Earth

Doing more with terahertz: Simplifying near-infrared spectroscopy systems

image: Configuration of comb-mode-resolved adaptive sampling THz-DCS, from Chen et al., doi: 10.1117/1.AP.2.3.036004

Image: 
SPIE

Spectroscopy has roots in early 19th century curiosity about interactions between matter and electromagnetic radiation. Thanks to advances in electronics and materials science, various spectroscopy techniques are now routinely used to study the composition of materials and the nature of their chemical bonds by analyzing how they absorb or reflect electromagnetic waves.

Different materials have different absorption profiles across a wide range of frequencies. Some important features in certain molecular systems, like the hydrogen bonds in aqueous systems or the self-assembly of proteins, can be appreciated in their absorption profiles only at frequencies in the order of terahertz (THz, 1000 billion Hertz), a near-infrared range. Scientists have been actively developing spectroscopy techniques compatible with such high frequencies, and a promising one is called THz dual-comb spectroscopy.

Although this method offers many advantages over others in the terahertz range, its use has been limited because of the high complexity of the measurement system, which typically requires two independent stable lasers as the radiation sources. Now, researchers from Tokushima University, Japan, Beihang University, China, and Université du Littoral Côte d'Opale, France, have reported a novel scheme for THz dual-comb spectroscopy that requires only a single laser source while still providing exceptional resolution.

To understand the main aspects of their method, it helps to understand the basics of THz dual-comb spectroscopy. The term "dual-comb" refers to the fact that the laser pulses, when plotted versus frequency, look like a series of equally spaced spikes (spectral lines) over a broad frequency range in the terahertz region, and hence a "comb." In dual-comb spectroscopy, two lasers with slightly different "combs" are used to measure the absorption profile of a sample. Because of the nature of the system, the signal that is actually measured, which results from the "mixing" of the two combs, occupies a much lower frequency range but still reflects all the high-frequency information of interest. The use of two lasers, however, can result in a problem with stabilization control.

To address the problem of stabilization, the researchers used a single laser to produce the two combs. However, when both combs are produced by the same laser source, a "jitter" or timing instability blurs the high-frequency information reflected in the final low-frequency signal that is measured. They corrected this undesirable phenomenon by using a technique called adaptive sampling, by which the signal to be digitally acquired is not sampled at equal time periods but at specific times calculated to minimize any drifts or errors in the relative timing between combs.

To demonstrate their method, the researchers carried out measurements on a mixture of air and the compound acetonitrile. This special gas exhibits characteristic features when irradiated with terahertz radiation and, most importantly, these features vary slightly with pressure. Because these variations are very small, previous dual-comb spectroscopy approaches using a single laser were unable to detect them due to their limited resolution. In contrast, the researchers could use the scheme proposed in this study to accurately observe many of these features. They report a remarkably narrow absorption linewidth (25 MHz) - the first achieved with a dual-comb fiber laser.

The researchers are already working on yet another complementary technique that could push the resolution of THz dual-comb spectroscopy with a single laser even further. The reduction in system complexity resulting from their use of the adaptive sampling technique could broaden the areas of application of precise THz spectroscopy, providing scientists with a powerful yet simple tool to further explore the material world.

Credit: 
SPIE--International Society for Optics and Photonics

Why the Victoria Plate in Africa rotates

image: Clouds reflecting in lake Magadi, Kenya, located in the Eastern Branch of the East African Rift System. The high rising flanks of the Rift's border faults can be seen in the background.

Image: 
Corinna Kalich, University of Potsdam

The East African Rift System (EARS) is a newly forming plate tectonic boundary at which the African continent is being separated into several plates. This is not a clean break. The system includes several rift arms and one or more smaller so-called microplates. According to GPS data, the Victoria microplate is moving in a counterclockwise rotation relative to Africa in contrast to the other plates involved.

Previous hypotheses suggested that this rotation is driven by the interaction of a mantle plume - an upward flow of hot rock within the Earth's mantle - with the microplate's thick craton and the rift system. But now, researchers from the German Research Centre for Geosciences GFZ in Potsdam around Anne Glerum have found evidence that suggests that the configuration of weaker and stronger lithospheric regions predominantly controls the rotation of continental microplates and Victoria in particular. Their findings were published in the journal Nature Communications.

In the paper, the researchers argue that a particular configuration of mechanically weaker mobile belts and stronger lithospheric regions in the EARS leads to curved, overlapping rift branches that under extensional motion of the major tectonic plates induces a rotation. They used 3D numerical models on the scale of the whole EARS to compute the lithosphere and upper mantle dynamics of the last 10 million years.

"Such large models run on high performance computing clusters", says Anne Glerum, main author of the study. "We tested the predictive strength of our models by comparing their predictions of velocity with GPS-derived data, and our stress predictions with the World Stress Map, a global compilation of information on the present-day crustal stress field maintained since 2009. This showed that the best fit was obtained with a model that incorporates the first order strength distributions of the EARS' lithosphere like the one we prepared."

There are many more continental microplates and fragments on Earth that are thought to rotate or have rotated. The lithosphere-driven mechanism of microplate rotation suggested in the new paper helps interpret these observed rotations and reconstruct plate tectonic motions throughout the history of the Earth.

Credit: 
GFZ GeoForschungsZentrum Potsdam, Helmholtz Centre

Preventing pancreatic cancer metastasis by keeping cells 'sheltered in place'

image: Cosimo Commisso, Ph.D., an associate professor in Sanford Burnham Prebys Medical Discovery Institute's NCI-designated Cancer Center and senior study author

Image: 
Sanford Burnham Prebys Medical Discovery Institute

Scientists at Sanford Burnham Prebys Medical Discovery Institute have shown that pancreatic cancer metastasis--when tumor cells gain the deadly ability to migrate to new parts of the body--can be suppressed by inhibiting a protein called Slug that regulates cell movement. The study, published in the Journal of Experimental Medicine, also revealed two druggable targets that interact with Slug and hold promise as treatments that may stop the spread of pancreatic cancer.

