Earth

Gene therapy generates new neurons to treat Huntington's disease

image: This is a a newly converted neuron (red) surrounded by astrocytes (green).

Image: 
Gong Chen and Zheng Wu

Huntington's disease (HD) is a rare disease characterized by abnormal chorea movement and caused by Huntingtin (Htt) gene mutation and neurodegeneration in a brain area called striatum. A research group led by Dr. Gong Chen, a former professor at Penn State University and now leading a brain repair center at Jinan University in China, has developed a novel gene therapy to regenerate functional new neurons in mouse models of HD. The work has been published in Nature Communications on February 27, 2020.

We are developing a series of NeuroD1-based gene therapies to reprogram brain internal glial cells directly into functional new neurons to treat a variety of brain disorders including Huntington's Disease, Alzheimer's disease, stroke, ALS, and many more," said Dr. Chen. Because every single neuron in our brain is surrounded by supporting glial cells, such direct glia-to-neuron conversion technology offers great advantages over stem cell transplantation therapy in terms of high efficiency of neuroregeneration and no worries about immunorejection," Dr. Chen added.

Dr. Chen is one of the early pioneers making use of brain internal glial cells to regenerate functional new neurons by overexpressing neural transcription factors in the mouse brain. NeuroD1 (neurogenic differentiation 1) is one such factor that promotes neuronal generation during normal brain development. Chen's team has previously demonstrated that expression of NeuroD1 in the mouse brain can directly convert cortical astrocytes (one subtype of glial cells) into functional neurons (Guo et al., Cell Stem Cell, 2014; Chen et al., Molecular Therapy, 2019; Zhang et al., BioRxiv, 2018). Recently, Chen's group further reported, for the first time, that such direct astrocyte-to-neuron conversion can be successfully reproduced in non-human primate brains (Ge et al., BioRxiv, 2019).

Chen's team has previously found that NeuroD1-generated neurons are mainly glutamatergic neurons, which account for more than 80% of the total neurons in the human brain and are the major driving force of brain activity. However, HD is caused by degeneration of GABAergic neurons, which is a type of inhibitory neurons that account for more than 90% of the neurons in the striatum region. In order to generate GABAergic neurons, we combined NeuroD1 together with another transcription factor Dlx2, which is known to generate GABAergic neurons during early brain development, and successfully converted striatal astrocytes into GABAergic neurons in HD mice," said the first author of this article Dr. Zheng Wu. Importantly, here we used the adeno-associated virus (AAV) vectors, which have been approved by FDA as a common gene therapy vector in many clinical trials, to develop a novel gene therapy for the treatment of HD," Dr. Wu emphasized on the AAV gene therapy approach.

In this HD mouse study, Dr. Chen and colleagues reported that 80% of the AAV-infected striatal astrocytes were directly converted into GABAergic neurons and the remaining astrocytes can proliferate to replenish themselves. Essentially all of the newly generated neurons are electrophysiologically functional, forming synaptic connections with other neurons. They further demonstrated that the newly generated neurons can project their axons to the right target areas, suggesting that they have integrated into global brain circuits. The most exciting findings of this HD study are the significant motor functional recovery and remarkable extension of life span among the gene therapy-treated HD mice," Chen said.

Our regenerative gene therapy approach is different from conventional gene therapy that typically aims at the mutant genes by either correcting the gene mutations or reducing the mutant gene product, such as reducing mHtt aggregates in HD patients," Dr. Chen said. Obviously, reducing mHtt aggregates at early stage might slowdown the disease progression but it cannot regenerate new neurons for the late stage patients. An ideal approach may be to combine our neuroregenerative approach together with gene correction technology to generate healthy new neurons in future studies," concluded Dr. Chen.

Credit: 
Guangdong-Hongkong-Macau Institute of CNS Regeneration, Jinan University

Extinction resistance, not speciation, shaped ecologically diverse modern marine fauna

Ecologically diverse clades came to dominate the modern oceans because they were better buffered against the successive mass extinctions events which reshaped marine animals over evolutionary time - not because of their higher rates of speciation, according to a new study. The findings overturn a long-held understanding of the role of ecology in the evolution of animal life. In the modern ocean, ecological differentiation and taxonomic diversity are closely correlated. However, the origin and nature of the relationship between the two remains unresolved. For decades it's been broadly assumed that the divergence of a species into different ecological niches (ecological differentiation) is required to fuel species origination, leading to greater taxonomic diversity within ecosystems. Thus, for many clades, ecological differentiation is often thought to be the cause and/or consequence of high speciation rate. However, this hypothesis has been difficult to test, particularly across paleontological timescales and the extinction events that punctuate the history of animal life on Earth. Matthew Knope and colleagues used a comprehensive data set featuring both living (30,074) and fossil (19,992) marine animals to evaluate the relationship between ecological and taxonomic diversity and how it evolved from the late Cambrian to the present day. According to Knope et al., the relationship is more complex than expected and the findings suggest that the cumulative effect of mass extinctions played a crucial role in creating the strong correlation between ecological diversity and genus richness observed in modern oceans. Contrary to the prevailing hypothesis, the authors found that ecological differentiation in marine animal classes was instead associated with lower rates of species origination and that ecologically diverse classes are the most genus-rich today because they have been buffered against extinction. The results show that the observed strong association between ecological differentiation and taxonomic diversity is a relatively recent development, though shaped over 500 million years of evolutionary history.

Credit: 
American Association for the Advancement of Science (AAAS)

Early intervention following traumatic brain injury reduces epilepsy risk

image: Viji Santhakumar is an associate professor at UC Riverside and an expert on traumatic brain injury and epilepsy.

Image: 
I. Pittalwala, UC Riverside.

RIVERSIDE, Calif. -- A research team led by a scientist at the University of California, Riverside, has found that brains treated with certain drugs within a few days of an injury have a dramatically reduced risk of developing epilepsy later in life.

The development of epilepsy is a major clinical complication after brain injury, and the disease can often take years to appear.

