Culture

The organ of balance in the inner ear is surrounded by the hardest bone in the body. Using synchrotron X-rays, researchers at Uppsala University have discovered a drainage system that may be assumed to play a major role in the onset of Ménière's disease, a common and troublesome disorder. These results are published in the journal Scientific Reports.

Ménière's disease is manifested in sudden onset of severe dizziness (vertigo) attacks, hearing impairment and tinnitus. Accumulation of excess fluid in the inner ear is thought to cause the disorder, from which approximately an estimated 30,000 people in Sweden suffer.

The researchers behind the new scientific article have investigated the organs in the human inner ear, which are very difficult to study. This part of the ear is enclosed by the body's hardest bone. Using synchrotron X-ray imaging, an advanced and powerful form of computer tomography (CT), the scientists were able to study the organ of balance with its surrounding blood vessels. Since the technology generates energy too high for use on living humans, donors' temporal bones were used.

The images of the inner ear were reconstructed to make a three-dimensional model in the software, Inside the hard bone, the researchers discovered a drainage system that is thought to explain how the fluid in the inner ear is absorbed. This discovery may bring about an improved understanding of how and why Ménière's disease arises.

The synchrotron imaging investigation was carried out in Saskatoon, in the Canadian province of Saskatchewan. The study was conducted jointly with Dr Sumit Agrawal and Dr Hanif Ladak, who are researchers in London, Ontario (Canada).

Bethesda, MD (May 19, 2020) -- Gastroenterology, the official journal of the American Gastroenterological Association (AGA), has released a special issue providing clinicians and researchers an up-to-date resource on the risk factors, natural history, diagnosis and treatment of nonalcoholic fatty liver disease (NAFLD).

The articles published in Gastroenterology's special issue, "Nonalcoholic Fatty Liver Disease in 2020" acknowledge the ever-changing nature of NAFLD, outlining the latest developments that improve our understanding and care of patients with this condition.

View the full Gastroenterology special issue . To receive any of the full studies or to speak with the authors, email media@gastro.org.

Introduction to the issue

Nonalcoholic Fatty Liver Disease in 2020 by Jacquelyn J. Maher, Jörn M. Schattenberg

Expert Review Articles

Nonalcoholic Fatty Liver Disease 2020: The State of the Disease by Thomas G. Cotter, Mary Rinella

Toward Genetic Prediction of Nonalcoholic Fatty Liver Disease Trajectories: PNPLA3 and Beyond by Marcin Krawczyk, Roman Liebe, Frank Lammert

Nonalcoholic Fatty Liver Disease: Modulating Gut Microbiota to Improve Severity? by Judith Aron-Wisnewsky, Moritz V. Warmbrunn, Max Nieuwdorp, Karine Clément

Adipose Tissue-Liver Cross Talk in the Control of Whole-Body Metabolism: Implications in Nonalcoholic Fatty Liver Disease by Vian Azzu, Michele Vacca, Samuel Virtue, Michael Allison, Antonio Vidal-Puig

Mechanisms of Fibrosis Development in Nonalcoholic Steatohepatitis by Robert F. Schwabe, Ira Tabas, Utpal B. Pajvani

Metabolic Inflammation--A Role for Hepatic Inflammatory Pathways as Drivers of Comorbidities in Nonalcoholic Fatty Liver Disease? by Nadine Gehrke, Jörn M. Schattenberg

Circadian Rhythms in the Pathogenesis and Treatment of Fatty Liver Disease by Anand R. Saran, Shravan Dave, Amir Zarrinpar

Nonalcoholic Fatty Liver Disease in Children: Unique Considerations and Challenges by Dana Goldner, Joel E. Lavine

Therapeutic Landscape for NAFLD in 2020 by Brent A. Neuschwander-Tetri

MAFLD: A Consensus-Driven Proposed Nomenclature for Metabolic Associated Fatty Liver Disease by Mohammed Eslam, Arun J. Sanyal, Jacob George (on behalf of the International Consensus Panel)

In a new study, researchers from the Colorado School of Public Health at the University of Colorado Anschutz Medical Campus call attention to the emergence of mosquito-borne viral outbreaks in West Africa, such as dengue (DENV), chikungunya (CHIKV) and Zika (ZIKV) viruses.

The findings are published in the current issue of Acta Tropica.

"Emerging viruses are at the forefront of everyone's attention due to the COVID-19 pandemic. It has underscored the importance of preparing for and preventing large viral outbreaks that can have massive public health and economic consequences," said lead researcher Andrea Buchwald, PhD, a postdoctoral fellow in the Colorado School of Public Health.