"Pancreatic cancer cells are notorious for their ability to escape from a tumor. Even when pancreatic cancer is caught early, tumor cells are already found circulating throughout the body," says Cosimo Commisso, Ph.D., an associate professor in Sanford Burnham Prebys' NCI-designated Cancer Center and senior study author. "Our study suggests that we may be able to create treatments that stop pancreatic cancer cells from untethering in the first place, which could reduce metastasis and help more people survive this deadly cancer."

Stopping the migration of hungry cancer cells

Pancreatic cancer cells, like all cancer cells, grow rapidly and quickly deplete the nutrients in their surrounding environment. To meet their energy needs, tumor cells boost metabolic pathways that normal cells don't use. Commisso is working to understand how pancreatic cancer cells respond to nutrient deprivation--focusing on the most commonly depleted nutrient, glutamine--with the goal of finding treatments that stop the growth of cancer cells without harming healthy cells.

In the study, the scientists used a mouse model of pancreatic cancer to show that, in response to glutamine deficiency, a protein called Slug drives metastasis by activating the epithelial-mesenchymal transition, or EMT--the process cells use to free themselves from tightly packed tissue. Inhibiting Slug reduced the cancer's ability to spread--demonstrated by a reduction in the number and size of secondary lung tumors. The scientists also established that patient samples with higher levels of Slug were linked to a poor prognosis--further indicating that blocking the protein may be beneficial.

"The field of pancreatic cancer research is still working to understand the role of EMT in metastasis. Our study shows that glutamine deficiency indeed activates EMT, through Slug, to allow pancreatic cancer cells to escape and look for nutrient-rich grounds," says Maria Victoria Recouvreux, Ph.D., a staff scientist in the Commisso lab at Sanford Burnham Prebys and the first author of the study. "In addition to revealing new therapeutic avenues that may halt pancreatic cancer metastasis, these findings might also apply to other tumors that rapidly consume glutamine, including lung and colon cancers."

Because Slug is considered "undruggable" due to inherent biological properties, the scientists continued to search for proteins that interact with Slug and could be targeted with a drug. Their research identified two promising targets: ERK and eIF2 alpha. ERK inhibitors are currently under evaluation in clinical trials for pancreatic and other cancers; and an eIF2 alpha inhibitor has completed animal testing.

New hope for a deadly cancer

Once pancreatic cancer metastasizes, the number of people who are alive five years later drops from 37% to only 3%. Of the 57,000 Americans expected to be diagnosed with pancreatic cancer in 2020, about 10% are diagnosed at an early stage and may benefit from a drug that prevents metastasis. For unknown reasons, pancreatic cancer is on the rise and predicted to become the second-leading cause of cancer-related deaths in the U.S.

Now that the researchers have established the important role of Slug in driving metastatic pancreatic cancer, they plan to expand their research to determine Slug's role in pancreatic cancer overall, including impact on disease aggressiveness and survival.

"To make progress in the fight against pancreatic cancer, it is critical that we have a strong scientific understanding of what is driving the tumor's growth and metastasis," says Lynn Matrisian, Ph.D., chief science officer at the Pancreatic Cancer Action Network (PanCAN), who wasn't involved in the study. "Today's findings reveal new insights into how pancreatic cancer metastasizes, providing both hope and important new directions for research that might be able to help more people survive the world's toughest cancer."

Credit: 
Sanford Burnham Prebys

Ultrathin nanosheets separate harmful ions from water

An international research team, led by Monash University and ANSTO (Australia's Nuclear Science and Technology Organisation), has created an ultrathin membrane with high porosity that can filter potentially harmful ions from water.

Researchers created this ultrathin molecular sieve membrane using 2D nanosheets, developed with water-stable Metal Organic Frameworks (MOFs).

The membrane has potential to deliver clean water for millions of people globally through purification and desalination processes. It can also be used in the separation of gases and solvents.

In a world-first, an international research team, led by Monash University and ANSTO, has created an ultrathin porous membrane to completely separate potentially harmful ions, such as lead and mercury, from water.

This innovation could enhance the desalination process and transform the dirtiest water into something potable for millions of people across the world.

The membrane performed steadily for more than 750 hours using limited energy. It could also be manufactured on a global scale, pending further testing.

Researchers for the first time developed water-stable monolayer aluminium tetra-(4-carboxyphenyl) porphyrin frameworks (termed AI-MOFs) nanosheets, and demonstrated their near perfection as building materials for membranes in ion separation from water.

These Al-MOFs nanosheets, exfoliated to just a nanoscale in thickness (one thousand-millionths of a metre), can help remove harmful carcinogens from the atmosphere by creating highly porous membranes to facilitate the separation processes of gases and organic solvents, such as paint.

Results from the study are published in the prestigious international journal, Science Advances.

The study was led by Professor Xiwang Zhang, Researcher in the Department of Chemical Engineering at Monash University and the Director of the ARC Research Hub for Energy-efficient Separation, and Dr Qinfen Gu, Principal Scientist at ANSTO's Australian Synchrotron.

"Owing to the rich porosity and uniform pore size, Metal Organic Frameworks (MOFs) offer significant advantages over other materials for the precise and fast membrane separation," Professor Zhang said.