"Working on rats, whose immune response system models that of humans, we identified that after brain injury a certain immune system receptor makes the brain more excitable, which promotes development of epilepsy," said Viji Santhakumar, an associate professor of molecular, cell, and systems biology at UC Riverside and the lead author of the study that appears in the Annals of Neurology. "If this receptor can be suppressed, preferably within a day after injury, the future development of epilepsy can be reduced if not entirely prevented."

The receptor in question is the Toll-like receptor 4, or TLR4, an innate immune receptor. Following a brain injury, TLR4 increases excitability in the dentate gyrus of the hippocampus, the brain structure that plays a major role in learning and memory.

Santhakumar explained two factors are involved in brain injury: a neurological complication and the immune system. These factors have traditionally been studied separately, she said.

"Our team, however, studied these factors together," she added. "This approach helped us understand that the immune system operates through a very different mechanism in the injured brain than in the uninjured brain. Understanding the difference can guide us on how best to target treatments aimed at preventing epilepsy after traumatic brain injury."

The team specifically studied concussions, the kind suffered by many football players, which can lead to cell death in the hippocampus, affecting the processing of memory. Cell death activates the immune system, including TLR4. TLR4, in turn, increases excitability in the hippocampus.

"What our rat studies on traumatic brain injury show is that if we target early changes in excitability, we can alter long-term pathology," Santhakumar said. "Blocking TLR4 signaling shortly after brain injury reduces neuronal excitability in the hippocampus and seizure susceptibility. This seizure susceptibility is not reduced if we delay the blocking of TLR4 signaling after injury."

Paradoxically, Santhakumar's team found that drugs such as Resatorvid, which block TLR4 in the injured brain, caused epilepsy in uninjured brains.

"This paradox is difficult to understand," Santhakumar said. "We are currently looking at molecular signaling pathways in injured and uninjured brains to make sense of it."

The study could have important implications for war veterans returning home with brain injuries.

"Most often, the consequences of their injuries don't show up a year later, but several years later," said Santhakumar, who came to UCR in 2018 from Rutgers University.

The study focused only on epilepsy, one of several pathologies that can follow brain injury.

"Deficits in memory, cognition, and social behaviors could also follow brain injury," Santhakumar said. "In future work, we plan to study co-morbidities associated with traumatic brain injury."

Credit: 
University of California - Riverside

Big data helps farmers adapt to climate variability

image: The study shines a light on how big data and digital technologies can help farmers better adapt to threats -- both present and future -- from a changing climate.

Image: 
Michigan State University

EAST LANSING, Mich. - A new Michigan State University study shines a light on how big data and digital technologies can help farmers better adapt to threats -- both present and future -- from a changing climate.

The study, published in Scientific Reports, is the first to precisely quantify soil and landscape features and spatial and temporal yield variations in response to climate variability. It is also the first to use big data to identify areas within individual fields where yield is unstable.

Between 2007 and 2016, the U.S. economy took an estimated $536 million economic hit because of yield variation in unstable farmland caused by climate variability across the Midwest. More than one-quarter of corn and soybean cropland in the region is unstable. Yields fluctuate between over-performing and underperforming on an annual basis.

Bruno Basso, MSU Foundation professor of earth and environmental sciences, and his postdoctoral research fellow, Rafael Martinez-Feria, set out to address the key pillars of the National Institute for Food and Agriculture's Coordinated Agricultural Project that Basso has led since 2015.

"First, we wanted to know why -- and where -- crop yields varied from year to year in the corn and soybean belt of the U.S.," Basso said. "Next, we wanted to find out if it was possible to use big data to develop and deploy climate-smart agriculture solutions to help farmers reduce cost, increase yields and limit environmental impact."

Basso and Martinez-Feria first examined soil and discovered that alone, it could not sufficiently explain such drastic yield variations.

"The same soil would have low yield one year and high yield the next," Basso said. "So, what is causing this temporal instability?"

Using an enormous amount of data obtained from satellites, research aircraft, drones and remote sensors, and from farmers via advanced geospatial sensor suites present in many modern combine harvesters, Basso and Martinez-Feria wove big data and digital expertise together.

What they found is that the interaction between topography, weather and soil has an immense impact on how crop fields respond to extreme weather in unstable areas. Terrain variations, such as depressions, summits and slopes, create localized areas where water stands or runs off. Roughly two-thirds of unstable zones occur in these summits and depressions and the terrain controls water stress experienced by crops.

With comprehensive data and the technology, the team quantified the percentage of every single corn or soybean field in the Midwest that is prone to water excess or water deficit. Yields in water-deficient areas can be 23 to 33% below the field average for seasons with low rainfall but are comparable to the average in very wet years. Areas prone to water excess experienced yields 26 to 33% below field average during wet years.

Basso believes their work will help determine the future of climate-smart agriculture technologies.

"We are primarily concerned with helping farmers see their fields in a new manner, helping them make better decisions to improve yield, reduce cost and improve environmental impact," Basso said. "Knowing that you have an area shown to be water deficient, you will plan your fertilizer applications differently. The amount of fertilizer for this area should be significantly lower than what you would apply in areas of the same field with more water available to the plants."

Credit: 
Michigan State University

Study reveals how green space can reduce violent crime

image: 'All of us had some sort of experience [with crime], personally or through family members. And we thought maybe we can do something about it,' said Hessam Sadatsafavi, PhD, of the University of Virginia School of Medicine.

Image: 
Dan Addison | UVA Communications

Properly designed and maintained outdoor green space has the potential to reduce violent crime and gun violence, to make communities safer and keep residents healthier, a new study suggests. Conversely, green space that is poorly designed and inadequately maintained can help crime take root and spread.

The findings come from a team of scientists that has assembled a big-picture review of research on the complicated relationship between nature and crime in urban areas. They identified several patterns that can help inform public policy, guide urban design and promote neighborhoods that are safe and pleasant to live in.