Buchwald adds, "We hope our research will prompt the development of early warning systems and adoption of control measures to prevent infectious outbreaks in West Africa. This will greatly impact the spread and severity of future outbreaks."

The researchers reviewed 50 years of literature on arboviruses in West Africa to evaluate evidence of DENV, ZIKV and CHIKV and the distribution of their Aedes mosquito vectors in the region. This research delivers updates to previous estimates made, providing a current, region-specific synthesis of this rapidly evolving public health challenge.

"Large arboviral outbreaks will occur around the world. It is merely a question of where and when. Building awareness and surveillance capacity before the outbreaks occur can help detect outbreaks early and enable prompt and effective response to reduce health impacts," said Elizabeth Carlton, assistant professor of environmental and occupational health at the Colorado School of Public Health and co-author of the study.

The researchers found that there is strong evidence that transmission of arboviral diseases including CHIKV, ZIKV and DENV is occurring in urban areas of West Africa and that the nature of transmission is distinct from the rural transmission of yellow fever virus that has historically been present in the region. The findings also provide evidence that the epidemiology of arboviral disease in West Africa has shifted and rapid urbanization and climate change have the potential to increase the risk of outbreaks in the future.

Carlton adds, "Our study shows how urbanization and climate change can impact mosquito-borne virus transmission in West Africa. However, it also highlights the need for steps to be taken in the region to fill critical information gaps so that we can better define the spatial and temporal patterns of arboviral disease risk."

The researchers outline some steps that can be taken to reduce the risk of major outbreaks, such as building testing capacity, investing in surveillance and implementing mosquito control measures.

ANN ARBOR, Michigan -- Recent large-scale efforts to categorize the molecular data of multiple cancer types has yielded so much information that researchers now have a new question: How to turn all this data into meaningful information that guides cancer research and patient care.

A new analytic tool developed by University of Michigan Rogel Cancer Center researchers combines multiple data sets to help sift the signal from the noise.

"Our idea was to combine three sources of data sets - molecular data from both cancer cell lines and patients and drug profiling data - to understand proper preclinical models that are most representative of these tumors," says Veerabhadran Baladandayuthapani, Ph.D., professor of biostatistics at the University of Michigan School of Public Health and senior author of a paper published in the Journal of Clinical Oncology Clinical Cancer Informatics that describes this new tool.

The tool, called TransPRECISE, uses data from 7,714 patient samples across 31 cancer types, collected as part of the Cancer Proteome Atlas. This is combined with 640 cancer cell lines from the MD Anderson Cell Lines Project and drug sensitivity data representing 481 drugs from the Genomics of Drug Sensitivity in Cancer model system.

"The good thing is this is a very dynamic process. We can have this whole system set up in a computer. As new patients come in or new data comes in, you can keep adding it," says Rupam Bhattacharrya, M.Stat., a doctoral student and first author on the paper.

The tool builds on an earlier model the team had created, which they called PRECISE. With an eye toward precision medicine, they created a model to look at what changes occur to the molecular structure of individual patients' individual tumors. TransPRECISE adds in data from cell lines and drug sensitivity, which will be helpful for researchers translating cancer cell biology into drug discovery.

"Now that we have tens of thousands of tumors on these patients we can evaluate what might be the potential therapeutic efficiency of these drugs. The key idea was to develop an analytic tool to do that," says Baladandayuthapani, who is also director of the Rogel Cancer Center's cancer data science shared resource.

In the JCO Clinical Cancer Informatics paper, researchers validated the tool by comparing known drug responses and clinical outcomes in patient data. TransPRECISE identified the differences in proteins among individual tumors and accurately tied it back to actual patient outcomes. In addition, they looked at several pathways to predict potential drug targets. This yielded results that mirrored current treatment recommendations or targets being tested in clinical trials, such as ibruutinib for BRCA-positive breast cancer, and lapatinib for colon cancer.

"We have so much data, how do we drill it down to make it more informative so an oncologist can understand? Our work would potentially help oncologists or researchers develop concrete hypotheses based on which mechanism is working, potentially bringing to the top drugs that might warrant more evaluation," Baladandayuthapani says.

As people get older, they often feel less energetic, mobile or active. This may be due in part to a decline in mitochondria, the tiny powerhouses inside of our cells, which provide energy and regulate metabolism. In fact, mitochondria decline with age not only in humans, but in many species. Why they do so is not well understood. Scientists at the Max Planck Institute for Biology of Ageing in Cologne set out to understand how mitochondrial function is diminished with age and to find factors that prevent this process. They found that communication between mitochondria and other parts of the cell plays a key role.