"However, it remains a daunting challenge to fabricate ultrathin MOFs membranes (less than 100 nanometres) for water-related processing, since most reported MOFs membranes are typically thick and suffer from insufficient hydrolytic stability.

"In this world-first study, we were able to use these ultrathin Al-MOFs to create a membrane that is permeable to water while achieving maximum porosity with nearly 100 percent rejection of ions. This study shows promise for the future application of this membrane to other filtration processes, such as gas separation."

Polymers are by far the most widespread membrane materials, largely owing to their easy processability and low cost, the study suggests.

However, traditional polymeric membranes for ion separation from water usually contain a dense selective layer, leading to limited selectivity. In contrast, nanoporous membranes, where uniform nanopores act as the sieving role, may overcome this limitation.

This breakthrough study confirms that the intrinsic nanopores of Al-MOFs nanosheets facilitate the ion/water separation by creating vertically-aligned channels as the main transport pathway for water molecules, and was enabled by the unique capability of the Australian Synchrotron to analyse materials at the molecular level.

"We use an instrument called the Powder Diffraction beamline at ANSTO's Australian Synchrotron, to understand the difference between the molecular structure of nanosheet samples, and samples at different temperatures, in order to test water purification performance," Dr Gu said.

"The technique, called in-situ, high temperature powder X-ray diffraction characterisation, was conducted on the nanosheets, and during the process there were no obvious variations in the samples at increasing temperature, demonstrating their robustness."

Credit: 
Monash University

Pinker flamingos more aggressive

video: Lesser flamingos feeding. A bird with pinker feathers can be seen being aggressive towards paler birds.

Image: 
Paul Rose

Bright pink flamingos are more aggressive than paler rivals when fighting over food, new research shows.

Pink plumage is a sign of good health in lesser flamingos, and a flush of colour often means they are ready to breed.

So when the birds squabble over food, the pinkest flamingos - both male and female - tend to push the others around.

The study, by the University of Exeter and WWT Slimbridge Wetland Centre, also found the birds fight more when food is available in a small area such as a bowl - so the findings suggest captive birds should be fed over a wide space where possible.

"Flamingos live in large groups with complex social structures," said Dr Paul Rose, of the University of Exeter.

"Colour plays an important role in this. The colour comes from carotenoids in their food, which for lesser flamingos is mostly algae that they filter from the water.

"A healthy flamingo that is an efficient feeder - demonstrated by its colourful feathers - will have more time and energy to be aggressive and dominant when feeding."

Dr Rose studied the behaviour of Slimbridge's lesser flamingos in different feeding situations: at an indoor feeding bowl, a larger indoor feeding pool, and outdoors with food available in a large pool.

In the outdoor pool, birds spent less than half as much time displaying aggression, while foraging time doubled (compared to when fed from a bowl).

"When birds have to crowd together to get their food, they squabble more and therefore spend less time feeding," Dr Rose said.

"It's not always possible to feed these birds outdoors, as lesser flamingos only weigh about 2kg and are native to Africa, so captive birds in places like the UK would get too cold if they went outside in the winter.

"However, this study shows they should be fed over as wide an area as possible.

"Where possible, creating spacious outdoor feeding areas can encourage natural foraging patterns and reduce excess aggression.

"This research shows that zoos don't have to make huge changes to how they keep their animals to make a big, beneficial difference to animal behaviour."

Lesser flamingos do not have a breeding season - they breed when they're in good enough condition.

This is often displayed by a "pink flush" in the feathers, Dr Rose said, and the birds then become paler again during the tiring days of early parenthood.

He added: "This study is a great example of why I love working with WWT Slimbridge.

"Based on my observations, I suggested some changes - and the keepers were willing to try them out.

"As a result, we get pinker, more relaxed flamingos."

The colour of individual birds in the study was scored from one (mainly white) to four (mainly pink).

No difference was found between males and females in rates of feeding or aggression.

Credit: 
University of Exeter

Climate change has degraded productivity of shelf sea food webs

image: A mixture of dinoflagellates and diatoms from the L4 coastal monitoring site off Plymouth, England.

Image: 
Claire Widdicombe

A shortage of summer nutrients as a result of our changing climate has contributed to a 50% decline in important North East Atlantic plankton over the past 60 years.

New research, published in Global Change Biology, shows that larger, nutritious plankton - vital to support fish, seabirds and marine mammals - are being replaced by tiny, primary producers that are of poorer food quality.

Changes from cloudier and wetter summers to longer periods of sunshine and drought have led to decreasing iron and nutrient supply to surface waters. This results in an increased period of suboptimal feeding conditions for zooplankton at a time of year when their metabolic demand is at its highest.

In some areas, large phytoplankton are being almost completely replaced by picoplankton, especially the cyanobacterium Synechococcus, that flourishes when iron and nitrogen levels in surface waters are very low.

However, its small size and lack of essential biomolecules mean it is unable to function in the same way as larger, more nutritious phytoplankton - a vital primary producer of omega-3 - and cannot sustain shelf sea food webs efficiently.

With Synechococcus prominent from the tropics to the Arctic, and its abundance increasing worldwide, scientists suggest that competition for scarce summer nutrients will become a key force in structuring shelf sea food webs. Shelf seas provide around 80% of the world's wild-captured seafood, and changes in their productivity will have major effects on humans.

The study was led by scientists at the University of Plymouth (funded through the Natural Environment Research Council's Shelf Sea Biogeochemistry Programme), working with colleagues from Plymouth Marine Laboratory, the Marine Biological Association, and the University of Southampton. It brought together experts from a range of fields including trace metal analysis, plankton taxonomy, and satellite data.