The project came about because members of the research team had been touched by crime, either directly or indirectly. "All of us had some sort of experience, personally or through family members. And we thought maybe we can do something about it," said Hessam Sadatsafavi, PhD, of the School of Medicine. "How to control violent crime is a polarizing issue. We are interested to see, as designers whose work is to shape the physical environment, if it's possible for us to contribute to this conversation and to take some actions to see if we, personally, can contribute to reducing crime."

The Weed of Crime Bears Bitter Fruit

The research, initiated at Cornell University, sought to synthesize the findings of many previous studies that looked at the effects of various forms of green space on crime and criminal behavior. "We said, OK, we have to start by understanding what is out there in terms of theory, what other people have found," Sadatsafavi said. "Green space can be a source of or increase the risk of crime in a neighborhood through some mechanism, and it can also reduce the risk. So why is that happening? Is there any way to find a solution to make the risk reduction more effective?"

The researchers initially considered more than 14,000 papers but ultimately winnowed those down to 45 done in the United States, which offered the most relevant insights into how access to nature might improve public safety.

The initial review was challenging because the topic is vast and can be approached from many angles. "You might talk about community gardens, you might talk about people's lawns," Sadatsafavi explained. "People who do the studies might go out and count the number of trees on sidewalks, or examine satellite images. Or look at the number of vacant lots that were turned into green space."

That, combined with the wide variety of crime examined and how it was reported, made it difficult for the researchers to draw specific conclusions. "But," Sadatsafavi said, "there are definitely patterns."

For example, nine studies looked at the effect of green space on gun violence. Six found that such interventions reduced crime, while three were inconclusive. "There is evidence that greening interventions at the urban level reduces violent crime, specifically gun violence," said Sadatsafavi, of UVA's Department of Emergency Medicine.

"By looking at all these studies, we were able to propose possible pathways [to reduce crime and] put together an overall picture of why this is happening, both in terms of gun violence and in terms of overall crime rate."

Using Nature to Reduce Crime

Sadatsafavi hopes that the researchers' findings, outlined in a paper in the International Journal of Environmental Research and Public Health, will lead to community interventions that keep people safe, decrease crime and promote better quality of life.

"The dream scenario for me, personally, is to raise awareness about the effectiveness and the cost effectiveness of these strategies," he said. "Our next goal as a team is to develop design guidelines for, say, how a community garden or small community park should be designed, to improve the positive effects of the green space and provide practical, hands-on information for people who are in the field, whether landscape architects or people who are starting their own community garden."

Credit: 
University of Virginia Health System

Anthropogenic seed dispersal: rethinking the origins of plant domestication

image: A photo of an ear from a wild barley plant, with the ripe seeds naturally shattering off due to the brittle rachis or stem structure at their base. In the wild, this brittle rachis allows the plant to spread its seed up to two meters from the parent plant, which is a rather weak dispersal mechanism and not characteristic of the other crop progenitor plants. The barley that we eat today evolved tougher rachises as part of the mutualistic relationship they evolved with humans. Humans have dispersed barley plants all over the world.

Image: 
Robert Spengler

The plants we consume for food have changed drastically in the 10,000 years since humans began practicing agriculture, but hominids have been intensively interacting with the plants and animals around them since before the dawn of our species. As humans became aware of the ability to modify crops through selective breeding, the evolution of new traits in plants greatly increased. However, plants have been evolving in response to human selective pressures since long before people began consciously altering them through breeding.

In a new study published in Trends in Plant Science, Dr. Robert Spengler examines these evolutionary responses and theorizes that all of the earliest traits to evolve in the wild relatives of modern domesticated crops are linked to human seed dispersal and the evolutionary need for a plant to spread its offspring.

Domestication syndrome and the emergence of similar traits

Many of the earliest traits of domestication in plants are similar across different crop species, a phenomenon evolutionary biologists refer to as parallel evolution. For example, in all large-seeded grass crops - e.g. wheat, barley, rice, oats - the first trait of domestication is a toughening of the rachis (the individual stem that holds a cereal grain to the ear). Likewise, in all large-seeded legumes, such as peas, lentils, fava beans, and kidney beans, the earliest trait of domestication is a non-shattering pod.

Archaeobotanists studying early plant domestication agree that the evolution of tougher rachises in cereal crops was a result of humans using sickles to harvest grains. During a harvest, the specimens with the most brittle rachises lost their seeds, whereas the plants with tougher rachises benefited from having their seeds protected and saved for the following year. Humans then cleared away competitive plants (weeding), tilled soil, sowed seeds, and maintained the crops until the next harvest. We can assume that the same process occurred for legumes.

For nearly a century, scholars have been aware of the fact that this parallel evolution was the result of similar selective pressures from people in different centers of domestication around the world, leading to what many researchers call "domestication syndrome." In the simplest biological sense, Spengler suggests, humans provide better seed-dispersal services for food crops than those plants would have had in the wild, causing them to evolve traits that facilitated agriculture and improved their own chances of reproduction.

The Evolution of Seed-Dispersal Traits in Crops

Archaeobotanists have studied seed-dispersal traits in the wild relatives of cereal and legume crops, but few have discussed how the wild relatives of other crops dispersed their seeds. In this manuscript, Spengler steps away from the heavy focus on these few plants and looks at the wild seed-dispersal processes in other crops.

Spengler notes that before the last Ice Age, megafaunal mammals, including humans, were key for the evolution of larger fruits in the wild. While some plants have mechanical methods of seed dispersal, the most common way plants spread their seeds is by recruiting animals to do it for them. Bright red cherries, for example, have evolved to entice birds with red-green color vision. The birds consume the sugary fruit, then fly to a new area and deposit the seed from the cherry. Larger fruits, however, require larger animals to distribute them, meaning the progenitor plants for most of the fruits in our produce markets today evolved to be spread by large mammals. Paleontologists have previously noted the parallel evolution of larger fruits to entice larger animals in many unrelated plant families, a process that Spengler reveals to be mirrored in the evolution of crops cultivated by humans.

