) and Korea's Institute for Basic Science. It could pave the way for improved in vitro fertilization (IVF) outcomes, as well as eventual cures for some of the thousands of diseases caused by mutations in single genes.
"Thanks to advances in stem cell technologies and gene editing, we are finally starting to address disease-causing mutations that impact potentially millions of people," says Juan Carlos Izpisua Belmonte, a professor in Salk's Gene Expression Laboratory and a corresponding author of the paper. "Gene editing is still in its infancy, so even though this preliminary effort was found to be safe and effective, it is crucial that we continue to proceed with the utmost caution, paying the highest attention to ethical considerations."
Hypertrophic cardiomyopathy (HCM) is the most common cause of sudden death in otherwise healthy young athletes, and affects approximately 1 in 500 people overall. It is caused by a dominant mutation in the MYBPC3 gene, but often goes undetected until it is too late. Since people with a mutant copy of the MYBPC3 gene have a 50 percent chance of passing it on to their own children, being able to correct the mutation in embryos would prevent the disease not only in affected children, but also in their descendants.
The researchers generated induced pluripotent stem cells from a skin biopsy donated by a male with HCM and developed a gene-editing strategy based on CRISPR-Cas9 that would specifically target the mutated copy of the MYBPC3 gene for repair. The targeted mutated MYBPC3 gene was cut by the Cas9 enzyme, allowing the donor's cells' own DNA-repair mechanisms to fix the mutation during the next round of cell division by using either a synthetic DNA sequence or the non-mutated copy of MYBPC3 gene as a template.
Using IVF techniques, the researchers injected the best-performing gene-editing components into healthy donor eggs newly fertilised with the donor's sperm. Then they analysed all the cells in the early embryos at single-cell resolution to see how effectively the mutation was repaired.
The scientists were surprised by just how safe and efficient the method was. Not only did a high percentage of embryonic cells get repaired, but also gene correction did not induce any detectable off-target mutations and genome instability – major concerns for gene editing. In addition, the researchers developed a robust strategy to ensure the repair occurred consistently in all the cells of the embryo (spotty repairs can lead to some cells continuing to carry mutations – see illustration below).
Professor Belmonte and his colleagues emphasise that, although promising, these are very preliminary results and more research will need to be done to ensure no unintended effects occur.
"Our results demonstrate the great potential of embryonic gene editing, but we must continue to realistically assess the risks as well as the benefits," adds Belmonte.
Future work will continue to assess the safety and effectiveness of the procedure and efficacy of the technique with other mutations.
However, this latest study has already been condemned by Dr David King, from the campaign group Human Genetics Alert, which described the research as "irresponsible" and a "race for first genetically modified baby".
"Perhaps the biggest question, and probably the one that will be debated the most, is whether we should be physically altering genes of an IVF embryo at all," said Darren Griffin, a professor of genetics at the University of Kent. "This is not a straightforward question. Equally, the debate on how morally acceptable it is not to act when we have the technology to prevent these life-threatening diseases must also come into play."
Researchers have discovered that stem cells in the brain's hypothalamus govern how fast aging occurs in the body.
Scientists from the Albert Einstein College of Medicine in New York have discovered that stem cells in the brain's hypothalamus govern how fast aging occurs in the body. This finding, made in mice, could lead to new strategies for warding off age-related diseases and extending lifespan. A paper was published online yesterday in Nature.
The hypothalamus was already known to regulate important processes including growth, development, reproduction and metabolism. In a 2013 paper, researchers from Einstein made the surprising finding that the hypothalamus also regulates aging throughout the body. Now, the scientists have pinpointed the cells in the hypothalamus that control aging: a tiny population of adult neural stem cells, which were known to be responsible for forming new brain neurons.
"Our research shows that the number of hypothalamic neural stem cells naturally declines over the life of the animal, and this decline accelerates aging," says Dongsheng Cai, Professor of Molecular Pharmacology. "But we also found that the effects of this loss are not irreversible. By replenishing these stem cells or the molecules they produce, it's possible to slow and even reverse various aspects of aging throughout the body."