Lead author Dr Katrin Schmidt, a plankton ecologist in the University of Plymouth's School of Geography, Earth and Environmental Sciences, said: "Zooplankton such as copepods are considered beacons of climate change, and the ~50% decline in their abundance over the last six decades is worrying. Our study is the first to provide a mechanism for such a wide-spread decline, and this understanding is essential to project future responses to climate change. We also need to explore the wider impacts and whether the changing nutrient supply could, for example, lead to reductions in omega-3 within the entire food chain."

The study was based on an area measuring 2,000km by 1,500km in the North East Atlantic, and used a combination of data generated by satellites and the MBA's Continuous Plankton Recorder (CPR) survey. It allowed scientists to identify both longer and shorter-term trends, the spatial extent of any changes and the months that are most affected.

It also used intensive field observations of the phytoplankton community and, by linking the two scales, provided a conceptual model of why the classical food web is increasingly under threat in temperate coastal and shelf areas.

In combination, both satellite and CPR data show similar changes over the longer (1958-2017) and shorter (1997-2018) terms. Between May and August/September in those years, numbers of diatoms, dinoflagellates and total copepods have all declined, while the proportion of picophytoplankton has increased.

Co-author Dr Luca Polimene, Senior Marine Ecosystem Modeller at Plymouth Marine Laboratory, said: "The increasing dominance of small phytoplankton species might have a broad impact on the marine ecosystem. Other than altering the food chain as suggested in this study, it could also change the biological carbon pump modifying the capacity of the ocean to store carbon. We need to make sure that the shift between large to small phytoplankton species is well captured by marine ecosystem models if we want to reliably simulate future oceans."

David Johns, Head of the Continuous Plankton Recorder Survey, added: "While the CPR Survey samples the larger plankton community, declines in some key groups over past decades can be linked to changes in the smallest plankton that are driven by climate change. We have previously witnessed direct climate impacts on the plankton community, from seasonality (temporal) to large scale movements (spatial), via changes in temperature. This study demonstrates a knock-on effect through the food web, and it is only by continuing our monitoring that we will identify multiple stressors acting on our marine environment, and hopefully sustain and protect our productive oceans."

Credit: 
University of Plymouth

T cell immunity in the elderly

image: Young vs an old T cell, showing how the mitochondria becomes more networked (indicative of increased metabolic state) with age.

Image: 
(C) Felix Kraus - Monash BDI

A study by Monash Biomedicine Discovery Institute (BDI) expands the understanding of the molecular pathways that control T cell function and survival and how it relates to declining T cell immunity in the elderly.

The findings, published in Nature Communications, led by Monash BDI's Professor Nicole La Gruta and Dr Kylie Quinn (formerly of Monash University BDI, now Vice-Chancellor's Research Fellow at RMIT University), outline that the increased metabolism of T cells observed with advanced age was an indication that they were working harder merely to survive.

This contradicts previous knowledge, which suggested an increased metabolism was indicative of T cell function, and will have implications for the development of targeted interventions such as vaccines or immunotherapies to treat age-related immune dysfunction.

T cells play an important role in the body's immune response to viral infections and tumors, but T cell immunity wanes as we age, thus increasing our susceptibility to these diseases.

"We've shown that an amped-up metabolism, rather than arming cells to fight pathogens better, is associated with T cell survival over a lifespan. The cells need to substantially increase their metabolism just to survive in the relatively hostile environment of the elderly," Professor La Gruta said.

"This work is important because one of the hallmarks of immune aging is the loss of T cells. So it provides clues on how we might promote T cell survival in the elderly, and so boost T cell immunity," Professor La Gruta said.

Dr Quinn said the discovery supported further research to develop therapies and interventions that support metabolism during ageing, to help our T cells survive and thrive.

"Ultimately we want to support healthy ageing by designing ways to improve T cell metabolism during cell-based immunotherapies such as CAR T cell therapy, and boosting T cell activation in new vaccines," she said.

Credit: 
Monash University

'Whispering gallery' effect controls electron beams with light

image: Artist's view of individual electrons interacting with an optical whispering gallery mode as it circles a silica sphere. The matching between the velocities of the electron and the light-wave it is riding changes the quantum state of the electron, illustrated as a wider halo.

Image: 
Dr Murat Sivis

When you speak softly in one of the galleries of St Paul's cathedral, the sound runs so easily around the dome that visitors anywhere on its circumference can hear it. This striking phenomenon has been termed the 'whispering gallery' effect, and variants of it appear in many scenarios where a wave can travel nearly perfectly around a structure. Researchers from the University of Göttingen have now harnessed the effect to control the beam of an electron microscope by light. The results were published in Nature.

In their experiments, the team of Dr Ofer Kfir and Professor Claus Ropers illuminated small spheres of glass with a laser, trapping light in a so-called 'optical whispering-gallery mode'. Similar to the acoustics example, the light wave travels around in these spheres almost without damping. In their electron microscope, the researchers then passed a beam of electrons near the edge of the sphere. By measuring the distribution of electron velocities, they discovered that the electrons and the light field had exchanged large amounts of energy.

According to first author Kfir, the strength of the interaction arises from two contributions: "First, the whispering gallery effect allows us to store light and use the time to build up a stronger wave. Second, the electrons run at the same velocity as the light wave on the glass sphere." He explains: "Think of a surfer that matches the speed of the wave in order to best use its energy." In the study, the physicists observed that individual electrons had picked up or given away the energy of hundreds of photons, the elementary particles of the light field.