Spengler also theorizes that megafaunal mammals may have been key to the dispersal of seeds in the progenitors of small-seeded grains, such as quinoa, millets, and buckwheat. With smooth, hard-shelled seeds that grow at the top of the plant, no secondary defensive compounds or thorns, and a rapid rate of growth, the foliage of these plants are the perfect food for grazing animals. The small size of these wild seeds may have been an evolutionary adaptation that allowed them to pass successfully through the digestive systems of hooved mammals, which often only allow seeds smaller than 2mm to pass. Conceptualizing domestication as seed-dispersal based evolution, as Spengler proposes, explains why the first traits of domestication in all of the small-seeded annual crops were thinning of the seed coat, an increase in seed size, and breaking of dormancy - a reversal of the traits that allowed for seed dispersal by grazing mammals. The domestication process severed the mutualistic ties these plants had with their wild seed dispersers and made them dependent upon humans for dispersal.

Understanding Plant Domestication as Seed-Dispersal-Based Mutualism

During the Early and Mid-Holocene, plants in specific locations around the world started to evolve new traits in response to human cultivation practices. As human populations increased in size and became more concentrated, the selective pressures that people placed on these plants increased. In the wild, plants often evolve mutualistic relationships in response to heavy herbivory pressures. The same evolutionary responses, Spengler argues, can be seen in farmers' fields during the early steps towards domestication, with plants developing traits to better use humans as seed dispersers.

"Humans are the best seed dispersers that have ever existed, dispersing plant species all over the world," Spengler says. "We are currently removing all competitive plant species across the Amazon to spread soybean seeds - a plant that originally evolved traits for a mutualistic relationship with humans in East Asia. Likewise, most of the prairies of the American Midwest have been removed in order to grow maize, a crop that evolved to recruit humans in tropical southern Mexico. Humans are powerful seed dispersers and plants will readily evolve new traits to spread their seeds and colonize new areas more successfully."

Dr. Spengler is the director of the archaeobotanical laboratories at the Max Planck Institute for the Science of Human History in Jena, Germany. "It is important look at the domestication of plants from an evolutionary ecology perspective and seek to find parallels between the evolution of plants in the wild and during early cultivation," says Spengler. "By modeling domestication as an equivalent process to evolution in the wild and setting aside the idea of conscious human innovation, we can more effectively study the questions of why and how this process occurred."

Credit: 
Max Planck Institute of Geoanthropology

Mount Sinai researchers discover new approach for use of stem cells to improve bone marrow transplantation

Mount Sinai researchers have discovered a way to enhance the potency of blood-forming stem cells, potentially opening the door to a new approach for bone marrow transplantation, according to a study published on February 27 in Cell Stem Cell.

The scarcity of blood-forming stem cells, known as hematopoietic stem cells (HSCs), severely limits bone marrow transplantation, which can cure many blood disorders and solid tumors. The Mount Sinai team reports that manipulation of metabolic activity around lysosomes, the storage and recycling centers within cells, can increase by more than 90-fold the potency of blood-forming stem cells in bone marrow transplantation.

"Hematopoietic stem cells lose their stem cell potential once they're cultured in a dish, which limits their ability to be easily propagated in the laboratory," says Saghi Ghaffari, MD, PhD, Professor of Cell, Developmental and Regenerative Biology in the Black Family Stem Cell Institute and The Tisch Cancer Institute at the Icahn School of Medicine at Mount Sinai, and lead investigator of the study. "In order for these stem cells to maintain optimal potency, they shouldn't be constantly dividing--putting them under metabolic stress that can alter their health and longevity. Instead, they should be in a dormant, or quiescent, state. But maintaining quiescence of blood stem cells outside of the body has been challenging. We discovered that lysosomes are key to the dormancy of these cells. We further learned that repressing lysosomal activity--rather than their stimulation--enhances stem cell quiescence and potency, and may have therapeutic value."

Through their extensive in vivo work in mice, the Mount Sinai scientists used an effective and specific lysosomal inhibitor that reduces lysosomal acidity and amino acid release in the cells. The net effect is to restore stem cells with activated lysosomes to a quiescent state. The study further found that the inhibition of glycolysis--the breakdown of glucose and other sugars by enzymes--also enhances quiescence and potency of hematopoietic stem cells, which are believed to rely on glycolysis for their energy.

Scientists have been trying for years to generate more HSCs in the laboratory for clinical use. "Our methodology is different from others in that it is based on quality rather than quantity," explains Dr. Ghaffari, a stem cell biologist and recognized expert in blood disorders. "By restraining lysosomal activity we produce fewer blood-forming stem cells for bone marrow transplantation, but they work much better because we've preserved and enhanced their potency."

This work could be used to generate blood stem cells from cultured pluripotent stem cells (master cells that can be turned into any type of mature cell), or to enhance the function of human blood stem cells for bone marrow transplantation, something that is being attempted in Dr. Ghaffari's lab. It has also led to many new questions regarding the contribution of lysosomes to stem cell quiescence and potency and their potential therapeutic applications. Still another impact of her lab's work could be identifying and targeting stem cells that propagate blood malignancies, including leukemia.

Credit: 
The Mount Sinai Hospital / Mount Sinai School of Medicine

Extra olive virgin oil keeps healthy properties when used for cooking

image: Researchers simulated the cooking conditions of a domestic kitchen. The aim was to see how the homemade sauté affects the polyphenols of extra virgin olive oil.

Image: 
UNIVERSITY OF BARCELONA

Consuming extra virgin olive oil has proved to have protecting effects for the health, especially due to its antioxidant content. However, there are not many studies on whether it is the best oil to use when cooking. A study by the University of Barcelona stated this kind of oil keeps the levels of antioxidants -regarded as health- when used for cooking, a common technique in the Mediterranean cuisine. These results could be relevant for future recommendations or nutritional guidelines.

The study, published by the journal Antioxidants, counts on the participation of a team of researchers from the Faculty of Pharmacy and Food Sciences of the UB, the Physiopathology of Obesity and Nutrition Networking Biomedical Research Centre (CIBERobn) and the University of São Paulo.