For their studies, the scientists used the simple roundworm, Caenorhabditis elegans, an important model system for ageing research. Over half the genes of this animal are similar to those found in humans, and their mitochondria also decline with age. From their research, the scientists found a nuclear protein called NFYB-1 that switches on and off genes affecting mitochondrial activity, and which itself goes down during ageing. In mutant worms lacking this protein, mitochondria don't work as well and worms don't live as long.

Unexpectedly, the scientists discovered that NFYB-1 steers the activity of mitochondria through another part of the cell called the lysosome, a place where basic molecules are broken down and recycled as nutrients. "We think the lysosome talks with the mitochondria through special fats called cardiolipins and ceramides, which are essential to mitochondrial activity," says Max Planck Director, Adam Antebi, whose laboratory spearheaded the study. Remarkably, simply feeding the NFYB-1 mutant worms cardiolipin restored mitochondrial function and worm health in these strains.

Because cardiolipins and ceramides are also essential for human mitochondria, this may mean human health and ageing can be improved by understanding on how such molecules facilitate communication between different parts of the cell. This work has been recently published in Nature Metabolism.

AUSTIN, Texas -- Seeing someone do something good for someone else motivates witnesses to perform their own helpful acts, an insight that could help drive cooperative behavior in communities navigating through the health crisis.

In a new study, psychology researchers at The University of Texas at Austin confirmed that people can be heavily influenced by others, especially when it comes to taking on prosocial behavior -- actions designed to benefit society as a whole. Understanding this is important now, when large-scale cooperation and adoption of protective behaviors -- wearing face masks and avoiding gatherings -- have important implications for the well-being of entire communities, the researchers said.

"Just like the deadly virus, cooperative behavior can also be transmitted across people," said Haesung (Annie) Jung, who led the study while earning a Ph.D. at UT Austin. "These findings remind the public that their behavior can impact what others around do; and the more individuals cooperate to stop the spread of the disease, the more likely others nearby will do the same."

Reviewing the evidence from decades of studies, the researchers found that exposing people to "prosocial models" -- watching someone perform an act of kindness -- elicited some subsequent helpful acts. This response was partly driven by "goal contagion," researchers said, whereby witnessing prosocial actions lead people to adopt the underlying goal associated with the observed behavior, such as caring for others' well-being.

"We found that people can readily improvise new forms of prosocial actions. They engaged in behaviors that were different from what they witnessed and extended help to different targets in need than those helped by the prosocial model," said Jung, who is now a postdoctoral researcher at the University of Illinois at Urbana-Champaign.

The magnitude of this type of influence varied across societies, with Asian countries most likely to be influenced by modeling, followed by European countries, then North American.

They also found that people were more motivated to help after witnessing other people benefit from the prosocial model than when they benefitted from the prosocial act. This shows that the effect triggered by adopting others' prosocial goals outweighed other potential motives triggered by self-benefit, such as doing it because they felt grateful.

The researchers suggested that adopting this type of framework could go a long way in influencing new prosocial behaviors amid the coronavirus pandemic.

"Many people may choose to avoid social distancing practices because they don't think they're likely to contract the virus or experience serious symptoms. So, one of the best things we can do is frame recommended practices as prosocial actions," said Marlone Henderson, associate professor of psychology at UT Austin. "By thinking of recommended practices as prosocial behavior, modeling then becomes a powerful tool for encouraging others to engage in such practices.

Scientists working at caesar have developed a small head-mounted microscope that allows access to the inner workings of the brain. The new system enables measurement of activity from neuronal populations located in the deep cortical layer with single-cell resolution, in an animal that is freely behaving.

Understanding how animals use their brain circuitry to generate behavior in response to their environment is one of the central goals of neuroscience. While it is possible to study animal behavior by observing how an animal solves problems, to gain an understanding of the brain's role in generating the behavior the brain circuit activity must be measured at the same time.

In vivo imaging is, of course, nothing new in biology: it dates back to the very beginnings of microscopy. To look inside the brain, special microscopes can be used that can see through the tissue enabling the observation of neuronal circuits at work. Using a microscope to image neural activity has the advantage of being relatively non-invasive. Mounted outside the brain, the microscope simply sends light into the brain, in turn receiving the light emitted out of the brain. While conventional microscopes are too heavy to enable functional imaging from freely behaving animals, over the last years significant effort has gone into developing head-mounted miniaturized microscopes.

In 2009, Jason Kerr's group, in collaboration with the group of Winfried Denk at the Max Planck Institute of Neurobiology (Martinsried), established a miniaturized head-mounted multiphoton microscope. It enabled recording of activity from neuronal populations located in the upper few layers in visual cortex of awake, freely moving rats. While this 'two-photon fiberscope' was a breakthrough in measuring brain activity from freely behaving animals, most of the cortical layers remained out of reach. To image the deeper layers of the cortex on a cellular level, a new approach was needed.