In a series of tests, mice were implanted with stem cells that made fresh neurons, which kept them more physically and mentally fit for months. They had their lives extended by up to 15% compared to untreated animals – the equivalent of boosting a human lifespan from 80 to 92.
"Of course humans are more complex," said Cai, who led the research. "However, if the mechanism is fundamental, you might expect to see effects when an intervention is based on it."
Dr. Cai and his colleagues found that the hypothalamic stem cells appear to exert their anti-aging effects by releasing molecules called microRNAs (miRNAs). These are not involved in protein synthesis, but instead play key roles in regulating gene expression. miRNAs are packaged inside tiny particles called exosomes, which hypothalamic stem cells release into the cerebrospinal fluid of mice.
The researchers extracted miRNA-containing exosomes from hypothalamic stem cells and injected them into the cerebrospinal fluid of two groups of mice: middle-aged mice whose hypothalamic stem cells had been destroyed; and normal middle-aged mice. This treatment significantly slowed aging in both groups of animals as measured by tissue analysis and behavioural testing that involved assessing changes in the animals' muscle endurance, coordination, social behaviour and cognitive abilities.
"It is a tour de force," said David Sinclair at Harvard Medical School. "It's a breakthrough. The brain controls how long we live. I can see a day when we are implanted with stem cells or treated with stem cell RNAs that improve our health and extend our lives. I would love to know which brain stem cell secretions extend a mouse's lifespan and if human stem cells make them too."
The researchers are now trying to identify the particular populations of microRNAs and perhaps other factors secreted by these stem cells that are responsible for these anti-aging effects – a first step toward possibly slowing the aging process and treating age-related diseases.
Astrophysicists report that tardigrade micro-animals may be one of the most resilient lifeforms on Earth, able to withstand global mass extinctions due to astrophysical events, such as supernovae, gamma-ray bursts, large asteroid impacts, and passing-by stars.
The world's most indestructible species, the tardigrade – an eight-legged micro-animal, also known as the water bear – will survive until the Sun dies, according to a new collaboration between Harvard and Oxford University.
Although much attention has been given to the potential impact of astrophysical events on human life, very little has been published about what it would take to kill the tardigrade and wipe out life on our planet. The new research implies that life will persist for as long as the Sun continues to shine. It also reveals that once life emerges, it is surprisingly resilient and difficult to destroy, boosting the odds of life on other planets.
The study, published in Scientific Reports, shows that the tiny creatures will survive the risk of extinction from all astrophysical catastrophes, and be around for billions of years – far longer than the human race.
Tardigrades are the toughest, most resilient animals on Earth – able to survive for up to 30 years without food or water, and endure temperature extremes of up to 150 degrees Celsius, the deep sea and even the frozen vacuum of space. The water-dwelling micro animal is only 0.5mm (0.02 inches) in size, but can live for up to 60 years. Researchers from the Universities of Oxford and Harvard concluded that they could most likely survive all astrophysical calamities.
Three potential events were considered as part of their research:
There are only a dozen known asteroids and dwarf planets with enough mass to boil the oceans (2x10^18 kg), these include Vesta (2x10^20 kg) and Pluto (10^22 kg). However, none of these objects will intersect the Earth's orbit and pose a threat to tardigrades.
In order to boil the oceans, an exploding star would need to be 0.14 light years away. The closest star to the Sun is 4.2 light years away and the probability of a massive star exploding close enough to Earth to kill all lifeforms on it, within the Sun's lifetime, is negligible.
Gamma-ray bursts are brighter and rarer than supernovae. Much like supernovas, gamma-ray bursts are too far away from Earth to be considered a viable threat. To boil the world's oceans, the burst would need to be within 40 light years, and the likelihood of a burst occurring so close is again, minor.
Gamma-ray burst. Credit: NASA
"Without our technology protecting us, humans are a very sensitive species," said Dr Rafael Alves Batista, Co-author and Post-Doctoral Research Associate in the Department of Physics at Oxford University. "Subtle changes in our environment impact us dramatically. There are many more resilient species on Earth. Life on this planet can continue long after humans are gone. Tardigrades are as close to indestructible as it gets on Earth, but it is possible that there are other resilient species examples elsewhere in the universe. In this context, there is a real case for looking for life on Mars and in other areas of the Solar System in general. If Tardigrades are Earth's most resilient species, who knows what else is out there?"