Simulation of cooking conditions in a domestic kitchen

Extra virgin olive oil is the main source of fat of the Mediterranean diet and shows a unique composition of fatty acids with a higher content of antioxidants than other edible oils. Its benefits for the health are mainly linked to these compounds, named polyphenols. "The effects of cooking on these polyphenols of oil have always been studied in a laboratory or industrial situation, which is far from the reality of our homes", says Rosa M. Lamuela, director of the Institute in Research on Nutrition and Food Safety (INSA-UB).

For this study, however, researchers simulated the cooking conditions of a domestic kitchen. The aim was to see how the homemade sauté affects the polyphenols of extra virgin olive oil. Researchers studied the effects of time -during a short and a long period of time- and temperature -at 120ºC and 170ºC- in the degradation of the antioxidants.

Results show that during the cooking process, the content of polyphenols decreased by 40% to 120ºC and by 75% at 170ºC, compared to the levels of antioxidants in raw oil. Moreover, the cooking time had an effect on individual phenols, such as hydroxytyrosol, but not on the total content of the phenol. As a whole, the levels of antioxidants keep fulfilling the parameters stated as healthy by the European Union: "Despite the decrease in concentration of polyphenols during the cooking process, this oil has a polyphenol level that reaches the declaration of health in accordance to the European regulation, which means it has properties that protect oxidation of LDL cholesterol particles", notes Julián Lozano, first signer of the publication, which is also part of his doctoral thesis.

Olive oil in Mediterranean cuisine

The Mediterranean diet, known for a high use of phytochemicals from vegetables, fruits and legumes, has been correlated to improvements in cardiovascular and metabolic health. This link is based on the results of the PREDIMED study, a multicenter clinical study conducted from 2003 to 2011 with more than 7,000 people, in which Rosa M. Lamuela took part as well.

However, the effects on health in the Mediterranean diet have been hard to reproduce in non-Mediterranean populations. According to the researchers, this fact could occur due to, probably, differences in cooking practices. In this context, the results are added to previous studies by the research group which analyzed the effects of extra virgin olive oil in the sauté -with positive results. Thus, this strengthens the idea of the Mediterranean gastronomy being beneficial for our health, not only for its food but also for the ways of cooking it.

According to the authors, the current objective is to analyze the effects of cooking with extra virgin olive oil with other food elements, such as legumes, meat, etc. "Moreover, we should conduct random research studies in humans, in which we would compare the potential benefits we obtain when cooking with quality extra virgin olive oil compared to other oils", concludes the researcher.

Credit: 
University of Barcelona

Bacteria loop-the-loop

image: Computer simulation by the Göttingen research team: a bacterium propelling itself along using flagella pointing forwards and behind.

Image: 
Sarah Mohammadinejed, University of Göttingen

The magnetotactic bacterium Magnetococcus marinus swims with the help of two bundles of flagella, which are thread-like structures. The bacterial cells also possess a sort of intracellular "compass needle", meaning that their movements can be controlled using a magnetic field. This means they can be used as a biological model for microrobots. An international team from the University of Göttingen, the Max Planck Institute of Colloids and Interfaces in Potsdam and the CEA Cadarache (France) has now found out how these bacteria move and determined their swimming speed. The results have been published in the scientific journal eLife.

The researchers used a combination of new experimental methods and computer simulations: they tracked the movement of the "microswimmers" using three-dimensional microscopy and analysed them using very high-frequency dark-field imaging. A team from the University of Göttingen supplemented the work with simulations to find out which mechanism is responsible for driving the observed swimming paths in the bacteria.

The results are astonishing: the two bundles of flagella, which are anchored close together on the cell body, point in opposite directions when swimming. This causes the bacterial cell to be pulled by one bundle and pushed by the other. This kind of propulsion has never been observed in any other microorganism. The resulting swimming paths describe double or even triple loops. In a way, the bacterium loops the loop as it moves forward. The actual speed is even greater than you might think, as the spiralling motion increases the distance covered considerably. The real speed is in the range of 400 to 500 microns (millionths of a meter) per second. The bacteria, which are about 1 micrometer in size, thus move over 500 body lengths per second. In comparison, Olympic swimmers only manage one body length per second.

What is the purpose of this unusual swimming method? "We assume that this type of swimming is advantageous in an environment full of sediment and other obstacles that can be bypassed by performing loops", says Professor Stefan Klumpp from the Institute for Dynamics of Complex Systems at the University of Göttingen. "This special feature could also be exploited in medical microrobotics to move around in patients' blood and, for example, quickly reach a tumour. In fact, these bacteria move into anaerobic environments by themselves. They could therefore bring chemotherapy drugs directly into the vicinity of a tumour, which is also an oxygen-deficient environment."

Credit: 
University of Göttingen

Sensor cube helps keep fish farming afloat

image: Nazek El-Atab with the team's multisensory system.

Image: 
© 2020 KAUST

Solar-powered water quality sensors could help fish farmers protect their aquatic assets and safeguard the future of food.

Aquaculture currently supplies more than half of the world's seafood, and in the last 10 years, the profits from global fish farming have quadrupled to more than $230 billion annually. However, pollution from industrial activities is seeping into commercial ponds and killing off millions of dollars' worth of fish. Agricultural fertilizers, for example, increase nutrients in the water leading to algal blooms. As the algae decomposes it uses up the oxygen supply, causing the fish to suffocate.

By keeping an eye on water quality, fish farmers can act when harmful levels of pollution are detected. However, most commercial sensors only monitor one thing at a time, such as acidity or oxygen levels, on individual devices that the farmer must check manually. The multifunctional alternatives are bulky, expensive and need an expert operator.

Creating electronic devices that do several things at once is challenging, and there is often a tradeoff between quality and quantity of functions. Electrical engineer Muhammad Hussain and his team created a small self-powered sensor that monitors multiple water quality characteristics and transmits the data via Bluetooth.

The researchers built this multisensory system using a multidimensional integrated circuit (MD-IC). "Integrating different functions on to one computer chip is complex and expensive," lead author Nazek El-Atab explains. "But we have combined several chips into a cube so that each face serves a different purpose." The connected chips then act as one device.