In collaboration with Philip Russell's group at the Max Planck Institute for the Science of Light, Kerr's group has now developed a small head-mounted multiphoton microscope, capable of imaging all cortical layers in a freely moving rat. Light is delivered through a custom designed and manufactured glass fiber, utilizing the 'three-photon effect' to image neuronal activity located in deep cortical layers. Compared to two-photon or one-photon fluorescence microscopy, three-photon is ideal for imaging deeper in scattering tissue, and enables clearer images of single cells deep in the tissue. The new microscope allows for continuous imaging of neuron populations, even when the animal runs or performs complex behavioral tasks, over extended periods of time.

The researchers expect the fiberscope to be widely applicable to behavioral research, as previous microscopes were limited in their imaging depth and unsuitable for use over extended periods of time, restricting the types of behaviors that could be observed. With this new approach, researchers are now able to understand the complex network dynamics that underlie neural computation which, in turn, forms the basis of perception and behavior.

WASHINGTON, May 19, 2020 -- As the infectious virus causing the COVID-19 disease began its devastating spread around the globe, an international team of scientists was alarmed by the lack of uniform approaches by various countries' epidemiologists to respond to it.

Germany, for example, didn't institute a full lockdown, unlike France and the U.K., and the decision in the U.S. by New York to go into a lockdown came only after the pandemic had reached an advanced stage. Data modeling to predict the numbers of likely infections varied widely by region, from very large to very small numbers, and revealed a high degree of uncertainty.

Davide Faranda, a scientist at the French National Centre for Scientific Research (CNRS), and colleagues in the U.K., Mexico, Denmark, and Japan decided to explore the origins of these uncertainties. This work is deeply personal to Faranda, whose grandfather died of COVID-19; Faranda has dedicated the work to him.

In the journal Chaos, from AIP Publishing, the group describes why modeling and extrapolating the evolution of COVID-19 outbreaks in near real time is an enormous scientific challenge that requires a deep understanding of the nonlinearities underlying the dynamics of epidemics.

Forecasting the behavior of a complex system, such as the evolution of epidemics, requires both a physical model for its evolution and a dataset of infections to initialize the model. To create a model, the team used data provided by Johns Hopkins University's Center for Systems Science and Engineering, which is available online at https://systems.jhu.edu/research/public-health/ncov/ or https://github.com/CSSEGISandData/COVID-19.

"Our physical model is based on assuming that the total population can be divided into four groups: those who are susceptible to catching the virus, those who have contracted the virus but don't show any symptoms, those who are infected and, finally, those who recovered or died from the virus," Faranda said.

To determine how people move from one group to another, it's necessary to know the infection rate, incubation time and recovery time. Actual infection data can be used to extrapolate the behavior of the epidemic with statistical models.

"Because of the uncertainties in both the parameters involved in the models -- infection rate, incubation period and recovery time -- and the incompleteness of infections data within different countries, extrapolations could lead to an incredibly large range of uncertain results," Faranda said. "For example, just assuming an underestimation of the last data in the infection counts of 20% can lead to a change in total infections estimations from few thousands to few millions of individuals."

The group has also shown that this uncertainty is due to a lack of data quality and also to the intrinsic nature of the dynamics, because it is ultrasensitive to the parameters -- especially during the initial growing phase. This means that everyone should be very careful extrapolating key quantities to decide whether to implement lockdown measures when a new wave of the virus begins.

"The total final infection counts as well as the duration of the epidemic are sensitive to the data you put in," he said.

The team's model handles uncertainty in a natural way, so they plan to show how modeling of the post-confinement phase can be sensitive to the measures taken.

"Preliminary results show that implementing lockdown measures when infections are in a full exponential growth phase poses serious limitations for their success," said Faranda.

WASHINGTON, May 19, 2020 -- Airborne transmission of viruses, like the virus causing COVID-19, is not well understood, but a good baseline for study is a deeper understanding of how particles travel through the air when people cough.

In a paper published in Physics of Fluids, from AIP Publishing, Talib Dbouk and Dimitris Drikakis discovered that with even a slight breeze of 4 kph, saliva travels 18 feet in 5 seconds.

"The droplet cloud will affect both adults and children of different heights," Drikakis said. "Shorter adults and children could be at higher risk if they are located within the trajectory of the traveling saliva droplets."

Saliva is a complex fluid, and it travels suspended in a bulk of surrounding air released by a cough. Many factors affect how saliva droplets travel, including the size and number of droplets, how they interact with one another and the surrounding air as they disperse and evaporate, how heat and mass are transferred, and the humidity and temperature of the surrounding air.