Besides the fundamental interest in this phenomenon, the researchers believe that their findings have considerable future relevance. "We investigate ways in which light can add functionality to electron microscopy," says Ropers from the Faculty of Physics, the leader of the team and Director at the Max Planck Institute for Biophysical Chemistry. "We can now use light to steer the beam of electrons in space and time. Enhancing the coupling of free electrons and photons may eventually lead to entirely new quantum technologies for nanoscale sensing and microscopy. We are confident that the present work is an important step in this direction."

Credit: 
University of Göttingen

Exercise levels can help doctors predict risk of heart disease and death among elderly

Asking elderly patients how much they exercise can help predict their risk of heart disease and death, Mount Sinai and collaborative researchers say. Their study, published in the Monday, June 5, issue of Mayo Clinic Proceedings: Innovations, Quality and Outcomes shows that a simple assessment of exercise activity during appointments for atherosclerosis screening can lead to earlier interventions and ultimately improve care among this population.

"With people now living longer, there is a growing need to determine how we can best detect latent heart disease and its associated clinical risk in older adults," says Alan Rozanski, MD, Professor of Medicine (Cardiology) at the Icahn School of Medicine at Mount Sinai, and Director of Nuclear Cardiology and Cardiac Stress Testing and Chief Academic Officer for the Department of Cardiology at Mount Sinai Morningside. "Our study showed that simply asking patients to rate their level of physical activity, while using a test to look at the plaque in their coronary arteries, markedly improved our ability to predict patients' risk for dying over their next decade of life."

A team of investigators assessed 2,318 patients between the ages of 65 and 84 who underwent coronary artery calcium (CAC) scanning--a chest computed tomography scan that detects and measures the amount of calcified plaque in patients' coronary arteries--between August 31, 1998, and November 16, 2016. Patients filled out a questionnaire before the scan, including a single item which asked them to rate their current level of physical activity on a scale from zero (none) to ten (always). Researchers also took note of the patients' resting heart rate, blood pressure, height, and weight. They also took their medical history into account, including hypertension, diabetes, and tobacco use.

The researchers followed the patients for ten years and looked at the death rate. They found a relationship between both the magnitude of CAC abnormality and mortality and physical activity and mortality. During the study period, 23 percent of the patients died, at an average rate of 2.3 percent per year. Those who reported less physical activity had the highest mortality rates (2.9 percent per year) compared to patients who reported more physical activity (1.7 percent).

Patients with low CAC scores (between 0-99)--meaning that they had little or no atherosclerosis--had low mortality rates regardless of their physical activity scores. However, among patients who had significant atherosclerosis (CAC scores greater than 400), there was a stepwise decrease in mortality risk with increasing levels of reported physical activity. The patients with high CAC scores who reported high physical activity had a measured mortality rate which was similar to that of patients who had low CAC scores but reported only low physical activity over the years of follow-up.

"Most notably, this valuable assessment of physical activity was easily obtained by asking patients just a single question about their physical activity" said Dr. Rozanski. "This emphasizes the well-touted importance of being active. Based on our data, there is no reason why this type of assessment should not become routine in clinical practice."

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

Interpreting DTC testing results imposes a major burden on genetics services

The increasing popularity of direct to consumer (DTC) genetic testing is having an impact on clinical genetics services, according to Australian researchers who will present their work to the 53rd annual conference of the European Society of Human Genetics, being held entirely on-line due to the Covid-19 pandemic, today [Saturday]. Many consumers are unsure about what to do with the results they receive, and many general practitioners are ill-equipped to advise them, meaning that they turn to clinical genetics services for help.

Ms Jane Tiller, Ethical, Legal and Social Adviser in Public Health Genomics, Monash University , Victoria, Australia, and colleagues analysed how often clinical genetics services were receiving referrals related to DTC testing, and what actions were taken by the clinic after receiving the referral. Until now, this subject has received little attention. &laquoWe knew that clinical genetics services had limited resources and long waiting lists. We wanted to explore the impact of DTC-related referrals in order to be able to forecast effects on the delivery of clinical genetics services and inform policymakers so that they could adjust resource needs accordingly,» she says.

The researchers surveyed eleven publicly-funded Australian clinical genetics services, asking questions related to the DTC-generated referrals they had received over the past ten years. They found that 83% of such referrals were made by general practitioners, in order to aid interpretation of results, and that over 30% of referrals were related to imputed disease risk estimates, where an online tool interprets raw genetic data to obtain a health risk profile. The services reported that DTCGT results were often unreliable; fewer than 10% of the results tested were validated.

Currently the national regulator, the Therapeutic Goods Administration (TGA) is considering the issue of DTC genetic testing. Because the sale of health-related DTC testing is prohibited in Australia, some Australians obtain this testing through overseas companies or use data from ancestry sites to obtain imputed health data.

&laquoIf the TGA relaxes these restrictions on DTC genetic testing, this could increase yet further the need for clinical genetics services by consumers of DTC tests,» says Ms Tiller. &laquoOur study raises many issues. There are tensions between the desire to allow consumers access to their genetic information and subsequently managing and funding the healthcare follow-up that they need, either to interpret their results, or to determine an individual risk management plan. Commercial companies who gain from selling these tests often neither consider nor contribute to the cost in downstream health management.»

In addition to the need for sufficient resources and funding for public genetics services, measures that could be taken to improve the situation include increasing the genomic knowledge of general practitioners. &laquoGP knowledge ranges from the extremely genomically literate to the extremely genomically illiterate. There is no way of guaranteeing that all GPs have a sufficient degree of genomic literacy to interpret potentially inaccurate DTC results. Improving genomic literacy across GPs would certainly assist with this aim, and is critical as genomic testing becomes more common,» she says.