The cube is designed to float with the sensors for pH, temperature, salinity and ammonia levels on the downward facing side. The casing is weighted to ensure it remains that way, even when disturbed by fish. "We wanted to create something small and light weight," says Nazek. "The farmer can simply throw the device into the water, and it rotates itself into the right position".

The other outer faces include sensors that monitor air pollution, solar cells to charge the battery sealed within the cube, and an antenna for transmitting data via Bluetooth to a mobile phone. "The concept of MD-ICs is unique, as it opens up opportunities for single devices with internet of things applications," explains Hussein. "And water is always an intriguing medium for electronics," he adds.

Preventing unnecessary fish deaths is a crucial step toward food security. "Saudi Arabia is investing 3.5 billion US dollars in aquaculture so it can produce 600,000 tons of seafood each year by 2030," says Nazek. The team hope their sensors will support this goal but also believes the little cubes could have a big future beyond the fish farm. "They could be sent down oil pipes to collect data on oil quality," she adds. The researchers are working on improving the device's self-cooling technology to stop it from overheating, and the next step will be to test it in the field.

Also important for the research was the assistance of the visiting undergraduate summer interns from Princess Noura University, the largest women's university in Saudi Arabia. "This exemplifies the commitment of KAUST to collaborate with in-Kingdom universities," Hussein says.

Credit: 
King Abdullah University of Science & Technology (KAUST)

New method converts carbon dioxide to methane at low temperatures

image: Hydrogenation of CO2 to CH4

Image: 
Sekine Laboratory, Waseda University

A new method developed by a team of Waseda University scientists led by Professor Yasushi Sekine may contribute to reducing the use of fossil fuels and help prevent global warming in the long-run.

The conversion of carbon dioxide to valuable chemicals such as methane has drawn great attention for use in supporting carbon capture and utilization. Especially, methane can be used not only as fuel but also as a hydrogen carrier, transporting town gas to existing infrastructure. For instance, some plants in Germany have already been launched based on the Power to Gas concept, which allows energy from electricity to be stored and transported in the form of compressed gas.

"To recycle carbon dioxide into methane, an established industrial method involves the reaction of hydrogen and carbon dioxide using a ruthenium-based catalyst at temperatures of 300 to 400 degrees Celsius, but this method limited how much and when methane could be produced since it requires such high temperature," Sekine says. "Additionally, operation at low temperatures was demonstrated to be favorable to improve carbon dioxide conversion and increase the amount of methane produced."

In this newly-developed method reported in Chemistry Letters, carbon dioxide can be converted into methane more efficiently and quickly in the 100 degrees Celsius range.

"This method involves a reaction of nanoparticles called cerium oxide with carbon dioxide in presence of ruthenium catalyst with an electric field," explains Sekine. "The results show that the catalyst exhibited high and stable catalytic activity for converting carbon dioxide to methane through hydrogenation with the electric field."

With this novel method, methane could be produced from carbon dioxide collected from the atmosphere, possibly enabling an unlimited amount of methane production by recycling carbon dioxide from the atmosphere released from factories into valuable energy resources.

Credit: 
Waseda University

Rare lizard fossil preserved in amber

image: A tiny lizard forefoot of the genus Anolis is trapped in amber that is about 15 to 20 million years old.

Image: 
© Foto: Jonas Barthel

The tiny forefoot of a lizard of the genus Anolis was trapped in amber about 15 to 20 million years ago. Every detail of this rare fossil is visible under the microscope. But the seemingly very good condition is deceptive: The bone is largely decomposed and chemically transformed, very little of the original structure remains. The results, which are now presented in the journal "PLOS ONE", provide important clues as to what exactly happens during fossilization.

How do fossils stay preserved for millions of years? Rapid embedding is an important prerequisite for protecting the organisms from access by scavengers, for example. Decomposition by microorganisms can for instance be prevented by extreme aridity. In addition, the original substance is gradually replaced by minerals. The pressure from the sediment on top of the fossil ensures that the fossil is solidified. "That's the theory," says Jonas Barthel, a doctoral student at the Institute for Geosciences at the University of Bonn. "How exactly fossilization proceeds is currently the subject of intensive scientific investigation."

Amber is considered an excellent preservative. Small animals can be enclosed in a drop of tree resin that hardens over time. A team of geoscientists from the University of Bonn has now examined an unusual find from the Dominican Republic: The tiny forefoot of a lizard of the genus Anolis is enclosed in a piece of amber only about two cubic centimeters in size. Anolis species still exist today.

Vertebrate inclusions in amber are very rare

The Stuttgart State Museum of Natural History has entrusted the exhibit to the paleontologists of the University of Bonn for examination. "Vertebrate inclusions in amber are very rare, the majority are insect fossils," says Barthel. The scientists used the opportunity to investigate the fossilization of the seemingly very well preserved vertebrate fragment. Since 2018 there is a joint research project of the University of Bonn with the German Research Foundation, which contributes to the understanding of fossilization using experimental and analytical approaches. The present study was also conducted within the framework of this project.

The researchers had thin sections prepared for microscopy at the Institute for Evolutionary Biology at the University of Bonn. The claws and toes are very clearly visible in the honey-brown amber mass, almost as if the tree resin had only recently dripped onto them - yet the tiny foot is about 15 to 20 million years old.

Scans in the micro-computer tomograph of the Institute for Geosciences revealed that the forefoot was broken in two places. One of the fractures is surrounded by a slight swelling. "This is an indication that the lizard had perhaps been injured by a predator," says Barthel. The other fracture happened after the fossil was embedded - exactly at the place where a small crack runs through the amber.

Amber did not protect from environmental influences

The analysis of a thin section of bone tissue using Raman spectroscopy revealed the state of the bone tissue. The mineral hydroxyapatite in the bone had been transformed into fluoroapatite by the penetration of fluorine. Barthel: "This is surprising, because we assumed that the surrounding amber largely protects the fossil from environmental influences." However, the small crack may have encouraged chemical transformation by allowing mineral-rich solutions to find their way in. In addition, Raman spectroscopy shows that collagen, the bone's elastic component, had largely degraded. Despite the seemingly very good state of preservation, there was actually very little left of the original tissue structure.