To study how saliva moves through air, Dbouk and Drikakis created a computational fluid dynamics simulation that examines the state of every saliva droplet moving through the air in front of a coughing person. Their simulation considered the effects of humidity, dispersion force, interactions of molecules of saliva and air, and how the droplets change from liquid to vapor and evaporate.

The computational domain in the simulation is a grid representing the space in front of a coughing person. The analysis involved running partial differential equations on 1,008 saliva droplets and solving approximately 3.7 million equations in total.

"Each cell holds information about variables like pressure, fluid velocity, temperature, droplet mass, droplet position, etc.," Dbouk said. "The purpose of the mathematical modeling and simulation is to take into account all the real coupling or interaction mechanisms that may take place between the main bulk fluid flow and the saliva droplets, and between the saliva droplets themselves."

Further studies are needed to determine the effect of ground surface temperature on the behavior of saliva in air and to examine indoor environments, where air conditioning significantly affects the particle movement through air.

"This work is vital, because it concerns health and safety distance guidelines, advances the understanding of spreading and transmission of airborne diseases, and helps form precautionary measures based on scientific results," said Drikakis.

MEDFORD/SOMERVILLE and BOSTON, Mass. (May 19, 2020) - A team of researchers at Tufts University's School of Engineering and its School of Medicine, and physicians at Tufts Medical Center have developed a method using fluorescence to detect precancerous metabolic and physical changes in epithelial cells lining the cervix. According to the researchers, the new imaging method opens the door to a non-invasive, early-stage bedside diagnostic. As described today in Cell Reports Medicine, the method can visualize both metabolic and structural changes within individual cells and at different depths of the epithelial tissue near the surface, while also being able to scan the surface in a completely non-destructive manner. The combined information provides a highly accurate assessment of metabolic states in tissues, often the first changes that occur in the transition to cancer.

The imaging method developed by the team looks at the intrinsic fluorescence of the cell, so it requires no contrast agents or radioactive tracers and can be observed using an optical microscope that shines light on the area examined and looks for a fluorescent "glow" at different wavelengths. Unlike biopsies, it requires no painful surgical incisions, and unlike PET imaging used for detecting metabolic signatures of cancer, the fluorescence imaging method provides much higher resolution for surface tissues, does not require intravenous injection of contrast agents, and could theoretically be applied at bedside as part of a routine regimen of monitoring.

Early detection is the most critical factor in the successful treatment and prevention of epithelial cancers, which include both skin and cervical cancers. Just as high risk individuals can reduce the risk of developing skin cancer with regular visits to the dermatologist to scan for precancerous lesions, cervical cancer could theoretically benefit from a similar strategy. However, the standard for diagnostics -- colposcopy followed by acetic acid application and selection of the worst appearing site for biopsy - is expensive, often requires multiple biopsies to obtain sufficient sensitivity in detection, and can be uncomfortable or even painful for patients. Previous studies have shown that the discomfort and inconvenience of the procedure has kept many women from keeping up with monitoring their condition.

"Although more work needs to be done to transition the method from the laboratory to the patient bedside, the technology enables us to gather more information on early cell states than is available by current diagnostic approaches, adding accuracy and precision to a convenient procedure," said Irene Georgakoudi, corresponding author of the study and a professor of biomedical engineering in the School of Engineering at Tufts.

Georgiakoudi added that even though metabolic transitions are an early hallmark of developing cancer, no current early detection methods examine metabolic states.

The method is based on the fluorescence of two important coenzymes -- biomolecules that work in concert with enzymes -- when excited by a laser beam. The coenzymes nicotinamide adenine dinucleotide (NADH) and flavin adenine dinucleotide (FAD) are involved in a large number of metabolic pathways in every cell; for example, determining how they use up glucose or oxygen or how they find alternative sources of energy when glucose or oxygen are in short supply. An examination of the ratio of these coenzymes, a measure of the intensity of their fluorescent signals, and the arrangement of mitochondria (the energy producing "batteries" of the cell), can help reveal whether the cell is undergoing changes that would lead it to cancerous growth. The method can also track the size and shape of individual cells - often an indicator of disease transition - and can gather this information from different depths, which can be useful in identifying the hallmark invasion of precancerous cells through different layers of the epithelium, resulting in the loss of definition in epithelial tissue structure.

"Just looking at the metabolic readouts of the cells is useful, but adding a third dimension, looking at how the cells in the cervical epithelium change their metabolism and structure at different depths, significantly enhances our ability to accurately identify disease when it shows up," said Dimitra Pouli, researcher at Tufts University's School of Engineering, pathology resident physician at Beth Israel Deaconess Medical Center and Harvard Medical School, and lead author of the study. "We put all these quantitative parameters into an automated diagnostic algorithm, which makes it more convenient for the physician or technician using the method to interpret the results."