Another problem that needs addressing is the lack of a consistent policy for referral management across Australia. Some services provide an appointment to all DTC-related referrals, some provide none, and some assess referrals on a case-by-case basis, leading to considerable inequalities in access. &laquoA uniform national policy regarding the treatment of DTCGT-related referrals should be developed to reduce inequality and ensure consistent decision-making by publicly-funded genetics services in this area.

&laquoNow we need to look in further detail at year on year rates of referral, rates of validation and specific disease risk. As DTC genetic testing continues to grow, we expect its impact on health services will increase. Although our study was carried out in Australia, our findings are relevant for other countries with publicly-funded or single-payer clinical genetics. Policymakers need to take note and act now in order to facilitate efficient operation of clinical genetics and to provide the maximum benefit to the population,» Ms Tiller will conclude.

Chair of the ESHG conference, Professor Joris Veltman, Dean of the Biosciences Institute at Newcastle University, Newcastle upon Tyne, UK, said: "Direct to consumer (DTC) genetics tests are becoming more widely available in society and this study asks the question whether this increases the workload for clinical genetics services in Australia. Overall, my impression is that the number of referrals related to these DTC tests is rather low, but it does make clear that most GPs do not know what to do with these and that shows a need for more education in this area."

Credit: 
European Society of Human Genetics

Comparing new use of flavored vs unflavored e-cigarettes with starting, quitting smoking

What The Study Did: This survey study looked at the association between starting to use flavored or unflavored e-cigarettes and subsequently starting or quitting smoking among adolescents and adults.

Authors: Abigail S. Friedman, Ph.D., of the Yale School of Public Health in New Haven, Connecticut, is the corresponding author.

To access the embargoed study: Visit our For The Media website at this link https://media.jamanetwork.com/

(doi:10.1001/jamanetworkopen.2020.3826)

Editor's Note: The article includes funding/support disclosures. Please see the article for additional information, including other authors, author contributions and affiliations, conflicts of interest and financial disclosures, and funding and support.

Credit: 
JAMA Network

Magnetic liquid structure elucidated through hybrid reverse Monte Carlo simulation

image: Magnetic ionic liquid structures were elucidated through hybrid reverse Monte Carlo simulation. The research results elucidated fundamental understanding of pure liquids with magnetic responses as well as lead to the development of MIL for a variety of practical applications.

Image: 
Ryusuke Futamura, Faculty of Science, Department of Chemistry, Shinshu University

A research team lead by Ryusuke Futamura of Shinshu University investigated the response of magnetic ionic liquids (MIL) to magnetic fields from the microscopic view points. Magnetic fluids, which can respond to magnetic fields, can be made by dispersing ferromagnetic nanoparticles in a solvent. Some pure liquids that are not mixtures also respond to magnetic feilds. For example, oxygen is a liquid around -200°C and is attracted to magnets. In this study, pure magnetic ionic liquids Emim[FeCl4] and Bmim[FeCl4] were examined in the microscopic scale. These liquids are attracted to magnets at room temperature, but the former also undergo a change from paramagnetic to antiferromagnetic behavior at 3.8K.

Ferromagnetism is found in the objects which we think of as "magnets", such as refrigerator magnets. Magnetic atoms or ions have magnetic dipoles (north and south) in the molecular scale that interact with each other and show ferro- or antiferro-magnetism over a long distance in their crystal structures. Bmim[FeCl4] does not crystalize even at low temperatures, and are amorphous, or formless. It was shown in this study that even in this amorphous state, there is structurality in the short range and several magnetic ions form an aligned association structure. This is thought to be the reason for the negative Curie-Weiss temperature, which can be observed as a macroscopic physical property.

It was difficult to investigate and understand the formation of the liquid structure of Emim[FeCl4] and Bmim[FeCl4]. Liquids and amorphous objects do not have a long-range ordered structure, which means structural analysis of such materials are performed through X-ray scattering measurements followed by radial distribution analysis. However, MILs are binary systems consisting of cations and anions. This makes examination by ordinary radial distribution analysis difficult. This is where the hybrid reverse Monte Carlo (HRMC) method helped. It combined the X-ray scattering measurement with molecular simulation to clearly demonstrate the precise coordination structures of the two MIL. This has made it possible to discuss the cation-cation, anion-anion, and cation-anion of the liquid structure.

By the use of spatial distribution function analysis, it has become possible to visualize the ion coordination structure. The temperature dependence of the spatial distribution function showing the coordination structure of the anions around the cations in the MIL can be seen that the lower the temperature, the wider the coordination sphere and more blurred the site. The researchers were able to clarify the characteristics of substances that appear in macroscopic physical properties from a microscopic perspective.

First author Futamura specializes in the nanospaces of porous materials. He hopes to synthesize new composite materials by combining porous materials and ionic liquids. By confining MIL in the nanospace of porous materials, he hopes to create new functional materials for various applications. These MIL are considered organic-inorganic hybrid functional materials that hold potential for outstanding chemical and physical uses.

Credit: 
Shinshu University

Can deep water masses in the Mediterranean cross the Sicily Strait?

image: The experts José Noel Pérez Asensio (UB) and Lucia Quirós-Collazos (ICM-CSIC) during the NextData Cruise on the CNR-Minerva Uno.

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UNIVERSITY OF BARCELONA

The Sicily Strait, an underwater relief connecting the Italian island with the Tunisian coasts, is not a geological barrier for the deep water circulation between eastern and western Mediterranean -which was always thought to be. Quite the contrary, the contribution of the eastern Mediterranean deep water flow towards the western one can reach 70%, according to a study recently published in the journal Process in Oceanography.