"A lot of previous work has focused on 'doomsday' scenarios on Earth – astrophysical events like supernovae that could wipe out the human race," explains Dr David Sloan, co-author from the same department at Oxford University. "Our study instead considered the hardiest species – the tardigrade. As we are now entering a stage of astronomy where we have seen exoplanets and are hoping to soon perform spectroscopy, looking for signatures of life, we should try to see just how fragile this hardiest life is. To our surprise we found that although nearby supernovae or large asteroid impacts would be catastrophic for people, tardigrades could be unaffected. Therefore it seems that life, once it gets going, is hard to wipe out entirely. Huge numbers of species, or even entire genera may become extinct, but life as a whole will go on."
In highlighting the resilience of life in general, the research broadens the scope of life beyond Earth, within and beyond the Solar System.
"It is difficult to eliminate all forms of life from a habitable planet," explains Professor Abraham Loeb, co-author and chair of the Astronomy department at Harvard University. "The history of Mars indicates that it once had an atmosphere that could have supported life, albeit under extreme conditions. Organisms with similar tolerances to radiation and temperature as tardigrades could survive long-term below the surface in these conditions. The subsurface oceans that are believed to exist on Europa and Enceladus would have conditions similar to the deep oceans of Earth where tardigrades are found, volcanic vents providing heat in an environment devoid of light. The discovery of extremophiles in such locations would be a significant step forward in bracketing the range of conditions for life to exist on planets around other stars."
Researchers at the University of Tokyo have made a "breathable" nanoscale mesh with an electronic sensor that can be worn on the skin for a week without discomfort, and could potentially monitor a person's health continuously for long periods.
Credit: 2017 Someya Laboratory
A hypoallergenic, electronic sensor can be worn on the skin continuously for a week without discomfort, and is so light and thin that users forget they even have it on, says a group of Japanese scientists. The elastic electrode, constructed of "breathable" nanoscale meshes, holds promise for the development of non-invasive e-skin devices that can monitor a person's health continuously over a long period.
Wearable electronics that monitor heart rate and other health signs have made headway in recent years, with next-generation gadgets employing lightweight, elastic materials attached directly to the skin for more sensitive, precise measurements. However, while the ultrathin films and rubber sheets in these devices adhere and conform well to the skin, their lack of breathability is deemed unsafe for long-term use: dermatological tests show the fine, stretchable materials prevent sweating and block airflow around the skin, causing irritation and inflammation, which could lead to lasting physiological and psychological effects.
"We learned that devices that can be worn for a week or longer for continuous monitoring were needed for practical use in medical and sports applications," says Professor Takao Someya at the University of Tokyo's Graduate School of Engineering. His research group has previously developed an on-skin patch for measuring oxygen in blood.
In their latest research, they developed an electrode constructed from nanoscale meshes containing a water-soluble polymer, polyvinyl alcohol (PVA), and a gold layer – materials considered safe and biologically compatible with the body. The device can be applied by spraying a tiny amount of water, which dissolves the PVA nanofibres and allows it to stick easily to the skin – it will conform seamlessly with curvilinear surfaces of human skin, such as sweat pores and the ridges of fingerprint patterns.
Credit: 2017 Someya Laboratory
The researchers conducted a skin patch test on 20 subjects and detected no inflammation of skin after they had worn the device for a week. The group also evaluated the permeability, with water vapour, of the nanomesh conductor – along with those of other substrates like ultrathin plastic foil and a rubber sheet – and found that its porous mesh structure exhibited superior gas permeability compared to other materials.
Furthermore, the scientists proved the device's mechanical durability through repeated bending and stretching, exceeding 10,000 times, of a conductor attached on the forefinger; they also established its reliability as an electrode for electromyogram recordings when its readings of the electrical activity of muscles were comparable to those obtained through conventional gel electrodes.