"We have to expect that at least in amber from the Dominican Republic, macromolecules are no longer detectable," says the supervisor of the study, Prof. Dr. Jes Rust from the Institute for Geosciences. It was not possible to detect more complex molecules such as proteins, but final analyses are still pending. The degradation processes in this amber deposit are therefore very advanced, and there is very little left of the original substance.

Acids in tree resin attack bone

Amber is normally considered an ideal preservative: Due to the tree resin, we have important insights into the insect world of millions of years. But in the lizard's bone tissue, the resin might even have accelerated the degradation processes: Acids in the tree secretion have probably attacked the apatite in the bone - similar to tooth decay.

Credit: 
University of Bonn

Physics meets brain science in Denver

image: Research from the session Architectural Principles and Predictive Modeling of the Mammalian Connectome

Image: 
Sz. Horvat (Center for Systems Biology, Dresden), F. Molnar and Z. Toroczkai (Univ. Notre Dame)

Please Note: The 2020 American Physical Society (APS) March Meeting that was to be held in Denver, Colorado from March 2 through March 6 has been canceled. The decision was made late Saturday (February 29), out of an abundance of caution and based on the latest scientific data available regarding the transmission of the coronavirus disease (COVID-19). See our official release on the cancelation for more details.

DENVER, COLO., FEBRUARY 28, 2020 -- Understanding the brain has been one of science's greatest challenges. Each discovery only seems to raise countless other questions about the inner workings of this incredibly complex organ. Brain research brings together disciplines like neuroscience, medicine, biochemistry, and even physics. At the 2020 American Physical Society March Meeting in Denver, scientists will present their latest research on the physics of the brain.

Mapping the Mammalian Connectome

University of Notre Dame researcher Zoltan Toroczkai will describe his work on mapping the physical connections between different areas of the brain. In particular, he is interested in which brain networks have been evolutionarily conserved across mammalian species, including our own.

"Our goal is to understand how the brain works, and for this, we need to understand how the brain is connected," said Toroczkai, a professor of physics, computer science, and engineering. "With this connectivity data, we want to look for any regularity in how the brain is wired."

Despite huge variations in the brain sizes of mammals, he and his collaborators have discovered that the organization of the brain follows a principle called the Exponential Distance Rule. It states that the wiring probability between two cortical areas decreases exponentially the further away they get from one another.

Shaping the Little Brain

Despite its small size, the human cerebellum--Latin for "little brain"--contains more neurons than the rest of the brain. It manages our body's muscle coordination and sense of balance. Like the cerebrum, it has two hemispheres, lobes that branch into smaller lobes, and intricate surface folds that form during the early stages of growth.

Jennifer Schwarz, a physicist at Syracuse University, investigates how the cerebellum gets its convoluted shape. She will report on a new "buckling without bending" model that predicts the formation of its intricate folds, lobes, and other morphological features.

Schwarz's model consists of a rigid core of cells surrounded by a fluid-like cortical layer of dividing cells. Shape change occurs as a result of mechanical constraints on the outer cortical layer as it continues to grow. The findings have possible implications for brain folding-related diseases, and additional applications for shape development in other parts of the body like the retina.

How Music Heals the Brain

Our brains respond to music in different ways. That may explain why music therapy works for some patients and not others, suggests new research by Rice University's Melia Bonomo, a PhD candidate in applied physics.

Bonomo and her colleagues scanned the brains of healthy people while they listened to their favorite song, familiar and unfamiliar music, and speech recordings. They found individual differences in whole-brain connection patterns and co-activation of regions responsible for autobiographical memory, prospection, and processing emotion.

As a next step, she wants to investigate whether these neural activity patterns could be used to find auditory stimuli that could successfully boost music therapy outcomes.

"In the short term, we're applying the results to a clinical trial that we've just started to test the mental health benefits of participating in a six-week creative music course for patients with mild cognitive impairment," she said.

Credit: 
American Physical Society

Intensive blood pressure control can extend life up to 3 years

Boston, MA -- A new study by investigators at Brigham and Women's Hospital puts the results of a landmark trial about blood pressure control into terms that may be easier to interpret and communicate to patients. When data from The Systolic Blood Pressure Intervention Trial (SPRINT) were published in 2015, the medical community responded enthusiastically to the news that reducing blood pressure lower than the normal targets could reduce overall death rates by 27 percent for adults at high cardiovascular risk. While these study results are being integrated into clinical practice, explaining what they mean and why they are important to patients can be challenging. Investigators from the Brigham describe how aggressively lowering blood pressure levels can extend a person's life expectancy. They report that having a blood pressure target of less than 120 mm Hg -- rather than the standard 140 mm Hg -- can add six months to three years to a person's lifetime, depending upon how old they are when they begin intensive blood pressure control. Results are published in JAMA Cardiology.

"When physicians discuss optimizing blood pressure, patients often wonder what benefits they may anticipate with intensive blood pressure control," said lead author Muthiah Vaduganathan, MD, MPH, a cardiologist at the Brigham. "That was the inspiration for our work: We've taken the data and reframed it to contextualize the results in a way that's most meaningful to patients."

Vaduganathan and colleagues used age-based methods to conduct their analysis. These methods are frequently used in other fields -- for instance, when projecting the long-term survival benefits of a new cancer drug -- but have not been commonly applied in studying cardiovascular disease.

By applying age-based methods to the data from SPRINT, the team could estimate the long-term benefits of intensive blood pressure control. The SPRINT study enrolled more than 9,000 adults who were 50 years or older, were at high cardiovascular risk but did not have diabetes, and had a systolic blood pressure between 130- and 180-mm Hg (130 mm Hg or higher is considered high blood pressure). Participants were randomized to intensive (at least 120 mm Hg) or standard (at least 140 mm Hg) systolic blood pressure targets. Participants were given antihypertensive therapies, free of cost, to achieve their blood pressure targets and were followed for an average of a little over three years.