The new study profiles an hydrodynamic map -so far unknown- between the eastern and western basins of the Mediterranean Sea, and is led by Leopoldo Pena and Isabel Cacho, members of the Faculty of Earth Sciences and the Consolidated Research Group on Marine Geosciences of the University of Barcelona. Other co-authors of the study are the experts Ester Garcia Solsona, Eduardo Paredes and Jose Pérez Asensio (UB research group on Marine Geosciences), Lucía Quirós Collazos, from the Institute of Marine Sciences (ICM-CSIC) and Fabrizio Lirer, from the Institute of Marine Sciences (ISMAR-CNR, Italy).

The innovative study sheds light on the oceanographic processes in the Mediterranean Sea using the pioneer application of neodymium (Nd) radiogenic isotopes and rare earth elements as geochemical tracers to study this complex marine area. Researchers could use this methodology thanks to the equipment of the new Laboratory of Radiogenic and Environmental Isotopes (LIRA) and the multicollector mass spectrometer PANTHALASSA of the University of Barcelona, a dual support infrastructure for research -the only one in Spain- perfect to identify radiogenic and environmental isotopes at trace levels. Scientifically coordinated by Isabel Cacho and Leopoldo Pena, the equipment was launched in 2019 in the Faculty of Earth Sciences and in the Scientific and Technological Centers of the UB (CCiTUB), respectively.

Underwater frontier between Mediterranean basins

The Mediterranean Sea is a semi-closed sea which communicates with the Atlantic Sea via the Gibraltar Strait. Surrounded by continental waters, it is divided in two basins of a similar size -eastern and western- with water masses with different properties (salinity, density, isotopic composition, topography, etc.) which connect through the Sicily Strait.

The effect of the particularly dry climate of the Mediterranean determines the creation of deep water in some areas of this marine region (Gulf of Lion, south of the Adriatic Sea, etc.). This oceanographic process takes place in some areas of the planet -North Atlantic or around the Antarctica- under different oceanographic and atmospheric conditions, and it is regarded as the engine of the global oceanographic circulation in the planet.

"The Sicily Strait is only 316 meters deep and the eastern Mediterranean basin goes beyond 5,000 meters. One of the processes that fascinated the field of oceanographic research is this exchange of water mass between the eastern and western basins through this strait", notes Isabel Cacho, Professor of the Department of Earth and Ocean Dynamics of the UB.

"According to the classic hypothesis -she continues- the strait was a physical barrier for the deep waters of the eastern Mediterranean to travel towards the western one. This oceanographic process was believed to be dominated by intermediate waters".

Radiogenic isotopes and rare earth elements: a new perspective on oceanography

The new oceanographic study uses rare earth elements and neodymium isotopes -chemical element from the lanthanide group- as conservative oceanographic tracers in the Mediterranean area. With this methodology, experts rebuilt the oceanographic structure of the Mediterranean basins using samples from water taken onboard in the oceanographic boat N/o Minerva Uno from the National Research Council (CNR, Italy). The samples were obtained in June 2016 during the oceanographic campaign in the Italian project NextData -in which the UB took part- in the central area of the Mediterranean.

"These new geochemical tools allow us to separate water masses formed in the eastern Mediterranean -warmer and salty- from the western one. The waters from the eastern basin show higher concentration of rare earth elements and a Nd isotopic composition which is more radiogenic than the western basin", notes Isabel Cacho, awardee of an ERC Consolidator Grant 2015, who contributed to promote new oceanographic research studies.

The conclusions suggest that the contribution of deep water from the eastern Mediterranean to the western area can reach about 70% of the deep waters in the Tyrrhenian Sea. This proportion -which oscillates between 30 and 70% in the eastern area of the Tyrrhenian- is higher than the calculated values with classic oceanographic parameters (temperature, salinity, etc.), in previous studies.

LIRA-PANTHALASSA: support to multidisciplinary research

Having multicollector mass spectometers (MC-ICP-MS) for the precise analysis of Nd radiogenic isotopes -present in low concentrations in the sea- is a must to conduct oceanographic studies in Spain with this new methodological perspective. The MC-ICP-MS PANTHALASSA -installed in CCiTUB and available for its users- allows users to determine the isotopic relation of most of the periodic table elements, with a high sensitivity (between 10 and 100 parts per million).

"These tools enable us to develop a leading science to study the current ocean -as seen in this study- but we can use them to see the conditions of the ocean in the past during the different climate changes. Therefore, these open new opportunities to understand the relation between climate and ocean better", notes Leopoldo Pena, member of the research group on Marine Geosciences of the UB, led by Professor Miquel Canals.

"Moreover, despite the large potential of application in disciplines related to earth sciences (oceanography, palaeoceanography, geochronology, petrology, hydrology, etc.), many knowledge fields related to environmental, archaeological, food and health studies can benefit from these leading analytic techniques".

Credit: 
University of Barcelona

Wearable brain scanner technology expanded for whole head imaging

image: 49 channel whole head brain scanner.

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University of Nottingham

Scientists from the University of Nottingham developed an initial prototype of a new generation of brain scanner in 2018 which is a lightweight device that can be worn on the head like a hat, and can scan the brain even whilst a patient moves. Their latest research has now expanded this to a fully functional 49 channel device that can be used to scan the whole brain and track electrophysiological processes that are implicated in a number of mental health problems. Their findings have been published in Neuroimage.

Professor Matt Brookes from the University of Nottingham has led the development of this wearable scanner, he said: "Understanding mental illness remains one of the greatest challenges facing 21st century science. From childhood illnesses such as Autism, to neurodegenerative diseases such as Alzheimer's, human brain health affects millions of people throughout the lifespan. In many cases, even highly detailed brain images showing what the brain looks like fail to tell us about underlying pathology, and consequently there is an urgent need for new technologies to measure what the brain actually does in health and disease."