It is estimated that the annual costs of screening and treating for cervical cancer in the U.S. alone are at least $8 billion (according to a 2012 CDC study). Availability of a non-invasive imaging method has the potential to not only improve the accuracy of detecting early stage cancer or even pre-cancerous lesions, but also could transform monitoring of the disease into a routine and significantly less costly procedure for patients at high risk.

(Boston)--The same genes that greatly increase the risk of breast cancer in U.S. white women, including women of Ashkenazi Jewish descent, also greatly increase breast cancer risk among African American women. These genes include the BRCA1, BRCA2 and PALB2 genes, each of which was associated with a more than seven-fold risk of breast cancer, as well as four other genes associated with a more moderate increase in risk. Previous studies of women of African ancestry were too small to assess genes other than BRCA1 and BRCA2.

"This means that the multi-gene panels that are currently available to test women diagnosed with breast cancer or women at high risk due to their family history will be useful for African American women," explained corresponding author Julie Palmer, ScD, director of BU's Slone Epidemiology Center and the Karin Grunebaum Professor in Cancer Research at Boston University School of Medicine.

Researchers at Boston University and the Mayo Clinic collaborated with members of the CARRIERS consortium to conduct sequencing of germline DNA from 5,054 African American women with breast cancer and 4,993 age-matched African American women without cancer for mutations in 23 cancer predisposition genes. They then estimated the risks of developing breast cancer associated with having a mutation in any of the genes.

More than seven percent of women with breast cancer had a mutation in one of the genes, as compared with two percent of the controls. Among women with breast cancers that lacked estrogen receptors, termed estrogen receptor negative breast cancer, more than 10 percent had a mutation, as compared with five percent in women with estrogen receptor positive breast cancer. "We also found that mutations in PALB2, RAD51C and RAD51D confer increased risks of estrogen receptor negative breast cancer in the African American population," said Fergus Couch, PhD, co-author of the study and the Zbigniew and Anna M. Scheller Professor of Medical Research at Mayo Clinic.

According to the researchers, testing for breast cancer predisposition genes can prevent breast cancer deaths, both in women who have never had breast cancer and in women with breast cancer. "Depending on results of the testing and an individual's own weighing of pros and cons, a woman with a mutation in any of these genes may choose more aggressive screening for cancer, and women with mutations in the high risk BRCA1 and BRCA2 genes may choose removal of her breasts and/or ovaries as a way to prevent initial breast cancer or recurrence," added Palmer who is also a professor of epidemiology at Boston University School of Public Health.

Currently, rates of breast cancer genetic testing are substantially lower in African American women with breast cancer than in white patients of the same ages. Differences in recommendations given to African American women has been identified as one of the drivers of this disparity. "To the extent that the differences in recommendations are the result of misconceptions among clinicians about the prevalence of genetic mutations and associated risks in African American women, awareness of our findings may serve to increase the proportion of African American women who are offered testing," added Palmer.

These findings appear online in the Journal of the National Cancer Institute.

Food production has always shaped the lives of humans and the surface of the Earth. Be it plough or refrigerator, time and again innovations have transformed the ways we grow, process, and consume food over the last millennia. Today, with almost 40 per cent of all land on Earth used for food production, the food system massively impacts climate and environment - from nitrogen flows to water use, from biodiversity to greenhouse gas emissions. In a new study published in the journal Nature Food, an international team of researchers has now assessed and categorised key innovations with a potential to transform the food system, from artificial meat or seafood to biofortified crops or improved climate forecasts - and established what is most needed to make them succeed.

From the invention of the wheel to artificial fertilisers, innovations have always shaped the food system. And agriculture, in turn, has shaped our planet. Of late, however, not to the better, states Alexander Popp, one of the study's authors and head of the land-use group at the Potsdam Institute for Climate Impact Research (PIK): "Nitrogen has boosted yields and lifted millions out of hunger, but if too much of it drains into nature, whole ecosystems can collapse. So, in light of an expanding world population, huge and rising dietary and nutritional needs, and rapidly shrinking space to remain within safe planetary boundaries, we need to identify innovations that can transform the food system, making it sustainable while feeding more people - and what it takes to make them fly." In order to do that, the authors have conducted a technological review spanning three millennia. From past successes like the plough or the greenhouse to innovations that are not yet rolled out. The focus is the latter as the researchers aim to answer the question what society should put her cards on.