"It will become possible to monitor patients' vital signs without causing any stress or discomfort," says Someya about the future applications. In addition to nursing care and medical uses, the new device could enable continuous, precise monitoring of athletes' physiological signals and bodily motion without impeding their training or performance. The team's research is published this week in Nature Nanotechnology.
An array of nanomesh conductors attached to a fingertip, top, and a scanning electron microscope (SEM) image
of a nanomesh conductor on a skin replica, bottom. Credit: 2017 Someya Laboratory.
Researchers have announced the development of a GM banana with higher levels of pro-vitamin A, which could improve the nutritional content of bananas in Africa.
Professor James Dale. Credit: QUT Media
Research by Queensland University of Technology has produced a golden-orange fleshed banana, rich in pro-vitamin A. The decade-long effort, led by Distinguished Professor James Dale, involved extensive laboratory tests at QUT, along with field trials in north Queensland. The results are published in the Plant Biotechnology Journal.
The genetic modification process had resulted in the identification and selection of banana genes that could be used to boost pro-vitamin A in bananas, Professor Dale said. The research, backed with $10 million from the Bill & Melinda Gates Foundation and the UK Government's Department for International Development, ultimately aims to improve the nutritional content of bananas in Uganda, where the fruit is a major staple food in daily diets.
"The East African Highland cooking banana is an excellent source of starch. It is harvested green then chopped and steamed," Professor Dale said. "But it has low levels of micronutrients – particularly pro-vitamin A and iron. The consequences of vitamin A deficiency are severe."
Worldwide, up to 700,000 children die from pro-vitamin A deficiency each year, with a further several hundred thousand going blind, according to the latest available figures.
"What we've done is take a gene from a banana that originated in Papua New Guinea and is naturally very high in pro-vitamin A, but has small bunches, and inserted it into a Cavendish banana," Professor Dale explained. "Over the years, we've been able to develop a banana that has achieved excellent pro-vitamin A levels, hence the golden-orange rather than cream-coloured flesh. Achieving these scientific results, along with their publication, is a major milestone in our quest to deliver a more nutritional diet to some of the poorest subsistence communities in Africa.
"We tried and tested hundreds of different genetic variations here in our lab and in field trials in Queensland until we got the best results. These elite genes have been sent to Uganda in test tubes, where they have been inserted into Ugandan bananas for field trials there."
If all goes according to plan, it is hoped that the new GM bananas could be used commercially in Uganda from 2021.
Scientists at Harvard have used the CRISPR gene-editing system to store a GIF animation in the DNA of bacteria.
For the first time, a primitive movie has been encoded in – and then played back from – DNA in living cells. Scientists funded by the National Institutes of Health say it is a major step toward a “molecular recorder”. In the future, this could make it possible to get read-outs, for example, of the changing internal states of neurons as they develop.
“We want to turn cells into historians,” says neuroscientist Seth Shipman, Ph.D., a post-doctoral fellow at Harvard Medical School, Boston. “We envision a biological memory system that’s much smaller and more versatile than today’s technologies, which will track many events non-intrusively over time.”
This proof-of-concept for a futuristic “molecular ticker tape” was published yesterday in the journal Nature. The ability to record sequential events like a movie at the molecular level could reinvent the concept of recording using molecular engineering, say the researchers. In this scheme, cells themselves could be induced to record molecular events – such as changes in gene expression over time – in their own genomes. Then the information could be retrieved simply by sequencing the genomes of the cells it is stored in.
"If we had those transcriptional steps, we could potentially use them like a recipe to engineer similar cells," added Shipman. "These could be used to model disease – or even in therapies."
The researchers first had to show that DNA can be used to encode not just genetic information, but any arbitrary sequential information into a genome. For this they turned to a revolutionary new gene editing technology, CRISPR. They encoded and retrieved an image of the human hand in DNA inserted into bacteria, before similarly encoding frames from a classic 1870s race horse in motion sequence of photos – an early forerunner of moving pictures.
Over the course of five days, they sequentially treated bacteria with a frame of translated DNA. Afterwards, they were able to reconstruct the movie with 90% accuracy by sequencing the bacterial DNA.