Brain cells operate and communicate by producing electrical currents. These currents generate tiny magnetic fields that can be detected outside the head. Researchers use MEG to map brain function by measuring these magnetic fields. This allows for a millisecond-by-millisecond picture of which parts of the brain are engaged when we undertake different tasks, such as speaking or moving.

Unlike the large cumbersome scanners where patients must remain very still, the wearable scanner allows the patient to move freely. The early prototype of this system in 2018 had just 13 sensors and could only scan limited sections of the brain. Further developments in 2019 enabled the first measurements in children.

The team worked with Added Scientific in Nottingham to develop a novel type of 3D printed helmet, which is key to the function of the 49 channel device. The higher channel count means that the system can be used to scan the whole brain. It can show the brain areas controlling hand movement and vision pinpointed with millimetre accuracy.

Ryan Hill lead author on this study said: "Although there is exciting potential, OPM-MEG is a nascent technology with significant development still required. Whilst multi-channel systems are available, most demonstrations still employ small numbers of sensors sited over specific brain regions and the introduction of a whole-head array is an important step forward in moving this technology towards effective commercial application."

This new whole head scanner unlocks a hots of new possibilities, like scanning children (who find it hard to keep still) or scanning epileptic patients during seizures to understand the abnormal brain activity that generates those seizures.

Professor Brookes continues: "Our group in Nottingham, alongside partners at UCL, are now driving this research forward, not only to develop a new understanding of brain function, but also to commercialise the equipment that we have developed. Components of the scanner have already been sold, via industrial partners, to brain imaging laboratories across the world. It is thought that not only will the new scanner be significantly better than anything that currently exists, but also that it will be significantly cheaper."

Credit: 
University of Nottingham

Diet, gut microbes affect cancer treatment outcomes, research suggests

image: UVA's Eyleen O'Rourke, PhD, discovered that what we eat can affect the outcome of chemotherapy -- and likely many other medical treatments -- because of ripple effects that begin in our gut.

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Dan Addison | UVA Communications

What we eat can affect the outcome of chemotherapy - and likely many other medical treatments - because of ripple effects that begin in our gut, new research suggests.

University of Virginia scientists found that diet can cause microbes in the gut to trigger changes in the host's response to a chemotherapy drug. Common components of our daily diets (for example, amino acids) could either increase or decrease both the effectiveness and toxicity of the drugs used for cancer treatment, the researchers found.

The discovery opens an important new avenue of medical research and could have major implications for predicting the right dose and better controlling the side effects of chemotherapy, the researchers report. The finding also may help explain differences seen in patient responses to chemotherapy that have baffled doctors until now.

"The first time we observed that changing the microbe or adding a single amino acid to the diet could transform an innocuous dose of the drug into a highly toxic one, we couldn't believe our eyes," said Eyleen O'Rourke, PhD, of UVA's College of Arts & Sciences, the School of Medicine's Department of Cell Biology and the Robert M. Berne Cardiovascular Research Center. "Understanding, with molecular resolution, what was going on took sieving through hundreds of microbe and host genes. The answer was an astonishingly complex network of interactions between diet, microbe, drug and host."

How Diet Affects Chemotherapy

Doctors have long appreciated the importance of nutrition on human health. But the new discovery highlights how what we eat affects not just us but the microorganisms within us.

The changes that diet triggers on the microorganisms can increase the toxicity of a chemotherapeutic drug up to 100-fold, the researchers found using the new lab model they created with roundworms. "The same dose of the drug that does nothing on the control diet kills the [roundworm] if a milligram of the amino acid serine is added to the diet," said Wenfan Ke, a graduate student and lead author of a new scientific paper outlining the findings.

Further, different diet and microbe combinations change how the host responds to chemotherapy. "The data show that single dietary changes can shift the microbe's metabolism and, consequently, change or even revert the host response to a drug," the researchers report in their paper published in Nature Communications.

In short, this means that we eat not just for ourselves but for the more than 1,000 species of microorganisms that live inside each of us, and that how we feed these bugs has a profound effect on our health and the response to medical treatment. One day, doctors may give patients not just prescriptions but detailed dietary guidelines and personally formulated microbe cocktails to help them reach the best outcome.

Researchers have observed microbes and diet affecting treatment outcomes before. However, the new research stands out because it is the first time that the underlying molecular processes have been fully dissected.

A New Model

The researchers' new model is an extremely simplified version of the complex microbiome - collection of microorganisms - found in people. Roundworms serve as the host, and non-pathogenic E. coli bacteria represent the microbes in the gut. In people, the relationships among diet, microorganisms and host is vastly more complex, and understanding this will be a major task for scientists going forward.

The research team noted that drug developers will need to take steps to account for the effect of diet and microbes during their lab work. For example, they will need to factor in whether diet could cause the microorganisms to produce substances, called metabolites, that could interfere or facilitate the effect of the drugs.

The researchers suggest that the complexity of the interactions among drug, host and microbiome is likely "astronomical." Much more study is needed, but the resulting understanding, they say, will help doctors "realize the full therapeutic potential of the microbiota."

"The potential of developing drugs that can improve treatment outcomes by modulating the microbes that live in our gut is enormous," O'Rourke said. "However, the complexity of the interactions between diet, microbes, therapeutics and the host that we uncovered in this study is humbling. We will need lots of basic research, including sophisticated computer modeling, to reveal how to fully exploit the therapeutic potential of our microbes."

Credit: 
University of Virginia Health System