"We regard transformation as a process of systemic change. This means we not only analyse technologies, but also values, policies and governance. With such lenses we have assessed what innovations there are, globally, how to categorise them, and how ready they are", Mario Herrero from the Commonwealth Scientific and Industrial Research Organisation in Australia explains. The ten categories identified by the researchers include food processing, gene technology, digital and even cellular agriculture. The innovations as such, in turn, are very broad, ranging from substitutes for livestock or seafood to biofortified crops or improved climate forecasts. "Amongst the things currently sprouting in the global incubators are very advanced elements like insects for food or meat substitutes, but even high-impact basic research like fine-tuning photosynthesis", Herrero lays out. Researchers are currently looking to boost light harvesting in photosynthesis to improve biomass yield.

+++The right climate for behavioural change+++

"Developing a new technology is yet not enough to kick-off a disruptive change in the food system. Innovations also need the right policy conditions and social acceptance to unfold. Plant-based meat and milk substitutes are a great example. The recipes for seitan, soymilk or tofu were out there for long times. But only in recent years, with rising consumer awareness for environmental issues, health, and animal welfare, we have the right climate for behavioural change - and companies are seeing the business opportunities: They are ready to refine the technology, making the products tastier and cheaper. And the final boost could come when environmental pollution gets priced, revealing the true costs of a beef burger versus a pea patty. Plant-based meat can become one of the largest transformations in our food system, and it might take off now."

Johan Rockström, PIK director and co-author of the study, summarises: "The Paris Agreement's stay well below two-degree target together with UNs 2030 goals of eradicating hunger, gives us the clear direction of where we are going. This research now shows us not only how to get there, but also provides confidence that it is indeed possible to succeed. We can feed humanity within planetary boundaries: what we need is to prepare the ground by implementing the right policies for sustainable innovators and actors that can scale change in the entire food industry, such as carbon and nitrogen pricing and science based targets for sustainable food. Thus we can kick-start a true transformation towards a safe and just food future for all on Earth."

A new study shows that when specific human brain cells are transplanted into animal models of multiple sclerosis and other white matter diseases, the cells repair damage and restore function. The study provides one of the final pieces of scientific evidence necessary to advance this treatment strategy to clinical trials.

"These findings demonstrate that through the transplantation of human glial cells, we can effectively achieve remyelination in the adult brain, " Steve Goldman, M.D., Ph.D., professor of Neurology and Neuroscience at the University of Rochester Medical Center (URMC), co-director of the Center for Translational Neuromedicine, and lead author of the study. "These findings have significant therapeutics implications and represent a proof-of-concept for future clinical trials for multiple sclerosis and potential other neurodegenerative diseases."

The findings, which appear in the journal Cell Reports, are the culmination of more than 15 years of research at URMC understanding support cells found in the brain called glia, how the cells develop and function, and their role in neurological disorders.

Goldman's lab has developed techniques to manipulate the chemical signaling of embryonic and induced pluripotent stem cells to create glia. A subtype of these, called glial progenitor cells, gives rise to the brain's main support cells, astrocytes and oligodendrocytes, which play important roles in the health and signaling function of nerve cells.

In multiple sclerosis, an autoimmune disorder, glial cells are lost during the course of the disease. Specifically, the immune system attacks oligodendrocytes. These cells make a substance called myelin, which, in turn, produce the "insulation" that allow neighboring nerve cells to communicate with one another.

As myelin is lost during disease, signals between nerve cells becomes disrupted, which results in the loss of function reflected in the sensory, motor, and cognitive deficits. In the early stages of the disease, referred to as relapsing multiple sclerosis, the lost myelin is replenished by oligodendrocytes. However, over time these cells become exhausted, can no longer serve this function, and the disease becomes progressive and irreversible.

In the new study, Goldman's lab showed that when human glia progenitor cells are transplanted into adult mouse models of progressive multiple sclerosis, the cells migrated to where needed in the brain, created new oligodendrocytes, and replaced the lost myelin. The study also showed that this process of remyelination restored motor function in the mice. The researchers believe this approach could also be applied to other neurological disorders, such as pediatric leukodystrophies - childhood hereditary diseases in which myelin fails to develop - and certain types of stroke affecting the white matter in adults.

This research is in the process of being developed by a University of Rochester start-up company Oscine Therapeutics. The company's experimental transplant therapy for multiple sclerosis and other glial diseases, such as Huntington's disease, is currently under early FDA review for clinical trials. Goldman is the scientific founder, an officer, and holds equity in the company.

Carbon dioxide emissions from fossil fuel sources reached a maximum daily decline of 17 per cent in April as a result of drastic decline in energy demand that have occurred during the COVID-19 pandemic.
The preliminary analysis, published today in Nature Climate Change, was conducted by researchers from the University of East Anglia, Stanford University, the CICERO Center for International Climate Research and CSIRO as part of the Global Carbon Project.