"The sequential nature of CRISPR makes it an appealing system for recording events over time," explained Shipman.
Although this technology could be used in a variety of ways, the researchers ultimately hope to use it to study the brain.
“We want to use neurons to record a molecular history of the brain through development,” said Shipman. “Such a molecular recorder will allow us to eventually collect data from every cell in the brain at once, without the need to gain access, to observe the cells directly, or disrupt the system to extract genetic material or proteins.”
A study of snail neurons, published in Current Biology, suggests memories that trigger anxiety and PTSD could be "erased" without affecting normal memory of past events.
Different types of memories stored in the same neuron of the marine snail Aplysia can be selectively erased, according to a new study by researchers at Columbia University Medical Center (CUMC) and McGill University. Published in Current Biology, the findings suggest that it may be possible to develop drugs to "delete" memories that trigger anxiety and post-traumatic stress disorder (PTSD) without affecting other important memories of past events.
During their experiments, researchers stimulated two sensory neurons connected to a single motor neuron of the snail; one sensory neuron was stimulated to induce an associative memory and the other to induce a non-associative memory. By measuring the strength of each connection, it was found that the increase in the strength of each connection produced by the different stimuli was maintained by a different form of a Protein Kinase M (PKM) molecule (PKM Apl III for associative synaptic memory and PKM Apl I for non-associative). They found that each memory could be erased – without affecting the other – by blocking one of these two molecules.
In addition, they found that specific synaptic memories may also be erased by blocking the function of distinct variants of other molecules that either help produce PKMs or protect them from breaking down.
The researchers say their results could be useful in understanding human memory, because vertebrates have similar versions of the snail proteins that create long-term memories. The PKM-protecting protein KIBRA is also expressed in humans, and mutations of this gene produce intellectual disability.
"Memory erasure has the potential to alleviate PTSD and anxiety disorders by removing the non-associative memory that causes the maladaptive physiological response," says Jiangyuan Hu, PhD, an associate research scientist in the Department of Psychiatry at CUMC and co-author of the paper. "By isolating the exact molecules that maintain non-associative memory, we may be able to develop drugs that can treat anxiety without affecting the patient's normal memory of past events."
"Our study is a 'proof of principle' that presents an opportunity for developing strategies and perhaps therapies to address anxiety," said co-author Samuel Schacher, PhD, a professor of neuroscience in the Department of Psychiatry at CUMC. "For example, because memories are still likely to change immediately after recollection, a therapist may help to 'rewrite' a non-associative memory by administering a drug that inhibits maintenance of non-associative memory."
Future studies in preclinical models are needed, the researchers say, to better understand how PKMs are produced and localised at the synapse before it can be determined which drugs may weaken non-associative memories.
Emma Morano passed away in April. At 117 years old, the Italian woman was the oldest known living human being. Super-centenarians, such as Morano and Jeanne Calment of France – who famously lived to be 122 years old – continue to fascinate scientists and have led them to wonder just how long humans can live for. A study published in Nature last October concluded that the upper limit of human age is peaking at around 115.
Now, however, a new study by McGill University biologists Bryan G. Hughes and Siegfried Hekimi comes to a starkly different conclusion. By analysing the lifespan of the longest-living individuals from the USA, the UK, France and Japan for each year since 1968, Hekimi and Hughes found no evidence for such an upper limit, and if such a maximum exists, it has yet to be reached or identified.
"We just don't know what the age limit might be. In fact, by extending trend lines, we can show that maximum and average lifespans could continue to increase far into the foreseeable future," Hekimi says. Many people are aware of what has happened with average lifespans. In 1920, for example, the average newborn Canadian could expect to live 60 years; a Canadian born in 1980 could expect 76 years, and today, life expectancy has jumped to 82. Maximum lifespan seems to follow the same trend.
It's impossible to predict what future lifespans in humans might look like, Hekimi says. Some scientists argue that technology, medical interventions, and improvements in living conditions could all push back the upper limit.
"It's hard to guess," Hekimi adds. "Three hundred years ago, many people lived only short lives. If we would have told them that one day most humans might live up to 100, they would have said we were crazy."