Vaduganathan and colleagues estimated that if people had continued taking their antihypertensive therapies for the remainder of their lives, those with the intensive blood pressure target could add six months to three years to their life expectancy, compared to those with the standard blood pressure target. This span depended upon the person's age -- for someone who began antihypertensive medications at 50 years old, they predicted a difference of 2.9 years; for someone 65 years old, a difference of 1.1 years; and for someone 80 years old, a difference of nine months.

The authors note that the analysis did not account for potential risks, including kidney injury and low blood pressure, that are associated with intensive blood pressure control. Estimates of survival benefits must be carefully weighed against these potential risks in the selection of blood pressure targets for individual patients.

"Our hope is that these findings offer a more easily communicated message when discussing the potential benefits and risks of sustained blood pressure control over time," said Vaduganathan. "These statistics about life expectancy may be more tangible and personalized for patients and more relatable when making these decisions."

Credit: 
Brigham and Women's Hospital

Nanosize device 'uncloaks' cancer cells in mice and reveals them to the immune system

image: A microscopic image of the nanoparticles used in the study. The black scale bar is 100 nm in size.

Image: 
Jordan Green and Stephany Tzeng

Scientists at Johns Hopkins report they have designed and successfully tested an experimental, super small package able to deliver molecular signals that tag implanted human cancer cells in mice and make them visible for destruction by the animals' immune systems. The new method was developed, say the researchers, to deliver an immune system "uncloaking" device directly to cancer cells.

Conventional immune therapies generally focus on manipulating patients' immune system cells to boost their cancer-killing properties or injecting drugs that do the same but often have toxic side effects.

Results of the proof-of-concept experiments were published online Feb. 7 in the Proceedings of the National Academy of Sciences.

A hallmark of cancer biology is a tumor cell's ability to essentially hide from the immune system cells whose job is to identify and destroy cancer cells. Current cellular immunotherapies, notably CAR-T, require scientists to chemically alter and enhance a patient's own harvested immune system T-cells -- an expensive and time-consuming process, say the researchers. Other weapons in the arsenal of immunotherapies are drugs, including so-called checkpoint inhibitors, which have broad effects and often lead to unwanted immune-system-associated side effects, including damage to normal tissue.

By contrast, the Johns Hopkins team sought an immune system therapy that can work like a drug but that also individually engineers a tumor and its surrounding environment to draw the immune system cells to it, says Jordan Green, Ph.D.

Green is the director of the biomaterials and drug delivery laboratory and a professor of biomedical engineering at the Johns Hopkins University School of Medicine. "And our process happens entirely within the body," Green says, "requiring no external manipulation of a patient's cells."

To develop the new system, Green and his team, including Stephany Tzeng, Ph.D., a research associate in the Department of Biomedical Engineering at Johns Hopkins, took advantage of a cancer cell's tendency to internalize molecules from its surroundings. "Cancer cells may be easier to directly genetically manipulate because their DNA has gone haywire, they divide rapidly, and they don't have the typical checks and balances of normal cells," says Green.

The team created a polymer-based nanoparticle -- a tiny case that slips inside cells. They guided the nanoparticles to cancer cells by injecting them directly into the animals' tumors.

"The nanoparticle method we developed is widely applicable to many solid tumors despite their variability on an individual and tumor type level," says Green, also a member of the Johns Hopkins Kimmel Cancer Center.

Once inside the cell, the water-soluble nanoparticle slowly degrades over a day. It contains a ring of DNA, called a plasmid, that does not integrate into the genome and is eventually degraded as the cancer cell divides, but it stays active long enough to alter protein production in the cell.

The additional genomic material from the plasmid makes the tumor cells produce surface proteins called 4-1BBL, which work like red flags to say, "I'm a cancer cell, activate defenses." The plasmid also forces the cancer cells to secrete chemicals called interleukins into the space around the cells. The 4-1BBL tags and interleukins are like magnets to immune system cells, and they seek to kill the foreign-looking cancer cells.

"Essentially, we're forcing the tumor to open itself up and instruct immune cells to kill it," says Tzeng.

In their animal experiments, Tzeng and the Johns Hopkins team injected the loaded nanoparticles into tumors created by implanting mice with either human melanoma or colon cancer cells.

A control group of mice implanted with melanoma cells received systemically an immunotherapy drug known as anti-PD-1 antibody. All of those mice died quickly, within 2.5 to three weeks, due to tumor growth.

Then, the research team injected other groups of mice, which were also injected with the cancer cells, with nanoparticles containing only one or both of the "uncloaking" signals -- the genetically encoded 4-1BBL tags and interleukins. In mice with implanted melanomas, the nanoparticles that combined the two signals had a stronger effect than either signal alone. The median, or midpoint, survival of the mice with the combo signal package was 40 days, and about 20% of them lived through the end of the 60-day study period.

The researchers also saw that some of the mice in the treated melanoma group developed vitiligo, a condition in which skin cells lose their pigment. It occurs in humans too, including in people undergoing immunotherapy for melanoma. "It's generally thought that vitiligo in melanoma patients is a sign that the immunotherapy treatment is working, and the immunotherapy is spreading to other parts of the body where other melanocytes reside," says Tzeng.

The tumor shrank away in all of the mice with implanted colon tumors that received the nanoparticles with both signals, and they survived through the entire 60-day study period. When the researchers reinjected human colon cancer cells into the sides of mice opposite the original tumors, unlike with age-matched controls, the newly implanted cancer cells failed to form a tumor, suggesting a lasting effect of the boosted immune system.

"The hope is that, eventually, we could develop nanoparticles that hold instructions for a variety of immune-related signals," says Green, who cautioned that use of the nanoparticle system will remain experimental for years to come. "We are developing this system as an 'off-the-shelf' therapy that can induce a personalized systemic anti-tumor response without needing to know the specific genetic makeup of the tumor beforehand."

Credit: 
Johns Hopkins Medicine