"Emissions reached their peak decline on 7 April, with a 17 per cent decline compared to the same time last year," CSIRO researcher and Global Carbon Project Director Dr Pep Canadell said.

"To put that figure in context, daily emissions declined on average between January to April by 8.6 per cent again compared to the same period last year."
The impact of COVID-19 on global emissions has been estimated based on a combination of energy, activity and policy data available up until the end of April 2020.

The data was drawn from 69 countries, including Australia, that represented 97 per cent of global emissions and 85 per cent of the world's population.

Estimates were then compared against daily emissions data from the same period in 2019.

"Decreases in emissions in 2020 were largest in China where industry and communities first locked down, followed by the US, Europe, and then India," Dr Canadell, who is also a co-author of the paper, said.

"The peak 17 per cent daily decline on 7 April was because China, the US, India, and all other major carbon-emitting countries were all in a high-level of lock-down at the same time."

Researchers estimated country level emissions based on a 'confinement index' representing the effect of different national policies and estimated impact to six sectors of the economy: electricity and heating (power), surface transport, industry, public buildings and commerce, residential and aviation.

They determined the decrease in emissions for each sector based on the severity of confinement (lock-down) and impact on the sector.

The global decrease in emissions has been triggered primarily by changes in numbers of cars and other vehicles on the road (the surface transport sector - which also includes shipping) leading to a 36 per cent decrease in emissions, equivalent to 7.5 megatonnes (5.9 to 9.6) carbon dioxide (CO2).

Lock downs of varying levels have restricted the ability of people to travel in passenger cars and commute to work.

"Across other sectors, the power sector ranked second and the industry sector (encompassing manufacturing and material productions) third in terms of their contributions to the global decrease in emissions in early April," Dr Canadell said.

"With people being urged to stay home and isolate there was a corresponding increase in global residential emissions (2.8 per cent) which saw a 0.2 megatonne (0.1 to 0.4) increase in CO2 at its peak decline."

The global aviation industry, which has been largely grounded as a result of COVID-19, saw a 60 per cent decline in early April emissions compared to 2019. This is equivalent to 1.7 megatonnes (1.3 to 2.2) CO2.

Overall emissions in 2020 will be dependent on how long and to what extent confinement lasts, the time it will take to resume normal activities, and the degree to which life will 'return to normal', said the co-authors of the paper.

If countries remain in lock down at varying levels until the end of the year, there is estimated to be an overall decrease by 7.5 per cent (2.7 to 12.9).

However, if economy and society-wide restrictions lift by mid-June, there is estimated to only be an overall decrease of 4.2 per cent (2.2 to 6.6).

Shimoda, Japan -- For some, sea urchins are a pretty addition to an aquarium, while for others they are simply an ingredient in a common type of sushi. However, for developmental biologists, they represent more than 100 years of research and education. Because their eggs are transparent, embryonic development and even the act of fertilization were easily viewed with microscopes in the 1800s. Beyond the embryo, sea urchins have long lives--some species living up to 200 years--making them interesting for developmental biologists who study aging.

However, along with their long lives comes a long breeding cycle. The most studied species of sea urchin have breeding cycles between one and two years. This is a severe limitation for research that focuses on knocking out, inserting, or editing genes, which rely on quickly produced offspring. As understanding the precise function of genes has come to dominate the field of developmental biology, sea urchins have fallen out of favor as a model animal.

Professor Shunsuke Yaguchi and his team at the University of Tsukuba Shimoda Marine Research Center feel that much can still be learned from sea urchin biology and set out to find a way to reduce the length of the breeding cycle. "We examined several species of sea urchins and modified their food supply and environment," explains Professor Yaguchi. Through these efforts, they found Temnopleurus reevesii, a species that has a breeding cycle of only half a year.

As a proof of concept study, the researchers focused on a gene that is responsible for producing the pigment that colors sea urchins. Using CRISPR technology, they knocked out a pigment gene in a natural T. reevesii mutant that has a deep magenta color. The procedure successfully produced albino mutants, but there was a catch: only male sea urchins survived. Therefore, to create first-generation mutants, the team used eggs from wild-type T. reevesii and sperm from the knockout mutants. Then they used first-generation males and females to produce second-generation mutants that lacked both copies of the pigment gene.

These sea urchins were albino and could metamorphosize into juveniles and advance into adulthood. But the survival rate was quite low. "Many of the albino sea urchin larvae from the F2 generation could not survive exposure to ultraviolet light," says Professor Yaguchi. "This suggests that the pigment might help protect sea urchins from UV light or fix the damaged tissue."

"Having shown that gene editing is both possible and practical in this species of sea urchin, future research can use these techniques in sea urchins to advance the field of developmental biology."